A Design of Tamper Resistant Prescription RFID Access Control System
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Name, Manufacturer, Brand, Registered Trademark注册商标, Product type, Product Code number产品代号 Specification规格, Material, Ingredient成 分, Main performance主要性能, Technical Specification技术指标 Name, Address, Number
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Do not bleach Drip dry Wool wash Tumble dry Iron on a low heat Do not dry clean
噻托溴铵reaxys_路线总结
Query1. QueryView in Reaxys87.7 %13:Tiotropium bromide31.5 g (0.1 mol) methylscopinium hexafluorophosphate (Example 9) and 30.5 g (0.10 mol) of 2,2'-methyl dithienylgly-colate are dissolved in 400 ml acetone and stirred in the presence of 90 g of zeolite of type 4A (Na12Al12Si12O48.x.nH2O) and 0.2 g (1 mmol) potassium-tert.-butoxide over a period of 20-24 hours at 0° C.The reaction mixture is filtered,the filtrate is combined with a solution of 8.7 g of LiBr (8.7 g 0.10 mol in 100 ml acetone).The product that crystallisesout is separated off by filtration, washed with acetone and then dried.A yield of 41.4 g (87.7percent) is obtained, witha 90percent conversion level.Stage 1:With potassium tert-butylate in acetone, Time= 20 - 24h, T= 0 °C , Molecular sieveStage 2:With lithium bromide in acetone, Product distribution / selectivityPatent; Brandenburg, Joerg; US2010/63289; (2010); (A1) EnglishView in Reaxys87.7 %6:EXAMPLE 6Tiotropium bromide31.5 g (0.1 mol) methylscopinium hexafluorophosphate (Example 1) and 30.5 g (0.10 mol) of 2,2'-methyl dithienylgly-colate are dissolved in 400 ml acetone and stirred in the presence of 90 g of zeolite of type 4 Å (Na12Al12Si12O48*nH2O) and 0.2 g (1 mmol) potassium-tert.-butoxide over a period of 20-24 hours at 0° C.The reaction mixture is filtered, the filtrate is combined with a solution of 8.7 g of LiBr (8.7 g 0.10 mol in 100 ml acetone).The product that crystallises out is separated off by filtration, washed with acetone and then dried.A yield of 41.4 g (87.7percent) is obtained, with a 90percent conversion level.Stage 1:With potassium tert-butylate, zeolite Na12Al12Si12O48*nH2O 4 Å in acetone, T= 0 °CStage 2:With lithium bromide in acetone, Product distribution / selectivityPatent; BOEHRINGER INGELHEIM PHARMA GMBH and CO. KG; US2010/105898; (2010); (A1) EnglishView in Reaxys48 %5:Example 5 Tiotropium Bromide 1.6 g (5 mmol) methylscopinium hexafluorophosphate (Example 1) and 1.25 g (5mmol) methyl dithienylglycolate are stirred in 50 ml acetone and in the presence of 2 g powdered molecular sieve 4A(Fluka) and 6 mg potassium-tert.-butoxide at 0° C. for 4 h. The reaction mixture is filtered, washed with 20 ml acetone,the filtrate is combined stepwise with a solution of 0.7 g LiBr (13 mmol) in 11 ml acetone. The unreacted material thatcrystallises out is separated off by filtration (fractionated precipitation). The crystal fractions were filtered off and dried.The composition of the fractions was determined by thin layer chromatography. The tiotropium bromide fractions weresuction filtered, washed with acetone, recrystallised from water, washed with acetone and dried. 1.2 g (48percent yieldbased on the compound according to Example 1 used). Tiotropium bromide was isolated in this way. Purity HPLC:99.8percent, TLC: no visible contaminationStage 1:With potassium tert-butylate in acetone, Time= 4h, T= 0 °C , Molecular sieveStage 2:With lithium bromide in acetone, Product distribution / selectivityPatent; Boehringer Ingelheim Pharma GmbH and Co. KG; US2007/27320; (2007); (A1) EnglishView in Reaxys35 %4:Example 2 Tiotropium Bromide 1.6 g (5 mmol) methylscopinium hexafluorophosphate (Example 1) and 2.0 g (7.8mmol) methyl dithienylglycolate are refluxed in 50 ml acetone and in the presence of 10 g molecular sieve 4A for 50-70hours. The reaction mixture is filtered, the filtrate is combined with a solution of 0.3 g of LiBr in 10 ml acetone. The stillunreacted N-methylscopinium bromide that crystallises out is separated off by filtration. After the addition of another0.6 g LiBr (dissolved in acetone) tiotropium bromide is precipitated in an isolated yield of 30percent (based on thecompound of Example 1 used).Stage 1:With 4-(N,N-dimethlyamino)pyridine in acetone, Time= 24h, Molecular sieve, Heating / refluxStage 2:With lithium bromide in acetone, Product distribution / selectivityPatent; Boehringer Ingelheim Pharma GmbH and Co. KG; US2007/27320; (2007); (A1) EnglishView in Reaxys30 %2:Example 2 Tiotropium Bromide 1.6 g (5 mmol) methylscopinium hexafluorophosphate (Example 1) and 2.0 g (7.8mmol) methyl dithienylglycolate are refluxed in 50 ml acetone and in the presence of 10 g molecular sieve 4A for 50-70hours. The reaction mixture is filtered, the filtrate is combined with a solution of 0.3 g of LiBr in 10 ml acetone. The stillunreacted N-methylscopinium bromide that crystallises out is separated off by filtration. After the addition of another0.6 g LiBr (dissolved in acetone) tiotropium bromide is precipitated in an isolated yield of 30percent (based on the compound of Example 1 used).Stage 1:in acetone, Time= 50 - 70h, Heating / reflux, Molecular sieveStage 2:With lithium bromide in acetone, Product distribution / selectivityPatent; Boehringer Ingelheim Pharma GmbH and Co. KG; US2007/27320; (2007); (A1) EnglishView in Reaxystropium bromide obtained was found to have the XRPD,DSC and TGA spectra shown in Figures 1, 2 and 3 respec-tively.Molar yield = 97.76percentHPLC purity = 99.83percentin dichloromethane, acetonitrile, Time= 30.3333h, T= 25 - 30 °CPatent; GENERICS [UK] LIMITED; MYLAN INDIA PRIVATE LIMITED; GORE, Vinayak Govind; MANOJKUMAR,Bindu; SHINDE, Dattatraya; KOKANE, Dattatrey; WO2011/15883; (2011); (A1) EnglishView in Reaxys97.76 %Tiotropium Bromide (1)The purified tiotropium base (3) (1 eq) was dissolved in DCM (10 vol) and acetonitrile (3 vol)and purged with methyl bromide gas for 20 minutes. The solution was kept at 25-300C for 30 hours. The precipitatedsolid was filtered and washed with DCM (20 vol). Drying of the solid at 25-300C under vacuum gave the product,tiotropium bromide (1), as a white solid.Molar yield = 97.76percentHPLC purity = 99.83percent1H NMR (300 MHz,CD3OD): 7.45 (2H dd), 7.23 (2H dd), 7.00 (2H dd), 5.27 (IH t), 4.60 (IH br s OH), 3.35 (8H m), 3.10 (2H s), 2.85 (2Hdt), 2.10 (2H d).MS: 392.3 (M+l)in dichloromethane, acetonitrile, Time= 30.3333h, T= 20 - 30 °CPatent; GENERICS [UK] LIMITED; MYLAN INDIA PRIVATE LIMITED; GORE, Vinayak Govind; MANOJKUMAR,Bindu; SHINDE, Dattatraya; KOKANE, Dattatrey; WO2011/15884; (2011); (A1) EnglishView in Reaxys97.2 %11:Example 11: Synthesis of tiotropium bromideExample 11: Synthesis of tiotropium bromide A solution of 22percent methyl bromide in acetone was prepared byscrubbing gas into a dark glass bottle containing 1.6 kg of acetone and placed on scales until obtaining 1.95 kg ofmethyl bromide solution in acetone.In a reaction flask were charged, in this order:scopine ester (3): 242.6g (0.6426moles, 1 eq) DMF: 388 mL,acetone: 1370 mL(acetone/DMF ratio: about 3.5:1)The suspension, maintained under me-chanical stirring, was heated to 40±5°C until obtaining complete dissolution of the solid.The clear (pale yellow colored)solution was cooled to 20°C and, keeping the flask immersed in a water bath, a 22.1percent (w/w) solution of methylbromide in acetone: 636 mL, equal to about 1.8 eq. of MeBr, was rapidly dropped, by addition funnel, on the clearsolution.In a few hours of stirring at room temperature, a progressive precipitation of white solid was observed.Thereaction mixture was maintained under stirring at room temperature. after about 4 days (90-100 h) a sampling wascarried out for reaction control.The reaction mixture appeared as a heterogeneous suspension made up of clear motherwaters and grainy and heavy solid, which tended to rapidly settle on the flask bottom.The solid was filtered, and flaskand solid were washed over a filter with: 863 mL of acetone/DMF mixture (5:1), 431 mL of acetone/DMF mixture (5:1),2x431 mL of acetone. The solid thus obtained was dried over the filter under Nitrogen current for 2-3h. At the end ofthe drying the solid appeared white and powdery.Crude dry Tiotropium bromide weight: 295.1 g (yield=97.2percent) .in N,N-dimethyl-formamide, acetone, T= 20 °CPatent; LUSOCHIMICA S.P.A.; CIPOLLONE, Amalia; FATTORI, Daniela; FINCHAM, Christofer Ingo;WO2013/46138; (2013); (A1) EnglishView in Reaxys97.3%2:preparation of crude tiotropium bromideN-demethyltiotropium (66 g; 0.17 mol) was dissolved in dimethylformamide (330 ml) and the solution was cooled to atemperature between 0 °C and 5 °C. A solution of bromomethane in 2-methyltetrahydrofuran (132 ml; 0.72 mol) wasadded and the reaction mixture stirred overnight at 0 °C - 5 °C. The content of N-demethyltiotropium in the reactionmixture was 3.6percent by HPLC. Then the reaction mixture was heated up to a temperature between 10 °C and 15°C and stirred at this temperature range over 2 hours. The content of N-demethyltiotropium in the reaction mixturedecreased to 1.7percent. The reaction mixture was heated to a temperature between 25 °C and 30 °C and stirred atthat temperature range over 1 hour. The content of N- demethyltiotropium in the reaction mixture decreased to 1.0per-cent by HPLC. 2- Methyltetrahydrofuran (594 ml) was added to the reaction mixture previously cooled to 0 °C - 5 °C,the suspension was stirred over 1 hour while maintaining the temperature between 0 °C and 5 °C, the product wasfiltered and washed with 2-methyltetrahydrofuran (297 ml) previously cooled to a temperature between.0 °C and 5 °C.The purity of the wet product was 99.48percent and the content of N-demethyltiotropium was 0.33percent (by HPLC).The wet product was re-s urried in dimethylformamide (297 ml) over 1 hour, was filtered, was washed with 2- methyl-tetrahydrofuran (297 ml) previously cooled' to 0 °C - 5 °C and dried. Crude tiotropium bromide (804 g; 97.3percent ofthe theoretical yield) was obtained with a purity of .99.77percent and with a residual content of N-demethyltiotropiumof 0.16percent (by HPLC) . -in 2-methyl tetrahydrofuran, N,N-dimethyl-formamide, T= 0 - 30 °CPatent; HOVIONE INTERNATIONAL LTD; KING, Lawrence; SOBRAL, Luis; TEMTEM Marcio; ANTUNES, Rafael;NUNES, Bruna; WO2013/117886; (2013); (A1) EnglishView in Reaxys95 %Preparation of Anhydrous Tiotropium Bromide from Scopine di-(2-thienyl)glycolatePreparation of Anhydrous Tiotropium Bromide from Scopine di-(2-thienyl)glycolateScopine di-(2-thienyl)glycolate (1 eq) was dissolved in acetone (35 vol) at 25-30° C. and methyl bromide in acetonitrile(50percent w/w solution, 5 vol) was added.The mixture was stirred at 25-30° C. for 24 hours and the precipitated solid was filtered and washed with acetone (5vol).The solid was dried at 60° C. under vacuum to afford the product as a white solid.The crude anhydrous tiotropium bromide obtained was found to have the XRPD, DSC and TGA spectra shown in , 2and 3 respectively.Molar yield=95percentHPLC purity=99.5-99.7percentPurification of Anhydrous Tiotropium Bromidein acetone, acetonitrile, Time= 24h, T= 25 - 30 °CPatent; GENERICE (UK) LIMITED; US2012/149725; (2012); (A1) EnglishView in Reaxys88 % 2.c:c) Preparation of the Tiotropium BromideMethyl bromide (5.1 kg) is piped into the scopine ester solution obtained by the method described above at 20° C. Thecontents of the apparatus are stirred at 30° C. for about 2.5 days. 70 L of DMF are distilled off at 50° C. in vacuo. Thesolution is transferred into a smaller apparatus. It is rinsed with DMF (10 L). Additional DMF is distilled off at 50° C. invacuo until a total amount of distillate of about 100 L is obtained. This is cooled to 15° C. and stirred for 2 hours at thistemperature. The product is isolated using a suction filter drier, washed with 15° C. cold DMF (10 L) and 15° C. coldacetone (25 L). It is dried at max. 50° C. for max. 36 hours in a nitrogen current. Yield: 13.2 kg (88percent); [0060]Melting point: 200-230° C. (depending on the purity of the starting product); [0061] The crude product thus obtained(10.3 kg) is added to methanol (66 L). The mixture is refluxed to dissolve it. The solution is cooled to 7° C. and stirredfor 1.5 h at this temperature. The product is isolated using a suction filter drier, washed with 7° C. cold methanol (11L) and dried for max. 36 h at about 50° C. in a nitrogen current. [0062] Yield: 9.9 kg (96percent); [0063] Melting point:228° C. (determined by TLC at a heating rate of 10 K/min). [0064] If desired, the product thus obtained may be convertedin the crystalline monohydrate of tiotropium bromide. The following method may be used. [0065] 15.0 kg of tiotropiumbromide are added to 25.7 kg of water in a suitable reaction vessel. The mixture is heated to 80-90° C. and stirred atconstant temperature until a clear solution is formed. Activated charcoal (0.8 kg), moistened with water, is suspendedin 4.4 kg of water, this mixture is added to the solution containing tiotropium bromide and rinsed with 4.3 kg of water.The mixture thus obtained is stirred for at least 15 min. at 80-90° C. and then filtered through a heated filter into anapparatus which has been preheated to an outer temperature of 70° C. The filter is rinsed with 8.6 kg of water. Thecontents of the apparatus are cooled to a temperature of 20-25° C. at a rate of 3-5° C. every 20 minutes. Using coldwater the apparatus is cooled further to 10-15° C. and crystallisation is completed by stirring for at least another hour.The crystals are isolated using a suction filter drier, the crystal slurry isolated is washed with 9 L of cold water (10- 15°C.) and cold acetone (10-15° C.). The crystals obtained are dried at 25° C. for 2 hours in a nitrogen current. [0066]Yield: 13.4 kg of tiotropium bromide monohydrate (86percent of theory). [0067] Melting point: 230° C. (determined byTLC at a heating rate of 10 K/min).in DMF (N,N-dimethyl-formamide), Time= 60h, T= 20 - 30 °CPatent; Boehringer Ingelheim Pharma GmbH and Co. KG; US2003/236409; (2003); (A1) EnglishView in Reaxys2; 3:Example 2: Preparation of crude Tiotropium bromide <n="29"/>[0109] 0.52 g of N-demethyl tiotropium (1.39 mmol)was suspended in 5.23 iriL of CH3CN under nitrogen.[0110] 1.35 g of CH3Br 50percent w/w solution in CH3CN (0.0071mol) were loaded, and the suspension was left under stirring at 220C for 12 hours. The product was filtered and washedwith ImI of CH3CN.[0111] 572 mg of wet Tiotropium bromide were obtained (HPLC purity 99.89percent, dithienylglycolicacid not detected).; Example 3 : Preparation of Tiotropium bromide[0112] 4.96g of N-demethyl tiotropium (13.2 mmol)were loaded in a flask under nitrogen with 49.6mL of CH3-CN. A suspension was obtained. 12.61g of CH3Br 50percentw/w -CH3CN solution- (0.066 mol) were loaded.[0113] The suspension was left under stirring at 22°C for 64 hours. Theproduct was filtered and washed with 2mL of CH3CN. [0114] 6.93g of wet Tiotropium were obtained, and dried undervacuum at 45°C for 22h (residual pressure 4 mbar) . 5.9 g of dry product (purity 99.8percent, dithienylglycolic acid-notdetected) were obtained.in acetonitrile, Time= 12 - 64h, T= 22 °C , Product distribution / selectivityPatent; SICOR INC.; WO2007/75838; (2007); (A2) EnglishView in ReaxysPreparation of anhydrous tiotropium bromide from scopine di-(2-thienyl)glycolateScopine di-(2-thienyl)glycolate (1 eq)was dissolved in acetone (35 vol) at 25-30°C and methyl bromide in acetonitrile (50percent w/w solution, 5 vol) wasadded. The mixture was stirred at 25-3O0C for 24 hours and the precipitated solid was filtered and washed with acetone(5 vol). The solid was dried at 60°C under vacuum to afford the product as a white solid. The crude anhydrous tiotropiumbromide obtained was found to have the XRPD, DSC and TGA spectra shown in Figures 1, 2 and 3 respectively.Molaryield = 95percentHPLC purity = 99.5-99.7percentPurification of anhydrous tiotropium bromideCrude anhydrous tio-teopium bromide (1 eq) was taken in DMSO (2 vol) and stirred for 1 hour at 25-3O0C. Acetone (25 vol) was slowlyadded and the mixture was chilled to 0-5°C and stirred at 0-5°C for 30 minutes. The solid was filtered and washed withacetone (3 vol) and dried under vacuum at 600C for 12 hours. The purified anhydrous tiotropium bromide obtained wasfound to have the XRPD, DSC and TGA spectra shown in Figures 1, 2 and 3 respectively.Molar yield = 98percentHPLCpurity > 99.9percentThe crude and purified samples of anhydrous tiotropium bromide prepared in the above exampleswere found to be substantially pure polymorphically with no levels of other- forms detected (>99.7percent polymorph-ically pure, as measured by XRPD). The purified anhydrous tiotropium bromide prepared was also found to be verystable chemically and polymorphically with no conversion over time to other polymorphs. The stability of the samplewas tested by subjecting the sample to accelerated stability conditions (400C + 2°C temperature and 75percent +/-5percent relative humidity) for 6 months. The chemical purity (measured by related substances and purity assays byHPLC) and polymorphic purity (measured by XRPD, DSC and TGA) were monitored for 6 months and the sample wasfound to be chemically and polymorphically stable even after 6 months under accelerated stability conditions.TheXRPDs were recorded on a Bruker D8 Advance Diffractometer, using Cu Kαl radiation as the X-ray source and LynxEyeas the detector, with a 2ψ range of from 3° to 50°, a step-size of 0.05° and a time/step of lsec.The DSCs were recordedon a Perkin Elmer Pyris 6 Instrument over a temperature range of from 250C to 25O0C at a rate of heating of 10°C/min.The TGAs were recorded on a Perkin Elmer Pyris 1 Instrument over a temperature range of from 250C to 250°C at arate of heating of 10°C/min.in acetone, acetonitrile, Time= 24h, T= 25 - 30 °CPatent; GENERICS [UK] LIMITED; MYLAN INDIA PRIVATE LIMITED; GORE, Vinayak Govind; MANOJKUMAR,Bindu; SHINDE, Dattatraya; KOKANE, Dattatrey; WO2011/15882; (2011); (A2) EnglishView in Reaxys2.65 g2:Example 22.0 g of scopine di(2-thienyl)glycolate (5.3 mmol) was dissolved in 20 ml of a mixture of dichloromethane (8 ml) andacetonitrile (12 ml) at 55°C. The solution was cooled down to 33°C and 5.46 g of 55percent MeBr in acetonitrile (5.1equivalents) was added. The solution was stirred and left to cool freely without stirring still for 48 hours. The formedcrystalline product was filtered, washed with 30 ml of dichloromethane, and dried in a vacuum oven at 35°C for 6 hours.2.65 g of white crystals were obtained,HPLC purity 99.60percent. The content of solvents (determined by GC): di-chloromethane 69,000 ppm, acetonitrile 8,200 ppm.in dichloromethane, acetonitrile, Time= 48h, T= 20 °C , Concentration, TimePatent; ZENTIVA K.S.; CERNA, Igor; RIDVAN, Ludek; KRAL, Vladimir; HAJICEK, Josef; DAMMER, Ondrej;WO2013/79040; (2013); (A1) EnglishView in Reaxys30.8 g3:Example 3 (Reference example according to the method of patent EP0418716)23.6 g of the scopine ester I (39.7 mmol) was dissolved in 230 ml of a mixture of dry dichloromethane (90 ml) and dryacetonitrile (140 ml) at 55°C, then the solution was cooled to 33°C and 54.0 g of 55percent MeBr in dry acetonitrile (5.0equivalents) were added. The solution was left to cool freely and then it was stirred at the room temperature for 19hours. The resulting crystalline product was filtered, washed with 900 ml of dichloromethane and dried in a vacuumdrier (5 kPa) at 35°C for 17 hours. 30.8 g of white crystals were obtained, HPLC purity 99.74percent. The content ofsolvents (measured with gas chromatography): dichloromethane 67000 ppm, acetonitrile 4300 ppm.in dichloromethane, acetonitrile, Time= 19h, T= 20 - 33 °CPatent; ZENTIVA, K.S.; CERNA, Igor; HAJICEK Josef; WO2013/135219; (2013); (A1) EnglishView in Reaxys30.8 g7; 9:Quaternization of the scopine ester I with methyl bromideExample 9 (Reference example reproducing the method of patent EP0418716) 23.6 g of the scopine ester I (39.7 mmol)was dissolved in 230 ml of a mixture of dry dichloromethane (90 ml) and dry acetonitrile (140 ml) at 55°C, then thesolution was cooled to 33°C and 54.0 g of 55percent MeBr in dry acetonitrile (5.0 equivalents) were added. The solutionwas left to cool down freely, and subsequently stirred at the room temperature for 19 hours. The resulting crystallineproduct was filtered, washed with 900 ml of dichloromethane and dried in a vacuum drier (5 kPa) at 35 °C for 17 hours.30.8 g of white crystals were obtained, UPLC purity 99.74percent. Solvent content (determined by gas chromatogra-phy): dichloromethane 67000 ppm, acetonitrile 4300 ppm.in dichloromethane, acetonitrile, Time= 19h, T= 20 - 33 °CPatent; ZENTIVA, K.S.; CERNA, Igor; HAJICEK, Josef; WO2013/143510; (2013); (A1) EnglishView in Reaxys15.51 g3:Preparation of Tiotropium Bromide (1) in NMPExample 3Preparation of Tiotropium Bromide (1) in NMPTo a solution of 13.2 g (39.1 mmol) desmethyl-tiotropium (4) in 30 mL NMP, 16.5 mL (115 mmol, 2.93 eq.) of a 1:1 (w/w) solution of methyl bromide in NMP were added.The mixture was stirred overnight at room temperature, whereupon a dense suspension formed.After addition of 20 mL acetonitrile, the suspension was filtered, washed with 20 mL acetonitrile, and dried with highvacuum overnight at 30° C., yielding 15.51 g of off-white powder.Residual solvents were detected by GC analysis.The XRPD pattern complied with the one shown in .1H-NMR (300 MHz, d-DMSO): 7.52 (dd, J=5.0 Hz, 1.1, 2H), 7.41 (s, 1H), 7.13 (dd, J=3.6, 1.1 Hz, 2H), 7.01 (dd, J=5.0,63.7 Hz, 2H), 5.12 (t, J=5.8 Hz, 1H),4.13 (bd, J=5.8 Hz, 2H), 3.50 (s, 2H), 3.25 (s, 3H), 3.05 (s, 3H), 2.8-2.6 (m, 2H),1.93 (s, 1H), 1.87 (s, 1H).13C-NMR (75.5 MHz, d-DMSO): 170.2, 147.1, 127.3, 126.7, 126.3, 76.8, 65.0, 64.2, 56.5, 54.1, 47.6, 28.7.6in 1-methyl-pyrrolidin-2-one, T= 20 °CPatent; CERBIOS-PHARMA SA; MEREU, Andrea; MOROSOLI, Moreno; PENNE', Umberto; PERSEGHINI,Mauro; US2014/303373; (2014); (A1) EnglishView in Reaxys(37.5 mmol) scopine methobromide are added and a solution of 2.59 g (38 mmol) imidazole and 1.52 g (38 mmol)sodium hydride (60percent) in 30 ml dimethylacetamide is added dropwise at 20° C. and the mixture is stirred for 1 hat 20° C. After cooling to -4° C. 50 ml of a 33percent solution of hydrogen bromide in glacial acetic acid are addeddropwise while the temperature does not exceed 20° C. Then 50 ml methanol are added and the mixture is stirred for3 h at 20° C. The reaction mixture is extracted with 500 ml toluene and, after separation of the toluene phase, crystallisedfrom 150 ml isopropanol at 0° C. The crude product is filtered off, washed with 30 ml cold isopropanol and dried invacuo. Yield 14.1 g (80percent, based on scopine methobromide).Stage 1:With chloro-trimethyl-silane, 1,1'-carbonyldiimidazole in isobutyramide, Time= 0.5h, T= 20 °CStage 2:With 1H-imidazole, sodium hydride in isobutyramide, Time= 1h, T= 20 °CStage 3:With methanol, hydrogen bromide in isobutyramide, acetic acid, Time= 3h, T= -4 - 20 °C , Product distribution /selectivityPatent; Boehringer Ingelheim Pharma GmbH and Co., KG; US2006/47120; (2006); (A1) EnglishView in Reaxys48 %9:17.9 g (165 mmol) chlorotrimethylsilane are added dropwise at 0° C. to a solution of 39.3 g (150 mmol) sodiumdithienylglycolate in 117 ml tetrahydrofuran. After 60 min stirring at 10-20° C. the mixture is cooled to 0° C. and a solutionof 24.3 g (150 mmol) carbonyldiimidazole in 105 ml dimethylformamide is added dropwise. After a further 30 min stirring30.3 g (121 mmol) scopine methobromide are added and the mixture is stirred for a further 60 min at 10-20° C. It iscooled to 10° C. and a solution of 16.8 g (150 mmol) potassium tert. butoxide in 90 ml tetrahydrofuran is added dropwiseat 10-20° C. and the mixture is stirred for 60 min at 20° C. After cooling to 0° C. 60 ml 62percent hydrobromic acid areadded dropwise while the temperature does not exceed 20° C. After 40 min stirring the reaction mixture is stirred into1150 ml isopropanol at 20° C. and cooled to 10° C. The crude product is filtered off, washed with 70 ml cold isopropanoland dried in vacuo. Yield 61.5 g reddish-brown crystals, TLC corresponds to comparison. The crude product is dissolvedin 615 ml methanol with 6.15 g activated charcoal at reflux temperature and filtered. Then 570 ml methanol are distilledoff and the solution is cooled to 10° C. The crystals are filtered off, washed with 35 ml cold methanol and dried. Yield40.9 g whitish-beige crystals, TLC corresponds to comparison. The crystals thus obtained are dissolved in 94 ml waterwith 2.2 g activated charcoal at 80° C. and filtered, and then washed with 24 ml water. After cooling to 15° C. thetiotropium bromide monohydrate which has crystallised out is filtered off, washed with 25 ml water and 35 ml acetoneand dried. Yield 28.6 g (48percent based on the scopine methobromide used).Stage 1:With chloro-trimethyl-silane, 1,1'-carbonyldiimidazole in tetrahydrofuran, DMF (N,N-dimethyl-formamide),Time= 1.5h, T= 0 - 20 °CStage 2:in tetrahydrofuran, DMF (N,N-dimethyl-formamide), Time= 1h, T= 10 - 20 °CStage 3:With potassium tert-butylate, hydrogen bromide, Product distribution / selectivity, more than 3 stagesPatent; Boehringer Ingelheim Pharma GmbH and Co., KG; US2006/47120; (2006); (A1) EnglishView in Reaxys48 %8:5.43 g (50 mmol) chlorotrimethylsilane are added dropwise at 20-30° C. to a solution of 13.1 g (50 mmol) sodiumdithienylglycolate in 25 ml tetrahydrofuran. After 60 min stirring 8.1 g (50 mmol) carbonyldiimidazole and after another30 min 10.01 g (40 mmol) scopine methobromide are added and the mixture is stirred for a further 30 min. Then asolution of 2.60 g (38 mmol) imidazole and 1.65 g (38 mmol) sodium hydride (55percent) in 25 ml dimethylformamideis added dropwise at 20° C. and the mixture is stirred for 1 h at 20° C. After cooling to 0° C. 20 ml 62percent hydrobromicacid are added dropwise while the temperature does not exceed 20° C. After 40 min stirring the reaction mixture isstirred into 350 ml isopropanol at 20° C. and cooled to 10° C. The crude product is filtered off, washed with 50 ml coldisopropanol and dried in vacuo. Yield 18.9 g reddish-brown crystals, TLC corresponds to the comparison. The crudeproduct is dissolved in 100 ml methanol with 2.2 g activated charcoal at reflux temperature and filtered. Then the solutionis evaporated down to 30 ml and cooled to 3° C. The crystals are filtered off, washed with 5 ml cold methanol and dried.Yield 12.1 g whitish-beige crystals, TLC corresponds to the comparison. The crystals thus obtained are dissolved in28 ml water with 1.2 g activated charcoal at 80° C. and filtered. After cooling to 15° C. the tiotropium bromide mono-hydrate which has crystallised out is filtered off and dried. Yield 9.4 g (48percent based on the scopine methobromideused).Stage 1:With chloro-trimethyl-silane, 1,1'-carbonyldiimidazole in tetrahydrofuran, Time= 1.5h, T= 20 - 30 °CStage 2:With 1H-imidazole, sodium hydride in tetrahydrofuran, DMF (N,N-dimethyl-formamide), Time= 1.5h, T= 20°CStage 3:With hydrogen bromide in tetrahydrofuran, DMF (N,N-dimethyl-formamide), isopropyl alcohol, Time=0.666667h, T= 0 - 20 °C , Product distribution / selectivityPatent; Boehringer Ingelheim Pharma GmbH and Co., KG; US2006/47120; (2006); (A1) EnglishView in Reaxys。
蒋跃考博单词1
a b e r r a n t a.畸变的;异常的;脱离常轨的a b l a t e v.切除，摘除a b s t i n e n c e n．节制；禁欲a c h r o m a t o p s i a n．色盲a c n e n．痤疮，粉刺a c o u s t i c a．声学的；听觉的a d d u c e v．引证；提出a d m o n i s h v．告诫a e r ob ic a．需氧的a f eb r i l e a．无热的a f f e r e n t a．传人的a f f i n i t y n.亲和力；密切关系a g i l e a．敏捷的，灵活的a g i t a t e v．搅动；激动,焦急不安a g u e n．疟疾；寒颤a l m i g h t y a．全能的；糟糕透的a l v e o l u s n．小窝，牙槽；肺泡a mb i e n t a．周围的，包围着的；环境的a mb i g u o u s n．模棱两可的a mb u l a n t a．走动的；适宜于下床活动的a m e l i o r a t e v．改善，改良，转好a m e n ab l e a．顺从的，有义务的;经得起检验的a m i ab l e a．亲切的，和蔼可亲的a n a l o g u e n.类似物a n a l o g y n.类似，相似；比拟;类推a n e s t h e s i a n．感觉缺失；麻醉a n e s t h e t i c a．麻木的n．麻醉剂a n g u i s h n.极度的痛苦v．感到极度痛苦a n h y d r o u s a．脱水的，无水的a n i m a t e v．使有生气，使活泼；激励a n i m a t i o n n．生气，活泼，兴奋；动画片a n o r e x i a n．食欲缺失；厌食a n o x i a n．缺氧(症)a n t i f eb r i l e a．退热的n．退热药a p p a l l i n g a．令人震惊的，骇人听闻的a p p a r a t u s n．器械，仪器，装置a p p r e h e n d v．理解，领悟；逮捕，拘押；畏惧，忧虑a r d e n t a．热情的，热烈的；强烈的，烈性的a r r h y t h m i a n．心律不齐；心律失常a r t i c u l a t e v．接合；清晰地发出音来；a．接合起来的；关节联接的a s p h y x i a n．窒息a s p i r a t e v．吸出；抽出a s s a s s i n a t e v．暗杀，行刺a s s e s s v.估价，评价a s s e s s m e n t n.估价，评价a s s e t n.财产；宝贵的人(或物)a s s i d u i t y n.刻苦，勤奋a s s i g n m e n t n.分配，委派，任务，(课外)作业a s s i m i l a t e v.吸收；同化a s t h m a n．气喘，哮喘a s t o n i s h v．使惊讶，使吃惊a s t o u n d v．使震惊，使大吃一惊a t r i u m n．心房a t r o p i n e n．萎缩，虚脱a t t e n u a t e v．变细(小)；减弱减毒;稀释a u s c u l t a t e v.听诊a u s p i c e n.预兆，先(前)兆;吉兆a u t h o r i t a r i a n a．独裁主义的n．独裁主义者a u t o c l a v e n．高压消毒锅a u x i l i a r y a.辅助的,从属的n.辅助者,补助者,助动词a v a i l v.有利,有益,有助a v a i l ab i l i t y n.可用性,有效性,可得性,可得到的人(或物)a v e r t v.转移，防止a x i l l a n.腋(窝)b a f f l e v．使挫折，阻碍，使困惑n．迷惑；缓冲板；遮护物b a l m n．香油，香脂；止痛药膏b a n k r u p tc y n．破产b a r b i t u r a t e n．巴比妥盐b a tc h n．一批，一炉b a t o n n．棍棒；指挥棒；警棍b a t t a l i o n n．营；部队；大队(的人)b a t t e r y n．电池(组)；一套，一组b e a k n．(鸟的)嘴；(器皿的)鸟嘴形口b e l l y-b u t t o n n．脐b e r i b e r i n．脚气病b e s e t v．镶嵌；困扰b ic a r b o n a t e n．碳酸氢盐b i l i a r y a.胆汁的b i z a r r e a．稀奇古怪的，异乎寻常的b l a nc h v．漂白；使变白；使(植物)不见日光而变白b l e ac h v.漂白n.漂白剂b l u n d e r n．大错v．犯大错；慌乱地走b l u r v．弄脏；(使)模糊不清b o m b a r d v．炮击；轰炸；攻击,痛斥b o n d n．结合；契约；债券b o n d a g e n．奴役，束缚b o t a n ic a l a．植物学的，植物的b o u t n．一回；发作b r e ac h n.破坏；破裂b r e a t h t a k i n g a．惊人的，激动人心的b r o nc h i t i s n．支气管炎b r o nc h u s n．支气管b r o t h n．肉汤b r u t a l a．残忍的，令人难受的b uc c a l a．颊的；口腔的b u l g e n．v．肿胀；膨出；隆起(物)b u m b l e v．犯大错；结巴地讲话；踉跄b u o y n．浮标，救生圈b u r g l a r n．窃贼c a l a m i t y n．灾害,祸患,不幸事件c a l l o u s a．起老茧的;无感觉的;冷淡的c a l l u s n．胼胝；骨痂，接骨质c a n c e l l o u s a．网眼状的；海绵状的；网状骨质的c a nd i d a．公正的,正直的；坦率的c a n i n e n．犬齿c a n k e r n．溃疡；口疮c a n n u l a n．套管，插管c a p t i o n n．(章节，文章等)标题；(图片的)解说词；(电影片)字幕c a rd i n a l a．主要的，基本的；深红的c a r i e s n．龋；骨疡；骨疽c a r t i l a g e n．软骨c a r t r id ge n．弹药筒；子弹；软片，胶卷c a s u a l t y n．严重伤亡事故;伤亡人员c a t a l y s t n.催化剂c a t a s t r o p h e n.大灾难，大变动c a t e r v．迎合，投合；供应伙食(f o r)c a t h e t e r n．导管C a t h o l i c a．天主教的n．天主教徒c a u s t i c a．腐蚀性的；n．腐蚀剂c e l e r i t y n．迅速,敏捷c e l e r y n．芹菜c e l i a c a．腹的；腹腔的c e l l u l o s e n．纤维素c e p h a l i c a.头的，头部的；头侧的c e r e b e l l u m n.小脑c e r e b r u m n．大脑c h a r v．／n．打杂，(做)家庭杂务c h l o r ide n．氯化物c h l o r i n e n．氯(气)c h l o r o p h y l n．叶绿素c h o l e r a n．霍乱c h o l e s t e r o l n．胆固醇c h r o n i c l e n．编年史；历史，记事c i l i a n．睫；纤毛c i n e r a r y a．灰的；骨灰的c i r c ad i a n a．生理节奏的c i r c u m s c r i b e v．在…周围划线；限制，约束c i r c u s n．马戏场，杂技场；马戏团c i r r h o s i s n．硬变；肝硬化c i t r u s n．柠檬；柑橘c l a m o(u)r v．n．吵闹，叫喊c l a s p n．扣子，钩子v．扣住;紧握，紧抱c l a v i c l e n．锁骨c l e a v a g e n．劈开；分裂；卵裂c l e a v e v．(c l a v e；c l e a v e d)粘着,粘住；坚持；依恋c l e a v e v．(c l e f t；c l e f t o r c l o v e n)劈开;把…分成几个小部分c l i m a c t e r i c n．更年期；绝经期；转折点c l u m s y a．笨拙的，愚笨的n．串，簇，束c l u t c h v．抓住，攫住c o a g u l a t e v．凝结，凝固c o l i c n．绞痛,急腹痛a.绞痛的;结肠的c o l i t i s n．结肠炎c o l l ide v．碰撞，冲突，抵触c o l l o c a t i o n n．排列；搭配；配置c o l l o id n．／a．胶体(的)，胶质(的)c o l l o q u i a l a．口语的，会话的c o l o n e l n．(陆军)上校c o l o s s a l n．巨像的，巨大c o m b u s t i o n n．燃烧；氧化c o m e t n．慧星c o m m e n c e v．开始c o m m e n c e m e n t n．开始；学位授予典礼(日);毕业典礼(日)c o m m e n t n．／v．解说，评论，意见c o m p a c t a．紧密的，坚实的v．压缩c o m p a r t m e n t n．分隔；空间；隔室c o m p a s s n．罗盘，指南针c o m p a s s i o n n．同情；怜悯c o m p a t i b l e a．相容的；一致的c o m p a t r i o t n．同胞c o m p i l e v．编辑，编制；搜集，汇编c o m p l a c e n c e n．自满，自鸣得意c o m p l e x i o n n．肤色；情况，局面；气质，性格c o m p r o m i s e v．／n．妥协，折衷c o m p u l s i v e a．强迫的，有强迫力的c o n c e i t n．自负,自高自大;想法,个人的意见c o n c e i v e v．设想,构想;以为;怀胎,怀有c o n c e s s i o n n．迁就，让步；特许；特许权；租界c o n c o m i t a n t a．伴随的；伴发的c o n c o rd n．和谐；协调c o nd u c i ve a．有助于…的，有益的c o nd u i t n．管道；导管c o n g e n i t a l a．先天的，天生的c o n g e s t v．充满；拥挤；充血c o n j e c t u r e v．推测；假设c o n j o i n v．结合，连接c o n j u g a t e n．结合，使成对c o n j u n c t i v a n．结膜c o n j u n c t u r e n．结合；紧要关头c o n s c i e n c e n．良心，良知c o n s c i e n t i o u s a．认真的；诚心诚意的；谨慎的c o n s c i o u s a．有意识的，知觉的c o n s e c u t i v e a．连续的，连贯的；顺序的c o n s e n s u s n．一致；舆论；同感，交感c o n s e n t v．／n．同意，答应c o n s e q u e n c e n．后果，影响；重要性c o n s e q u e n t a．作为结果的，随后发生的n．当然的结果，推论c o n s e r v a t i o n n．保存，保护；守恒c o n s e r v e v．保存，保藏；保养c o n s ide r a t e a．考虑周到的，体谅的c o n s ide r a t i o n n．考虑，思考；体谅c o n s i s t e n t a．前后一致的，始终如一的c o n s o l e v．安慰，慰问c o n s o l id a te v．巩固，加强；合并，联合c o n s o n a n c e n．调和，一致；共鸣．c o n s p i c u o u s a．明显的；惹人注目的c o n s t i p a t i o n n．便秘c o n s t i t u e n t a．形成的，组成的n．选民；成分c o n s t i t u t e v．组成，构成c o n s t i t u t i o n n．构成，机构,成分,体格,体质；宪法c o n s t r a i n t n．强逼，强制；紧张感，紧张状态c o n s t r i c t v．压缩，收缩；阻塞c o n s u l t v．商量，咨询；会诊c o n s u l t a n t n．请教者；商议者；顾问,会诊医生c o n s u m e v．消费，消耗c o n s u m p t i o n n．消费，消耗；肺结核；结核c o n t a c t v.／n．接触，联系，交往c o n t a g i o u s a.传染的c o n t a i n v.容纳,含有，装有c o n t a i n e r n.容器,集装箱c o n t a m i n a t e v.弄脏,污染；传染c o n t a m i n a t i o n n.污染,沾染物c o n t e m p l a t e v.注视,沉思；期待,仔细考虑c o n t e m p o r a r y a．现代的，当代的n.同时代的人，同年龄的人c o n t e m p t n．轻蔑，藐视；受辱,丢脸c o n t e nd v．竞争，斗争；争论c o n t e n t n．内容，目录；容量，含量n．／a．满足(的)，甘愿(的)c o n t e s t v．竞赛，比赛；争夺c o n t e x t n．上下文，前后关系c o n t i n e n c e n．自制，节制；节欲c o n t i n e n t n．大陆，洲c o n t i n g e n t a．可能(发生)的，偶然的，意外的；应急的n．意外事件；代表团；小分队c o n t o u r n．轮廓，外形c o n t r a c e p t i v e a．避孕的n．避孕药物／用具c o n t r a c t n．契约，合同，包工v．收缩；得(病)c o n t r a c t i l e a．可收缩的c o n t r a c t o r n．订约人；承包人；收缩肌c o n t r ad i c t v．反驳；同…矛盾，同…抵触c o n t r ad i c t i o n v．矛盾；反驳c o n t r a i nd i c a te v．禁忌c o n t r a l a t e r a l a．对侧的c o n t r a s t v.对照,对比v.形成对比,使对照c o n t r o v e r s i a l a．争论的；爱争论的；引起争论的c o n t r o v e r s y n．争论，论战；争吵c o n v a l e s c e n t a．恢复健康的，渐愈的；恢复期的n．恢复中的病人c o n v e n i e n c e n．便利，方便；(p l.)便利设备c o n v e n i e n t a．便利的，方便的c o n v e n t i o n n．大会，会议；习俗，惯例；公约，协定c o n v e n t i o n a l a．惯例的，常规的,传统的;协定的c o n v e r g e v．会聚，集中c o n v e r s a t i o n n．会话，谈话c o n v e y v．运送，运输；传达，传播c o n v i c t i o n n．定罪；深信，确信c o n v i n c e v．使信服，使确信c o n v u l s i o n n．震动；痉挛，惊厥c o o p e r n．制桶工人，修桶工人v.修桶；挫败；毁掉c o o rd i n a te a．同等的，对等的，并列的v．使成为同等；使协调c o o r d i n a t i o n n．同等，调整；协作；协调c o p e v．应付，对付c o p i o u s a．丰富的，大量的c o p y r i g h t n．版权，著作权c o rd n．绳，索；索状组织c o rd i a l a．诚恳的，亲切的，热诚的;刺激的；强心的n.兴奋剂c o r k n．软木塞c o r n e a n．角膜c o r o n a r y a．冠状的c o r p o r a t e a．社团的；共同的；全体的c o r p o r a t i o n n．团体，公司c o r p s n．军团，部队c o r p s e n．死尸，尸体c o r p u s c l e n．小体，细胞，血球；微粒c o r r id o r n．走廊c o r r o s i o n n．腐蚀，侵蚀；锈c o r r u p t a．腐化的，贪污的v．腐蚀；贿赂c o r t e x n．皮质c o s m e t i c n．化妆品a．化妆用的，美容的c o s m i c a．宇宙的，广大无边的c o s m o s n．宇宙；秩序，和谐c o s t a l a.肋骨的c o s t u m e n.服装，戏装c o t t a g e n.村舍，别墅c o u n c i l n．理事会，委员会，议事机构c o u n s e l n．商议；忠告；法律顾问，辩护人v．劝告，忠告c o u n t e n a n c e a．面部表情；脸色c o u n t y n；郡，县c o u r t e o u s a．有礼貌的c o u r t e s y n．礼貌；殷勤；好意c o u s i n n．堂(表)兄弟，堂(表)姐妹c o v e r t a．隐藏的；暗地里的c o w a rd n．懦夫c o z y n．暖和舒服的；舒适的c r a c k n．裂纹，龟裂v．破裂，砸开；发爆炸声c r ad le n．摇篮；婴儿时期c r a m p n．夹，钳；(病性)痉挛，绞痛c r a n e n．鹤；起重机v．伸(颈)；用起重机起吊c r a n i u m v．头盖(骨)；颅c r a v e v．渴望，热望76c r ed u l o u s a．轻信的c r e ed n．信条；信念,纲领c r i p p l e n．跛子；残废的人(或动物)c r i s i s n．危机c r i s p a．松脆的；清新的，爽快的；干脆的v．使发脆c r i t e r i o n n．标准，准则c r i t i c i s m n．批评；评论c r i t i c i z e v．批评；评论c r o o k n．钩；钩状物c r o o k ed a.弯的，歪的；扭曲的,不正当的c r o w n n．王冠；牙冠c r u c i a l a．决定性的，紧要关头的；严酷的，极困难的c r u e l a．残酷的，残忍的c r u e l t y n．残酷，残忍；残酷行为c r u i s e v．巡航；巡游；(出租汽车)兜客n．巡航，巡游c r u m b n．碎屑；面包屑；点，滴，少许v．弄碎c r u m p l e v．把…弄皱；打垮c r u s t n．面包皮；外壳;痂皮c r u t c h n．拐杖；支柱v.支撑c r u x a．十字形；难事,关键,最重要点c r o t h e r a p y n．冷冻疗法c u c k o o n．杜鹃，布谷鸟c u c u m b e r n．黄瓜c u e n．(人或车等候着的)长队；发辫c u f f n．袖口；护腕c u l t i v a t e v.耕作，栽培，养殖；培养c u l t u r a l a．文化的；教养的；栽培的c u n n i n g a．／n．狡猾(的)，狡诈(的)c u p b o a rd n．碗柜，木橱c u r b n．／v.控制、抑制、约束c u r i o s i t y n．好奇心；珍品；古玩c u r l v.卷曲，蜷缩n．卷发c u r r i c u l u m n．学校的全部课程；(一门)课程c u r s e v．诅咒,咒骂c u r t a i n n．窗帘,幕(布)c u r v e v．弄弯,使成曲线n.曲线，弯曲c u s h i o n n．垫子，坐垫c u s p n．尖，尖端c u s t o m a r y a．通常的，常例的，习惯的c u t a n e o u s a．皮的c u t e a．伶俐的，逗人爱的c y l i nde r n．圆柱体，圆筒；气缸c y s t n．囊(肿)c y t o g e n e t i c s n．细胞遗传学c y t o l o g y n．细胞学d a g ge r n．匕首；短剑；剑号d a i r y n.牛奶场，奶店d a m n n.／v．诅咒d a n de r n.头皮屑；怒火d a n d r u f f n.头垢；头皮屑d a n g le v.摇晃地悬挂着d a t u m n.(p1．)资料，材料d e b r i s n.瓦砾堆，废墟,碎片d e c a y v.／n．腐朽，腐烂，衰败d e c e i t n.欺骗；虚假；欺骗行为d e c e i v e v.欺骗，蒙蔽d e c e n t a.体面的，像样的,相当好的;正派的，得体的d e c e p t i o n n．欺骗，蒙蔽；骗术d e c i b e l n．分贝d e c i l i t e r(d e c i l i t r e)n．分升，十分之一升d e c i m a l a．小数的，十进制的d e c k n．甲板；桥面；层面d e c o l o u r i z e v．使…脱色；将…漂白d e c o m p e n s a t e v．代偿失调d e c o m p o s e v．分解，使腐败，使腐烂d e c o r a t e v.装饰，装潢，布置d e c u b i t u s n.褥疮d e d i c a t e v.奉献，献身,致力d e d u c e v.演绎，推演,推断d e d u c t i o n n.推论；演绎,扣除d e e m v.认为，相信d e f e a t v．／n．战胜，挫败d e f e c a t e v．澄清，净化；排粪，通大便d e f e c t n．缺点，缺陷d e f e n c e n．防御，保卫；(p l．)防务，工事d e f e n d v．保卫，防守；辩护；答辩d e f e n s e n．防御，保卫；防务(p l．)防御工事；辩护d e f e n s i v e a．防御的，保卫的n.防御,守势d e f e r e n c e n．听从；敬重d e f e r e n t a.输送的;输出的;输精的d e f e r v e s c e n c e n.退热d e f i c i e n c y n.缺乏，不足；营养缺乏症d e f i c i t n.短缺；赤字d e f i n i t e a.明确的，确定的，限定的d e f i n i t i o n n.定义，解释；明确性d e f l a t e v.排放…(空)气；解除气胀d e f l e c t i o n n.偏离；偏转d e f o r m v.损坏…的形状，使…变形d e f o r m a t i o n n．形状损坏；变形；畸形d e f o r m i t y n．变形，畸形；畸形的人d e f y v．向…挑战；公然对抗，蔑视d e g e n e r a t e v．蜕化；变质；变性d e g r a d a t i o n n．降级；低落；退化；陵削；降解；衰变d e g r e s s i o n n．下降；递减d e h y d r a t i o n n．脱水d e l e g a t e n．代表d e l e t e r i o u s a．(对身心)有害的；有毒的d e l i b e r a t e a．深思熟虑的，审慎的，蓄意的v．仔细考虑d e l i b e r a t e l y a d．审慎地；故意地，蓄意地d e l i c a t e a．纤弱的，娇嫩的；易碎的；优美的，精美的，精致的d e l i n e a t e v．描绘；叙述d e l i t e s c e n c e n．潜伏期；潜伏状态；(炎症)突然消退d e l u s i o n n．幻想；妄想；错觉d e m e n t i a n．痴呆d e m o c r a c y n．民主；民主政体d e m o c r a t i c a．民主的，民主主义的;民主政体的d e m o g r a p h y n.人口统计学d e m o n s t r a t e v.表明；演示；论证，证明d e m o n s t r a t i o n n.表明，示范；论证；示威d e n i a l n.否认，拒绝；拒绝相信d e n o m i n a t e v.给…命名；称呼…为d e n o t e v.指示；意味着d e n o u n c e v.斥责；告发，揭发；废除d e n s e a.密的，稠密的，浓厚的d e n s i t y n.密度，密集；稠密d e n t a l a.牙齿的；牙科的d e n t i s t r y n.牙科学d e n t u r e n.一副牙齿；假牙；全口假牙d e o d o r a n t a.除臭的n．除臭剂d e p a r t v.出发，离开d e p a r t u r e n.出发，离开d e p e n d a n t n.受赡养者；侍从d e p i c t v.描绘，描述d e p i c t u r e v.描述，描绘；想象d e p i l a t e v.拔去…毛；脱去…毛d e p l e t e v．弄空；排除，减轻；减少…体液；放去…的血d e p o s i t v．存放，寄存；储蓄；沉淀n．存款；押金；沉淀d e p o s i t i o n n．免职，罢官；作证；沉淀；沉淀物d e p o t n．兵站；仓库d e p r a v i t y n．堕落；腐败d e p r e c i a t i o n n.价值低落,贬值,蔑视,贬低d e p r e s s v.压抑，降低d e p r e s s i o n n.消沉；萧条；抑郁症d e p r i v e v.夺去，剥夺，使丧失d e p u r a t e v．净化，提纯d e p u t y n．代理人，代表；副…d e r i v a t i o n n．引出；起源，由来;衍生,衍生物d e r i v e v.取得;派生出;引申出d e r m a n.真皮d e r m a t i t i s n.皮炎d e r m a t o l o g y n.皮肤病学d e c e n d a n t n.子孙，后代d e s e r v e v．应受，值得d e s i g n a t e v．指明，标示；选派，指定；把…叫做d e s i r a b l e a．合乎需要的，令人满意的d e s o l a t e a．荒凉的，荒芜的；孤独的，凄凉的v．使荒芜，使孤寂d e s p a i r v．／n．失望，绝望d e s p e r a t e a．绝望的，危急的；不顾一切的，铤而走险的d e s p i s e v．轻视，蔑视d e s t i n a t i o n n．目的地；目标d e s t i n e v．命定，注定，预定，指定d e s t i n y n．命运d e s t i t u t e a．没有的；缺乏的d e s t r u c t i o n n．破坏，毁灭d e s t r u c t i v e a．破坏性的，毁灭性的，危害的d e t a c h v．分开，分离，拆开；分遣d e t a c h m e n t n．分开，拆开，分离；分遣；分遣队d e t e c t v．察觉，发现；探测d e t e c t i o n n．察觉，发现；探测;检波d e t e c t i v e a．侦探的，探测的n．侦探d e t e n t i o n n.拘留，扣押；阻留，滞留d e t e r g e n t a.使清洁的n．清洁剂；去垢剂d e t e r i o r a t e v.恶化；变坏；退化d e t e r m i n a t i o n n．决心，决定d e t e r m i n e v．决定，决心；确定,测定d e t o x i f y v．解毒，除去…毒物,去除…放射性沾染d e v a l u e v．降低价值；贬值d e v i a t i o n n.背离，偏离d e v i c e n.设备，装置；方法，设计d e v i l n.魔鬼d e v i s e v.设计，想出d e v o i d v.缺乏，没有d e v o t i o n n.献身；忠诚；热爱d e v o u r v．吞没；狼吞虎咽地吃d e w n．露水，露d e x t r a l a．右边的；用右手的；右旋的d i a be t e s n．糖尿病d i a g r a m n．图解，图表d i a l n．标度盘，钟面，拨号盘v．拨号，打电话d i a le c t n．方言；行话d i a le c t i c a l a．辩证的；辩证法的d i a l y s i s n．透析，渗析；分离,分解d i a pe r n．尿布d i a p h o re s i s n．发汗；出汗d i a p h r a g m n．膈，膈膜d i a r r he a n．腹泻d i a s t o le n．(心)舒张期d i c t a te v.听写，口授，口述d i c t a t i o n n.口授笔录，听写d i c t i o n n.措词；词令d i f f u se v.扩散；渗出d i ge s t v.消化n．摘要d i g i t a l a.数字的d i g n i t y n.尊贵，高贵，庄严，尊严d i l a te v.膨胀，扩大d i le m m a n.窘境，进退两难d i l i ge n c e n.勤奋，努力d i l i ge n t a.勤奋的，孜孜不倦的d i l u te v.冲淡；稀释d i m a.暗淡的，模糊的，朦胧的v.(使)变暗淡d i me n s i o n n.尺寸；面积；容积d i me n s i o n a l a.尺寸的，…维的d i m i n i s h v.缩小，减少，递减d i ne v.吃饭，进餐d i o x i de n.二氧化碳d i p v./n.蘸,浸d i p h t he r i a n．白喉d i p l o m a n．文凭，证书d i p l o m a t i c a．外交上的；有策略的d i re c t o r y n．姓名地址录；(美)董事会a．指导(性)的d i s a p p o i n t v．令失望，使扫兴d i s a s te r n．灾害，灾祸，灾难d i s a s t r o u s a．灾难性的；造成惨重损失的d i s c n．圆盘，盘状物；唱片v．把…灌成唱片d i s c a r d v．丢弃；遗弃；垫牌n．抛弃，被弃的物(或人)；垫牌d i s ce r n v．看出；辨出；觉察，了解；辨别d i s c h a r ge v．／n．卸货；排出；释放;出院d i s c i p l i ne n．纪律；训练；学科v.训练；惩诫d i s c l o se v．揭开，泄露d i s c o n ne c t v．分离，断开；拆开d i s c o n te n t n．不满意，不满的人a.不满的v．令(人)不满d i s c o u n t n．／v．折扣d i s c o u r se n．讲话，演讲；论说；论文d i s c re p a n c y n.差异；不一致，不符合d i s c re t e a.分离的；稀疏的d i s c r i m i n a te v.区别，辨别，有差别地对待d i s c r i m i n a t i o n n.辨别，区别；识别力，辨别力；不公平待遇，歧视d i s d a i n v.n．轻视；不屑一顾d i s g o r ge v.吐出，呕吐d i s g r a ce n．失宠；耻辱；丢脸v．玷污；使丢脸d i s g u i se n．／v．假装，伪装d i s g u s t n．恶心，厌恶v．使恶心，使厌恶d i s i n ce n t i v e a．阻止的，抑制的n．(在生产等方面)起抑制作用的行动(或措施) d i s i nf e c t v．杀菌，消毒d i s i n te g r a t e v．崩溃，分裂；分解；蜕变；衰变d i s l o c a t i o n n．关节脱位，脱臼d i s m a l a．忧郁的d i s m a y n．灰心惊愕，沮丧v.使惊愕，使沮丧；使灰心d i s p a t c h v．派遣，发送；调度，调遣n.急件，快信d i s pe n s a r y n.药房d i s pe n s e v.分配；配(方)；发(药)d i s pe r s e v．使疏开；使分散，解散；散布，传播a．分散的，弥散的d i s p o s a b le a．可处理的；可随意使用的；用一次就丢掉的d i s p o s a l n．配置，布置；处理，处置；卖掉，让与；控制d i s p u te v．争论，辩驳n．争论，争端d i s r u p t v．分裂；破坏d i s se c t v．分割；解剖d i s se m i n a t e v.散播,传播,散布d i s se r t v.论述,写论文d i s se r t a t i o n n．专题论述；(学位)论文d i s s i p a te v．驱散；浪费，挥霍；放荡；酗酒d i s s o l ve v.溶解,融化;解除,解散,取消d i s s u a de v．劝阻，阻止d i s t a l a．远侧的；末梢的；远中的d i s te n d v．扩张；肿胀d i s t i l(l)v．蒸馏；滴下d i s t o r t v．歪曲，扭曲；变形d i s t r a c t v．分散，分心；弄昏，迷惑，使发狂d i s t r i c t n．区，地区，行政区d i s t u r b v．扰乱，妨碍；打扰，使不安d i t c h n．沟，渠，水沟d i ve v．／n．潜水；跳水；俯冲d i ve r n．跳水员，潜水员d i ve r g e v．分叉；分歧；离题；使…岔开，使转向d i ve r s e a．不一样的；多种多样的;多变化的；形形色色的d i ve r s i t y n．差异；多样性；变化d i ve r t v．转移；转向；转换d i v i ne a．神的，神圣的d i v i s i o n n．分，分裂；除法；部门d i v o r ce v．／n．离婚，离异；脱离，分离d i z z y a．眩晕的，头晕眼花的d o c k n．船坞，码头v．入坞，靠码头d o c t r i ne n．教义，主义，学说d o c u me n t n．文件，文献d o c u me n t a r y a．文件的n．纪录片d o l l n．玩偶，玩具娃娃d o m a i n n．范围，领域d o me s t i c a．家里的，家庭的；国内的，国产的；驯养的d o m i n a n t a．支配的，统治的；占优势的；显性的n．主因，要素，主要的人(或物)；显性基因d o m i n a te v．支配，统治；俯视；处于优势地位；高耸d o n a te v.捐献，赠送d o n ke y n．驴d o n o r v．捐赠者；供血(输血)者d o o m n．厄运；毁灭v．注定，命定d o r s u m n．背，背部；背状部分d o ve n．鸽子d o w n p o u r n．倾盆大雨d o ze v．打瞌睡；在瞌睡中度过n．瞌睡，打盹d r a f t n．草稿，草案，起草，草拟d r a i n n.排水管，导管；排(水)，排液；引流d r a i n a ge n．排水，排水法；排水设备(或系统)；流域；导液法；引流法d r a m a n．剧本；戏剧；戏剧艺术(或事业)d r a m a t i c a．戏剧的，戏剧性的；显著的d r a s t i c a．激烈的，严厉的n．剧泻药；剧药d r a u g h t n．拉，牵引，拖；一网（饮，吸，阵)；顿服药量，通风，v.起草，设计d r a w b a c k n．弊端，障碍；退款，退税d r a we r n.抽屉；拖曳者；制图员；开票人d re a d n./v．恐惧，害怕，担心d re a df u l a.可怕的；糟透的；令人敬畏的d re n c h v．浸透；淋透d r i f t v．／n．漂，漂流d r i l l v．／n．练习，操练，训练；钻孔，打孔d r i z z le v．下细雨d r o p le t n.小滴；飞沫d r o p o u t n.中途退出；退学d r o p s y n.水肿病(浮肿病)d r o u g h t n.旱灾，干旱d r o w n v.淹死，淹没d r o w s y a.昏昏欲睡的；催眠的d u a l a．双重的；二元的d ue a．应付的，到期的；应有的，充分的n．应得物，当然权利d u ke n．公爵d u l l a．愚笨的，迟钝的；阴暗的；沉闷的；单调的v．使迟钝，使阴暗，减轻d u m b a．哑的，无声的d u m p n．堆垃圾的地方；垃圾堆v.倾倒垃圾d u m p l i n g n．饺子d u o de n u m n．十二指肠d u p l i c a te n．复制品，副本,复制，复写d w a r f n.矮子,侏儒d y n a m i c a．动力的；能动的；机能上的；有生气的d y n a m i c a l=d y n a m i cd y n a m i c s n．力学，动力学,动力,原动力；动态d y n a s t y n．王朝；朝代d y se n t e r y n．痢疾d y s f u n c t i o n n．功能障碍,功能不良/死调d y s pe p s i a n．消化不良d y s p h a g i a n．吞咽困难d y s p l a s i a n．发育不良,发育异常d y s p ne a n．呼吸困难d y s t r o p h y n．营养不良,营养障碍e a g l e n．鹰E a s t e r n.复活节e b b n.v．落潮；退潮e c c e n t r i c a.古怪的，偏执的,不同圆心的e c l i p s e n.日蚀，月蚀v．把…遮暗e c o l o g i c a l a.生态的；生态学的e c o l o g y n.生态学e c s t a s y n.狂喜；出神，入迷e c t o p i c a.异位的e c z e m a n..湿疹e d e m a n．水肿(浮肿)e d i b l e a．可以吃的，食用的n．食品e d i t v．编辑，编纂e d i t i o n n．版，版本，版次e d i t o r n．编辑，编者e d i t o r i a l n．社论a．编辑的e f f e r e n t a．传出的e f f i c a c y n．功效；效验e f f i c i e n c y n.效率；功效，效能，实力e f f i c i e n t a．效率高的，有能力的e f f l u e n t a．发出的；流出的e f f o r t n．努力；努力的成果e f f u s i o n n．流出；渗出液E g y p t n.埃及E g y p t i a n a．埃及的；埃及人的n．埃及人；埃及语e j a c u l a t e v.突然喊出,射出(液体)e j e c t v.逐出;喷射;吐出,排出e l a b o r a t e a．详尽的，精心的，精巧的v．详细说明，用心做e l a p s e v．(时间)过去，消逝n．(时间的)过去，消逝e l a s t i c a．弹性的；有弹力的；灵活的；可伸缩的；易顺应的n．橡皮带，松紧带e l b o w n．肘，弯头，弯管v．用肘挤e l e c t r i c i a n n．电工；电学家e l e c t r i c i t y n．电，电流，电学e l e c t r if y v．使充电；使电气化;使触电；使震惊；使兴奋e l e c t r o l y t e n．电解质e l e c t r o m a g n e t i c a．电磁的e l e c t r o n i c s n．电子学e l e g a n t a．优雅的，优美的；精致的e l e v a t e v．提高，抬高，举起e l e v a t i o n n．高度；仰角；海拔;提高;高地e l i c i t v．得出，引出，诱出e l i g i b l e a．合格的；适宜的e l i m i n a t e v．排除，消除，消灭e l i m i n a t i o n n．排除，消除，消灭e l o n g a t e v．拉长；伸长；延长e l o q u e n c e n．雄辩，口才e l u c i d a t e v．阐明；说明，解释e m a c i a t e v．衰弱；消瘦e m a n c i p a t e v．解放e m b a r k v．上船，上飞机；从事,开始搞e m b a r r a s s v.使窘迫，使困惑，使为难e m b a s s y n.大使馆e m b e d v.嵌入；包埋e m b o d y v.体现；使具体化；包含，收录e m b o l i s m n.栓塞e m b o l u s n.栓子e m b r a c e v.／n．抱,拥抱,包括,包含e m b r y o l o g y n.胚胎学e m i g r a n t a．移居的，移民的n．移居外国的人，移民e m i g r a t e v．移居国外，移民e m i g r a t i o n n．移居；移民出境;(总称)移民e m i n e n c e n．卓越，显赫；高地，高处；名家e m i n e n t a．著名的，杰出的；突出的，优良的e m i s s i o n n．散发，发射；发出物，发射物e m i t v．散发，发射；发表；发行e m o t i o n n．情感，情绪e m o t i o n a l a．感情上的；情绪上的;易激动的；激动人心的e m p e r o r n．皇帝e m p h a s i s n．强调，重点e m p h a s i z e v．强调，着重e m p h y s e m a n．(肺)气肿e m p i r e n．帝国e m p i r i c a l a．经验主义的；以经验为根据的e n a m e l n.搪瓷；(牙齿的)珐琅质e n c o d e v.译成电码(密码)e n c o u n t e r v.／n．遇到，遭遇e n c u m b e r v.妨碍，阻碍；阻塞；牵累e n c y c l o p e d i a n.百科全书；某科全书e n c y s t v.包在囊内e n d a n g e r v.危害，危及e n d e a v o u r v.／n．努力，尽力，力图e n d e m i c a.地方性的；地方病的e n d e r m i c a.经皮的，皮下的e n d o c r i n e a.内分泌的e n d o g e n i c a.内源的e n d o r s e v.背签；批注e n d o s c o p e n.内镜e n d o t o x i n n.内毒素e n d o w v.资助；捐赠；赋予e n e r g e t i c a.精力旺盛的e n e r g y n．精力，气力，活力；能，能量e nf o r c e v．实行，执行，强制e n g a g e v．雇用，聘用；使订婚；使从事，使忙于e n g a g e m e n t n.订婚,婚约,约定,约会e n g r a v e v.刻上；铭记e n g r o s s v.使全神贯注e n h a n c e v.提高，增加;增强;提高…的价值e n l i g h t e n v.启发，启蒙，教导e n o r m o u s a.庞大的，巨大的e n o u g h a./n.足够的,充足的a d.足够地e n r o l l v.登记，编人，招收e n s u e v.接着发生；结果是e n s u r e v.确保，保证e n t a i l v.使承担;把(疾病)遗传给；引起；伴有e n t e r p r i s e n．事业，企业；事业心，进取心e n t e r t a i n v.招待，款待;使欢乐,使娱乐e n t e r t a i n m e n t n．招待，款待,表演会,文娱节目e n t h u s i a s m n．热心，热情，积极性e n t i t y n．实体；本质；病(种)e n u m e r a t e v.数,点;列举e n v e l o p v./n.包,封;包围,围绕87e n v e l o p e n．信封；外壳e n v i o u s a．妒忌的；羡慕的e n v y v．／n．妒忌，羡慕n．妒忌对象，羡慕目标e n z y m e n．酶e p i d e m i c a．流行性的，传染的n.流行病，时疫；传播；流行e p i d e m i o l o g y n．流行病学e p i l e p s y n.癫痫e p i s o d e n.事件,(一段)情节，插曲;发作e p i t h e l i u m n.上皮e p o c h n.时代；纪元e q u a t i o n n．平衡；平均；相等；等式；反应式e q u a t o r n．赤道e q u i l i b r a t e v．平衡；相称e q u i t y n．公平；公道e q u i v a l e n t a．相等的，相当的，相同的n．等价物，等量e r a d i c a t e v．根除；消灭e r a s e r n.橡皮擦e r e c t v.树立，建立，设立；竖立a．直立的，竖立的e r o d e v．侵蚀；受腐蚀e r o s i o n n．腐蚀；侵蚀；侵害；糜烂e r r a n d n．差事e r y t h r o c y t e n.红细胞e s c a l a t e v.逐步上升,逐步升级e s c a l a t o r n.自动电梯e s o p h a g u s n．食管e s t a t e n．等级；社会阶层；房地产；财产，遗产e s t e e m v．尊重，尊敬，珍重；认为，感到n．尊重，尊敬e s t i m a t e v．／n．估计，估价，评价,预算e t e r n a l a．永久的，永存的，无穷的e t h e r n．以太；乙醚e t h i c a l a．伦理学的；伦理的；道德的e t h i c s n．伦理学；道德学；伦理观，道德观；道德标准e t h n i c a l a.种族的；人种学的e t i o l o g y n.病因学e u p h e m i s m n.委婉语；婉词e v a c u a t e v．遣送；搬空；抽出；排泄；大(小)便e v a d e v．逃避；回避e v a l u a t e v．把……定值;估…的价;评价e v a l u a t i o n n．估价，评价e v a p o r a t e v．使蒸发；使脱水；挥发e v i l a．坏的，邪恶的n.灾祸,邪恶e v o c a t i v e a．唤起…的，引起…的e x a c e r b a t e v．恶化，加剧；触惹e x a n i m a t e a．已死的；无生命的；无生气的；没精神的e x a s p e r a t e v．激怒；使(疾病)加剧,使恶化e x c e l v．胜过，优于e x c e s s i v e a．过度的，过分的，极度的e x c h a n g e v．／n．交换，调换，兑换n.交换台，交易所e x c i s e v．删去；切除e x c i t e v．激动，使兴奋e x c i t e m e n t n．刺激；兴奋，激动;骚动;刺激的事物e x c l a i m v．呼喊，惊叫,大声说e x c l a m a t i o n n．叫喊，感叹e x c l u d e v．拒绝，排除，排斥e x c l u s i v e a．除外的；排外的；孤傲的；专有的n．独家新闻；孤傲的人e x c r e t e v．排泄；分泌e x c u r s i o n n．短途旅行，集体游览e x e c u t e v．实行，执行，实施；处死，处决e x e c u t i o n n．实行；履行；处死刑e x e c u t i v e a．执行的，实施的n．执行者，行政官，高级官员e x e m p l if y v．举例说明；作为…的例子e x e m p t v．免除；豁免e x e r t v．尽力；发挥；施加e x h a l a t i o n n．呼气；蒸发；散发e x h a l e v．呼气；发散出e x h a u s t v．用尽，耗尽，竭力；使衰竭，使精疲力竭n．排出；排出的气e x i l e n.放逐,流亡；被流放者v.放逐,流亡e x o g e n o u s a.外生的；外源的；外因的e x o t i c a.外(国)来的；异国情调的n.外来物e x o t o x i n n.外毒素e x p e c t o r a t e v．咳出(痰)；吐(血，唾液等)e x p e d i t i o n n．探险，远征：探险队,考察队e x p e l v．驱逐；开除；排出e x p e n d i t u r e n．支出，消费;花费,使用,支出额；经费e x p e r i m e n t n．／v．试验，实验e x p e r i m e n t a l a．实验性的，试验性的e x p e r i m e n t a t i o n n．实验，试验；实验法e x p e r t i s e n．专门知识，专长；专家评价；鉴定e x p i r a t i o n n．满期，届期；呼气，吐气e x p i r e v．满期；终止；开始无效；呼气e x p l i c i t a．明晰的，清楚的,直率的;详述的；e x p l o d e v．使暴发；使爆炸；破除；戳穿；突发e x p l o i t v．开拓，开发，开采；利用，剥削n．功绩，功勋e x p l o i t a t i o n n．开发，开采；剥削；利用e x p l o r a t i o n n．探究，探索；钻研；考察；测定；探险e x p l o s i o n n．爆炸，暴发e x p l o s i v e a．爆炸性的n．炸药e x p o r t v.／n．出口，输出n．出口商品e x p o s e v．暴露，揭露；接触e x p o s i t i o n n．说明，讲解，评注；展览会，博览会；暴露e x p o s u r e n．暴露，揭露，揭发；接触e x p o u n d v．详述；解释；阐述e x p r e s s v．表示，表达a．特快的，迅速的n．快车，快运e x p r e s s i o n n．表示，表现；措辞；词句；表情，脸色e x p r e s s i v e a．表现的，表达…的，富于表情的e x t e r i o r a．外部的；外来的；对外的，外交上的n．外部，外表；表面e x t e r m i n a t e v．根除；灭绝；扑灭e x t e r n a l a．外部的，外面的；外用的e x t i n c t a．绝灭的；熄灭了的；失效的e x t i n g u i s h v．熄灭；扑灭，灭绝；废除；使无效e x t r a c t v．拔出，抽出；榨取，提取n．摘录；提取物；浸膏e x t r a o r d i n a r y a．非常的，非凡的，特别的e x t r a t e r r e s t r i a l a．地球外的，地球大气圈外的e x t r e m e a．尽头的，末端的；极端的，极度的n．极端e x t r e m e l y a d．极其，非常e x t r e m i t y n．末端；肢e x u d a t e s n．渗出物，渗出液e y e l i d n.眼睑f a b l e n.寓言f a b r i c n.织物,纺织品f a b r i c a t e v.制作,装配,组合;捏造;伪造f a c e t n．面；某一方面f a c i l i t a t e v．使容易,使便利,推进,促进f a c i l i t y n．便利，设备,工具,敏捷;熟练，灵巧f a c u l t y n．才能，本领，能力；全体教员；院，系f a d e v．褪色，凋谢；消失，衰弱F a h r e n h e i t a．华氏(温标)的n．华氏温度计f a i n t v．／n．发晕，昏过去a．微弱的，模糊的；虚弱的f a i t h n．信任，信用：信念,信心,信仰f a i t h f u l a．忠诚的，忠实的f a k e v．伪造；伪装n．冒牌货，赝品a．假的，冒充的f a l s e a．假的；谬误的；假造的,人造的f a m e n．名声，名望f a m i l i a l a．家庭的；家族的f a m i l i a r a．熟悉的；通晓的；亲密的,交情好的n．熟友，常客f a m i n e n．饥荒，饥饿f a n a t i c a．狂热的；盲信的f a n c y n．／v.想象，幻想n．爱好，喜爱a．花式的；奇特的；品种珍贵的f a n t a s t i c a．空想的；奇异的，古怪的f a n t a s y n．幻想；怪念头；幻想曲：幻想作品；想象力的产物；想入非非v．想象；空想f a r e n．车费，船费v．过活，进展f a r e w e l l i n t．再会，别了n．告别a．告别的f a r t h e s t a．／a d．最远的(地)f a s c i n a t e v．迷住；吸引住f a s c i n a t i o n n．迷惑力，魅力；迷恋，强烈爱好f a s t e n v.扣住；扎牢；闩上f a s t e n e r n．扣件；钮扣，揿钮,钩扣;扣钉f a t ig u e n．疲乏，劳累v．使疲劳f a u l t y a．有错误的，有缺点的，不完善的f a v o r i t e n．最喜爱的人(或物)a．最喜爱的f e a s i b l e a．可行的，行得通的，可能的f e a s t n．盛宴，筵席v．盛宴款待f e a t n．功绩；武艺，技艺a．灵巧的，漂亮的，合适的f e a t u r e n．面貌，容貌；特征,特色v．以…为特色f e b r i f ug e n．退热药；解热药f e b r i l e a．发热的；热性的f e c e s n．粪便；排泄物；渣滓f e e b l e a．虚弱的；微弱的；薄弱的f e m i n i n e a．女性的；妇女的f e m u r n．股骨；大腿f e r m e n t n．v．发酵；酵素f e r r o u s a．铁的；含铁的；亚铁的,二价铁的f e r r y n．摆渡；渡口；渡船v.渡运，运送f e r t i l e a．肥沃的；富饶的；多产的；丰富的f e r t i l i z e v．使肥沃；使多产；使受精f e r t i l i z e r n．化肥，肥料f e s t i v a l n．节日；喜庆a．节日的；喜庆的f e t c h v．(去)拿来；请来；带来f e t u s n．胎儿f i b r i l n．原纤维f i b r i l l a t i o n n．纤维性颤动；原纤维形成作用f i b r o s i s n．纤维变性；纤维化f i e r c e a．凶猛的；凶恶的；猛烈的；强烈的f i l t e r n．滤纸；过滤器v.过滤,滤过f i l t r a t e v．过滤n．滤液f i n a n c e n．财政，金融v．提供资金;筹措资金f i n a n c i a l a.财政的；金融的f i n i t e a.有限的,限定的。
化工厂常用PSSR检查表
PSSR Checklist Example A-1 PSSR青单示例A-1Comments讨论PSSR Checklist Example A-2PSSR Checklist Example A-3ATTACHMENTA - PROCESS PR5RTUP S/FETY REVIEW CHECKLISTAREA CR PLANT UNDER REVIEW:DATE:LISTCF PSSFTEAM MEMBERSInstructions for using Ihis form:1. Rsviewtheetie checklisfrid mark acheck incdimn Ato irdicae an iten cr area tobe included inthe raiew2. If the areissies to be esdved after the inta re/iew conpleteAttachment B PSSRPctertia Isue-FiidingFarm3. Fo each iten or area Wtha check incdimn A, pace a check incdimn B when tl® iten orarea has beensasfactoilyieVewed cr a poentia ^旳的 has been esdved.Column A Column B Category/PSSRIfem to EvaluateInclude CompletedLocation and layoutSiteConditiosDrainageFlod cantdl/pdtectidlPrevailig windAirorweter pdlition ejposuiesOther sitexndition equiring attentionSoil pdectioi instoage, maerias handing&process aeasNearby operationsHazards fomHazards toTraficVehicua/iai loac/pedestranClearances, hazardsAdeqjacy of taffisigisSecuritySpecia rqiiementsm posed ty newfacilityStorage and handlingof chemicalsBuried pipes, tanks o chemic^sewerLeak detection and coitainmertAbove ground storage tanksAdeqjate secGncbry canterrment providedCpa^atingerd maintenance access 吐中左玄！! sfeAdeqjate and accessitiemanwaysUnobstucted prssueAacuum ielif 'entsMerifOdrg cf vets eviewedvent siZg basisprocess saetymanuals)Wnteizaion (ncljCirg iistument c(nnecticrs)Adeqjate ligtirgLabeling 卩33&小用 f hazardsOther in;taleiol detailsColumn A Column B Ca：egory/PSSRItem to EvaluateIndude CompletedFlammableand combustibe liqiidsTark pacenent and spacing adequateStesl sipports equirng feprocfingFlammableliaUd beether vents pxcvidsd withflame arestcs cccnservaticnvsrtsNoflane arestcrs cn emergency ielif ventsSafevent dsclarge lcratiorsVapcr-space ignitions hazardsCcrpcrate leccmmended/aoprcved fie pctectian systemsinpaceFlammablegases cr liqjefiedflmmable gassesCcrpcrate lecammended/aDploved fie pctecticn systemsinpaceBulk drychemicalsDust eplcsici pdentia ajdtessedTanks truck and railcar unloajing and loading sationsSpill cntainment aid sfe inpoundingAccess pafcm sfetyLighting adsquateGrcundng cabesFixd unloading pump and backflowfreverterEmergencystcp button 血血Ccmectidns lcckaoleandclcsedPlajardng cf hazardsRemotdy operated emergencystcp vdve fovehicls carynghaardousmateriasFusibeHrk fe valve onvehicls withbottcm unlcading fflanmdDlePcrtablefie eXirguishe a ground level orflanmaoleSafety shower and eyewashunitsRecommended firq)otecti(n systems inplaosElostrcaProcessGenera wokpaceSafecpelatoraocessBuildng eXtsmarkedLighting adsquateSaetyshower and e/ewashunitsAccessibleLocked cn each deckLocked inccrtrd r(o mPcrtabefie eXirguishesAccessibleLocked on each deckLocked inccrtrd r(o mHuman FavorsLaoeling cf equipment, ppng crticavaves,fied iistuments,switclesLcc^ion cf fild instrumentsSampliig poirisColumn A Column B CO:egory/PSSRIfem to EvaluateInclude CompletedOperatortask safetyOperatortask ergcncmicsOpporturitie for cperatcr e r orNcr-rcutinetasksChemical E:posire FbzarcSPotertia exoosLresEngireering cortiols dequateBUICig verlil^ioT/fesh air irlakesToXc gsmoritos, aaimsProtectiveaquipmert IccstioiPlacarcirgProcess PipingCo-stiuctioi appopratefor dutyMaeriOs qalityassuarce (rcludingflange bolts) if CCal,cUrng corstiuctiarWakmarshipfor exampe no shot flange bolts)Routing saisfatoyAcbqjateysipportsC andgjicbdAllowance for thermal exparsioT/ro referencesNosmall Cbmeter connectiois vjlreraDletobroakage/f^ueE>pansioi bdlovs pjcpely irstalel/ppng nd able tomovesicbways/bellovedUndamaged during irstalaionFleXblepiprg connectos cdrectlyirst^ec/undamaged (forexample kiked) duingiistalaionNecessay dr^ns prcvicl^dHazardous outlets pugged C I OBG CThermal hyCrost^ic)pressure rdie (ncludnghettiacedssitiois)Sidht gasses and gauge gassesExtenal corosioi protectionFreeze prdectidnInsiJationaCequate fopersoral potectioiProtectiv百lange covesAppoved hoses and hose and connectos (TO impovisetiois)Process VeitsFlammableliqjid beether verts povidsd withflame airestaso conservationMentsTdltaepressue gauge or otherirCicetor povideC betweenrupture disc ad relif $lve where a disc isstaleC belowa elifvaveDisclarge piping fom emergency pessuie rdif cbvicesunestrct创 by 90 cbgree dls.Excessive leigth or flme arrestersProvisions such as dan holes toprevent ajcimula：ion frainwator in discharge pipingDisclarge piping aCequEtelysu^ported towithstard reactivefaces f pressuie ventingSafevert dsclarge loEatiorsManifddng cf vets eviewedVent siing basis;cCcumentati(nColumn A Column B Catagary/PSSRIfem to EvaluateInclude CompletedDuctworkCleanoutsHeat Exchangers,由cketsVent, afeirsThermal hydrostaic)pessue relieM^rtenance access tube binde)MachineryGuardngLocW emergency step buttonEmergencyldDric^icn of crticdmachneryMartenarce povisionLocW exhaust vntiiaicn lequired forslaftsealsPumpsBackflw preventionCamectiig piping adfequateysipportedtoimit foces oncasingsSeal spay戸威血®Isdekid fe m^ntenancePreparaticr for martenarce (diainand vent po/icted)ContainmentSpill coainmentFirewater unofProcess 6*『008*『01 R^omoom iiherert saety/s. pocess hazards)VentiiaonEmergercyli(htiigFirepatecticnFiddwirngsexritySystem cbe securityPower sipplyOpa^atarinerfaDe(s)Alarm systemsEmergercyshJtcawlr-nermal and emergencySoftwaie access/s^iritySoftwaie back-upUtlitesWater SupplyNomunicipal/potdDlewatertothe pocessSteam Boiles and DstributonFesdwaterteatmentchemicals landingGas ppng outingCcmDusticn caltalsHigh and lowcrum water leel Warms poVcIbdBypass aound Fedwater regulator accessiDlefam 呼£^0 le/dand locked whereDrum level gauge gass c⑧ be seenTwo imfependert lowwater levl tips provided for unattendedbDilesDual saetyrelif vdvs insaviceColumn A Column B Ca：egory/PSSRIfem to EvaluateInclude CompletedRdie dsclargs piping a(eqi£telysipportedand cranedNcn-retirnvalve onsteam autieDistbUicn piping -se Pocess ppngCcndensste dainageadequateCompressed Air SystemsNcn-lubrica：edccnstiuctio or non-flammaDlesyrtheticlbricants used forcampresscrDischarge pressues dDove 100 psigElectricalTransfcrmer 血血Mctor colrd ceiters)Standby Emegency UtilitySystemsReviewpro/isiois tosaisy proceecls sdietyiequiiementsWaste Handli ng/Teatme ntInspect newfacilit einthe samemanner as pocess facit i esWarehouseFlammableand combustibe liqiidsFoklift and Motcrized Hand TrucksTrdfficsfetyNon combustibefueRecommended FiePrctectioi Systems inPaceMantanance Areaand ShopGeneralLocOI eXhaust '/ntil^oi po/ided fo weldingLocker Room and Lunch RDomAdeqjate spacePro/siois toprotect。
押题(卫生C)--职称英语卫生类
阅读理解：第五篇U. S. Eats Too Much Salt第十六篇Eat to Live第三篇Cooking Oil Fumes Cause Tumor第十五篇Warm People Likely to Keep Cold at Bay第十二篇Common-cold Sense第十三篇Drug Reactions — a Major Cause of Death完型填空：第四篇Diet, Alcohol Linked to Nearly One Third of Cancers第一篇Better Control of TB Seen If a Faster Cure Is Found第二篇A Biological Clock第三篇One Good Reason to Let Smallpox Live第五篇U. S. Eats Too Much SaltPeople in the United States consume more than twice the recommended amount of salt, raising their risk for high blood pressure, heart attacks and strokes, govemment health experts said on Thursday.They found nearly 70 percent of U. S. adults are in high-risk groups that would benefit from a lower-salt diet of no more than l,500 mg per day, yet most consume closer to 3,500 mg per day.The study in CDC's weekly report on death and disease used national survey data to show that two out of three adults should be consuming no more than l,500 mg of sodium per day because they are black or over the age of 40-which are considered high-risk groups.Yet studies show most people in the United States eat 3,436 mg of sodium per day, according to a 2005 - 2006 CDC estimate.Most of the sodium eaten comes from packaged, processed and restaurant foods. The CDC said it will join other agencies in the Health and Human Services department in working with major food manufacturers and chain restaurants to reduce sodium levels in the food supply.Nationwide, 16 million men and women have heart disease and 5. 8 million are estimated to have had a stroke. Cutting salt consumption can reduce these risks, the CDC said.1. Too much salt raises one's risk for _________.A. strokesB. heart attacksC. high blood pressureD. all of the above2. The recommended sodium intake for most U. S. adults is ________.A. closer t0 3,500 mg per dayB. as much as 3,436 mg per dayC. no more than l,500 mg per dayD. less than 3,500 mg per day3. A heart-healthy diet is one that contains ________.A. a low level of sodiumB. a lot of potassium and calciumC. no salt at allD. both A and B4. Nearly 70 percent of U. S. adults are in high-risk groups,________.A. for they are inactiveB. for they are black or over the age of 40C. for they frequently eat outD. for they consume sodium every day5. Packaged, processed and restaurant foods are known to beA. good in tasteB. low in priceC. poor in nutritionD. high in salt解析：1.D [解析]由第一段的People in the United States consume more than twice the recom. mended amount of salt，raising their risk flor high blood pressure，heart attacks and strokes，government health experts said on Thursday.可知，A、B、C都出现了，因此选D。
宠物专业英语 Unit 5 Pet Nutrition
Unit 5 Pet NutritionUnit ObjectivesIn Section 1 Oral Practice, learn how to start a conversation with others about the topic of “pet nutrition”.In Section 2 Reading-centered Activities, master the key words and structures by finishing the comprehensive tasks after Passage 1; Understand Passage 2 and finish the reading, translating and writing tasks after it.In Section 3 Related Information, learn and memorize the list of common ingredients of pet food and see how many of them you are familiar with.Section 1 Oral PracticeWarm-upMatch the key words with the pictures given below.1---B 2---D 3---A 4---C 5---F 6---ESpeaking Task 1Language points:1. formula n.公式，准则；方案；婴儿食品There is no standard multivitamin formula.复合维他命剂的配方并没有通用标准。
This year, the country’s indexing formula has set the minimum wage increase at 6 per cent.按照与通胀挂钩的计算公式，该国已将今年的最低薪资涨幅设在6%。
畜牧兽医专业英语
Embryo Transfer
The process of transferring embryos from one animal to another
Vocabulary related to veterinary medicine and vaccinVeetserinary Diagnostics
02
Professional English vocabulary for animal husbandry and veterinary medicine
Vocabulary related to animal diseases
Infectious Diseases
Tuberculosis, Pneumonia, Salmonellosis, Ringworm, Distemper
Learning Methods for Animal Husbandry and Veterinary Professional English
• Specialized Textbooks: It is recommended to use English textbooks or translated materials that are specifically designed for animal husbandry and veterinary medicine to ensure accuracy and authentication of language usage
Professional English for Animal Husbandry and Veterinary Medicine
目录
• Overview of English for Animal Husbandry and Veterinary Medicine
此次作业完成的认真细致,分析比较详尽,解析言之成理(药理)的
此次作业完成的认真细致，分析比较详尽，解析言之成理（药理）的国贸031班梁莹、张玉明、冯诗卉、陈双萍After-class practice要求：以下是某厂家销售〝乌鸡白风丸〞所附的中文说明书与英译文。
认真分析中文原文的文字特点及其信息特点，从作为消费者的英语读者同意的信息需求特点角度看，从经济简明和信息结构层次明晰的翻译原那么看，如何改进现有的英译文，请提交一份通过修订的英译文，并附有理据说明。
具有补气养血，调经止带之功效，主治气血两虚引起的躯体瘦弱〔指虚弱，并不指瘦〕、腰酸腿软、阴虚〔缘故〕盗汗〔症状〕，经血不调，子宫虚寒〔？〕、行经腹痛、崩漏带下〔重复〕、产后失血等症。
方中专饲专供的纯种优质乌鸡，补肝肾、养气血〔重复〕，养阴退热之功效显著。
全方配伍，药性平和，不寒不躁〔即平和也！〕，最适合〔〝最〞得没道理，难道比较适合的是男士？〕妇女补血调经之用，专门是在透达血分虚热方面功效更为显著。
The WUJI BAIFENG BOLUS has the effect of invigorating the vital energy and nourishing blood, regulating menstruation and stopping leukorrhea.It is suitable for treatment of symptoms caused by deficiency of both the vital energy and blood, such as weakness and leanness, lassitude in the loins and knees, night sweat due to insufficiency of refined materials in the viscera, irregular menstruation( repetition!), asthenia-cold of uterus, dysmenorrhea, leukorrhagia and postpartum bleeding. The silky fowl？in the prescription (处方子中有竹丝鸡?)is specially bred and supplied, quality and purebred, which, which has the remarkable effect on nourishing the liver ad kidney, invigorating the vital energy and blood, nourishing the refined materials in the viscera and clearing away pathogenic heat. The medicine(西药), with even property, neither cold nor dry ( 该药本身既不是冰冷的也不是干燥的), is most suitable for nourishing blood and regulating menstruation ( repeated 3 times) in women, especially efficacious on expelling pathogenic heat due to deficiency from blood system.分析：1、第一，Nourish, keep (a person, an animal or a plant) alive and well with food.在那个地点用于形容〝养血〞不大恰当。
广东省大湾区2022-2023学年高二上学期期末联考英语试题(含解析)
Being an ice-cream inventor does have its own rewards-who wouldn’t want a chance to create a new ice cream flavor? For Spors, it’s terrific to know his work makes others happy when he goes to the grocery store and seessomeone buy ice cream he developed.
阅读下列短文,从每题所给的A、B、C、D四个选项中选出最佳选项。
A
China Media Group, the country’s state broadcaster, released the country’s top 4 science and technology news stories in 2021 on Monday.
2024年教师资格(初级中学)-英语知识与教学能力(高中)考试历年真题摘选附带答案版
2024年教师资格（初级中学）-英语知识与教学能力（高中）考试历年真题摘选附带答案第1卷一.全考点押密题库(共100题)1.(单项选择题)(每题2.00 分) —Do you mind if I______the TV a bit?—Yes, I do, because Fm busy with my homework now.A. turn onB. turn upC. turndownD. turnoff2.(单项选择题)(每题 2.00 分) A Chinese student makes a sentence as follows： He is a rich man who like traveling. The error in that sentence is the result of______.A. negative transferB. positive transferC. overgeneralizationD. pragmatic failure3.(单项选择题)(每题 2.00 分) The party’s reduced vote was______of lack of support for its policies.A. indicativeB. positiveC. revealingD. evident4.(单项选择题)(每题 2.00 分) Which of the following assumptions about vocabulary learning contradicts the modem language teaching theories?A. The best way to learn words is to use them.B. The best way to learn vocabulary is via rote learning.C. An English dictionary is an important aid to students.D. Learning a word involves learning more than just the word itself.5.(单项选择题)(每题 2.00 分) I will always remember my mother^ last few days in this worlD.On February 14th,2000, my class went on a field trip to the beach. I had so much fun. When we returned to school, my teacher told me to go t o the headmaster’s office. When I got into the office，I saw a police officer. Suddenly I realized something was wrong. The police officer told me what had happened and we went to pick my sister up. After that, we went to the hospital and waiteD. Time went slowly.Finally, we got to see our mother, it was terrible.On the next day, the headmaster came and told my two teachers what had happeneD. I was taking a rest that day. I knew it had something to do with my mother. I kept thinking that she either died or had got better. How I wished that she had got better. When my teacher took me outside, my sister ran up to me. She started crying, “She’s gone. Teresa mommy’s gone. She’s deaD. ”1 couldn’t believe it. We jumped into the car and drove straight to the hospi tal. Most of my family were there. The silence was terrible. I knew I had to say goodbye.Today when I look back, I still miss my mother very much, but I know that I will live. My mother was a strong mother，who had the biggest heart. My mother was an angel walking on the earth. I will always remember her as she is living. When someone is asked who their heroes are ,they usually say someone famous, like Michael Jordan or Britney Spears. When someone asks me who my hero is, I tell them, my mother. My mother lives every day. That is what makes her a true hero.What did the headmaster tell the two teachers on the next day?______.A. Her mother had been very ill.B. Her mother had been deaD.C. Her mother had gotten better.D. Her sister came to see her.6.(单项选择题)(每题 2.00 分) The men who race the cars are generally small, with a tight, nervous look. They range from the early 20s to the middle 40s, and it is usually their nerves that go first.Fear is the driver’s constant companion, and tragedy can be just a step behinD. Scarcely a man in the 500 does not carry the scars of accident crashes. The mark of the plastic surgeon is everywhere, and burned skin is common. Sometimes a driver^ scars are invisible, part of his heritage. Two young drivers, Billy Vukovich and Gary Bettenhausen, raced in their first 500 in 1968. Less than 20 years before, their fathers also competed against one another on the Indy track-and died there.All this the drivers accept. Over the years, they have learned to trust their own techniques, reflexes, and courage. They depend, too, on a trusted servant-scientific engineering. Though they may not have had a great deal of schooling (an exception is New Zealand’s Bruce McLaren, who had an engineering degree), many drivers are gifted mechanics， with a feeling for their engines that amount to kinship.A few top drivers have become extremely wealthy, with six-figure incomes from prize money, endorsement, and jobs with auto-product manufacturers. Some have businesses of their own. McLaren designs racing chassis (底盘).Dan GumeyJs California factory manufactured the chassis of three of the first four cars in the 1968 Indy 500, including his own second place car. Yet money is not the only reason why men race cars. Perhaps it isn’t even the major reason. Three times Indy winner(1961, 1964, 1967).A. J. Foyt, for example, can frequently be found competing on dirty tracks in minor-league races, where money, crowds and safety features are limiteD. and only the danger is not. Why does he do it? Sometimes Foyt answers, “It’s in my blooD. ’’Other times he says, “It is good practice.” Now and then he replies, “Don’t ask dumb questions. ’’A. J. Foyt often takes part in minor-league races fo r______ .A. prize moneyB. blood testC. cheers from the crowdD. enjoyment7.(单项选择题)(每题 2.00 分)A teacher may encourage students to__________ when they come acrossnew words infast reading.A. take notesB. ask for helpC. guess meaning from contextD. look up the words in a dictionary8.(单项选择题)(每题 2.00 分) You II find this Travel Guide to be of great ( ) in helping you and your children to get around Malaysia.A. costB. priceC. valueD. expenditure9.(单项选择题)(每题 2.00 分) If a teacher attempts to implement the top-down model to teachA. new word sifter playing the tapeB. new words before playing the tapeC. background information after playing the tapeD. background information before playing the tape10.(单项选择题)(每题 2.00 分) I’ve tried very hard to improve my English. But by no means______with my progress.A. the teacher is not satisfiedB. is the teacher not satisfiedC. the teacher is satisfiedD. is the teacher satisfied11.(单项选择题)(每题 2.00 分) What stage can the following grammar activity be usedat?______.The teacher asks the students to arrange the words of the sentences into different columns marked subject, predicate, object, object complement, adverbial and so on.A. PresentationB. PracticeC. ProductionD. Preparation12.(单项选择题)(每题 2.00 分) Operations which left patients______and in need of long periods of discovery time now leave them feeling relaxed and comfortable.A. unhealthyB. exhaustedC. fearfulD. upset13.(单项选择题)(每题 2.00 分) Mr. King works in a shop and drives a car for the manager. He drives carefully and can keep calm in time of danger, and he has escaped from several accidents. The manager pays him more and the traffic policemen often speak highly of him.Mr. Baker, one of his friends, works in a factory outside the city. Ifs far from his house and he has to go to work by bus. As the traffic is crowded in the morning, sometimes he’s late for the work. His manager warns the young man that he will be sent away unless he gets to his office on time. He hopes to buy a car，but he hasn’t enough money. He decides to buy an old one. He went to the flea market and at last he chose a beautiful but cheap car. He said he wan— ted to have a trial drive, and the seller agreeD. He called Mr. King and asked him to give a hanD.Mr. King examined the car at first and then drove it away. It was five in the morning and there were few cars in the street. At first he drove slowly and it worked well. Then he drovefailed and nearly hit an old woman who was crossing the street. A policeman told him to stop, but the car went on until it hit a big tree by the roaD.“Didn’t you hear me?” the policeman asked angrily.“Yes，I did，sir，” said Mr. King，“ Since it doesn’t listen to me，can it obey you?”Mr. Baker went to the flea market to______.A. buy a second-hand carB. have a trial driveC. choose a new carD. sell his old car14.(单项选择题)(每题 2.00 分)What is the author′ s attitude towards America′ s policies on global warming?A. Critical.B. Indifferent.C. Supportive.D. Compromising.15.(单项选择题)(每题 2.00 分) Which of the following activities helps to train the skill of listening for gist?A. After listening, the students are required to figure out the relationship between the characters.B. After listening, the students are required to sequence the sentences according to the story.C. After listening, the students are required to identify the characters appearing in the story.D. After listening, the students are required to decide upon the title for the text.16.(单项选择题)(每题 2.00 分) —Did you return Tom?s call?—I didn’t need to______, Fll see him tomorrow.A. thoughtB. unlessC. whenD. because17.(单项选择题)(每题 2.00 分) This skirt was made______your mother______her own measure.A. for; toC. to; toD. for; by18.(单项选择题)(每题 2.00 分)She is __________ , from her recording, the diaries of Simon Forman.A. transcribingB. keepingC. paraphrasingD. recollecting19.(单项选择题)(每题 2.00 分) There is no doubt______you will pass the exam this time. You have worked so hard in the past months.A. whetherB. thatC. ifD. what20.(单项选择题)(每题 2.00 分) 阅读下面的短文，从每题所给的四个选项中选出最佳选项（请选择唯一正确的答案）Passage OneThere are many wetlands in China and some of them have become the world’s important wetlands. The Chinese Yellow Sea Wetlands are among them. They are in Yancheng, Jiangsu Province. They are home for many different kinds of birds and animals. The worlds largest Milu Deer Nature Reserve is in them. More than 700 milu deer live freely there. There are not many red-crowned cranes in the world, but every winter you can see some in the Red-crowned Cranes Nature Reserve in the Yellow Sea Wetlands.The temperature in the wetlands is usually neither too high nor too low. There is a lot of rain and sunshine, too. They are really good places for wildlife. Offering food and home for some special kinds of animals and birds is not the only reason why we need to protect wet-lands. Wetlands are important because they can also prevent floods. But some people want to change the wetlands to make more space for farms and buildings. This means there will be less and less space for wildlife.Luckily, more and more people are beginning to realize the importance Of wetlands and wildlife. Every year, on February 2, many activities are held to tell people more about wet-lands.The World Wetlands Day is on. ______ .B. June 25C. February 2D. March 2221.(单项选择题)(每题 2.00 分)The committee __________ a conclusion only after days of discussion.A. releasedB. achievedC. reachedD. accomplished22.(单项选择题)(每题 2.00 分) Passage OneMove over Methuselah. Future generations could be living well into their second century and still doing Sudoku, if life expectancy predictions are true. Increasing by two years every decade, they show no signs of flattening out. Average lifespan worldwide is already double what it was 200 years ago. Since the 1980s, experts thought the increase in life expectancy would slow down and then stop, but forecasters have repeatedly been proved wrong.The reason behind the steady rise in life expectancy is “the decline in the death rate of the elderly”, says Professor Tom Kirkwood from Newcas tle University. He maintains that our bodies are evolving to maintain and repair themselves better and our genes are investing in →this process ←to put off the damage which will eventually lead to death. As a result, there is no ceiling imposed by the real ities of the ageing process. “There is no use-by-date when we age. Ageing is not a fixed biological process," Tom says.A large study of people aged 85 and over carried out by Professor Kirkwood discovered that there were a remarkable number of people enjoying good health and independence in their late 80s and beyonD. With people reaching old age in better shape, it is safe to assume that this is all due to better eating habits, living conditions, education and medicine.There are still many people who suffer from major health problems, but modem medicine means doctors are better at managing long-term health conditions like diabetes, high blood pres- sure and heart disease. “We are reaching old age with less accumulative damage than previous generations, we are less damaged," says Professor KirkwooD. Our softer lives and the improvements in nutrition and healthcare have had a direct impact on longevity.Nearly one-in-five people currency in the UK will live to see their 100th birthday, the Office for National Statistics predicted last year. Life expectancy at birth has continued to increase in the UK——from 73.4 years for the period 1991 to 1993 to 77.85 years for 2007 to 2009. A report in Science from 2002 which looked at life expectancy patterns in different countries since 1840 concluded that there was no sign of a natural limit to life.Researchers Jim Oeppen and Dr. James Vaupel found that people in the country with the highest life expectancy would live to an average age of 100 in about six decades. But they stopped short of predicting anything more."This is far from eternity: modest annual increments in life expectancy will never lead to immortality,” the researchers saiD.We do not seem to be approaching anything like the limits of life expectancy, says Professor David Leon from the London School of Hygiene and Tropical Medicine. “There has been no flattening out of the best the groups which everyone knows have good life expectancy and→ low mortality←. ”he says.These groups, which tend to be in the higher social and economic groups in society, can live for several years longer than people in lower social groups, prompting calls for an end to inequalities within societies.Within populations, genes also have an important role to play in determining how long we could survive for, but environment is still the most important factor.It is no surprise that healthy-living societies like Japan have the highest life expectancies in the worlD. But it would still be incredible to think that life expectancy could go on rising forever. “I would bet there will be further increases in life expectancy and then it will probably begin to slow,” says Tom, “but we just don’t know.”The underlined phrase “low mortality” in Paragraph 8 could best be replaced by “→←".A. short life spanB. low death rateC. low illness rateD. good health condition23.(单项选择题)(每题 2.00 分) For grammar teaching, if the rule is given first and explained and the student then has to apply the rule to given situation, the method is definedas______methoD.A. deductiveB. inductiveC. Grammar-translationD. audio-translation24.(单项选择题)(每题 2.00 分)The most suitable question type to check students′ comprehension and developtheir critical thinking is __________.A. rhetorical questionsB. referential questionsC. close questionsD. display questions25.(单项选择题)(每题 2.00 分) Which of the following is NOT the advantage of group work?A. creating some peaceful and quiet time in classB. encouraging cooperation and negotiation skills among studentsC. encouraging different opinions and contributions to the workD. promoting students5 autonomy rather than follow the teachers26.(单项选择题)(每题 2.00 分)--Would you like some noodles, Celia?--Yes, just___________, please.A. a fewB. fewC. a littleD. little27.(单项选择题)(每题 2.00 分) Modem scientists divide the process of dying into two stages-clinical or temporary death and biological death. Clinical death occurs when the vital organs, such as the heart or lungs, have ceased to function, but have not suffered permanent damage. The organism can still be reviveD. Biological death occurs when changes in the organism lead to the disintegration of vital cells and tissues. Death is then irreversible and final.Scientists have been seeking a way to prolong the period of clinical death so that the organism can be revived before biological death occurs. The best method developed so far involves cooling of the organism, combined with narcotic sleep. By slowing down the body^ metabolism, cooling delays the processes leading to biological death.To illustrate how this works, scientists performed an experiment on a six-year-old female monkey called KetA. The scientists put Keta to sleep with a narcotic. Then they surrounded her body with ice-bags and began checking her body temperature. When it had dropped to 28 degrees the scientists began draining blood from its body. The monkey’s blood pressure decreased and an hour later both the heart and breathing stopped; clinical death set in.this point the scientists pumped blood into its body in the direction of the heart and started artificial breathing. After two minutes the monkey’s heart became active once more. Aft er fifteen minutes, spontaneous breathing began, and after four hours Keta opened her eyes and lifted her heaD. After six hours, when the scientists tried to give her a penicillin injection. Keta seized the syringe and ran with it around the room. Her behavior differed little from that of a healthy animal.One characteristic of clinical death is______.A. lasting damage to the lungsB. destruction of the tissuesC. temporary non-functioning of the heartD. that the organism cannot be revived28.(单项选择题)(每题 2.00 分) Which of the following activities actually does not involve writing?→ ←.A. Completion according to outlines.B. Completion with multiple choices.C. Completion according to topic sentences.D. Completion with detailed examples related to the topiC.29.(单项选择题)(每题 2.00 分) English teachers often ask students to ______ a passage to get the gist of it.A. skimB. scanC. predictD. describe30.(单项选择题)(每题 2.00 分) —Must I finish the work today, Mom?__No, you_____. You can finish it tomorrow.A. mustn’tB. can’tC. shouldn’tD. needn’t31.(单项选择题)(每题 2.00 分) ______ she heard her grandfather was bom in Germany.A. That was from her mumB. It was her mum thatC. It was from her mum thatD. It was her mum whom32.(单项选择题)(每题 2.00 分) When we analyze the salt salinity (盐浓度)of ocean waters, we find that it varies only slightly from place to place. Nevertheless, some of these small changes are important. There are three basic processes that cause a change in oceanic salinity. One of these is the subtraction of water from the ocean by means of evaporation. In thisextreme, of course, white salt would be left behind; this, by the way, is how much of the table salt we use is actually obtaineD.The opposite of evaporation is precipitation, such as rain, by which water is added to the ocean. Here the ocean is being diluted so that the salinity is decreaseD. This may occur in areas of high rainfall or in coastal regions where rivers flow into the ocean. Thus salinity may be increased by the subtraction of water by evaporation, or decreased by the addition of fresh water by precipitation.Normally, in hot regions where the sun is very strong, the ocean salinity is somewhat higher than it is in other parts of the world where there is not as much evaporation. Similarly, in coastal regions where rivers dilute the sea, salinity is somewhat lower than in other oceanic areas.A third process by which salinity may be altered is associated with the formation and melting of sea ice. When seawater is frozen, the dissolved materials are left behinD. In this manner, seawater directly beneath freshly formed sea ice has a higher salinity than it did before the ice appeareD. Of course, when this ice melts, it will tend to decrease the salinity of the surrounding water.In the Weddell Sea, the densest water in the ocean is formed as a result of this freezing process, which increases the salinity of cold water. This heavy water sinks and is found in the deeper portion of the oceans of the worlD.It can be known from the passage that increase in the salinity of ocean water is caused by______.A. melting of sea iceB. precipitationC. evaporationD. supplement of salt33.(单项选择题)(每题 2.00 分) Mr. King works in a shop and drives a car for the manager. He drives carefully and can keep calm in time of danger, and he has escaped from several accidents. The manager pays him more and the traffic policemen often speak highly of him.Mr. Baker, one of his friends, works in a factory outside the city. Ifs far from his house and he has to go to work by bus. As the traffic is crowded in the morning, sometimes he’s late for the work. His manager warns the young man that he will be sent away unless he gets to his office on time. He hopes to buy a car，but he hasn’t enough money. He decides to buy an old one. He went to the flea market and at last he chose a beautiful but cheap car. He said he wan— ted to have a trial drive, and the seller agreeD. He called Mr. King and asked him to give a hanD.Mr. King examined the car at first and then drove it away. It was five in the morning and there were few cars in the street. At first he drove slowly and it worked well. Then he drovefailed and nearly hit an old woman who was crossing the street. A policeman told him to stop, but the car went on until it hit a big tree by the roaD.“Didn’t you hear me?” the policeman asked angrily.“Yes，I did，sir，” said Mr. King，“ Since it doesn’t listen to me，can it obey you?”What is a flea market?______.A. A market where fleas are solD.B. A market where cars are solD.C. A market where used and cheap goods are soldD. A supermarket.34.(单项选择题)(每题 2.00 分) To their credit the Department of Energy______these ideas and funded a detailed study.A. took toB. took onC. took overD. took up35.(单项选择题)(每题 2.00 分) The phoneme/n/in the first word of all the following phrases changes to/m/except______.A. moon shineB. moon beamC. common propertyD. common wealth36.(单项选择题)(每题 2.00 分)The author holds that the current collective doctrine shows__________.A. generally distorted valuesB. unfair wealth distributionC. a marginalized lifestyleD. a rigid moral code37.(单项选择题)(每题 2.00 分) Which of the following can be regarded as a communicative language task? ______ .A. Information-gap activityC. Sentence transformationD. Blank-filling38.(单项选择题)(每题 2.00 分) Passage OneMove over Methuselah. Future generations could be living well into their second century and still doing Sudoku, if life expectancy predictions are true. Increasing by two years every decade, they show no signs of flattening out. Average lifespan worldwide is already double what it was 200 years ago. Since the 1980s, experts thought the increase in life expectancy would slow down and then stop, but forecasters have repeatedly been proved wrong.The reason behind the stead y rise in life expectancy is “the decline in the death rate of the elderly”, says Professor Tom Kirkwood from Newcastle University. He maintains that our bodies are evolving to maintain and repair themselves better and our genes are investing in →this process ←to put off the damage which will eventually lead to death. As a result, there is no ceiling imposed by the realities of the ageing process. “There is no use-by-date when we age. Ageing is not a fixed biological process," Tom says.A large study of people aged 85 and over carried out by Professor Kirkwood discovered that there were a remarkable number of people enjoying good health and independence in their late 80s and beyonD. With people reaching old age in better shape, it is safe to assume that this is all due to better eating habits, living conditions, education and medicine.There are still many people who suffer from major health problems, but modem medicine means doctors are better at managing long-term health conditions like diabetes, high blood pres- sure and heart disease. “We are reaching old age with less accumulative damage than previous generations, we are less damaged," says Professor KirkwooD. Our softer lives and the improvements in nutrition and healthcare have had a direct impact on longevity.Nearly one-in-five people currency in the UK will live to see their 100th birthday, the Office for National Statistics predicted last year. Life expectancy at birth has continued to increase in the UK——from 73.4 years for the period 1991 to 1993 to 77.85 years for 2007 to 2009. A report in Science from 2002 which looked at life expectancy patterns in different countries since 1840 concluded that there was no sign of a natural limit to life.Researchers Jim Oeppen and Dr. James Vaupel found that people in the country with the highest life expectancy would live to an average age of 100 in about six decades. But they stopped short of predicting anything more."This is far from eternity: modest annual increments in life expectancy will never lead to immortality,” the researchers saiD.We do not seem to be approaching anything like the limits of life expectancy, says Professor David Leon from the London School of Hygiene and Tropical Medicine. “There has been no flattening out of the best the group s which everyone knows have good life expectancy and→ low mortality←. ”he says.for several years longer than people in lower social groups, prompting calls for an end to inequalities within societies.Within populations, genes also have an important role to play in determining how long we could survive for, but environment is still the most important factor.It is no surprise that healthy-living societies like Japan have the highest life expectancies in the worlD. But it would still be incredible to think that life expectancy could go on rising forever. “I would bet there will be further increases in life expectancy and then it will probably begin to slow,” says Tom, “but we just don’t know.”Which statement below is TRUE concerning life expectancy according to thepassage?→←.A. Life expectancy goes on rising forever.B. There could be further increases in life expectancy.C. Life expectancy has slowed down since 1980s and it will stop.D. Life expectancy in Japan doubles what it was 200 years ago.39.(单项选择题)(每题 2.00 分)The message came to the villagers __________ the enemy had already fledthe village.A. whichB. whoC. thatD. where40.(单项选择题)(每题 2.00 分)Which of the letter "u"in the following words has a different pronunciation from others?A. abuseB. useC. excuseD. lure41.(单项选择题)(每题 2.00 分)Based on the experiment, which of the following may signal that the subjectis nearing the solution?A. The subject is begging to work.B. The subject looks away at something else.C. The subject is distracted from the given words.D. The subject concentrates on the given words all the time.42.(单项选择题)(每题 2.00 分) New curriculum promotes the three-dimensional teaching objective which includes_______.A. knowledge, skills and method sB. emotional attitude and valuesC. knowledge, skills and emotionD. knowledge and skills； process and methods； emotional attitude and values43.(单项选择题)(每题 2.00 分) Which of the following nominating patterns can a teacher adopt to ensure that all students are actively involved in classroom activities?→ ←.A. Nominating those who are good at English.B. Asking questions in a predicable sequence.C. Nominating students after the question is given.D. Nominating students before giving the question.44.(单项选择题)(每题 2.00 分) Electronic books could revolutionize reading, but people ought to consider their far-reaching. “The e-book promises to wreak a slow havoc on life as we know it,” Jason Ohler, professor of technology assessment, University of Alaska Southeast in Juneau, warned the World Future Society, Bethesda, MD. His assessment weighed the pros and cons of e-book technology’s impact on social rela tionships, the environment, the economy，etC. Before you curl up with an e-book, consider the disadvantages.They increase eyestrain due to poor screen resolution, replace a relatively cheap commodity with a more expensive one, and displace workers in print book production and traditional publishing. E-books make it easy to share data, thereby threatening copyright agreements and reducing compensation of authors, as well as creating no biodegradable trash. On the other hand, e-books save paper and trees, reduce the burden of the carrying and storing of printed books, promote self- sufficiency in learning, and make reading a collaborative experience online. They also create new jobs for writers and artists and encourageself-publishing. In final analysis, Ohler points out, e-books should gain society’s approval if a few conditions are met: make them biodegradable and recyclable，solve the problem of eye fatigue，be sure the “have-nots” get the technology，and support e-book training in schools and business.What is e-books negative impact on social relationships?______.A. They create new jobs only for writers.B. Fewer and fewer people have access to new technology.C. They may threaten some traditional trades.。
肺炎链球菌核酸检测试剂国家参考品的研制及验证
肺炎链球菌核酸检测试剂国家参考品的研制及验证李康** 黄洋* 王春娥 李江姣 梁丽 陈驰 刘茹凤 叶强 中国食品药品检定研究院生物制品检定所细菌多糖和结合疫苗室，北京102629［基金项目］国家科技重大专项课题(2018ZX10102 - 001-002、2018ZX09738006-006)；国家科技基础条件平台一国家菌种资源库课题(NMRC-2020-2)遥［作者简介］李康(1982.5-),男，博士，主要从事呼吸道细菌 疫苗质量控制、国家标准医学菌种检定和诊断试剂研究工作。
*共同第一作者［通讯作者］叶强(1964.12-),男，硕士，主任技师，中国食品 药品检定研究院细菌多糖和结合疫苗室主任，主要从事细 菌多糖和结合疫苗质量控制和国家标准医学菌种资源的保藏、研究及应用工作。
［摘要］目的研制肺炎链球菌核酸检测试剂国家参考品,并进行适用性验证。
方法选择10株肺炎链球菌和10株 非肺炎链球菌细菌制备成阳性参考品、阴性参考品、重复性参考品和最低检出限参考品遥对参考品的分装均匀性和稳定性进行评估。
采用4家企业生产的肺炎链球菌核酸检测试剂盒对制备的肺炎链球菌国家参考品进行准确 性、特异性、重复性和最低检出限验证。
结果参考品的分装均匀度良好，循环阈值的变异系数均在5.00%.以内。
2~8益、室温(25益)和37益放置3、7 d 及反复冻融3、5次都不影响参考品的稳定性。
4家企业的试剂盒的准确性、特异性及重复性检测结果均符合要求。
1家企业的试剂盒的最低检出限为1.0伊104个/mL,其他3家企业的试剂盒的最低检出限为1.0伊103个/mL 遥结论研制完成一套肺炎链球菌核酸检测试剂国家参考品，能够用于肺炎链球 菌核酸检测试剂盒的质量控制和评价。
［关键词］肺炎链球菌；核酸检测试剂；国家参考品；质量评价冲图分类号］R378.1［文献标识码］A［文章编号］1673-7210(2021)05(C )-0141-04Preparation and validation of a national reference for nucleic acid testreagent of Streptococcus pneumoniaeLI Kang' HUANG Yang' WANG Chun ' e LI Jiangioo LIA NG Li CHEN Chi LIU Rufe n g YE QiangDivision of BacLerial Polysaccharide and Conjugate Vaccines, InsLiLuLe for Biological ProducL ConLrol, National InsLi-LuLes for Food and Drug ConLrol, Beijing 102629, China[Abstract] Objective To prepare a naLional reference for nucleic acid LesL reagenL of Streptococcus pneumonicae andvalidaLe iLs applicabiliLy. Methods Ten sLrains of Streptococcus pneumoniae and Len sLrains of non -Streptococcuspneumoniae were selecLed Lo prepare posiLive reference, negaLive reference, repeaLable reference and minimum deLec-Lion limiL reference. The uniformiLy and sLabiliLy of Lhe reference package was evaluaLed. The accuracy, specificiLy, re- producibiliLy and minimum deLecLion limiL of Lhe prepared naLional reference of Streptococcus pneumoniae were vali-daLed by using nucleic acid deLecLion kiLs of Streptococcus pneumoniae produced by four enLerprises. Results The packing uniformiLy of Lhe reference was good, and Lhe coefficienL of variaLion of Lhe cycle Lhreshold values were allwiLhin 5.00%、The sLabiliLy of Lhe reference was noL affecLed by being placed for Lhree or seven days aL 2-8益，room LemperaLure （25益） and 37益 and repeaLed freezing-Lhawing for Lhree or five Limes. The accuracy, specificiLy and repro-ducibiliLy of Lhe kiLs from Lhe four enLerprises were all in line wiLh Lhe requiremenLs. The minimum deLecLion limiL of Lhe kiLs from one enLerprise was 1.0x104/mL, and Lhe minimum deLecLion limiL of Lhe kiLs from Lhe oLher Lhree enLer prises was 1.0x103/mL. Conclusion A seL of naLional reference reagenLs for nucleic acid LesL reagenL of Streptococcuspneumoniae has been prepared, which can be used for Lhe qualiLy conLrol and evaluaLion of Streptococc us pneumoniae nucleic acid deLecLion kiLs.[Key words] Streptococcus pneumoniae; Nucleic acid LesL reagenL; NaLional reference; QualiLy evaluaLion肺炎链球菌是引起儿童肺炎链球菌性疾病的主要病原菌［1］遥肺炎链球菌也是新型冠状病毒肺炎感染病例合并感染的主要呼吸道病原菌［2-4］遥根据荚膜多糖 抗原的不同,肺炎链球菌可以分为90多种血清型叫 早期及时准确的诊断有助于肺炎链球菌性疾病的临床治疗。
家装涂料 赫里塔奇天鹅绒哑光 技术数据表说明书
[Type here]HERITAGE VELVET MATTTechnical Data Sheet Dulux Heritage Velvet Matt is a luxury washable matt emulsion. It is formulated with premium quality pigments to guarantee excellent depth of colour and with speciallyblended clays for effortless application, and an irresistible soft to touch finish.KEY BENEFITS• Durable and washable • Effortless application • Soft to touch finish •Excellent opacityPRODUCT INFORMATIONTypical UseSuitable for all normal interior walls and ceilingsIn conditions subject to very frequent heavy condensation (e.g. some kitchens and bathrooms). Dulux Trade Diamond Eggshell is more suitable.Pack Size1L, 2.5L and 5LColour RangeHeritage colour range plus other Dulux trade and retail colour ranges including colour match.Film PropertiesChemical Resistance: Not suitableHeat Resistance: Not suitable on heated surfaces e.g radiatorsWater Resistance: Will tolerate the levels of atmospheric humidity present in normal interior environments.Composition (nominal)Pigment: Lightfast Pigments. Binder: Acrylic. Solvent: Water.Volume Solids40% (nominal). Other colours will varySURFACE PREPARATIONTo get the best results with Dulux Heritage Velvet Matt, prior to painting make sure surfaces to be painted are sound, clean and dry. (new surfaces particularly must be fully dry).Remove all loose and defective paint. Special precautions should be taken during surface preparation of pre-1960s paint surfaces as they may contain harmful lead.Where necessary, wash the surface to remove dirt, grease and powdery or dusty residues. Rinse with clean water and allow to dry. Seal surfaces that remain powdery after thorough preparation with an appropriate plaster sealer.Where necessary, rub down and then wipe off with a damp, lint free cloth to avoid dust.Any surface defects should be filled with the appropriate Polycell Polyfilla product.[Type here]HERITAGE VELVET MATT.SYSTEMS INFORMATIONSTIR THOROUGHLY BEFORE USE. Seal new or bare surfaces with a thinned first coat (up to 10% water) of Dulux Heritage. The normal finishing process is two full coats of Dulux Heritage Velvet Matt.For the best colour consistency, purchase sufficient tinted paint for each job including touch-in at one time from the same location.APPLICATION METHODBrush, roller. As with other water-based paints, do not apply at temperatures below 7⁰C (as recommended by British Standard BS 6150).To get the best finish from Heritage Velvet Matt you might choose to use a good quality short pile microfibre roller when applying to walls and ceilings. We do not advise the use of spray with Heritage Velvet Matt.Practical CoverageA guide to the practical coverage which can be achieved under normal conditions is up to 13m² per litre.ThinningSealing new or bare surfaces: A thinned first coat (up to 10% water) of Dulux Heritage.Drying TimesSingle coat at standard thickness:Touch Dry; Dependent on temperature and humidity. Recoat: 2-4 hours.Cleaning Up and RecyclingAfter use, remove as much product as possible from equipment before cleaning with water.When this paint container is empty please ask your stockist about recycling. Don’t waste unwanted paint. Leftover product may be taken to a Community RePaint collection point. Make a small difference to someone else at Transportation & StorageDo not use or store in extremes of temperature and protect from frost. Always store in an upright position and to prevent spillage transport in a secure and upright position.VOCEU limit value for this product (cat: A/a): 30g/l (2010). This product contains max. 10g/l VOC. VOC content: Low (0.30-7.99%).HERITAGE VELVET MATTFURTHER SUPPORTIf you need further support, please contact the Dulux Technical Advice Centre on *********** Always read full Health, Safety & Environmental Information on can before use. Safety datasheet is available free on request by telephoning the Dulux Technical Advice Centre or by visiting AkzoNobel, the AkzoNobel logo, the Flourish logo, Heritage, Dulux Trade Polycell, The Dog, Polyfilla, Community RePaint are trademarks of the AkzoNobel gr o up. © AkzoNobel 2021[Type here]。
药学英语翻译练习1
2. 动词等转换为汉语名词 1）动词转换为汉语名词 含义比较抽象的动词，有时难于用对应的汉语动 词表达，可转换为汉语名词。 The skeletal system is defined as the frame work of bones and cartilage that protects our organs and allows us to move. 骨骼系统的定义为：由骨和软骨组成的保护器官 并产生运动的框架。 (define转换为汉语名词“定义”) This paper aims at discussing the pathogenesis of atherosclerosis as well as treatment. 本文的目的在于：不仅讨论动脉粥样硬化的治疗， 而且讨论其发病机理。
•It has been reported that DMSO has some desirable properties that are considered to be useful in managing the brain trauma patient. •报道称二甲亚砜具备一些可取的特质，被认为可 用于治疗创伤性脑损伤。
• 3）副词转换为汉语名词 • Adverse drug reactions often occur early in therapy. • 译文：药物不良反应通常发生在治疗的早期。 • The erosion of the plug can be controlled enzymatically. • 译文：酶能控制栓塞的侵蚀。
• Nature should be so rich in potential lead compounds. • 自然界富含潜在先导化合物。 • Obviously this system is applicable only to drugs that can be ionized. • 该系统显然只适用于可以被离子化的药物。 • Just as the body is dependent on the skeleton for its structural stability, so is the skeleton dependent on the body for its maintenance. • 正如身体依赖骨骼以维持其结构的稳定性那样， 骨骼依靠身体以维持其生存。
超声增强的输送的物料进入并通过皮肤翻译
超声增强的输送的物料进入并通过皮肤翻译Ultrasound-enhanced delivery of materials into and through the skinA method for enhancing the permeability of the skin or other biological membrane to a material such as a drug is disclosed. In the method, the drug is delivered in conjunction with ultrasound having a frequency of above about 10 MHz. The method may also be used in conjunction with chemical permeation enhancers and/or with iontophoresis.图片(11)权利要求(21)We claim:1. A method for enhancing the rate of permeation of a drug medium into a selected intact area of an individual's body surface, which method comprises:(a) applying ultrasound having a frequency of above 10 MHz to said selected area, at an intensity and for a period of timeeffective to enhance the permeability of said selected area;(b) contacting the selected area with the drug medium; and(c) effecting passage of said drug medium into and through said selected area by means of iontophoresis.2. The method of claim 1, wherein said ultrasound frequency is in the range of about 15 MHz to 50 MHz.3. The method of claim 2, wherein said ultrasound frequency is in the range of about 15 to 25 MHz.4. The method of claim 1, wherein said period of time is in the range of about 5 to 45 minutes.5. The method of claim 4, wherein said period of time is in the range of about 5 to 30 minutes.6. The method of claim 1, wherein said period of time is less than about 10 minutes.7. The method of claim 1, wherein said intensity of said ultrasound is less than about 5.0W/cm.sup.2.8. The method of claim 7, wherein said intensity of said ultrasound is in the range of about 0.01 to 5.0 W/cm.sup.2.9. The method of claim 8, wherein said intensity of said ultrasound is in the range of about 0.05 to 3.0 W/cm.sup.2.10. The method of claim 1, wherein said area of the stratum corneum is in the range of about 1 to 100 cm.sup.2.11. The method of claim 10, wherein said area of the stratum corneum is in the range of about 5 to 100 cm.sup.2.12. The method of claim 11, wherein said area of the stratum corneum is in the range of about 10 to 50 cm.sup.2.13. The method of claim 1 wherein said drug medium comprises a drug and a coupling agent effective to transfer said ultrasound to the body from an ultrasound source.14. The method of claim 13 wherein said coupling agent is a polymer or a gel.15. The method of claim 13 wherein said coupling agent is selected from the group consisting of glycerin, water, and propylene glycol.16. The method of claim 1 wherein said drug medium further comprises a chemical permeation enhancer.17. The method of claim 1, wherein steps (a) and (b) are carried out approximately simultaneously.18. The method of claim 1, wherein step (b) is carried out before step (a).19. The method of claim 1, wherein step (a) is carried out before step (b).20. The method of claim 1, wherein the ultrasound is applied continuously.21. The method of claim 1, wherein the ultrasound is pulsed.说明This application is a division of application Ser. No. 07/844,732 filed Mar. 2, 1992, now U.S. Pat. No. 5,231,975 which is a divisional of application Ser. No. 07/484,560, now U.S. Pat. No. 5,115,805, filed Feb. 23, 1990.TECHNICAL FIELDThis invention relates generally to the field of drug delivery. More particularly, the invention relates to a method of enhancing the rate of permeation of topically, transmucosally or transdermally applied materials using high frequency ultrasound.BACKGROUNDThe delivery of drugs through the skin ("transdermal drug delivery" or "TDD") provides many advantages; primarily, such a means of delivery is a comfortable, convenient and non-invasiveway of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences--e.g., gastrointestinal irritation and the like--are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug.Skin is a structurally complex, relatively impermeable membrane. Molecules moving from the environment into and through intact skin must first penetrate the stratum corneum and any material on its surface. They must then penetrate the viable epidermis, the papillary dermis, and the capillary walls into the blood stream or lymph channels. To be so absorbed, molecules must overcome a different resistance to penetration in each type of tissue. Transport across the skin membrane is thus a complex phenomenon. However, it is the stratum corneum, a layer approximately 5-15 micrometers thick over most of the body, which presents the primary barrier to absorption of topical compositions or transdermally administered drugs. It is believed to be the high degree of keratinization within its cells as well as their dense packing and cementation by ordered, semicrystalline lipids which create in many cases a substantially impermeable barrier to drug penetration. Applicability of transdermal drug delivery is thus presently limited, because the skin is such an excellent barrier to the ingress of topically applied materials. For example, many of the new peptides and proteins now produced as a result of the biotechnology revolution cannot be delivered across the skin in sufficient quantities due to their naturally low rates of skin permeability.Various methods have been used to increase skin permeability, and in particular to increase the permeability of thestratum corneum (i.e., so as to achieve enhanced penetration, through the skin, of the drug to be administered transdermally). The primary focus has been on the use of chemical enhancers, i.e., wherein drug is coadministered with a penetration enhancing agent (or "permeation enhancer"). While such compounds are effective in increasing the rate at which drug is delivered through the skin, there are drawbacks with many permeation enhancers which limit their use. For example, many permeation enhancers are associated with deleterious effects on the skin (e.g., irritation). In addition, control of drug delivery with chemical enhancement can be quite difficult.Iontophoresis has also been used to increase the permeability of skin to drugs, and involves (1) the application of an external electric field, and (2) topical delivery of an ionized form of drug (or of a neutral drug carried with the water flux associated with ion transport, i.e., via "electroosmosis"). While permeation enhancement via iontophoresis has, as with chemical enhancers, been effective, there are problems with control of drug delivery and the degree of irreversible skin damage induced by the transmembrane passage of current.The presently disclosed and claimed method involves the use of ultrasound to decrease the barrier function of the stratum corneum and thus increase the rate at which a drug may be delivered through the skin. "Ultrasound" is defined as mechanical pressure waves with frequencies above 20,000 Hz (see, e.g., H. Lutz et al., Manual of Ultrasound: 1. Basic Physical and Technical Principles (Berlin: Springer-Verlag, 1984)).As discussed by P. Tyle et al. in Pharmaceutical Research 6(5):355-361 (1989), drug penetration achieved via "sonophoresis" (the movement of drugs through skin under theinfluence of an ultrasonic perturbation; see D. M. Skauen and G. M. Zentner, Int. J. Pharmaceutics 20:235-245 (1984)), is believed to result from thermal, mechanical and chemical alteration of biological tissues by the applied ultrasonic waves. Unlike iontophoresis, the risk of skin damage appears to be low.Applications of ultrasound to drug delivery have been discussed in the literature. See, for example: P. Tyle et al., supra (which provides an overview of sonophoresis); S. Miyazaki et al., J. Pharm. Pharmacol. 40:716-717 (1988) (controlled release of insulin from a polymer implant using ultrasound); J. Kost et al., Proceed. Intern. Symp. Control. Rel. Bioact. Mater.16(141):294-295 (1989) (overview of the effect of ultrasound on the permeability of human skin and synthetic membranes); H. Benson et al., Physical Therapy 69(2):113-118 (1989) (effect of ultrasound on the percutaneous absorption of benzydamine); E. Novak, Arch. Phys. Medicine & Rehab. 45:231-232 (1964) (enhanced penetration of lidocaine through intact skin using ultrasound); J. E. Griffin et al., Amer. J. Phys. Medicine 44(1):20-25 (1965) (ultrasonic penetration of cortisol into pig tissue); J. E. Griffin et al., J. Amer. Phys. Therapy Assoc.46:18-26 (1966) (overview of the use of ultrasonic energy in drug therapy); J. E. Griffin et al., Phys. Therapy 47(7):594-601 (1967) (ultrasonic penetration of hydrocortisone); J. E. Griffin et al., Phys. Therapy 48(12):1336-1344 (1968) (ultrasonic penetration of cortisol into pig tissue); J. E. Griffin et al., Amer. J. Phys. Medicine 51(2):62-72 (1972) (same); J. C. McElnay, Int. J. Pharmaceutics 40:105-110 (1987) (the effect of ultrasound on the percutaneous absorption of fluocinolone acetonide); and C. Escoffier et al., Bioeng. Skin 2:87-94 (1986) (in vitro study of the velocity of ultrasound in skin).In addition to the aforementioned art, U.S. Pat. Nos. 4,767,402 and 4,780,212 to Kost et al. relate specifically to the use of specific frequencies of ultrasound to enhance the rate of permeation of a drug through human skin or through a synthetic membrane.While the application of ultrasound in conjunction with drug delivery is thus known, results have for the most part been disappointing, i.e., enhancement of skin permeability has been relatively low.SUMMARY OF THE INVENTIONThe present invention provides a novel method for enhancing the rate of permeation of a given material through a selected intact area of an individual's body surface. The method comprises contacting the selected intact area with the material and applying ultrasound to the contacted area. The ultrasound preferably has a frequency of above about 10 MHz, and is continued at an intensity and for a period of time sufficient to enhance the rate of permeation of the material into and through the body surface. The ultrasound can also be used to pretreat the selected area of the body surface in preparation for drug delivery, or for diagnostic purposes, i.e., to enable non-invasive sampling of physiologic material beneath the skin or body surface.In addition to enhancing the rate of permeation of a material, the present invention involves increasing the permeability of a biological membrane such as the stratum corneum by applying ultrasound having a frequency of above about 10 MHz to the membrane at an intensity and for a period of time sufficient to give rise to increased permeability of the membrane. Once the permeability of the membrane has been increased, it is possible to apply a material thereto and obtain an increased rate of flowof the material through the membrane.It is accordingly a primary object of the invention to address the aforementioned deficiencies of the prior art by providing a method of enhancing the permeability of biological membranes and thus allow for an increased rate of delivery of material therethrough.It is another object of the invention to provide such a method which is effective with or without chemical permeation enhancers.It is still another object of the invention to minimize lag time in such a method and provide a relatively short total treatment time.It is yet another object of the invention to provide such a method in which drug delivery is effected using ultrasound.It is a further object of the invention to enable sampling of tissue beneath the skin or other body surface by application of high frequency (>10 MHz) ultrasound thereto.A further feature of the invention is that it preferably involves ultrasound of a frequency greater than about 10 MHz.Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention.BRIEF DESCRIPTION OF THE DRAWINGSFIGS. 1A, 1B and 1C are theoretical plots of energy dissipation within the skin barrier versus frequency of applied ultrasound.FIGS. 2, 3 and 4 are graphic representations of the amount of salicylic acid recovered from the stratum corneum after ultrasound treatment at different frequencies.FIGS. 5 and 6 represent the results of experiments similar to those summarized in FIGS. 2, 3 and 4, but with a shorter treatment time.FIGS. 7, 8, 9 and 10 are plots of enhancement versus "tape-strip number," as described in the Example.FIG. 11 illustrates the effect of ultrasound on the systemic availability of salicylic acid following topical application.DETAILED DESCRIPTION OF PREFERRED EMBODIMENTSBefore the present method of enhancing the rate of permeation of a material through a biological membrane and enhancing the permeability of membranes using ultrasound are disclosed and described, it is to be understood that this invention is not limited to the particular process steps and materials disclosed herein as such process steps and materials may, of course, vary. It is alto to be understood that the terminology used herein is used for purpose of describing particular embodiments only and is not intended to be limiting since the scope of the present invention will be limited only by the appended claims.It must be noted that as used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to "a drug" includes mixtures of drugs and their pharmaceutically acceptable salts, reference to "an ultrasound device" includes one or more ultrasound devices of the type necessary for carrying out the present invention, and reference to "the method of administration" includes one or more different methods of administration known to those skilled in the art or which will become known to those skilled in the art upon reading this disclosure.In one aspect of the invention a method is provided forenhancing the permeation of a given material such as a drug, pharmacologically active agent, or diagnostic agent into and/or through a biological membrane on an individual's body surface, which method comprises: (a) contacting the membrane with the chosen material in a pharmacologically acceptable carrier medium; and (b) applying ultrasound of an intensity and for a treatment time effective to produce delivery of the material through the membrane. The material is preferably a drug and it is preferable to obtain a desired blood level of the drug in the individual. The ultrasound is of a frequency and intensity effective to increase the permeability of the selected area to the applied drug over that which would be obtained without ultrasound. The ultrasound preferably has a frequency of more than 10 MHz, and may be applied either continuously or pulsed, preferably continuously. The ultrasound may be applied to the skin either before or after application of the drug medium so long as administration of the ultrasound and the drug medium is relatively simultaneous, i.e., the ultrasound is applied within about 6, more preferably within about 4, most preferably within about 2 minutes of drug application.The invention is useful for achieving transdermal permeation of pharmacologically active agents which otherwise would be quite difficult to deliver through the skin or other body surface. For example, proteinaceous drugs and other high molecular weight pharmacologically active agents are ideal candidates for transdermal, transmucosal or topical delivery using the presently disclosed method. In an alternative embodiment, agents useful for diagnostic purposes may also be delivered into and/or through the body surface using the present method.The invention is also useful as a non-invasive diagnostictechnique, i.e., in enabling the sampling of physiologic material from beneath the skin or other body surface and into a collection (and/or evaluation) chamber.The present invention will employ, unless otherwise indicated, conventional pharmaceutical methodology and more specifically conventional methodology used in connection with transdermal delivery of pharmaceutically active compounds and enhancers.In describing the present invention, the following terminology will be used in accordance with the definitions set out below.A "biological membrane" is intended to mean a membrane material present within a living organism which separates one area of the organism from another and, more specifically, which separates the organism from its outer environment. Skin and mucous membranes are thus included."Penetration enhancement" or "permeation enhancement" as used herein relates to an increase in the permeability of skin to a material such as a pharmacologically active agent, i.e., so as to increase the rate at which the material permeates into and through the skin. The present invention involves enhancement of permeation through the use of ultrasound, and, in particular, through the use of ultrasound having a frequency of greater than 10 MHz."Transdermal" (or "percutaneous") shall mean passage of a material into and through the skin to achieve effective therapeutic blood levels or deep tissue therapeutic levels. While the invention is described herein primarily in terms of "transdermal" administration, it will be appreciated by those skilled in the art that the presently disclosed and claimed methodalso encompasses the "transmucosal" and "topical" administration of drugs using ultrasound. "Transmucosal" is intended to mean passage of any given material through a mucosal membrane of a living organism and more specifically shall refer to the passage of a materialfrom the outside environment of the organism, through a mucous membrane and into the organism. "Transmucosal" administration thus includes delivery of drugs through either nasal or buccal tissue. By "topical" administration is meant local administration of a topical pharmacologically active agent to the skin as in, for example, the treatment of various skin disorders or the administration of a local anaesthetic. "Topical" delivery can involve penetration of a drug into the skin but not through it, i.e., topical administration does not involve actual passage of a drug into the bloodstream."Carriers" or "vehicles" as used herein refer to carrier materials without pharmacological activity which are suitable for administration with other pharmaceutically active materials, and include any such materials known in the art, e.g., any liquid, gel, solvent, liquid diluent, solubilizer, or the like, which is nontoxic and which does not interact with the drug to be administered in a deleterious manner. Examples of suitable carriers for use herein include water, mineral oil, silicone, inorganic gels, aqueous emulsions, liquid sugars, waxes, petroleum jelly, and a variety of other oils and polymeric materials.By the term "pharmacologically active agent" or "drug" as used herein is meant any chemical material or compound suitable for transdermal or transmucosal administration which can either (1) have a prophylactic effect on the organism and prevent an undesired biological effect such as preventing aninfection, (2) alleviates a condition caused by a disease such as alleviating pain caused as a result of a disease, or (3) either alleviates or completely eliminates the disease from the organism. The effect of the agent may be local, such as providing for a local anaesthetic effect or it may be systemic. Such substances include the broad classes of compounds normally delivered through body surfaces and membranes, including skin. In general, this includes: anti-infectives such as antibiotics and antiviral agents; analgesics and analgesic combinations; anorexics; antihelminthics; antiarthritics; antiasthmatic agents; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antihistamines; antiinflammatory agents; antimigraine preparations; antinauseants; antineoplastics; antiparkinsonism drugs; antipruritics; antipsychotics; antipyretics; antispasmodics; anticholinergics; sympathomimetics; xanthine derivatives; cardiovascular preparations including potassium and calcium channel blockers, beta-blockers, and antiarrhythmics; antihypertensives; diuretics; vasodilators including general coronary, peripheral and cerebral; central nervous system stimulants; cough and cold preparations, including decongestants; hormones such as estradiol and other steroids, including corticosteroids; hypnotics; immunosuppressives; muscle relaxants; parasympatholytics; psychostimulants; sedatives; and tranquilizers. By the method of the present invention, both ionized and nonionzed drugs may be delivered, as can drugs of either high or low molecular weight.Proteinaceous and polypeptide drugs represent a preferred class of drugs for use in conjunction with the presently disclosed and claimed invention. Such drugs cannot generally be administered orally in that they Are often destroyed in the G.I.tract or metabolized in the liver. Further, due to the high molecular weight of most polypeptide drugs, conventional transdermal delivery systems are not generally effective. It is also desirable to use the methodof the invention in conjunction with drugs to which the permeability of the skin is relatively low, or which give rise to a long lag-time (application of ultrasound as described herein has been found to significantly reduce the lag-time involved with the transdermal administration of most drugs).By a "therapeutically effective" amount of a pharmacologically active agent is meant a nontoxic but sufficient amount of a compound to provide the desired therapeutic effect. The desired therapeutic effect may be a prophylactic effect, in preventing a disease, an effect which alleviates a system of the disease, or a curative effect which either eliminates or aids in the elimination of the disease.As noted above, the present invention is a method for enhancing the rate of permeation of a drug through an intact area of an individual's body surface, preferably the human skin. The method involves transdermal administration of a selected drug in conjunction with ultrasound. Ultrasound causes thermal, mechanical and chemical alterations of biological tissue, thereby enhancing the rate of permeation of a given material therethrough.While not wishing to be bound by theory, applicants propose that the use of higher frequency ultrasound as disclosed herein specifically enhances the permeation of the drug through the outer layer of skin, i.e., the stratum corneum, by causing momentary and reversible perturbations within (and thus short-term, reversible reduction in the barrier function of) the layer ofthe stratum corneum. It will be appreciated by those skilled in the art of transdermal drug delivery that a number of factors related to the present method will vary with the drug to be administered, the disease or injury to be treated, the age of the selected individual, the location of the skin to which the drug is applied, and the like.As noted above, "ultrasound" is ultrasonic radiation of a frequency above 20,000 Hz. As may be deduced from the literature cited above, ultrasound used for most medical purposes typically employs frequencies ranging from 1.6 to about 10 MHz. The present invention, by contrast, employs ultrasound frequencies of greater than about 10 MHz, preferably in the range of about 15 to 50 MHz, most preferably in the range of about 15 to 25 MHz. It should be emphasized that these ranges are intended to be merely illustrative of the preferred embodiment; in some cases higher or lower frequencies may be used.The ultrasound may be pulsed or continuous, but is preferably continuous when lower frequencies are used. At very high frequencies, pulsed application will generally be preferred so as to enable dissipation of generated heat.The preferred intensity of the applied ultrasound is less than about 5.0 W/cm.sup.2, more preferably is in the range of about 0.01 to 5.0 W/cm.sup.2, and most preferably is in the range of 0.05 to 3.0 W/cm.sup.2. The total treatment time, i.e., the period over which drug and ultrasound are administered, will vary depending on the drug administered, the disease or injury treated, etc., but will generally be on the order of about 30 seconds to 60 minutes, preferably 5 to 45 minutes, more preferably 5 to 30 minutes, and most preferably 5 to 10minutes. It should be noted that the aforementioned ranges represent suggested, or preferred, treatment times, but are not in any way intended to be limiting. Longer or shorter times may be possible and in some cases desirable. Virtually any type of device may be used to administer the ultrasound, providing that the device is callable of producing the higher frequency ultrasonic waves required by the present method. A device will typically have a power source such as a small battery, a transducer, a reservoir in which the drug medium is housed (and which may or may not be refillable), and a means to attach the system to the desired skin site.As ultrasound does not transmit well in air, a liquid medium is generally needed to efficiently and rapidly transmit ultrasound between the ultrasound applicator and the skin. As explained by P. Tyle et al., cited above, the selected drug medium should contain a "coupling" or "contacting" agent typically used in conjunction with ultrasound. The coupling agent should have an absorption coefficient similar to that of water, and furthermore be nonstaining, nonirritating to the skin, and slow drying. It is clearly preferred that the coupling agent retain a paste or gel consistency during the time period of ultrasound administration so that contact is maintained between the ultrasound source and the skin. Examples of preferred coupling agents are mixtures of mineral oil and glycerine and propylene glycol, oil/water emulsions, and a water-based gel. A solid-state, non-crystalline polymeric film having the above-mentioned characteristics may also be used. The drug medium may also contain a carrier or vehicle, as defined alone.A transdermal patch as well known in the art may be used in conjunction with the present invention, i.e., to deliver the drugmedium to the skin. The "patch", however, must have the properties of the coupling agent as described in the preceding paragraph so as to enable transmission of the ultrasound from the applicator, through the patch, to the skin.As noted earlier in this section, virtually any chemical material or compound suitable for transdermal, transmucosal or topical administration may be administered using the present method. Again, the present invention is particularly useful to enhance delivery of proteinaceous and other high molecular weight drugs.The method of the invention is preferably carried out as follows. The drug medium, i.e., containing the selected drug or drugs in conjunction with the coupling agent and optionally a carrier or vehicle material, is applied to an area of intact body surface. Ultrasound preferably having a frequency greater than about 10 MHz may be applied before or after application of the drug medium, but is preferably applied immediately before application of the drug so as to "pretreat" the skin prior to drug administration.It should also be pointed out that the present method may be used in conjunction with a chemical permeation enhancer as known in the art, wherein the ultrasound enables the use of much lower concentrations of permeation enhancer--thus minimizing skin irritation and other problems frequently associated with such compounds--than would be possible in the absence of ultrasound. The permeation enhancer may be incorporated into the drug medium or it maybe applied in a conventional transdermal patch after pretreatment of the body surface with ultrasound.The present invention may also be used in conjunction with。
国医大师王琦辨湿热体质论治疾病的临床思路
•临证经验•国医大师王琦辨湿热体质论治疾病的临床思路董思颖u,孟翔鹤王济K2r北京中医药大学中医学院，北京100029; 2国家中医体质与治未病研究院，北京100029)摘要：国医大师王琦教授创立了九种体质学说，并将自己的特色诊疗经验发展成为辨体-辨病-辨证的特色诊疗模式，开创了中医“以人为本”临床诊疗思路的先导，为中医学的现代发展提供了新经验。
文章从形成原因、体质特点以及与疾病的相关性3个方面对湿热体质进行了介绍，同时从辨体-辨病-辨证、治疗原则、调体方药、主病主方论4个方面对王琦教授调治湿热体质的相关经验进行了归纳总结，以期为湿热体质的调体与相关疾病治疗提供借鉴。
关键词：名老中医经验；湿热体质；辨体论治；王琦；临床思路基金资助：科技部国家重点研发计划项目（N〇.2018Y F C1704100, N〇.2018Y F C1704101)T C M master W A N G Qi's clinical thought on treating diseases by differentiatingd a m p-he a t constitutionDONG Si-ying1'2,MENG Xiang-he12,WANG Ji12('College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;'National Institute of TCM Constitution and Preventive Medicine, Beijing 100029, China )Abstract：Professor WANG Qi, a master of Chinese medicine, created nine kinds of constitution theory and developedhis own diagnosis and treatment experience into a model of constitution differentiation-disease differentiation-syndrome differentiation, and pioneering the lpeople-oriented, clinical diagnosis and treatment of Chinese medicine. It has provided new experience for the modern development of Chinese medicine. In this paper, the cause of formation, constitutional characteristics,and the relationship between diseases are introduced about damp-heat constitution, and it was summarized from constitution differentiation-disease differentiation-syndrome differentiation, treatment principles, treatment with constitution regulation, theoryof main prescription matched to main disease for treating damp-heat constitution related diseases. Therefore, professor WANGQi's experience in the treatment of damp-heat constitution is summarized to provide reference for constitution adjustment andtreating related diseases of damp-heat constitution.K e y W o r d s：Experience of famous experts of TCM; Damp-heat constitution; Treating by constitutions differentiation;WANG Qi; Clinical thinkingF u n d i n g:National Key R&D Program Project of Ministry of Science and Technology (No.2018YFC1704100,N〇.2018YFC1704101)体质是在先天遗传和后天获得的基础上，表现 出的形态结构、生理机能和心理状态等方面综合的、相对稳定的特质n1。
ANSI Z97.1-2004
Printed in the United States of America
ANSI Z97.1 copyright 2004 ANSI Z97.1 Accredited Standards Commis forward is not part of ANSI Z97-1-2004) This standard was developed under procedures accredited as meeting the criteria for American National Standards. The consensus committee that approved the Standard was balanced to ensure that individuals from competent and concerned interests have had an opportunity to participate. It was developed within the approved scope as stated in Section 1.1 of the standard. This Standard is available for public review on a continuing basis. This provides an opportunity for additional public input from industry, academia, regulatory agencies, and the public-at-large. The use of an addenda system will allow revisions made in response to public review or committee actions to be published as required. This standard, which is the result of extended and careful consideration of available knowledge and experience on the subject, is intended to provide minimum requirements that are recommended for use, adoption, enforcement by federal, state and local authorities and by model codes. It is recommended that this standard be referenced but not incorporated in any statute. The impact tests described in this standard are based on realistic information and criteria but it must be acknowledged that in a small number of cases, involving rare coincidence, somewhat larger impact forces could be developed. This Standard does not recommend where safety glazing should be used or, when it is used, what type of glazing material should be used. For this information one should consult other codes, standards and manufacturer's information. Neither the standards committee nor the secretariat feel that this standard is perfect or in its ultimate form. It is recognized that, although safety-glazing materials are widely used and accepted, new developments are to be expected and revisions of the standards are necessary as the art progresses and further experience is gained. The accredited standards committee (ASC) has carefully considered the inclusion of a widely used center punch fragmentation test in the standard as a secondary method for testing tempered glass. The ASC decided that while this test is a common quality control method used in the tempering industry, the actual evaluation and reporting of the test results needs further study. The tempering division of the Glass Association of North America (GANA) has agreed to pursue the development of this test and will propose a center punch fragmentation test for consideration at the next review of this standard. This standard is a successor standard to the 1994 edition. The 1994 standard was a reaffirmation of the 1984 standard with various editorial changes and the 1984 standard succeeded those of the 1975, 1972 and 1966 editions. For communication with the Committee please refer to the following page.
奥美拉唑Label-阿斯利康
_______________________________________________________________________________________________________________________ HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PRILOSEC safely and effectively. See full prescribing information for PRILOSEC. PRILOSEC (omeprazole) delayed-release capsules PRILOSEC (omeprazole magnesium) for delayed-release oral suspension INITIAL U.S. APPROVAL: 1989 -------------------------RECENT MAJOR CHANGES----------------------------Warnings and Precautions, Interactions with Diagnostic Investigations for Neuroendocrine Tumors (5.8) 03/2014 Indications and Usage, Treatment of Gastroesophageal Reflux Disease (GERD) (adults and pediatric patients) (1.3) 12/2014 Dosage and Administration, Maintenance of Healing of Erosive Esophagitis (2.5) 12/2014 Warnings and Precautions, Acute Interstitial Nephritis (5.3) 12/2014 Warnings and Precautions, Cyanocobalamin (vitamin B-12) Deficiency (5.4) 12/2014 --------------------------INDICATIONS AND USAGE----------------------------PRILOSEC is a proton pump inhibitor indicated for: • Treatment in adults of duodenal ulcer (1.1) and gastric ulcer (1.2) • Treatment in adults and children of gastroesophageal reflux disease (GERD) (1.3) and maintenance of healing of erosive esophagitis (1.4) • Pathologic Hypersecretory Conditions (1.5) The safety and effectiveness of PRILOSEC in pediatric patients <1 year of age have not been established. (8.4) -----------------------DOSAGE AND ADMINISTRATION----------------------Indication Omeprazole Dose Frequency Treatment of Active Duodenal Ulcer (2.1) 20 mg Once daily for 4 weeks. Some patients may require an additional 4 weeks • Acute interstitial nephritis has been observed in patients taking PPIs. (5.3) • Cyanocobalamin (vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. (5.4) • PPI therapy may be associated with increased risk of Clostridium difficile associated diarrhea. (5.5) • Avoid concomitant use of PRILOSEC with clopidogrel. (5.6) • Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (5.7) • Hypomagnesemia has been reported rarely with prolonged treatment with PPIs. (5.8) • Avoid concomitant use of PRILOSEC with St. John’s Wort or rifampin due to the potential reduction in omeprazole concentrations. (5.9, 7.3) • Interactions with diagnostic investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in hypergastrinemia and enterochromaffin-like cell hyperplasia and increased Choromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. (5.10, 12.2) -------------------------------ADVERSE REACTIONS--------------------------Adults: Most common adverse reactions in adults (incidence ≥ 2%) are • Headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence (6) Pediatric patients (1 to 16 years of age): Safety profile similar to that in adults, except that respiratory system events and fever were the most frequently reported reactions in pediatric studies. (8.4) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or /medwatch. --------------------------------DRUG INTERACTIONS--------------------------H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence (2.2) Triple Therapy: PRILOSEC 20 mg Each drug twice daily for 10 Amoxicillin 1000 mg days Clarithromycin 500 mg Dual Therapy : PRILOSEC 40 mg Once daily for 14 days Clarithromycin 500 mg Three times daily for 14 days Gastric Ulcer (2.3) 40 mg Once daily for 4 to 8 weeks GERD (2.4) 20 mg Once daily for 4 to 8 weeks Erosive Esophagitis (2.5) 20 mg Once daily* Pathological Hypersecretory Conditions (2.6) 60 mg (varies with individual patient) Once daily Pediatric Patients (1 to 16 years of age) (2.7) GERD** And Maintenance of Healing of Erosive Esophagitis Weight Dose 5 < 10 kg 5 mg 10< 20 kg 10 mg > 20 kg 20 mg Once daily **4 to 8 weeks ----------------------DOSAGE FORMS AND STRENGTHS--------------------• PRILOSEC Delayed-Release Capsules, 10 mg, 20 mg and 40 mg (3) • PRILOSEC For Delayed-Release Oral Suspension, 2.5 mg or 10 mg (3) ---------------------------CONTRAINDICATIONS-------------------------------Known hypersensitivity to any component of the formulation or substituted benzimidazoles (angioedema and anaphylaxis have occurred). (4) -----------------------WARNINGS AND PRECAUTIONS-----------------------• Symptomatic response does not preclude the presence of gastric malignancy. (5.1) • Atrophic gastritis: has been noted with long-term therapy. (5.2) • Atazanavir and nelfinavir: PRILOSEC reduces plasma levels of atazanavir and nelfinavir. Concomitant use is not recommended. (7.1) • Saquinavir: PRILOSEC increases plasma levels of saquinavir. Monitor for toxicity and consider dose reduction of saquinavir. (7.1) • May interfere with drugs for which gastric pH affects bioavailability (e.g., ketoconazole, iron salts, erlotinib, ampicillin esters, digoxin and mycophenolate mofetil ). Patients treated with PRILOSEC and digoxin may need to be monitored for increases in digoxin toxicity. (7.2) • Clopidogrel: PRILOSEC decreases exposure to the active metabolite of clopidogrel. (7.3, 12.3) • Cilostazol: PRILOSEC increases systemic exposure of cilostazol and one of its active metabolites. Consider dose reduction of cilostazol. (7.3) • Drugs metabolized by cytochrome P450 (e.g., diazepam, warfarin, phenytoin, cyclosporine, disulfiram, benzodiazepines): PRILOSEC can prolong their elimination. Monitor and determine need for dose adjustments. (7.3) • Patients treated with proton pump inhibitors and warfarin may need to be monitored for increases in INR and prothrombin time. (7.3) • Combined inhibitor of CYP2C19 and 3A4 (e.g. voriconazole) may raise omeprazole levels. (7.3) • Tacrolimus: PRILOSEC may increase serum levels of tacrolimus. (7.4) • Methotrexate: PRILOSEC may increase serum levels of methotrexate. (7.7) ------------------------USE IN SPECIFIC POPULATIONS----------------------• Pregnancy: Based on animal data may cause fetal harm. (8.1) • Patients with hepatic impairment: Consider dose reduction, particularly for maintenance of healing of erosive esophagitis. (12.3) See 17 for PATIENT COUNSELING INFORMATION and FDA-Approved Medication Guide. REVISED: 12/2014FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE1.1 Duodenal Ulcer (adults)1.2 Gastric Ulcer (adults)1.3 Treatment of Gastroesophageal Reflux Disease (GERD)(adults and pediatric patients)1.4 Maintenance of Healing of Erosive Esophagitis (adults andpediatric patients)1.5 Pathological Hypersecretory Conditions (adults)2 DOSAGE AND ADMINISTRATION2.1 Short-Term Treatment of Active Duodenal Ulcer2.2 H. pylori Eradication for the Reduction of the Risk ofDuodenal Ulcer Recurrence2.3 Gastric Ulcer2.4 Gastroesophageal Reflux Disease (GERD)2.5 Maintenance of Healing of Erosive Esophagitis2.6 Pathological Hypersecretory Conditions2.7 Pediatric Patients2.8 Alternative Administration Options3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Concomitant Gastric Malignancy5.2 Atrophic Gastritis5.3 Acute Interstitial Nephritis5.4 Cyanocobalamin (vitamin B-12) Deficiency5.5 Clostridium difficile associated diarrhea5.6 Interaction with Clopidogrel5.7 Bone Fracture5.8 Hypomagnesemia5.9 Concomitant Use of PRILOSEC with St. John’s Wort orrifampin5.10 Interactions with Diagnostic Investigations forNeuroendocrine Tumors5.11 Concomitant use of PRILOSEC with Methotrexate6 ADVERSE REACTIONS6.1 Clinical Trials Experience with PRILOSEC Monotherapy6.2 Clinical Trials Experience with PRILOSEC in CombinationTherapy for H. pylori Eradication6.3 Post-marketing Experience 7 DRUG INTERACTIONS7.1 Interference with Antiretroviral Therapy7.2 Drugs for Which Gastric pH Can Affect Bioavailability7.3 Effects on Hepatic Metabolism/Cytochrome P-450 Pathways7.4 Tacrolimus7.5 Interactions with Investigations of Neuroendocrine Tumors7.6 Combination Therapy with Clarithromycin7.7 Methotrexate8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Hepatic Impairment8.7 Renal Impairment8.8 Asian Population10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics12.4 Microbiology13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility13.2 Animal Toxicology and/or Pharmacology14 CLINICAL STUDIES14.1 Duodenal Ulcer Disease14.2 Gastric Ulcer14.3 Gastroesophageal Reflux Disease (GERD)14.4 Erosive Esophagitis14.5 Pathological Hypersecretory Conditions14.6 Pediatric GERD15 REFERENCES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are not listed._______________________________________________________________________________________________________________________1FULL PRESCRIBING INFORMATION INDICATIONS AND USAGE1.1 Duodenal Ulcer (adults)PRILOSEC is indicated for short-term treatment of active duodenal ulcer in adults. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.PRILOSEC in combination with clarithromycin and amoxicillin, is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults.PRILOSEC in combination with clarithromycin is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori in adults.Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14.1) and Dosage and Administration (2)].Among patients who fail therapy, PRILOSEC with clarithromycin is more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [s ee Microbiology section (12.4)], and the clarithromycin package insert, Microbiology section.1.2 Gastric Ulcer (adults)PRILOSEC is indicated for short-term treatment (4-8 weeks) of active benign gastric ulcer in adults [s ee Clinical Studies (14.2)].1.3 Treatment of Gastroesophageal Reflux Disease (GERD) (adults and pediatric patients)Symptomatic GERDPRILOSEC is indicated for the treatment of heartburn and other symptoms associated with GERD in pediatric patients and adults for up to 4 weeks.Erosive EsophagitisPRILOSEC is indicated for the short-term treatment (4-8 weeks) of erosive esophagitis that has been diagnosed by endoscopy in pediatric patients and adults [s ee Clinical Studies (14.4)].The efficacy of PRILOSEC used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of erosive esophagitis or GERD symptoms (eg, heartburn), additional 4-8 week courses of omeprazole may be considered.1.4 Maintenance of Healing of Erosive Esophagitis(adults and pediatric patients)PRILOSEC is indicated to maintain healing of erosive esophagitis in pediatric patients and adults.Controlled studies do not extend beyond 12 months [s ee Clinical Studies (14.4)].1.5 Pathological Hypersecretory Conditions (adults) PRILOSEC is indicated for the long-term treatment of pathological hypersecretory conditions (eg, Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults.2 DOSAGE AND ADMINISTRATIONPRILOSEC Delayed-Release Capsules should be taken before eating. In the clinical trials, antacids were used concomitantly with PRILOSEC.Patients should be informed that the PRILOSEC Delayed-Release Capsule should be swallowed whole.For patients unable to swallow an intact capsule, alternative administration options are available [s ee Dosage and Administration (2.8)].2.1 Short-Term Treatment of Active Duodenal Ulcer The recommended adult oral dose of PRILOSEC is 20 mg once daily. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.2.2 H. pylori Eradication for the Reduction of the Risk of Duodenal Ulcer RecurrenceTriple Therapy (PRILOSEC/clarithromycin/amoxicillin) — The recommended adult oral regimen is PRILOSEC 20 mg plus clarithromycin 500 mg plus amoxicillin 1000 mg each given twice daily for 10 days. In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of PRILOSEC 20 mg once daily is recommended for ulcer healing and symptom relief.Dual Therapy (PRILOSEC/clarithromycin) — The recommended adult oral regimen is PRILOSEC 40 mg once daily plus clarithromycin 500 mg three times daily for 14 days. In patients with an ulcer present at the time of initiation of therapy, an additional 14days of PRILOSEC 20 mg once daily is recommended for ulcer healing and symptom relief.2.3 Gastric UlcerThe recommended adult oral dose is 40 mg once daily for 4-8 weeks.2.4 Gastroesophageal Reflux Disease (GERD)The recommended adult oral dose for the treatment of patients with symptomatic GERD and no esophageal lesions is 20 mg daily for up to 4 weeks. The recommended adult oral dose for the treatment of patients with erosive esophagitis and accompanying symptoms due to GERD is 20 mg daily for 4 to 8 weeks.2.5 Maintenance of Healing of Erosive EsophagitisThe recommended adult oral dose is 20 mg daily. Controlled studies do not extend beyond 12 months [s ee Clinical Studies (14.4)].2.6 Pathological Hypersecretory ConditionsThe dosage of PRILOSEC in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 120 mg three times daily have been administered. Daily dosages of greater than 80 mg should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously with PRILOSEC for more than 5 years.2.7 Pediatric PatientsFor the treatment of GERD and maintenance of healing of erosive esophagitis, the recommended daily dose for pediatric patients 1 to 16 years of age is as follows:Patient Weight Omeprazole Daily Dose5 < 10 kg 5 mg10 < 20 kg 10 mg>20 kg 20 mgOn a per kg basis, the doses of omeprazole required to heal erosive esophagitis in pediatric patients are greater than those for adults.Alternative administrative options can be used for pediatric patients unable to swallow an intact capsule [s ee Dosage and Administration (2.8)].2.8 Alternative Administration OptionsPRILOSEC is available as a delayed-release capsule or as a delayed-release oral suspension.For patients who have difficulty swallowing capsules, the contents of a PRILOSEC Delayed-Release Capsule can be added to applesauce.One tablespoon of applesauce should be added to an empty bowl and the capsule should be opened. All of the pellets inside the capsule should be carefully emptied on the applesauce. The pellets should be mixed with the applesauce and then swallowed immediately with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The pellets should not be chewed or crushed. The pellets/applesauce mixture should not be stored for future use.PRILOSEC For Delayed-Release Oral Suspension should be administered as follows:• Empty the contents of a 2.5 mg packet into a container containing 5 mL of water.• Empty the contents of a 10 mg packet into a container containing 15 mL of water.• Stir• Leave 2 to 3 minutes to thicken.• Stir and drink within 30 minutes.• If any material remains after drinking, add more water, stir and drink immediately.For patients with a nasogastric or gastric tube in place:• Add 5 mL of water to a catheter tipped syringe andthen add the contents of a 2.5 mg packet (or 15 mL ofwater for the 10 mg packet). It is important to only usea catheter tipped syringe when administeringPRILOSEC through a nasogastric tube or gastric tube.• Immediately shake the syringe and leave 2 to 3minutes to thicken.• Shake the syringe and inject through the nasogastric or gastric tube, French size 6 or larger, into the stomachwithin 30 minutes.• Refill the syringe with an equal amount of water.• Shake and flush any remaining contents from thenasogastric or gastric tube into the stomach.3 DOSAGE FORMS AND STRENGTHSPRILOSEC Delayed-Release Capsules, 10 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 606 on cap and PRILOSEC 10 on the body.PRILOSEC Delayed-Release Capsules, 20 mg, are opaque, hard gelatin, amethyst colored capsules, coded 742 on cap and PRILOSEC 20 on the body.PRILOSEC Delayed-Release Capsules, 40 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 743 on cap and PRILOSEC 40 on the body.PRILOSEC For Delayed-Release Oral Suspension, 2.5 mg or 10 mg, is supplied as a unit dose packet containing a fine yellow powder, consisting of white to brownish omeprazole granules and pale yellow inactive granules.4 CONTRAINDICATIONSPRILOSEC Delayed-Release Capsules are contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [s ee Adverse Reactions (6)].For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with PRILOSEC, refer to the CONTRAINDICATIONS section of their package inserts.5 WARNINGS AND PRECAUTIONS5.1 Concomitant Gastric MalignancySymptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy.5.2 Atrophic GastritisAtrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole.5.3 Acute Interstitial NephritisAcute interstitial nephritis has been observed in patients taking PPIs including PRILOSEC. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue PRILOSEC if acute interstitial nephritis develops [see Contraindications (4)].5.4 Cyanocobalamin (vitamin B-12) DeficiencyDaily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo-or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acidsuppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.5.5 Clostridium difficile associated diarrheaPublished observational studies suggest that PPI therapy like PRILOSEC may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)].Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with PRILOSEC, refer to WARNINGS and PRECAUTIONS sections of those package inserts.5.6 Interaction with ClopidogrelAvoid concomitant use of PRILOSEC with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 80 mg omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours apart. When using PRILOSEC, consider alternative anti-platelet therapy [see Drug Interactions (7.3) and Pharmacokinetics (12.3)].5.7 Bone FractureSeveral published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) and Adverse Reactions (6.3)].5.8 HypomagnesemiaHypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals mayconsider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.3)].5.9 Concomitant use of PRILOSEC with St. John’s Wort or rifampinDrugs which induce CYP2C19 or CYP3A4 (such as St. John’s Wort or rifampin) can substantially decrease omeprazole concentrations [see Drug Interactions (7.3)]. Avoid concomitant use of PRILOSEC with St. John’s Wort or rifampin.5.10 Interactions with Diagnostic Investigations for Neuroendocrine TumorsSerum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop omeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.5.11 Concomitant use of PRILOSEC with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7.7)].6 ADVERSE REACTIONS6.1 Clinical Trials Experience with PRILOSEC MonotherapyBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The safety data described below reflects exposure to PRILOSEC Delayed-Release Capsules in 3096 patients from worldwide clinical trials (465 patients from US studies and 2,631 patients from international studies). Indications clinically studied in US trials included duodenal ulcer, resistant ulcer, and Zollinger-Ellison syndrome. The international clinical trials were double blind and open-label in design. The most common adverse reactions reported (i.e., with an incidence rate ≥ 2%) from PRILOSEC-treated patients enrolled in these studies included headache (6.9%), abdominal pain (5.2%), nausea (4.0%), diarrhea (3.7%), vomiting (3.2%), and flatulence (2.7%).Additional adverse reactions that were reported with an incidence≥1% included acid regurgitation (1.9%), upper respiratory infection (1.9%), constipation (1.5%), dizziness (1.5%), rash (1.5%), asthenia (1.3%), back pain (1.1%), and cough (1.1%).The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65 years of age or less.The clinical trial safety profile in pediatric patients who received PRILOSEC Delayed-Release Capsules was similar to that in adult patients. Unique to the pediatric population, however, adverse reactions of the respiratory system were most frequently reported in both the 1 to <2 and 2 to 16 year age groups (75.0% and 18.5%, respectively). Similarly, fever was frequently reported in the 1 to 2 year age group (33.0%), and accidental injuries were reported frequently in the 2 to 16 year age group (3.8%) [see Use in Specific Populations (8.4)].6.2 Clinical Trials Experience with PRILOSEC in Combination Therapy for H. pylori EradicationIn clinical trials using either dual therapy with PRILOSEC and clarithromycin, or triple therapy with PRILOSEC, clarithromycin, and amoxicillin, no adverse reactions unique to these drug combinations were observed. Adverse reactions observed were limited to those previously reported with omeprazole, clarithromycin, or amoxicillin alone.Dual Therapy (PRILOSEC/clarithromycin)Adverse reactions observed in controlled clinical trials using combination therapy with PRILOSEC and clarithromycin (n = 346) that differed from those previously described for PRILOSEC alone were taste perversion (15%), tongue discoloration (2%), rhinitis (2%), pharyngitis (1%) and flu-syndrome (1%). (For more information on clarithromycin, refer to the clarithromycin prescribing information, Adverse Reactions section.)Triple Therapy (PRILOSEC/clarithromycin/amoxicillin)The most frequent adverse reactions observed in clinical trials using combination therapy with PRILOSEC, clarithromycin, and amoxicillin (n = 274) were diarrhea (14%), taste perversion (10%), and headache (7%). None of these occurred at a higher frequency than that reported by patients taking antimicrobial agents alone. (For more information on clarithromycin or amoxicillin, refer to the respective prescribing information, Adverse Reactions sections.)6.3 Post-marketing ExperienceThe following adverse reactions have been identified during post-approval use of PRILOSEC Delayed-Release Capsules. Because these reactions are voluntarily reported from a population of uncertainsize, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure.Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue; malaise; Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema Endocrine: GynecomastiaGastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued. Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with PRILOSEC. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin] Infections and Infestations: Clostridium difficile associated diarrhea Metabolism and Nutritional disorders: Hypoglycemia, hypomagnesemia, with or without hypocalcemia and/or hypokalemia, hyponatremia, weight gainMusculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fractureNervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia; vertigoRespiratory: Epistaxis, pharyngeal painSkin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis Special Senses: Tinnitus, taste perversionOcular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double visionUrogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular painHematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leucocytosis。
AMT Pump Company 水泵维修指南说明书
Please read and save this Repair Parts Manual. Read this manual and the General Operating Instructions carefully before attempting to assemble, install, operate or maintain the product described. Protect yourself and others by observing all safety information. The Safety Instructions are contained in the General Operating Instructions. Failure to comply with the safety instructions accompanying this product could result in personal injury and/or property damage! Retain instructions for future reference. AMT reserves the right to discontinue any model or change specifications at any time without incurring any obligation.©2015 AMT Pump Company, A Subsidiary of The Gorman-Rupp Company, All Rights Reserved.Periodic maintenance and inspection is required on all pumps to ensure proper operation. Unit must be clear of debris and sediment. Inspect for leaks and loose bolts. Failure to do so voids warranty.High Head Centrifugal Pedestal PumpsRefer to pump manual 1808-634-00 for General Operating and Safety Instructions.MAINTENANCEMake certain that the unit is disconnected from the power source beforeattempting to service or remove any components!REMOVAL OF OLD SEAL Should the mechanical seal (Ref. No. 6) require replacement, proceed asfollows and refer to Figures No. 1 and 2.IMPORTANT: Always replace both the seal seat and seal head to ensureproper mating of components! Also, the impeller seal (Ref. No. 9) should bereplaced any time the impeller lock nut (Ref. No. 10) has been removed.1. Remove four bolts (Ref. No. 3) connecting the casing (Ref. No. 11) to theadapter (Ref. No. 4).2. Remove the casing.Care should be taken not to “pinch” or “shave” the O-ring gasket (Ref.No. 5) between the adapter and the casing.3. Use a box and/or socket wrench to remove the impeller nut (Ref. No.10).Remove the impeller seal (Ref. No. 9) and the impeller (Ref. No. 8).NOTE: Pump shaft must be held in place to remove impeller. Impeller (Ref.No. 8) and lock nut (Ref. No. 10) unscrew CCW when looking at the front ofthe pump.4. The seal head (part of Ref. No. 6) can now be pulled from the shaft. (SeeFigure 2).5. Pry the seal seat (part of Ref. No. 6) from the adapter (Ref. No. 4). (SeeFigure 2).INSTALLATION OF NEW SEAL The precision faces on the mechanical seal are easily damaged. Handle your replacement seal carefully. Do not touch the carbon/ceramic seal faces.IMPORTANT: Be sure that shaft shoulder does not damage carbon face.1. Thoroughly clean all surfaces of the seal seat cavity in adapter (Ref. No. 4).2.Using a clean cloth, wipe the shaft and shaft sleeve to make certain thatthey are perfectly clean.3. Wet the rubber portion of the new seal seat (part of Ref. No. 6) with a lightcoating of soapy water. While wearing clean gloves or using a clean lightrag, press seal seat squarely into adapter recess. Place the cardboardwasher (usually supplied with new seal) over the polished surface anduse a piece of pipe or dowel rod to press in firmly, but gently. Avoidscratching the white ceramic face.4. Dispose of cardboard washer. Check again to see that ceramic surface is free of dirt and all other foreign particles and that it has not been scratched or damaged.5. Wet the inside rubber portion of the new seal head 9 part of Ref. No. 6) with a light coating of soapy water. Slide head onto the motor shaft with the sealing surface (Carbon) facing the seal seat (See Figure 1). This completes seal installation.NOTE: A short “run-in” period may be necessary to provide completely leakproof seal operation.Rotation (Threaded Shaft Model)1. Remove pump components from pedestal assembly:a. Remove bolts (Ref. No. 3) from casing; remove casing and o-ring(Ref. No. 5).b. Remove impeller nut (Ref. No.10), unscrew CCW. Pedestal shaftmust be held in place to loosen nut.c. Remove impeller o-ring (Ref. No. 9) and impeller (Ref. No. 8) turningCCW while holding pedestal shaft in place. Remove impeller shims(Ref.No. 7).d. Replace seal as described in “Removal of Old Seal”.e. Remove bolts (Ref. No. 13); remove adapter.Reverse instructions to install pump on repaired pedestal assembly.Failure to follow above information may cause impeller to unscrew anddamage pump head, cause property damage and/or personal injury. DESCRIPTION These pumps are non self-priming units designed for use where higher heads are required to handle liquid transfer, heating and cooling applications where no suction lift is required. Pump construction features investment cast stainless steel closed impeller. The discharge port on all models can be rotated in 90º incre-ments to accommodate specific applications. All units are for use with non-flammable liquids compatible with pump component materials. Units are suitable for direct coupling or pulley drive. Pump rotation is CCW facing the front of the pump. No motor is supplied with these units.Figure 1 - Mechanical SealPEDESTAL ASSEMBLY MAINTENANCEDisconnect from power source before servicing or inspecting pump for any reason.Bearing Housing Service1. Remove shaft bearings (Ref. No. 3) and shaft (Ref. No. 4) as an assemblyby first removing snap ring (Ref. No. 6) then wave washer (Ref. No. 5). 2. Push shaft/bearing assembly out of bearing housing (Ref. No. 2) byrapping on pump end of shaft with soft mallet or block of wood and a hammer.3. Shaft bearings can now be removed from shaft.4. If shaft bearings have been removed from shaft and bearing housing,replace by sliding bearing or shaft to shoulder.5. Replace shaft bearing assembly by sliding assembly into housing, pumpend first. Push shaft bearing assembly completely in by gently tapping on key way end of shaft with soft mallet.6. Replace wave washer and snap ring.7. Reassemble pump to pedestal (See pump manual “Maintenance”)For Repair Parts contact dealer where pump was purchased. Please provide following information:-Model Number-Serial Number (if any)Part description and number as shown in parts listFigure 2 - Repair Parts Illustrations1 Pedestal/Bearing Housing 3890-090-09 3890-090-09 3890-090-09 1Pedestal Assembly 3891-999-99 3891-999-99 3891-999-99 1 (includes Ref. Nos. 1, 14, 15, 16, 17, 18 and 19)3 3/8-16 x 1" Hex Head Cap Screw* ** 44 Adapter Kit - Cast Iron4890-030-954900-030-954900-030-95 1Adapter Kit - Bronze4890-030-974900-030-974900-030-971 Adapter Kit - Stainless Steel4890-030-984900-030-984900-030-98(includes Ref. Nos. 4 and 13)5 O-Ring - Buna N Incl. w/Ref KIT Incl. w/Ref KIT Incl. w/Ref KIT 1O-Ring - Viton Incl. w/Ref KIT Incl. w/Ref KIT Incl. w/Ref KIT1 6 Seal Assembly - Buna N1640-161-96 1640-161-96 1640-161-96 1Seal Assembly - Viton1640-161-97 1640-161-97 1640-161-97 17 Impeller Shim Kit1806-044-90 1806-044-90 1806-044-90 18 Impeller Kit4891-010-984901-010-984905-010-98 1(includes Ref. Nos. 7, 8 and 10)9 O-Ring - Buna N Incl. w/Ref KIT Incl. w/Ref KIT Incl. w/Ref KIT 1O-Ring - Viton Incl. w/Ref KIT Incl. w/Ref KIT Incl. w/Ref KIT110 7/16-20 Acorn Nut 1784-001-00 1784-001-00 1784-001-00 111 Casing Kit - Cast Iron4890-001-954900-001-954900-001-95 1Casing Kit - Bronze4890-001-974900-001-974900-001-971 Casing Kit - Stainless Steel4890-001-984900-001-984900-001-971 (includes Ref. Nos. 3, 11 and 12)12 3/8" Pipe Plug** * 113 3/8 x 3/4" Hex Head Cap Screw * ** 414 Ball Bearing 1695-031-00 1695-031-00 1695-031-00 215 Shaft 1696-066-00 1696-066-00 1696-066-00 116 Shaft Key 1517-000-00 1517-000-00 1517-000-00 117 Wave Washer 1806-023-00 1806-023-00 1806-023-00 118 Snap Ring 1695-034-00 1695-034-00 1695-034-00 119 q Bearing Shim Kit 1696-008-90 1696-008-90 1696-008-90 120 1696-075-00 Thread Sealant 1696-075-00 1696-075-00 1696-075-00 1 KIT O-Ring Kit - Buna N4890-300-904900-300-904900-300-901 O-Ring Kit - Viton4890-301-904900-301-904900-301-901 (*)Standard hardware item, available locally.q Not ShownNOTES:NOTES:。
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ORIGINAL PAPERA Design of Tamper Resistant Prescription RFID Access Control SystemYu-Yi Chen &Der-Chen Huang &Meng-Lin Tsai &Jinn-Ke JanReceived:1June 2011/Accepted:7July 2011/Published online:13July 2011#Springer Science+Business Media,LLC 2011Abstract In this paper,we propose a tamper resistant prescription RFID access control protocol for different authorized readers.Not only the authentication mechanism but also the access right authorization mechanism is designed in our scheme.Only the specific doctor,usually the patient ’s doctor,can access the tag.Moreover,some related information of patient ’s prescription is attached to a RFID tag for tamper resistance.The patients ’rights will be guaranteed.Keywords RFID .Access control .Authentication .Authorization .SecurityIntroductionAn RFID system consists of three parts:RFID tags (also called transponders),readers (also called interrogators),andthe back-end database server.Readers broadcast queries to tags in their wireless transmission ranges for information contained in tags,and tags reply with required information such as identification (ID)numbers.The readers are connected to the back-end database that store information associated with tagged objects in order to use data obtained from readers in a useful way.As an alternative to barcodes,RFID tags have advantages like data capacity,read/write capability,and no requirement of line-of-sight.Current research and development on RFID focuses on manufacturing and retail sectors to improve supply chain efficiency and learn more about consumer behavior.Health-care is considered to be the next home for RFID after manufacturing and retail [1–3].As we know,some hospitals and medical institutes are starting to conduct their own small-scale RFID testing projects,such as patient identifi-cation [4–6],drug administration,access to medical records [7–9],transfusion,and equipment,patient,and staff tracking [10].The main purpose of these innovations is to improve patients safety,eliminates paper-based document,cost savings,increases efficiency and productivity,prevent/reduce medical errors,and so on.Essentially,the RFID systems work by placing unique electronic identifiers on items or on people.For example,RFIDs have been embedded in patient bracelets so that medical staff can electronically identify patients before surgery and before administering medications and blood transfusions.RFID technology provides a method to transmit and receive data from a patient to medical professionals without human intervention.Improving safe-ty,quality,and value of health care is the focus of most hospitals.The application of RFID in healthcare has,in fact,just begun.In 2006,John Ayoade [11]proposed a framework for paperless electronic health record (EHR)system [12].JohnY .-Y .ChenDepartment of Management Information System,National Chung Hsing University,250Kuo Kuang Road,402,Taichung,Taiwan,Republic of China e-mail:chenyuyi@.twD.-C.Huang (*):M.-L.Tsai :J.-K.JanDepartment of Computer Science and Engineering,National Chung Hsing University,250Kuo Kuang Road,402,Taichung,Taiwan,Republic of China e-mail:huangdc@.tw M.-L.Tsaiemail:phd9810@.tw J.-K.Jane-mail:jkjan@.twJ Med Syst (2012)36:2795–2801DOI 10.1007/s10916-011-9758-2Ayoade pointed out the authority of readers should be different for accessing different tags.In such situation,those proposed RFID access control mechanisms [13–19]are not suitable.And John Ayoade did not propose how to make it work in practical.In this paper,we focus on RFID access control system for different authorized readers.The tag ’s access should be under some control mechanisms.Only the specific doctor,usually the patient ’s doctor,can access the tag.Moreover,some related information of patient ’s prescription should be attached to a RFID tag for tamper resistance.Our schemeIn this section,we will introduce how our protocol works.There are three components involved in our scheme as follows.▪Tag:it is usually used for identification as accessed by RF signal.Each tag is assigned to a patient.▪Reader:it is used for tags access.Unlike most of the proposed RFID access control schemes,the commu-nication between the reader and the back-end database server is supposed wireless and insecure.▪Back-end database server:it is responsible for recording all tags ’detail such as tag ’s identifier,the hash value of the tag ’s identifier,the tag ’s key,etc.Before describing more details of our design,we introduce the notations used in our scheme as follows.▪Key S :the back-end database server ’s key.▪ID T :the tag ’s identifier.▪HID T :the hash value of the tag ’s identifier ID T ,acting as the primary index of the prescription database for retrieving the tag ’s key Key T .▪Key T :the tag ’s key.▪ID R :the reader ’s identifier.▪Key R :the reader ’s key which is assigned as Key R =h (Key S ,ID R )▪Asc RT :the association proof Asc RT =h (Key T ,Key R )of the tag and the reader which is stored in the tag only.▪P i :the patient ’s i th prescription recorded by the back-end database server.▪HP i :the hash value of prescription P i .▪HC i :the hash prescription chain,it is computed as HC i =h (P i −1,P i ).▪⊕:exclusive-or operation.▪h ():a one-way hash function.▪E Key i ðÞ:the symmetric encryption function using the secret value Key i to encrypt the message.▪D Key i ðÞ:the symmetric decryption function using the secret value Key i to decrypt the message.There are two phases in our scheme:authentication phase and access control phase.The authentication phaseAs a doctor uses his reader to access his patient ’s tag,the reader and the tag should be authenticated by the back-end database server.The procedure of this phase is shown in Fig.1.Step 1.The reader generates a random number N R 1andthen emits this number to the tag.Step 2.The hash value HID T of the tag ’s identifier ID T isgenerated first.HID T ¼h ðID T ÞTwo numbers N T 1and N T 2are randomly selected and the first one is embedded in the following message X T 1for secure delivery.X T 1¼Key T ÈN T 1Using the random number N R 1,the tag uses its key Key T to generate the following response message R T 1.R T 1¼h ðKey T ;N R 1;N T 1ÞMoreover,the second response message R T 2is the hash value of the association proof Asc RT and two random numbers N R 1,N T 2.R T 2¼h ðAsc RT ;N R 1;N T 2ÞFor some access control purpose in the next phase,the check value V T 1should be prepared now.V T 1¼h ðHP i À1;N T 1ÞFinally,the tag emits the messages (HID T ,X T 1,N T 2,R T 1,R T 2,V T 1)to the reader.Step ing the random number N T 2,the reader uses itskey Key R to generate the following response message R R 1.R R 1¼h ðKey R ;N T 2ÞFor the use of next phase,the doctor writes out a prescription which is encrypted by the reader ’s key Key R .C ¼E Key R ðM ÞA number N R 2is randomly selected and used for generating the following values.V R 1¼h ðC ;N R 2ÞX R 2¼Key R ÈN R 2V R 2¼h ðKey R ;N R 2ÞAfter,the tag ’s messages (HID T ,X T 1,N T 2,R T 1,R T 2,V T 1)are forwarded and additional generated messages (ID R ,R R 1,N R 2,C ,V R 1,X R 2,V R 2)are trans-mitted to the back-end database server.Step ing the hash value HID T ,the tag ’s key Key T 0can be retrieved.Then the number N T 10can be obtained as follows.N T 10¼X T 1ÈKey T 0After,the correctness of the tag ’s key Key T 0and the number N R 1can be verified.R T 1¼?h ðKey T 0;N R 1;N T 10ÞUsing the reader ’s identifier ID R ,the reader ’s key Key R 0can be generated as follows.Key R 0¼h ðKey S ;ID R ÞThe correctness of the reader ’s key Key R 0and the number N T 2can be verified.R R 1¼?h ðKey R 0;N T 2ÞBoth of the tag and the reader are authenticat-ed,their association proof should be also verified as follows.Asc RT ¼h ðKey T 0;Key R 0ÞR T 2¼?h ðAsc RT 0;N R 1;N T 2ÞNow,the authentication procedure is completed.Furthermore,those messages (V T 1,C ,V R 1,X R 2,V R 2)will be used for the access control in the nextphase.Fig.1The authentication phase of our protocolThe access control phaseAfter the reader is authenticated and authorized to access the tag,the patient’s prescription can be recorded in the database.Moreover,the digest of the prescription will be duplicated to the tag in securely.The procedure of this phase is shown in Fig.2.Step1.For assuring the integrity of the prescription,the last prescription’s hash value HP iÀ10is retrievedfrom the database and then verified.V T1¼?hðHP iÀ10;N T10ÞUsing the received value X R2and the generated key Key R0,the number N R20can be got as follows.N R20¼X R2ÈKey R0Then the correctness of the ciphertext C and the number N R20can be verified.V R1¼?hðC;N R20ÞV R2¼?hðKey R0;N R20ÞAfter,the ciphertext C can be decrypted by the reader’s key Key R0.M¼D KeyR0ðCÞThe back-end database server writes the plain-text M into the i th record of the patient’s prescription P i.And the following two hash values are generated and recorded in the database for the use of next round.HP i¼hðP iÞHC i¼hðP iÀ1;P iÞThen the hash values HP i and HC i are encrypted by the tag’s Key T0as follows.X S1¼E Key0TðHP iÞX S2¼E Key0TðHC iÞFor assuring the integrity in the transmission, the check value V S1is generated as follows.V S1¼hðX S1;X S2;N T10ÞFig.2The access control phaseof our protocolUsing the generated number N T10,the back-end database server uses the tag’s key Key T0togenerate the following response message R S1.R S1¼hðKey T0;N T10ÞThis message R S1will be used for the authen-tication by the tag.Moreover,the tag’s identifier ID T should be refreshed to ID T0in the server’s database and thetag’s memory for next round.ID T0¼ID TÈN T10However,ID T should still be held in the server to defend against the de-synchronization attack.Finally,the messages(X S1,X S2,V S1,R S1)are sent to the reader.Step2.As the reader receives the messages from the back-end database server,it just needs to forwardthe messages(X S1,X S2,V S1,R S1)to the tag. Step3.The tag uses its key Key T to verify the response message from the back-end database server.R S1¼?hðKey T;N T1ÞIf the equality is held,it means the response message is indeed from the back-end databaseserver with the share secret.Based on the servercan be trusted,the tag understands that the readerhad been authenticated and authorized to access it.For assuring the integrity of X S1and X S2,the check value V S1should be verified as follows.V S1¼?hðX S1;X S2;N T1ÞThen the encrypted hash values X S1and X S2 can be decrypted by the tag’s Key T.HP i0¼D Key TðX S1ÞHC i0¼D Key TðX S2ÞThose two hash values HP i,HC i are appended to the proof list.This list will be used for assuringthe patient’s rights.Finally,the tag updates its identifier to be ID T0 which is generated as follows.ID T0¼ID TÈN T10Analysis of our protocolIn this section,we will analyze our scheme about man-in-the-middle attack,spoofed reader attack,spoofed tag attack,mutual authentication,location privacy and practicability.1.Issue of man-in-the-middle attackSince the communication between the reader and the tag,and between the back-end database server and the reader can be eavesdropped or intercepted,how to avoid man-in-the-middle attack is the most important issue.For against the replay attack,the“challenge-response”approach is used and more details will be analyzed in the following issue.To defend against the eavesdropping attack,all of the critical parameters for mutual authentication are protected by one-way hash ter,the accessed data is also protected by encryption.Moreover,the integrity verification of the access data is involved in our design for against modification attack.2.Issue of spoofed reader attackIn our design,a unique secret value Key T had been embedded in the tag issued by the server.It is the key to generate the authentication message from the tag to the reader.We use the strategy called“challenge-response”to avoid the kind of replay attack.In step1of the authentication phase,the challenge number N R1is generated by the reader.Then the tag should response the correct message R T1in step2.R T1¼hðKey T;N R1;N T1ÞBoth of the challenge number N R1and the response message R T1will be forwarded to the server.Moreover, the hash value HID T of the tag’s identifier ID T and the message X T1with the embedded random number N T1are forwarded to the ing the hash value HID T,the tag’s key Key T0can be retrieved.Then the number N T10 can be got.After,the message R T1can be verified in step4.R T1¼?hðKey T0;N R1;N T10ÞIf the equality is held,it means the tag is issued by the server.Clearly,the attacker cannot spoof the reader to replay the response since it depends on the random challenge from the reader.3.Issue of spoofed tag attackIf the reader tries to access a tag,it should be able to response the message embedded with the correct key Key T from the server to response the tag’s challenge.We use the same strategy called“challenge-response”.First,the reader should prove itself to the server.In step 2of the authentication phase,the challenge number N T2 is generated by the tag.Then the reader should generate the correct message R R1in step3.R R1¼hðKey R;N T2ÞThe reader’s identifier ID R,the challenge number N T2,and the message R R1will be transmitted to the ing the reader’s identifier ID R,the reader’s key Key R0can be generated.Then message R R1can be verified in step4.R R1¼?hðKey R0;N T2ÞIf the equality is held,it means the reader is issued by the server.After the reader is authenticated by the server,the response message R S1for the tag’s challenge is generated in step1of the access control phase.R S1¼hðKey T0;N T10ÞThe response message R S1will be forwarded via the reader to the tag to be verified in step3.R S1¼?hðKey T;N T1ÞIf the equality is held,it means the reader is authorized by the server to response the challenge.Clearly,the attacker cannot spoof the tag to replay the response since it depends on the random challenge from the tag.4.Mutual authenticationThe strategy called“challenge-response”is used twice in our design.It achieves mutual authentication between the reader and the tag,then the above attacks can be avoided.5.Location privacyRFID tags have the character of outstanding trace-ability.Suppose a tag’s information is intercepted and collected by an attacker on different locations,maybe the history of the tag’s locations can be identified.It means the attacker can keep track of the tag’s owner.For the purpose of keeping the tag’s location private, the tag’s response message in each access can not be recognized it is emitted by the same tag.In our design, the tag’s identifier is updated in each access.Clearly, the attacker cannot trace the hash value of the tag’s identifier.Moreover,the other messages emitted be-tween the tag and the reader are randomized and not useful to identify the tag.Therefore,the tag’s location privacy can be guaranteed in our design.6.PracticabilityFor improving patients’safety,the tamper resistant prescription issue is considered to reduce forged and altered prescriptions,and deter drug abuse in Canada and America.In2006,the department of health and community services in Newfoundland and Labradorestablished a tamper resistant prescription drug pad program in Canada[20].And a new law will go into effect July1,2010that requires the use of tamper-resistant pads or paper for prescriptions in Washington[21].Our design will be a practical solution for thisissue.In our scheme,the tag’s access is under control.Only the specific doctor,usually the patient’s doctor, can access the tag.And some related information of patient’s prescription is attached to a RFID tag.In step 1of the access control phase,according to the patient’s prescription,the two hash values HP i and HC i are generated and recorded in the database and will be duplicated to the patient’s tag securely.HP i¼hðP iÞHC i¼hðP iÀ1;P iÞThe hash value HP i is used for verifying the integrity of the patient’s prescription.For each access, the hash value HP i is also used for verifying the consistent of records between the server and the tag.It can against the forgeries or alterations of prescription.Moreover,each prescription is strong connected with the pre-and post-prescription based on the hash chain value HC i.Therefore,no prescription can be erased or altered.ConclusionsIn this paper,we propose an efficient and secure RFID access control scheme for tamper resistant prescription. Not only the authentication mechanism but also the access right authorization mechanism is designed in our scheme. Moreover,some related information of patient’s prescription is attached to a RFID tag.The patients’rights can be guaranteed.Furthermore,we also analyze the security features including:man-in-the-middle attack,spoofed read-er attack,spoofed tag attack,mutual authentication, location privacy,and practicability.References1.J.Ericson,RFID for Hospital Care,The E-Business ExecutiveDaily.(2004).2.Fisher,J.A.,and Monahan,T.,Tracking The Social Dimensionsof RFID Systems in Hospitals.International Journal of Medical Informatics77(3):176–183,2008.3.Wang,S.-W.,Chen,W.-H.,Ong,C.-S.,Liu,L.,Chuang,Y.-W.RFID Applications in Hospitals:A Case Study on A Demonstra-tion RFID Project in A Taiwan Hospital,Proceedings of The39th Hawaii International Conference on System Sciences.(2006).4.Chowdhury, B.,Khosla,R.,RFID-Based Hospital Real-TimePatient Management System,6th IEEE/ACIS International Con-ference on Computer and Information Science(ICIS2007).(2007).5.Nahas,H.A.,Deogun,J.S.,Radio Frequency IdentificationApplications in Smart Hospitals,The Twentieth IEEE Internation-al Symposium on Computer-Based Medical Systems.(2007).6.Xiao,Y.,Shen,X.,Sun,B.,Cai,L.Security and Privacy in RFIDand Applications in Telemedicine,IEEE Communications Maga-zine.(2006)64–72.7.Aguilar,A.,van der Putten,W.,and Kirrane,F.,Positive PatientIdentification using RFID and Wireless Networks,In HISI11th Annual Conference and Scientific Symposium.Dublin,Ireland, 2006.8.Bardram,J.Hospitals of The Future—Ubiquitous ComputingSupport for Medical Work in Hospitals,The Second International Workshop on Ubiquitous Computing for Pervasive Healthcare Application.(2003).9.Bardram,J.Applications of Context-Aware Computing in Hospi-tal Work:Examples and Design Principles,Proceedings of the 2004ACM symposium on Applied Computing.(2004)1574–1579.10.V.Boginski,I.K.Mun,Y.Wu,K.P.Mason,C.Zhang,Simulationand Analysis of Hospital Operations and Resource Utilization Using RFID Data,2007IEEE International Conference on RFID Gaylord Texan Resort,Grapevine,TX,USA,March26–28 (2007).11.Ayoade,J.,Security Implications in RFID and AuthenticationProcessing puters&Security25(3):207–212, 2006.12.C.-H.Kuo,H.-G.Chen,The Critical Issues about DeployingRFID in Healthcare Industry by Service Perspective,Proceedings of The41st Hawaii International Conference on System Sciences.(2008).13.H.-Y.Chien,Secure Access Control Schemes for RFID Systemswith Anonymity,International Conference On Mobile Data Management.(2006)96–99.14.X.Gao,Z.Xiang,H.Wang,J.Shen,J.Huang,S.Song,AnApproach to Security and Privacy of RFID System for Supply Chain,The E-Commerce Technology for Dynamic E-Business.(2004)164–168.15.H.-W.Kim,S.-Y.Lim,H.-J.Lee,Symmetric Encryption in RFIDAuthentication Protocol for Strong Location Privacy and Forward-Security,IEEE International Conference on Hybrid Information Technology(ICHIT′06).(2006)718–723.16.H.-S.Kim,J.-H.Oh,J.-Y.Choi,Analysis of The RFID SecurityProtocol for Secure Smart Home Network,International Confer-ence on Hybrid Information Technology(ICHIT′06).2(2006) 356–363.17.S.A.Weis,Security and Privacy in Radio-Frequency IdentificationDevices,Master’s Thesis,Massachusetts Institute of Technology.(2003).18.S.A.Weis,S.E.Sarma,R.L.Rivest,D.W.Engels,Security andPrivacy Aspects of Low-Cost Radio Frequency Identification Systems,International Conference on Security in Pervasive Computing,Lecture Notes in Computer Science.(2004)201–212.19.Zhang,L.,Zhou,H.,Kong,R.,and Yang, F.,An ImprovedApproach to Security And Privacy of RFID Application System, International Conference on Wireless work-ing and Mobile Computing.2:1195–1198,2005.20.Tamper Resistant Prescription Drug Pad Program,A Project of TheDepartment of Health and Community Services,Government of Newfoundland and Labrador .nl.ca/health/ nlpdp/Brochure_Updated_April_2009_Info_Pamphlet.pdf(2006).21.WANURSES,New Tamper Resistant Prescription Pad Law,Nursing Practice Blog,/nursing-practice-update/index.php/2009/09/new-tamper-resistant-prescription-pad-law/.(2009).。