Mifepristone_84371-65-3_DataSheet_MedChemExpress

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Fumonisin B1_PP5PP2CαPP2APP1γ2PP2B抑制剂_116355-83-0_Apexbio

产品说明书
化学性质
产品名: Cas No.: 分子量: 分子式:
Fumonisin B1 116355-83-0 721.83 C34H591 修订日期: 6/30/2016
化学名: SMILES: 溶解性: 储存条件: 一般建议:
运输条件:
2-[2-[19-amino-6-(3,4-dicarboxybutanoyloxy)-11,16,18-trihydroxy-5, 9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid
产品描述:
Mycotoxin produced by Fusarium moniliforme. Potently inhibits sphingosine N-acyltransferase (ceramide synthase), causing an accumulation of sphingoid bases (IC50 ~ 75 nM). Also inhibits protein phosphatases; IC50 values are 80, 300, 400, 500 and 3000 μM for PP5, PP2Cα, PP2A,
ApexBio Technology
CCCCC(C)C(C(CC(C)CC(CCCCC(CC(C(C)N)O)O)O)OC(=O)CC(CC(=O)O)C (=O)O)OC(=O)CC(CC(=O)O)C(=O)O
Limited solubility
Store at 4°C
For obtaining a higher solubility , please warm the tube at 37°C and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

ProMinent gamma L 电动隔膜计量泵说明书

P r o M i n e n t®Operating Instructions Manual ProMinent ® gamma/ L Solenoid Dosing PumpPrintingPrinting:Operating Instructions ProMinent® gamma/ L© ProMinent Dosiertechnik GmbH, 1999Address:ProMinent Dosiertechnik GmbHIm Schuhmachergewann 5-11D-69123 HeidelbergPostfach 101760D-69007 Heidelberg*****************www.prominent.deSubject to technical alteration.Please fold out this page! ÈOperating-/Settings DiagramContinuous displayFunction DescriptionOperating modes Operating modes are selected using the MODE menu (depending upon identity code, someoperating modes may be absent)..“Analogue” operating mode: (Identity code, control variant: analogue current)The stroke rate is controlled via an analogue electrical signal via the “external control” terminal.Signal processing is pre-selected at the controller.“Manual” operating mode: (Identity code, control variant: manual, standard function)The stroke rate is controlled manually via the controller.“Contact” operating mode: (Identity code, control variant: external 1:1 / external with pulsecontrol)This operating mode offers the opportunity to make fine adjustments with small increase/decrease factors. Dosing can be activated by a pulse via the “external control” terminal or by asemiconductor element. With the “pulse control” option it is possible to pre-set a feed quantity(batch) or number of strokes (factor 0.01 to 99.99) via the control unit.“Batch” operating function: (identity code, control variant, external 1:1 / external with pulsecontrol)This operating mode offers the option of working with larger transfer factors (up to 65535).Metering can be triggered by pressing the P key or a pulse from the “external control” terminalvia a contact or semiconductor element. A batching quantity or number of strokes can be pre-selected via the control unit.Functions The following functions can be selected using the SET menu:“Calibrate” function:The gamma/ L can be operated in all operating modes including in calibrating mode. Thecorresponding continuous displays can show the actual feed quantity or the feed rate.Calibration is maintained within the stroke frequency range 0 - 180 strokes/ min. Calibration isalso maintained when a stroke frequency is altered up to ± 10 %.“Pressure level” function:It is possible to set different pressure levels.“Auxiliary frequency” function:It is possible to set a stroke rate in the SET menu, which may be activated via the “externalcontrol” terminal. This auxiliary frequency overrides all other pre-set stroke rate frequencies.“Flow” function:Stops the gamma/ L when the flow is insufficient. In the SET menu, the number of failed strokesis entered after which the pump will be turned off.The following functions are available as standard:“Float switch” function:Information on the liquid level in the feed chemical container is transmitted to the gamma/ L.This option requires the installation of a 2-stage float switch. This is connected to the “floatswitch” terminal.“Pause” function:The gamma/ L can be stopped by remote control via the “external control” terminal. The “pau-se” function operates only via the “external control” terminal.The following functions are activated by keystrokes:“Stop” function:The gamma/ L can be stopped by pressing the STOP/START key without disconnecting fromthe mains power supply.Function Description“Prime” function:Priming (short term feed at maximum frequency) is activated by pressing both arrow keys at thesame time.Optional relay The gamma/ L has two connection options.“Fault indicating relay” option:In the event of fault signals, warning signals or float switch activation signals, connects anelectrical circuit to trigger alarm sirens etc. The relay is retrofitted via an aperture in the powerend.“Fault indicating and pacing relay” option:Along with the fault indicating relay, the pacing relay produces an electrical impulse for everystroke. The relay is retrofitted via an aperture in the power end.Function and errorindicators The operating and error status is shown via the three LEDs and the “error” indicator on the LCD (see also section 12):LCD indicator If a fault occurs “error” will appear along with an additional fault warning.LED indicator Operating indicator (green)This indicator is lit as long as the gamma/ L is operating correctly.Warning indicator (yellow)This warning light appears if the gamma/ L electronics detect a situation that could lead to afault, e.g. “liquid levels low 1st stage”.Warning indicator (red)This warning light appears if a fault occurs, e.g. “liquid levels low 2nd stage”.Hierarchy of operating modes, functions and fault statusesThe different operating modes, functions and fault statuses each have a differing effect onwhether and how the gamma/ L functions. These effects are given below:1.Prime2.Fault, stop, pause3.Auxiliary frequency4.Manual, analogue, contact, batchto:1.“Prime” can be activated in any pump status (as long as it is operable)2.“Fault”, “stop” and “pause” stop all system parts up to “prime”.3.The stroke rate of the “auxiliary frequency” always overrides the existing operating strokerate.Commissioning / Operating8.2Diagrams for setting feed capacityGeneralS Open out the page showing the diagram of your pump type (see appendix).S Calculate the correction factor. Mark the operating pressure for your application in the dia-gram “correction factor depending upon operating pressure”.S Trace a line from this value vertically up to the curve and then horizontally left. Read off thecorrection factor.S Divide the required feed rate by the correction factor determined as above. Mark this value(l/h) on the “l/h” axis in the diagram “feed rate depending upon stroke length and strokerate”.S Trace a line horizontally from this value to the left. Trace a line from the intersection with thestraight line for the adjustable stroke frequencies vertically downwards to the “strokelength” axis.S Set the gamma/ L to one of the stroke frequencies determined in this way, and thecorresponding stroke length.The measurements for determining the feed rate for the following diagrams were carried outusing water and the correction factor was determined at a 70 % stroke length. Distribution ofthe feed rate across all material versions: -5 to +15 %.9OperatingThis section describes all operating options available to you when the gamma/ L is incontinuous display mode (no P key symbol in the LCD display).GUIDELINE•Open out the fold-out page following the title page fully! There you will find theoverviews “control elements and key functions” and “operating settings dia-gram”.•Look at the overview “continuous displays”. This page shows you which displaysare available in which operating mode, and which values are directly alterable inthe corresponding continuous displays.9.1Manual operationSet stroke length Stroke length is continually adjustable within a range of 0 - 100 %. The recommended strokelength range, which will practically guarantee technical reproducibility, is 30 - 100 % (SEK type:50 - 100 %).The following operating options are available via the different keys (see also figure on the nextpage):Stop/Start gamma/ L To stop gamma/ L: press STOP/START key.To start gamma/ L: press STOP/START key.Start batch Press the P key briefly in “batch” operating mode.Load factory settings Press the P key for 15 s to load factory calibration settings!Current settings will be deleted.Change to settings mode WeIf you press the P key for 2 s in any continuous display the gamma/ L will change to settingsmode (see section 7).If CODE 1 is set, the code must be entered after pressing the P key.Check adjustable values Each time you press the i key you will see a different continuous display. The number ofcontinuous displays depends upon the identity code, the selected operating mode and theconnected accessories.Change directlyalterable values To change a value (see below) directly in the corresponding continuous display, press one of thearrow keys until “set” appears in the LCD display. The delay has been programmed in to preventinadvertent changing of values.If CODE 2 has been set, this code must be entered after pressing the arrow key.Directly alterable values are as follows:。

Enhancement of CO2 Adsorption and CO2_N2 Selectivity on ZIF-8 via Postsynthetic Modi

Enhancement of CO2Adsorption and CO2/N2Selectivity on ZIF-8via Postsynthetic ModiﬁcationZhijuan ZhangSchool of Chemistry and Chemical Engineering,South China University of Technology,Guangzhou,510640,P.R.ChinaDept.of Chemistry and Chemical Biology,Rutgers University,Piscataway,New Jersey,08854Shikai Xian,Qibin Xia,Haihui Wang,and Zhong LiSchool of Chemistry and Chemical Engineering,South China University of Technology,Guangzhou,510640,P.R.ChinaJing LiDept.of Chemistry and Chemical Biology,Rutgers University,Piscataway,New Jersey,08854DOI10.1002/aic.13970Published online January11,2013in Wiley Online Library()Imidazolate framework ZIF-8is modiﬁed via postsynthetic method using etheylenediamine to improve its adsorption per-formance toward CO2.Results show that the BET surface area of the modiﬁed ZIF-8(ED-ZIF-8)increases by39%,and its adsorption capacity of CO2per surface area is almost two times of that on ZIF-8at298K and25bar.H2O uptake on the ED-ZIF-8become obviously lower compared to the ZIF-8.The ED-ZIF-8selectivity for CO2/N2adsorption gets signiﬁcantly improved,and is up to23and13.9separately at0.1and0.5bar,being almost twice of those of the ZIF-8. The isosteric heat of CO2adsorption(Q st)on the ED-ZIF-8becomes higher,while Q st of N2gets slightly lower com-pared to those on the ZIF-8Furthermore,it suggests that the postsynthetic modiﬁcation of the ZIF-8not only improves its adsorption capacity of CO2greatly,but also enhances its adsorption selectivity for CO2/N2/H2O signiﬁcantly. V C2013American Institute of Chemical Engineers AIChE J,59:2195–2206,2013Keywords:ZIF-8,modiﬁcation,adsorption/gas,isosteric heat of adsorption,selectivityIntroductionCO2has often been cited as the primary anthropogenicgreenhouse gas(GHG)as well as the leading culprit inglobal climate change.The development of a viable carboncapture and sequestration technology(CCS),is therefore,ascientiﬁc challenge of the highest order.1–4Currently,a vari-ety of methods,such as membrane separation,chemicalabsorption with solvents,and adsorption with solid adsorb-ents,have been proposed to sequester CO2from theﬂuegases of power plant.Thereinto,the adsorption is consideredto be one of the most promising technologies for capturingCO2fromﬂue gases because of their easy control,low oper-ating and capital costs,and superior energy efﬁciency.5–7Many adsorbents have been investigated for CO2adsorptionincluding activated carbons,zeolites,hydrotalcites and metaloxides.8–14However,although some zeolite materials havebeen claimed to be most adequate for CO2separation fromﬂue streams,it is difﬁcult to regenerate them without signiﬁ-cant heating which leads to low productivity and greatexpense.15,16Recently,metal-organic frameworks(MOFs)haveattracted great attention and present a promising platform forthe development of next-generation capture materialsbecause of their high capacity for gas adsorption and tunablepore surfaces that can facilitate highly selective binding ofCO2.17–26To optimize a MOF for a particular application,itis important to be able to tailor its pore metrics and function-ality in a straightforward fashion.However,tailoring MOFsmaterials by modifying their textural properties(e.g.,surfacearea and pore volume)and surface chemistry(acid–baseproperties,functional groups)for adsorption application isstill a difﬁcult task.27Many researchers have given insightinto modiﬁcation of the MOF materials so as to develop newand better adsorbents.Strategies reported include ligandfunctionalization,24,28–39framework interpenetration,22,23introduction of alkali-metal cations,40–42control of poresize32,43–47and incorporation of open metal sites(OMSs).39,48–51However,because of the instability underconditions for the synthesis of MOFs or the competitivereaction with some framework components,it may be difﬁ-cult for certain functional groups to incorporate into MOFsusing aforementioned strategies.Another strategy for gener-ating desired functionalities in MOFs is the postsynthesis Additional Supporting Information may be found in the online version of thisarticle.Correspondence concerning this article should be addressed to Z.Li atcezhli@.V C2013American Institute of Chemical EngineersAIChE Journal2195June2013Vol.59,No.6modiﬁcation of preconstructed,robust precursor MOFs.52–55 For example,An et al.33demonstrated that postsynthetic exchange of extra-framework cations within anionic bio-MOF-156can be used as a means to systematically modify its pore dimensions and metrics.Farha et al.57synthesized a series of cavity modiﬁed MOFs by replacing coordinated sol-vents with several different pyridine ligands.They found that a p-(CF3)NC5H4-modiﬁed MOF showed considerable improvements in the CO2/N2selectivities compared to the parent framework.46Long and his coworkers58previously reported the grafting of ethylenediamine(en)within a water-stable MOF H3[(Cu4Cl)3(BTTri)8](CuBTTri),and found that the en modiﬁed sample had more greater attraction of CO2 at low pressures and the CO2/N2selectivity also increased over the entire pressure range measured.More recently, Long and coworkers59incorporated the N,N0-dimethylethyle-nediamine(mmen)into the CuBTTri MOF,and showed that the CO2uptake was drastically enhanced.Zhang et al.60 reported that after ZIF-8was modiﬁed by ammonia impreg-nation,the surface basicity was greatly increased and there-fore the CO2uptake was enhanced.Park et al.61reported a postsynthetic reversible incorporation of organic linkers3,6-di(4-pyridyl)-1,2,4,5-tetrazine(bpta)into SNU-30 [Zn2(TCPBDA)(H2O)2]Á30DMFÁ6H2O through single-crystal-to-single-crystal transformations,and found that the desol-vated SNU-310exhibited enhanced selective adsorption of CO2over N2.Xiang et al.62incorporated the CNTs into HKUST-1,and then modiﬁed it with Li1.The results showed that the hybrid Li@CNT@[Cu3(btc)2],which is formed by the combination of Li doping and CNT incorpora-tion,having an enhancement of CO2uptakes by about 305%.However,to this date,no work has been reported out on the postsynthetic modiﬁcation of ZIF-8to enhance its functionality.In this work,the postsynthetic modiﬁcation of the ZIF-8is proposed to prepare a novel adsorbent with higher CO2 adsorption capacity and CO2/N2selectivity.The postsyn-thetic modiﬁcation of the ZIF-8crystals would be carried out by using ethylenediamine treatment.Then the surface groups of the modiﬁed ZIF-8samples(ED-ZIF-8)would be characterized.Single-component isotherms of CO2and N2 on the modiﬁed ZIF-8samples would be measured sepa-rately.Furthermore,the CO2/N2selectivity is estimated by using IAST on the basis of single-component isotherms of CO2and N2.The inﬂuence of the textural structures and sur-face chemistry of the original and modiﬁed ZIF-8samples on their adsorption capacities for CO2and selectivity of CO2/N2would be discussed and reported here.This informa-tion will be valuable for selecting appropriate adsorbents for CO2capture process.Methods and MaterialsMaterials and instrumentsZinc nitrate hexahydrate(Zn(NO3)2Á6H2O,98%,extra pu-rity)and2-methylimidazole(H A MeIM)(99%purity)were purchased from J&K Chemicals.N,N A Dimethylacetamide (DMF)was purchased from Qiangshen Chemicals Co.,Ltd. of Jiangshu(Jiangshu,China),and it was further puriﬁed by 4A molecular sieve to eliminate the water.Maganetic suspension balance RUBOTHERM was sup-plied by Germany.Its precision was0.000001g.ASAP 2010sorptometer was supplied by Micromeritics Co., Norcross,GA,USA.AdsorbentsSynthesis of ZIF-8was performed following the reported procedures63with a few modiﬁcations.First,a solid mixture of zinc nitrate hexahydrate Zn(NO3)2Á6H2O(0.956g, 3.2 mmol)and2-methylimidazole(H A MeIM)(0.24g, 3.4 mmol)was dissolved in70mL of DMF solvent.The mixture was quickly transferred to a100mL autoclave and sealed. Second,the autoclave was heated at a rate of5K/min to 413K in a programmable oven and held at this temperature for24h under autogenous pressure by solvothermal synthe-sis,followed by cooling at a rate of0.3K/min to room tem-perature.Third,after removal of mother liquor from the mix-ture,chloroform(40mL)was added to the autoclave.The as-synthesized ZIF-8crystals were then isolated byﬁltration. Colorless polyhedral crystals were collected from the upper layer,washed with DMF(10mL33),and dried at383K overnight.To further remove the guest species from the framework and prepare the evacuated form of ZIF-8crystals for modiﬁ-cation and gas-sorption analysis,the as-synthesized ZIF sam-ples were immersed in methanol at ambient temperature for 48h,and evacuated at ambient temperature for5h,and sub-sequently at an elevated temperature673K for2h. Postsynthetic modiﬁcation of adsorbentsThe as-synthesized ZIF-8crystals(labeled as ZIF-8)were dried at383K for24h for postsynthetic modiﬁcation.The subsequent treatment applied to the modiﬁcation of ZIF-8crystals consists of the following steps:The modiﬁed ZIF-8sample(labeled as ED-ZIF-8)was synthesized using ethylenediamine as a linker.In a typical procedure,the ZIF-8sample was added to30%ethylenediamine solution and then the mixture was placed in a stainless high-pressure autoclave.The autoclave was heated in an oven at416K for 1h and then381K for6h.The light yellow product wasﬁl-tered and washed with deionized water.Finally,the sample was dried at383K overnight.Characterization of adsorbentsThe speciﬁc surface area and pore volume of original ZIF-8and modiﬁed ZIF-8crystals were measured on a Micrometrics gas adsorption analyzer ASAP2010instrument equipped with commercial software for calculation and analysis.Powder X-ray diffraction data were collected using a D8 advance h-2h diffractometer(Bruker)in reﬂectance Bragg-Brentano geometry employing Cu K a line focused radiation with40kV voltages and40mA current.The X-ray scanning speed was set at2 /min and a step size of0.02 in2h.A Jade5XRD pattern processing software(MDI,Inc.,Liver-more,CA)was used to analyze the XRD data collected on the ZIF-8samples.The surface organic molecules were analyzed by taking FTIR spectra on a Bruker550FTIR instrument equipped with a diffuse reﬂectance accessory that included a reaction cell.Data acquisition was performed automatically using an interfaced computer and a standard software package.The samples were dried in vacuo at423K prior to mixing with KBr powder.The samples were run in ratio mode allowing for subtraction of a pure KBr baseline.The sample chamber2196DOI10.1002/aic Published on behalf of the AIChE June2013Vol.59,No.6AIChEJournalwas kept purged with nitrogen during the entire experiment.The spectrometer collected 64spectra in the range of 400–4,000cm 21,with a resolution of 4cm 21.CO 2and N 2adsorption measurementsThe CO 2and N 2adsorption-desorption isotherms at 298K,308K,318K,and 328K were obtained on a RUBO-THERM magnetic suspension balance.The initial activa-tion of the modiﬁed sample was carried out at 423K for 12h in a vacuum environment.He (ultra-high purity,U-sung)was used as a purge gas in this study.The adsorp-tion processes were carried out using high purity CO 2and N 2(99.999%)gas.A feed ﬂow rate of 60mL/min of CO 2,40mL/min of N 2and 30mL/min of He,respec-tively,were controlled with the mass ﬂow controllers (MFC)to the sample chamber.Both adsorption and de-sorption experiments were conducted at the same tempera-ture.The temperature of the sorption chamber can be adjusted and maintained constant by an internal tempera-ture sensor.However,the pressure can be changed step-wise through the gas ﬂow rate.Typically,there are four steps for ﬁnishing determination of an isotherm of CO 2or N 2by using Rubotherm magnetic suspension balance.These detail steps are shown by the operation manual of Rubotherm maganetic suspension balance.H 2O adsorption measurementsThe water adsorption measurements were conducted on a computer-controlled DuPont Model 990TGA.The partial pressure of water was varied by changing the blending ratios of water-saturated nitrogen and pure nitrogen gas streams.Before measurement,the modiﬁed ZIF-8samples were acti-vated at 423K for 6h.Results and DiscussionStructure and pore characterizationFigure 1exhibits the adsorption-desorption isotherms of N 2at 77K on the two samples ZIF-8and ED-ZIF-8.It can be seen that both samples show type-I behavior,indicating they are microporous in nature.Table 1lists structure param-eters of the two samples.These data indicate that the BET surface area and micropore volume of the ED-ZIF-8sample are signiﬁcantly higher than those of the original ZIF-8sam-ple,with an increase of $39%and 35.6%,respectively.Yaghi and his coworkers reported a pore volume of 0.66cm 3/g for ZIF-8from the single crystal structure.For the ZIF-8sample,the total pore volume is calculated to be 0.54cm 3/g,because part of the pores might be blocked.However,after the postsynthetic modiﬁcation,the blocked pores were reopened,and at meanwhile,some new pores were formed.64,65Thus,the total pore volume of the ED-ZIF-8sample is greatly improved.Figure 2shows the powder X-ray diffraction (PXRD)pat-tern of the modiﬁed ZIF-8sample.It can be seen that the main peaks of the modiﬁed ZIF-8sample are very clear,and similar to those of the original ZIF-8sample,indicating that the integrity of the modiﬁed ZIF-8sample maintains well af-ter the postsynthetic modiﬁcation.However,for a deep look-ing,it can be found that the major peaks of ED-ZIF-8all shifted to the left side (low-angle area)a little bit,which means after modiﬁcation,the lattice distance increased.In order to obtain information concerning changes in the surface groups,FTIR experiments were carried out to char-acterize the samples.Figure 3a shows the FTIR spectra of the original ZIF-8and the ED-ZIF-8sample.It is noticed that the spectra for the two samples show high similarities,and the main peaks of both ZIF-8samples match well with the published FTIR spectra for the ZIF-8.However,someTable 1.Porous Structure Parameters of the Modiﬁed ZIF-8CrystalsSample BET surface area (m 2.g 21)Langmuir surface area (m 2.g 21)Micropore volume(cm 3.g 21)Total pore volume (cm 3.g 21)Micropore diameter (nm)Mesopore diameter (nm)ZIF-8102513520.450.540.352 4.43ED-ZIF-8142818970.610.750.5444.53Figure 1.N 2adsorption-desorption isotherms of ZIF-8and ED-ZIF-8samples.[Color figure can be viewed in the online issue,which is available at .]Figure2.PXRD patterns of ZIF-8and ED-ZIF-8samples.[Color figure can be viewed in the online issue,which is available at .]AIChE Journal June 2013Vol.59,No.6Published on behalf of the AIChE DOI 10.1002/aic2197differences are also observed.For example,the spectrum of the ED-ZIF-8sample is different from that of the ZIF-8sam-ple in that (1)as shown in Figure 3b there is a new peak at 3381cm 21which is assigned to N A H group appeared on the spectrum of the ED-ZIF-8sample,suggesting some N A H groups have been introduced on the surfaces of the sample ED-ZIF-8,and (2)a peak at 3626cm 21assigned to O A H of the adsorbed H 2O is present in the spectrum of the ZIF-8sample,which is absent in the spectrum of the ED-ZIF-8sample,as shown in Figure 3b.CO 2and N 2adsorption isothermsFor comparison,Figure 4shows the isotherms of CO 2on the ZIF-8and ED-ZIF-8samples.It is visible that the amount adsorbed of CO 2increases as temperature decreases.This suggests that the adsorption of CO 2is mainly physical adsorption.More importantly,it is found that the ED-ZIF-8sample had higher CO 2adsorption capacities compared to the ZIF-8sample,indicating that the adsorption capacities of the modiﬁed ZIF-8toward CO 2are greatly improved,nearly being twice as much as the ZIF-8.One of the reasons is that the surface area (BET)of the ED-ZIF-8increases by 39%,as indicated in Table 1.The other reason is that adsorptioncapacity per unit surface area of the ED-ZIF-8for CO 2increases due to an introduction of N A H groups by postsyn-thetic modiﬁcation.To further understand that,Figure 4a and 4b are separately transferred into Figure 5a and 5b in which the equilibrium uptakes of CO 2based on unit surface area (BET)of the two samples are plotted as a function of CO paring Figure 5b and Figure 5a shows that the CO 2uptake per surface area (BET)of the ED-ZIF-8is obvi-ously higher than that of the ZIF-8,which is mainly ascribed to the introduction of N A H groups,as shown in Figure 3.Figure 6a and 6b show the N 2adsorption isotherms on the two samples.It is visible that the N 2uptakes on the modiﬁed ZIF-8samples are slightly higher than that on the ZIF-8due to its larger surface area and pore volume after modiﬁcation.However,after Figure 6a and 6b are converted into Figure 7a and 7b in which the equilibrium uptakes of N 2based on unit surface area of the two samples are plotted as a function of pressure,it is found from Figure 7that the equilibrium uptakes of N 2per surface area of the ED-ZIF-8are slightly lower than that of the ZIF-8,which means that ED-ZIF-8sample has less afﬁnity toward N 2than ZIF-8sample.This will be helpful to enhance the adsorption selectivity for CO 2/N 2.Figure 3.a.FTIR spectra of the modified ZIF-8crystalsbetween 4,000–400cm 21;b.FTIR spectra of the modified ZIF-8crystals between 4000–2,400cm 21.[Color figure can be viewed in the online issue,which is available at .]Figure 4.a.Isotherms of CO 2on the ZIF-8sample withdifferent temperatures; b.isotherms of CO 2on the ED-ZIF-8sample with different temperatures.[Color figure can be viewed in the online issue,which is available at .]2198DOI 10.1002/aicPublished on behalf of the AIChE June 2013Vol.59,No.6AIChEJournalMultiple cycles of CO 2adsorption-desorption on the ED-ZIF-8To evaluate the regeneration performance of the modiﬁed sample or the reversibility of CO 2adsorption on the modi-ﬁed sample,the experiments of multiple cycles of CO 2adsorption-desorption on the ED-ZIF-8were performed in the Rubotherm system at 298K.For adsorption process,the adsorption pressure were targeted for 25bar;while for de-sorption process the system pressure was targeted for 1mbar,and then the desorption system was quickly depressur-ized by using vacuum pumping.Figure 8shows the variation curve of the amounts adsorbed of CO 2on the ED-ZIF-8dur-ing four consecutive cycles of CO 2adsorption-desorption experiments at 298K.It was visible clearly that during the desorption,the amounts adsorbed of CO 2on the ED-ZIF-8sample decreased sharply with time,and then reached a very low content,about 2.21wt %of residual CO 2which was present on the sample after desorption at 1mbar.The efﬁ-ciency of CO 2desorption was nearly up to 98%over the entire four circles.It indicated further that CO 2adsorption was reversible with very little accumulation of irreversible bound CO 2on the ED-ZIF-8framework.In addition,it wasalso observed from Figure 8that the curves representing the cycles of CO 2adsorption-desorption experiments were very similar,suggesting that adsorption and desorption properties of the sample ED-ZIF-8for CO 2were stable or repeatable.It also proved that the pressure swing was effective in strip-ping adsorbed CO 2from the ED-ZIF-8.H 2O adsorption isothermsFigure 9shows the water isotherms on the modiﬁed ZIF-8samples at 298K.The water uptake on the ED-ZIF-8sample is less than that on the ZIF-8sample,indicating that the sur-face of the modiﬁed sample became more hydrophobic com-pared to the ZIF-8sample.It also means that the interaction of the water molecule with the modiﬁed sample became weaker as compared to that with the ZIF-8.Ideal adsorbed solution theory (IAST)selectivity of CO 2/N 2The ideal adsorbed solution theory (IAST)developed by Myers and Praunitz 66provides an effective method to predict the adsorption selectivity and the adsorption equilibrium of gas mixtures from the isotherms of the pure components.Figure 5.a.Isotherms of CO 2on the ZIF-8samplebased on unit surface area;b.isotherms of CO 2on the ED-ZIF-8sample based on unit surface area.[Color figure can be viewed in the online issue,which is available at .]Figure 6.a.Isotherms of N 2on the ZIF-8sample atdifferent temperatures;b.isotherms of N 2on the ED-ZIF-8sample at different temperatures.[Color figure can be viewed in the online issue,which is available at .]AIChE JournalJune 2013Vol.59,No.6Published on behalf of the AIChE DOI 10.1002/aic2199Previous work reported that the IAST can accurately predict gas mixture adsorption in a number of zeolites and MOF materials.10,48,67–70The IAST assumes that the adsorbed mixture is an ideal solution at constant spreading pressure and temperature,where all the components in the mixture conform to the rule analogous to Raoult’s law,and the chemical potential of the adsorbed solution is considered equal to that of the gas phase at equilibrium.From the IAST,the spreading pressure p is given byp 0i ðp 0i Þ5RT A ðp 0iqd ln p (1)p Ã5p A 5ðp 0i 0q i dp (2)Where A is the speciﬁc surface area of the adsorbent,p andp *are the spreading pressure and the reduced spreading pres-sure,separately.p 0i is the gas pressure of component i corre-sponding to the spreading pressure p of the gas mixture.At a constant temperature,the spreading pressure of single component is the samep Ã15p Ã25…5p Ãn 5p(3)For binary adsorption of component 1and 2,the IASTrequiresy 1p t 5x 1p 1ð12y 1Þp t 5ð12x 1Þp 2(4)Where y 1and x 1denote the molar fractions of component 1in the gas phase and in the adsorbed phase,respectively.p t is the total gas pressure,p 1and p 2are the pressures of com-ponent 1and 2at the same spreading pressure as that of the mixture,respectively.Adsorption selectivity in a binary mixture of component 1and 2is deﬁned asS 125x 1x 2 y 2y 1 (5)For the application of IAST to predict adsorption separa-tion selectivity,the following two conditions are necessary:good quality adsorption data of each single component;and excellent curve ﬁtting model for such data.48,71,72In order to perform the integrations of Eqs.(1)and (2)required by IAST,the single-component isotherms should be ﬁtted by a proper isotherm model.In practice,several meth-ods are available.In this work,it is found that the dual-site Langmuir-Freundlich (DSLF)equation can be successful to ﬁt this set of adsorption data.The dual-site Langmuir-Freundlich model can be expressed as followsq 5q m ;13b 1p 1=n 111b 1p 11q m ;23b 2p 1=n 211b 2p 2(6)Where p is the pressure of the bulk gas at equilibrium with the adsorbed phase (kPa),q m,1,q m,2are the saturation capaci-ties of sites 1and 2(mmol/g),b 1and b 2are the afﬁnity coefﬁcients of sites 1and 2(1/kPa),and n 1and n 2are the deviations from an ideal homogeneous surface.Figure 10shows a comparison of the model ﬁts and the isotherm data.It is visible that the DSLF model can be applied favorably for ﬁtting experimental data of CO 2and N 2adsorption.Table 2presents the ﬁtting parameters ofFigure 7.a.Isotherms of N 2on the ZIF-8sample basedon unit surface area;b.isotherms of N 2on the ED-ZIF-8sample based on unit surface area.[Color figure can be viewed in the online issue,which is available at .]Figure 8.Recycle runs of CO 2adsorption-desorptionon the ED-ZIF-8at 298K and 25bar for adsorption and 1mbar for desorption.[Color figure can be viewed in the online issue,which is available at .]2200DOI 10.1002/aicPublished on behalf of the AIChE June 2013Vol.59,No.6AIChEJournalDSLF equation as well as the correlation coefﬁcients (R 2).Examination of the data shows that this DSLF model is able to ﬁt the adsorption data well since the correlation coefﬁ-cients R 2are up to 0.9997.In this work,the equilibrium adsorption data of single component CO 2as well as N 2are available,and the DSLF model can ﬁt the experimental isotherms of CO 2and N 2adsorption very well.Therefore,the DSLF model can be combined with the ideal adsorbed solution theory (IAST)to predict the mixture adsorption isotherms and calculate the selectivities of the two samples for CO 2/N 2adsorption.Figure 11a and 11b present,respectively,the adsorption isotherms predicted by IAST for equimolar mixtures of CO 2/N 2in the samples ZIF-8and ED-ZIF-8as a function of total bulk pressure.It can be seen that CO 2is preferentially adsorbed over N 2on the two samples because of stronger interactions between CO 2and the ZIF-8sample,and the amount adsorbed of N 2is much lower in the mixtures than that in single-component adsorption because of competition adsorption from CO 2,which adsorbs more strongly.Figure 12shows the IAST-predicted selectivities of the two samples for equimolar CO 2and N 2mixtures at 298K as a function of total bulk pressure.It can be seen that the adsorption selectivity of the two samples for CO 2/N 2dropped with an increase in the pressure.More importantly,Figure 9.H 2O adsorption isotherms on the modifiedZIF-8samples at 298K.[Color figure can be viewed in the online issue,which is available at .]Table 2.The Fitting Parameters of the Dual-site Langmuir-Freundlich Equations for the Pure Isotherms of CO 2and N 2at 298KZIF-8ED-ZIF-8CO 2N 2CO 2N 2R 20.99970.99990.99970.9999q m,1(mmol/g)27.2527.8748.8828.32q m,2(mmol/g) 2.122 1.919 4.672 1.847b 1(atm 21)0.015330.0011700.012590.001388b 2(atm 21)0.0068950.026090.029480.02504n 1 1.6000.7875 1.4040.7704n 20.32440.96340.44300.8671Figure 10.DSLF fitting of the CO 2and N 2isotherms onZIF-8and ED-ZIF-8at 298K.[Color figure can be viewed in the online issue,which is available at .]Figure11.a.The IAST -predicted isotherm forequimolar CO 2/N 2mixtures of the ZIF-8sample at 298K as a function of total bulk pressure; b.the IAST -predicted isotherm for equimolar CO 2/N 2mixtures of the ED-ZIF-8sample at 298K as a function of total bulk pressure.[Color figure can be viewed in the online issue,which is available at .]AIChE Journal June 2013Vol.59,No.6Published on behalf of the AIChE DOI 10.1002/aic2201the adsorption selectivity of CO 2/N 2on the sample ED-ZIF-8is always higher than that on the sample ZIF-8,especially in the low-pressure region.For example,at 0.1and 0.5bar,the selectivity of the sample ED-ZIF-8for CO 2/N 2were up to 23and 13.9separately,which is almost twice of those of the sample ZIF-8.Figure 13a and 13b show,respectively,the IAST-pre-dicted selectivities of the samples ZIF-8and ED-ZIF-8for CO 2/N 2at different mixture compositions and different pres-sures.It is noticed that the selectivity increases rapidly as the gas-phase mole fraction of N 2approaches unity.For example,at yN 250.9,a typical feed composition of ﬂue gas,high selectivities are obtained.Even at yN 250.5,the selectivity of the ED-ZIF-8for CO 2/N 2is in the range of 6–24,much higher than those on the ZIF-8sample and many other MOF samples such as ZIF-7030,ZIF-6830and MOF-508b.73This property is very important since some separa-tion processes could be operated at low pressures,such as vacuum swing adsorption (VSA),which could be extremely efﬁcient by using the sample ED-ZIF-8because its selectiv-ity increases dramatically with decreasing pressure.Ideal adsorbed solution theory (IAST)selectivity of CO 2/N 2/H 2OThe major challenge of CO 2capture from power plant ﬂue gas wastes is the separation of CO 2/N 2.In addition,competition adsorption of water molecule must be taken into account,because these ﬂue gas wastes are usually saturated with certain amount of water (5–7%by volume)for the industrial postcombustion processes.Thus,for real industrial use of adsorbents,the effect of water on CO 2/N 2selectivity is another crucial factor that needs to be considered and evaluated.Here,the IAST was adopted to evaluate the ter-nary mixture CO 2/N 2/H 2O adsorption on the modiﬁed ZIF-8samples.First,the experimental isotherms of water on the modiﬁed ZIF-8samples at 298K were ﬁtted using the DSLF model.Table 3presents the ﬁtting parameters of DSLF equation as well as the correlation coefﬁcients.It can be seen that theDSLF model ﬁts the H 2O adsorption on both samples very well.Second,the DSLF model was combined with the ideal adsorbed solution theory (IAST)to predict the mixture adsorption isotherms,and then calculate the selectivities of the two samples for CO 2/N 2adsorption.Figure 14shows the predicted isotherms of ternary mix-ture CO 2/N 2/H 2O on the modiﬁed ZIF-8samples at 298K.It can be observed that in comparison with the ZIF-8,after modiﬁcation,the CO 2adsorption capacity of the ED-ZIF-8in the ternary mixture obviously increased,and its N 2adsorption capacity somewhat increased,which made CO 2/N 2adsorption selectivity of the ED-ZIF-8increase.More importantly,its water adsorption capacity in the ternary mix-ture became lower compared to the ZIF-8,and it was also lower than the single component water uptake.It means the competition adsorption of H 2O in the ternary mixture was weakened on the surfaces of the ED-ZIF-8sample.Figure 12.The IAST -predicted selectivity for equimolarCO 2and N 2at 298K as a function of total bulk pressure.[Color figure can be viewed in the online issue,which is available at .]Figure 13.a.The IAST predicted selectivities atdifferent mixture compositions and different pressures for the ZIF-8sample at 298K;b.the IAST predicted selectivities at different mixture compositions and different pressures for the ED-ZIF-8sample at 298K.[Color figure can be viewed in the online issue,which is available at .]2202DOI 10.1002/aicPublished on behalf of the AIChE June 2013Vol.59,No.6AIChEJournal。

美得理电子数字钢琴DP378说明书

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装箱单尊敬的用户，当您选购本乐器后，请检查以下物品是否齐全：琴体左支撑板右支撑板后面板踏板组件（包括踏板连接线）一包螺母用户说明书售后保修证书调音台23踏板功能..................................................................23功能菜单音调设置....................................................................24键盘分离点设置.........................................................25节拍种类设置.............................................................25节拍器音量设置.........................................................25踏板定义设置.............................................................25混响深度设置.............................................................26合唱深度设置.............................................................26和声类型设置.............................................................26和声速度设置.............................................................27MIDI接收设置............................................................27MIDI发送设置............................................................27定时关机设置.............................................................27演奏帮助节拍设置.. (27)恢复出厂设置..........................................................28面板注册记忆设置将设置保存到注册记忆..............................................28调出注册记忆.............................................................28选择记忆库................................................................28伴奏锁定.. (29)歌本功能..................................................................29录制自己的歌曲 (30)开始录音....................................................................30停止录音....................................................................31回放已录制的歌曲.....................................................31删除已录制的歌曲.. (31)播放及控制歌曲欣赏歌曲....................................................................32歌曲控制....................................................................32歌曲学习模式. (32)和弦字典..................................................................34MIDI功能什么是MIDI?..............................................................35上传数据到电脑/下载数据到设备. 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DERSIMELAGON 产品说明书

488 Scientific AbstractsSystemic sclerosis, myositis and related syndromes - aetiology, pathogenesis and animal modelsPOS0467 DERSIMELAGON, A NOVEL ORAL MELANOCORTIN1 RECEPTOR AGONIST, DEMONSTRATES DISEASE-MODIFYING EFFECTS IN PRECLINICAL MODELS OFSYSTEMIC SCLEROSISM. Kondo1, T. Suzuki1, Y. Kawano1, S. Kojima2, M. Miyashiro1, A. Matsumoto1, G. Kania3, P. Blyszczuk3, R. Ross4, P. Mulipa4, F. Del Galdo4, Y. Zhang5, J. H. W. Distler5. 1Mitsubishi T anabe Pharma Corporation, Research Unit/Immunology & Inflammation, Souyaku Innovative Research Division, Y okohama, Japan;2Mitsubishi T anabe Pharma Corporation, Discovery T echnology Laboratories, Souyaku Innovative Research Division, Y okohama, Japan;3University Hospital Zurich, University of Zurich, Center of Experimental Rheumatology, Department of Rheumatology, Schlieren, Switzerland;4University of Leeds, Leeds Instituteof Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, Leeds, United Kingdom;5Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Department of Internal Medicine 3—Rheumatology and Immunology, Erlangen, GermanyBackground: Activation of melanocortin 1 receptor (MC1R) is known to have broad anti-inflammatory and anti-fibrotic effects. The bleomycin (BLM)-induced skin fibrosis murine model is well-established for systemic sclerosis (SSc). α-mel-anocyte-stimulating hormone, an endogenous ligand of MC1R, inhibits skin fibro-sis and MC1R knock-out enhances skin fibrosis in this model. These pieces of evidence suggest that MC1R agonism has potential in the treatment of SSc. Objectives: Dersimelagon phosphate (MT-7117) is an investigational small molecule that is an orally administered, selective agonist for MC1R. The purpose of this study is to investigate the potential of MT-7117 as a therapeutic agent for SSc by evaluat-ing its efficacy and mechanism of action in complementary preclinical models. The expression and distribution of MC1R in the skin of SSc patients was investigated. Methods: The effects of MT-7117 on skin fibrosis and lung inflammation were eval-uated in BLM-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation. Microarray-based gene expression analysis and serum pro-tein profiling were performed to investigate the mechanism of action of MT-7117 in the BLM-induced SSc models. The effect of MT-7117 on TGF-β-induced activation of human dermal fibroblasts was evaluated in vitro. Immunohistochemical analyses of MC1R expression in skin samples from SSc patients were performed. Results: Prophylactic treatment with MT-7117 (≥0.3 mg/kg/day p.o.) significantly inhibited the increase in collagen content of the skin, the serum level of sur-factant protein D, and the weight of the lungs from BLM-induced skin fibrosis and lung inflammation model. Therapeutic treatment with MT-7117 (≥3 mg/kg/ day p.o.) significantly suppressed skin thickening and the numbers of myofi-broblasts in pre-established BLM-induced skin fibrosis model. Gene array anal-ysis using the BLM-induced SSc model demonstrated changes in numerous categories related to macrophages, monocytes, and neutrophils, followed by endothelial cell-related categories after treatment with MT-7117. In the analy-sis that focused on biological functions, categories of inflammatory response, activation of antigen-presenting cells, angiogenesis, atherosclerosis, vascu-logenesis, and vaso-occlusion were suppressed by MT-7117. In the analysis that focused on molecular signaling pathways, triggering receptor expressed on myeloid cells-1, IL-6, and oncostatin M involved in inflammation, and perox-isome proliferator-activated receptor that is related to fibrosis were all affected by MT-7117. Serum protein profiling using BLM-induced SSc model revealed that multiple SSc-related biomarkers including P-selectin, osteoprotegerin, cys-tatin C, growth and differentiation factor-15 and S100A9 were suppressed by MT-7117. MT-7117 inhibited the activation of human dermal fibroblasts by sup-pressing TGF-β-induced ACTA2 (encoding α-smooth muscle actin) mRNA ele-vation in vitro. Immunohistochemical analyses showed that MC1R positivity was observed in 40 of 50 diffuse cutaneous SSc patients. MC1R was expressed by monocytes/macrophages, neutrophils, blood vessels (endothelial cells), fibro-blasts, and epidermis (keratinocytes) in the skin of SSc patients. Conclusion: MT-7117 demonstrates disease-modifying effects in preclinical mod-els of SSc. Investigations of its mechanism of action and target expression anal-yses indicate that MT-7117 exerts its positive effects by affecting the pathologies of inflammation, vascular dysfunction, and fibrosis through inflammatory cells, endothelial cells, and fibroblasts. In view of its potent beneficial impact on all these three main pathologies of SSc, MT-7117 is a potential therapeutic agent for the treatment of clinically challenging SSc, which has diverse and difficult to treat symp-toms. A phase 2 clinical trial investigating the efficacy and tolerability of MT-7117 in patients with early, progressive diffuse cutaneous SSc is currently in progress. Disclosure of Interests: Masahiro Kondo Employee of: Mitsubishi Tanabe Pharma Corporation, Tsuyoshi Suzuki Employee of: Mitsubishi Tanabe Pharma Corporation, Yuko Kawano Employee of: Mitsubishi Tanabe Pharma Corpora-tion, Shinji Kojima Employee of: Mitsubishi Tanabe Pharma Corporation, Masa-hiko Miyashiro Employee of: Mitsubishi Tanabe Pharma Corporation, Atsuhiro Matsumoto Employee of: Mitsubishi Tanabe Pharma Corporation, Gabriela Kania: None declared, Przemyslaw Blyszczuk: None declared, rebecca ross:None declared, Panji Mulipa: None declared, Francesco Del Galdo Grant/ research support from: Prof. F. Del Galdo received fees and research supportfrom Abbvie, AstraZeneca, Boehringer-Ingelheim, Capella, Chemomab, Kymab, Janssen and Mitsubishi-Tanabe., Yun Zhang: None declared, Jörg H.W. DistlerGrant/research support from: Prof. J.H.W. Distler received consulting fees, lec-ture fees, and/or honoraria from Actelion, Active Biotech, Anamar, ARXX, aTyr,Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, Sanofi-Aventis, RedX, RuiYi and UCB. J. H. W.Distler is stock owner of 4D Science and Scientific head of FibroCure.DOI: 10.1136/annrheumdis-2022-eular.29POS0468 EXTRACELLULAR VESICLES FROM SERUM OFMYOSITIS PATIENTS AS CIRCULATING BIOMARKERSAND DISEASE MEDIATORSS. Kivity1,2, H. Kravitz3, C. Cohen3, D. Margoulis3, M. Amar3, G. Kazimirsky3,D. Ozeri4, A. Dori5, C. Brodie3. 1Meir Medical Center, Rheumatology Unit, KefarSava, Israel;2T el Aviv University, Sackler faculty of Medicine, T el Aviv-Y afo, Israel;3Bar-Ilan University, The Mina and Everard Goodman Faculty of Life Sciences,Ramat Gan, Israel;4T el-HaShomer The Sheba Medical Center, ZabludowiczCenter for Autoimmune Disease, Ramat Gan, Israel;5T el-HaShomer The ShebaMedical Center, Department of Neurology, T alpiot Medical Leadership Program,Sackler Faculty of Medicine, T el Aviv University, Ramat Gan, IsraelBackground: Inflammatory myopathies (IM) are a heterogeneous group of disor-ders characterized by autoimmune inflammatory destruction of skeletal muscles.It is many times associated with lung, skin and joint involvement. Identifying bio-markers that can differentiate IM from other muscle disorders may elucidate the pathophysiology of IM, guide novel therapies, monitor disease activity/responseto treatments and predict prognosis. Exosomes are membrane-bound nanove-sicles with diameters of 30-150 nm that contain multiple proteins, nucleic acid,lipids and other molecules in a tissue- and cell-specific manner. Exosomes are secreted by a large variety of cells, play major roles in cell-cell interactions, andhave recently emerged as circulating biomarkers in a variety of pathological con-ditions, including several autoimmune diseases.Objectives: To characterize exosomes from serum of IM patients, analyze pro-tein expression and study their potential mediators of disease pathologies.Methods: Serum was collected from patients suffering from IM(n=5) and from patients suffering from Becker (BMD) and Duchenne (DMD) muscular dystro-phies (n=6). Exosomes were isolated by Exoquick precipitation and analyzedfor size distribution and by nanoparticle tracking analysis (NTA) and by Westernblot for exosome markers. The effects of the isolated EVs on human satellitecell proliferation and differentiation and macrophage activation were examined. Results: Exosomes from IM patients decreased human satellite cell proliferation (51%, P<0.01) and inhibited their myogenic differentiation as indicated by lower fusionindex (24% inhibition, P<0.01) and expression of myosin heavy chain (72% inhibi-tion, P<0.001). Similar results were obtained also with exosomes derived from DMDand BMD patients; however, their inhibitory effect were more pronounced on MyoG expression. T reatment of macrophages with exosomes from IM patients significantly increased the expression of IL-10 (3-fold, P<0.001), compared to exosomes of healthy controls and DMD patients. Another significant difference was in the expression of sig-naling molecules: Thus, exosomes from BMD patients increased the phosphorylationof Erk and p38, whereas a smaller effect was induced by IM exosomes.Conclusion: Exosomes from IM patients decrease satellite cell proliferationand myogenic differentiation compared to healthy exosomes. In addition, these exosomes increased the expression of IL-10 in macrophages. These effects areunique to exosomes of IM patients compared to muscular dystrophies. These promising results suggest that serum exosomes should be further investigatedas a novel biomarker with potential therapeutic implications.Disclosure of Interests: Shaye Kivity Speakers bureau: BI, Abbvie, Lilly, Pfizer, Janssen, Neopharm, Grant/research support from: Sobi, Haya Kravitz: None declared, Coral Cohen: None declared, Darya Margoulis: None declared, MosheAmar: None declared, Gila Kazimirsky: None declared, David Ozeri Speakers bureau: Neopharm, Consultant of: Abbvie, Amir Dori Grant/research supportfrom: Biogen, Chaya Brodie Grant/research support from: Biogen.DOI: 10.1136/annrheumdis-2022-eular.63POS0469 ENDOTHELIAL TO MESENCHYMAL TRANSITIONAND SENESCENCE ARE PART OF THE FIBROTICPATHOGENESIS IN SYSTEMIC SCLEROSISY. H. Chiu1,2, J. Spierings1, J. M. Van Laar1, J. De Vries-Bouwstra3, M. VanDijk4, R. Goldschmeding4. 1University Medical Center Utrecht, Departmentof Rheumatology and Clinical Immunology, Utrecht, Netherlands;2T ri-ServiceGeneral Hospital, Division of Rheumatology/Immunology/Allergy, T aipei, T aiwan, Republic of China;3Leiden University Medical Center, The Department of on December 24, 2023 by guest. Protected by copyright./ Ann Rheum Dis: first published as 10.1136/annrheumdis-2022-eular.29 on 23 May 2022. Downloaded from。

美诺芬成分

美诺芬成分
（原创版）
目录
1.美诺芬的定义与背景
2.美诺芬的主要成分
3.美诺芬的药理作用与应用
4.美诺芬的副作用与注意事项
5.美诺芬的未来发展前景
正文
【美诺芬的定义与背景】
美诺芬（Minoxidil）是一种用于治疗高血压和心衰的药物，由美国辉瑞制药公司研发并在 1979 年首次上市。

美诺芬属于一类称为“ACE 抑制剂”的药物，其作用机制是通过抑制血管紧张素转换酶（ACE）的活性，从而降低血压和减轻心脏负担。

【美诺芬的主要成分】
美诺芬的主要成分是 Minoxidil，化学名为 3-[[2-[(2-甲基 -3-硝基 -4-羟基苯基) 甲基]-1H-咪唑 -1-基] 甲基]-2-硝基 -4-羟基苯酚。

【美诺芬的药理作用与应用】
美诺芬的药理作用主要是通过抑制 ACE 的活性，减少血管紧张素Ⅱ的生成，从而降低血压和减轻心脏负担。

此外，美诺芬还可以减少醛固酮的分泌，减少水钠潴留，进一步降低血压。

美诺芬主要用于治疗高血压和心衰，也可用于降低糖尿病和肾脏疾病患者的高血压。

【美诺芬的副作用与注意事项】
美诺芬的常见副作用包括头痛、乏力、低血压、皮疹、瘙痒等。

在服
用美诺芬期间，应注意监测血压，避免出现低血压的情况。

此外，孕妇、哺乳期妇女、儿童以及对美诺芬过敏的患者应慎用或禁用。

【美诺芬的未来发展前景】
随着对美诺芬研究的深入，科学家们发现美诺芬除了具有降压作用外，还具有其他多种生物活性。

例如，美诺芬可以通过抗氧化、抗炎等作用保护心血管系统，降低心血管疾病的发生风险。

此外，美诺芬在神经保护、抗肿瘤等方面也具有一定的潜力。

Mifepristone_84371-65-3_DataSheet_MedChemExpress

Product Name:Mifepristone CAS No.:84371-65-3Cat.No.:HY-13683Product Data SheetCat. No.:HY 13683MWt:429.59Formula:C29H35NO2Purity :>98%25°C:DMSO 86mg/mL;Water<1Solubility:Mechanisms:Biological Activity:D i tiPathways:GPCR/G protein; Target:Glucocorticoid ReceptorPathways:Others; Target:Progesterone Receptor 25C: DMSO 86 mg/mL; Water 1mg/mL; Ethanol 79 mg/mLDescription:IC50 Value: 0.2 nM (Progesterone receptor); 2.6 nM (Glucocorticoid receptor) [1]Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesteronereceptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. Mifepristone is also a powerful glucocorticoid receptor antagonist,and has occasionally been used in refractory Cushing's Syndrome.in vitro: Mifepristone had no effect onHeLa cell proliferation inhibition rate during 24 and 48 hours (p > 0.05). Mifepristone at low concentrations (< or = 10 micromol/l) combined withcisplatin cansignificantly enhance the inhibitory effect of cisplatin on HeLa cell line [2]The effect of mifepristone References:[1]. Jiang W, Allan G, Fiordeliso JJ, New progesterone receptor antagonists: phosphorus-containing11beta-aryl-substituted steroids. Bioorg Med Chem. 2006 Oct 1;14(19):6726-32. Epub 2006 Jun 27.[2]. Li C, Ye H. Mifepristone sensitizing cisplatin for cervical adenocarcinoma HeLa cell sensitivity to significantly enhance the inhibitory effect of cisplatin on HeLa cell line [2]. The effect of mifepristone on cytotoxicity of cisplatin could be mediated, at least partially, by an increase of intracellularcisplatin accumulation, ...chemotherapy and itsmechanism. Eur J Gynaecol Oncol. 2013;34(2):142-7.[3]. Jurado R, Lopez-Flores A, Alvarez A, Cisplatin cytotoxicity is increased by mifepristone incervical carcinoma: an in vitro and in vivo study. Oncol Rep. 2009 Nov;22(5):1237-45.[4]. Sharrett-Field L, Butler TR, Berry JN, Mifepristone Pretreatment Reduces Ethanol WithdrawalSeverity In Vivo. Alcohol Clin Exp Res. 2013 Mar 25.Caution: Not fully tested. For research purposes onlyMedchemexpress LLC18W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c om。

Polyhedral oligomeric silsesquioxane(POSS)-based polymers

Polyhedral Oligomeric Silsesquioxane (POSS)-Based PolymersJoseph J.Schwab 1*and Joseph D.Lichtenhan 21Hughes STX Corporation,Phillips Laboratory,Propulsion Directorate Edwards AFB,CA 93524,USA 2Phillips Laboratory,Propulsion Directorate,Edwards AFB,CA 93524,USAA diverse and entirely new class of monomer and polymer technology based on polyhedral oligo-meric silsesquioxane (POSS)reagents has been developed.POSS reagents are unique in thatthey are physically large (approx.15A˚diameter and 1000amu)and are composed of a robust silicon–oxygen framework that can be easily functionalized with a variety of organic sub-stituents.Appropriate functionalization of POSS cages allows for their incorporation into tradi-tional thermoplastic resins without modiﬁcation of existing manufacturing processes.The incor-poration of POSS segments into linear copoly-mer systems results in increased glass transition and decomposition temperatures,increased oxy-gen permeability and reduced ﬂammability and heat evolution,as well as modiﬁed mechanical properties relative to conventional organic systems.#1998John Wiley &Sons,Ltd.Keywords:polyhedral oligomeric silsesquiox-ane;hybrid;thermoplastic;polymerReceived 17June 1997;accepted 2September 1997INTRODUCTIONSince their discovery almost 70years ago,synthetic polymers have played an increasingly important role in daily life.This is especially true today,when polymers and plastics are ﬁnding their way into an evermore diverse array of products and applica-tions.However,along with this increased use have come more demanding requirements,such as higher temperatures of use and greater resistance to oxidation.Although the polymer industry hasbeen able to keep abreast of these demands,through the use of additive,ﬁller and blend technologies,as well as increased empirical understanding of polymer microstructures,new developments tend to be incremental and the existing technology and knowledge are rapidly being pushed to their limits by the more demanding requirements of end-users.Although the range and types of plastic and polymer systems are quite impressive,much of this work has been accomplished using a relatively limited number of basic chemical building blocks,i.e.the monomers which make up the primary structure of the polymer system.Without excep-tion,these monomers are based on organic systems and the pool of available building blocks has remained almost static over the past 25years.A recent approach to meeting these demands has been the development of new plastics that have properties intermediate between those of traditional organic systems (i.e.polymers)and those of traditional inorganic systems (i.e.ceramics).This interest,along with the concomitant research effort,has given rise to the ﬁeld of hybrid materials research,which endeavors to combine the proper-ties of traditional organic polymer systems (i.e.processability,toughness,cost)with the properties of inorganic compounds (i.e.thermal and oxidative stability)(Fig.1).For reviews and leading refer-ences on recent progress in hybrid materials,the reader should consults Refs1–3.Figure 1Schematic representation of the area of hybridmaterials.APPLIED ORGANOMETALLIC CHEMISTRY anometal.Chem.12,707–713(1998)#1998John Wiley &Sons,C 0268–2605/98/100707–07$17.50*Correspondence to:Joseph J.Schwab,Hughes STX Corporation,Phillips Laboratory,Propulsion Directorate Edwards AFB,CA 93524,USA.Contract/grant sponsor:US Air Force Ofﬁce of Scientiﬁc Research,Directorate of Chemistry.Contract/grant sponsor:Phillips Laboratory,Propulsion Directorate.Using this basic idea,several broad classes of hybrid plastics have been developed and are shown schematically in Fig.2.Examples of these include the sol–gel networks,which are three-dimensional crosslinked systems having a dispersed inorganic, silica-like phase in a polymer matrix;preceramic polymers,such as the polyphosphazenes,polycar-bosilanes,polysilanes and polysiloxanes;and inorganic/organic polymer blends.Furthermore,a revitalization of clay-ﬁller technology has occurred with the development of methods for exfoliating layered clays into sheets which then become dispersed on aﬁner level than previously possible. More recently a diverse and entirely new chemical technology of polyhedral oligomeric silsesquioxane (POSS)nanocomposites has been developed.This technology affords the possibility of preparing plastics that contain nanoscale reinforcements (POSS segments)directly bound to the polymer chains.Unlike previous hybrid systems,the POSS technology materials have the additional advantage of being employable in the same manner as organic monomers or in the form of blendable resins. Here we describe some of our preliminary efforts to prepare well-deﬁned,nanoreinforced,thermo-plastic polymeric hybrids with enhanced properties that can be understood and tailored at the molecular level.RESULTSWhereas the majority of the work on the synthesis of hybrid materials has been directed towards use of the sol–gel process,4our approach has been to prepare hybrid materials which can be incorporated into traditional linear,thermoplastic polymer sys-tems.The hybrid materials developed in our laboratory are based on POSS precursors.5,6POSS precursors are discrete,structurally well-deﬁned compounds composed of a silicon–oxygen frame-work having the general formula(RSiO3/2)n,and are prepared via the hydrolysis of organotrichloro-silanes as shown in Scheme1.7,8,9Although some of the POSS precursors isolated from the hydrolysis mixture can be used directly in polymerization reactions,additional functionaliza-tion is often required.In order to incorporate the POSS reagents into linear polymer systems and thus avoid the formation of intractable,crosslinked networks,it is necessary to limit the number of functional groups to no more than one or two. Functionalization of the POSS framework is most easily accomplished by corner capping of the POSS-trisilanols with silane coupling agents con-taining organic groups suitable for polymerizations and/or grafting reactions(Scheme2).Isolated yields from the corner capping reactionsexceed Figure2Schematic representations of different hybrid plastics.#1998John Wiley&Sons,anometal.Chem.12,707–713(1998) 708J.J.SCHWAB AND J.D.LICHTENHANScheme 1POSS products from the hydrolysis of cyclohexyltrichlorosilane,(R =c-C 6H 11).Scheme 2Synthesis of polymerizable POSS reagents (R =non-reactive functionality;R '=polymerizable or graftablefunctionality).Scheme 3POSS functional groupinterconversion.Figure 3Some of the functionalities which can be prepared from POSS-trisilanol precursors.#1998John Wiley &Sons,Ltd.anometal.Chem.12,707–713(1998)POSS-BASED POLYMERS 70990%and are typically greater than 95%if care is taken to exclude moisture from the system.In cases where the appropriate functionality is not directly available by the corner capping sequence,subsequent functional group transforma-tions of the reactive group on the unique silicon arepossible.For example,the conversion of POSS-a -oleﬁns to POSS-epoxides using m -chloroperben-zoic acid (MCPBA)is shown in Scheme 3.Using these methods,we have built up a large catalogue of POSS reagents containing polymeriz-able and/or graftable functionalities.ThismakesFigure 4Polymer architectures available from POSS monomers:(A)pendant;(B)AB multiblock ‘bead’,(C)ABA triblock;(D)star.#1998John Wiley &Sons,Ltd.anometal.Chem.12,707–713(1998)710J.J.SCHWAB AND J.D.LICHTENHANpossible the incorporation of POSS units into traditional resin systems.Some typical functional-ities are listed in Fig.3.These POSS reagents have a number of desirable physical properties.For example,they are highly soluble in common organic solvents such as tetrahydrofuran (THF),toluene,chloroform and hexane.They have high thermal stabilities,10and can be polymerized using standard polymerization protocol (i.e.radical polymerizations,condensation polymerizations,ring opening polymerizations etc.)to provide polymers with a variety of architectures as illustrated in Fig.4.Whereas hybrid materials produced from either the sol–gel process or from multifunctional POSS precursors 11(i.e.with functionality b 2)are highly crosslinked network polymers (akin to thermoset plastics)and as such tend to be difﬁcult to process,our reagents can be used to produce thermoplastic polymers in which the inorganic portion of the hybrid is covalently linked to the organic polymer chain.It is this unique ability to start from well-deﬁned hybrid monomers that makes it possible tocontrol the polymer architecture and ultimately to tailor the polymer properties at the molecular level.Incorporation of POSS-silanol,12POSS-acry-late,13POSS-styrene,14,15POSS-norborna-diene,16,17and POSS-bisphenol A monomers 18,19into the respective polysiloxanes,polyacrylates,polystyrenes,polynorbornadienes and polyur-ethanes has been demonstrated.All of the POSS-hybrid polymers prepared so far show thermoplas-tic behavior,and the POSS-urethanes exhibit full thermoplastic elasticity.To our knowledge these are the ﬁrst hybrid organic/inorganic polymers to exhibit this behavior.Incorporation of POSS monomers into ordinary polymers can have dramatic effects on the copoly-mer properties.For example,Fig.5shows the thermomechanical (TMA)data for a set of cyclopentyl-POSS-methacrylate/butyl methacry-late copolymers.Copolymers containing 10mol%POSS have a softening point almost 130°C higher than the 20°C glass transition temperature (T g )for atactic poly(butyl methacrylate).The value of T g for atactic poly(butyl methacrylate)is takenfromFigure 5TMA data from cyclopentyl-POSS-methacrylate/butyl methacrylate copolymers:top,50:50copolymer;middle,20:80copolymer,bottom:10:90copolymer.(Au proportions in mol%.)#1998John Wiley &Sons,Ltd.anometal.Chem.12,707–713(1998)POSS-BASED POLYMERS 711Ref 20which also reports a range of 13–35°C.Incorporation of 20mol%POSS results in a further increase in the softening point by approximately 70°C,while a 50:50(mol/mol)copolymer has a softening point over 220°C higher than poly(butyl methacrylate).To date,similar results have been observed in every POSS copolymer system we have studied.Furthermore,as a result of their high formula weights,incorporation of only a small mol percentage of POSS monomer is necessary to achieve incorporation of a high weight percentage of POSS (Fig.6).We also ﬁnd that relatively small amounts of POSS monomer are necessary to achieve many of these property enhancements.For example,in cyclopentyl-POSS-methacrylate/methyl methacry-late copolymers we ﬁnd that addition of only 5mol%(35wt%)POSS results in a 50°C increase in T g .Moreover,the relationship between the percentage POSS incorporation and the increase in T g appears to be roughly linear up to the decomposition point,thus demonstrating the tailor-ability of POSS-containing hybrid polymers.In addition to increased T g ,we have also observed increased T dec ,increased resistance to oxidation,increased oxygen permeability,reduced ﬂammabil-ity,reduced heat evolution,increased char yields and enhanced miscibility.Although we are only now beginning to develop an understanding of the effects that POSS frame-works have on polymer microstructure and the resulting effects on macroscopic properties,we believe that the observed property enhancements arise in part from the ability of the POSS segments to dominate polymer chain pared with traditional organic monomers,POSS mono-mers are physically very large.For example,the area swept out by an octomeric POSS monomer containing cyclohexyl substituents is approxi-mately 15A˚,in diameter with an inner Si–Si diameter of 5.4A˚.Furthermore,POSS monomers have formula weights of greater than 1000amu.By way of comparison,the dimensions or crystal lamellae in semicrystalline polymers are of theorder of 10–25A˚Â0.1–1m m with the amorphous layer thickness ranging from 5to 10nm.21It therefore seems reasonable to consider POSS frameworks as macromeric with respect to polymer chain dimensions.SUMMARYThe development of POSS-based reagents has provided polymer and materials scientists with a new class of hybrid building blocks.POSS reagents are discrete,well-deﬁned monomers that can be incorporated into polymer systems using estab-lished polymerization protocol.The hybrid poly-mer systems into which POSS hasbeenFigure 6Relationship between mol as percentage and weight percentage of POSS in cyclopentyl-POSS-methacrylate/methyl methacrylate copolymers.#1998John Wiley &Sons,Ltd.anometal.Chem.12,707–713(1998)712J.J.SCHWAB AND J.D.LICHTENHANincorporated have been shown to be thermoplastic in nature,and to have enhanced thermal,mechan-ical and oxidative properties relative to the non-POSS-containing polymers.In addition,the proper-ties of a particular polymer system can be rationally tailored by controlling the percentage of POSS incorporated.Acknowledgments We gratefully acknowledge the Air Force Ofﬁce of Scientiﬁc Research,Directorate of Chemistry and Life Sciences,and the Phillips Laboratory,Propulsion Directorate, forﬁnancial support.REFERENCES1.J.E.Mark,Y.-C.C.Lee and P.A.Bianconi(eds),HybridOrganic–Inorganic Composites,ACS Symp.Ser.No.585, American Chemical Society,Washington,DC,1995.2.L.Mascia,Trends Polym.Sci.3,61(1995).3.C.Sanchez and F.Ribot,Nouv.J.Chem.18,1007(1995).4.P.Judeinstein and C.Sanchez,J.Mater.Chem.6,511(1996).5.J.D.Lichtenhan,in:Polymeric Materials Encyclopedia,Salamone,J.C.(ed.),CRC Press,New York,1996,pp 7769–7778.6.J.D.Lichtenhan,Comments Inorg.Chem.17,115(1995).7.J.F.Brown and L.H.Vogt,J.Am.Chem.Soc.87,4313(1965).8.F.J.Feher,D.A.Newman and J.F.Walzer,J.Am.Chem.Soc.111,1741(1989).9.F.J.Feher,T.A.Budzichowski,R.L.Blanski,K.J.Wellerand J.W.Ziller,Organometallics10,2526(1991).10.R.A.Mantz,P.F.Jones,K.P.Chaffee,J.D.Lichtenhan,J.W.Gilman,I.M.Ismail and M.J.Burmeistr,Chem.Mater.8,1250(1996).11.A.Sellinger and ine,Macromolecules29,2327(1996).12.J.D.Lichtenhan,N.Q.Vu,J.A.Carter,J.W.Gilman andF.J.Feher,Macromolecules26,2141(1993).13.J. D.Lichtenhan,Y.Otonari and M.J.Carr,Macro-molecules28,8435(1995).14.T.S.Haddad and J.D.Lichtenhan,Macromolecules29,7302(1996).15.T.S.Haddad,E.Choe and J.D.Lichtenhan,Mater Res.Soc.Symp.Proc.435,25(1996).16.T.S.Haddad,A.R.Farris and J.D.Lichtenhan,Polym.Prep.38,127(1997).17.T.S.Haddad,J.J.Schwab,P.T.Mather,A.Romo-Uribe,Y.Otonari,M.J.Carr and J.D.Lichtenhan,Soc.Plast.Eng.ANTEC97Conf.Proc.,1997,Vol.2,p.1814.18.J.J.Schwab,J.D.Lichtenhan,P.T.Mather,A.Romo-Uribe and F.J.Feher,211th Meeting of the American Chemical Society New Orleans LA1996.19.F.J.Feher,J.J.Schwab,D.M.Tellers and A.Burstein,Main Group Chem.2,123(1998).20.W.A.Lee and R.A.Rutherford,in:Polymer Handbook,Brandrup,J.and Immergut,E.H.(eds),John Wiley,New York,1975.21.F.J.Balta´Calleja,Trends Polym.Sci.2,419(1994).#1998John Wiley&Sons,anometal.Chem.12,707–713(1998) POSS-BASED POLYMERS713。

碧云天BeyoPure

BeyoPure™ Ultrapure Water (PCR 级, Sterile)产品编号产品名称包装 ST873-100mlBeyoPure™ Ultrapure Water (PCR 级, Sterile)100ml产品简介：碧云天的BeyoPure™ Ultrapure Water (PCR 级, Sterile)，BeyoPure™ Ultrapure Water (PCR grade, Sterile)，即用于普通PCR 、qPCR 、RT-PCR 等分子生物学级别的无菌、无核酸酶的超纯水，是采用了Merck Millipore 先进的反渗透技术，辅以核子级离子交换树脂、高能量双波长紫外灯和Q-Gard ®超纯水柱，并配合BioPak ®终端超滤器而生产出的无热原(pyrogen-free)、无核酸酶(DNase/RNase-free)、无蛋白酶(Protease-free)、无细菌(bacteria-free)的超纯水。

主要用于PCR 等分子生物学实验中各种缓冲液和溶液的配制。

实验室常用的水有：超纯水(ultrapure water)也称为UPW 或高纯水(high-purity water)、去离子水(deionized water)、反渗透水(reverse osmosis water ，即RO 水，也常称为纯水)、蒸馏水(distilled water)、双蒸水(double-distilled water/dd H 2O)和三蒸水(triple-distilled water)。

其中超纯水是纯度非常高的水，可以满足绝大部分实验用水要求，特别是高灵敏度ICP/MS(电感耦合等离子体质谱)、同位素分析、以及疾控中心、药检所、质检所、环监站、高校和科研院所等实验室及各种高端精密仪器用水。

实验室常用水的特征、制备工艺及比较参考下表。

除超纯水外，其它水的最终水质和制备用水源的质量关系极大。

染色及助剂环保标准--2009年要求

§64 LFGB B 82.02.9
邻氨基偶氮甲苯
97-56-3
４氨基联苯
92-67-1
５硝基邻甲苯胺
99-55-8
邻氨基苯甲醚
90-04-0
联苯胺
92-87-5
对氯苯胺
106-47-8
４氯邻甲苯胺
95-69-2
２甲氧基５甲基苯胺
120-71-8
２，４二氨基苯甲醚
615-05-4
４，４二氨基二苯甲烷
2682-20-4
五氯化苯酚(PCP)
87-86-5
未检出
§64 LFGB B 82.02.8(RL=0.5)
四氯苯酚(TeCP)
25167-83-3
富马酸二甲酯
624-49-7
禁止使用
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IV) Bisphenol-A (BPA)双酚A
化学物质
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4,4dihydroxy2,2diphenylpropane
80-05-7
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V)抗光敏性致癌的分散染料及其它染料
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DIN54231单位：
毫克/升（RL：5）
分散蓝1
2475-45-8
分散蓝3
2475-46-9
分散蓝7
4098-71-9
游离型:1
封闭型: 100
四甲基苯二甲基二异氰酸酯
(TMXDI)
2778-42-9
游离型:1
封闭型: 100
甲苯异氰酸酯
(TDI)

J. Label. Compd. Radiopharm. 2004, 47, 821–835.

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALSJ Label Compd Radiopharm2004;47:821–835.Published online in Wiley InterScience().DOI:10.1002/jlcr.870Research ArticleIsotope labeled‘HEA Moiety’in the synthesisof labeled HIV-protease inhibitors–Part1I.Victor Ekhato1,*,Yuan Liao1,2and Mihaela Plesescu1,31Bristol-Myers Squibb Company,Pharmaceutical Research Institute,5Research Parkway,Wallingford,CT06492,USA2Pﬁzer Global Research and Development,Ann Arbor,MI48105,USA3Millennium Pharmaceuticals,Cambridge,MA023139,USASummary[(S)-10-((N-tert-Butyloxycarbonyl)amino)-2S-[2H5]phenyl-ethyl]oxirane11,made from [2H5]-bromobenzene,was transformed into the HIV-protease inhibitors[2H5]-DPH 153893and[2H5]-DPH140662.Both compounds are members of the hydroxyethy-lamine class of protease inhibitors(HIV-PIs).The method of synthesis is applicable to members of this class and the HEE group of HIV-PIs.Copyright#2004John Wiley &Sons,Ltd.Key Words:protease inhibitor;anti-HIV;AIDS;[2H5]-HEA isostereIntroductionDPH153893and DPH140662,like amprenavir1and saquinavir,2are members of the hydroxyethylamine(HEA)isostere class of HIV protease inhibitors(HIV-PIs).3The two compounds are highly potent HIV-aspartyl protease inhibitors with an average IC90of4–8nM against wild-type viruses. Both were selected for pre-clinical evaluation as potential new generation anti-HIV drugs.4Aspects of the studies involved LC-MS analysis and the stable isotope-labeled forms of DPH153893and DPH140662were needed as internal standards.We wanted to make the penta-deuterated DPH153893and DPH 140662molecules in which the[2H5]is situated at the core as the[phenyl ring-2H5]-HEA.We preferred to make the penta-deuterated analog based on the calculation that the molecular weight is suﬃciently increased,such that overlap with other ions due to isotopic mass distribution is avoided.*Correspondence to:I.V.Ekhato,Bristol-Myers Squibb Company,Pharmaceutical Research Institute, 5Research Parkway,Wallingford,CT06492,USA.E-mail:ihoezo.ekhato@Copyright#2004John Wiley&Sons,Ltd.Received15July2003Since both compounds possess the HEA core structure,we planned to prepare DPH153893and DPH140662from a common labeled precursor bearing the elements of the[phenyl ring-2H5]-HEA moiety.We believe that the phenyl group of the HEA sub-unit is metabolically stable,since metabolites have not been reported.5Similarly,these metabolites are absent from our internal study6of DPH153893or DPH140662.As a result,we were encouraged to explore the current synthesis with the prospect that a protease inhibitor containing the[phenyl ring-2H5]-HEA moiety might,in addition to our initial reason for synthesis,be suitable for in vivo investigation.By routine reactions we made the required[2H5]-intermediate from[2H5]-bromobenzene and transformed this compound into[2H5]-DPH153893and[2H5]-DPH 140662.Results and discussionIn the synthetic literature on anti-HIV protease inhibitors,unlabeled(1S,2S)-(1-oxiranyl-2-[2H5]phenylethyl)-carbamic acid tert-butyl ester11is extensively used as an intermediate3,7for synthesis of aspartyl protease inhibitors.We considered11to be an attractive key intermediate from which to make[2H5]-protease pound11,Figure1,has the epoxide functionality from which to build[2H5]-DPH153893and[2H5]-DPH140662.In addition,11 provides the[phenyl ring-2H5]-HEA isostere core of both inhibitors.Unlike previous work,7the present approach does not draw on any chiral pools of reagents,such as optically pure amino acids or derivatives,to construct11. Therefore,constructing the[2H5]-labeled carbon skeleton from[2H5]-bromo-benzene1with the desired1S,2S-conﬁguration in11was a challenging task. To address this point,we implemented a facially selective syn-aldol condensation reaction with S-4-benzyl-(3-[2H5]phenylpropionyl)-oxazolidin-2-one5.[2H5]-Bromobenzene was used to prepare compound5,and theSYNTHESIS OF LABELED HIV-PROTEASE INHIBITORS823 sequence of routine reactions that was employed is shown in Scheme1.Thus, following a lithium-halogen exchange reaction with[2H5]-bromobenzene1, DMF was added and acid workup provided the aldehyde,2.A Wittig-type homologation protocol8with compound2furnished3-[2H5]phenylacrylic acid ethyl ester,3.The carboxylic acid made by the hydrolysis of3was activated as the mixed pivaloyl anhydride,and reacted with(S)-(-)-4-benzyl-N-lithio-2-oxazolidinone,according to a literature procedure,9to form(S)-4-benzyl-3-(3-[2H5]phenylacryloyl)-oxazolidin-2-one,pound4was saturated by subjecting it to Pd/C catalyzed hydrogenation to furnish(S)-4-benzyl-3-(3-[2H5]phenylpropionyl)-oxazolidin-2-one,5.2222Et4Scheme1.Conversion of[2H5]-bromobenzene into the acyl oxazolidinone5to enable the asymmetric synthesis of11To complete the required carbon skeleton and simultaneously achieve the desired(S,S)-conﬁguration,compound5was condensed with(benzyloxy) acetaldehyde,10as shown in Scheme2.The combination of dibutylboron triﬂate and diisopropylethylamine reagent resulted in the highly diastereofa-cially selective syn-aldol condensation reaction yielding6.In the manner described in the literature,11lithium peroxide was used to cleave the amide bond in compound6to obtain(2S,3S)-[(2-[2H5]benzyl-4-(benzyloxy)-3-hydroxybutyric acid,7,in84%pound7was reﬂuxed in a solution of toluene containing diphenylphosphoryl azide and triethylamine to produce 8,an oxazolidinone.Formation of compound8is explained by the intra-molecular cyclization reaction of the intermediate isocyanate with the participation of the neighboring hydroxy group,as described in the literature.10The deprotection of8and the formation of(1S,2S)-1-[N-tert-butyloxycarbonyl)amino]-1-[25H5]benzyl-3-(benzyloxy)propan-2-ol,9,wasachieved in a one-pot pound5was subsequently hydrogenated under Pd/C catalysis to yield10(see Scheme2).The diol grouping in10was converted to the epoxide ring by a modiﬁed literature protocol12to give11(Scheme3).Speciﬁcally,compound10was treated with1-(bromocarbonyl)-1-methylethyl acetate in ethanol-free chloro-form at08C,converting it to an intermediate bromohydrin.The bromohydrin was cyclized by treatment with a solution of sodium methoxide in THF to provide(1S,2S)-(1-oxiranyl-2-[2H5]phenyl-ethyl)-carbamic acid tert-butyl ester,11,in73%yield.From intermediate11we proceeded to make[2H5]-DPH153893and[2H5]-DPH140662.At the second step in the reaction sequence isobutylamine wasreacted with11in hot isopropyl alcohol to pound12is the lastintermediate common to both synthetic targets,i.e.the reaction step after 12is the point of divergence of the reaction sequences to DPH 140662and DPH 153893.In order to make [2H 5]-DPH 140662,compound 12was treated with 4-nitro-benzenesulfonyl chloride in the presence of potassium carbonate as acid scavenger.After removal of the Boc group,13was obtained as the methanesulfonic acid salt in 80%overall yield over the two steps.By a standard coupling method with EDC.HCl,4-methylmorpholine and HOBt 13in DMF,compound 13and Boc-l -tert -leucine formed the Boc protected 14.We found that the stepwise sequence of coupling Boc-l -tert -leucine to make the Boc protected 14,the removal of Boc to yield 14and the coupling reaction of compound 14with IS066(IS066was generously supplied bythe 11into 14via compound 12,a commonintermediate to [2H 6]-DPH 153893and [H 5]-DPH 140662SYNTHESIS OF LABELED HIV-PROTEASE INHIBITORS 825Department of Chemical Process,DuPont Pharmaceuticals Company,Wilmington,DE)to give 15,as shown in Scheme 4,was the best sequence for making [2H 5]-DPH 140662.An alternative single coupling reaction to DPH 140662from 13was complicated by intra-molecular cyclization of the dipeptide reagent under our reaction conditions.Chromatographic puriﬁca-tion was required to obtain 15,and then only in poor yield.The single coupling approach was therefore abandoned.A standard coupling protocol in DMF containing EDC.HCl,HOBt and 4-methylmorpholine as acid scavenger converted 14to compound 15.After Pd/C catalyzed hydrogenation of 15to the 4-aminobenzenesulfonamide,the Boc group was removed with TFA-Et 3SiH and the reaction mixture was neutralized with NaHCO 3to provide [2H 5]-DPH 140662in 61%yield.By substituting 3-nitrobenzenesulfonyl chloride for 4-nitrobenzenesulfonyl chloride in Scheme 3,and following a sequence of reactions analogous to Schemes 3and 4,we accomplished the synthesis of [2H 5]-DPH 153893in comparable yield.ConclusionTwo HIV protease inhibitors were speciﬁcally labeled with [2H 5]at the HEA sub-unit by transforming [2H 5]-bromobenzene into a common intermediate for these agents.The intermediate was made using established reactionsthat 14into [2H 5]-DPH 140662I.V.EKHATO ET AL.826included an asymmetric reaction step.The intermediate was used to create the[phenyl ring-2H 5]labeled HEA core structure of DPH 140662and DPH 153893.Very high deuterium incorporation was achieved by the sequence we have described and the synthetic approach may be applicable,with some modiﬁcations,to other HIV-protease inhibitors.ExperimentalAll reactions were carried out under an atmosphere of argon unless otherwise speciﬁed.Solvents were commercial grade and used without puriﬁcation or drying.Column chromatography was carried out on Merck Kiesegel 60(230m)silica gel.Flash chromatographic separations were on a Biotage Flash System using a pre-packed silica gel cartridge.TLC visualization reagents included (10%iodine plus 10%AcOH)in 40%aqueous KI.1H NMR spectra were recorded at 300,400or 500MHz.Chemical shifts are given in ppm relative to tetramethylsilane (TMS).Only the important IR absorptions (cm À1)and the molecular ion and/or base peaks in MS are given.HPLC columns used include Zorbax Rx C 18,Discovery Amide C 16,and Waters Symmetry C 18columns.4S-Benzyl-3-(3-[2H 5]phenyl-propionyl)-oxazolidin-2-one,%5To a stirred solution of [2H 5]-phenylacrylic acid (10.1g,65.07mmol,see Scheme 1for preparation)and 4-methylmorpholine (7.15ml,65.07mmol)in dry THF (120ml)maintained at À788C with a dry ice-acetone bath was added trimethylacetyl chloride (8.01ml,65.07mmol).After 30min the cold bath was replaced with an ice-water bath and the reaction was stirred for another 45min.The precipitate was removed by ﬁltration,and the ﬁltrate was transferred to a solution of N -lithio-oxazolidinone that was pre-generated as follows.(S)-(-)-4-Benzyl-2-oxazolidinone (11.53g,65.07mmol)in dry THF (120ml)was stirred under argon atmosphere at À788C while BuLi (1.6M solution in hexanes,40.6ml,65.07mmol)was added dropwise.The solution was stirred at À788C for 1.0h and the above ﬁltrate,a solution of mixed anhydride in THF,was added in one portion.The reaction was quenched after 1h with saturated NH 4Cl solution (100ml)and the organic phase was separated.The aqueous portion was further extracted with ethyl acetate (3Â200ml),the combined organic extract was dried and evaporated to dryness to give (S)-4-benzyl-3-(3-[2H 5]phenylacryloyl)-oxazolidin-2-onepound 4was dissolved in ethyl acetate (150ml)and a suspension of 10%Pd/C (1.2g)in ethyl acetate (20ml)was added.After the reaction mixture was degassed,it was stirred under a hydrogen atmosphere for 3h and ﬁltered through a pad of Celite to remove the spent catalyst.The ﬁltrate was evaporated to a product which crystallized from EtOAc-hexane to give 5(17.10g,84%).1H NMR (400MHz)d 2.74(dd,1H),3.03(m,2H),3.28(m,SYNTHESIS OF LABELED HIV-PROTEASE INHIBITORS 8273H),4.16(m,2H),4.65(m,1H),7.17(d,2H)and 7.32(m,3H).13C NMR (75MHz)d 30.30,37.12,37.94,55.17,66.26,127.4,128.0,128.2,129.0,129.5,140.4,153.4and 172.5.IR n max (CHCl 3)2276,1785,1699,1490,1478,1390,1372,and 1202cm À1.4S-Benzyl-3-[(2S-[2H 5]benzyl-4-(benzyloxy)-3S-hydroxy-butyryl)]-oxazoli-din-2-one,%6To a stirred solution 4S-benzyl-3-(3-[2H 5]phenylpropionyl)-oxazolidin-2-one 5(23.68g,75.3mmol)in CH 2Cl 2(140ml)at 08C was added dibutylboron triﬂate (1.0M solution in dichloromethane,98.0ml,98mmol)followed by diisopro-pylethylamine (19.67ml,112.97mmol).After stirring the mixture for 1h at room temperature it was cooled to À788C and a solution of (benzyloxy)ace-taldehyde (20g,133.17mmol)in CH 2Cl 2(30ml)was added.The reaction mixture was stirred for 30min at À788C and warmed to room temperature for 2h.A phosphate buﬀer of pH 7.3(40ml)was added and while the reaction was cooled to 08C,methanol (140ml)was added followed by a mixture of (2:1)MeOH and 30%H 2O 2(180ml).The resulting mixture was stirred for 1h,concentrated to a small volume and extracted with EtOAc (2Â200ml).The organic portions were combined and washed with saturated NaHCO 3(200ml),brine (200ml)and dried over anhydrous magnesium sulfate.Evaporation of the solvent gave the crude product which was puriﬁed by chromatography on silica gel.The column was eluted with 10–25%ethyl in hexane to give 6(25g,71.46%).1H NMR (500MHz)d 2.10(dd,Hz,1H),2.64(brs,1H),2.83(dd,1H),3.08(q,Hz,1H),3.17(q,1H),3.59(m,2H),3.78(tr,1H),3.86(q,1H),4.18(q,1H),4.42(m,1H),4.50(s,2H),4.64(m,1H),6.93(dd,2H),7.20–7.343(m,10H).IR n max (CHCl 3)2274,1778,1694,1496,1386,1210,and 1104cm À1.S-2-[2H 5]Benzyl-4-(benzyloxy)-3S-hydroxy-butyric acid,%7To a stirred solution of 4S-benzyl-3-[(2S-[2H 5]benzyl-4-(benzyloxy)-3S-hydro-xy-butyryl)]-oxazolidin-2-one 6(23.1g,49.72mmol)in 50%aqueous THF (105ml)at 08C were added 30%H 2O 2(25ml,220mmol)and LiOH.H 2O (4.25g,101.2mmol)in succession.The reaction mixture was stirred in an ice bath and monitored by TLC until acyloxazolidinone was consumed in a calculated 6h.Saturated sodium metabisulﬁte (100ml)was added and the mixture was extracted with EtOAc (3Â200ml).After acidiﬁcation of the aqueous portion to pH 2with dilute HCl,it was extracted with EtOAC (2Â120ml).The organic portions were combined,dried over anhydrous Na 2SO 4,ﬁltered and evaporated to an oil.TLC on silica gel (ether:pet.ether:acetic acid,60/40/1v/v/v)showed fast running desired product and slow running oxazolidinone.The mixture was applied to a column of silica gel and I.V.EKHATO ET AL.828eluted with (ether:pet.ether:acetic acid 60/40/1,v/v/v/)to aﬀord crystalline (CH 2Cl 2-hexane)7(12.98g,84%).1H NMR (500MHz)d 2.95(m,1H),3.10(2H),3.49(dd,1H),3.59(dd,1H),4.03(m,1H),4.54(s,2H),7.31–7.36(m,5H).13C NMR (75MHz)d 33.67,50.09,70.38,71.64,73.57,127.9,128.0,128.2,128.3,128.6,137.6,138.6,and 177.9.IR n max (CHCl 3)3254,2275,1728,1454and 1169cm À1.S-4-[2H 5]Benzyl-5S-((benzyloxymethyl)-oxazolidin-2-one,%8A mixture of S-(2-[2H 5]benzyl-4-(benzyloxy)-3S-hydroxy-butyric acid 7(11.0g,36.0mmol),diphenylphosphoryl azide (9.84ml,45.66mmol)and triethylamine (6.68ml,47.92mmol)in toluene (78ml)was reﬂuxed for 4h and cooled to room temperature.Ethyl acetate (250ml)was added and the solution was washed with saturated NaHCO 3(100ml),dried and evaporated to give a residue that was chromatographed on silica gel.The fast running impurities were ﬁrst eluted with 25%EtOAc in hexane,and 35%EtOAc in hexane was used to elute the desired product 8(11.7g,98%).1H NMR (300MHz)d 2.75(dd,1H),2.92(dd,1H),3.797(d,2H),4.12(m,1H),5.62(s,2H),5.8(m,2H)and 7.40(m,5H).(S)-1-[N-tert-Butyloxycarbonyl)amino]-1-[2H 5]benzyl-3-(benzyloxy)propan-2S-ol,%9S-4-[2H 5]Benzyl-5S-(benzyloxymethyl)-oxazolidin-2-one 8(11.7g,38.74mmol)in 50%aqueous ethanol (40ml)containing KOH (9.0g,160.4mmol)was heated at 708C for 3h and then cooled to room temperature.The solution was adjusted to pH 7with 1.0M HCl and concentrated under reduced pressure.Di-tert -butyl dicarbonate (16.99g,77.84mmol)in CH 2Cl 2(60ml)was added at 08C and the reaction was stirred for 2h at room temperature.Saturated NH 4Cl solution (40ml)was added.The mixture was extracted with CH 2Cl 2(2Â50ml),the combined organic portions were dried and evaporated to yield a solid residue.The crude product was applied to a column of silica gel and the excess di-tert -dibutyl dicarbonate was eluted with 10%EtOAc in hexane.Further elution with 35%EtOAc in hexane gave a solid which crystallized from hexane to aﬀord 9(15.2g,94%).1H NMR (300MHz)d 1.35(s,9H),2.62(brs),2.88(d,2H),3.56(m,2H),3.73(brs,1H),3.93(brs,1H),4.51(s,2H),4.72(d,1H),7.33(m,C 6H 5).13C NMR (75MHz)d 28.34,36.36,54.20,71.72,71.82,73.68,79.53,125.9(tr)127.8,127.9,128.1,128.5,129.1(tr),137.8,137.9and 155.9.IR n max (CHCl 3)1685,2273,1526,and 1172cm À1.S-1-[N-tert-Butyloxycarbonyl)amino]-1-[2H 5]benzyl-propan-2S,3-diol,10To a solution of S-1-[N -tert -butyloxycarbonyl)amino]-1-[2H 5]benzyl-3-(benzy-loxy)-propan-2S-ol 9(14.0g,37.18mmol)in EtOAc (140ml)was added a SYNTHESIS OF LABELED HIV-PROTEASE INHIBITORS 829suspension of 5%Pd/C (1.40g)in ethyl acetate (10ml).The stirred reaction mixture was purged to remove air and stirred under hydrogen atmosphere for 18h.The spent catalyst was ﬁltered oﬀand the ﬁltrate was concentrated to a white solid that crystallized from hexane-ethyl acetate to give 10(10.48g,%100%).1H NMR (500MHz)d 1.37(s,9H),1.59(brs,1H),2.75(d,1H),2.91(dd,1H),3.09(dd,1H),3.33(brs,2H),3.65(m,2H),3.82(m,1H),4.53(d,1H).13C NMR (75MHz)d 28.30,36.55,52.59,63.06,73.27,80.41,126.2(tr),128.2(tr),129.0(tr),137.3,and 157.1.IR n max (CHCl 3)3356,2273,1685,1525,1445,1250,and 1171cm À1.[(S)-10-((N-tert-Butyloxycarbonyl)amino)-2S-[2H 5]phenyl-ethyl]oxirane,111-Bromocarbonyl-1-methylethyl acetate (2.0ml,13.63mmol)was added to a stirred suspension of (S)-1-[N -tert -butyloxycarbonyl)amino]-1-[2H 5]benzyl-propan-2S,3-diol 10(3.0g,10.48mmol)in dry,ethanol free,chloroform (30ml)maintained at 08C in an ice water bath.After 3h at room temperature the reaction was quenched by the addition of saturated NaHCO 3solution (20ml)and extracted with EtOAc (3Â30ml).The organic extract was washed with brine (30ml),dried over anhydrous Na 2SO 4and evaporated to give a solid.The solid was stirred as a solution in dry THF (40ml),cooled to 08C in an ice bath and NaOCH 3(0.92g,17.03mmol)was added.After stirring the reaction mixture at room temperature for 4h,saturated ammonium chloride solution (30ml)was added and the mixture extracted with EtOAc (3Â30ml).The organic extract was dried over anhydrous Na 2SO 4,ﬁltered,and the ﬁltrate was evaporated to a small volume.The material was applied to a column of silica gel and the compound was eluted with 22%EtOAc in hexane to give a white solid 11(2.08g,73%).1H NMR (300MHz)d 1.75(d,J =7.0Hz,3H),2.45(s,3H),4.97(q,J =7.0Hz,1H),7.10–7.27(m,3H),7.32–7.43(m,2H),7.51(d,J =8.2Hz,2H)and 7.75(d,J =7.3Hz,1H).13C NMR (75MHz)d 28.34,37.65,41.61,46.81,53.3,79.71,126.2(tr),128.1(tr),129.1(tr),136.7and 155.3.IR n max (CHCl 3)2275,1679,1523and 1168cm À1.3S-[N-(tert-Butyloxycarbonyl)amino-1-(2-methylpropyl)amino-4-[2H 5]phe-nylbutan-2R-ol,12To a solution of 2S-[10-(S)-((N -tert -butyloxycarbonyl)amino)-2-[2H 5]phenyl-ethyl]-oxirane 11(2.06g,7.20mmol)in isopropanol (6ml)was added isobutylamine (6ml,111.5mmol)and heated at 868C for 4h under argon atmosphere.The solvent was evaporated after cooling to room temperature.The white solid obtained was crystallized from ether-petroleum ether to give 12(2.32g,%100%).1H NMR (500MHz)d 0.89(dd,6H),1.35(s,9H),1.70(m,1H),2.39(d,3H),2.68(d,2H),2.86(dd,1H),2.98(dd,1H),3.44(m,1H),3.79(brs,1H),4.67(d,1H).IR n max (CHCl 3)3365,1648,1521,and 1173cm À1.I.V.EKHATO ET AL.830N-(3S-Amino-2R-hydroxy-4-[2H5]phenyl-butyl)-N-isobutyl-4-nitro-benzene-sulfonamide,13A solution of K2CO3(430mg,3.11mmol)in water(3ml)was added to a solution of3S-[N-(tert-butyloxycarbonyl)amino-1-(2-methylpropyl)amino-4-[2H5]phenylbutan-2R-ol12(575.19mg,1.68mmol)in isopropyl acetate(3ml). The mixture was stirred at568C to attain solution.4-Nitro-benzenesulfonyl chloride(360mg,1.62mmol)in isopropyl acetate(3ml)was added and stirring continued for30min after the addition was completed.A solid product separated upon cooling the reaction to room temperature,and it was collected byﬁltration.This material(Boc protected amine)(885.8mg,1.681mmol)was stirred in isopropyl acetate(18ml)and the temperature was brought to858C under argon atmosphere.Methanesulfonic acid(130.9m l, 2.0mmol)in isopropyl acetate(5ml)was added slowly and the reaction mixture was stirred for another30min.Upon cooling to room temperature a crystalline product separated and it was collected byﬁltration to aﬀord13(722.6mg, 80%).1H NMR(300MHz)(DMSO-d6)d0.89(dd,6H),1.80(m,1H),2.36(s, 3H),2.85(m,2H),3.10(m,3H),3.49(dd,1H),3.95(m,1H),5.58(d,1H),7.80 (brs,2H),8.15(d,1H),8.40(d,1H).2-Amino-N-{1-[2H5]benzyl-2-hydroxy-3-[isobutyl-(4-nitro-benzenesulfonyl)-amino]-propyl-3,3-dimethylbutyramide,14N-tert-Butyloxycarbonyl tert-butylglycine(Boc-l-tert-leucine)(360.80mg, 1.56mmol),1-hydroxybenzotriazole hydrate(210.8mg,1.56mmol)in anhy-drous DMF(10ml)was treated with4-methylmorpholine(343m l,3.12mmol) followed by1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (298.8mg,1.56mmol).Compound13(680mg,1.302mmol)was added and the reaction mixture was stirred under argon atmosphere overnight.The reaction mixture was concentrated to a small volume,partitioned between ethyl acetate(20ml)and water(15ml),and the aqueous portion was separated.The aqueous portion was further extracted with ethyl acetate (3Â20ml)and the combined organic portions were washed sequentially with saturated NH4Cl solution(20ml),saturated K2CO3solution(20ml),brine (20ml)and dried.Theﬁltrate was evaporated to a residue(843mg),and then dissolved in isopropyl acetate(10ml).While the stirred solution was maintained at858C,methanesulfonic acid(102m l,1.85mmol)in isopropyl acetate(3ml)was added dropwise.The reaction mixture was cooled to room temperature after30min,and concentrated to a small volume.Upon the addition of ether,a crystalline solid precipitated,and the material was collected byﬁltration to aﬀord14(708mg,84%).HPLC analysis on a Zorbax Rx C18column4.6Â250mm at aﬂow rate of1.0ml/min under isocratic conditions using40%water in acetonitrile containing0.05%TFA gave aretention time of3.3min.1H NMR(300MHz)(DMSO-d6)d0.75(dd,6H), 0.96(s,9H),1.89(m,1H),2.28(s,3H),2.65(dd,1H),2.82(m,1H),2.96(dd, 1H),3.08(dd,1H),3.40(m,2H),3.65(m,1H),3.85(brs),4.10(m,1H),7.85 (brs,2H),8.10(d,1H),8.38(d,1H).IR n max(CHCl3)2276,1691,1530,1352, 1350,and1150cmÀ1.[{1-{1-[2H5]Benzyl-2-hydroxy-3-[isobutyl-{4-nitro-benzenesulfonyl)-amino]-propylcarbamoyl}-2,2-dimethyl-propylcarbamoyl}-methyl](3-ﬂuoro-benzyl)-carbamic acid tert-butyl ester,15To a solution of N-[(tert-butyloxycarbonyl)-(3-ﬂuorobenzyl)]glycine(IS066) (373.95mg,1.32mmol),1-hydroxybenzotriazole hydrate(HOBT),178.38mg,1.32mmol)in anhydrous DMF(5ml)was added4-methylmorpholine(290m l,2.64mmol)followed by EDC.HCl(252.56mg, 1.32mmol).While stirring under an argon atmosphere,14(700mg,1.1mmol)was added.After stirring overnight,the mixture was concentrated under high vacuum to a small volume and partitioned between EtOAc(20ml)and water(15ml).The organic phase was separated and the aqueous portion was further extracted with ethyl acetate(2Â20ml).The combined organic portions were washed with water (20ml),saturated NH4Cl solution(20ml),saturated K2CO3(20ml),brine (20ml)and dried over magnesium sulfate.The solvent was evaporated to givea foamy solid15(880mg,91%).HPLC analysis on a Zorbax Rx C18column4.6Â250mm at aﬂow rate of1.0ml/min under isocratic conditions using40% water in acetonitrile containing0.05%TFA gave a retention time of 11.12min.N-{3-[(4-Amino-benezenesulfonyl)-isobutyl-amino]-1-[2H5]benzyl-2-hydroxy-propyl}-2-[2-(3-ﬂuorobenzylamino)-acetylamino]-3,3-dimethyl-butyramide, [2H5]-DPH140662To a solution of15(700mg,0.869mmol)in methanol(25ml)was added a suspension of10%Pd/C(224mg)in methanol(8ml).The reaction mixture was stirred at room temperature in an atmosphere of hydrogen for3h and thenﬁltered.The solvent was evaporated to yield a foamy solid.Triﬂuor-oacetic acid(2.616ml)and triethylsilane(Et3SiH)(0.4ml)were added successively to a solution of the solid in methylene chloride(18ml).The mixture was stirred at room temperature and the reaction was monitored by TLC(3%MeOH in dichloromethane).After2h the reaction mixture was evaporated to a residue and,EtOAc(20ml),water(15ml),and solid NaHCO3 (1.3g)were added.The mixture was stirred for20min and the organic portion was separated.The aqueous portion was further extracted with ethyl acetate (2Â20ml)and the combined organic extract was dried over MgSO4. The product was puriﬁed by chromatography on silica gel column eluted with8%EtOH in toluene to give an oil.Trituration of the oil with ether gave[2H5]-DPH140662(385mg,61%;D598.9%,D4, 1.1%).[a]20D–15.648 (c=0.41%in MeOH).The product was analyzed by HPLC on a Discovery Amide C16Supelco250Â4.6mm,5m m column.The solvent combination of A (10mmol ammonium formate)and B(acetonitrile)was used under gradient conditions of20–30%B in0–5min,30–50%B in5–18min and20–30%B in 18–20min at aﬂow rate of ml/min.The product peak was detected by UV at a wavelength of254nm and gave>98%chemical purity at a retention time of 14.13min.IR n max(CHCl3)1314,1285,and1143cmÀ1.1H NMR(300MHz, d6-DMSO)d0.85(m,15H),1.82(m,1H),2.52(dd,1H),2.68(m,1H),2.85(m, 2H),2.95(dd,1H),3.05(s),3.22(dd,1H),3.30(s,3H),3.50(s),3.60(m,1H), 3.89(m,1H),4.18(d,1H),4.89(d,1H),5.98(brs,2H),6.60(d,2H),7.12(m, 3H),7.42(m,3H),7.78(d,1H),7.98(d,1H).HRMS(TOF MS ES+;M+1); calcd.675.3762,found675.3766.ESI full ms gave z at675(M+1,100%)and 397(5%),372(15%)and354(2%).N-{1-[2H5]Benzyl-2-hydroxy-3-[isobutyl-(3-nitro-benzenesulfonyl)-amino]-propyl}-2-[2-(3-ﬂuorobenzylamino)-acetylamino]-3,3-dimethyl-butyramide, [2H5]-DPH153893N-[(tert-butyloxycarbonyl)-(3-ﬂuorobenzyl)]glycine(356.0mg, 1.256mmol) was reacted with2-amino-N-{1-[2H5]benzyl-2-hydroxy-3-[isobutyl-(3-nitro-benzenesulfonyl–amino]-propyl-3,3-dimethyl-butyramide methanesulfonic acid salt17(799mg, 1.256mmol)to make[(1{1-[2H5]benzyl-2-hydroxy-3-[isobutyl-(3-nitro-benzenesulfonyl)-amino]-propyl-carbamoyl}-2,2-dimethyl-propylcarbamoyl)-methyl]–(3-ﬂuorobenzylcarbamic acid tert-butyl ester (902mg,89%)as described under experiment15.Sequential hydrogenolysis and boc deprotection with methanesulfonic acid in isopropyl acetate gave N-{1-[2H5]benzyl-2-hydroxy-3-[isobutyl-(3-nitro-benzenesulfonyl)-amino]pro-pyl}-2-[2-(3-ﬂuorobenzylamino)-acetylamino]-3,3-dimethyl-butyramide[2H5]-DPH153893(947mg, 1.09mmol,98%;D5,98.9%,D4, 1.1%)as the methanesulfonic acid salt.[a]20D–17.848(c=0.43%in MeOH).HPLC analysis on Discovery Amide C16Supelco250Â4.6mm,5m m column with elution solvent combination of A(10mmol ammonium formate)and B(acetonitrile), under the gradient conditions of20–30%B in0–5min,30–50%B in5–18min and20–30%B in18–20min and aﬂow rate of1.0ml/min.The product peak was detected by UV at a wavelength of254nm,and gave>99.6%chemical purity at a retention time of10.7min.HRMS(TOF MS ES+;M+1);calcd. 675.3762,found675.3765.1H NMR(300MHz,d6-DMSO)d0.85(dd,and s, overlapped,15H),1.92(m,1H),2.50(dd,1H overlapped with DMSO),2.80 (m,2H),2.90(m,2H),3.03(s),3.50(s),3.60(m,1H),3.95(m,1H),4.20(d, 1H),4.90(d,1H),5.51(brs),6.70(d,1H),6.80(d,1H),6.90(s,1H),7.10(m, 3H),7.30(m,1H),6.65(d,1H),7.90(d,1H).ESI full MS gave z675(M+1, 100%),397(2%),372(18%),and354(5%).AcknowledgementsThe authors are grateful to Dr Gerald Miwa and Shimoga Prakash (Millennium Pharmaceuticals)for their support.IVE gratefully acknowledges D.R.Schroeder and S.Huang(DAS,BMS Wallingford,CT)for NMR support;Julie Nielsen(DAS,BMS,Wallingford,CT)for the determination of Optical Rotations of Protease Inhibitors and Richard E.Gedamke(ARD, BMS,Lawrenceville,NJ)for the determination of at%D.References1.(a)Kim EE,Baker CT,Dwyer MD,Murcko MA,Rao BG,Tung RD,NaviaMA.J Am Chem Soc1995;117:1181–1182.(b)Tung RD,Murcko MA,Bhissetti GR.Vertex Pharmaceuticals Inc.,1994;WO94/05639.2.(a)Roberts NA,Martin JA,Kinchington D,Broadhurst AV,Craig JC,DuncanIB,Gaplin SA,Handa BA,Kay J,Kroehn A,Lambert RW,Merret JH, Mills JS,Parkes KEB,Redshaw S,Ritchie AJ,Taylor DL,Thomas GJ, Machin PJ.Science1990;248:358.(b)Skinner C,Sedwick A,Bragman K, Pinching AJ,Weber J.Abstracts at the9th International Conference on AIDS,Berlin,1993.(c)Parkes KEB,Bushnell DJ,Crackett PH, Dunsdon SJ,Freeman AC,Gunn MP,Hopkins RA,Lambert RW,Martin JA, Merrett JH,Redshaw S,Spurden WC,Thomas GJ.J Org Chem1994;59: 3656–3664.3.(a)Rich DH,Green J,Toth MV,Marshall GR,Kent SBH.J Med Chem1990;33:1285–1287.(b)Rich DH,Sun CQ,Vara Prasad JVN,Pathiasseril A, Toth MV,Marshall GR,Clara M,Mueller RA,Houseman KJ.J Med Chem 1991;34:1222–1225.(c)Beaulieu PL,Wernic D.J Org Chem1996;61: 3635–3645.4.Kaltenbach III RF,Trainor D,Getman G,Harris S,Diamond M,Saye JJ,Erickson-Viitanen S.Antimicrobial Agents Chemother2001;45:3021–3028.5.Treluyer JM,Bowers G,Cazali N,Sonnier M,Rey E,Pons G,Cresteil T.DrugMetab Dispos2003;31:275–281.6.Solon EG,Yang TD.Dept of Drug Metabolism and Pharmacokinetics,DupontPharmaceutical Company,Newark,DE19714;Personal Communication.7.Albeck A,Persky R.Tetrahedron1994;50:6333–6346.(b)Thottahthil JK,Polniaszek RP.Synlett2000;6:902–904.(c)Rotella DP.Tetrahedron Lett1995;35:5453–5456.(d)Beaulieu PL,Wernic D,Duceppe J-S,Guindon Y.Tetrahedron Lett1995;36:3317–3319.(e)Beier C,Schaumann E,Adiwidjaja G.Synlett1998;1:42–44.8.(a)Lombardo L,Taylor RJK.Synthesis1978;2:131–132.(b)Coutrot P,SnoussiM,Savignac P.Synthesis1978;2:133–134.(c)Monache GD,Di Giovanni MC, Maggio F,Misiti D,Zappia G.Synthesis1995;9:1155–1158.9.Dobarro A,Velasco D.Tetrahedron1996;52:13525–13530.10.(a)Ghosh AK,Hussain KA,Fidanze S.J Org Chem1997;62:6080–6082.(b)Ghosh AK,Fidanze S.J Org Chem1998;63:6146–6152.。

雷美替胺结构编号

雷美替胺结构编号1. 介绍雷美替胺（Levetiracetam）是一种常用的抗癫痫药物，属于嘌呤类化合物。

它的结构编号是2S-(2α,5α,6β)-2-(2-氨基-4-氧代-5-苯基-6H-[1,2,4]三嗪-6-基)乙酰胆碱。

雷美替胺通过调节神经递质的释放和抑制异常兴奋，从而发挥抗癫痫作用。

2. 结构式雷美替胺的结构式如下所示：3. 结构解析根据结构式，我们可以对雷美替胺的结构进行解析：首先，在化合物名称中，“2S”表示该分子中有一个手性中心，其中S表示“sinister”（左旋）的意思。

这意味着雷美替胺存在两个立体异构体，即左旋和右旋形式。

接下来，“(2α,5α,6β)”表示了分子中其他三个手性中心的相对配置。

这些配置通过它们与基团的连接方式来确定。

然后，我们看到“2-(2-氨基-4-氧代-5-苯基-6H-[1,2,4]三嗪-6-基)乙酰胆碱”。

这部分描述了雷美替胺的化学成分。

最后，“乙酰胆碱”表示该化合物是乙酰胆碱的衍生物，即其结构中含有乙酰胆碱基团。

4. 化学性质雷美替胺是一种白色结晶性粉末，在水中溶解度较高。

它在酸性条件下比较稳定，但在碱性条件下会发生水解反应。

雷美替胺的熔点约为115°C。

5. 药理作用雷美替胺通过调节神经递质（如谷氨酸和GABA）的释放来发挥抗癫痫作用。

它主要通过与突触囊泡蛋白SV2A结合，抑制谷氨酸释放，并减少突触前膜上钙离子通道的活动。

此外，雷美替胺还可增加GABA能神经元的抑制效应，从而抑制异常兴奋。

6. 临床应用雷美替胺是一种广泛用于治疗癫痫的药物。

它可用于单纯性癫痫、复杂性部分发作以及全身性发作的治疗。

雷美替胺也可以作为辅助治疗用于其他抗癫痫药物无效或不耐受的患者。

7. 药代动力学雷美替胺经口服后，快速吸收并达到峰值浓度。

它在体内通过非酶催化的水解反应代谢，主要由肾脏排泄。

由于雷美替胺的半衰期较长，通常需要进行两次或三次每日剂量。

8. 不良反应雷美替胺在临床使用中常见的不良反应包括头晕、嗜睡、乏力和消化系统不适等。

ReducingSubstances,Urine

Lab Dept: Urine/Stool Test Name:REDUCING SUBSTANCES, URINE General InformationLab Order Codes:URS Synonyms: Urine Reducing Substance; Carbohydrate, urine; Disaccharidescreening; Monosaccharide screeningCPT Codes: 81002 – urinalysis, by dip stick or tablet, non-automated, without microscopyTest Includes:Reducing substance in urine LogisticsTest Indications: Useful for detecting any reducing substance in urine which may bepresent as a result of an inherited metabolic disorder.Lab Testing Sections: Urinalysis612-813-6280Phone Numbers:Minneapolis: Saint Paul: 651-220-6550Test Availability:Daily, 24 hours Turnaround Time:2 hours Special Instructions: Send to lab within 30 minutes of collection. SpecimenSpecimen Type:Urine Container:Urine cup Draw Volume:12 mL (Minimum: 1 mL) urine Processed Volume:Entire volume submittedCollection: A specimen collected by catheterization is optimal; however, a clean-catch or mid-stream specimen is also acceptable. Random, voidedspecimens will be accepted, but are the least desirable and are notrecommended if a urine culture is also being requested. In all cases, afirst morning specimen is most desirable.Special Processing: Transport immediately since glucose and other reducing substancesare consumed by bacteria. Refrigerate specimen if it cannot betransported or processed immediately.Patient Preparation: Collect a clean-catch urine specimen as follows:Males: Clean glans with soap and water. Rinse area with wet gauzepads. While holding foreskin retracted, begin voiding. After several mL’shave passed, collect midstream portion without stopping flow of urine.Place the cap on the cup and tighten securely. Refrigerate specimenafter collection and promptly forward to the lab.Females: Thoroughly clean urethral area with soap and water. Rinsearea with wet gauze pads. While holding labia apart, begin voiding.After several mL’s have passed, collect midstream portion withoutstopping the flow of urine. Place the cap on the cup and tightensecurely. Refrigerate specimen after collection and promptly forward tothe lab.Note: Indicate type of specimen (catheterized or void) and time ofcollection on the label.Sample Rejection: <1 mL urine submitted, contamination with feces; urine in cotton balls;specimen decomposition (e.g., pH >9.0); bacterial overgrowth;mislabeled or unlabeled specimensInterpretiveReference Range: NegativeCritical Values: N/ALimitations: Clinitest is not specific for glucose and will react with sufficientquantities of any reducing substance in the urine. These includelactose, fructose, galactose, and pentoses.Methodology: Clinitest®, Copper Reduction Tablet TestContraindications:Interfering Substances:Creatinine/Urine AcidMay cause false positive Homogentisic Acid Positive Ascorbic Acid (large amounts) False trace positive (false positive, brown color) Cephalosporins (Keflin, etc) Negative L-Dopa (large amounts) False positive Nalidixic Acid False positive Probenecid False positive x-ray dye (diatrizoates) Black color Hydrogen peroxide May inhibit positive testNote: Other drugs implicated in copper reduction are amino acids, caronamide, choral, chloroform, chloramphenicol, formaldehyde, hippuric acid, isoniazid, thiazides, oxytetracycline, p-aminosalicylic acid, penicillin, phenols, streptomycin, phenothiazine and sulfonamides. Bruist NR, British Medical Journal 2:745 Clinitest® Package Insert, Bayer Corporation, Diagnostic Division References: Strasinger SK (1989) Urinalysis and Body Fluids, 2nd ed, FA Davis Company。

优泌乐25说明书

PV 5551 AMPHUMALOG® Mix75/25TM75% INSULIN LISPRO PROTAMINE SUSPENSION AND25% INSULIN LISPRO INJECTION(rDNA ORIGIN)100 UNITS PER ML (U-100)DESCRIPTIONHumalog® Mix75/25™ [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is a mixture of insulin lispro solution, a rapid-acting blood glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting blood glucose-lowering agent. Chemically, insulin lispro is Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions 28 and 29 on the insulin B-chain are reversed. Insulin lispro is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered to produce insulin lispro. Insulin lispro protamine suspension (NPL component) is a suspension of crystals produced from combining insulin lispro and protamine sulfate under appropriate conditions for crystal formation.Insulin lispro has the following primary structure:Insulin lispro has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH.CLINICAL PHARMACOLOGYAntidiabetic ActivityThe primary activity of insulin, including Humalog Mix75/25, is the regulation of glucose metabolism. In addition, all insulins have several anabolic and anti-catabolic actions on many tissues in the body. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.Insulin lispro, the rapid-acting component of Humalog Mix75/25, has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog® has the sameglucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration. Humalog Mix75/25 has a similar glucose-lowering effect as compared with Humulin® 70/30 on a unit for unit basis.PharmacokineticsAbsorption — Studies in nondiabetic subjects and patients with type 1 (insulin-dependent) diabetes demonstrated that Humalog, the rapid-acting component of Humalog Mix75/25, is absorbed faster than Regular human insulin (U-100). In nondiabetic subjects given subcutaneous doses of Humalog ranging from 0.1 to 0.4 U/kg, peak serum concentrations were observed 30 to 90 minutes after dosing. When nondiabetic subjects received equivalent doses of Regular human insulin, peak insulin concentrations occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes.Figure 1: Serum Immunoreactive Insulin (IRI) Concentrations, After Subcutaneous Injection of Humalog Mix75/25 or Humulin 70/30 in Healthy Nondiabetic Subjects. Humalog Mix75/25 has two phases of absorption. The early phase represents insulin lispro and its distinct characteristics of rapid onset. The late phase represents the prolonged action of insulin lispro protamine suspension. In 30 healthy nondiabetic subjects given subcutaneous doses(0.3 U/kg) of Humalog Mix75/25, peak serum concentrations were observed 30 to 240 minutes (median, 60 minutes) after dosing (see Figure 1). Identical results were found in patients with type 1 diabetes. The rapid absorption characteristics of Humalog are maintained with Humalog Mix75/25 (see Figure 1).Figure 1 represents serum insulin concentration versus time curves of Humalog Mix75/25 and Humulin 70/30. Humalog Mix75/25 has a more rapid absorption than Humulin 70/30, which has been confirmed in patients with type 1 diabetes.Distribution — Radiolabeled distribution studies of Humalog Mix75/25 have not been conducted. However, the volume of distribution following injection of Humalog is identical to that of Regular human insulin, with a range of 0.26 to 0.36 L/kg.Metabolism — Human metabolism studies of Humalog Mix75/25 have not been conducted. Studies in animals indicate that the metabolism of Humalog, the rapid-acting component of Humalog Mix75/25, is identical to that of Regular human insulin.Elimination — Humalog Mix75/25 has two absorption phases, a rapid and a prolonged phase, representative of the insulin lispro and insulin lispro protamine suspension components of the mixture. As with other intermediate-acting insulins, a meaningful terminal phase half-life cannot be calculated after administration of Humalog Mix75/25 because of the prolonged insulin lispro protamine suspension absorption.PharmacodynamicsStudies in nondiabetic subjects and patients with diabetes demonstrated that Humalog has a more rapid onset of glucose-lowering activity, an earlier peak for glucose-lowering, and a shorter duration of glucose-lowering activity than Regular human insulin. The early onset of activity of Humalog Mix75/25 is directly related to the rapid absorption of Humalog. The time course of action of insulin and insulin analogs, such as Humalog (and hence Humalog Mix75/25), may vary considerably in different individuals or within the same individual. The parameters of Humalog Mix75/25 activity (time of onset, peak time, and duration) as presented in Figures 2 and 3 should be considered only as general guidelines. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables (see General under PRECAUTIONS).In a glucose clamp study performed in 30 nondiabetic subjects, the onset of action and glucose-lowering activity of Humalog, Humalog® Mix50/50™, Humalog Mix75/25, and insulin lispro protamine suspension (NPL component) were compared (see Figure 2). Graphs of mean glucose infusion rate versus time showed a distinct insulin activity profile for each formulation. The rapid onset of glucose-lowering activity characteristic of Humalog was maintained in Humalog Mix75/25.In separate glucose clamp studies performed in nondiabetic subjects, pharmacodynamics of Humalog Mix75/25 and Humulin 70/30 were assessed and are presented in Figure 3. Humalog Mix75/25 has a duration of activity similar to that of Humulin 70/30.Figure 2: Insulin Activity After Injection of Humalog, Humalog Mix50/50, Humalog Mix75/25, or Insulin Lispro Protamine Suspension (NPL Component) in 30 NondiabeticSubjects.Figure 3: Insulin Activity After Injection of Humalog Mix75/25 and Humulin 70/30 inNondiabetic Subjects.Figures 2 and 3 represent insulin activity profiles as measured by glucose clamp studies in healthy nondiabetic subjects.Figure 2 shows the time activity profiles of Humalog, Humalog Mix50/50, HumalogMix75/25, and insulin lispro protamine suspension (NPL component).Figure 3 is a comparison of the time activity profiles of Humalog Mix75/25 (see Figure 3a) and of Humulin 70/30 (see Figure 3b) from two different studies.Special PopulationsAge and Gender — Information on the effect of age on the pharmacokinetics of HumalogMix75/25 is unavailable. Pharmacokinetic and pharmacodynamic comparisons between men and women administered Humalog Mix75/25 showed no gender differences. In large Humalog clinical trials, sub-group analysis based on age and gender demonstrated that differences between Humalog and Regular human insulin in postprandial glucose parameters are maintained across sub-groups.Smoking — The effect of smoking on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied.Pregnancy — The effect of pregnancy on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied.Obesity — The effect of obesity and/or subcutaneous fat thickness on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. In large clinical trials, which included patients with Body Mass Index up to and including 35 kg/m2, no consistent differences were observed between Humalog and Humulin® R with respect to postprandial glucose parameters.Renal Impairment — The effect of renal impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. In a study of 25 patients with type 2 diabetes and a wide range of renal function, the pharmacokinetic differences between Humalog and Regular human insulin were generally maintained. However, the sensitivity of thepatients to insulin did change, with an increased response to insulin as the renal function declined. Careful glucose monitoring and dose reductions of insulin, including HumalogMix75/25, may be necessary in patients with renal dysfunction.Hepatic Impairment — Some studies with human insulin have shown increased circulating levels of insulin in patients with hepatic failure. The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. However, in a study of 22 patients with type 2 diabetes, impaired hepatic function did not affect the subcutaneous absorption or general disposition of Humalog when compared with patients with no history of hepatic dysfunction. In that study, Humalog maintained its more rapid absorption and elimination when compared with Regular human insulin. Careful glucose monitoring and dose adjustments of insulin, including Humalog Mix75/25, may be necessary in patients with hepatic dysfunction.INDICATIONS AND USAGEHumalog Mix75/25, a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin), is indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia. Humalog Mix75/25 has a more rapid onset of glucose-lowering activity compared with Humulin 70/30 while having a similar duration of action. This profile is achieved by combining the rapid onset of Humalog with the intermediate action of insulin lispro protamine suspension.CONTRAINDICATIONSHumalog Mix75/25 is contraindicated during episodes of hypoglycemia and in patients sensitive to insulin lispro or any of the excipients contained in the formulation.WARNINGSHumalog differs from Regular human insulin by its rapid onset of action as well as a shorter duration of activity. Therefore, the dose of Humalog Mix75/25 should be given within 15 minutes before a meal.Hypoglycemia is the most common adverse effect associated with the use of insulins, including Humalog Mix75/25. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes.Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (e.g., Regular, NPH, analog), species, or method of manufacture may result in the need for a change in dosage.PRECAUTIONSGeneralHypoglycemia and hypokalemia are among the potential clinical adverse effects associated with the use of all insulins. Because of differences in the action of Humalog Mix75/25 and other insulins, care should be taken in patients in whom such potential side effects might be clinically relevant (e.g., patients who are fasting, have autonomic neuropathy, or are using potassium-lowering drugs or patients taking drugs sensitive to serum potassium level). Lipodystrophy and hypersensitivity are among other potential clinical adverse effects associated with the use of all insulins.As with all insulin preparations, the time course of Humalog Mix75/25 action may vary in different individuals or at different times in the same individual and is dependent on site of injection, blood supply, temperature, and physical activity.Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stress.Hypoglycemia — As with all insulin preparations, hypoglycemic reactions may be associated with the administration of Humalog Mix75/25. Rapid changes in serum glucose concentrations may induce symptoms of hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, or intensified diabetes control.Renal Impairment — As with other insulins, the requirements for Humalog Mix75/25 may be reduced in patients with renal impairment.Hepatic Impairment — Although impaired hepatic function does not affect the absorption or disposition of Humalog, careful glucose monitoring and dose adjustments of insulin, including Humalog Mix75/25, may be necessary.Allergy — Local Allergy — As with any insulin therapy, patients may experience redness, swelling, or itching at the site of injection. These minor reactions usually resolve in a few days to a few weeks. In some instances, these reactions may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique.Systemic Allergy — Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be life threatening. Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient. Antibody Production — In clinical trials, antibodies that cross-react with human insulin and insulin lispro were observed in both human insulin mixtures and insulin lispro mixtures treatment groups.Information for PatientsPatients should be informed of the potential risks and advantages of Humalog Mix75/25 and alternative therapies. Patients should not mix Humalog Mix75/25 with any other insulin. They should also be informed about the importance of proper insulin storage, injection technique, timing of dosage, adherence to meal planning, regular physical activity, regular blood glucose monitoring, periodic hemoglobin A1c testing, recognition and management of hypo- and hyperglycemia, and periodic assessment for diabetes complications.Patients should be advised to inform their physician if they are pregnant or intend to become pregnant.Refer patients to the Patient Information leaflet for information on normal appearance, timing of dosing (within 15 minutes before a meal), storing, and common adverse effects.For Patients Using Insulin Pen Delivery Devices: Before starting therapy, patients should read the Patient Information leaflet that accompanies the drug product and the User Manual that accompanies the delivery device and re-read them each time the prescription is renewed. Patients should be instructed on how to properly use the delivery device, prime the Pen to a stream of insulin, and properly dispose of needles. Patients should be advised not to share their Pens with others.Laboratory TestsAs with all insulins, the therapeutic response to Humalog Mix75/25 should be monitored by periodic blood glucose tests. Periodic measurement of hemoglobin A1c is recommended for the monitoring of long-term glycemic control.Drug InteractionsInsulin requirements may be increased by medications with hyperglycemic activity such as corticosteroids, isoniazid, certain lipid-lowering drugs (e.g., niacin), estrogens, oral contraceptives, phenothiazines, and thyroid replacement therapy.Insulin requirements may be decreased in the presence of drugs that increase insulin sensitivity or have hypoglycemic activity, such as oral antidiabetic agents, salicylates, sulfa antibiotics, certain antidepressants (monoamine oxidase inhibitors), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blocking agents, beta-adrenergic blockers, inhibitors of pancreatic function (e.g., octreotide), and alcohol. Beta-adrenergic blockers may mask the symptoms of hypoglycemia in some patients.Carcinogenesis, Mutagenesis, Impairment of FertilityLong-term studies in animals have not been performed to evaluate the carcinogenic potential of Humalog, Humalog Mix75/25, or Humalog Mix50/50. Insulin lispro was not mutagenic in a battery of in vitro and in vivo genetic toxicity assays (bacterial mutation tests, unscheduled DNA synthesis, mouse lymphoma assay, chromosomal aberration tests, and a micronucleus test). There is no evidence from animal studies of impairment of fertility induced by insulin lispro. PregnancyTeratogenic Effects — Pregnancy Category B — Reproduction studies with insulin lispro have been performed in pregnant rats and rabbits at parenteral doses up to 4 and 0.3 times, respectively, the average human dose (40 units/day) based on body surface area. The results have revealed no evidence of impaired fertility or harm to the fetus due to insulin lispro. There are, however, no adequate and well-controlled studies with Humalog, Humalog Mix75/25, or Humalog Mix50/50 in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing MothersIt is unknown whether insulin lispro is excreted in significant amounts in human milk. Many drugs, including human insulin, are excreted in human milk. For this reason, caution should be exercised when Humalog Mix75/25 is administered to a nursing woman. Patients with diabetes who are lactating may require adjustments in Humalog Mix75/25 dose, meal plan, or both. Pediatric UseSafety and effectiveness of Humalog Mix75/25 in patients less than 18 years of age have not been established.Geriatric UseClinical studies of Humalog Mix75/25 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should take into consideration the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population.ADVERSE REACTIONSClinical studies comparing Humalog Mix75/25 with human insulin mixtures did not demonstrate a difference in frequency of adverse events between the two treatments.Adverse events commonly associated with human insulin therapy include the following:Body as a Whole — allergic reactions (see PRECAUTIONS).Skin and Appendages — injection site reaction, lipodystrophy, pruritus, rash.Other — hypoglycemia (see WARNINGS and PRECAUTIONS).OVERDOSAGEHypoglycemia may occur as a result of an excess of insulin relative to food intake, energy expenditure, or both. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise, may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneousglucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. DOSAGE AND ADMINISTRATIONTable 1*: Summary of Pharmacodynamic Properties of Insulin Products (Pooled Cross-Study Comparison)Insulin Products Dose, U/kg Time of Peak Activity, Hours After Dosing Percent of Total Activity Occurring in the First 4 Hours Humalog 0.3 2.4 (0.8 - 4.3) 70% (49 - 89%) Humulin R 0.32 (0.26 - 0.37) 4.4 (4.0 - 5.5) 54% (38 - 65%) Humalog Mix75/25 0.3 2.6 (1.0 - 6.5) 35% (21 - 56%) Humulin 70/30 0.3 4.4 (1.5 - 16) 32% (14 - 60%) Humalog Mix50/50 0.3 2.3 (0.8 - 4.8) 45% (27 - 69%) Humulin 50/50 0.3 3.3 (2.0 - 5.5) 44% (21 - 60%) NPH 0.32 (0.27 - 0.40) 5.5 (3.5 - 9.5) 14% (3.0 - 48%) NPL component 0.3 5.8 (1.3 - 18.3) 22% (6.3 - 40%) * The information supplied in Table 1 indicates when peak insulin activity can be expected and the percent of the total insulin activity occurring during the first 4 hours. The information was derived from 3 separate glucose clamp studies in nondiabetic subjects. Values represent means, with ranges provided in parentheses.Humalog Mix75/25 is intended only for subcutaneous administration. Humalog Mix75/25 should not be administered intravenously. Dosage regimens of Humalog Mix75/25 will vary among patients and should be determined by the healthcare provider familiar with the patient’s metabolic needs, eating habits, and other lifestyle variables. Humalog has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog has the same glucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration. Humalog Mix75/25 has a similar glucose-lowering effect as compared with Humulin 70/30 on a unit for unit basis. The quicker glucose-lowering effect of Humalog is related to the more rapid absorption rate of insulin lispro from subcutaneous tissue.Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal. The rate of insulin absorption and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables. As with all insulin preparations, the time course of action of Humalog Mix75/25 may vary considerably in different individuals or within the same individual. Patients must be educated to use proper injection techniques.Humalog Mix75/25 should be inspected visually before use. Humalog Mix75/25 should be used only if it appears uniformly cloudy after mixing. Humalog Mix75/25 should not be used after its expiration date.HOW SUPPLIEDHumalog Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is available in the following package sizes: each presentation containing 100 units insulin lispro per mL (U-100).10 mL vials NDC 0002-7511-01 (VL-7511)5 x 3 mL prefilled insulin delivery devices (Pen) NDC 0002-8794-59 (HP-8794)5 x 3 mL prefilled insulin delivery devices (KwikPen™) NDC 0002-8797-59 (HP-8797)Storage — Humalog Mix75/25 should be stored in a refrigerator [2° to 8°C (36° to 46°F)], but not in the freezer. Do not use Humalog Mix75/25 if it has been frozen. Unrefrigerated [below 30°C (86°F)] vials must be used within 28 days or be discarded, even if they still contain Humalog Mix75/25. Unrefrigerated [below 30°C (86°F)] Pens, and KwikPens must be used within 10 days or be discarded, even if they still contain Humalog Mix75/25. Protect from direct heat and light. See table below:Not In-Use (Unopened) Room Temperature [Below 30°C (86°F)] Not In-Use (Unopened)RefrigeratedIn-Use (Opened) RoomTemperature [Below30°C (86°F)]10 mL Vial 28 days Until expiration date 28 days,refrigerated/roomtemperature.3 mL Pen and KwikPen (prefilled) 10 days Until expiration date 10 days. Do notrefrigerate.Literature revised March 16, 2009KwikPens manufactured byEli Lilly and Company, Indianapolis, IN 46285, USAPens manufactured byEli Lilly and Company, Indianapolis, IN 46285, USA orLilly France, F-67640 Fegersheim, FranceVials manufactured byEli Lilly and Company, Indianapolis, IN 46285, USA orLilly France, F-67640 Fegersheim, Francefor Eli Lilly and Company, Indianapolis, IN 46285, USACopyright © 2007, 2009, Eli Lilly and Company. All rights reserved.PV 5551 AMP PRINTED IN USA。

BPS4000产品规格说明书

1 2 3 4 5 6 7 8 9Specification StatusChange Made atBPS4000 revRev revDate Attachments Org Title supersededBy specialNotes latestSupersedingDoc reviewBy 160-006AM040322BHTI Alternate Materials List M&P 299-947-100-690115BHTI Procurement Specification for Epoxy Adhesive, Heat Resistant M&P 299-947-320-820507BHTIAdhesive Film and Primer System, Intermedite Cure Temperature (260-290º F) ServiceTemerature 67-225º F)M&P 68A900000G011101BAC Finish Spec:F-15M&P 74A900000E990308BAC Finish Specification for F18 Aircraft M&P 74A900004L010501BAC Ctrl:Fract Crit Parts, F-18M&P 74A901001F981208BAC Std Finish Codes:F-18 A\C M&P 901-947-002CA D950510BHTI Finish Specification for the V-22 Aircraft (Bell Boeing) Model 901) EMD Aircraft M&P10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26A-A-208B951120Notice 2 Notice 3FED Ink, Marking, Stencil, Opaque M&P A-A-2962Cancelled no s/s spec A980810canc notice 2-060106FED Commercial Item Description Enamel, Alkyd, Exterior, Solvent Based, Low Voc ok to use canc spec M&P A-A-3097BK-970506Notice 3FEDCommercial Item Description Adhesives, Cyanoacrylate, Rapid Room Temperature-Curing,SolventlessM&P A-A-3165CA A071116Notice 2FED Lacquer, Gloss, for A/C Use M&P A-A-52080B980523Notice 1FED Tape, Lacing, and Tying, Nylon M&P A-A-52081B980523FED Tape, Lacing, and Tying, Polyester M&P A-A-52082CE C070904Notice 1FED Tape, Lacing and Tying, TFE-Fluorocarbon M&P A-A-52083BJ C040223FED Tape, Lacing, and Tying, Glass M&P A-A-52084B980523Notice 1FED Tape, Lacing and Tying, Aramid M&P A-A-55829-970204Notice 1DLA Acetic Acid, Glacial, Technical M&P A-A-56032CN D030521Notice 1FED Commercial Item Description (CIDS) Ink, Marking, Epoxy Base M&P A-A-59126-970926FED Terminals, Feedthru (Insulated) and Terminals, Stud (Insulated and Noninsulated)ENG A-A-59132CR A100607Validation Notice 1DLA Amyl Acetate, Technical M&P A-A-59135CR-971028FED Commercial Item Description Packaging Material, Sheet M&P A-A-59136CR-971028FED Cushioning Material, Packaging, Closed Cell Foam Plank M&P A-A-59178CL A041012USGOVT Nipple, Electrical Terminal ENG A-A-59503CG B081020FED Commercial Item Description Nitrogen, Technical M&P A A59551Wire Electrical Copper(Uninsulated)27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44A-A-59551CP A091022USGOVT Wire, Electrical, Copper (Uninsulated) M&P A-A-59569CK C090122DLA Qualification Sampling and Testing of Steels for Transverse Tensile Properties ENG A-A-59588BK A050707FED Commercial Item Description Rubber, Silicone M&P A-A-59877CT-100909FED Comemrcial Item Description Insulating Compound, Electrical, Embedding M&P AIR4127CG - 071101SAE Steel: Chemical Composition and Hardenability M&P AISI-1010Unavailable-AISI Low Carb Stl Unavailable M&P AISI-50100Unavailable-AISI Bearing Stl Unavailable M&P AISI-52100Unavailable-AISI Bearing Stl Unavailable M&P AISI-B-1112Unavailable-AISI Low Carb Free Mach Stl Unavailable M&P AISI-C-1212Unavailable-AISI Matl Spec, Stl Unavailable M&P AISI-C-1213Unavailable-AISI Low Carb Free Mach Stl Unavailable M&P AISI-C-1214Unavailable-AISI Matl Spec, Stl Unavailable M&P AMS 2175CR A100601SAE Castings, Classification and Inspection of M&PAMS 2201Cancelled CN Can940901SAETolerances Aluminum and Aluminum Alloy Bar, Rod, Wire, and Forging Stock Rolled or Cold-FinishedANSI H35.2M&PAMS 2221G060201SAE Tolerances, Copper and Copper Alloy Bars and Rods M&P AMS 2222BG J060201SAE Tolerances, Copper and Copper Alloy Sheet, Strip, and Plate M&P AMS 2223BF H060201SAE Tolerances Copper and Copper Alloy Seamless Tubing M&P AMS 2224G060201SAE Tolerances Copper and Copper Alloy Wire M&P AMS2241Tolerances,Corrosion and Heat-Resistant Steel,Iron Alloy,Titanium,and Titanium Alloy Bars and45 46 47 4849 50 51 52 53 54 55 56 57 58AMS 2241CN R070701SAETolerances, Corrosion and Heat Resistant Steel, Iron Alloy, Titanium, and Titanium Alloy Bars andWireM&P AMS 2242CC G080604SAETolerances Corrosion and Heat Resistant Steel, Iron Alloy, Titanium and Titanium Alloy Sheet,Strip and PlateM&P AMS 2243BJ H060501SAE Tolerances Corrosion and Heat-Resistant Steel Tubing M&P AMS 2248CN F060501SAEChemical Check Analysis Limits Corrosion and Heat-Resistant Steels and Alloys, Maraging andother Highly-Alloyed Steels, and Iron AlloysM&PAMS 2249CN G090701SAEChemical Check Analysis Limits Titanium and Titanium AlloysM&PAMS 2259CN E071201SAE Chemical Check Analysis Limits Wrought Low-Alloy and Carbon Steels M&P AMS 2269CN F060501SAE Chemical Check Analysis Limits Nickel, Nickel Alloys, and Cobalt Alloys M&P AMS 2300BF K031001SAE Steel Cleanliness, Premium Aircraft-Quality Magnetic Particle Inspection Procedure M&P AMS 2301CT K100801SAE Steel Cleanliness, Aircraft Quality Magnetic Particle Inspection Procedure M&P AMS 2303CT F100801SAESteel Cleanliness, Aircraft Quality, Martensitic Corrosion Resistant Steels Magnetic ParticleInspection ProcedureM&P AMS 2304CN A060301SAE Steel Cleanliness, Special Aircraft-Quality Magnetic Particle Inspection Procedure M&P AMS 2310BE F060201SAE Qualification Sampling and Testing of Steels for Transverse Tensile Properties M&P AMS 2315CN F080101SAE Determination of Delta Ferrite Content M&PAMS 2350Cancelled no s/s spec CN BA891001SAEStandards and Test Methodsok to use canc spec M&P1Specification Status Change Made atBPS4000 revRev revDate Attachments Org Title supersededBy specialNotes latestSupersedingDoc reviewBy59 60 61 62 63 64AMS 2355CN J090701SAEQuality Assurance Sampling and Testing Aluminum Alloys and Magnesium Alloy WroughtProducts (Except Forging Stock), and Rolled, Forged, or Flash Welding RingsM&P AMS 2360CN D070701SAE Room Temperature Tensile Properties of Castings M&P AMS 2370CN J071101SAEQuality Assurance Sampling and Testing Carbon and Low-Alloy Steel Wrought Products andForging StockM&P AMS 2371CN H071101SAEQuality Assurance Sampling and Testing Corrosion and Heat-Resistant Steels and Alloys WroughtProducts and Forging StockM&P AMS 2372CN E070601SAE Quality Assurance Sampling and Testing Carbon and Low-Alloy Steel Forgings M&P AMS 2375CN D070601SAE Control of Forgings Requiring First Article Approval M&PA l d C t l f P i Q lit Tit i All65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82AMS 2380CN F080601SAE Approval and Control of Premium-Quality Titanium Alloys M&P AMS 2400BV W070701SAE Plating, Cadmium M&P AMS 2401CN H071101SAE Plating, Cadmium Low Hydrogen Content Deposit M&P AMS 2403BM L041001SAE Plating, Nickel General Purpose M&P AMS 2404CH F081201SAE Plating, Electroless Nickel M&P AMS 2405Noncurrent CN C841010SAE Electroless Nickel Plate, Low Phosphorous M&P AMS 2406BV L070501SAE Plating, Chromium Hard Deposit M&P AMS 2408CF J081101SAE Plating, Tin M&P AMS 2410CR K100401SAE Plating, Silver Nickel Strike, High Bake M&P AMS 2411CB G080201SAE Plating, Silver for High Temperature Applications M&P AMS 2412CN J091201SAE Plating, Silver Copper Strike, Low Bake M&P AMS 2416K040301SAE Plating, Nickel-Cadmium Diffused M&P AMS 2417G040701SAE Plating, Zinc-Nickel Alloy M&P AMS 2418G060101SAE Plating, Copper M&P AMS 2419BM C030501SAE Plating, Cadmium-Titanium M&P AMS 2420D021201SAE Plating of Aluminum for Solderability Zinc Immersion Pre-Treatment Process M&PAMS 2423**See special notes CE D020401SAE Plating, Nickel Hard DepositContinue to use AMS-QQ-N-290 for Class2 NickelM&PAMS 2424CR F100401SAE NI Plate, Low Stressed Deposit M&P AMS2426D Coating Cadmium Vacuum Deposition83 84 85 86 87 88 89 90 91 92 93 94AMS 2426BT020901SAE Coating, Cadmium Vacuum Deposition M&P AMS 2429C011101SAE Bronze Plate Masking M&P AMS 2430CN R100101SAE Shot Peening, Automatic M&P AMS 2433C041001SAE Plating, Nickel-Thallium-Boron or Nickel-Boron M&P AMS 2434CN C060501SAE Plating, Tin-Zinc Alloy M&P AMS 2435Noncurrent CN G070601SAE Coating, Tungsten Carbide-Cobalt Coating, Detonation Process M&P AMS 2437BN C710111SAE Coating, Plasma Spray Deposition M&P AMS 2438CL D090701SAE Plating, Chromium Thin, Hard, Dense Deposit M&P AMS 2444BM A001201SAE Coating, Titanium Nitride Physical Vapor Deposition M&P AMS 2451BN B060501SAE Plating, Brush General Requirements M&PAMS 2460See special notes CA-070701SAE Plating, ChromiumIf dwg requires chrome plate per AMS-QQ-C-320 then stress relief and embritlmnt(emb) bake relief per BPS4620. If dwg req'schrome plate per AMS 2460 then stressrelief and bake relief per AMS 2460 unlessthe dwg specifically req's BPS 4620M&PAMS 2468Cancelled CN G981001SAE Hard Anodic Coating Treatment of Aluminum Alloys AMS 2469M&P AMS 2469CG H080701SAEHard Anodic Coating Treatment of Aluminum and Aluminum Alloys Processing and PerformanceRequirementsM&P95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111qAMS 2470CN M070401SAE Anodic Treatment of Aluminum Alloys Chromic Acid Process M&P AMS 2471CN G081201SAE Anodic Treatment of Aluminum Alloys Sulfuric Acid Process, Undyed Coating M&P AMS 2481CP J100201SAE Phosphate Treatment Antichafing M&PAMS 2482CN D100101SAEHard Anodic Coating on Aluminum Alloys Polytetrafluoroethylene (PTFE)-Impregnated orCodepositedM&PAMS 2485BY K080101SAE Coating, Black Oxide M&P AMS 2486CR E100501SAE Conversion Coating of Titanium Alloys Fluoride-Phosphate Type M&P AMS 2487CN A000301SAE Anodic Treatment of Titanium and Titanium Alloys Solution pH 12.4 Maximum M&P AMS 2488D000606SAE Anodic Tr:Ti,Ti Alys M&P AMS 2515BM E900101SAE Polytetrafluoroethylene (PTFE) Resin Coating Low Build, 370 to 400 °C (698 to 752 °F) Fusion M&P AMS 2516BM D900101SAE Polytetrafluoroethylene (PTFE) Resin Coating High Build, 370 to 400 °C (698 to 752 °F) Fusion M&P AMS 2525C030401SAE Graphite Coating, Thin Lubricating Film Impingement Applied M&P AMS 2526BW C071001SAE Molybdenum Disulfide Coating, Thin Lubricating Film Impingement Applied M&P AMS 2615BM F060901SAE Pressure Testing Hydraulic Pressure as Specified M&P AMS 2630CR C100101SAE Inspection, Ultrasonic Product Over 0.5 Inch (12.7 mm) Thick M&P AMS 2631CN C090701SAE Ultrasonic Inspection Titanium and Titanium Alloy Bar and Billet M&P AMS 2632BN A950301SAEInspection, Ultrasonic, Of Thin Materials 0.50 Inch (12.7 mm) and Under in Cross-SectionalThicknessM&P1Specification Status Change Made atBPS4000 revRev revDate Attachments Org Title supersededBy specialNotes latestSupersedingDoc reviewBy112 113 114 115 116 117 118 119 120AMS 2635Cancelled Can810701SAE Radiographic Insp ASTM E1742M&P AMS 2640Cancelled CH Can960401SAE Magnetic Particle Inspection ASTM E1444M&P AMS 2645Cancelled CH Can950201SAE Fluorescent Penetrant Inspection ASTM E1417M&P AMS 2649CA C080101SAE Etch Inspection of High Strength Steel Parts M&P AMS 2658CN C091001SAE Hardness and Conductivity Inspection of Wrought Aluminum Alloy Parts M&P AMS 2664CH F950701SAE Brazing, Silver For Use Up to 800 °F (427 °C)M&P AMS 2665G030101SAE Brazing, Silver for Use up to 400 °F (204 °C)M&P AMS 2666Cancelled Can840101SAE Ag Braz,High Temp AMS 2664M&P AMS 2670BK J060601SAE Brazing, Copper M&P121 122 123 124 125 126 127 128 129 130 131 132 133 134135AMS 2671Cancelled CH Can920101SAE Copper Brazing Corrosion and Heat Resistant Steels and Alloys AMS 2670M&P AMS 2672BM F010301SAE Brazing, Aluminum Torch or Furnace M&P AMS 2673BM D010301SAE Brazing, Aluminum and Aluminum Alloys Molten Flux (Dip)M&P AMS 2675G020501SAE Brazing, Nickel Alloy Filler Metal M&P AMS 2680C010601SAE Electron--Beam Welding for Fatigue Critical Applications M&P AMS 2681B000301SAE Electron Beam Welding M&P AMS 2685Noncurrent CP E071001SAE Welding, Tungsten Arc, Inert Gas GTAW Method M&P AMS 2689Noncurrent CH A980201SAE Fusion Welding Titanium and Titanium Alloys M&P AMS 2694BR B070201SAE In-Process Welding of Castings M&PAMS 2700CF C081101SAE Passivation of Corrosion Resistant SteelsIf no Method & Type are specified must useMethod 1, Type 2,6,7 or 8 depending on thebase material. All acceptance testing shallbe per Class 4.M&PAMS 2728BM A050301SAE Heat Treatment of Wrought Copper Beryllium Alloy Parts M&P AMS 2745CJ A071201SAE Induction Hardening of Steel Parts M&P AMS 2750BN D050901SAE M&P AMS 2753CF C080801SAE Liquid Salt Bath Ferritic Nitrocarburizing Non-Cyanide Bath M&P AMS 2755Cancelled CM Can090701SAE Nitriding, Molten Salt BathProcess not available, consider AMS 2753as replacementM&P136137 138 139140 141 142 143 144 145as replacement.AMS 2759CE E081001SAE Heat Treatment of Steel Parts General Requirements M&P AMS 2759/1CJ E090201SAEHeat Treatment of Carbon & Low-Alloy Steel Parts Minimum Tensile Strength Below 220 ksi (1517Mpa)Supersedes MIL-H-6875 for carbon & low-alloy steels below 220 KSIM&P AMS 2759/10CN A060601SAE Automated Gaseous Nitriding Controlled by Nitriding Potential M&P AMS 2759/11BW-050401SAE Stress Relief of Steel Parts M&P AMS 2759/2CR F100501SAE Heat Treatment of Low-Alloy Steel Parts Minimum Tensile Strength 220 ksi (1517 Mpa) and HigherSupersedes MIL-H-6875 for low-alloysteels, 220 KSI & higher M&P AMS 2759/3CE E080801SAE Heat Treatment Precipitation-Hardening Corrosion-Resistant & Maraging Steel PartsSupersedes MIL-H-6875 for precipitationhardening & maraging steelM&P AMS 2759/4CA C080301SAE Heat Treatment Austenitic Corrosion-Resistant Steel PartsSupersedes MIL-H-6875 for austenticsteelsM&P AMS 2759/5D040601SAE Heat Treatment Martensitic Corrosion Resistant Steel PartsSupersedes MIL-H-6875 for martensiticsteelsM&P AMS 2759/6BM B051101SAE Gas Nitriding & Heat Treatment of Low - Alloy Steel Parts Use Standard Drawing Notes per BDS2240M&P AMS 2759/7CT B100501SAE Carburizing and Heat Treatment of Carburizing Grade Steel Parts M&P1. Infrared pyrometry may be used to146 147 148 149 150 151 152 153 154 155 156AMS 2759/8CG A070601See Special Notes SAE Ion Nitridingmeasure temperature. 2. The nitridingtemperature may be less than 50 degreesbelow the tempering or aging temperatureprovided that the core hardness is notreduced. 3. For small loads, a minimum oftwo acceptance testing specimens may beused in lieu of four, provided that at leastone specimen is placed in each layer.M&P AMS 2759/9CL D090501SAE Hydrogen Embrittlement Relief (Baking of Steel Parts)Supersedes MIL-H-6875 for stress relievingsteelsM&P AMS 2762Noncurrent CP B020101SAE Carburizing Carbon and Low-Alloy Steel Parts M&P AMS 2768CR C100701SAE Heat Treatment of Magnesium Alloy Castings M&P AMS 2770BJ H060801SAE Heat Treatment of Wrought Aluminum Alloy Parts M&P AMS 2771C040701SAE Heat Treatment of Aluminum Alloy Castings M&P AMS 2772BY E080201SAE Heat Treatment of Aluminum Alloy Raw Materials M&P AMS 2774CG B080801SAE Heat Treatment Wrought Nickel Alloy and Cobalt Alloy Parts M&P AMS 2800CN D060801SAE Identification Finished Parts M&P AMS 2801B030301SAE Heat Treatment of Titanium Alloy Parts M&P AMS 2807CF B080201SAEIdentification Carbon and Low-Alloy Steels, Corrosion and Heat-Resistant Steels and Alloys Sheet,Strip, Plate and Aircraft TubingM&P1Specification Status Change Made atBPS4000 revRev revDate Attachments Org Title supersededBy specialNotes latestSupersedingDoc reviewBy157 158 159 160161162AMS 3025CN C090901SAE Polyalkylene Glycol Heat Treat Quenchant M&P AMS 3106Cancelled Can830401SAE Primer, Adhesive,Corr Inhib AMS 3107M&P AMS 3107A910401SAE Primer, Adhesive,Corr-Inhibiting M&P AMS 3195E920101SAE Silicone Rubber Sponge M&PAMS 3216G050901SAE Fluorocarbon (FKM) Rubber High-Temperature - Fluid Resistant Low Compression Set 70 to 80M&P AMS 3218C050901SAE Fluorocarbon (FKM) Rubber High-Temperature - Fluid Resistant Low Compression Set 85 to 95M&P AMS3276Sealing Compound,Integral Fuel Tanks and General Purpose,Intermittent Use to360°F(182°C)163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180AMS 3276CB E080301SAE Sealing Compound, Integral Fuel Tanks and General Purpose, Intermittent Use to 360 F (182 C)M&PAMS 3301G900401SAE Silicone Rubber, Gen Purp,35-45M&P AMS 3305H900401SAE Silicone Rubber, Gen Purp,75-85M&P AMS 3374C050701SAE Sealing Compound Aircraft Firewall M&P AMS 3410J981001SAE Flux,Ag Braz M&P AMS 3411D981001SAE Flux Silver Brz, High Temp M&P AMS 3644BL G060901SAE Plastic: Polyimide For Molded Rod, Bar, and Tube, Plaque, and Formed Parts M&P AMS 3645CN C010101SAE Polychlorotrifluoroethylene (PCTFE), Compression Molded Heavy Sections, Unplasticized M&P AMS 3650CN C910101SAE Rods, Sheets, and Molded Shapes, Polychlorotrifluoroethylene (PCTFE) Unplasticized M&P AMS 3651Cancelled Can870401SAE Ptfe AMS 3667M&P AMS 3651Cancelled Can870401Ptfe AMS 3652M&P AMS 3651Cancelled Can870401Ptfe AMS 3656M&P AMS 3651Cancelled Can870401Ptfe AMS 3660M&P AMS 3652C930101SAE Ptfe Film,Non-Crit Grade M&P AMS 3656CT G080301SAE Ptfe Extrusions,Norm Strength, As Sintered M&P AMS 3657CC D080301SAE Ptfe, Extrusions, Premium M&P AMS 3658CC D080301SAE Ptfe, Extrusions, Premium M&PAMS 3659CR E100501SAE Polytetrafluoroethylene (PTFE) Extrusions, Premium Strength, Sintered and Stress-Relieved M&P AMS3660D100601Polytetrafluoroethylene Moldings M&P181 182 183 184 185 186 187 188 189190191192193194AMS 3660CR SAE Polytetrafluoroethylene MoldingsAMS 3666D930701SAE Ptfe Sht, Glass Reinforced M&P AMS 3667CA D080301SAE Polytetrafluorethylene Sheet, Molded General Purpose Grade, As Sintered M&P AMS 3668CT D100501SAE Ptfe, Moldings, Premium Grade, A Sintered M&P AMS 3670/1B950401SAE Unfilled Polyamide-Imide, Bar M&P AMS 3824CN C950901SAE Cloth, Glass Finished for Resin Laminates M&P AMS 4001Cancelled CK Can070701SAE Aluminum Sheet and Plate 0.12Cu (1100-0) Annealed ASTM B209M&P AMS 4013CN F070501SAE Aluminum Sheet, Laminated Surface Bonded M&P AMS 4015CN L070201SAE Aluminum Alloy, Sheet and Plate 2.5Mg - 0.25Cr (5052-0) Annealed M&PAMS 4016CN L060901SAEAluminum Alloy, Sheet and Plate 2.5Mg - 0.25Cr (5052-H32) Strain Hardened, Quarter Hard, andStabilizedM&P AMS 4017CN K041201SAEAluminum Alloy Sheet and Plate 2.5Mg - 0.25Cr (5052-H34) Strain-Hardened, Half Hard, andStabilizedM&P AMS 4023CN E840401SAEAluminum Alloy Sheet and Plate Alcalad 1.0Mg - 0.60Si - 0.28Cu - 0.20Cr (Alclad 6061; -T6 Sheet,-T651 Plate)M&P AMS 4025CE L080701SAE Aluminum Alloy, Sheet and Plate 1.0Mg - 0.60Si-0.28Cu-0.20Cr(6061-0) Annealed AMS-QQ-A-250/11A - cancelled - 2008M&P AMS 4026CE M080701SAEAluminum Alloy, Sheet and Plate 1.0Mg -0.60Si-0.28Cu-0.20Cr (6061;-T4 Sheet, T-451 Plate)Solution Heat Treated and Naturally AgedAMS-QQ-A-250/11A - cancelled - 2008M&P AMS4027Aluminum Alloy,Sheet and Plate1.0Mg-0.60Si-0.28Cu-0.20Cr(6061;-T6Sheet,T-651Plate)AMS QQ A250/11A ll d2008195 196 197 198 199 200 201 202 203 204AMS 4027CE N080701SAEAluminum Alloy, Sheet and Plate 1.0Mg 0.60Si0.28Cu0.20Cr (6061;T6 Sheet, T651 Plate)Solution and Precipitation Heat TreatAMS-QQ-A-250/11A - cancelled - 2008M&P AMS 4037CN N030701SAEAluminum Alloy, Sheet and Plate 4.4Cu - 1.5Mg - 0.60Mn (2024; - T3 Flat Sheet, T351 Plate)Solution Heat TreatedM&P AMS 4080CN N091201SAE Aluminum Alloy, Drawn Seamless Tubing 1.0Mg - 0.60Si - 0.28Cu - 0.20Cr (6061-O) Annealed M&P AMS 4081CC J080601SAEAluminum Alloy Tubing, Hydraulic, Seamless, Drawn, Round 1.0Mg - 0.60Si - 0.28Cu - 0.20Cr(6061-T4) Solution Heat Treated and Naturally AgedM&P AMS 4083BW K000901SAEAluminum Alloy Tubing, Hydraulic, Seamless, Drawn, Round 1.0Mg - 0.60Si - 0.28Cu - 0.20Cr-(6061-T6) Solution and Precipitation Heat TreatedM&P AMS 4086BL N060901SAEAluminum Alloy, Drawn, Round, Seamless Hydraulic Tubing 4.4Cu-1.5Mg-0.60Mn (2024-T3)Solution Heat Treated, Cold Worked, and Naturally AgedM&P AMS 4088BT K070301SAEAluminum Alloy, Drawn, Seamless Tubing 4.4Cu-1.5Mg-0.60Mn (2024-T3) Solution Heat Treatedand Cold WorkedM&P AMS 4107F051101SAE Alum Aly Die Forg, (7050-T14)M&P AMS 4113CH E030701SAEAluminum Alloy, Extruded Profiles 1.0Mg - 0.60Si - 0.28Cu - 0.20Cr (6061-T6) Solution andPrecipitation Heat TreatedM&P AMS 4116CN H090701SAEAluminum Alloy, Bars, Rods, and Wire 1.0Mg - 0.60Si - 0.3Cu - 0.20Cr (6061-T4) Cold Finished,Solution Heat Treated and Naturally AgedM&P1Specification Status Change Made atBPS4000 revRev revDate Attachments Org Title supersededBy specialNotes latestSupersedingDoc reviewBy205 206 207AMS 4117CM J090701SAEAluminum Alloy, Rolled or Cold Finished Bars, Rods, and Wire and Flash Welded Rings 1.0Mg -0.60Si - 0.28Cu - 0.20Cr (6061; - T6, -T651) Solution and Precipitation Heat TreatedM&P AMS 4119Cancelled CN Can900101SAEAluminum Alloy Bars, Rolled, Drawn, or Cold Finished 4.4Cu - 1.5Mg - 0.60Mn (2024-T351) StressRelief StretchedAMS 4120M&P AMS 4120R020901SAEAluminum Alloy, Rolled or Cold Finished Bars, Rods, and Wire 4.4Cu - 1.5 Mg - 0.60Mn (2024)Solution Heat Treated and Naturally Aged (T4) Solution Heat Treated, Cold Worked, and NaturallyAged (T351)M&P AMS4121Aluminum Alloy Bars, Rods, and Wire, Rolled or Cold Finished 4.5Cu - 0.85Si - 0.80Mn - 0.50Mg208 209 210 211 212 213 214 215 216AMS 4121CA H071101SAE(2014-T6) Solution and Precipitation Heat TreatedM&P AMS 4123CN H060101SAEAluminum Alloy, Rolled or Cold Finished Bars and Rods (7075-T651) Solution and PrecipitationHeat TreatedM&P AMS 4124BU D050801SAEAluminum Alloy, Rolled or Cold Finished Bars, Rods, and Wire 5.6Zn-2.5Mg-1.6Cu-0.23Cr (7075-T7351) Solution Heat Treated, Stress Relieved by Stretching and OveragedM&P AMS 4128CN D071001SAEAluminum Alloy Bars, Rolled or Cold Finished 1.0Mg - 0.60Si - 0.30Cu - 0.20Cr (6061-T451)Solution Heat Treated and Stress Relieved by StretchingM&P AMS 4132CF F081201SAEAluminum Alloy, Die and Hand Forgings, Rolled Rings, and Forging Stock 2.3Cu-1.6Mg-1.1Fe-1.0Ni-0.18Si-0.07Ti (2618-T61) Solution and Precipitation Heat TreatedM&P AMS 4133CN E090301SAEAluminum Alloy Forgings and Rolled Rings 4.4Cu -0.85Si -0.80Mn - 0.50Mg (2014-T6) Solutionand Precipitation Heat TreatedM&P AMS 4135Cancelled CN Can860401SAEAluminum Alloy Forgings 4.5Cu - 0.85Si - 0.80Mn - 0.50Mg (2014-T6) Solution and PrecipitationHeat TreatedAMS 4133M&P AMS 4141CE F081001SAEAluminum Alloy Die Forgings 5.6Zn - 2.5Mg - 1.6Cu - 0.23Cr (7075-T73) Solution and PrecipitationHeat TreatedM&P AMS 4144BN F060501SAEAluminum Alloy, Hand Forgings and Rolled Rings 6.3Cu - 0.30Mn - 0.18Zr - 0.10V - 0.06Ti (2219-T852/T851) Solution Heat Treated, Mechanically Stress Relieved, and Precipitation Heat-TreatedM&P AMS 4149D020901SAEAluminum Alloy, Die and Hand Forgings 5.6n - 2.5Mg - 1.6Cu - 0.23Cr (7175-T74) Solution andPrecipitation Heat TreatedM&P217218219220 221 222 223 224 225 226 227 228 229230Precipitation Heat TreatedAMS 4150CN L030801SAEAluminum Alloy, Extrusions and Rings 1.0Mg - 0.60Si - 0.28Cu - 0.20Cr - (6061-T6) Solution andPrecipitation Heat TreatedM&P AMS 4162D030701SAEAluminum Alloy, Extrusions 6.3Cu - 0.30Mn - 0.18Zr - 0.10V - 0.06Ti (2219-T8511) SolutionTreated, Stress Relief Stretched, Straigtened, and Precipitation Heat TreatedM&P AMS 4173CN E030701SAEAluminum Alloy, Extrusions 1.0Mg - 0.60Si - 0.30Cu - 0.20Cr (6061-T6511) Solution HeatTreated,Stress Relieved by Stretching, Straightened, and Precipitation Heat TreatedM&P AMS 4181C030401SAE Aluminum Alloy, Welding Wire 7.0Si - 0.38Mg - 0.10Ti (4008) (UNS A94008)M&P AMS 4182CN G091201SAE Alum Aly Wire, Annealed 5.0Mg - 0.12Mn - 0.12Cr (5056-0) Annealed M&P AMS 4185D000701SAE Fill Mtl, Alum Braz,12SI,(4047)M&P AMS 4188Cancelled Can861001SAE Wldg Wire AMS 4181M&P AMS 4188Cancelled Can861001SAE Wldg Wire AMS 4233M&P AMS 4188Cancelled Can861001SAE Wldg Wire AMS 4244M&P AMS 4188Cancelled Can861001SAE Wldg Wire AMS 4245M&P AMS 4188Cancelled Can861001SAE Wldg Wire AMS 4246M&P AMS 4210CN K050301SAE Aluminum Alloy, Castings 5.0Si - 1.2Cu - 0.50Mg (355.0-T51) Precipitation Heat Treated M&P AMS 4212CN J051001SAEAluminum Alloy Castings 5.0Si - 1.2Cu - 0.50Mg (355.0-T6) Solution and Precipitation HeatTreatedM&P AMS 4214CN J080601SAECastings, Aluminum Alloy Sand 5.0Si - 1.2Cu - 0.50Mg (355.0 T71) Solution Heat Treated andOveragedM&P231 232 233 234 235 236 237 238 239 240 241O e agedAMS 4215CN H080301SAEAluminum Alloy, Castings 5.0Si - 1.2Cu - 0.50Mg (C355.0-T6) Solution and Precipitation HeatTreatedM&P AMS 4217CN H070401SAEAluminum Alloy, Castings 7.0Si - 0.32Mg (A356.0-T6) (Formerly T6P Temper) Solution andPrecipitation Heat TreatedM&P AMS 4218CN J100101SAEAluminum Alloy Castings 7.0Si-0.35Mg (A356.0-T6) (Formerly T6P Temper) Solution andPrecipitation Heat TreatedM&P AMS 4223CN D070401SAEAluminum Alloy, Castings 4.5Cu - 0.70Ag - 0.30Mn - 0.25Mg - 0.25Ti (A201.0-T4) Solution HeatTreated and Naturally AgedM&P AMS 4224Cancelled no s/s spec CN C100101SAEAluminum Alloy Castings, Sand 4.0Cu - 2.1Ni - 2.0Mg - 0.30Cr - 0.30Mn - 0.13T - 0.13V (243.0)Stabilizedok to use canc spec M&P AMS 4225CN D070601SAEAluminum Alloy, Heat Resistant, Castings 5.0Cu - 1.5Ni - 0.25Mn - 0.25Sb - 0.25Co - 0.20Ti -0.20Zr (203.0-T6) Solution Heat Treated and Precipitation Heat TreatedM&P AMS 4226Noncurrent CN A830101SAEAluminum Alloy Castings, High Strength 5.0Cu - 0.35Mn - 0.18Zr- 0.10V (224.0) Solution andPrecipitation Heat Treated (Overaged)M&P AMS 4227Cancelled no s/s spec CN E050701SAE Aluminum Alloy, Casting, Sand, 8.0Cu 6.0Mg 0.50Mn 0.50Ni, As Cast ok to use canc spec M&P AMS 4229CN D010501SAEAluminum Alloy Castings, High Strength 4.5Cu - 0.7Ag - 0.30Mn - 0.25Mg - 0.25Ti (A201.0-T7)Solution Heat Treated and OveragedM&P AMS 4233C030301SAE Aluminum Alloy, Welding Wire 4.5 Cu - 0.70Ag - 0.30Mn - 0.25Mg - 0.25Ti (201) (UNS A02010)M&P1Specification Status Change Made atBPS4000 revRev revDate Attachments Org Title supersededBy specialNotes latestSupersedingDoc reviewBy242 243 244 245AMS 4235CN B080301SAEAluminum Alloy Castings 4.6Cu - 0.35Mn - 0.25Mg - 0.22Ti (A206.0-T71) Solution andPrecipitation Heat TreatedM&P AMS 4236CN B070801SAEAluminum Alloy Castings 4.6Cu - 0.35Mn - 0.25Mg - 0.22Ti (A206.0-T4) Solution Heat Treated andNaturally AgedM&P AMS 4237Cancelled no s/s spec CN B070401SAEAluminum Alloy Castings, Sand 4.6Cu - 0.35Mn - 0.25Mg - 0.22Ti (206.0 - T71) Solution HeatTreated and Naturally Agedok to use canc spec M&P AMS 4241CN D091101SAEAluminum Alloy Castings 7.0Si - 0.58Mg - 0.15Ti -0.06Be (D357.0 - T6) Solution and PrecipitationHeat Treated Dendrite Arm Spacing (DAS) ControlledM&P AMS4244Aluminum Alloy,Welding Wire4.6Cu-0.35Mn-0.25Mg-0.22Ti for Welding A206.0Type Alloys246 247 248 249 250 251 252 253 254 255 256 257AMS 4244CE B080701SAE Aluminum Alloy, Welding Wire 4.6Cu 0.35Mn 0.25Mg 0.22Ti for Welding A206.0 Type Alloys M&PAMS 4245Noncurrent CR E100401SAE Aluminum Alloy, Welding Wire 5.0Si - 1.2Cu - 0.50Mg (355) (UNS A03550)M&P AMS 4246Noncurrent CP D080201SAE Aluminum Alloy, Welding Wire 7.0Si - 0.52Mg (357) (UNS A03570)M&PAMS 4260Not Acceptable to Useat Parker HannifinAerospaceCL G080601SAE Alum Aly Cast, Invest(356.0-T6)BPS4829AMS4260G unacceptable for Parker Use.BPS4829 created as replacement.M&P AMS 4261CN F091201SAE Aluminum Alloy Castings, Investment 7.0Si - 0.32Mg (356.0 - T51) Precipitation Heat Treated M&P AMS 4280CN J080601SAEAluminum Alloy Castings, Permanent Mold 5.0Si - 1.2Cu - 0.5Mg (355.0-T71) Solution HeatTreated and OveragedM&P AMS 4284CN H080601SAEAluminum Alloy Castings, Permanent Mold 7.0Si - 0.30Mg (356.0-T6) Solution and PrecipitationHeat TreatedM&P AMS 4289CN-011101SAEAluminum Alloy Castings 7.0Si - 0.55Mg - 0.12Ti (F357.0-T6) Solution and Precipitation HeatTreatedM&PAMS 4291CT H101001SAE Aluminum Alloy, Die Castings 8.5Si - 3.5Cu (A380.0-F) (See AS1990) As Cast M&PAMS 4315CK-050701SAEAluminum Alloy Sheet and Plate 5.6Zn - 2.5Mg - 1.6Cu - 0.23Cr 7075: (-T76 Sheet, -T7651 Plate)Solution and Precipitation Heat TreatedM&PAMS 4316CN-050701SAE Aluminum Alloy, Alclad Sheet and Plate 5.6Zn - 2.5Mg M&PAMS 4437CN E080501SAE Magnesium Alloy Castings, Sand 8.7Al - 0.70Zn (AZ91C-T6) Solution Heat Treated and Aged M&P258 259 260 261 262 263 264 265 266 267 268 269AMS 4507BW H011101SAE Copper Alloy (Brass), Sheet, Strip, and Plate 70Cu - 30Zn Half Hard (H02)M&P AMS 4510CN G010501SAE Phosphor Bronze, Sheet, Strip, and Plate 94.5Cu - 4.0Sn - 0.19P Spring Temper (H08)M&PAMS 4511A040701SAECopper Beryllium Alloy Castings 97Cu-2.1Be-0.52(Co+Ni)-0.28Si Solution and Precipitation HeatTreated (TFOO)M&P AMS 4530G050201SAE Copper -Beryllium Alloy Sheet, Strip, and Plate 98Cu - 1.9Be Solution Heat Treated (TB00)M&P AMS 4533CL C090701SAECopper-Beryllium Alloy, Bars and Rods 98Cu - 1.9Be Solution and Precipitation Heat Treated(TF00, formerly AT)-UNS C17200M&P AMS 4597CN-060801SAECopper-Nickel-Tin Alloy, Bars and Rods 77Cu - 15Ni - 8Sn Solution Annealed, Cold Finished andSpinodal Hardened (TX TS)M&PAMS 4631Noncurrent CL E880401SAE Aluminum Bronze Rods, Bars, and Forgings 90.5Cu - 7.5Al - 1.95: Stress Relieved M&PAMS 4633CL A031201SAEBronze, Aluminum Silicon, Rods, Bars, and Forgings 90Cu - 7.0Al - 1.8Si Drawn and StressRelieved (HR50)M&PAMS 4634CL B090301SAE Aluminum Bronze Bars, Rods, and Forgings 905Cu - 7.5Al - 1.9Si Stress Relieved M&P AMS 4635CL F090701SAE Aluminum Bronze Bars, Rods, and Forgings 87Cu - 9Al - 3Fe Stress Relieved M&P AMS 4640G050801SAEAluminum Bronze, Bars, Rods, Shapes, Tubes, and Forgings 81.5Cu - 10.0Al - 4.8Ni - 3.0FeDrawn and Stress Relieved (HR50) or Temper Annealed (TQ50)M&P AMS 4650L040301SAECopper-Beryllium Alloy, Bars, Rods, Shapes and Forgings 98Cu - 1.9Be Solution Heat TreatedTB00 (A)M&P270271 272 273 274 275 276 277 278279280281282283()AMS 4651CN C050701SAE Copper-Beryllium Alloy, Bars and Rods 98Cu - 1.9Be (CDA 172) Hard Temper (TD04)M&PAMS 4674CN G060901SAE Nickel - Copper Alloy, Corrosion-Resistant, Bars and Forgings 67Ni - 30Cu - 0.04S Free Machining M&PAMS 4701CN G091001SAE Copper Wire, Oxygen-Free 99.95 (Cu+Ag) Annealed M&P AMS 4730CN G080701SAE Nickel-Copper Alloy Wire, Corrosion-Resistant 67Ni-31Cu Annealed (400)M&P AMS 4765E990501SAE Braz Fill Mtl M&P AMS 4769F990501SAE Braz Fill Mtl M&P AMS 4770K990501SAE Braz Fill Mtl M&P AMS 4772J990501SAE Braz Fill Mtl M&P AMS 4774F990501SAE Braz Fill Mtl M&PAMS 4775CT J101001SAENickel Alloy, Brazing Filler Metal 73Ni - 0.75C - 4.5Si - 14Cr - 3.1B - 4.5Fe 1790 to 1970 °F (977 to1077 °C) Solidus-Liquidus RangeM&P AMS 4776CT H101001SAENickel Alloy, Brazing Filler Metal 73Ni - 4.5Si - 14Cr - 3.1B - 4.5Fe (Low Carbon) 1790 to 1970 °F(977 to 1077 °C) Solidus-Liquidus RangeM&P AMS 4777CT H101001SAENickel Alloy, Brazing Filler Metal 82Ni - 4.5Si - 7.0Cr - 3.1B - 3.0Fe 1780 to 1830 °F (971 to 999°C) Solidus-Liquidus RangeM&P AMS 4786CN H090701SAEGold-Palladium-Nickel Alloy, Brazing Filler Metal, High Temperature 70 Au - 8.0Pd - 22Ni 1845 to1915 °F (1007 to 1046 °C) Solidus-Liquidus RangeM&P AMS 4787F000401SAE Gold-Nickel Alloy, Brazing Filler Metal, High Temperature 70Au - 8.0Pd - 22Ni 1845 to 1915M&P。

A new antibiotic kills pathogens without detectable resistance

factors through the chambers enables growth of uncultured bacteria in their natural environment. The growth recovery by this method approaches 50%, as compared to 1% of cells from soil that will grow on a nutrient Petri dish10. Once a colony is produced, a substantial number of uncultured isolates are able to grow in vitro14. Extracts from 10,000 isolates obtained by growth in iChips were screened for antimicrobial activity on plates overlaid with S. aureus. An extract from a new species of b-proteobacteria provisionally named Eleftheria terrae showed good activity. The genome of E. terrae was sequenced (Supplementary Discussion). Based on 16S rDNA and in silico DNA/DNA hybridization, this organism belongs to a new genus related to Aquabacteria (Extended Data Fig. 2, Supplementary Discussion). This group of Gram-negative organisms is not known to produce antibiotics. A partially purified active fraction contained a compound with a molecular mass of 1,242 Da determined by mass spectrometry, which was not reported in available databases. The compound was isolated and a complete stereochemical assignment has been made based on NMR and advanced Marfey’s analysis (Fig. 1, Extended Data Figs 3 and 4 and Supplementary Discussion). This molecule, which we named teixobactin, is an unusual depsipeptide which contains enduracididine, methylphenylalanine, and four D-amino acids. The biosynthetic gene cluster (GenBank accession number KP006601) was identified using a homology search (Supplementary Discussion). It consists of two large non-ribosomal peptide synthetase (NRPS)-coding genes, which we named txo1 and txo2, respectively (Fig. 1). In accordance with the co-linearity rule, 11 modules are encoded. The in silico predicted adenylation domain specificity perfectly matches the amino acid order of teixobactin (Fig. 1), and allowed us to predict the biosynthetic pathway (Extended Data Fig. 5).

Fluke i6000s Flex AC Current Probe 说明书

®i6000s FlexAC Current ProbeHoja de instrucciones IntroducciónLas sondas de corriente de CA i6000s 24 Flex e i6000s 36 Flex (en adelante, “las sondas”) se utilizan con osciloscopios,multímetros digitales, grabadoras o registradores de datos. Las sondas pueden usarse para medir corriente de CA hasta 6000 A.La cabeza de medición flexible permite realizar mediciones de corriente en conductores difíciles de alcanzar o que resultan inaccesibles usando las típicas sondas de pinzas.Las sondas proporcionan una salida de baja tensión (3 V CA)que es proporcional a la corriente que se está midiendo. Las sondas proporcionan lecturas directas de escala completa para60 A, 600 A y 6000 A.SímbolosLa tabla siguiente muestra los símbolos usados en el producto oen este manual.Símbolo Descripción ~No se deshaga de este producto como un residuonormal utilizando los servicios municipales. Visite el sitioWeb de Fluke para conocer información sobre elreciclado.W Información importante. Consulte el manual.X Voltaje peligroso. Peligro de descarga eléctrica.T Aislamiento doble y reforzado.-No aplicar alrededor de o quitar de los conductoresGARGADOS PELIGROSOS.P Cumple las normas estándar europeas.>Se adapta a las normas de Underwriters’ Laboratory, Inc.;Cumple con las normas australianas.PN 2842359June 2007 (Spanish)©2007 Fluke Corporation. All rights reserved. Printed in China.Instrucciones de seguridadEn esta hoja de instrucciones, una Advertencia identifica las situaciones y acciones que suponen peligro para el usuario. Una Precaución identifica situaciones y acciones que pueden causar daños en el calibrador o en los instrumentos de prueba.WX AdvertenciaPara evitar descargas eléctricas o lesiones físicas:•Si las sondas se utilizan de una manera noespecificada en estas instrucciones de uso,podría verse afectada la protección provista porlas sondas.•Utilice las sondas solamente si está calificadopara hacerlo.•Tenga cuidado durante la instalación y el uso delas sondas; puede haber altas tensiones ycorrientes presentes en el circuito bajo prueba.•Proteja las sondas contra el agua y la humedad.•Use ropa de protección y guantes, según seanecesario.•No instale este producto en conductorescargados. Desenergice siempre el circuito enpruebas antes de instalar la cabeza de mediciónflexible.•Inspeccione siempre la unidad electrónica, elcable de conexión y la cabeza de mediciónflexible para comprobar si tienen daños antes deusar la sonda.•No utilice la sonda si está dañada.•Conecte siempre la sonda a la pantalla antes deinstalar la cabeza de medición flexible.•Nunca cambie las baterías con la cabeza demedición instalada en el conductor.•Nunca conecte o desconecte la fuente dealimentación externa con la cabeza de medicióninstalada en un conductor.•Use sólo originales o los accesoriosespecificados.•Utilice la sonda de corriente sólo siguiendo lasespecificaciones de las instrucciones defuncionamiento; en caso contrario, puede quelas funciones de seguridad dela sonda de corriente no le protejan.•Siga los códigos de seguridad localesy nacionales. En lugares donde hayaconductores energizados expuestos,se debe utilizar equipo de protección individualpara evitar lesiones por descargas eléctricas yarcos.•Un equipo CAT III está diseñado para protegercontra corrientes transitorias en los equiposempleados en instalaciones de equipo fijo, talescomo los paneles de distribución, alimentadores,circuitos de ramales cortos y los sistemas deiluminación de grandes edificios.EspecificacionesCaracterísticas eléctricasRangos de corriente 60 A / 600 A / 6000 A CA rms Sensibilidad de salida(acoplada a CA) 50 mV / 5 mV / 0,5 mV por A Impedancia de carga 100 kΩ como mínimo Exactitud (a 25 ºC) ± 1 % del rango (45 Hz – 65 Hz) Linealidad(10 % a 100 % del rango) ± 0,2 % de la lecturaRuido 8 mV CA rms (60 A)2 mV CA rms (600/6000 A) Rango de frecuencia 10 Hz a 50 kHz (-3 dB)Error de fase <± 1° (45 Hz – 65 Hz),± 10° (a 20 kHz)Sensibilidad de laposición(con cable > 25 mmdesde el acoplamiento)± 2 % del rangoCampo externo(con cable > 200 mmdesde el cabezal)± 1 % del rangoAlimentación de energía 2 x AA MN 1500 LR6 alcalina 400 horas, indicador de batería con poca carga o suministroeléctrico externo dedicadoCoeficiente detemperatura ± 0,08 % de la lectura por °C Voltaje de trabajo 600 V CA rms o CCCaracterísticas generalesLongitud del cable del cabezal (con aislamiento doble) 610 mm (24 pulg.) i6000s Flex-24 915 mm (36 pulg.) i6000s Flex-36Diámetro delcable 14,3 mm (0,562 pulg)Radio de flexión 38,1 mm (1,5 pulg)Longitud del cable 2 m de largo (78,7 pulg) (cabezal acomponentes electrónicos)Conexión de salida 0,5 m de cable terminado con conector BNC de seguridad suministrado con un adaptador de enchufe de seguridad de 4 mmTemperatura de operación -20 °C a +90 °C (-4 °F a 194 °F) (cabezal)-20 °C a +85 °C (-4 °F a 185 °F) (componentes electrónicos)Temperatura de almacenamiento -40 °C a +105 °C (-40 °F a 221 °F) (cabezal)-20 °C a +85 °C (-4 °F a 185 °F) (componentes electrónicos)Humedad deoperación 15 % a 85 % (sin condensación)Peso 180 g (cabezal), 190 g (componenteselectrónicos)Normas de seguridadEN 61010-1: 2001EN 61010-2-032: 2002EN 61010-031: 2002600 V rms Categoría III, Grado de contaminación 2.El uso de las sondas en conductores no aislados está limitado a 600 V CA rms o CC y a frecuencias por debajo de 1 kHz. Normas EMCEN 61326: 1998 +A1, A2 y A3Instrucciones de funcionamientoA Cabeza de mediciónB Acoplamiento de la cabeza de mediciónC Cable de salida de la cabezaD CajaE Encendido/Selector de rangoF Indicador de batería bajaG Indicador de encendidoH Cable de salidaI Conector BNC de seguridadJ Entrada de la fuente de alimentación externaInstalación de las bateríasXW AdvertenciaPara evitar descargas eléctricas o lesiones físicas:•Retire la sonda de los circuitos energizados antes de abrir la puerta de la batería.•Nunca ponga en funcionamiento la unidad sin lacubierta de la batería instalada.La sonda requiere dos baterías alcalinas AA/MN1500/LR6 para su correcto funcionamiento. Se accede al compartimiento de las baterías desde el extremo posterior de la caja de componentes electrónicos.Las baterías deben reemplazarse cuando el LED esté encendido de forma continua o cuando no se encienda. Compruebe que la sonda esté siempre alejada de los conductores cargados con corriente y que la salida esté desconectada de otros equipos. Para instalar la batería:1.Utilice una moneda o herramienta similar para girar lacubierta de la batería (¼ de vuelta) hasta que el puntoquede alineado con el símbolo de desbloqueo.2.Retire la cubierta de la batería.3.Instale las baterías asegurándose de que la polaridades correcta.4.Reemplace la cubierta de la batería y gire el cierrehasta que el punto se alinee con el símbolo de cierre. Fuente de alimentación externaHay disponible una fuente de alimentación externa opcional clase II en Fluke. La fuente de alimentación se ha diseñado para asegurar que la sonda cumple las normas de seguridad especificadas. Se recomienda no usar una fuente dealimentación de otro proveedor.XW AdvertenciaPara evitar las descargas eléctricas o las lesiones, retire lasonda y todas las demás conexiones de los circuitosenergizados antes de conectar el suministro eléctricoexterno al instrumento.Medición de corrienteXW Advertencia•Para evitar descargas eléctricas o lesiones, lea lasinstrucciones de seguridad antes de manejar esteproducto•Compruebe que los conductores que se van acomprobar están desenergizadosPara medir corriente:1.Conecte la salida de los sistemas electrónicos a laentrada de un osciloscopio u otro dispositivo degrabación de datos.XW AdvertenciaPara evitar descargas eléctricas o lesiones, las sondas decorriente flexibles no deben usarse en conductores quetengan un potencial mayor de 600 V.2.Enrolle la cabeza de medición flexible alrededor delconductor que vaya a comprobar de forma que quedeperfectamente acoplada.3.Energice el circuito en pruebas.4.Para obtener una medición más exacta, centre lacabeza flexible alrededor del conductor.5.Coloque el acoplamiento lejos de losconductores cercanos.WX AdvertenciaPara evitar descargas eléctricas o lesiones:•No utilice las sondas de corriente flexibles para medir conductores sin aislamiento a menos que estéusando vestimenta de protección apropiada para eltrabajo a alta tensión.•Utilice siempre el equipo apropiado de protecciónpersonal. Cuando se instale en conductores o barrasde distribución sin aislante, el producto debe estardentro de una caja adecuada.FuncionamientoPara activar la unidad, mueva el conmutador de la posición de apagado al rango de medición que requiera. Si se desconoce el valor de la corriente que se está midiendo, seleccione el rango de corriente de 6000 A y luego reduzca según corresponda. Estado de la bateríaEl estado de la batería aparece indicado mediante un LED en la parte delantera de las sondas. Este LED parpadea una vez cuando se enciende la unidad. La duración de cada parpadeo aumentará a medida que se reduce la duración de la batería. Un encendido momentáneo del LED indica que las baterías están en buen estado de carga. Si se enciende de forma continua, indica que la batería está descargada y requiere un cambiocuanto antes. Si no se enciende, indica que las baterías están gastadas y requieren un cambio inmediatamente. MantenimientoWX AdvertenciaPara evitar descargas eléctricas o lesiones, no utilice lasonda si está dañada.•No utilice las sondas si están dañadas.•Siempre inspeccione la unidad de componenteselectrónicos, el cable de conexión y el cabezal demedición flexible en busca de daños, antes deusarlos.•Para evitar las descargas eléctricas, mantenga lassondas limpias y libres de contaminación desuperficie.Utilice alcohol isopropílico para limpiar la unidad de control y el cabezal de medición. Asegúrese de que el cabezal de medición flexible, el cable de conexión y la caja de componenteselectrónicos estén secos antes de continuar usándolos. GARANTÍA LIMITADA Y LIMITACIÓN DE RESPONSABILIDADEste producto de Fluke estará libre de defectos en los materiales y en la mano de obra durante un año a partir de la fecha de adquisición. Esta garantía no incluye fusibles, baterías desechables ni daños por accidente, negligencia, mala utilización, modificación, contaminación o condiciones anómalas de funcionamiento o manipulación. Los distribuidores no están autorizados a extender ninguna otra garantía en nombre de Fluke. Para obtener servicio de garantía, póngase en contacto con el centro de servicio autorizado por Fluke más cercano para obtener información sobre autorización de devoluciones, y envíe el producto a dicho centro de servicio con una descripción del problema.ESTA GARANTÍA CONSTITUYE SU ÚNICO RESARCIMIENTO. NO SE EXTIENDE NINGUNA OTRA GARANTÍA, EXPRESA O IMPLÍCITA, TAL COMO LA GARANTÍA DE IDONEIDAD PARA UN PROPÓSITO DETERMINADO. FLUKE NO SE RESPONSA-BILIZA POR PÉRDIDAS NI DAÑOS ESPECIALES, INDIRECTOS, IMPREVISTOS O CONTINGENTES QUE SURJAN DE CUALQUIER TIPO DE CAUSA O TEORÍA. Debido a que ciertos estados o países no permiten la exclusión o limitación de una garantía implícita o de los daños contingentes o resultantes,esta limitación de responsabilidad puede no regir para usted.Fluke CorporationP.O. Box 9090 Everett, WA 98206-9090 EE.UU. Fluke Europe B.V. P.O. Box 1186 5602 BD Eindhoven Países Bajos。

MedBio_84371-65-3_Mifepristone资料说明

2、Mifepristone技术资料：
体外研究
第一种竞争性黄体酮拮抗剂米非司酮的发现刺激了对更有效和更具选择性的抗孕激素的强烈追求[1]。在10μM暴露于米非司酮4天后评估细胞生长，浓度接近人类可达到的血浆浓度。当与米非司酮联合给予HeLa细胞时，顺铂的抗增殖作用增强。在HeLa细胞中，顺铂与米非司酮组合的IC50比单独顺铂（34.2μM）低（14.2μM），差异大约为2.5倍。用米非司酮治疗后，细胞内顺铂在HeLa细胞中的积累量增加了2倍，显着差异（p = 0.009），与单独的顺铂相比，从0.79到1.52μg/ mg蛋白质[2]。
体内研究
宫颈肿瘤异种移植模型仅用顺铂治疗，与对照组相比存在肿瘤生长抑制。然而，在所用剂量下，顺铂和米非司酮联合使用时肿瘤体重减轻更为显着（p <0.05），与研究结束时单独治疗相比，减少了约50％[2]。对成年雄性Sprague-Dawley大鼠进行4天狂欢样EtOH给药方案（每8小时3至5g / kg / ig，设计产生<300mg / dL的峰值血液EtOH水平（BELs））。动物亚组接受皮下注射米非司酮（花生油中20或40 mg / kg）。尽管米非司酮对未经过EtOH治疗的动物的行为没有显着改变，但米非司酮（40 mg / kg）的预处理显着降低了EtOH戒断的严重程度。饮食和药物之间的显着相互作用，F（5,55）= 3.92，p <0.05，使得接受载体的EtOH处理的动物或20mg / kg米非司酮显示出比接受该物质的未接受EtOH的动物显着更多的EtOH戒断迹象。药物治疗。重要的是，用40 mg / kg米非司酮治疗可以剂量依赖的方式显着降低EtOH戒断的严重程度[3]。
3、Mifepristone同类产品列表：
品牌
货号

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Product Name:
Mifepristone CAS No.:
84371-65-3Cat. No.:
HY-13683Product Data Sheet
MWt:
429.59Formula:
C29H35NO2Purity :>98%
Solubility:
DMSO 86 mg/mL; Water <1y Mechanisms:
Biological Activity:
Mifepristone(RU 38486;RU486)is a progesterone receptor antagonist(IC50=02nM)used as an
Pathways:Others; Target:Progesterone Receptor g ;mg/mL; Ethanol 79 mg/mL
Mifepristone(RU-38486; RU486) is a progesterone receptor antagonist(IC50= 0.2 nM) used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive.
IC50 Value: 0.2 nM (Progesterone receptor); 2.6 nM (Glucocorticoid receptor) [1]
Target: Progesterone receptor Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone
receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. Mifepristone is also a powerful glucocorticoid receptor antagonist,
and has occasionally been used in refractory Cushing's Syndrome.in vitro: Mifepristone had no effect onHeLa cell proliferation inhibition rate during 24 and 48 hours (p References:
[1]. Jiang W, Allan G, Fiordeliso JJ, New progesterone receptor antagonists: phosphorus-containing
11beta-aryl-substituted steroids. Bioorg Med Chem. 2006 Oct 1;14(19):6726-32. Epub 2006 Jun 27.[2]. Li C, Ye H. Mifepristone sensitizing cisplatin for cervical adenocarcinoma HeLa cell sensitivity to p p g (p > 0.05). Mifepristone at low concentrations (< or = 10 micromol/l) combined withcisplatin can significantly enhanc...
chemotherapy and itsmechanism. Eur J Gynaecol Oncol. 2013;34(2):142-7.[3]. Jurado R, Lopez-Flores A, Alvarez A, Cisplatin cytotoxicity is increased by mifepristone in
cervical carcinoma: an in vitro and in vivo study. Oncol Rep. 2009 Nov;22(5):1237-45.[4]. Sharrett-Field L, Butler TR, Berry JN, Mifepristone Pretreatment Reduces Ethanol Withdrawal
Severity In Vivo. Alcohol Clin Exp Res. 2013 Mar 25.Caution: Not fully tested. For research purposes only
Medchemexpress LLC
18 W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S A
E m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。