Tolazoline_hydrochloride_HNMR_16408_MedChemExpress
分子结构图
1、盐酸醋丁洛尔（Acebutolol Hydrochloride）化学名：N-[3-乙酰基-4-[2羟基-3-[（1-甲基乙基）氨基]丙氧基]苯基]丁酰胺盐酸盐；英文名：N-[3-Acetyl-4-[2-hydroxy-3-[（l-methylethyl）amino]Propoxy ]phenyl ]butanamide hydrochloride分子式：C18H28N2O4·HCl分子量：371．891\对丁酰胺基苯酚3\对丁酰胺基苯乙酮5\2-羟基-5-丁酰胺基苯乙酮8\2-环氧乙基甲氧基-5-丁酰胺基-苯乙酮10\醋丁洛尔2、醋谷胺铝（Aceglutamide Aluminum）化学名：N2-乙酰-L-谷氨酰胺四羟基三铝英文名：N2-Acetyl-L-glutamine aluminium complcx分子式：C35H59Al3N10O24分子量：1084．861\N-乙酰谷酰胺3、阿克他利(Actarit)化学名：4-乙酰胺基苯乙酸英文名：4-(Acetylamino)benzeneacetic acid 分子式：C10H11NO3分子量：193．211\4-氨基苯乙酸2\4-氨基苯乙酸乙酯3\4-乙酰胺基苯乙酸乙酯4\4-乙酰胺基苯乙酸，阿克他利4、阿昔洛韦（Acyclovir）化学名：2-氨基1,9-二氢-9-[(2-羟基乙氧基)甲基]-6H-嘌呤-6-酮英文名：2-amino-l,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one 分子式：C8H11N5O3分子量：225．2１＼鸟嘌呤３＼９-(2-苯甲酰氧基乙氧基甲基) 鸟嘌呤４＼阿昔洛韦阿苯达唑(Albendazole)化学名：［５-(丙硫基)-l H-2-苯并咪唑基］氨基甲酸甲酯英文名：[5-(propylthio)-l H-benzimidazol-2-yl]carbamic acid methyl ester 分子式：C12H15O2S分子量：265．34１＼３-氯-6-硝基乙酰苯胺３＼2-硝基-5-丙硫基苯胺４＼4-丙硫基-邻苯二胺5＼2-氨基-5-丙硫基苯并咪唑===================================6、阿拉普拉(Alacepril)化学名：(S)-N-[l-[3-(乙酰硫基)-2-甲基丙酰]-L-脯氨酰]-L-苯丙氨酸英文名：(S)N-[l-[3-(Acetylthio)-2-methyl-l-oxopropyl]-L-prolyl]-L-phenylalanine 分子式：C20H26N2O5S分子量：406．501\l-(D-3-乙酰硫基-2-甲基丙酰)-L-脯氨酸2\L-苯丙氨酸-叔丁酯盐酸盐4\l-(D-3-乙酰硫基-2-甲基丙酰)-L-脯氨酰-L-苯丙氨酸-叔丁酯6\阿拉普拉7、阿氯芬酸(Alclofenac)化学名：3-氯-4-(2-丙烯氧)苯乙酸英文名：3-Chloro-4-(2-propenyloxy)benzeneacetic acid分子式：C11H11O3Cl分子量：2261\邻氯苯酚3\邻氯烯丙氧苯5\2-氯-4-氯甲基-烯丙氧苯6\3-氯-4-烯丙氧苯乙腈7\3-氯-4-(2-丙烯氧)苯乙酸,阿氯芬酸8、阿法骨化醇(Alfacalcidol)化学名：（1α，3β，5Z，7E）-9，10-并环胆甾-5，7，10（19）三烯-1，3-二醇英文名：（1α，3β，5Z，7E）-9，10-Secocholesta-5,7,10(19)-triene-1,3-diol分子式：C27H44O2分子量：400641\胆固醇2\ 3β-羟基-5α-胆甾烷-6-酮3\ 6-亚乙二氧基-5α-胆甾烷-3β-醇4\ 6-亚乙二氧基-胆甾烷-3 –酮4\\ 2α-溴-6-亚乙二氧基-胆甾烷-3-酮5\ 6-亚乙二氧基-l-胆甾烯-3-酮6\6-亚乙二氧基-lα ,2α–环氧胆甾烷-3-酮7\6,6-亚乙二氧基-胆甾烷-lα ,3(α,β)-双醇8\5α-胆甾烷-6-酮-lα,3(α,β)-双醇8\5α-胆甾烷-lα,3(α,β)-二乙酰氧-6-酮9\5α-胆甾烷-lα,3β-二乙酰氧-6-醇10\ lα,3β-二乙酰氧胆固醇10\\lα,3β-二乙酰氧-7-溴-胆固醇11\ lα,3β-二乙酰氧-胆甾-5,7-二烯12\ lα,3β-二乙酰氧-前维生素D313 lα,3β-二乙酰氧-维生素D314\ lα-羟维生素D39、阿明洛芬(Alminoprofen)化学名：2-[对-(2-甲基烯丙基)-氨基苯基]丙酸；α-甲基-4-[（2-甲基-2-丙烯基）氨基]苯乙酸英文名：α-Methyl-4-[(2-methyl-2-propenyl)amino]benzeneacetic acid分子式：C13H17NO2分子量：219．291\2-（对硝基苯基）丙酸甲酯2\2-（对氨基苯基）丙酸甲酯4\2-[对（2-甲基烯丙基）氨基苯基]丙酸甲酯盐酸盐5\阿明洛芬10阿普唑仑（Alprazolam）化学名：8-氯-l-甲基-6-苯基-4H-[1,2,4]三唑并[4,3-α][1,4]苯并二氮杂草英文名：8-Chloro-l-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-α][1,4]benzodiazepine 分子式：C17H13ClN4分子量：308．771\ (2-氨基础理论-氯苯基)-苯甲酮2\ 甘氨酸乙酯盐酸盐3\7-氯-5-苯基-2-氧代-2,3-二氢-l H-1,4苯并二氨杂卓5\7-氯-5-苯基-2-硫代-2,3-二氢-l H-1,4苯并二氮杂卓7\ 2-(2-乙酰肼基)-7-氯-5-苯基-3 H-1,4苯并二氮杂卓8\阿普唑仑11盐酸阿普洛尔(Alprenolo Hydrochloride)化学名：1-[(1-甲基乙基)氨基]-3-[2-(2-丙烯基)苯氧基]-2-丙醇盐酸盐英文名：1-[(1-Methylethyl)amino]-3-[2-(2-propenyl)phenoxy]-2-propanol hydrochloride 分子式：C15H23O2N·HCl分子量：285．821\ 2-丙烯苯酚2\ 表氯醇3\ 1-(邻丙烯苯氧)-2,3-环氧丙烷5\1-(邻丙烯苯氧)-2-羟-3-异丙氨-丙烷,阿普洛尔12盐酸氨溴索(Ambroxol Hydrochloride)化学名：4-[[(2-氨基-3,5-二溴苯基)甲基]氨基]环已醇盐酸盐英文名：4-[[(2-Amino-3,5-dibromophenyl)methyl]amino]cyclohexanol hydrochloride 分子式：C13H18Br2N2O·HCl分子量：414．571\ 2-氨基-3,5-二溴-N-(羟基环已基)苯甲酰胺2\ 4-(2-氨基-3,5-二溴苄胺基)-环已醇3\ 盐酸氨溴索13氨芬酸钠(Amfenac Sodium)化学名：2-氨基-3-苯甲酰苯乙酸钠二水合物英文名：2-Amino-3-benzoylbenzeneacetic acid sadinmsalt dihydrate 分子式：C15H2NO3Na·2H2O分子量：277．181\ 1-氨基-1,3-二氢吲哚-2-酮2\苯基丙酮3\1-(2-甲基苯亚乙基亚氨基)1,3-二氢吲哚-2-酮4\ 2-(2-甲基-3-苯基吲哚-7-基)乙酸乙酯5\ 2-乙酰胺基-3-苯甲酰苯乙酸乙酯6\ 7-苯甲酰1,3-二氢吲哚-2-酮7\ 2-氨基-3-苯酰苯乙酸8\氨芬酸钠14苯磺酸氨氨地平(Amlodipine Besilate)化学名：(±)-2-(2-氨基乙氧甲基)-4-(2-氯苯基)-1,4-二氢-6-甲基-3,5-吡啶二羧酸-3-乙酯-5-甲酯苯磺酸盐英文名：(±)-2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxy lic acid-3-ethyl-5-methylester Benzenesulfonate分子式：C20H25ClN2O5·C6H5SO3H分子量：567．06１、２-氯苯甲醛２、乙酰乙酸甲酯３、2-（2-氯苄叉基）乙酰乙酸甲酯４、4-氯-3-氧代丁酸乙酯，氯乙酰乙酸乙酯５、2-叠氮乙醇６、2-叠氮乙氧基乙酰乙酸乙酯７、2-[（2-叠氮乙氧基）甲基]-4-（2-氯苯基）-3-乙氧羰基-5-甲氧羰基-6-甲基-1，4二氢吡啶氨氯地平15盐酸氨磺洛尔（Amosulalol Hydrochloride）化学名：5-(±)-5-[1-羟基-2-[[2-(2-甲氧基苯氧基)乙基]氨基]乙基]-2-甲基苯磺酰胺盐酸盐英文名：5-(±)-5-[1-Hydroxy-2-[[2-(2-methoxyphenoxy)ethyl]amino]ethyl]-2-methylbenzenesalfonamide hydrochloride分子式：C18H24N2O5S·HCl分子量：416．931\ 5-溴乙酰-2-甲基苯磺酰胺2\ N-[2(2-甲氧基)苯氧基乙基]苄胺3\ 5-[N-苯甲基-N-[[2-(2-甲氧基)苯氧基]乙基]氨基]乙酰-2-甲基苯磺酰胺4\ 5-[1-羟基-2-[[N-苯甲基-N-2-(2-甲氧基)苯氧基乙基]氨基]乙基]-2-甲基苯磺酰胺5\5-[1-羟基-2-[[2-(2-甲氧基苯氧基)乙基]氨基]乙基]-2-甲基苯磺酰胺盐酸盐,盐酸氨磺洛尔16阿莫西林(Amoxicillin)化学名：[2S-[2α,5α,6β(S﹡)]]-6-[[氨基(4-羟苯基)乙酰基]氨基]-3,3-二甲基-7-氧代-4-硫-1-氮杂二环[3,2,0]庚烷-2-羧酸英文名：[2S-[2α,5α,6β(S ﹡)]]-6-[[Amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3,2,0]h eptane-2-carboxylic acid分子式：C16H19N3O5·3H2O分子量：419．411\ ( ±)苄氧甲酰氨-4-羟苯乙酸2\ (－)苄氧甲酰氨-对羟苯乙酸3\ 6-氨基-青霉烷酸4\6-[(－)-苄氧甲酰氨-对羟基苯乙酰胺]青霉烷酸5\ 阿莫西林17氨苄西林(Ampicillin)化学名：[2S-[2α,5α,6β(S﹡)]]-6-[(氨基苯乙酰)氨基]-3,3-二甲基7-氧代-4-硫杂-1-氮杂二环[3,2,0]庚烷-2-羧酸英文名：[2S-[2α,5α,6β(S ﹡)]]-6-[(Aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3,2,0]heptane-2-car boxylic acid分子式：C16H19N3O4S分子量：．349．421\D(－)-α-氨基-α-苯乙酸2\ 氯甲酸苄酯3\ D(－)-苄氧基甲酰氨基-α-苯乙酸4\ 氯甲酸乙酯5\[3]和[4]的混合酸无水物6\ 6-氨基青霉烷酸7\ 6-[D(－)-α-(苄氧基甲酰氨基)苯乙酰氨]青霉烷酸8\氨苄西林18、氨力农（Amrinone）化学名：5-氨基-(3,4′-双吡啶)-6(1H)-酮英文名：5-Amino-(3,4′-bipyridin)-6(1H)-one 分子式：C10H9N3O分子量：187．201\ 4-甲基吡啶2\ 2-(4-吡啶基)-3-二甲胺基丙烯醛3\ 氰基乙酰胺4\ 3-氰基-5-(-4-吡啶基)-2(1H)-吡啶酮5\ 3-氨甲酰基-5-(-4-吡啶基)-2(1H)-吡啶酮19\阿加曲班(Argatroban)化学名：1-[5-[(氨基亚氨基甲基)氨基]-1-氧代-2[[(1,2,3,4四氢-3-甲基-8-喹啉基)磺酰]氨基]戊基]-4-甲基-2-哌啶羧酸英文名：1-[5-[(Aminoiminomethyl)amino]-1-oxo-2-[[(1,2,3,4-tetrahydro-3-methyl-8-quinolinyl)sulfonyl]a mino]pentyl]-4-methyl-2-piperidinecarboxylic acid分子式：C23H36N6O5S分子量：508．6420盐酸阿罗洛尔(Arotinolol Hydrochloride)化学名：(±)-5-[2-[[3-[(1,1-二甲基乙基)氨基]-2-羟基丙基]硫]-4-噻唑基]-2-噻吩酰胺盐酸盐英文名：(±)-5-[2-[[3-[(1,1-Dimethylethyl)amino]-2-hydroxypropyl]thio]-4-thiazolyl]-2-thiophenecarboxa mide hydrochloride分子式：C15H21N3O2S3·HCl分子量：．408．11\ 5-乙酰基噻吩-2-羧酸2\ 5-乙酰噻吩-2-甲酰氨3\ 5-溴乙酰噻吩-2-甲酰氨4\ 二硫代氨基甲酸铵5\ 5-(2-巯基4-噻唑基)-2-噻吩甲酰氨7\ 5-[2-(3’-叔丁基氨基-2’-羟基丙基硫)-4-噻唑基]-2-噻吩甲酰氨8\ 盐酸阿罗洛尔21阿司咪唑(Astemizole)化学名：1-[(4-氟苯基)甲基]-N-[1-[2-(4-甲氧苯基)乙基]-4-哌啶基]-1H-2-苯并唑咪基胺英文名：1-[(4-Fluorophenyl)methyl] -N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl] -1H-benzimidazol-2-amine分子式：C28H31FN4O分子量：．458．251\ 1-异硫氰基-2-硝基苯酯2\ 4-氨基-1-哌啶甲酸乙酯3\ N-(2-硝基苯基)-N’-(1-乙氧甲酰-4-哌啶基)硫脲4\ N-(2-氨基苯基)-N’-(1-乙氧甲酰-4-哌啶基)硫脲5\ 2-(1-乙氧甲酰-4-哌啶基氨基)苯并咪唑6\ 4-氟苄基氯7\1-(4-氟苄基)-2-(1-乙氧甲酰-4-哌啶基氨基)苯并咪唑8\1-(4-氟苄基)-2-(4-哌啶基氨基)苯并咪唑9\甲磺酸对甲氧苯基乙酯10 阿司咪唑22阿替洛尔(Atenolol)化学名：4[2-羟基-3-[(1-甲基乙基)氨基]丙氧基]苯乙酰胺英文名：4-[2-Hydroxy-3-[(1-methylethyl)amino]propoxy]benzeneacetamide 分子式：C14H22N2O3分子量：266．341\ 2-(4-环氧乙烷基甲氧苯基)-乙酰胺2\ 异丙胺3\1-对氨基甲酰甲基苯氧基-3-异丙胺基-2-丙醇,阿替洛尔23盐酸阿扎司琼(Azasetron Hydrochloride)化学名：（±）-N-1-氮杂二环[2,2,2]-3-辛基-6-氯-3,4-二氢-4-甲基-3-氧代-2H-1,4-苯并噁嗪-8-甲酰胺盐酸盐英文名：（±）-N-1-Azabicyclo[2,2,2]oct-3-yl-6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carb oxamide hydrochloride分子式：C17H20ClN3O3·HCl分子量：368．281\ 5-氯-2-羟基苯甲酸甲酯2\ 5-氯-2-羟基-3-硝基苯甲酸甲酯3\ 5-氯-2-羟基-3-氨基苯甲酸甲酯5\氯乙酰氯6\ 6-氯-4-甲基-3-氧代-3，4-二氢-2H-1，4-苯并噁嗪-8-甲酸甲酯7\ 6-氯-4-甲基-3-氧代-3，4-二氢-2H-1，4-苯并噁嗪-8-甲酸8\ 6-氯-4-甲基-3-氧代-3，4-二氢-2H-1，4-苯并噁嗪-8-甲酰氯9\ 1-氮杂-3-二环[2，2，2]辛基胺10\ 盐酸阿扎司琼24盐酸氮卓斯丁（Azelastine Hydrochloride）化学名：4-[(4-氯苯基)甲基]-2-(六氢-1-甲基-1H-4-氮杂卓基)-1(2H)-酞嗪酮盐酸盐英文名：4-[(4-Chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinonehydroc hloride分子式：C22H25N3Cl2O分子量：418．371、2-4氯苯乙酰酰基苯甲酸2、硫酸肼3、4-（4-氯苄基）-1（2H）-酞嗪酮2-（2-氯乙基）-N-甲基吡咯烷盐酸盐5、4-（4-氯苄基）-2[N-甲基全氢化氮杂卓基-（4）-]-1（2H）-酞嗪酮6、4-（4-氯苄基）-2-[N-甲基全氢化氮杂卓基-（4）-]-1-（2H）酞嗪酮盐酸盐，盐酸氮卓斯丁25奥（Azulene）化学名：环戊二烯并环庚三烯英文名：Cyclopentacycloheptene 分子式：C10H8分子量：128．161\ 1,6-己二酸2\ 6-羰基-壬二酸3\ 5-(2-乙酰基-1-环戊烯基)-戊酸4\ 2,3,5,6,7,8-六氢-1H–奥-4-酮5\ 八氢,奥-4-酮6\ 十氢奥-4-醇7\奥26盐酸巴氨西林(Bacampicillin Hydrochloride)化学名：[2S-[2α,5α,6β(S﹡)]]-6-[(氨基苯基乙酰)氨基]-3,3-二甲基-7-氧代4-硫杂-1-氮杂二环[3,2,0]庚烷-2-羧酸-1-[(乙氧羰基)氧基]乙酯盐酸盐英文名：[2S-[2α,5α,6β(S﹡)]]-6-[(Aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3,2,0]heptane-2-car boxylic acid 1-[(ethoxycarbonyl)oxy]ethyl ester hydrochloride分子式：C21H27N3O7S·HCl分子量：502．001\ 碳酸-1-氯乙酯乙酯3\碳酸-1-溴乙酯乙酯4\ 6-[(氨基苯基乙酰)氨基]-3,3-二甲基7-氧代号-硫杂志-氮杂二环[3,2,0]庚烷-2-羧酸5\ 乙酰乙酸甲酯6\ 6-[2-(甲氧羰基)-1-甲基乙烯基氨基苯基(乙酰)氨基]-3,3-二甲基-7-氧代-4-硫杂-1-氮杂二环[3,2,0]庚烷-2-羧酸7\ 盐酸巴氨西林27巴氯芬(Baclofen)化学名：β-(氨甲基)-4-氯苯丙酸英文名：β-(Aminomethyl)-4-chlorobenzenepropanoic acid分子式：C10H12ClNO2分子量：213．661\ 对氯肉桂酸乙酯2\ 硝基甲烷3\ β-硝甲基4-氯苯丙酸乙酯4\ 4-(对氯苯)-2-吡咯烷酮28苄达酸(Bendazac)化学名：[(1-苄基-1H-3-吲唑基)氧基]乙酸英文名：[(1-Phenylmethyl) -1H-indazol-3-yl]-oxy]-acetic acid 分子式：C16H14H2O3分子量：282．301\ 1-苄基-1H-3-吲唑醇钠2\ 氯乙晴3\ 1-苄-3-吲唑-氧乙腈4\ 苄达酸29盐酸苄丝肼(Benserazide Hydrochloride)化学名：DL-丝氨酸-2-[(2,3,4-三羟苯基)甲基]酰肼盐酸盐英文名：DL-Serine-2-[(2,3,4-trihydroxyphenyl)methyl]-hydrazidc hydrochloride 分子式：C10H15N3O5·HCL分子量：293．711\ DL-丝氨酰肼盐酸盐2\ 2,3,4-三羟苯甲醛3\ DL-丝氨酰-2-(2,3,4-三羟基亚苄基)酰肼盐酸盐4\ 盐酸苄丝肼30苯溴马隆(Benzbromarone)化学名：(3,5-二溴-4-羟基苯基)-(2-乙基-3-苯并呋喃)-甲酮英文名：(3,5-Dibromo-4-hydroxyphenyl)(2-ethyl-3-benzofuranyl)methanone 分子式：C17H12Br2O3分子量：424．091\ 水杨醛2\ 一氯丙酮3\2-乙酰苯并呋喃4\ 水合肼5\ 2-乙基苯并呋喃6\ 对甲氧基苯甲酰氯7\ 2-乙基3-茴香酰-苯井呋喃8\ 吡啶盐酸盐9\2-乙基地-3-(对-羟-苯甲酰)-苯并呋喃10\ 苯溴马隆31二丙酸倍他米松(Betamethasone Dipropionate)化学名：(11β,16β)-9-氟-11,17,21-三羟-16-甲基-孕甾-1,4-二烯-3,20-双酮-17,21-二丙酸酯英文名：(11β,16β)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione-17,21-dipropionate分子式：C28H37FO7分子量：504．591\ 9α-氟-11β,17α,21-三羟基-16β-甲基-5α-孕甾烷-3,20-二酮-21-乙酸酯3\ 11β三甲基硅烷氧基-9α-氟-17α,21-二羟基-16β-甲基-5α-孕甾烷-3,20-二酮-21-乙酸酯4\ 11β三甲基硅烷氧基-9α-氟-17α,21-二羟基-16β-甲基-5α-孕甾烷-3,20-二酮5\ 丙酸酐6\对甲苯磺酸7\11β三甲基硅烷氧基-9α-氟-17α,21-二羟基-16β-甲基-5α-孕甾烷-3,20-二酮-17,21-二丙酸酯8\ 2,3-二氯-5,6-二腈-苯醌(DDQ)9\ 11β三甲基硅烷氧-17α,21-二羟基-基-9α-氟-16β-甲基孕甾-1,4-二烯-3,20-二酮-17,21-二丙酸酯10\ 9α-氟-11β,17α,21-三羟基-16β-甲基孕甾-1,4-二烯-3,20-二酮-17,21-二丙酸酯, 二丙酸倍他米松32倍他米松磷酸钠(Betamethasone Sodium phosphate)化学名：9α-氟-11β,17α,21-三羟基-16β-甲基孕甾-1,4-二烯3,20-二酮-21-(二氢磷酸酯)二钠盐英文名：(11β,16β)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione-21-(dihydrogenph osphate)disodium salt分子式：C22H29FNaO8P分子量：494．431\ 3α-乙酰氧基-16-孕甾烯-11,20-二酮3\ 3α-乙酰氧基-16α,17α-亚甲偶氮孕甾-11,20-二酮4\ 3α-乙酰氧基-16-甲基-16-孕甾烯- 11,20-二酮6\ 16α,17α-环氧-3α-羟基-16β-甲基孕甾-11,20-二酮7\ 3α,17α-二羟基-16β-甲基孕甾- 11,20-二酮8\ 21-溴-3α,17α-二羟基-16β-甲基孕甾- 11,20-二酮10\ 3α,17α-21-三羟基-16β-甲基孕甾- 11,20-二酮-21-乙酸酯11\N-溴琥珀酰亚胺12\ 17α,21-二羟基-16β-甲基孕甾- 3,11,20-三酮-21-乙酸酯13\ 4-溴-17α,21-二羟基-16β-甲基孕甾-3, 11,20-三酮-21乙酸酯14\ 盐酸氨基脲15\ 17α,21-二羟基-16β-甲基-4-孕甾烯- 3,11,20-三酮-21-乙酸酯的-3-缩氨基脲16\ 17α,21-二羟基-16β-甲基-4-孕甾烯- 3,11,20-三酮-21-乙酸酯17\ 17α,21-二羟基-16β-甲基-4-孕甾烯- 3,11,20-三酮-21-乙酸酯的-3,20-二缩氨基脲19\11β,17α,21-三羟基-16β-甲基-4-孕甾烯- 3,,20-二酮的-3,20-二缩氨基脲20\ 11β,17α,21-三羟基-16β-甲基-4-孕甾烯- 3,20-二酮21\ 乙酐22\ 11β,17α,21-三羟基-16β-甲基-4-孕甾烯- 3,,20-二酮-21-乙酸酯23\ 甲磺酰氯24\ 17α,21-三羟基-16β-甲基-4,9(11)-孕甾二烯- 3,,20-二酮-21-乙酸酯25\ 9α-溴-11β,17α,21-三羟基-16β-甲基-4-孕甾烯- 3, 20-二酮-21-乙酸酯27\ 9β,11β-环氧- 17α,21-二羟基-16β-甲基-4-孕甾烯- 3, 20-二酮-21-乙酸酯28\ 9α-氟-11β,17α,21-三羟基-16β-甲基-4-孕甾烯- 3, 20-二酮-21-乙酸酯30\9α-氟-11β,17α,21-三羟基-16β-甲基-1,4-孕甾二烯- 3, 20-二酮-21-乙酸酯31\倍他米松32\ 9α-氟-11β,17α,21-三羟基-16β-甲基-4-孕甾烯- 3, 20-二酮-21-甲磺酸酯33\ 9α-氟-16β-甲基-11β,17α–二羟基- 3, 20-二氧代-21-碘-1,4-孕甾二烯34\ 9α-氟-16β-甲基11β,17α,21-三羟基- 3, 20-二氧代1,4-孕甾二烯-21-磷酸二氢酯35\倍他米松磷酸钠33\盐酸贝凡洛尔(Bevantolol Hydrochloride)化学名：1-[[2-(3,4-二甲氧基苯基)乙基]胺基]-3-(3-甲苯氧基)-2-丙醇盐酸盐英文名：1-[[2-(3,4-Dimethoxyphenyl)ethyl]amino]-3-(3-methylphenoxy)-2-propanol hydrochloride分子式：C20H27NO4·HCl分子量：381．901\ 3-甲基苯酚2\ 氯甲基环氧乙烷3\ 3-甲苯氧基环氧乙烷4\2-(3,4-二甲氧苯基)乙胺5\盐酸贝凡洛尔34\盐酸溴己新(Bromhexine Hydrochloride)化学名：2-氨基-3,5二溴-N-环已基- N-甲基苯甲铵盐酸盐英文名：2-Amino-3,5-dibromo-N-cyclohexyl-N-methylbenzenemethanamine hydrochloride 分子式：C14H21N2Br2Cl分子量：412．631\ 2-硝基溴苄2\ N-甲基环已胺3\ N-(2-硝基苄)- N-甲基环已胺5\ N-(2-氨基苄)- N-甲基环已胺6\盐酸溴已新35\溴哌利多(Bromperidol)化学名：4[4-(4-溴苯基)-4羟基-1-哌啶基]-1-(4-氟苯基)-1-丁酮英文名：4[4-(4-Bromophenyl)-4-hydroxy-1-piperidinyl]-1-(-4-fluorophenyl)-1-butanone 分子式：C21H23BrFNO2分子量：420．331\4-溴苯基溴化镁2\ 1-(乙氧羰基)-4-氧代哌啶3\ 1-(乙氧羰基)-4-羟基-4-(4-溴苯基)哌啶4\ 4-羟基-4-(4-溴苯基)哌啶5\ 1-(4-氯丁酰)-4氟苯6\ 溴哌利多36\溴替唑仑(Brotizolam)化学名：2-溴-4-(2-氯苯基)-9-甲基-6H-噻嗯并-[3,2-f ]-[1,2,4]-三唑并-[4,3-α]-[1,4]-二氮杂卓英文名：2-Bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno-[3,2-f ]-[1,2,4]-triazolo-[4,3-α]-[1,4]-diazepine 分子式：C22H19Br分子量：363．311\ 7-溴-5-(2-氯苯基)-1,3-二氢噻嗯-[2,3-e]-1,4-二氮杂卓-2-酮2\ 7-溴-5-(2-氯苯基)-1,3-二氢-[2,3-e]-噻嗯-1,4-二氮杂卓-2-硫酮3\ 7-溴-5-(2-氯苯基)-2-肼基-1,3-二氢-[2,3-e]- 噻嗯-1,4-二氮杂卓4\ 正乙酸二乙酯5\溴替唑仑37富马酸溴长春胺(Brovincamine Fumarate)化学名：(3α,14β,16α)-11-溴-14,15-二氢-14-羟基象牙烯宁-14-羧酸甲酯富马酸盐英文名：(3α,14β,16α)-11-Bromo-14-15-dihydro-14-hydroxyeburnamenine-14-carboxylic acid methylester fumarate分子式：C21H25BrN2O3·C4H4O4分子量：549．351\ (3α,14β,16α)-长春胺2\溴长春胺38布地奈德（Budesonide）化学名：(11β,16α)-16,17-[亚丁基双(氧)]-11,21-二羟基孕甾-1,4-二烯-3-20-二酮英文名：(11β,16α)-16,17-[Butylidenebis(oxy)]-11,21-dihydroxypregna-1,4-diene-3,20-dione分子式：C25H34O6分子量：430．551\ 16α-羟基泼尼松龙2\布地奈德39\盐酸布那唑嗪(Bunazosin Hydrochloride)化学名：1-(4-氨基-6,7-二甲氧基-2-喹唑啉基)-6-氢-4-(1-氧代丁基)-1H-1,4-二氮卓盐酸盐英文名：1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)hexahydro-4-(1-oxobutyl)-1H-1,4-diazepinehydrochlo ride分子式：C19H27N5O3·HCl分子量：409．931\ 2-氯-4-氨基-6,7-二甲氧基喹唑啉2\ N-甲酰高哌嗪3\ 2-(N-甲酰高哌嗪基)-4-氨基-6,7二甲氧基喹唑啉4\ 2-高哌嗪基-4-氨基-6,7-二甲氧基喹唑啉盐酸盐5\ n-丁酰氯6\ 盐酸布那唑嗪40盐酸布尼洛尔(Bunitrolol Hydrochloride)化学名：2-[3-[(1,1-二甲基乙基)氨基]-2羟基丙氧基]苄腈盐酸盐英文名：2-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]benzonitrile hydrochloride 分子式：C14H20ON2O2·HCl分子量：248．81\ 2-环氧乙烷甲氧基-苄腈3\盐酸布尼洛尔。
托马托花肽洒胶水产品说明说明书
SAFETY DATA SHEET1. IdentificationProduct identifierTomato Blossom Spray RTU Other means of identificationProduct code 32042Recommended use Agricutlural/ Horticultural Use- Foliar Fertilizer- Refer to product label Recommended restrictionsNone known.Manufacturer/Importer/Supplier/Distributor information Manufacturer Lawn and Garden Products, Inc.AddressPO Box 35000Company name Website Telephone Emergency Contact Number 1-559-994-9144Emergency phone numberCHEMTREC (24 hours):USA, Canada, Puerto Rico 1-800-424-3900E-mail Fresno, CA 937452. Hazard(s) identificationNot classified.Physical hazards Category 4Acute toxicity, oral Health hazardsCategory 2Skin corrosion/irritationCategory 2ASerious eye damage/eye irritationNot classified.Environmental hazards Not classified.OSHA defined hazardsLabel elementsSignal word WarningHazard statement Harmful if swallowed. Causes skin irritation. Causes serious eye irritation.Precautionary statementPreventionWash thoroughly after handling. Do not eat, drink or smoke when using this product. Wear protective gloves. Wear eye/face protection.ResponseIf swallowed: Call a poison center/doctor if you feel unwell. If on skin: Wash with plenty of water. If in eyes: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Specific treatment (see this label). Rinse mouth. If skin irritation occurs: Get medical advice/attention. If eye irritation persists: Get medical advice/attention. Take off contaminated clothing and wash before reuse.Storage Store away from incompatible materials.DisposalDispose of contents/container in accordance with local/regional/national/international regulations.Hazard(s) not otherwise classified (HNOC)None known.Supplemental information99.28% of the mixture consists of component(s) of unknown acute oral toxicity.3. Composition/information on ingredientsMixturesCAS number% Chemical name Common name and synonyms7664-38-2Phosphoric AcidOther components below reportable levels99.27692544710.7230745526*Designates that a specific chemical identity and/or percentage of composition has been withheld as a trade secret.4. First-aid measuresInhalation Move to fresh air. Call a physician if symptoms develop or persist.Skin contact Remove contaminated clothing. Wash with plenty of soap and water. If skin irritation occurs: Getmedical advice/attention. Wash contaminated clothing before reuse.Eye contact Immediately flush eyes with plenty of water for at least 15 minutes. Remove contact lenses, ifpresent and easy to do. Continue rinsing. Get medical attention if irritation develops and persists. Ingestion Rinse mouth. If vomiting occurs, keep head low so that stomach content doesn't get into the lungs.Get medical advice/attention if you feel unwell. Get medical attention if symptoms occur.Most importantsymptoms/effects, acute and delayed Symptoms may include stinging, tearing, redness, swelling, and blurred vision. May cause redness and pain. Severe eye irritation.Indication of immediate medical attention and special treatment needed Provide general supportive measures and treat symptomatically. Keep victim warm. Keep victim under observation. Symptoms may be delayed.General information Ensure that medical personnel are aware of the material(s) involved, and take precautions toprotect themselves. Show this safety data sheet to the doctor in attendance.5. Fire-fighting measuresSuitable extinguishing media Water fog. Foam. Dry chemical powder. Carbon dioxide (CO2).Unsuitable extinguishingmediaDo not use water jet as an extinguisher, as this will spread the fire.Specific hazards arising fromthe chemicalDuring fire, gases hazardous to health may be formed.Special protective equipmentand precautions for firefightersSelf-contained breathing apparatus and full protective clothing must be worn in case of fire.Fire-fightingequipment/instructionsMove containers from fire area if you can do so without risk.Specific methods Use standard firefighting procedures and consider the hazards of other involved materials. General fire hazards No unusual fire or explosion hazards noted.6. Accidental release measuresPersonal precautions, protective equipment and emergency procedures Keep unnecessary personnel away. Keep people away from and upwind of spill/leak. Wear appropriate protective equipment and clothing during clean-up. Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Ensure adequate ventilation. Local authorities should be advised if significant spillages cannot be contained. For personal protection, see section 8 of the SDS.Methods and materials for containment and cleaning up This product is miscible in water.Large Spills: Stop the flow of material, if this is without risk. Dike the spilled material, where this is possible. Cover with plastic sheet to prevent spreading. Absorb in vermiculite, dry sand or earth and place into containers. Following product recovery, flush area with water.Small Spills: Wipe up with absorbent material (e.g. cloth, fleece). Clean surface thoroughly to remove residual contamination.Never return spills to original containers for re-use. For waste disposal, see section 13 of the SDS.Environmental precautions Avoid discharge into drains, water courses or onto the ground.7. Handling and storagePrecautions for safe handling Do not taste or swallow. Avoid contact with eyes, skin, and clothing. Avoid contact with eyes. Avoidprolonged exposure. Provide adequate ventilation. Wear appropriate personal protectiveequipment. When using, do not eat, drink or smoke. Wash hands thoroughly after handling.Observe good industrial hygiene practices.Conditions for safe storage, including any incompatibilities Store in original tightly closed container. Keep container tightly closed. Store away from incompatible materials (see Section 10 of the SDS).8. Exposure controls/personal protectionOccupational exposure limitsUS. OSHA Table Z-1 Limits for Air Contaminants (29 CFR 1910.1000)Value Components TypePEL 1 mg/m3 Phosphoric Acid (CAS7664-38-2)US. ACGIH Threshold Limit ValuesValue Components TypeSTEL 3 mg/m3 Phosphoric Acid (CAS7664-38-2)TWA 1 mg/m3 US. NIOSH: Pocket Guide to Chemical HazardsValue Components TypeSTEL 3 mg/m3 Phosphoric Acid (CAS7664-38-2)TWA 1 mg/m3 Biological limit values No biological exposure limits noted for the ingredient(s).Appropriate engineering controls Good general ventilation (typically 10 air changes per hour) should be used. Ventilation rates should be matched to conditions. If applicable, use process enclosures, local exhaust ventilation, or other engineering controls to maintain airborne levels below recommended exposure limits. If exposure limits have not been established, maintain airborne levels to an acceptable level. Eye wash facilities and emergency shower must be available when handling this product.Individual protection measures, such as personal protective equipmentEye/face protection Face shield is recommended. Wear safety glasses with side shields (or goggles).Skin protectionHand protection Wear appropriate chemical resistant gloves.Other Wear appropriate chemical resistant clothing. Use of an impervious apron is recommended.Respiratory protection In case of insufficient ventilation, wear suitable respiratory equipment. Respiratory protection notrequired.Thermal hazards Wear appropriate thermal protective clothing, when necessary.General hygiene considerations Keep away from food and drink. Always observe good personal hygiene measures, such as washing after handling the material and before eating, drinking, and/or smoking. Routinely wash work clothing and protective equipment to remove contaminants.9. Physical and chemical properties Appearance Liquid.Physical state Liquid.Form Liquid.Color Colorless Odor Slight. Pungent Odor threshold Not available. pH 2.2Salt-Out / Crystallization Temp Not available. Melting point/freezing point Not available. Initial boiling point and boilingrangeNot available. Flash point Not available. Evaporation rate Not available. Flammability (solid, gas)Not available. Upper/lower flammability or explosive limits Flammability limit - lower(%)Not available.Flammability limit - upper(%)Not available.Explosive limit - lower (%)Not available.Explosive limit - upper (%)Not available.Vapor pressure 0.00001 hPa estimated Vapor density Not available.Relative density Not available.Solubility(ies)Solubility (water)Miscible Partition coefficient (n-octanol/water)Not available.Auto-ignition temperature Not available.Decomposition temperature Not available.ViscosityNot available.Other informationPercent volatile98.49 % estimated Pounds per gallon8.38 lb/gal typical10. Stability and reactivityReactivity The product is stable and non-reactive under normal conditions of use, storage and transport.Chemical stability Material is stable under normal conditions.Possibility of hazardous reactionsNo dangerous reaction known under conditions of normal use.Conditions to avoid Contact with incompatible materials.Incompatible materials Strong oxidizing agents.Hazardous decomposition productsNo hazardous decomposition products are known.11. Toxicological informationInformation on likely routes of exposureIngestionHarmful if swallowed.Inhalation Prolonged inhalation may be harmful.Skin contact Causes skin irritation.Eye contactCauses serious eye irritation.Symptoms related to thephysical, chemical andtoxicological characteristics Symptoms may include stinging, tearing, redness, swelling, and blurred vision. Skin irritation.Severe eye irritation. May cause redness and pain.Information on toxicological effectsAcute toxicity Harmful if swallowed. Not known.Test ResultsComponentsSpeciesPhosphoric Acid (CAS 7664-38-2)LD50Rabbit Dermal Acute 2740 mg/kg LD50RatOral 1530 mg/kg* Estimates for product may be based on additional component data not shown.Skin corrosion/irritation Causes skin irritation.Serious eye damage/eyeirritationCauses serious eye irritation.Respiratory or skin sensitizationRespiratory sensitizationNot available.Skin sensitizationThis product is not expected to cause skin sensitization.Germ cell mutagenicity No data available to indicate product or any components present at greater than 0.1% aremutagenic or genotoxic.Carcinogenicity This product is not considered to be a carcinogen by IARC, ACGIH, NTP, or OSHA.OSHA Specifically Regulated Substances (29 CFR 1910.1001-1050)Not listed.Reproductive toxicity This product is not expected to cause reproductive or developmental effects.Specific target organ toxicity -single exposureNot classified.Specific target organ toxicity -repeated exposureNot classified.Aspiration hazard Not available.Chronic effects Prolonged inhalation may be harmful.12. Ecological informationEcotoxicity The product is not classified as environmentally hazardous. However, this does not exclude thepossibility that large or frequent spills can have a harmful or damaging effect on the environment. Persistence and degradability No data is available on the degradability of this product.Bioaccumulative potential Not available.Mobility in soil No data available.Other adverse effects No other adverse environmental effects (e.g. ozone depletion, photochemical ozone creationpotential, endocrine disruption, global warming potential) are expected from this component. 13. Disposal considerationsDisposal instructions Collect and reclaim or dispose in sealed containers at licensed waste disposal site. Dispose ofcontents/container in accordance with local/regional/national/international regulations.Local disposal regulations Dispose in accordance with all applicable regulations.Hazardous waste code The waste code should be assigned in discussion between the user, the producer and the wastedisposal company.Waste from residues / unused products Dispose of in accordance with local regulations. Empty containers or liners may retain some product residues. This material and its container must be disposed of in a safe manner (see: Disposal instructions).Contaminated packaging Empty containers should be taken to an approved waste handling site for recycling or disposal.Since emptied containers may retain product residue, follow label warnings even after container isemptied.14. Transport informationDOTNot regulated as dangerous goods.IATANot regulated as dangerous goods.IMDGNot regulated as dangerous goods.15. Regulatory informationUS federal regulations This product is a "Hazardous Chemical" as defined by the OSHA Hazard CommunicationStandard, 29 CFR 1910.1200.All components are on the U.S. EPA TSCA Inventory List.This product is not known to be a "Hazardous Chemical" as defined by the OSHA HazardCommunication Standard, 29 CFR 1910.1200.TSCA Section 12(b) Export Notification (40 CFR 707, Subpt. D)Not regulated.CERCLA Hazardous Substance List (40 CFR 302.4)Phosphoric Acid (CAS 7664-38-2)Listed.SARA 304 Emergency release notificationNot regulated.OSHA Specifically Regulated Substances (29 CFR 1910.1001-1050)Not listed.Superfund Amendments and Reauthorization Act of 1986 (SARA)Hazard categories Immediate Hazard - YesDelayed Hazard - NoFire Hazard - NoPressure Hazard - NoReactivity Hazard - NoSARA 302 Extremely hazardous substanceNot listed.NoSARA 311/312 HazardouschemicalSARA 313 (TRI reporting)Not regulated.Other federal regulationsClean Air Act (CAA) Section 112 Hazardous Air Pollutants (HAPs) ListNot regulated.Clean Air Act (CAA) Section 112(r) Accidental Release Prevention (40 CFR 68.130)Not regulated.Not regulated.Safe Drinking Water Act(SDWA)US state regulationsUS. Massachusetts RTK - Substance ListPhosphoric Acid (CAS 7664-38-2)US. New Jersey Worker and Community Right-to-Know ActPhosphoric Acid (CAS 7664-38-2)US. Pennsylvania Worker and Community Right-to-Know LawPhosphoric Acid (CAS 7664-38-2)US. Rhode Island RTKPhosphoric Acid (CAS 7664-38-2)US. California Proposition 65WARNING: This product contains a chemical known to the State of California to cause cancer and birth defects or otherreproductive harm.International InventoriesCountry(s) or region Inventory name On inventory (yes/no)* Australia Australian Inventory of Chemical Substances (AICS)Yes Canada Domestic Substances List (DSL)Yes Canada Non-Domestic Substances List (NDSL)No China Inventory of Existing Chemical Substances in China (IECSC)Yes Europe European Inventory of Existing Commercial ChemicalYesSubstances (EINECS)Europe European List of Notified Chemical Substances (ELINCS)No Japan Inventory of Existing and New Chemical Substances (ENCS)No Korea Existing Chemicals List (ECL)No New Zealand New Zealand InventoryYes Philippines Philippine Inventory of Chemicals and Chemical SubstancesNo(PICCS)United States & Puerto Rico Toxic Substances Control Act (TSCA) InventoryYes *A "Yes" indicates that all components of this product comply with the inventory requirements administered by the governing country(s)A "No" indicates that one or more components of the product are not listed or exempt from listing on the inventory administered by the governingcountry(s).16. Other information, including date of preparation or last revisionIssue date07-21-2015Revision date07-22-2015Version #04Disclaimer Lawn and Garden Products cannot anticipate all conditions under which this information and itsproduct, or the products of other manufacturers in combination with its product, may be used. It isthe user’s responsibility to ensure safe conditions for handling, storage and disposal of theproduct, and to assume liability for loss, injury, damage or expense due to improper use. While theinformation contained herein are presented in good faith and believed to be accurate, it is providedfor your guidance only. Because many factors may affect processing or application, werecommend that you make tests to determine the suitability of a product for your particular purposeprior to use. No warranties of any kind, either expressed or implied, including warranties ofmerchantability or fitness for a particular purpose, are made regarding products described orinformation set forth, or that the products, or information may be used without infringing theintellectual property rights of others. In no case shall the information provided be considered apart of our terms and conditions of sale. Further, you expressly understand and agree that theinformation furnished by our company hereunder are given gratis and we assume no obligation orliability for the information given or results obtained, all such being given and accepted at your risk.。
大肠杆菌高产L丙氨酸
APPLIED GENETICS AND MOLECULAR BIOTECHNOLOGYProduction of L-alanine by metabolically engineered Escherichia coliXueli Zhang&Kaemwich Jantama&J.C.Moore&K.T.Shanmugam&L.O.IngramReceived:23May2007/Revised:13August2007/Accepted:16August2007/Published online:15September2007 #Springer-Verlag2007Abstract Escherichia coli W was genetically engineered to produce L-alanine as the primary fermentation product from sugars by replacing the native D-lactate dehydroge-nase of E.coli SZ194with alanine dehydrogenase from Geobacillus stearothermophilus.As a result,the heterolo-gous alanine dehydrogenase gene was integrated under the regulation of the native D-lactate dehydrogenase(ldhA) promoter.This homologous promoter is growth-regulated and provides high levels of expression during anaerobic fermentation.Strain XZ111accumulated alanine as the primary product during glucose fermentation.The methyl-glyoxal synthase gene(mgsA)was deleted to eliminate low levels of lactate and improve growth,and the catabolic alanine racemase gene(dadX)was deleted to minimize conversion of L-alanine to D-alanine.In these strains,re-duced nicotinamide adenine dinucleotide oxidation during alanine biosynthesis is obligately linked to adenosine triphosphate production and cell growth.This linkage provided a basis for metabolic evolution where selection for improvements in growth coselected for increased glycolytic flux and alanine production.The resulting strain, XZ132,produced1,279mmol alanine from120g l−1 glucose within48h during batch fermentation in the mineral salts medium.The alanine yield was95%on a weight basis(g g−1glucose)with a chiral purity greater than99.5%L-alanine.Keywords Alanine.Fermentation.E.coli.Evolution. GlycolysisIntroductionWorldwide production of L-alanine has been estimated at 500tons per year(Ikeda2003).In pharmaceutical and veterinary applications,L-alanine is used with other L-amino acids as a pre-and postoperative nutrition therapy(Hols et al.1999).Alanine is also used as a food additive because of its sweet taste(Lee et al.2004).The use of L-alanine is limited in part by the current high cost.L-Alanine is pro-duced commercially by the enzymatic decarboxylation of L-aspartic acid using immobilized cells or cell suspensions of Pseudomonas dacunhae as a biocatalyst with a yield greater than90%(Shibatani et al.1979).The substrate for this enzymatic production process,L-aspartate,is usually pro-duced from fumarate by enzymatic catalysis with aspartate ammonia-lyase.Fumaric acid is produced primarily from petroleum,a nonrenewable feedstock.An efficient fermen-tative process with a renewable feedstock such as glucose offers the potential to reduce L-alanine cost and facilitate a broad expansion of the alanine market into other products.Alanine is a central intermediate(Fig.1)and an essential component of cellular proteins.Most microorganisms produce alanine only for biosynthesis using a glutamate–pyruvate transaminase(Hashimoto and Katsumata1998). Some organisms such as Arthrobacter oxydans(Hashimoto and Katsumata1993;Hashimoto and Katsumata1998; Hashimoto and Katsumata1999),Bacillus sphaericus (Ohashima and Soda1979),and Clostridium sp.P2Appl Microbiol Biotechnol(2007)77:355–366DOI10.1007/s00253-007-1170-yElectronic supplementary material The online version of this article (doi:10.1007/s00253-007-1170-y)contains supplementary material, which is available to authorized users.X.Zhang:J.C.Moore:K.T.Shanmugam:L.O.Ingram(*) Department of Microbiology and Cell Science,University of Florida,Box110700,Gainesville,FL32611,USAe-mail:ingram@K.JantamaDepartment of Chemical Engineering,University of Florida, Gainesville,FL32611,USA(Orlygsson et al.1995)produce alanine from pyruvate and ammonia using an reduced nicotinamide adenine dinucleo-tide (NADH)-linked alanine dehydrogenase (ALD).How-ever,fermentations are slow,and yields from the best natural producers are typically 60%or less because of coproduct formation (Hashimoto and Katsumata 1998;Table 1).Plasmid-borne genes encoding NADH-linked ALD have been tested as an approach to develop improved biocatalysts with varying degrees of success (Table 1).Engineered strains of Zymomonas mobilis CP4expressing the B.sphaericus alaD gene produced low levels of racemic alanine during the anaerobic fermentation of 5%glucose (Uhlenbusch et al.1991).A native chromosomal lactate dehydrogenase gene (ldhA )-deleted strain of Lactococcus lactis containing a mutation in alanine racemase was engineered in a similar fashion and produced 12.6g l −1L -alanine from 1.8%glucose (Hols et al.1999).An Escherichia coli aceF ldhA double mutant containing pTrc99A-alaD plasmid produced 32g l −1racemic alanine in 27h during a two-stage (aerobic and anaerobic)fermentation with a yield of 0.63g alanine g −1glucose (Lee et al.2004).With further gene deletions and process optimization,the racemic alanine titer wasincreasedFig.1Alanine pathway in recombinant E.coli .a Native and recom-binant fermentation pathways.The foreign gene,G.stearothermophilus alaD ,is shown in bold .G.stearothermophilus alaD coding region and transcriptional terminator were integrated into the native ldhA gene under transcriptional control of the ldhA promoter.Solid stars represent deletions of native genes in XZ132.Note that the native biosynthetic route for alanine production is omitted for simplicity.ackA Acetate kinase,adhE alcohol/aldehyde dehydrogenase,alaD alanine dehydro-genase (Geobacillus stearothermophilus XL-65-6),aldA aldehyde dehydrogenase A,aldB aldehyde dehydrogenase B,alr alanine race-mase 1,dadX alanine racemase 2,frd fumarate reductase,gloA glyoxalase I,gloB glyoxalase II,gloC glyoxalase III,ldhA D -lactate dehydrogenase,mdh malate dehydrogenase,mgsA methylglyoxal synthase,pflB pyruvate –formate lyase,ppc phosphoenolpyruvate carboxylase,pta phosphate acetyltransferase.b Coupling of ATP production and growth to NADH oxidation and L -alanine production.Glucose is metabolized to pyruvate,ATP,and NADH.Energy conserved in ATP is utilized for growth and homeostasis,regenerating ADP.NADH is oxidized by alanine formation allowing glycolysis and ATP production to continueT a b l e 1C o m p a r i s o n o f a l a n i n e -p r o d u c i n g s t r a i n sO r g a n i s m s M o d i f i e d p r o p e r t yM e d i a ,s u b s t r a t e a n d p r o c e s s c o n d i t i o n sT i m e (h )A l a n i n e (g l −1)Y i e l d (%)L -A l a n i n ep u r i t y (%)R e f e r e n c e E .c o l i X Z 132I n t e g r a t e d G .s t e a r o t h e r m o p h i l u s a l a D ;Δp f l ,Δa c k A ,Δa d h E ,Δl d h A ,Δm g s A ,Δd a d XM i n e r a l m e d i u m ,b a t c h ,g l u c o s e 120g l −148.0114.095>99T h i s s t u d yA r t h r o b a c t e r o x y d a n s H A P -1M i n e r a l m e d i u m ,t w o -s t a g e f e d -b a t c h ,g l u c o s e 150g l −1120825560.0H a s h i m o t o a n d K a t s u m a t a 1998A .o x y d a n s D A N 75A l a n i n e r a c e m a c e d e f i c i e n tM i n e r a l m e d i u m ,t w o -s t a g e f e d -b a t c h ,g l u c o s e 150g l −1,0.2g l −1D -a l a n i n e120775198H a s h i m o t o a n d K a t s u m a t a 1998E c o l i A L 1(p O B P 1)P l a s m i d w i t h A .o x y d a n s H A P -1a l a D M i n e r a l m e d i u m ,g l u c o s e 20g l −1,l i m i t e d o x y g e n40841N o t r e p o r t e dK a t s u m a t a a n d H a s h i m o t o 1996C o r y n e b a c t e r i u m g l u t a m i c u m A L 107(p O B P 107)P l a s m i d w i t h A .o x y d a n s H A P -1a l a DC o r n s t e e p l i q u o r ,g l u c o s e 200g l −1,4g l −1D L -a l a n i n e ,l i m i t e d o x y g e n 707136>99K a t s u m a t a a n d H a s h i m o t o 1996Z y m o m o n a s m o b i l i s C P 4(p Z Y 73)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D M i n e r a l s a l t s m e d i u m ,s i m p l e b a t c h ,g l u c o s e 50g l −126816N o t r e p o r t e dU h l e n b u s c h e t a l .1991L a c t o c o c c u s l a c t i s N Z 3950(p N Z 2650)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h AR i c h m e d i u m (M 17),g l u c o s e 18g l −117137085–90H o l s e t a l .1999L .l a c t i s P H 3950(p N Z 2650)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h A ,Δa l rR i c h m e d i u m (M 17),g l u c o s e 18g l −1,0.2g l −1D -a l a n i n e 17N o t k n o w nN o t k n o w n >99H o l s e t a l .1999E .c o l i A L S 887(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h A ,Δa c e FY e a s t e x t r a c t ,t w o -s t a g e b a t c h ,g l u c o s e 50g l −1,a e r o b i c a i r 1l m i n −1273263N o t r e p o r t e d L e e e t a l .2004E .c o l i A L S 929(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δp f l ,Δp p s ,Δp o x B ,Δl d h A ,Δa c e E FY e a s t e x t r a c t a n d c a s a m i n o a c i d s ,t w o -s t a g e b a t c h (a e r o b i c c e l l g r o w t h a n d a n a e r o b i c f e r m e n t a t i o n )223486N o t r e p o r t e d S m i t h e t a l .2006E .c o l i A L S 929(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δp f l ,Δp p s ,Δp o x B ,Δl d h A ,Δa c e E FY e a s t e x t r a c t a n d c a s a m i n o a c i d s ,t w o -s t a g e f e d -b a t c h (a e r o b i c c e l l g r o w t h a n d a n a e r o b i c f e r m e n t a t i o n )4888100N o t r e p o r t e d S m i t h e t a l .2006to88g l−1in a more complex process with yields ap-proaching the theoretical maximum(Smith et al.2006). However,this strain produced only racemic alanine,utilized multicopy plasmids requiring antibiotic selection,and required complex media with a complex multistage fermen-tation process(Smith et al.2006).In this study,we developed novel biocatalysts that pro-duce chirally pure L-alanine in batch fermentations without using plasmid-containing biocatalysts,antibiotics,or com-plex nutrients.The resulting strains are based on a deriva-tive of E.coli W(strain SZ194)that produces D-lactate (Zhou et al.2006b).The ldhA gene in SZ194was replaced with a single,chromosomally integrated copy of the ALD gene from the thermophile,Geobacillus stearothermophilus XL-65-6(formerly B.stearothermophilus;Lai and Ingram 1993).After additional deletions of alanine racemase (dadX)and methylglyoxal synthase(mgsA)and metabolic evolution,the resulting strain produced L-alanine at high titers(over1M)and yields in batch fermentations using the mineral salts medium.Materials and methodsStrains,plasmids,media,and growth conditionsThe strains and plasmids used in this study are listed in Table2.Strain SZ194was previously engineered from a derivative of E.coli W(ATCC9637)and served as a starting point for constructions(Zhou et al.2006b).G. stearothermophilus XL-65-6(Lai and Ingram1993)was used for cloning the ALD gene.During sequencing of chro-mosomal genes,we discovered a20-year-old error in culture labeling.Strain SZ194,the parent used to construct the alanine strains,is a derivative of E.coli W(ATCC9637). Other constructs for ethanol production and lactate produc-tion that have been reported previously as derivatives of E. coli B are now known to be derivates of E.coli W(ATCC 9637).Primers used in this study are listed in Table3.During strain construction,cultures were grown aerobi-cally at30,37,or39°C in Luria broth(10g l−1Difco tryptone,5g l−1Difco yeast extract,and5g l−1NaCl) containing2%(w/v)glucose or5%(w/v)arabinose. Ampicillin(50mg l−1),tetracycline(12.5mg l−1), kanamycin(50mg l−1),or chloramphenicol(40mg l−1) were added as needed.For initial tests of fermentative alanine production,strains were grown without antibiotics at37°C in NBS mineral salts medium(Causey et al.2004) supplemented with100mM ammonia sulfate,1mM betaine,and2%(w/v)glucose.Fermentation experiments (2–12%sugar)were carried out in NBS medium and AM1 medium(Martinez et al.2007).Broth was maintained at pH 7by the automatic addition of5M NH4OH.Genetic methodsStandard methods were used for genomic deoxyribonucleic acid(DNA)extraction(Qiagen,Valencia,CA),polymerase chain reaction(PCR)amplification(Stratagene,La Jolla CA,and Invitrogen,Carlsbad,CA),transformation,plas-mid extration(Qiagen),and restriction endonuclease diges-tion(New England Biolabs,Ipswich,MA).Methods for foreign gene(alaD)integration and for chromosomal gene (mgsA and dadX)deletion are described below.DNA sequencing was provided by the University of Florida Interdisciplinary Center for Biotechnology Research.The Biocyc and Metacyc databases(Karp et al.2005)were instrumental in the design and completion of these studies. Cloning the alanine dehydrogenase gene alaD from G. stearothermophilus XL-65-6and detection of the enzyme activityThe primers for amplifying alaD from G.stearothermophilus XL-65-6were designed based on the alaD sequence of G. stearothermophilus strain10.The forward primers(5′–3′GGAAAAA GGAGGAAAAAGTG ATGAAGATCGG CATT)included the ribosomal-binding region(bold)and the amino terminus(italicized).The reverse primer(5′–3′GAA GGAGTTGATCATTGTTTAACGAGAGAGG)was down-stream from the putative transcriptional terminator region (Table3).ALD was verified in clones using an activity stain (Kuroda et al.1990).E.coli TOP10F′harboring plasmids containing alaD was grown on Luria–Bertani(LB)plates at 37°C,then transferred to a Whatman7.0-cm filter paper. The filter was immersed in10mM potassium phosphate buffer(pH7.2)and incubated for20min at80°C for lysis of the cells and denaturation of the E.coli proteins.The dried filter paper was assayed in a reaction mixture containing50mM L-alanine,50mM Tris–HCl buffer (pH9.0),0.625mM NAD+,0.064mM phenazine metho-sulfate,and0.24mM nitro blue tetrazolium.The cells with ALD appeared as blue spots on the filter.Integration of alaD into E.coli SZ194The alaD gene was integrated into the chromosomal ldhA gene of SZ194.The fragment(Sma I–Kpn I,1.7kb)con-taining a tet gene flanked by two FRT sites was isolated from pLOI2065and cloned into pLOI4211between a unique Bam HI site(Klenow-treated)and Kpn I site to produce plasmid pLOI4213(6.0kb).In this plasmid,transcription of alaD and tet are oriented in the same direction.The Apa I(treated with T4DNA polymerase to produce a blunt end)–Kpn I fragment(2.2kb)containing alaD and tet was isolated from pLOI4213and cloned into pLOI2395Table2 E.coli strains and plasmids used in this studyRelevant characteristics Source or referenceStrainsSZ194plfB frd adhE ackA deletions Zhou et al.2006bXZ103-110SZ194,ldhA::FRT-tet-FRT::This studyG.stearothermophilus alaDXZ111XZ105,ldhA::G.stearothermophilus alaD This studyXZ112XZ111,metabolic evolution in NBS medium with2%glucose This studyXZ113XZ112,metabolic evolution in NBS medium with5%glucose This studyXZ115XZ113,metabolic evolution in NBS medium with8%glucose This studyXZ121XZ115,mgsA deletion This studyXZ123XZ121,metabolic evolution in NBS medium with8%glucose This studyXZ126XZ123,dadX deletion This studyXZ129XZ126,metabolic evolution in NBS medium with8%glucose This studyXZ130XZ129,metabolic evolution in AM1medium with8%glucose This studyXZ131XZ130,metabolic evolution in AM1medium with10%glucose This studyXZ132XZ131,metabolic evolution in AM1medium with12%glucose This studyPlasmidspCR2.1-TOPO bla kan;TOPO TA cloning vector InvitrogenDatsenko and Wanner2000pKD46Blaγβexo(Red recombinase),temperature conditionalpSC101repliconpFT-A Bla flp,temperature conditional pSC101replicon Posfai et al.1997pEL04cat-sacB targeting cassette Lee et al.2001;Thomason et al.2005 pLOI2224kan;R6K conditional integration vector Martinez-Morales et al.1999pLOI2065bla;FRT-tet-FRT cassette Zhou et al.2003bpLOI2395bla;ldhA franked by two Asc I site Zhou et al.2003apLOI3421 1.8kbp SmaI fragment containing aac Wood et al.2005pLOI4151bla cat;cat-sacB cassette This studyalaD integrationThis studypLOI4211bla kan alaD;alaD(PCR)from G.stearothermophilus XL-65-6cloned into pCR2.1-TOPO vectorpLOI4213bla kan;alaD-FRT-tet-FRT Kpn I-Sma I fragment(FRT-tet-FRT)This studyfrom pLOI2065cloned into Kpn I-BamH I(blunted)site of pLOI4211This studypLOI4214bla kan;ldhA’-alaD-FRT-tet-FRT-ldhA”Apa I(blunted)-Kpn I fragment(alaD-FRT-tet-FRT)from pLOI4213cloned into ldhA at Hinc II-Kpn Isites of pLOI2395This studypLOI4215kan;ldhA’-alaD-FRT-tet-FRT-ldhA”Asc I fragment(ldhA’-alaD-FRT-tet-FRT-‘ldhA)from pLOI4214cloned into Asc I sites of pLOI2224mgsA deletionThis studypLOI4228bla kan;yccT’-mgsA-helD’(PCR)from E.coli W clonedinto PCR2.1-TOPO vectorThis studypLOI4229cat-sacB cassette PCR amplified from pLOI4151(Eco RV digested)cloned into mgsA in pLOI4228This studypLOI4230PCR fragment amplified from pLOI4228(using mgsA-1/mgsA-2primers),kinase treated,and self-ligateddadX deletionThis studypLOI4216bla kan;dadA’-dadX-cvrA’(PCR)from E.coli W clonedinto PCR2.1-TOPO vectorpLOI4218cat-sacB cassette PCR amplified from pLOI4151(Eco RV digested)This studycloned into dadX in pLOI4216This studypLOI4220PCR fragment amplified from pLOI4216(using dadX-4/dadX-5primers),kinase treated,and self-ligated(Hinc II to Kpn I sites)to produce pLOI4214(6.5kb).In this plasmid,ldhA ,alaD ,and tet genes are transcribed in the same direction.The Asc I fragment (4.3kb)containing these three genes was isolated from pLOI4214and cloned into the R6K integration vector pLOI2224to produce pLOI4215(6.2kb).Plasmid pLOI4215contains resistance genes for both tetracycline and kanamycin (Fig.2).The Asc I fragment (4.3kb)containing ldhA ,alaD ,and tet genes was isolated from pLOI4215,further cut by Xmn I to eliminate any remaining uncut plasmid DNA,and electroporated into SZ194containing the Red recombinase plasmid pKD46(Datsenko and Wanner 2000).Integrants were selected for tetracycline resistance,confirmed by sensitivity to kanamycin and ampicillin and by PCR analysis using the primers of ldhA and its neighboring genes ydbH and hslJ (Table 3).Deletion of mgsA and dadX genesA modified method for deleting E.coli chromosomal genes was developed using two steps of homologous recom-bination (Thomason et al.2005).With this method,no antibiotic genes or scar sequences remain on the chromo-some after gene deletion.In the first recombination,part of the target gene was replaced by a DNA cassette containing a chloramphenicol resistance gene (cat )and levansucrase gene (sacB ).In the second recombination,the cat –sacBcassette was removed by selection for resistance to sucrose.Cells containing the sacB gene accumulate levan during incubation with sucrose and are killed.Surviving recombi-nants are highly enriched for loss of the cat –sacB cassette.A new cassette was constructed as a template to facilitate gene deletions.The cat –sacB region was amplified from pEL04(Lee et al.2001;Thomason et al.2005)by PCR using the JM catsacB up Nhe I and JM catsacB down Nhe I primers (Table 3),digested with Nhe I,and ligated into the corresponding site in pLOI3421to produced pLOI4151.The cat –sacB cassette was amplified by PCR using pLOI4151as a template with the cat -up2and sacB -down2primers (Eco RV site included in each primer),digested with Eco RV ,and used in subsequent ligations.The mgsA gene and neighboring 500-bp regions (yccT ′–mgsA –helD ′,1,435bp)were amplified using the mgsA -up and mgsA -down primers and cloned into the pCR 2.1-TOPO vector (Invitrogen)to produce plasmid pLOI4228.A 1,000-fold diluted plasmid preparation of this plasmid served as a template for inside-out amplification using the mgsA -1and mgsA -2primers (both within the mgsA gene and facing outward).The resulting 4,958-bp fragment containing the replicon was ligated to the Eco RV-digested cat –sacB cassette from pLOI4151to produce pLOI4229(Fig.3a).This 4,958-bp fragment was also used to construct a second plasmid,pLOI4230(Fig.3b),by phosphorylation and self-ligation.In pLOI4230,the central region of mgsA is deleted (yccT ′–mgsA ′–mgsA ″–helD ′).After digestion of pLOI4229and pLOI4230with Xmn I (within the vector),each served as a template for amplifica-tion using the mgsA -up and mgsA -down primers to produce linear DNA for integration step 1(yccT ′–mgsA ′–cat –sacB –mgsA ″–helD ′)and step II (yccT ′–mgsA ′–mgsA ″–helD ′),respectively.After electroporation of the step 1fragment into XZ115containing pKD46(Red recombinase)and 2h ofTable 3Primers used in this study Primers SequencealaD -forward GGAAAAAGGAGGAAAAAGTGATGAA GATCGGCATTalaD -reverse GAAGGAGTTGATCATTGTTTAACGA GAGAGGldhA -forward AGTACCTGCAACAGGTGAAC ldhA -reverse CAGGCGACGGAATACGTCAT ldhA -up (ydbH )CTGATAACGCAGTTGCTGGA ldhA -down (hslJ )TTCATTAAATCCGCCAGCTTJM catsacB up NheI TTAGCTAGCATGTGACGGAAGATC ACTTCGJM catsacB down NheI CCGCTAGCATCAAAGGGAAAACTGT CCATATcat -up2AGAGAGGATATCTGTGACGGAAGAT CACTTCGsacB -down2AGAGAGGATATCGAATTGATCCGGT GGATGACmgsA -up CAGCTCATCAACCAGGTCAA mgsA -down AAAAGCCGTCACGTTATTGG mgsA -1AGCGTTATCTCGCGGACCGT mgsA -2AAGTGCGAGTCGTCAGTTCC dadX -up AGGCTACTCGCTGACCATTC dadX -down GGTTGTCGGTGACCAGGTAG dadX -4TGGGCTATGAGTTGATGTGC dadX -5CTGTATCGGACGGGTCATCTFig.2Integration vector used for chromosomal insertion of G.stearothermophilus alaD into E.coli ldhA .Sequence encoding the N-terminal and C-terminal regions are designated ldhA ′and ldhA ″,respectivelyincubation at 30°C to allow expression and segregation,recombinants were selected for chloramphenicol (40mg l −1)and ampicillin (50mg l −1)resistance in Luria broth at 30°C (18h).Three clones were selected,grown in Luria broth containing ampicillin and 5%(w/v)arabinose (to induce expression of red recombinase),and prepared for electro-poration.After electroporation with the step 2fragment,cells were incubated at 30°C for 4h and then transferred into a 250-ml flask containing 100ml of modified LB (100mM 3-(N -morpholino)propanesulfonic acid [MOPS]buffer added and NaCl omitted)containing 10%sucrose.After overnight incubation (30°C),clones were selected on modified LB plates (no NaCl;100mM MOPS added)containing 6%sucrose (39°C,16h).Resulting clones were tested for loss of ampicillin and chloramphenicol resistance.Construction was confirmed by PCR using the mgsA-up/down primer set.A clone containing a deletion in the central region of mgsA was selected and designated XZ121.The dadX gene was deleted in a manner analogous to that used to delete the mgsA gene.Primers for dadX deletion are shown in Table 3,and the corresponding plasmids are shown in Table 2.FermentationNBS mineral salts medium (Causey et al.2004)with 1mM betaine (Zhou et al.2006a )was used in the initial fermentation (pH 7.0).Preinoculum was grown by inocu-lating three colonies into a 250ml flask (100ml NBS medium,2%glucose,and 100mM ammonium sulfate).After 16h (37°C,120rpm),this preinoculum was diluted into 500-ml fermentation fleakers containing 300ml NBS medium (2–8%glucose,100mM ammonium sulfate,and 1mM betaine)with 33mg cell dry weight (CDW)l −1.In early experiments,pH was maintained at 7.0by automat-ically adding 2M potassium hydroxide.In later experi-ments,5M ammonium hydroxide was used to maintain pH,and a low salt medium,AM1(Martinez et al.2007),was used to replace the NBS medium for fermentation (8–12%glucose).AM1medium contains much less salt and has been optimized for E.coli .Metabolic evolutionCells from pH-controlled fermentations were serially transferred at 24-h intervals to facilitate metabolic evolution through competitive,growth-based selection (Fig.1b).At the beginning,sequentially transferred cultures were inoc-ulated with an initial density of 33mg CDW l −1.As growth increased,the inoculum was changed to a 1:100dilution and subsequently to a 1:300dilution.Periodically,clones were isolated from these experiments,assigned new strain designations,and frozen for storage.AnalysesCell mass was estimated by measuring the optical density at anic acids and glucose concentrations were mea-sured by high-performance liquid chromatography (HPLC,Underwood et al.2002).Analysis of fermentation products by mass spectroscopy and amino acid analyzer were provided by the University of Florida Interdisciplinary Center for Bio-technology Research.Alanine was found to be the predominant product.The alanine concentration and isomeric purity were further measured by HPLC using the Chiralpak MA(+)chiral column (Chiral Technologies,West Chester,PA).ResultCloning of the alanine dehydrogenase geneALD is found in Bacillus (and Geobacillus )species where it plays a pivotal role in energy generation during sporulation (Ohashima and Soda 1979;Kuroda et al.1990).ALD from B.sphaericus IFO3525has beenwidelyFig.3Plasmids used to delete mgsA .Plasmid pLOI4229(a )was used to delete the mgsA gene and insert the cat-sacB cassette in the first recombina-tion step.Plasmid pLOI4230(b )was used to remove the cat-sacB cassette to create a deletion devoid of foreign sequence.Se-quence encoding the N-terminal and C-terminal regions are des-ignated mgsA ′and mgsA ″,respectivelyused with varying degrees of success to engineer alanine production in recombinant bacteria(Uhlenbusch et al. 1991;Hols et al.1999;Lee et al.2004;Smith et al.2006). Selection of the B.sphaericus IFO3525is presumed to be due in part to the high specific activity(Ohashima and Soda 1979).In contrast,we have selected a thermostable ALD from the thermophile,G.stearothermophilus XL-65-6, based on our prior experience in expressing genes from this organism in recombinant E.coli(Burchhardt and Ingram 1992;Lai and Ingram1993;Lai and Ingram1995).The ribosomal-binding region,coding region,and tran-scriptional terminator of alaD were amplified from G. stearothermophilus XL-65-6and sequenced(EF154460in GenBank).The deduced amino acid sequence was identical to that reported for Geobacillus kaustophilus HTA426and very similar to G.stearothermophilus strain10(99%iden-tity)and G.stearothermophilus strain IFO12550(94% identity).The nucleotide sequence(65%identity)and the deduced ALD amino acid sequence(74%identity)were quite different from the B.sphaericus IFO3525gene,the gene pre-viously used for alanine production in recombinant bacteria.Modification of E.coli W for homoalanine productionE.coli W strain SZ194(pflB frdBC adhE ackA)was previously constructed to produce only D-lactic acid.All major fermentation pathways except lactate have been blocked in this strain by gene deletions(Fig.1a).To convert this strain to the production of alanine,part of the native ldhA-coding region was replaced by a DNA fragment containing the ribosomal-binding region,coding region,and transcriptional terminator of alaD from G. stearothermophilus XL-65-6.The promoterless alaD was oriented in the same direction as ldhA to allow expression from the native ldhA promoter(Fig.2).After electroporation,approximately500colonies were recovered with tetracycline resistance and sensitivity to kana-mycin,consistent with a double-crossover event.These colo-nies were further examined by PCR using ldhA forward and reverse primer set(Table3).Only eight colonies of the500 tested were correct based on an analysis of PCR fragments. These eight colonies were further verified using primer sets for alaD,ldhA forward and alaD reverse,alaD forward and ldhA reverse,and ldhA outside primers(Table3)and de-signated XZ103,XZ104,XZ105,XZ106,XZ107,XZ108, XZ109,and XZ110,respectively.These eight strains were initially tested in15-ml screw-cap tubes containing NBS medium with2%glucose and100mM ammonium sulfate, which were filled to the brim.Strain XZ105appeared to grow faster than the other strains(37°C for48h)and was selected for further development.XZ105was transformed with pFT-A,which contains an inducible flippase(FLP)recombinase(Martinez-Morales et al.1999;Posfai et al.1997).The chromosomal FRT-flanked tet gene in XZ105was removed by inducing the FLP recombinase.After growing in39°C to eliminate the temperature-sensitive plasmid pFT-A,resulting strain was designated XZ111.Expression of G.stearothermophilus alaD in XZ111is transcriptionally regulated by the ldhA promoter,the same promoter that regulates the production of lactate dehydrogenase(dominant fermentation pathway) in native E.coli.pH-controlled batch fermentation for alanine production Alanine production by strain XZ111was tested in500-ml fermentation vessels containing300ml NBS medium, 20g l−1glucose,100mM ammonium sulfate,and1mM betaine.Broth pH was automatically controlled by adding 2N potassium hydroxide.After96h,181mM alanine was produced.The alanine yield from total glucose was 81%(g/g),and84%based on glucose that had been metabo-lized.The chiral purity of L-alanine was96.1%(Table4). Very low levels of other products(lactate,succinate,ace-tate,ethanol)were present,typically below1mM.This result demonstrated that the integrated G.stearothermophilus alaD gene as a single chromosomal copy under the control of the native ldhA promoter can provide sufficient levels of ALD to support E.coli growth from the production of alanine as the sole fermentation product.Metabolic evolution of strain XZ111Although XZ111could accumulate alanine as the primary product,incubation times were long,and volumetric productivity was limited.When using a high-glucose concentration(80g l−1),growth and alanine productivity were further reduced(Table4).In this strain,adenosine triphosphate(ATP)production and growth are tightly coupled to NADH oxidation and alanine production by ALD(Fig.1b).This coupling provided a basis for strain improvement by selecting for increased growth during serial cultivation,i.e.,metabolic evolution.Cells with increased growth because of spontaneous mutations will successively displace their parents while coselecting for increased alanine productivity.Serial transfers of XZ111were carried out at24-h intervals in NBS mineral salts medium with1mM betaine.Cultures were first transferred in the medium containing20g l−1 glucose,and the pH was controlled by automatically adding 2N potassium hydroxide.However,after ten transfers to strain XZ112,little improvement was observed(data not shown).Because ammonia is essential for alanine pro-duction,it was thought that ammonia may be limiting for fermentation.Two normals potassium hydroxide containing 1N ammonia carbonate and5N ammonia hydroxide alone。
盐酸多巴酚丁胺-安全技术说明书MSDS
第一部分化学品及企业标识化学品中文名：盐酸多巴酚丁胺化学品英文名：4-[2-[[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl]pyrocatechol hydrochloride CAS No.：49745-95-1分子式：C18H24ClNO3产品推荐及限制用途：工业及科研用途。
第二部分危险性概述紧急情况概述吞咽有害。
皮肤接触有害。
吸入有害。
怀疑对生育能力或胎儿造成伤害。
GHS危险性类别急性经口毒性类别 4急性经皮肤毒性类别 4急性吸入毒性类别 4生殖毒性类别 2标签要素：象形图：警示词：警告危险性说明：H302 吞咽有害H312 皮肤接触有害H332 吸入有害H361 怀疑对生育能力或胎儿造成伤害●预防措施：—— P264 作业后彻底清洗。
—— P270 使用本产品时不要进食、饮水或吸烟。
—— P280 戴防护手套/穿防护服/戴防护眼罩/戴防护面具。
—— P261 避免吸入粉尘/烟/气体/烟雾/蒸气/喷雾。
—— P271 只能在室外或通风良好处使用。
—— P201 使用前取得专用说明。
—— P202 在阅读并明了所有安全措施前切勿搬动。
●事故响应：—— P301+P312 如误吞咽：如感觉不适，呼叫解毒中心/ 医生—— P330 漱口。
—— P302+P352 如皮肤沾染：用水充分清洗。
—— P312 如感觉不适，呼叫解毒中心/医生—— P362+P364 脱掉沾染的衣服，清洗后方可重新使用—— P304+P340 如误吸入：将人转移到空气新鲜处，保持呼吸舒适体位。
—— P308+P313 如接触到或有疑虑：求医/就诊。
●安全储存：—— P403+P233 存放在通风良好的地方。
保持容器密闭。
—— P405 存放处须加锁。
●废弃处置：—— P501 按当地法规处置内装物/容器。
物理和化学危险：无资料。
健康危害：吞咽有害。
皮肤接触有害。
吸入有害。
硫酸锌溶液萃取去除氯离子的研究
作者简介:(1985-),。
1前言在锌电解沉积过程中，氯含量超过100mg/L时，会给锌电积工序带来严重危害；硫酸锌溶液常规的氯去除方法有：硫酸银沉淀除氯、铜镉渣除氯、离子交换除氯法、絮凝沉淀法以及电极指示法[1,3]。
本文研究的是采用溶剂萃取的方法从硫酸锌溶液中脱除氯离子。
因为氯多以负价离子形态存在，所以要采用阴离子萃取剂，即碱性萃取剂。
碱性萃取剂中主要的是胺类萃取剂—碱性强弱：季铵盐＞叔胺＞仲胺＞伯胺。
对酸的萃取能力：叔胺＞仲胺＞伯胺。
本文所研究用的是N235萃取剂。
本试验的工艺流程见图1。
12试验原理及步骤2.1试验原理针对本文萃取Cl -所用的萃取剂（N235）所属类周虹(四川省冶金设计研究院,四川成都610041)摘要：本文以人工配制含氯离子杂质的硫酸锌溶液为原料，研究硫酸锌溶液溶剂萃取脱除氯离子，试验研究得出以下结论：N235对氯的萃取具有良好的选择性，其萃取氯的饱和容量为25.125g/L 。
在有机相组成为20%N235+20%TBP+60%260#溶剂油、游离硫酸30g/L 、相比O/A=1:1、萃取级数3级的条件下，氯的萃取率可达95%以上，最高达为99.02%。
以25%氨水溶液为反萃剂，在相比O/A=10:1，混合和静置分层时间均为5分钟的条件下，单级反萃，氯的反萃率可达97.89%。
关键词：硫酸锌溶液;溶剂萃取;反萃中图分类号：TF843文献标志码：AStudy How to Removal of Chloride ion by Zinc sulfate Solution ExtractionZHOU Hong(Sichuan Metallurgical Design &Research Institute,Chengdu,610041,China )Abstract :The paper studies how to remove chloride ion from the prepared solution which contains.Some meaningful conclusions were drawn as follows:Chlorine can be selectively extracted by N235extractant,and saturated capacity of chlorine is 25.125g/L.The extraction ratio of chlorine can reach 95%,the best extraction ratio of chlorine is 99.02%,under the conditions when the organic phase component is 20%N235+20%TBP+60%260#white spirit,Phase ration and extraction grade is 1:1and 3,ing 25%concentration of ammonia solution as stripping agent,the stripping ration of chlorine is higher than 97%,when the phase ration (O/A)is 10:1and single-stage stripping is applied.The mixing time and silent period both are 5min.Key words:zinc sulfate solution;solvent extraction;strippin1硫酸锌溶液萃取去除氯离子的研究型，下面将重点介绍阴离子交换萃取剂的萃取机理与影响因素。
盐酸头孢唑兰的结构确证
盐酸头孢唑兰的结构确证辛玉峰1，曲晓华（曲阜师范大学，曲阜273165）摘要目的：建立利用仪器分析盐酸头孢唑兰化学结构的方法。
方法：通过元素分析仪分析盐酸头孢唑兰的元素组成，并利用核磁共振（NMR ）、质谱（MS ）、红外光谱（IR ）对盐酸头孢唑兰进行结构分析。
结果：通过实验证实盐酸头孢唑兰的结构为（6R ，7R ）－7－［（Z ）－2－（5－氨基－1，2，4－噻二唑－3－基）－2－甲氧亚氨基乙酰胺基］－3－（1H －咪唑并［1，2－b ］哒嗪－4－嗡－1－基－甲基）－8－氧代－5硫杂－1－氮杂双环［4.2.0］辛－2－烯－2－乙酸内盐单盐酸盐。
结论：该方法准确可行，可为以后盐酸头孢唑兰的结构鉴定提供依据。
关键词：盐酸头孢唑兰；结构确证中图分类号：R917文献标识码：A文章编号：0254－1793（2011）03－0433－05Structural confirmation of cefozopran hydrochlorideXIN Yu －fengQU Xiao －hua（Shandong Qufu Normal University ，Qufu 273165，China ）Abstract Objective ：To establish a method for the determination of the chemical structure of cefozopran hydro-chloride．Method ：Elemental analysis （EA ），nuclear magnetic resonance （NMR ），the infrared spectra （IR ）and the MS were adopted to analyze the chemical structure of cefozopran hydrochloride．Result ：The chemical structure of cefozopran hydrochloride is （6R ，7R ）－7－［（Z ）－2－（5－amino －1，2，4－thiadiazol －3－yl ）－2－methoxyimi-noacetylamino ］－3－（1H －imidazo ［1，2－b ］pyridazin －4－ium －1－ylmethyl ）－8－oxo －5－thia －1－azabi-cyclo ［4.2.0］oct －2－ene －2－carboxylic acid chloride．Conclusion ：The result of the method is accurate ，general and can provide a comprehensive reference for production and identification of cefozopran hydrochloride．Key words ：cefozopran hydrochloride ；structure elucidation 第一作者Tel ：（0537）4458576；E －mail ：xinyufeng520@163．com盐酸头孢唑兰（cefozopran hydrochloride ）是日本武田药品工业公司研发的第4代注射用头孢菌素，目前在日本已作为院外感染初期的首选药物被广泛应用于包括新生儿感染在内的各科感染症的治疗［1］。
二硫缩烯酮
School of Chemical Sciences, Mahatma Gandhi University, Priyadarshini Hills P. O., Kottayam 686 560, India Fax +91(481)2731009; E-mail: asokancv@ Received 2 April 2005; revised 4 July 2005
二硫缩烯酮 convenientpreparation 5-aroyl-2-oxo-1,2-dihydro-2-pyridinecarbonitriles preparation 2-aroyl-3,3-bis(alkylsulfanyl)acrylaldehydesengoor anabha,chittoorthekkathil asokan*school chemicalsciences, mahatma gandhi university, priyadarshini hills kottayam686 560, india fax +91(481)2731009; e-mail: asokancv @ received april2005; revised july2005 erally, a-formyl derivatives ketenedithioacetals obtainedindirectly from correspondingbis(methylsul- fanyl)ethylene carboxylates via process.rudorf et al. reported fromaroylacetaldehydes treatingthem carbondisulfide abstract: aroylketenedithioacetals vilsmei-er–haack reagent, prepared from pocl undermild con- ditionsgave 2-aroyl-3,3-bis(alkylsulfanyl)acrylaldehydes excellentyields. cyclization 2-[2-aroyl-3,3-bis(methylsulfanyl)-2-propylidene]malononitriles derivedfrom concentratedhydrochloric acid tertiarybutanol afforded 2-pyridone derivatives base,followed alkylation.most havekey words: ketene dithioacetals, knoevenagel condensations, cy- already been reporte
CAS1204313-51-8_Icotinib Hydrochloride_MedBio相关资料
在体外激酶测定中，将2.4 ng /μLEGFR蛋白与32 ng /μLCrk在含有1μM冷ATP和1μCi32P-γ-ATP的25μL激酶反应缓冲液中混合。将混合物与Icotinib在0,0.5,2.5,12.5或62.5nM下在冰上温育10分钟，然后在30℃温育20分钟。用SDS样品缓冲液在100℃猝灭4分钟后，通过在10％SDS-PAGE凝胶中电泳分离蛋白质混合物。然后暴露干燥的凝胶以检测放射性。量化由软件[1]执行。
CAS
1、产品物理参数：
常用名
凯美纳
英文名
Icotinib Hydrochloride
CAS号
1204313-51-8
分子量
427.881
密度
无资料
沸点
无资料
分子式
C22H22ClN3O4
熔点
无资料
闪点
无资料
2、技术资料：
体外研究
与Iconitib在0.5μM孵育导致激酶活性抑制分别为91％，99％，96％，61％和61％。 Iconitib抑制A431和BGC-823 A549，H460和KB细胞系的增殖，IC50分别为1,4.06,12.16,16.08,40.71μM。当用88种激酶进行分析时，Icotinib仅对EGFR及其突变体显示出有意义的抑制活性。 Icotinib阻断人表皮样癌A431细胞系中EGFR介导的细胞内酪氨酸磷酸化（IC50 = 45 nM）并抑制肿瘤细胞增殖[1]。
10mM (in 1mL DMSO)
≥98%
1172133-28-6
5mg
≥98%
品牌
货号
中文名称
英文名称
CAS
包装
纯度
MedBio
雅D-苯甘氨酸甲酯盐酸盐制备及纯化工艺研究-化学工程与技术专业毕业论文
D-苯甘氨酸甲酯盐酸盐制备及纯化工艺研究-化学工程与技术专业毕业论文河北科技大学硕士学位论文IIAbstract=========；暑=；昌昌============；==≈==；穹皇=========；号皇；=兰===昌==暑=======置==宣号=== =：AbstractD。
phenylglycine methyl ester hydrochloride，a type of white crystalline powder and important p harmaceutical i ntermediate，iS a n e ssential active side chain f or t he production of cephalexin，cefaclor,and other IMactam antibiotics．In this paper,the synthesis and crystallization purification technique of D-phenylglycine methyl ester hydrochloride is systematically studied．The study on the synthesis of D—phenylglycine methyl ester hydrochloride．A preliminary synthetic route of D·phenylglycine methyl ester hydrochloride was designed，and sulfoxide chloride method was determinedexperimentally as a preferred syntheticroute．In the experiment，the synthesis technique conditions such as thesequence of adding reagents，the ratio of reagents，the reaction temperature，the reflux time，and the adding rate of sulfoxide chloride were investigated and optimized．After the completion of the reaction，the vacuum azeotropic distillation and cooling crystallization with the temperature controlling should be done to the mother liquor．Finally through the post‘pmcessing，we can get．t11e crystal product of D—phenylglycine methyl ester hydrochloride．The purity of the product detected by using HPLC is more than 98．5％．with the yield more than 96％．The study on the thermodynamics of D-phenylglycine methyl ester hydrochloridecrystallization．Thesolubility and supersolubility of D—phenylglycine methylesterhydrochloride in six pure solvents(water，methanol，ethanol，acetone，ethyl acetate，and toluene)as well as in two kinds of binary mixed solvents with different compositions (methanol—ethyl acetate and methanol—toluene)were measured under the conditions of atmospheric pmssure and the temperature range of 283．1 5K-333．1 5K by using Laser Dynamics Method．Then the Apelblat equation，CNIBS／Redlich．Kister equation．and NRTL equation were used to correlate the data of solubility，and it showeda satisfactoryresult．Finally，thermodynamic properties in the dissolution process wereanalyzed systematically，and changes of the free energy of standard molar enthalpy，Standard molar entropy and Standard Gibbs of D-phenylglycine methyl ester hydrochloride in the dissolution process in different solvents were calculated．The study on thermodynamics of crystallization of D—phenylglycine methyl ester hydrochloride provides a theoretical reference and data base forthe development of its crystallizationtechnique．IIlThe crystallization kinetics of D．phenylglycine methyl ester hydrochloride was studied by batch dynamic methods．Samples of different times were measuredunderdifferent processing conditions．Then the CSD Was analyzedby laserCrystallization dynamic models of D．phenylglycine methyl ester granulometer．hydrochloride were established based on the mass balance equation and population balance equation．ARertransformation of moments on theexperimental data，the mathematical models for crystal growth rate and secondary nucleation rate were obtained，and the operating parameterswhich affected the crystallographicprogress were analyzed．The study on the crystallizationtechnique of D-phenylglycine methyl esterhydrochloride．The crystallization technique of D．．phenylglycinemethyl ester hydrochloride Was studied on the basis of crystallization thermodynamics and dynamics．The influence of crystallization method and process conditions on the quality and vield of product Wasstudied．A new crystallization and purification technique ofD-phenylglycinemethyl ester hydrochloride Was developed．The crystals produced by this new technique is of high purity，high yield，and good color level(1evel 1)，and their particle size increaSed anduniformed obviously．With stablequality of the product，low production COst aS wellas easy operation control，this technique has applied for China National invention patent．Andthousand tons has been realized．the industrialization of the annualoutput ofKey words D-phenylglycine methyl ester hydrochloride；Synthesis technique；Crystallization thermodynamics；Crystallization kinetics；The crystallizationtechniqueIV物理量名称及符号表物理量名称及符号表4一Apelblat方程参数；尸一压强；彳一晶体外表积：尸一系统搅拌强度量；40一指数因子；Qi-粒数密度；B—Apelblat方程参数：B一为生函数；Qi-引入结晶器的晶浆流量；矿一总成核速率；Q一引出结晶器的晶浆流量；啷一均相成核速率；，．一晶核半径；召s一二次成核速率；R一气体常量；C--Apelblat方程参数；R2一相关指数；C一溶液主体浓度；仅，，一与溶剂有关的非随机参数；Ci一溶液界面浓度；Gl，一NRTL模型参数；C。
Helena 0-0-21 植物滋养剂说明书
0-0-21CONCENTRATED POTASH SOLUTION AND OXIDIZED SULFURGUARANTEED ANALYSIS :Soluble Potash (K 2O) . . . . . . . . . . . . . . . . . . . . . . ……………………………….21.00% Sulfur (S)………………………………………………………………………………13.00% 13.00% Combined Sulfur (S)Derived from potassium thiosulfate. KEEP OUT OF REACH OF CHILDREN WARNINGMay be harmful if swallowedMay be harmful in contact with skin Causes serious eye irritation Causes skin irritation May be harmful if inhaledWEIGHT PER GALLON: 11.47 lbs. (5.20 kg) @ 68°F SN 041415/0815G FREEZING TEMPERATURE:.30°F NET CONTENTS: □ 5 gal (18.93 L) □ 30 gal (113.56 L)□ 250 gal (946.25 L) □ 275 gal (1040.99 L) □ Bulk ____________Information about the components of this lot of fertilizer may be obtained by writing to Helena Chemical Company, 225 Schilling Boulevard, Suite 300, Collierville, TN 38017 and giving the lot number which is found on the container.Information regarding the contents and levels of metals in this product is available on the Internet at /metals.htm F224MANUFACTURED FORHELENA CHEMICAL COMPANY225 SCHILLING BOULEVARD, SUITE 300 COLLIERVILLE, TN 38017 901-761-0050PRECAUTIONARY STATEMENTSHAZARDS TO HUMANS AND DOMESTIC ANIMALSWARNINGBEFORE USING THIS PRODUCT, READ ALL PRECAUTIONS, DIRECTIONS FOR USE, CONDITIONS OF SALE–LIMITED WARRANTY AND LIMITATIONS OF LIABILITY AND REMEDIES.May be harmful if swallowed. May be harmful in contact with skin. Causes serious eye irritation. Causes skin irritation. May be harmful if inhaled. Keep product locked up and out of the reach of children. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum or smoking tobacco. Remove and wash contaminated clothing before reuse. Do not take internally. Avoid contact with or inhalation of spray application mist if present. Do not apply this product in such a manner as to directly expose workers or other persons. If product is being mixed with pesticides and/or spray adjuvants, follow all precautionary statements on the accompanying product(s) labeling. Not for human or animal consumption.Personal Protective Equipment (PPE): Wear protective eyewear (goggles or face shield), chemical-resistant gloves, long-sleeved shirt and long pants, and shoes plus socks when using this product. Take off any contaminated clothing and wash before reuse. FIRST AID IF IN EYES: ∙ Rinse cautiously with water for several minutes. Removecontact lenses, if present and easy to do. Continue rinsing. ∙ Call a poison control center or doctor for treatmentadvice.IF SWALLOWED: ∙ Call a POISON CENTER or doctor immediately.∙ Rinse mouth. Do NOT induce vomiting. ∙ Do not give anything by mouth to an unconscious person.∙ Immediately call a POISON CENTER or doctor.IF INHALED:∙ Move person to fresh air and keep at rest in a position comfortable for breathing if they feel unwell.∙ If not breathing, call 911 or an ambulance, then give artificial respiration, preferably mouth-to-mouth if possible.∙ Call a POISON CENTER or doctor for treatment advice. IF ON SKIN ORHAIR:∙ Take off immediately all contaminated clothing. Rinse skin with water or shower.∙ Get medical attention if irritation develops or persists. ∙Wash contaminated clothing before reuse.HOT LINE NUMBERHave the product container or label with you when calling a poison control center or doctor, or going for treatment. You may also contact 1-800-424-9300 for emergency medical treatment information.STORAGE AND DISPOSALKeep container tightly closed and do not allow water to be introduced into it. Store in a dry place. Temperatures below 25°F may result in product crystallization. The product will readily reconstitute, however, with warmer temperatures and gentle agitation of the container.Do not contaminate water sources by cleaning of equipment or disposal of spray waste.Dispose of empty containers by triple rinsing with detergent solution or puncture and discard empty containers in a landfill in accordance with current local, state, and federal regulations. GENERAL INFORMATIONNUCLEUS® 0-0-21 is a highly concentrated water-based solution of potash and oxidized sulfur useful in the correction of nutritional deficiencies in plants. The unique formulation of NUCLEUS® 0-0-21 provides a non-corrosive liquid that is stable at cold temperatures. Applications of NUCLEUS® 0-0-21 through mixing, application, and irrigation equipment may reduce the rate and degree of corrosion that occurs when this equipment is exposed to fertilizer solutions. When used as directed this product does not supply all nutrients required by plants and is to supplement a soil fertility program based on soil tests.APPLICATION AND MIXING GUIDEApplication rates for general use are 2-6 gallons per acre.TURF: Apply 2 to 10 fl. ounces per 1,000 sq. ft. using 2 to 5 gallons of water per 1,000 sq. ft. Use lower rate during summer applications. Apply as needed.DO NOT APPLY NEAR WATER, STORM DRAINS, OR DRAINAGE DITCHES. DO NOT APPLY IF HEAVY RAIN IS EXPECTED. APPLY THIS PRODUCT ONLY TO YOUR LAWN/GARDEN. MIXING:NUCLEUS® 0-0-21 provides a neutral or slightly acidic pH value when diluted with water. This characteristic makes it compatible with most pesticides. In any mixing operation, NUCLEUS® 0-0-21 should be introduced in the following sequence: 1. Water2. NUCLEUS® 0-0-213. Other Fertilizer Products4. Pesticides5. Spray AdjuvantsCompatibility tests are always recommended prior to preparing a spray mixture of NUCLEUS® 0-0-21 with other products.CONDITIONS OF SALE–LIMITED WARRANTY AND LIMITATIONS OF LIABILITY AND REMEDIES Read the Conditions of Sale–Warranty and Limitations of Liability and Remedies before using this product. If the terms are not acceptable, return the product, unopened, and the full purchase price will be refunded.This label is believed to be reliable and must be followed carefully. Injury to the crop to which the product is applied may result from the occurrence of extraordinary or unusual weather conditions or the failure to follow the label directions or goodapplication practices, all of which are beyond the control of Helena Chemical Company (the "Company") or seller. In addition, failure to follow label directions may cause injury to crops, animals, man or the environment. The Company warrants that this product conforms to the chemical description on the label and is reasonably fit for the purpose referred to subject to the factors noted above which are beyond the control of the Company. The Company makes no other warranties or representations of any kind, express or implied, concerning the product, including no implied warranty of merchantability or fitness for any particular purpose, and no such warranty shall be implied by law.The exclusive remedy against the Company for any cause of action relating to the handling or use ofthis product shall be limited to, at Helena Chemical Company’s election, one of the following:1.Refund of the purchase price paid by buyer or user for product bought, or2.Replacement of the product usedTo the extent allowed by law, the Company shall not be liable and any and all claims against the Company are waived for special, indirect, incidental, or consequential damages or expense of any nature, including, but not limited to, loss of profits or income. The Company and the seller offer this product and the buyer and user accept it, subject to the foregoing conditions of sale and limitation of warranty, liability and remedies.© Copyright Helena Holding Company, 2015NUCLEUS® is a registered trademark of Helena Holding Company.。
世界卫生组织癌症研究机构三类致癌物清单
2013 2010 2013 2010 2010 2010 2010 2010 2013 2010 2010 2010 2010 2010 1999 1999 1987 1999 1999 1999 1999 1999 1999 1992 1987 1987 1999 1999 1999 2006 1999 1987 1991 2010 1987 1987 1987 1987 2017 2017 1987
3类致癌物清单（共502种）
3类致癌物：对人类致癌性可疑，尚无充分的人体或动物数据。 序号 英文名称 中文名称 1 Acenaphthene 二氢苊 Acepyrene (3,4Acepyrene (3,4-二氢环戊二烯并[cd] 2 dihydrocyclopenta[cd]pyre 芘]) ne) 3 Aciclovir 阿昔洛韦 4 Acridine orange 吖啶橙 5 Acriflavinium chloride 吖啶黄 6 Acrolein 丙烯醛 7 Acrylic acid 丙烯酸 8 Acrylic fibres 丙烯酸（类）纤维 Acrylonitrile-butadiene9 丙烯腈-丁二烯-苯乙烯共聚物 styrene copolymers 10 Actinomycin D 放线菌素D 11 Agaritine 伞菌氨酸（蘑菇氨酸） 12 Aldicarb 涕灭威 13 Allyl chloride 烯丙基氯 14 Allyl isothiocyanate 异硫氰酸烯丙酯 15 Allyl isovalerate 异戊酸烯丙酯 16 Amaranth 苋菜红 1-Amino-217 1-氨基-2-甲基蒽醌 methylanthraquinone 18 4-Amino-2-nitrophenol 4-氨基-2-硝基苯酚 19 2-Amino-4-nitrophenol 2-氨基-4-硝基苯酚 20 2-Amino-5-nitrophenol 2-氨基-5-硝基苯酚 21 2-Amino-5-nitrothiazole 2-氨基-5-硝基噻唑 22 5-Aminoacenaphthene 5-氨基二氢苊 23 2-Aminoanthraquinone 2-氨基蒽醌 24 11-Aminoundecanoic acid 11-氨基十一酸 25 Amitrole 杀草强 26 Ampicillin 氨苄青霉素 27 Anaesthetics, volatile 有挥发性的麻醉药 Angelicin plus ultraviolet 28 白芷素伴紫外线A辐射 A radiation 29 Aniline 苯胺 30 Anthanthrene 二苯并[cd,jk]芘 31 Anthracene 蒽 32 Anthranilic acid 邻氨基苯甲酸 33 Antimony trisulfide 三硫化二锑 34 Apholate 环磷氮丙啶 Arsenobetaine and other organic arsenic compounds 砷甜菜碱和人不能代谢的其它有机 35 that are not metabolized in 砷化合物 humans 36 Atrazine 阿特拉津 37 Aurothioglucose 金硫葡糖 38 2-(1-Aziridinyl)ethanol 2-1-吖丙啶乙醇 39 Aziridyl benzoquinone 氮丙啶基苯醌 40 Azobenzene 偶氮苯 时间（年） 2010 2010 2000 1987 1987 1995 1999 1987 1987 1987 1987 1991 1999 1999 1999 1987 1987 1987 1993 1993 1987 1987 1987 1987 2001 1990 1987 1987 1987 2010 2010 1987 1989 1987 2012 1999 1987 1987 1987 1987
重组贻贝粘蛋白的表征及功效评价
生物技术进展 2023 年 第 13 卷 第 4 期 596 ~ 603Current Biotechnology ISSN 2095‑2341研究论文Articles重组贻贝粘蛋白的表征及功效评价李敏 ， 魏文培 ， 乔莎 ， 郝东 ， 周浩 ， 赵硕文 ， 张立峰 ， 侯增淼 *西安德诺海思医疗科技有限公司，西安 710000摘要：为了推进重组贻贝粘蛋白在医疗、化妆品领域的应用，对大肠杆菌规模化发酵及纯化生产获得的重组贻贝粘蛋白进行了表征及功效评价。
经Edman 降解法、基质辅助激光解吸电离飞行时间质谱、PITC 法、非还原型SDS -聚丙烯酰胺凝胶电泳法、凝胶法、改良的Arnow 法对重组贻贝粘蛋白进行氨基酸N 端测序、相对分子量分析、氨基酸组成分析、蛋白纯度分析、内毒素含量测定、多巴含量测定；通过细胞迁移、斑马鱼尾鳍修复效果对重组贻贝粘蛋白进行功效评价。
结果显示，获得的重组贻贝粘蛋白与理论的一级结构一致，蛋白纯度达95%以上，内毒素<10 EU ·mg -1,多巴含量大于5%；重组贻贝粘蛋白浓度为60 μg ·mL -1时能够显著促进细胞增殖的活性（P <0.01）；斑马鱼尾鳍面积样品组与模型对照组相比极显著增加（P <0.001）。
研究结果表明，重组贻贝粘蛋白具有显著的促细胞迁移和修复愈合的功效，具备作为生物医学材料的潜质。
关键词：贻贝粘蛋白；基因重组；生物材料；表征；功效评价DOI ：10.19586/j.20952341.2023.0021 中图分类号：S985.3+1 文献标志码：ACharacterization and Efficacy Evaluation of Recombinant Mussel Adhesive ProteinLI Min ， WEI Wenpei ， QIAO Sha ， HAO Dong ， ZHOU Hao ， ZHAO Shuowen ， ZHANG Lifeng ，HOU Zengmiao *Xi'an DeNovo Hith Medical Technology Co.， Ltd ， Xi'an 710000， ChinaAbstract ：In order to promote the application of recombinant mussel adhesive protein in the medical and cosmetics field ， the recombi⁃nant mussel adhesive protein obtained from scale fermentation and purification of Escherichia coli was characterized and its efficacy was evaluated. Amino acid N -terminal sequencing ， relative molecular weight analysis ， amino acid composition analysis ， protein purityanalysis ， endotoxin content ， dihydroxyphenylalanine （DOPA ） content of recombinant mussel adhesive protein were determined by the following methods ： Edman degradation ， matrix -assisted laser desorption ionization time -of -flight mass spectrometry （MALDI -TOF -MS ）， phenyl -isothiocyanate （PITC ）， nonreductive SDS -polyacrylamide gel electrophoresis （SDS -PAGE ）， gel method ， modified Ar⁃now. The efficacy of recombinant mussel adhesive protein was evaluated by cell migration and repairing effect of zebrafish tail fin. Re⁃sults showed that the obtained recombinant mussel adhesive protein was confirmed to be consistent with the theoretical primary structure ， protein purity of more than 95%， endotoxin <10 EU ·mg -1， DOPA content above 5%. When the recombinant mussel adhesive protein concentration was 60 μg ·mL -1， the effect of promoting cell proliferation was the most obvious ， and it had very significant activity （P <0.01）. The caudal fin area of zebrafish in sample group was significantly increased compared with model control group （P <0.001）. The results indicated that recombinant mussel adhesive protein can promote cell migration and repair healing and has the potential to be used as biomedical materials.Key words ：mussel adhesive protein ； gene recombination ； biological materials ； representation ； efficacy evaluation贻贝粘蛋白（mussel adhesive protein ， MAP ）也称作贻贝足丝蛋白（mussel foot protein ，Mfps ），收稿日期：2023⁃02⁃24； 接受日期：2023⁃03⁃31联系方式：李敏 E -mail:*******************;*通信作者 侯增淼 E -mail:***********************.cn李敏，等：重组贻贝粘蛋白的表征及功效评价是海洋贝类——紫贻贝（Mytilus galloprovincalis）、厚壳贻贝（Mytilus coruscus）、翡翠贻贝（Perna viri⁃dis）等分泌的一种特殊的蛋白质，贻贝中含有多种贻贝粘蛋白，包括贻贝粘蛋白（Mfp 1～6）、前胶原蛋白（precollagens）和基质蛋白（matrix proteins）等［1］。
执业药师药理学真题
B.水溶液呈中性 D. 可用 Vitali 反应鉴别B. 左旋体 D. 内消旋体B.与香草醛试液反应 D.Vitali 反应按题干要求在五个备选答案中选出一个最佳答案 , 最佳选择题 ．下列不属于免疫抑制药物是： 1A •巯嘌吟B •肾上腺皮质激素类C. 卡介苗 D •环磷酰胺E .环抱素2．下列不属于免疫增强药物是： A •干扰素 B •转移因子C. 左旋咪唑 D •抗淋巴细胞球蛋白E .胸腺素3 •下列哪种叙述与胆碱受体激动剂不符A. 乙酰胆碱的乙酰基部分为芳环或较大分子量的基团时，转变为胆碱受体拮抗剂B. 乙酰胆碱的亚乙基桥上 ?位甲基取代， M 样作用大大增强，成为选择性 M 受体激动剂C. Carbachol 作用较乙酰胆碱强而持久D. Bethanechol Chloride 的S 构型异构体的活性大大高于 R 构型异构体E. 中枢 M 胆碱受体激动剂是潜在的抗老年痴呆药物 4 •下列有关乙酰胆碱酯酶抑制剂的叙述不正确的是A. Neostigmine Bromide 是可逆性乙酰胆碱酯酶抑制剂，其与 AChE 结合后形成的二甲氨基甲酰 化的酶结合物，水解释出原酶需要几分钟B. Neostigmine Bromide 结构中N, N -二甲氨基甲酸酯较 Physostigmine 结构中N-甲基氨基甲酸酯 稳定C. 中枢乙酰胆碱酯酶抑制剂可用于抗老年痴呆D. 经典的乙酰胆碱酯酶抑制剂结构中含有季铵碱阳离子、芳香环和氨基甲酸酯三部分E. 有机磷毒剂也是可逆性乙酰胆碱酯酶抑制剂 5 •下列叙述哪个不正确A. Scopolamine 分子中有三元氧环结构，使分子的亲脂性增强B. 托品酸结构中有一个手性碳原子， S 构型者具有左旋光性C. Atropine 水解产生托品和消旋托品酸D. 莨菪醇结构中有三个手性碳原子 C1、C3和C5,具有旋光性E. 山莨菪醇结构中有四个手性碳原子C1、C3、C5和C6,具有旋光性 6 •关于硫酸阿托品，下列说法不正确的是 A. 现可采用合成法制备 C.在碱性溶液较稳定E.制注射液时用适量氯化钠作稳定剂 7 •临床应用的阿托品是莨菪碱的 A. 右旋体 C.外消旋体 E.都在使用8•阿托品的特征定性鉴别反应是 A. 与 AgNO3 溶液反应 C.与CuSO4试液反应 E.紫脲酸胺反应选择题呫吨基的是9-胆碱受体拮抗剂分子中，具有M •下列合成9.A. Glycopyrr onium BromideB. Orphe nadr ineD. Ben actyz ine C. Propa ntheli ne BromideE. Pire nzep ine10Adrenaline不符的叙述是•下列与可激动饱和水溶液呈弱碱性和受体 A. B.R含邻苯二酚结构，易氧化变质构型为活性体，具右旋光性 D.-碳以C.E.直接受到单胺氧化酶和儿茶酚氧位甲基转移酶的代谢)-Ephedrine的结构是11.临床药用(OHOHNN B.A.(1S2S)(1S2ROO C. D. (1R2S(1R2R)上述四种的混合物E.受体拮抗剂的哪种结构类型12. Diphenhydramine属于组胺H1哌嗪类A.乙二胺类 B.D. C.丙胺类三环类氨基醚类E.13. 下列何者具有明显中枢镇静作用A. Chlorphe nami neB. Clemast ineC. AcrivastineD. LoratadineE. Cetirizi ne14. 若以下图代表局麻药的基本结构，则局麻作用最强的X为OCnNArXA. —O —B. —NH —C. —S—D. —CH2 —E. —NHNH —15. Lidocaine比Procaine作用时间长的主要原因是A. Procaine有芳香第一胺结构B. Procaine有酯基C. Lidocaine有酰胺结构D. Lidocaine的中间部分较Procaine短E.酰胺键比酯键不易水解16. 盐酸普鲁卡因最易溶于哪种试剂A.水B.酒精C.氯仿D.乙醚E.丙酮17. 盐酸鲁卡因因具有( )，故重氮化后与碱性B萘酚偶合后生成猩红色偶氮染料A.苯环B.伯氨基C.酯基D.芳伯氨基E.叔氨基18. 盐酸利多卡因的乙醇溶液加氯化钻试液即生成蓝绿色沉淀B. 结晶性沉淀A.D. 紫色沉淀 C.黄色沉淀E. 红色沉淀比较配伍题。
Natrix Q 蛋白质膜产品说明书
Figure 1. The Natrix ® Q chromatography membrane family offers scalable polishing from R&D to clinical to commercial manufacturing.Data SheetKey Benefits• Best-in-class HCP , DNA, endotoxin and virus removal • Salt and pH tolerance even in phosphate buffer • High capacity final polishing with high mAb throughput (>10 kg/L)• Simple, low-cost purification in a single-use formatInnovative Membrane TechnologyThe unique Natrix ® Q membrane is a porous polyacrylamide hydrogel containing a high density of pendant quaternary ammonium (Q) binding groups physically reinforced by an inert fiber web (see Figure 2). The interconnected pore structure (nominal pore size, 0.4 μm) and high ligand density provides a large surface area for protein binding, high permeability and enables fast flow rates with high throughput to extremely high loads (> 10 kg per liter of membrane for some mAbs) while maintaining excellent impurity clearance at these extreme operating conditions. In combination with the well-established Q ligand chemistry, these features make the Natrix ® chromatography membrane an excellent choice for reliable purification in commercial scale.Natrix ® QChromatography MembraneFor single-use, scalable purificationNatrix ® chromatography membrane is a high capacity, high throughput strong anion exchange device designed to purify biomolecules. It combines the capacity of high performing resins with the exceptional flow properties of chromatography membranes. The Natrix ® chromatography membrane platform is fully scalable from0.2 mL devices to production-scale and delivers enhancements in productivity, flexibility, and process robustness for any bioprocess.The Life Science business of Merck operates as MilliporeSigma in the U.S. and Canada.2Flexible polymeric support web physically reinforces functional hydrogel.Web is enclosed by and filled with porous functionalized hydrogel,establishing pore size.Figure 2. Structure of Natrix ® membrane technology Composed of a porous, functionalized 3-dimensional hydrogel polymerized within and around a flexible fiber web support.SpecificationsNatrix ® Q PilotCatalogue No.NXF-10Pack size1 unitMembrane material Porous polyacrylamide hydrogel reinforced with inert polymeric web LigandQuaternary amine (Q)Membrane configuration Pleated Number of layers2Nominal membrane bed thickness0.5 mm Typical membrane bubble point pore diameter 1.4 μm Typical membrane flow pore diameter 0.4 μm Nominal unit membrane volume 15 mLTypical unit flow rate range75–375 mL/minMaximum operating pressure & temperature (liquids)75 psi/5.2 bar at 32–100 °F/0–38 °C Nominal unit weight110 gLength (connector-connector)Approximately 165 mm/6.5 in.Width (weld diameter)Approximately 69.9 mm/2.75 in.ConnectorsInlet, outlet: 3/4 in. sanitary (TC) Vent: Luer Drain: Luer Housing material (polypropylene), biological reactivity USP <88> ClassVI Membrane cytotoxicityISO 10993-53Natrix ® Q Process 150Catalogue No.NXF-20Pack size1 unitMembrane material Porous polyacrylamide hydrogel reinforced with inert polymeric web LigandQuaternary amine (Q)Membrane configuration Pleated Number of layers2Nominal membrane bed thickness0.5 mm Typical membrane bubble point pore diameter 1.4 μm Typical membrane flow pore diameter 0.4 μm Nominal unit membrane volume 115 mL Typical unit flow rate range0.6–3.0 L/minMaximum operating pressure & temperature (liquids)90 psi/6.2 bar at 32–100 °F/0–38 °C Nominal unit weight 665 gLength (base to vent tip)Approximately 330 mm/13.0 in.Width (connector-connector)Approximately 133.4 mm/5.25 in.Width (diameter)Approximately 88.4 mm/3.48 in.ConnectorsInlet, outlet: 1 in. sanitary (TC) Vent: SanitaryDrain: 1/4 in. Sanitary Housing material (polypropylene), biological reactivity USP <88> ClassVI Membrane cytotoxicityISO 10993-5Natrix ® Q 150Capsule Dimensions4Natrix ® Q Process 600Catalogue No.NXF-50Pack size1 unitMembrane material Porous polyacrylamide hydrogel reinforced with inert polymeric web LigandQuaternary amine (Q)Membrane configuration Pleated Number of layers2Nominal membrane bed thickness0.5 mm Typical membrane bubble point pore diameter 1.4 μm Typical membrane flow pore diameter 0.4 μm Nominal unit membrane volume 460 mL Typical unit flow rate range2.3–11.5 L/minMaximum operating pressure & temperature (liquids)90 psi/6.2 bar at 32–100 °F/0–38 °C Nominal unit weight 2080 gLength (base to vent tip)Approximately 1049 mm/41.3 in.Width (connector-connector)Approximately 133.4 mm/5.25 in.Width (diameter)Approximately 88.4 mm/3.48 in.ConnectorsInlet, outlet: 1 in. sanitary (TC) Vent: SanitaryDrain: 1/4 in. Sanitary Housing material (polypropylene), biological reactivity USP <88> ClassVI Membrane cytotoxicityISO 10993-5Natrix ® Q 600Capsule DimensionsTable 1. Primary characteristics of the Natrix® Q chromatography membrane technologyHydrogel Porous polyacrylamideFunctional group Quaternary amineTypical flow rate5–25 mL/minNominal pore size0.4 μmBSA binding capacity>200 mg/mLDNA binding capacity>20 mg/mLChemical compatibility Compatible with most buffers and solvents commonly used in chromatographic biomolecule purificationprocesses (see the Validation Guide for complete and detailed information)Incompatible chemicals Hypochlorite (1%); SDS (1%)Shipment conditions Dry, ready to use (free of preservatives or wetting agents)Storage conditions Store at room temperature prior to useTable 2. Natrix® Q Chromatography Membrane Properties21Natrix® Q Micro Scaled down laboratory model toscreen and fine-tune parameters.1–5mL/min Flat sheet20.040.2Natrix® Q Pilot Intermediate scale, intended to verifyand adjust operating parameters. Pilotmay be used for smallscale clinical orcommercial manufacturing.75–375mL/minPleated150315Natrix® QProcess 150 Process scale designed forclinical and commercialmanufacturing of proteins.0.6–3L/min115023115Natrix® Q Process 6002–10L/min4600924601B ased on typical process streams and loading up to 10 kg mAb/L-membrane. Loading capacity is not limited to 10 kg/L and depends on the total impurity content.2T ypical flow-rate range is based on 5–25 membrane volumes/minute. Specific flow-rates can be determined to accommodate process requirements (e.g. maximum back pressure, improved process time, etc.).Ordering InformationNatrix® Q Micro0.210NXF-00 Natrix® Q Pilot151NXF-10 Natrix® Q Process 1501151NXF-20 Natrix® Q Process 6004601NXF-505For additional informationplease visit To place an order orreceive technical assistanceplease visit /contactPS Merck KGaAFrankfurter Strasse 250 64293 Darmstadt, Germany© 2022 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved. Merck, the vibrant M, Millipore, and Natrix are trademarks of Merck KGaA, Darmstadt, Germany or its affiliates. All other trademarks are the property of their respective owners. Detailed information on trademarks is available via publicly accessible resources.MK_DS2158EN Ver. 1.04136207/2022。
高效液相色谱-串联质谱法检测泮托拉唑钠原料药中的水合肼
·药物研发·高效液相色谱-串联质谱法检测泮托拉唑钠原料药中的水合肼赵会明 张振洋 樊华军［英格尔检测技术服务（上海）有限公司 上海 201100］摘要建立了泮托拉唑钠原料药中的基因毒性杂质水合肼的高效液相色谱-串联质谱（LC-MSMS）检测方法。
采用反相色谱，以水-乙腈（含0.1%甲酸）为流动相，梯度洗脱，流速0.5 mL/min，以ESI正离子多反应监测（MRM）模式进行质谱检测。
结果显示，水合肼的检测限和定量限可达到0.23、0.47 ng/mL，其在0.47~9.37 ng/mL浓度范围内线性关系良好（r=0.999 9），准确度试验中低、中、高浓度回收率均在81.6%~90.9%之间。
在3批次泮托拉唑钠原料药中均未检出水合肼。
关键词高效液相色谱-串联质谱法基因毒性杂质泮托拉唑钠水合肼痕量检测中图分类号：R917; O657 文献标志码：A 文章编号：1006-1533(2022)11-0072-04引用本文 赵会明, 张振洋, 樊华军. 高效液相色谱-串联质谱法检测泮托拉唑钠原料药中的水合肼[J]. 上海医药, 2022, 43(11): 72-75.Determination of hydrazine hydrate in pantoprazole sodium by high performance liquid chromatography-tandem mass spectrometryZHAO Huiming, ZHANG Zhenyang, FAN Huajun[ICAS Testing Technology Service (Shanghai) CO., LTD., Shanghai 201100, China]ABSTRACT To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MSMS) method for the determination of hydrazine hydrate in active pharmaceutical ingredient (API) pantoprazole sodium. HPLC was carried out by reverse chromatography using water-acetonitrile containing 0.1% formic acid as flow phase and gradient elution at a flow rate of 0.5 mL/min. Mass spectrometry was performed with multi-reaction monitoring (MRM) in positive ESI mode. The detection and quantitative limits of hydrazine hydrate reached 0.23, 0.47 ng/mL and hydrazine hydrate showed good linear relationship in the range of 0.47-9.37 ng/mL (r=0.999 9). The recoveries of samples at low, medium and high-level concentrations reached81.6% to 90.9% in the accuracy experiment. No hydrazine hydrate was detected in 3 batches of pantoprazole sodium.KEY WORDS HPLC-tandem mass spectrometry; genotoxic impurities; pantoprazole sodium; hydrazine hydrate; trace determination上消化道出血是近年的临床疾病中常见且多发的一种疾病，其临床表现为呕血、黑便等，如得不到及时有效治疗，可能引发失血性休克。
FDA兽药管理目录4
Section 2.0 - Active IngredientsApplicationActive Ingredients Trade NameNumber005-2362-Mercaptobenzothiazole Sulfodene® Medication for Dogs015-030Acepromazine Maleate PromAce® Injectable032-702Acepromazine Maleate PromAce® Tablets117-531Acepromazine Maleate Acepromazine Maleate Injection117-532Acepromazine Maleate Acepromazine Maleate Tablets200-319Acepromazine Maleate Acepromazine Maleate Injection200-361Acepromazine Maleate Acepromazine Maleate Injection011-582Acetazolamide Sodium Vetamox Soluble Powder011-700Acetylsalicylic Acid, Methylprednisolone Cortaba® Tablets141-406Afoxolaner NexGard™014-250Aklomide, Sulfanitran Novastat Type A Medicated Premix034-536Aklomide, Roxarsone Aklomix Type A Medicated Article, Aklomix-3034-537Aklomide, Roxarsone, Sulfanitran Novastat-3 Type A Medicated Article035-388Aklomide, Sulfanitran Novastat-W110-048Albendazole Valbazen®128-070Albendazole Valbazen®140-934Albendazole Valbazen®141-180Albuterol Sulfate Torpex™141-342Alfaxalone Alfaxan®131-310Altrenogest Regu-Mate®141-222Altrenogest Matrix®127-892Amikacin Sulfate Amiglyde-V200-178Amikacin Sulfate Amikacin Sulfate Injection200-181Amikacin Sulfate AmiMax™ E Solution043-078Aminopentamide Hydrogen Sulfate Centrine Oral Tablets043-079Aminopentamide Hydrogen Sulfate Centrine Injectable092-116Aminopentamide Hydrogen Sulfate, Ketamine Ketaset® PlusHydrochloride, Promazine Hydrochloride011-877Aminopropazine Fumarate Jenotone Tablets013-181Aminopropazine Fumarate, Neomycin Sulfate Jenomycin Tablets034-477Aminopropazine Fumarate Jenotone Solution120-299Amitraz Mitaban® Liquid Concentrate009-339Ammonium Chloride, Caramiphen Edisylate Carafen Cough Syrup, Carafen Cough Tablets055-078Amoxicillin Trihydrate Amoxi-Tabs055-080Amoxicillin Trihydrate Amoxi-DoserFDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 1 of 70Number055-081Amoxicillin Trihydrate Amoxi-Tabs055-085Amoxicillin Trihydrate Amoxi-Drop® Oral Suspension055-087Amoxicillin Trihydrate Amoxi-Bol055-088Amoxicillin Trihydrate Amoxi-Sol055-089Amoxicillin Trihydrate Amoxi-Inject (Cattle)055-091Amoxicillin Trihydrate Amoxi-Inject (Dogs and Cats)055-099Amoxicillin Trihydrate, Clavulanate Potassium Clavamox® Tablets055-100Amoxicillin Trihydrate Amoxi-Mast055-101Amoxicillin Trihydrate, Clavulanate Potassium Clavamox® Drops065-492Amoxicillin Trihydrate Biomox065-495Amoxicillin Trihydrate Biomox®141-004Amoxicillin Trihydrate Robamox®-V141-005Amoxicillin Trihydrate Robamox®-V TabletsKanfosone Ointment043-784Amphomycin Calcium, Hydrocortisone Acetate,Kanamycin Sulfate047-997Amphomycin Calcium, Hydrocortisone Acetate,Amphoderm OintmentKanamycin Sulfate055-013Ampicillin Anhydrous Omnipen 250 mg055-084Ampicillin Sodium Amp-Equine200-335Ampicillin sodium Ampicillin Sodium055-030Ampicillin Trihydrate Polyflex®055-036Ampicillin Trihydrate Princillin Capsules 125 mg, Princillin Capsules 250 mg,Princillin Capsules 500 mg055-042Ampicillin Trihydrate Ampi-Tab055-050Ampicillin Trihydrate Princillin Soluble Powder055-056Ampicillin Trihydrate Princillin Bolus055-061Ampicillin Trihydrate Princillin "125" For Oral Suspension055-064Ampicillin Trihydrate Princillin Injection055-066Ampicillin Trihydrate Princillin Injection055-071Ampicillin Trihydrate Princillin Injection 200 mg055-074Ampicillin Trihydrate Ampi-Bol055-079Ampicillin Trihydrate Ampi-Ject200-180Ampicillin Trihydrate Ampicillin Trihydrate012-350Amprolium Amprovine 25%, CORID® 25% Type A Medicated Article 013-149Amprolium Amprovine 9.6% Solution013-461Amprolium, Ethopabate, Roxarsone Broiler PMX No.1620, Amprol Plus®, Amprol Hi-E®, AmprolPlus + Nitro®013-663Amprolium Purina® Liquid Amprol033-165Amprolium Amprovine 20% Soluble Powder, Corid 20% Soluble Powder FDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 2 of 70NumberAmprol HI-E® Plus036-304Amprolium, Bacitracin Methylene Disalicylate,EthopabateAmp Ethopabate CTC® Sodium Sulfate 036-361Amprolium, Chlortetracycline Calcium Complex,Ethopabate, Sodium SulfateErythro® (Low Lev) / Amp plus Etho 038-242Amprolium, Arsanilic Acid, ErythromycinThiocyanate, Ethopabate041-178Amprolium, Ethopabate, LincomycinAmprol® Plus / Lincomix® / RoxarsoneHydrochloride Monohydrate, RoxarsoneLincomix® / Amprol Plus044-820Amprolium, Ethopabate, LincomycinHydrochloride Monohydrate049-179Amprolium, Ethopabate, Roxarsone Amprol HI-E® / RoxarsoneAmprol HI-E® / BMD® / Roxarsone 049-180Amprolium, Bacitracin Methylene Disalicylate,Ethopabate, Roxarsone095-543Amprolium, Bambermycins, Ethopabate Amprol HI-E® & Bambermycins, Amprol HI-E® / Flavomycin®3-Nitro® / Amprol HI-E® / Flavomycin®095-547Amprolium, Bambermycins, Ethopabate,Roxarsone095-548Amprolium, Bambermycins, Roxarsone3-Nitro® / Amprol / Flavomycin®095-549Amprolium, Bambermycins, Ethopabate,3-Nitro® / Amprol / Flavomycin®RoxarsoneAmprol HI-E® / Baciferm® / 3-Nitro®105-758Amprolium, Bacitracin Zinc, Ethopabate,Roxarsone114-794Amprolium, Bacitracin Zinc, Ethopabate Baciferm® / Amprol HI-E® Premix118-507Amprolium, Carbarsone Amprol® / Carb-O-Sep®122-822Amprolium, Ethopabate, Virginiamycin Amprol HI-E® / Stafac®130-185Amprolium, Bambermycins Flavomycin® / Amprolium3-Nitro® / Amprol® / BMD®141-142Amprolium, Bacitracin Methylene Disalicylate,Roxarsone141-156Amprolium, Bacitracin Methylene Disalicylate Amprol® / BMD®200-205Amprolium, Bacitracin Zinc, Ethopabate Albac® / Amprol Hi-E®3-Nitro® / Albac® / Amprol Hi-E®200-214Amprolium, Bacitracin Zinc, Ethopabate,Roxarsone3-Nitro® / Albac® / Amprol Hi-E®200-217Amprolium, Bacitracin Zinc, Ethopabate,Roxarsone200-389Amprolium Amprolium 9.6% Oral Solution200-463Amprolium Amprolium 9.6% Oral Solution200-464Amprolium Ampromed™ for Calves200-482Amprolium AmproMed™ for Calves200-488Amprolium Ampromed™ P for Poultry200-496Amprolium AmproMed™ P for Poultry200-514Amprolium Boviprol™ 9.6% Oral Solution106-964Apramycin Sulfate Apralan® Soluble Powder126-050Apramycin Sulfate Apralan® 75 Soluble PowderErythro® (High Lev) / Zoalene plus Arsanilic Acid 038-241Arsanilic Acid, Erythromycin Thiocyanate,ZoaleneFDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 3 of 70Number038-242Amprolium, Arsanilic Acid, ErythromycinErythro® (Low Lev) / Amp plus EthoThiocyanate, Ethopabate038-624Arsanilic Acid, Erythromycin Thiocyanate Pro-Gallimycin-10006-623Arsenamide Sodium Caparsolate Sodium141-033Atipamezole Hydrochloride Antisedan®013-248Atropine, Trichlorfon Freed No. 10, Freed No. 25035-650Atropine, Trichlorfon Dyrex Powder042-548Attapulgite, Bismuth Subcarbonate, KanamycinAmforol® SuspensionSulfateAmforol® Veterinary Oral Tablets042-841Attapulgite, Bismuth Subcarbonate, KanamycinSulfate115-732Azaperone Stresnil InjectionAmprol HI-E® Plus036-304Amprolium, Bacitracin Methylene Disalicylate,Ethopabate039-646Bacitracin Methylene Disalicylate, Carbarsone Carb-O-GainBMD® 15 / Coyden 25®041-541Bacitracin Methylene Disalicylate, Clopidol,Roxarsone046-592Bacitracin Methylene Disalicylate BMD® 50 Granular A Type A Medicated Article, BMD® 30Type A Medicated ArticleAmprol HI-E® / BMD® / Roxarsone 049-180Amprolium, Bacitracin Methylene Disalicylate,Ethopabate, Roxarsone049-463Bacitracin Methylene Disalicylate, Monensin USP Coban® plus BMD®Coban® plus 3-NITRO® plus BMD®049-464Bacitracin Methylene Disalicylate, MonensinUSP, RoxarsoneEntromycin Powder065-107Bacitracin Methylene Disalicylate, StreptomycinSulfate065-280Bacitracin Methylene Disalicylate Soluble Fortracin Concentrate065-470Bacitracin Methylene Disalicylate BMD® Soluble, BMD® Soluble 50%, Solu-tracin 200, Solu-tracin 50Bac MD / Robenz®097-085Bacitracin Methylene Disalicylate, RobenidineHydrochloride098-378Bacitracin Methylene Disalicylate, Nicarbazin Nicarb® 25% and bacitracin methylene disalicylate099-150Bacitracin Methylene Disalicylate, Clopidol BMD® / Coyden 25®107-996Bacitracin Methylene Disalicylate, Lasalocid Avatec® / Fortracin Premix3-Nitro® / Avatec® / BMD®116-082Bacitracin Methylene Disalicylate, Lasalocid,Roxarsone116-088Bacitracin Methylene Disalicylate, Monensin3-Nitro® / BMD® / Coban®, 3-Nitro® / Coban® / Fortracin Sodium, Roxarsone3-Nitro® / Avatec® / Fortracin Broiler Premix 131-894Bacitracin Methylene Disalicylate, Lasalocid,Roxarsone3-Nitro® / Bio-Cox® / BMD®135-321Bacitracin Methylene Disalicylate, Roxarsone,Salinomycin Sodium135-746Bacitracin Methylene Disalicylate, SalinomycinBio-Cox® / BMD®SodiumFDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 4 of 70Number138-456Bacitracin Methylene Disalicylate, MonensinSodiumCoban® / BMD®140-533Bacitracin Methylene Disalicylate, HalofuginoneHydrobromide, Roxarsone3-Nitro® / BMD® / Stenorol®140-584Bacitracin Methylene Disalicylate, HalofuginoneHydrobromideBMD / Stenorol®140-852Bacitracin Methylene Disalicylate, Narasin,Roxarsone3-Nitro® / BMD® / Monteban®140-853Bacitracin Methylene Disalicylate, Narasin BMD® / Monteban®140-919Bacitracin Methylene Disalicylate, HalofuginoneHydrobromideBMD® / Stenorol®140-926Bacitracin Methylene Disalicylate, Narasin,NicarbazinBMD® / Maxiban®140-937Bacitracin Methylene Disalicylate, MonensinSodiumBMD® / Coban®141-058Bacitracin Methylene Disalicylate, Roxarsone,Semduramicin Sodium3-Nitro® / Aviax™ / BMD®141-059Bacitracin Methylene Disalicylate,Chlortetracycline BMD® 10, 25, 30, 40, 50, 60, 75 / CTC® 50, 65, 70, BMD® 25, 30, 40, 50, 60, 75 / ChlorMax™®- 50, 60, 70, MICRO-CTC® 100141-065Bacitracin Methylene Disalicylate, SemduramicinSodiumAviax™ / BMD®141-085Bacitracin Methylene Disalicylate, Zoalene BMD® / Zoamix®141-088Bacitracin Methylene Disalicylate, Nitarsone BMD® / Histostat®141-097Bacitracin Methylene Disalicylate, Ivermectin BMD® / Ivomec® Premix for Swine141-100Bacitracin Methylene Disalicylate, Decoquinate,Roxarsone3-Nitro® / BMD® / Deccox®141-102Bacitracin Methylene Disalicylate, Decoquinate BMD® / Deccox®141-112Bacitracin Methylene Disalicylate, Narasin,Nicarbazin, Roxarsone3-Nitro® / BMD® / Maxiban®141-121Bacitracin Methylene Disalicylate, Roxarsone,Salinomycin Sodium3-Nitro® / Bio-Cox® / BMD®141-124Bacitracin Methylene Disalicylate, Narasin,NicarbazinBMD® / Maxiban®141-136Bacitracin Methylene Disalicylate, SalinomycinSodiumBio-Cox® / BMD®141-138Bacitracin Methylene Disalicylate, Monensin,Roxarsone3-Nitro® / BMD® / Coban®141-140Bacitracin Methylene Disalicylate, Monensin BMD® / Coban®141-142Amprolium, Bacitracin Methylene Disalicylate,Roxarsone3-Nitro® / Amprol® / BMD®141-144Bacitracin Methylene Disalicylate, Fenbendazole BMD® / Safe-Guard®141-153Bacitracin Methylene Disalicylate, Diclazuril BMD® / Clinacox™141-154Bacitracin Methylene Disalicylate, RobenidineHydrochlorideBMD® / Robenz®FDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 5 of 70Number141-155Bacitracin Methylene Disalicylate, RobenidineHydrochloride, Roxarsone3-Nitro® / BMD® / Robenz®141-156Amprolium, Bacitracin Methylene Disalicylate Amprol® / BMD®141-179Bacitracin Methylene Disalicylate, Lasalocid Avatec® / BMD®141-190Bacitracin Methylene Disalicylate, Diclazuril,Roxarsone3-Nitro® / BMD® / Clinacox™141-194Bacitracin Methylene Disalicylate, Diclazuril BMD® / Clincox®141-195Bacitracin Methylene Disalicylate, Diclazuril Clinacox™/ Flavomycin®141-279Nicarbazin, Bacitracin methylene disalicylate Nicarb® 25% plus BMD®200-081Bacitracin Methylene Disalicylate, Roxarsone,Salinomycin Sodium3-Nitro® / BMD® / Sacox®200-082Bacitracin Methylene Disalicylate, SalinomycinSodiumBMD® / Sacox®200-164Bacitracin Methylene Disalicylate, Nicarbazin BMD® / Nicarmix 25®200-242Bacitracin Methylene Disalicylate,Chlortetracycline Calcium Complex BMD®-25, -30, -40, -50, -60, or -75 / Aureomycin® -50, -70, -80, -90 or -100200-358Bacitracin Methylene Disalicylate,Chlortetracycline HydrochloridePennchlor/ BMD044-016Bacitracin Zinc, Clopidol, Roxarsone Coyden 25® with Roxarsone and Bacitracin Zinc045-348Bacitracin Zinc, Decoquinate Albac® / Deccox®, Broiler Finisher Medicated046-920Bacitracin Zinc Baciferm® - 10, Baciferm® - 25, Baciferm® - 40, Baciferm® -50047-933Bacitracin Zinc, Monensin, USP Coban® plus Baciferm®049-934Bacitracin Zinc, Clopidol Coyden 25® with Bacitracin Zinc065-015Bacitracin Zinc, Hydrocortisone Acetate,Neomycin Sulfate, Polymyxin B Sulfate Bacitracin-Neomycin-Polymyxin with Hydrocortisone Acetate Ophthalmic Ointment, Vetropolycin HC Ophthalmic Ointment065-016Bacitracin Zinc, Neomycin Sulfate, Polymyxin B Sulfate Bac-Neo-Poly Ophthalmic Ointment, Vetropolycin Ophthalmic Ointment065-114Bacitracin Zinc, Neomycin Sulfate, Polymyxin BSulfateMycitracin® Sterile Ophthalmic Ointment065-313Bacitracin Zinc Baciferm® Soluble 50065-476Bacitracin Zinc, Hydrocortisone Acetate,Neomycin Sulfate, Polymyxin B SulfateCortisporin Veterinary Ophthalmic Ointment065-485Bacitracin Zinc, Neomycin Sulfate, Polymyxin BSulfateNeosporin Ophthalmic Ointment091-326Bacitracin Zinc, Decoquinate, Roxarsone3-Nitro® / Deccox® / Albac®096-933Bacitracin Zinc, Robenidine Hydrochloride Robenz® Plus Zn Bacitracin098-452Bacitracin Zinc Albac® 50 Type A Medicated Article105-758Amprolium, Bacitracin Zinc, Ethopabate,RoxarsoneAmprol HI-E® / Baciferm® / 3-Nitro®114-794Amprolium, Bacitracin Zinc, Ethopabate Baciferm® / Amprol HI-E® Premix123-154Bacitracin Zinc, Monensin Sodium, Roxarsone3-Nitro®-10 / Baciferm® / Coban® Premix126-052Bacitracin Zinc, Lasalocid, Roxarsone3-Nitro® / Avatec® / Baciferm®134-830Bacitracin Zinc, Monensin Sodium Albac® / Coban®FDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 6 of 70Number136-484Bacitracin Zinc, Carbarsone Baciferm® / Carb-O-Sep®137-536Bacitracin Zinc, Roxarsone, Salinomycin Sodium3-Nitro® / Albac® / Bio-Cox®138-703Bacitracin Zinc, Monensin Sodium, Roxarsone3-Nitro® / Albac® / Coban®139-190Bacitracin Zinc, Roxarsone, Salinomycin Sodium3-Nitro® / Bio-Cox® / Baciferm®139-235Bacitracin Zinc, Salinomycin Sodium Baciferm® / Bio-Cox®140-865Bacitracin Zinc, Narasin Baciferm® / Albac®, Baciferm® / Monteban®141-083Bacitracin Zinc, Lasalocid Avatec® / Baciferm®141-109Bacitracin Zinc, Lasalocid Avatec® / Baciferm®141-146Bacitracin Zinc, Nicarbazin Nicarb® / Baciferm®141-181Bacitracin Zinc, Lasalocid Avatec® / Albac®200-086Bacitracin Zinc, Roxarsone, Salinomycin Sodium3-Nitro® / Albac® / Sacox®200-089Bacitracin Zinc, Salinomycin Sodium Baciferm® / Sacox®200-143Bacitracin Zinc, Roxarsone, Salinomycin Sodium3-Nitro® / Baciferm® / Sacox®200-203Bacitracin Zinc, Carbarsone Albac® / Carb-O-Sep®200-204Bacitracin Zinc, Salinomycin Sodium Albac® / Bio-Cox®200-205Amprolium, Bacitracin Zinc, Ethopabate Albac® / Amprol Hi-E®200-206Bacitracin Zinc, Decoquinate, Roxarsone3-Nitro® / Albac® / Deccox®200-207Bacitracin Zinc, Clopidol, Roxarsone3-Nitro® / Albac® / Coyden 25®200-208Bacitracin Zinc, Lasalocid, Roxarsone Avatec® / 3-Nitro® / Albac®200-209Bacitracin Zinc, Roxarsone, Salinomycin Sodium3-Nitro® / Albac® / Sacox®200-210Bacitracin Zinc, Salinomycin Sodium Albac® / Sacox®200-211Bacitracin Zinc, Monensin, Roxarsone3-Nitro® / Albac® / Coban®200-212Bacitracin Zinc, Robenidine Hydrochloride Albac® / Robenz®200-213Bacitracin Zinc, Decoquinate Albac® / Deccox®3-Nitro® / Albac® / Amprol Hi-E®200-214Amprolium, Bacitracin Zinc, Ethopabate,Roxarsone200-215Bacitracin Zinc, Roxarsone, Salinomycin Sodium3-Nitro® / Albac® / Bio-Cox®200-217Amprolium, Bacitracin Zinc, Ethopabate,3-Nitro® / Albac® / Amprol Hi-E®Roxarsone200-218Bacitracin Zinc, Clopidol Albac® / Coyden 25® / Albac®200-223Bacitracin Zinc Albac® 50 Type A Medicated Article031-555Balsam Peru Oil, Castor Oil, Trypsin Trypzyme® Aerosol039-583Balsam Peru Oil, Castor Oil, Trypsin Granulex Aerosol Spray044-759Bambermycins Flavomycin® 4095-543Amprolium, Bambermycins, Ethopabate Amprol HI-E® & Bambermycins, Amprol HI-E® / Flavomycin®3-Nitro® / Amprol HI-E® / Flavomycin®095-547Amprolium, Bambermycins, Ethopabate,Roxarsone095-548Amprolium, Bambermycins, Roxarsone3-Nitro® / Amprol / Flavomycin®3-Nitro® / Amprol / Flavomycin®095-549Amprolium, Bambermycins, Ethopabate,RoxarsoneFDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 7 of 70Number098-340Bambermycins, Monensin Sodium Flavomycin® / Monensin098-341Bambermycins, Monensin, Roxarsone3-Nitro® / Coban® / Flavomycin®101-628Bambermycins, Roxarsone, Zoalene3-Nitro® / Flavomycin® / Zoalene101-629Bambermycins, Zoalene Flavomycin® / Zoalene112-687Bambermycins, Lasalocid, Roxarsone3-Nitro® / Avatec® / Flavomycin®130-185Amprolium, Bambermycins Flavomycin® / Amprolium130-661Bambermycins, Carbarsone Carb-O-Sep / Flavomycin®131-413Bambermycins Flavomycin® 0.4, Flavomycin® 2132-448Bambermycins Flavomycin®134-185Bambermycins, Roxarsone, Salinomycin Sodium3-Nitro® / Bio-Cox® / Flavomycin®134-284Bambermycins, Salinomycin Sodium Bio-Cox® / Flavomycin®137-483Bambermycins, Halofuginone Hydrobromide Flavomycin® / Stenorol®140-339Bambermycins, Nicarbazin Flavomycin®, Nicarb®140-843Bambermycins, Narasin, Roxarsone3-Nitro® / Flavomycin® / Monteban®140-845Bambermycins, Narasin Flavomycin® / Monteban®140-918Bambermycins, Halofuginone Hydrobromide Flavomycin® / Stenorol®140-942Bambermycins, Narasin, Nicarbazin Flavomycin® / Maxiban®141-034Bambermycins Gainpro® Type A Medicated Article141-129Bambermycins, Lasalocid Avatec® / Flavomycin®141-158Bambermycins, Diclazuril Clinacox™ / Flavomycin®200-080Bambermycins, Roxarsone, Salinomycin Sodium3-Nitro® / Flavomycin® / Sacox®200-080Bambermycins, Roxarsone, Salinomycin Sodium3-Nitro® / Flavomycin® / Sacox®200-083Bambermycins, Salinomycin Sodium Flavomycin® / Sacox®200-388Gentamicin Sulfate, Betamethason Valerate GB Topical Spray034-010Betamethasone Acetate, Betamethasone SodiumBetavet Soluspan SuspensionPhosphate034-267Betamethasone Acetate, Gentamicin Sulfate Gentocin® Durafilm Ophthalmic SolutionBetasone Aqueous Suspension049-185Betamethasone Dipropionate, BetamethasoneSodium Phosphate034-010Betamethasone Acetate, Betamethasone SodiumBetavet Soluspan SuspensionPhosphateBetasone Aqueous Suspension049-185Betamethasone Dipropionate, BetamethasoneSodium Phosphate046-821Betamethasone Valerate, Gentamicin Sulfate Gentocin® Otic Solution113-231Betamethasone Valerate, Gentamicin Sulfate Topagen® Ointment132-338Betamethasone Valerate, Gentamicin Sulfate Gentocin® Topical SprayOtomax®140-896Betamethasone Valerate, Clotrimazole,Gentamicin Sulfate200-183Betamethasone Valerate, Gentamicin Sulfate Gentavet® Otic Solution200-188Betamethasone Valerate, Gentamicin Sulfate Betagen™ Topical SprayFDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 8 of 70NumberTri-Otic Ointment200-229Betamethasone Valerate, Clotrimazole,Gentamicin SulfateVetro-Max®200-283Betamethasone Valerate, Clotrimazole,Gentamicin SulfateGBC Ointment™200-287Betamethasone Valerate, Clotrimazole,Gentamicin Sulfate200-415Betamethasone Valerate, Gentamicin Sulfate Gentamicin Sulfate Topical Spray200-416Gentamicin sulfate and Betamethasone valerate Gentamicin Topical SprayAmforol® Suspension042-548Attapulgite, Bismuth Subcarbonate, KanamycinSulfate042-841Attapulgite, Bismuth Subcarbonate, KanamycinAmforol® Veterinary Oral TabletsSulfate034-705Boldenone Undecylenate Equipoise®140-872Bovine Somatotropin (Sometribove Zinc)Posilac 1 Step®035-016Bunamidine Hydrochloride Scolaban 400045-738Buquinolate, Lincomycin HydrochlorideLincomix® / Bonaid, Lincomycin & BuquinolateMonohydrate130-872Butacaine Sulfate, Nitrofurazone Nitrofurazone Anesthetic Dress.104-184Butamisole Hydrochloride Styquin132-533Butamisole Hydrochloride Styquin Parenteral 1.1%102-990Butorphanol Tartrate Torbutrol® Injection103-390Butorphanol Tartrate Torbutrol® Tablets135-780Butorphanol Tartrate Torbugesic®141-047Butorphanol Tartrate Torbugesic-SA®200-239Butorphanol Tartrate Dolorex®200-322Butorphanol Tartrate Butorphanol Tartrate Injection200-332Butorphanol Tartrate Butorphic™ Injection200-408Butorphanol Tartrate Butorphanol Tartrate Injection200-448Butorphanol Tartrate, Melengestrol Acetate,Heifermax® plus Optaflexx® and Rumensin®Monensin Sodium, Ractopamine Hydrochloride094-642Cambendazole Camvet Suspension Horse Wormer096-506Cambendazole Camvet Horse Wormer Pellets096-731Cambendazole Camvet Horse Wormer Paste 45%009-339Ammonium Chloride, Caramiphen Edisylate Carafen Cough Syrup, Carafen Cough Tablets041-061Carbadox Mecadox® Premix 10092-955Carbadox, Pyrantel Tartrate Banminth® / Mecadox®141-211Carbadox, Oxytetracycline Dihydrate Mecadox® 10 / Terramycin® 100, Mecadox® 10 / Terramycin®200, Mecadox® 10 / Terramycin® 50 039-646Bacitracin Methylene Disalicylate, Carbarsone Carb-O-Gain118-507Amprolium, Carbarsone Amprol® / Carb-O-Sep®130-661Bambermycins, Carbarsone Carb-O-Sep / Flavomycin®136-484Bacitracin Zinc, Carbarsone Baciferm® / Carb-O-Sep®FDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 9 of 70Number200-203Bacitracin Zinc, Carbarsone Albac® / Carb-O-Sep®038-879Carbarsone, Zoalene Carb-O-Sep® / Zoamix®038-879Carbarsone, Zoalene Carb-O-Sep® / Zoamix®032-946Carbomycin, Oxytetracycline Hydrochloride Magna Terramycin® Soluble Powder139-633Carfentanil Citrate Wildnil®139-879Carnidazole Carnidazole, Spartrix®141-053Carprofen Rimadyl® Caplets for Dogs141-111Carprofen Rimadyl® Chewable Tablets141-199Carprofen Rimadyl® Injectable200-366Carprofen Novocox Caplets200-397Carprofen Vetprofen™200-498Carprofen Carprieve™200-555Carprofen Librevia™031-555Balsam Peru Oil, Castor Oil, Trypsin Trypzyme® Aerosol039-583Balsam Peru Oil, Castor Oil, Trypsin Granulex Aerosol Spray119-688Cefadroxil Cefa-Tabs®140-684Cefadroxil Cefa-Drops®141-285Cefovecin sodium Convenia®141-232Cefpodoxime proxetil Simplicef®200-543Cefpodoxime proxetil Cefpodoxime Proxetil Tablets141-209Ceftiofur Crystalline Free Acid Excede™ Sterile Suspension141-235Ceftiofur Crystalline Free Acid Excede™ For Swine140-890Ceftiofur Hydrochloride Excenel Sterile Suspension, Excenel® RTU, Excenel® SterilePowder141-238Ceftiofur Hydrochloride Spectramast™ LC Sterile Suspension141-239Ceftiofur Hydrochloride Spectramast™ DC Sterile Suspension141-288Ceftiofur Hydrochloride Excenel® RTU EZ140-338Ceftiofur Sodium Naxcel® Sterile Powder200-420Ceftiofur Sodium Ceftiofur Sodium Sterile Powder200-421Ceftiofur sodium Ceftiofur for Injection141-326Cephalexin Rilexine® Chewable Tablets108-114Cephapirin Benzathine Cefa-Dri®, Tomorrow® Infusion097-222Cephapirin Sodium Cefa-Lak®, Today® Intramammary Infusion046-789Chloral Hydrate, Magnesium Sulfate, ChloropentPentobarbital055-002Chloramphenicol Tevcocin055-051Chloramphenicol Chloromycetin Tablets 100 mg, Chloromycetin Tablets 250 mg,Chloromycetin Tablets 500 mg055-059Chloramphenicol Viceton® Tablets065-137Chloramphenicol Amphicol-VFDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 10 of 70Number065-149Chloramphenicol Chloromycetin Ophthalmic Ointment065-150Chloramphenicol Chloramphenicol Capsules065-241Chloramphenicol Mychel-Vet Capsules (50 mg)065-460Chloramphenicol Chloramphenicol 1% Ophthalmic, Vetrocloricin OphthalmicOintment065-461Chloramphenicol Anacetin Tablets065-463Chloramphenicol Mychel-Vet Injection065-489Chloramphenicol Mychel-Vet Tabs065-491Chloramphenicol Medichol Tablets055-047Chloramphenicol Palmitate Chloromycetin Palmitate Oral Suspension009-782Chlorhexidine Acetate Nolvasan® Antiseptic Ointment200-301Chlorhexidine Acetate Privasan™ Antiseptic Ointment009-809Chlorhexidine Hydrochloride Nolvasan® Cap-Tabs®010-434Chlorhexidine Hydrochloride Nolvasan® Suspension006-983Chlorobutanol, Doxylamine Succinate A-H Injection141-245Chloroquine Phosphate, Embutramid, Lidocaine Tributame™ Euthanasia Solution011-678Chlorothiazide Diuril® Tablet012-734Chlorothiazide Diuril®038-160Chlorphenesin Carbamate Maolate® Tablets, Maolate® Veterinary048-761Chlortetracycline Aureomycin® 100 Granular, Aureomycin® 50 Granular,Aureomycin® 90 Granular, Aureomycin® 90 Meal138-935Chlortetracycline Pennchlor™ 100MR, Pennchlor™ 50, Pennchlor™ 50-G,Pennchlor™ 90, Pennchlor™ 90-G, Pennchlor™ 100-G,Pennchlor™ 100 Hi-Flo141-059Bacitracin Methylene Disalicylate,Chlortetracycline BMD® 10, 25, 30, 40, 50, 60, 75 / CTC® 50, 65, 70, BMD® 25, 30, 40, 50, 60, 75 / ChlorMax™®- 50, 60, 70, MICRO-CTC® 100141-147Chlortetracycline, Decoquinate Chloromax® / Deccox®141-185Chlortetracycline, Decoquinate Aureomycin® / Deccox®141-201Chlortetracycline, Laidlomycin PropionatePotassiumAureomycin® / Cattlyst®141-250Chlortetracycline, Lasalocid Aureomycin® and Bovatec®200-259Chlortetracycline, Roxarsone, SalinomycinSodium3-Nitro® / ChlorMax™ / Sacox®200-260Chlortetracycline, Roxarsone, SalinomycinSodium3-Nitro® / Bio-Cox® / ChlorMax™200-261Chlortetracycline, Salinomycin Sodium Bio-Cox® / ChlorMax™200-262Chlortetracycline, Salinomycin Sodium ChlorMax™ / Sacox®200-263Chlortetracycline, Monensin Sodium ChlorMax™ / Coban®200-314Chlortetracycline, Sulfamethazine Pennchlor S®200-355Chlortetracycline, Roxarsone, SalinomycinSodiumPennchlor™ / Bio-Cox® / 3-Nitro®FDA APPROVED PRODUCTS January 2014Section 2.0 - Active Ingredients Page 11 of 70。
二氯萘醌-化学品安全技术说明书中文MSDS文档
化学品安全技术说明书二氯萘醌第一部分化学品及企业标识化学品中文名：二氯萘醌化学品英文名：dichlone；2,3-dichloro-1,4-naphthalenedione供应商名称：天津****化工有限公司供应商地址：天津市**区**路**号**室供应商电话：4571-5858****邮编：248***供应商传真：4571-5858****电子邮件地址：4527**************产品推荐及限制用途：用作农用杀菌剂。
第二部分危险性概述紧急情况概述：吞咽有害。
GHS危险性类别：皮肤腐蚀/刺激-类别2;严重眼损伤/眼刺激-类别2;危害水生环境-急性危害-类别1;危害水生环境-长期危害-类别1标签要素：象形图：警示词：警告危险信息：H315:造成皮肤刺激H319:造成严重眼刺激H410:对水生生物毒性极大并具有长期持续影响防范说明：预防措施：P264:作业后彻底清洗……。
P280:戴防护手套/穿防护服/戴防护眼罩/戴防护面具。
P273:避免释放到环境中。
应急响应：P302+P352:如皮肤沾染：用大量肥皂和水清洗。
P321:具体治疗(见本标签上的.....)。
P332+P313:如发生皮肤刺激：求医/就诊。
P362+P364:脱掉所有沾染的衣服，清洗后方可重新使用。
P305+P351+P338:如进入眼睛：用水小心冲洗几分钟。
如戴隐形眼镜并可方便地取出，取出隐形眼镜。
继续冲洗。
P337+P313:如仍觉眼刺激：求医/就诊。
P391:收集溢出物。
安全储存：废弃处置：P501:处置内装物/容器……物理和化学危险：可燃，其粉体与空气混合，能形成爆炸性混合物。
健康危害：本品有毒。
对眼睛、皮肤和黏膜有刺激作用。
大剂量时，对中枢神经系统有抑制作用。
受热分解放出有毒的氯气烟雾。
环境危害：对水生生物毒性非常大并具有长期持续影响。
其他危害：暂无资料。
第三部分成分/组成信息√物质混合物第四部分急救措施急救：- 皮肤接触：立即脱去污染的衣着，用流动清水彻底冲洗。
罗氟司特片说明书(美国,FDA,英文)
5 10 15 20 25 30 35 40 1 HIGHLIGHTS OF PRESCRIBING INFORMATION2 These highlights do not include all the information needed3 to use DALIRESP safely and effectively. See full4 prescribing information for DALIRESP. 6 DALIRESP ®(roflumilast) tablets 7 Initial U.S. Approval: 20XX 8 9 ------------------------INDICATIONS AND USAGE----------------------DALIRESP is indicated as a treatment to reduce the risk of11 COPD exacerbations in patients with severe COPD associated 12 with chronic bronchitis and a history of exacerbations. (1, 14) 13 14 Limitations of Use: DALIRESP is not a bronchodilator and is notindicated for the relief of acute bronchospasm. (1, 14) 16 17 ----------------DOSAGE AND ADMINISTRATION--------------------18 The recommended dosage for patients with COPD is one 50019 mcg tablet per day, with or without food. (2)21 ------------------DOSAGE FORMS AND STRENGTHS--------------- 22 Tablets: 500 mcg (3) 23 24 ----------------------CONTRAINDICATIONS---------------------------- • Moderate to severe liver impairment (Child-Pugh B or C) 26 (4)27 28 ----------------WARNINGS AND PRECAUTIONS---------------------- 29 • Acute bronchospasm: Do not use for the relief of acutebronchospasm. (5.1) 31 • Psychiatric Events including Suicidality: Advise patients ,32 their caregivers, and families to be alert for the emergence33 or worsening of insomnia, anxiety, depression, suicidal34 thoughts or other mood changes, and if such changesoccur to contact their healthcare provider. Carefully weigh36 the risks and benefits of treatment with DALIRESP in 37 patients with a history of depression and/or suicidal 38 thoughts or behavior. (5.2) 39 •Weight Decrease: Monitor weight regularly. If unexplainedor clinically significant weight loss occurs, evaluate weight41loss and consider discontinuation of DALIRESP. (5.3)7542•Drug Interactions: Use with strong cytochrome P45043 enzyme inducers (e.g. rifampicin, phenobarbital,44 carbamazepine, phenytoin) is not recommended. (5.4)45 46 -----------------------------ADVERSE REACTIONS----------------------47 Most common adverse reactions (≥ 2%) are diarrhea, weight48 decrease, nausea, headache, back pain, influenza, insomnia, 49 dizziness and decreased appetite. (6.1) 50 51 To report SUSPECTED ADVERSE REACTIONS, Contact52 Forest Laboratories, Inc. at 1-800-678-1605 or FDA at 1-80053 FDA-1088 or /medwatch. 54 55 ----------------------DRUG INTERACTIONS------------------------------ 56 •Use with inhibitors of CYP3A4 or dual inhibitors of 57 CYP3A4 and CYP1A2 (e.g, erythromycin, ketoconazole,58 fluvoxamine, enoxacin, cimetidine) will increase roflumilast59 systemic exposure and may result in increased adverse60 reactions. The risk of such concurrent use should be61 weighed carefully against benefit. (7.2) 62 63 ---------------------USE IN SPECIFIC POPULATIONS----------------64 •Nursing Mothers: DALIRESP should not be used by 65 women who are nursing as excretion of roflumilast and/or 66 its metabolites into human milk is probable and there are67 no human studies that have investigated effects of68 DALIRESP on breast-fed infants. (8.3)69 70 See 17 for PATIENT COUNSELING INFORMATON AND71 MEDICATION GUIDE 72 73 74REVISED XX/20XX76FULL PRESCRIBING INFORMATION: CONTENTS*1. INDICATIONS AND USAGE 11. DESCRIPTION2. DOSAGE AND ADMINISTRATION 12. CLINICAL PHARMACOLOGY3. DOSAGE FORMS AND STRENGTHS 12.1 Mechanism of Action4. CONTRAINDICATIONS 12.2 Pharmacodynamics5. WARNINGS AND PRECAUTIONS 12.3 Pharmacokinetics5.1 Treatment of Acute Bronchospasm 13. NONCLINICAL TOXICOLOGY5.2 Psychiatric Events including Suicidality 13.1 Carcinogenesis, Mutagenesis, Impairment ofFertility5.3 Weight Decrease 14. CLINICAL STUDIES5.4 Drug Interactions 14.1 Chronic Obstructive Pulmonary Disease6. ADVERSE REACTIONS 16. HOW SUPPLIED/STORAGE AND HANDLING6.1 Adverse Reactions in Clinical Trials 16.1 How Supplied7. DRUG INTERACTIONS 16.2 Storage and Handling7.1 Drugs that induce Cytochrome P450 (CYP) 17. PATIENT COUNSELING INFORMATIONEnzymesDrugs7.2 that inhibit Cytochrome P450 (CYP) 17.1 BronchospasmEnzymes7.3 Oral combination contraceptives containing 17.2 Psychiatric Events including Suicidalitygestodene and ethinyl estradiol8. USE IN SPECIFIC PATIENT POPULATIONS 17.3 Weight Decrease8.1 Pregnancy 17.4 Drug Interactions8.2 Labor and Delivery8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Hepatic Impairment8.7 Renal Impairment10. OVERDOSAGE10.1 Human Experience10.2 Management of Overdose*Sections or subsections omitted from the full prescribinginformation are not listed77 FULL PRESCRIBING INFORMATION7879 1 INDICATIONSUSAGEAND80 DALIRESP® is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with81 chronic bronchitis and a history of exacerbations.8283 Limitations of Use84 DALIRESP is not a bronchodilator and is not indicated for the relief of acute bronchospasm.8586 2 DOSAGEADMINISTRATIONAND87 The recommended dose of DALIRESP is one 500 microgram (mcg) tablet per day, with or without food.8889 3 DOSAGE FORMS AND STRENGTHS90 DALIRESP is supplied as white to off-white, round tablets, embossed with “D” on one side and “500” on the other side. Each tablet91 contains 500 mcg of roflumilast.9293 4 CONTRAINDICATIONS94 The use of DALIRESP is contraindicated in the following conditions:95 •Moderate to severe liver impairment (Child-Pugh B or C) [see Clinical Pharmacology (12.3) and Use in Special Populations (8.6)].9697 5 WARNINGS AND PRECAUTIONS9899 5.1 Treatment of Acute Bronchospasm100 DALIRESP is not a bronchodilator and should not be used for the relief of acute bronchospasm.101102 5.2 Psychiatric Events including Suicidality103 Treatment with DALIRESP is associated with an increase in psychiatric adverse reactions. In 8 controlled clinical trials 5.9% (263) of 104 patients treated with DALIRESP 500 mcg daily reported psychiatric adverse reactions compared to 3.3% (137) treated with placebo. 105 The most commonly reported psychiatric adverse reactions were insomnia, anxiety, and depression which were reported at higher 106 rates in those treated with DALIRESP 500 mcg daily (2.4%, 1.4%, and 1.2% for DALIRESP versus 1.0%, 0.9%, and 0.9% for placebo, 107 respectively) [see Adverse Reactions (6.1)]. Instances of suicidal ideation and behavior, including completed suicide, have been 108 observed in clinical trials. Three patients experienced suicide-related adverse reactions (one completed suicide and two suicide 109 attempts) while receiving DALIRESP compared to one patient (suicidal ideation) who received placebo.110111 Before using DALIRESP in patients with a history of depression and/or suicidal thoughts or behavior, prescribers should carefully 112 weigh the risks and benefits of treatment with DALIRESP in such patients. Patients, their caregivers, and families should be advised of 113 the need to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes, and if 114 such changes occur to contact their healthcare provider. Prescribers should carefully evaluate the risks and benefits of continuing 115 treatment with DALIRESP if such events occur.116117 5.3 WeightDecrease118 Weight loss was a common adverse reaction in DALIRESP clinical trials and was reported in 7.5% (331) of patients treated with 119 DALIRESP 500 mcg once daily compared to 2.1% (89) treated with placebo [see Adverse Reactions (6.1)]. In addition to being 120 reported as adverse reactions, weight was prospectively assessed in two placebo-controlled clinical trials of one year duration. In 121 these studies, 20% of patients receiving roflumilast experienced moderate weight loss (defined as between 5-10% of body weight) 122 compared to 7% of patients who received placebo. In addition, 7% of patients who received roflumilast compared to 2% of patients 123 receiving placebo experienced severe (>10% body weight) weight loss. During follow-up after treatment discontinuation, the majority of 124 patients with weight loss regained some of the weight they had lost while receiving DALIRESP. Patients treated with DALIRESP 125 should have their weight monitored regularly. If unexplained or clinically significant weight loss occurs, weight loss should be 126 evaluated, and discontinuation of DALIRESP should be considered.127128 5.4 Drug Interactions129 A major step in roflumilast metabolism is the N-oxidation of roflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2. The 130 administration of the cytochrome P450 enzyme inducer rifampicin resulted in a reduction in exposure, which may result in a decrease 131 in the therapeutic effectiveness of DALIRESP. Therefore, the use of strong cytochrome P450 enzyme inducers (e.g. rifampicin, 132 phenobarbital, carbamazepine, phenytoin) with DALIRESP is not recommended. [see Drugs That Induce Cytochrome P450 (CYP) 133 Enzymes (7.1) and Clinical Pharmacology (12.3)].134135 6 ADVERSE REACTIONS136 The following adverse reactions are described in greater detail in other sections:137 • Psychiatric Events Including Suicidality [see Warnings and Precautions (5.2)]138 • Weight Decrease [see Warnings and Precautions (5.3)]139140 6.1 Adverse Reactions in Clinical Studies141 Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug 142 cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.143144 The safety data described below reflect exposure of 4438 patients to DALIRESP 500 mcg once daily in four 1-year placebo-controlled 145 trials, two 6-month placebo-controlled trials, and two 6-month drug add-on trials [see Clinical Studies (14.1)]. In these trials, 3136 and 146 1232 COPD patients were exposed to DALIRESP 500 mcg once daily for 6 months and 1-year, respectively.147148 The population had a median age of 64 years (range 40-91), 73% were male, 92.9% were Caucasian, and had COPD with a mean 149 pre-bronchodilator forced expiratory volume in one second (FEV1) of 8.9 to 89.1% predicted. In these trials, 68.5% of the patients 150 treated with DALIRESP reported an adverse reaction compared with 65.3% treated with placebo.151152 The proportion of patients who discontinued treatment due to adverse reaction was 14.8% for DALIRESP-treated patients and 9.9% 153 for placebo-treated patients. The most common adverse reactions that led to discontinuation of DALIRESP were diarrhea (2.4%) and 154 nausea (1.6%).155156 Serious adverse reactions, whether considered drug-related or not by the investigators, which occurred more frequently in DALIRESP157 treated patients include diarrhea, atrial fibrillation, lung cancer, prostate cancer, acute pancreatitis, and acute renal failure.158159 Table 1 summarizes the adverse reactions reported by ≥ 2% of patients in the DALIRESP group 8 controlled COPD clinical trials. 160161 Table 1: Adverse Reactions Reported by ≥ 2% of Patients162 Treated with DALIRESP 500 mcg daily and Greater Than PlaceboTreatmentAdverse Reactions (Preferred Term) DALIRESP Placebo (N=4438) (N=4192) n (%) n (%)Diarrhea 420 (9.5) 113 (2.7)Weight decreased 331 (7.5) 89 (2.1)Nausea 209 (4.7) 60 (1.4)Headache 195 (4.4) 87 (2.1)Back pain 142 (3.2) 92 (2.2)Influenza 124 (2.8) 112 (2.7)Insomnia 105 (2.4) 41 (1.0)Dizziness 92 (2.1) 45 (1.1)Decreased appetite 91 (2.1) 15 (0.4)163164 Adverse reactions that occurred in the DALIRESP group at a frequency of 1 to 2% where rates exceeded that in the placebo group 165 include:166167 Gastrointestinal disorders - abdominal pain, dyspepsia, gastritis, vomiting168 Infections and infestations - rhinitis, sinusitis, urinary tract infection,169 Musculoskeletal and connective tissue disorders - muscle spasms170 Nervous system disorders - tremor171 Psychiatric disorders - anxiety, depression172173 7 DRUGINTERACTIONS174 A major step in roflumilast metabolism is the N-oxidation of roflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2 [see Clinical 175 Pharmacology (12.3)].176177 7.1 Drugs That Induce Cytochrome P450 (CYP) Enzymes178 Strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness of 179 DALIRESP. Therefore the use of strong cytochrome P450 inducers (e.g., rifampicin, phenobarbital, carbamazepine, and phenytoin) 180 with DALIRESP is not recommended [see Drug Interactions (5.4) and Clinical Pharmacology (12.3)].181182 7.2 Drugs That Inhibit Cytochrome P450 (CYP) Enzymes183 The co-administration of DALIRESP (500 mcg) with CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 184 simultaneously (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) may increase roflumilast systemic exposure and 185 may result in increased adverse reactions. The risk of such concurrent use should be weighed carefully against benefit. [see Clinical 186 Pharmacology (12.3)].187188 7.3 Oral Contraceptives Containing Gestodene and Ethinyl Estradiol189 The co-administration of DALIRESP (500 mcg) with oral contraceptives containing gestodene and ethinyl estradiol may increase190 roflumilast systemic exposure and may result in increased side effects. The risk of such concurrent use should be weighed carefully 191 against benefit [see Clinical Pharmacology (12.3)].192193 8 USE IN SPECIFIC POPULATIONS194195 8.1 Pregnancy196 Teratogenic effects: Pregnancy Category C: There are no adequate and well controlled studies of DALIRESP in pregnant women. 197 DALIRESP was not teratogenic in mice, rats, or rabbits. DALIRESP should be used during pregnancy only if the potential benefit 198 justifies the potential risk to the fetus.199200 DALIRESP induced stillbirth and decreased pup viability in mice at doses corresponding to approximately 16 and 49 times, 201 respectively, the maximum recommended human dose (MRHD) (on a mg/m2 basis at maternal doses > 2 mg/kg/day and 6 mg/kg/day, 202 respectively). DALIRESP induced post-implantation loss in rats at doses greater than or equal to approximately 10 times the MRHD 203 (on a mg/m2 basis at maternal doses ≥ 0.6 mg/kg/day). No treatment-related effects on embryo-fetal development were observed in204 mice, rats, and rabbits at approximately 12, 3, and 26 times the MRHD, respectively (on a mg/m2 basis at maternal doses of 1.5, 0.2, 205 and 0.8 mg/kg/day, respectively).206207 Nonteratogenic effects: DALIRESP has been shown to adversely affect pup post-natal development when dams were treated with the 208 drug during pregnancy and lactation periods in mice. These studies found that DALIRESP decreased pup rearing frequencies at 209 approximately 49 times the MRHD (on a mg/mg2 basis at a maternal dose of 6 mg/kg/day) during pregnancy and lactation. DALIRESP 210 also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at approximately 97 times the MRHD 211 (on a mg/m2 basis at a maternal dose of 12 mg/kg/day) during pregnancy and lactation.212213 8.2 Labor and Delivery214 DALIRESP should not be used during labor and delivery. There are no human studies that have investigated effects of DALIRESP on 215 preterm labor or labor at term; however, animal studies showed that DALIRESP disrupted the labor and delivery process in mice. 216 DALIRESP induced delivery retardation in pregnant mice at doses greater than or equal to approximately 16 times the MRHD (on a 217 mg/m2 basis at a maternal dose of > 2 mg/kg/day).218219 8.3 NursingMothers220 Roflumilast and/or its metabolites are excreted into the milk of lactating rats. Excretion of roflumilast and/or its metabolites into human 221 milk is probable. There are no human studies that have investigated effects of DALIRESP on breast-fed infants. DALIRESP should not 222 be used by women who are nursing.223224 8.4 PediatricUse225 COPD does not normally occur in children. The safety and effectiveness of DALIRESP in pediatric patients have not been established. 226227 8.5 GeriatricUse228 Of the 4438 COPD subjects exposed to DALIRESP for up to 12 months in 8 controlled clinical trials, 2022 were > 65 years of age and 229 471 were > 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger 230 subjects and other reported clinical experience has not identified differences in responses between the elderly and younger patients, 231 but greater sensitivity of some older individuals cannot be ruled out. Based on available data for roflumilast, no adjustment of dosage 232 in geriatric patients is warranted [see Clinical Pharmacology (12.3)].233234 8.6 Hepatic Impairment235 Roflumilast 250 mcg once daily for 14 days was studied in subjects with mild-to-moderate hepatic impairment classified as Child-Pugh 236 A and B (8 subjects in each group). The AUCs of roflumilast and roflumilast N-oxide were increased by 51% and 24%, respectively in 237 Child-Pugh A subjects and by 92% and 41%, respectively in Child-Pugh B subjects, as compared to age-, weight- and gender238 matched healthy subjects. The C max of roflumilast and roflumilast N-oxide were increased by 3% and 26%, respectively in Child-Pugh A 239 subjects and by 26% and 40%, respectively in Child-Pugh B subjects, as compared to healthy subjects. DALIRESP 500 mcg has not 240 been studied in hepatically impaired patients. Clinicians should consider the risk-benefit of administering DALIRESP to patients who 241 have mild liver impairment (Child-Pugh A). DALIRESP is not recommended for use in patients with moderate or severe liver 242 impairment (Child-Pugh B or C) [see Contraindications (4) and Clinical Pharmacology (12.3)].243244 8.7 RenalImpairment245 In twelve subjects with severe renal impairment administered a single dose of 500 mcg roflumilast, the AUCs of roflumilast and 246 roflumilast N-oxide were decreased by 21% and 7%, respectively and C max were reduced by 16% and 12%, respectively. No dosage 247 adjustment is necessary for patients with renal impairment [see Clinical Pharmacology (12.3)].248249 10 OVERDOSAGE250251 10.1 Human Experience252 No case of overdose has been reported in clinical studies with DALIRESP. During the Phase I studies of DALIRESP, the 253 following symptoms were observed at an increased rate after a single oral dose of 2500 mcg and a single dose of 5000 mcg: 254 headache, gastrointestinal disorders, dizziness, palpitations, lightheadedness, clamminess and arterial hypotension.255256 10.2 Management of Overdose257 In case of overdose, patients should seek immediate medical help. Appropriate supportive medical care should be provided. Since 258 roflumilast is highly protein bound, hemodialysis is not likely to be an efficient method of drug removal. It is not known whether 259 roflumilast is dialyzable by peritoneal dialysis.260261 11 DESCRIPTION262 The active ingredient in DALIRESP tablets is roflumilast. Roflumilast and its active metabolite (roflumilast N-oxide) are selective 263 phosphodiesterase 4 (PDE4) inhibitors. The chemical name of roflumilast is N-(3,5-dichloropyridin-4-yl)-3-cyclopropylmethoxy-4264 difluoromethoxy-benzamide. Its empirical formula is C17H14Cl2F2N2O3 and the molecular weight is 403.22.265266 The chemical structure is:267268269270271 The drug substance is a white to off-white non-hygroscopic powder with a melting point of 160°C. It is practically insoluble in water and 272 hexane, sparingly soluble in ethanol and freely soluble in acetone.273274 DALIRESP is supplied as white to off-white, round tablets, embossed with “D” on one side and “500” on the other side. Each tablet 275 contains 500 mcg of roflumilast.276277 Each tablet of DALIRESP for oral administration contains the following inactive ingredients: lactose monohydrate, corn starch, 278 povidone and magnesium stearate.279280 12 CLINICALPHARMACOLOGY281282 12.1 Mechanism of Action283 Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors of phosphodiesterase 4 (PDE4). Roflumilast and 284 roflumilast N-oxide inhibition of PDE4 (a major cyclic-3′,5′-adenosine monophosphate (cyclic AMP)-metabolizing enzyme in lung 285 tissue) activity leads to accumulation of intracellular cyclic AMP. While the specific mechanism(s) by which DALIRESP exerts its 286 therapeutic action in COPD patients is not well defined, it is thought to be related to the effects of increased intracellular cyclic AMP in 287 lung cells.288289 12.2 Pharmacodynamics290 In COPD patients, 4 week treatment with DALIRESP 500 mcg oral once daily reduced sputum neutrophils and eosinophils by 31%, 291 and 42%, respectively. In a pharmacodynamic study in healthy volunteers, DALIRESP 500 mcg once daily reduced the number of total 292 cells, neutrophils and eosinophils found in bronchoalveolar lavage fluid following segmental pulmonary lipopolysaccharide (LPS) 293 challenge by 35%, 38% and 73%, respectively. The clinical significance of these findings is unknown.294295 12.3 Pharmacokinetics296 Absorption297 The absolute bioavailability of roflumilast following a 500 mcg oral dose is approximately 80%. Maximum plasma concentrations (C max) 298 of roflumilast typically occur approximately one hour after dosing (ranging from 0.5 to 2 hours) in the fasted state while plateau-like 299 maximum concentrations of the N-oxide metabolite are reached in approximately eight hours (ranging from 4 to 13 hours). Food has 300 no affect on total drug absorption, but delays time to maximum concentration (T max) of roflumilast by one hour and reduces C max by 301 approximately 40%, however, C max and T max of roflumilast N-oxide are unaffected. An in vitro study showed that roflumilast and 302 roflumilast N-oxide did not inhibit P-gp transporter.303304 Distribution305 Plasma protein binding of roflumilast and its N-oxide metabolite is approximately 99% and 97%, respectively. Volume of distribution for 306 single dose 500 mcg roflumilast is about 2.9 L/kg. Studies in rats with radiolabeled roflumilast indicate low penetration across the 307 blood-brain barrier.308309 Metabolism310 Roflumilast is extensively metabolized via Phase I (cytochrome P450) and Phase II (conjugation) reactions. The N-oxide metabolite is 311 the only major metabolite observed in the plasma of humans. Together, roflumilast and roflumilast N-oxide account for the majority 312 (87.5%) of total dose administered in plasma. In urine, roflumilast was not detectable while roflumilast N-oxide was only a trace 313 metabolite (less than 1%). Other conjugated metabolites such as roflumilast N-oxide glucuronide and 4-amino-3,5-dichloropyridine N314 oxide were detected in urine.315316 While roflumilast is three times more potent than roflumilast N-oxide at inhibition of the PDE4 enzyme in vitro, the plasma AUC of 317 roflumilast N-oxide on average is about 10-fold greater than the plasma AUC of roflumilast.318319 In vitro studies and clinical drug-drug interaction studies suggest that the biotransformation of roflumilast to its N-oxide metabolite is 320 mediated by CYP 1A2 and 3A4. Based on further in vitro results in human liver microsomes, therapeutic plasma concentrations of 321 roflumilast and roflumilast N-oxide do not inhibit CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11. Therefore, there is 322 a low probability of relevant interactions with substances metabolized by these P450 enzymes. In addition, in vitro studies 323 demonstrated no induction of the CYP 1A2, 2A6, 2C9, 2C19, or 3A4/5 and only a weak induction of CYP 2B6 by roflumilast.324325 Elimination326 The plasma clearance after short-term intravenous infusion of roflumilast is on average about 9.6 L/h. Following an oral dose, the 327 median plasma effective half-life of roflumilast and its N-oxide metabolite are approximately 17 and 30 hours, respectively. Steady 328 state plasma concentrations of roflumilast and its N-oxide metabolite are reached after approximately 4 days for roflumilast and 6 days 329 for roflumilast N-oxide following once daily dosing. Following intravenous or oral administration of radiolabeled roflumilast, about 70%330 of the radioactivity was recovered in the urine.331332 Special Populations333334 Hepatic Impairment335 Roflumilast 250 mcg once daily for 14 days was studied in subjects with mild-to-moderate hepatic impairment classified as Child-Pugh 336 A and B (8 subjects in each group). The AUC of roflumilast and roflumilast N-oxide were increased by 51% and 24%, respectively in 337 Child-Pugh A subjects and by 92% and 41%, respectively in Child-Pugh B subjects, as compared to age-, weight- and gender338 matched healthy subjects. The C max of roflumilast and roflumilast N-oxide were increased by 3% and 26%, respectively in Child-Pugh A 339 subjects and by 26% and 40%, respectively in Child-Pugh B subjects, as compared to healthy subjects. DALIRESP 500 mcg has not 340 been studied in hepatically impaired patients. Clinicians should consider the risk-benefit of administering DALIRESP to patients who 341 have mild liver impairment (Child-Pugh A). DALIRESP is not recommended for use in patients with moderate or severe liver 342 impairment (Child-Pugh B or C) [see Contraindications (4) and Use in Specific Populations (8.6)].343344 Renal Impairment345 In twelve subjects with severe renal impairment administered a single dose of 500 mcg roflumilast, roflumilast and roflumilast N-oxide 346 AUCs were decreased by 21% and 7%, respectively and C max were reduced by 16% and 12%, respectively. No dosage adjustment is 347 necessary for patients with renal impairment [see Use in Specific Populations (8.7)].348349 Age350 Roflumilast 500 mcg once daily for 15 days was studied in young, middle aged, and elderly healthy subjects. The exposure in elderly 351 (> 65 years of age) were 27% higher in AUC and 16% higher in C max for roflumilast and 19% higher in AUC and 13% higher in C max for 352 roflumilast-N-oxide than that in young volunteers (18-45 years old). No dosage adjustment is necessary for elderly patients [see Use in 353 Specific Populations (8.5)].354355 Gender356 In a Phase I study evaluating the effect of age and gender on the pharmacokinetics of roflumilast and roflumilast N-oxide, a 39% and 357 33% increase in roflumilast and roflumilast N-oxide AUC were noted in healthy female subjects as compared to healthy male subjects. 358 No dosage adjustment is necessary based on gender.359360 Smoking361 The pharmacokinetics of roflumilast and roflumilast N-oxide were comparable in smokers as compared to non-smokers. There was no 362 difference in C max between smokers and non-smokers when roflumilast 500 mcg was administered as a single dose to 12 smokers and 363 12 non-smokers. The AUC of roflumilast in smokers was 13% less than that in non-smokers while the AUC of roflumilast N-oxide in 364 smokers was 17% more than that in non-smokers.365366 Race367 As compared to Caucasians, African Americans, Hispanics, and Japanese showed 16%, 41%, and 15% higher AUC, respectively, for 368 roflumilast and 43%, 27%, and 16% higher AUC, respectively, for roflumilast N-oxide. As compared to Caucasians, African Americans, 369 Hispanics, and Japanese showed 8%, 21%, and 5% higher C max, respectively, for roflumilast and 43%, 27%, and 17% higher C max, 370 respectively, for roflumilast N-oxide. No dosage adjustment is necessary for race.371372 Drug Interactions373 Drug interaction studies were performed with roflumilast and other drugs likely to be coadministered or drugs commonly used as 374 probes for pharmacokinetic interaction [see Drug Interactions]. No significant drug interactions were observed when 500 mcg oral 375 roflumilast was administered with inhaled salbutamol, formoterol, budesonide and oral montelukast, digoxin, theophylline, warfarin, 376 sildenafil, midazolam, or antacids.377378 The effect of concomitant drugs on the exposure of roflumilast and roflumilast N-oxide is shown in the Figure 1 below.379380。
阿拉丁L-精氨酸盐酸盐产品安全技术说明书
GHS07:感叹号在眼睛接触的情况下无数据资料如果误服用水雾，耐醇泡沫，干粉或二氧化碳灭火。
4.2最重要的症状和影响，急性的和滞后的最重要的症状和健康影响据我们所知，此化学，物理和毒性性质尚未经完整的研究。
4.3及时的医疗处理和所需的特殊处理的说明和指示如有必要，佩戴自给式呼吸器进行消防作业。
5消防措施5.1灭火介质火灾特征无数据资料灭火方法及灭火剂碳氧化物,氮氧化物,氯化氢气体5.2源于此物质或混合物的特别的危害避免粉尘生成。
避免吸入蒸气、气雾或气体。
5.3救火人员的预防无数据资料5.4进一步的信息无数据资料6泄露应急处理6.1人员的预防,防护设备和紧急处理程序扫掉和铲掉。
放入合适的封闭的容器中待处理。
6.2环境预防措施丢弃处理请参阅第5797节6.3抑制和清除溢出物的方法和材料在有粉尘生成的地方,提供合适的排风设备。
6.4参考其他部分贮存在阴凉处。
使容器保持密闭，储存在干燥通风处。
7安全操作与储存7.1安全操作的注意事项无数据资料7.2安全储存的条件,包括任何不兼容性无数据资料7.3特定用途常规的工业卫生操作。
8接触控制/个体防护8.1控制参数最高容许浓度成分 CAS No. 值控制参数基准L-精氨酸盐酸盐L-Arginine hydrochloride 1119-34-2PC-TWA请使用经官方标准如NIOSH(美国)或EN166(欧盟)检测与批准的设备防护眼部。
《工作场所有害因素职业接触限值》国家标准中的工作场所时间加权平均容许浓度无数据资料无数据资料 无数据资料8.2暴露控制适当的技术控制根据危险物质的类型，浓度和量，以及特定的工作场所选择身体保护措施。
,防护设备的类型必须根据特定工作场所中的危险物的浓度和数量来选择。
Sigma-Aldrich-A5131页码4的6人身保护设备眼/面保护无数据资料皮肤保护戴手套取手套在使用前必须受检查。
请使用合适的方法脱除手套(不要接触手套外部表面),避免任何皮肤部位接触此产品.使用后请将被污染过的手套根据相关法律法规和有效的实验室规章程序谨慎处理.请清洗并吹干双手身体保护无数据资料呼吸系统防护不需要保护呼吸。