克拉霉素

克拉霉素用途

Clarithromycin是大环内脂类抗生素,还是CYP3A4抑制剂。

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克拉霉素作用

用途大环内酯类抗生素，为红霉素的衍生物，把红霉素A的6位上的OH基改为OCH3，即为克拉霉素。对革兰阳性菌和阴性菌、衣原体以及分枝杆菌有效，几乎能有效地抑制所有呼吸系统病原菌。对胃酸稳定，口服吸收好，血药浓度高，血半衰期长。其用途和红霉素相似，对呼吸道、泌尿道、皮肤、耳鼻喉科等多种感染有效。
用途属大环内酯类抗生素，用于治疗上、下呼吸道感染，皮下软组织感染等

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克拉霉素名称

[ CAS 号 ]:
81103-11-9

[ 中文名 ]:
克拉霉素

[ 英文名 ]:
Clarithromycin

[中文别名 ]:

[英文别名 ]:

Resclar
Clarithromycin
TE-031
Infex
te-03
Claris
6-O-Methylerythromycin
Kladd
Clarosip
Veclam

克拉霉素生物活性

[ 描述 ]:

Clarithromycin是大环内脂类抗生素,还是CYP3A4抑制剂。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

信号通路 >> 抗感染 >> 细菌

信号通路 >> 代谢酶/蛋白酶 >> 细胞色素P450

研究领域 >> 感染

[参考文献]

[1]. http://en.wikipedia.org/wiki/Clarithromycin

[2]. Niemi, M., P.J. Neuvonen, and K.T. Kivisto, The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide. Clin Pharmacol Ther, 2001. 70(1): p. 58-65.

[相关活性小分子]

克拉霉素物理化学性质

[ 密度 ]:
1.2±0.1 g/cm3

[ 沸点 ]:
805.5±65.0 °C at 760 mmHg

[ 熔点 ]:
217-220ºC

[ 分子式 ]:
C₃₈H₆₉NO₁₃

[ 分子量 ]:
747.953

[ 闪点 ]:
440.9±34.3 °C

[ 精确质量 ]:
747.476868

[ PSA ]:
182.91000

[ LogP ]:
3.16

[ 外观性状 ]:
白色至灰白色结晶粉末

[ 蒸汽压 ]:
0.0±6.5 mmHg at 25°C

[ 折射率 ]:
1.526

[ 储存条件 ]:
室温，密封

[ 水溶解性 ]:
水溶性：实际上不溶；易溶于：丙酮,氯仿；可溶于：乙醚,乙醇,甲醇

克拉霉素MSDS

克拉霉素毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KF4997000

CHEMICAL NAME :: Erythromycin, 6-O-methyl-

CAS REGISTRY NUMBER :: 81103-11-9

LAST UPDATED :: 199807

DATA ITEMS CITED :: 16

MOLECULAR FORMULA :: C38-H69-N-O13

MOLECULAR WEIGHT :: 748.08

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 30 mg/kg/3D-I

TOXIC EFFECTS :: Cardiac - pulse rate increase, without fall in BP Cardiac - change in rate

REFERENCE :: AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 30,542,1997

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1270 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1433,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 669 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 36(Suppl 3),274,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Skin and Appendages - corrosive (after topical exposure)

REFERENCE :: NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 36(Suppl 3),274,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1230 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1433,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 850 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 36(Suppl 3),274,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Skin and Appendages - corrosive (after topical exposure)

REFERENCE :: NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 36(Suppl 3),274,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 173 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,769,1991

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - nausea or vomiting Blood - hemorrhage

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1453,1988 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5600 mg/kg/28D-I

TOXIC EFFECTS :: Gastrointestinal - other changes Liver - changes in liver weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :: NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 36(Suppl 3),289,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 7280 mg/kg/26W-I

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), diffuse Liver - other changes Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :: NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 36(Suppl 3),311,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 420 mg/kg/21D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - urine volume increased Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1606,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 11200 mg/kg/28D-I

TOXIC EFFECTS :: Liver - other changes Blood - normocytic anemia Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1453,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 8400 mg/kg/4W-I

TOXIC EFFECTS :: Liver - other changes Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1485,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 3640 mg/kg/26W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Behavioral - food intake (animal) Gastrointestinal - nausea or vomiting

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1533,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 11200 mg/kg/28D-I

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), diffuse Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Related to Chronic Data - death

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,1502,1988

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克拉霉素安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 警示性声明 ]:
P301 + P312 + P330

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xi: Irritant;Xn: Harmful;

[ 风险声明 (欧洲) ]:
R22

[ 安全声明 (欧洲) ]:
26-36

[ 危险品运输编码 ]:
NONH for all modes of transport

[ RTECS号 ]:
KF4997000

[ 海关编码 ]:
29419000

克拉霉素合成路线

克拉霉素上下游产品

克拉霉素上游产品

克拉霉素下游产品

克拉霉素制备

1.以红霉素为原料，水解脱去氨基上的一个甲基，再和氯甲酸苄酯反应，对5位侧链四氢吡喃环上的羟基和氨基进行保护，然后在二甲亚砜和四氢呋喃中和碘甲烷反应，对6位上的羟基进行甲基化，再催化氢解脱去保护基，和甲醛反应对氨基进行羟甲基化，最后还原为甲基，即为克拉霉素。

2.(1)红霉素A肟(019-2)的制备

在反应瓶中加入无水乙醇50ml和红霉素(019-1)10.0g(13.6mmol),搅拌下滴加冰醋酸,溶液呈透明后,加入盐酸羟胺7.0g(100.0mmol),在适当的酸碱缓冲体系下,升温至50~60 ºC ,搅拌反应8~24h.TLC跟踪确认反应达终点后,终止反应.冷至室温,过滤除去无机盐,滤液减压蒸发至干,得白色固体.将该固体溶于20ml乙酸乙酯中,搅拌下加入4mol/L NaOH溶液,调至pH>=12.静置分层,有机层用适量水洗涤2~3次后,真空浓缩至干,得白色固体,干燥至恒重,得019-2 9.98g,收率99.9%.含019-2 93.5%,其中E-肟 82.9%,Z-肟10.6%,红霉素降解产物红霉素A 8,9-脱水-6,9-半缩酮<=2%(HPLC法).将019-2重结晶得019-2.纯品，收率95.6%。

（2）2’,4”-O-双(三甲基硅)红霉素A 9-O-(1-乙氧基环己基)肟[2’,4’’-Obis(trimethylsilyl)-eryth-romycin A 9-O91-ethoxycyclohexyl]oxime](019-4)的制备

在反应瓶中加入乙腈500ml、019-2 50.0g(67mmol)和盐酸吡啶15.0g(134mmol),搅拌下加

入1-乙氧基环己烯(EOCHE)30.0ml(223mmol),在室温(28 ºC)下搅拌反应,反应液逐渐变清无色,3h后全部转化为红霉素A9-O-(1-乙氧基环己基)肟(019-3),再加入1,1,1,3,3,3-六甲基二硅氨烷(HMDS)50.0ml(240mmol),反应液立即呈白色浊态.搅拌反应2h后,加入4mol/L NaOH溶液调至PH>=10,用乙酸乙酯(200ml*2)提取,有机相用水洗,饱和食盐水洗,无水MgSO4干燥过夜.过滤,滤液减压蒸除溶剂得019-4,mp108~110 ºC.

(3)2’,4’’-O-双(三甲基硅)6-O-甲基红霉素A 9-O-(1-乙氧基环己基)肟[2’,4’’-Obis(trimethylsilyl)-6-O-methylerythromycin A 9-O-(1-ethoxycyclohexyl)oxime](019-5)的制备。

在反应瓶中加入DMSO/THF(体积比1：1)400ml和019-4(上步一批量),搅拌溶解，再加入碘甲6.0ml(96mmol)和82%的KOH粉末6.0g(88mmol),于0 ºC 搅拌反应1h.加水200ml,用乙酸乙酯提取(200ml*2),无水MgSO4干燥有机相,过滤,滤液蒸除溶剂得019-5,mp127~129 ºC .直接用于下步反应.

(4)克拉霉素(019)的合成

在反应瓶中加入250ml乙醇和水,再加入019-5(上步一批得量),搅拌溶解,搅拌下加入甲酸5.0ml(132mmol),反应数小时后,TLC跟踪显示得6-O-甲基红霉素A 9-O-(1-乙氧基环己基)肟和6-O-甲基红霉素 A-9-肟，再补加NaHSO3 50.0g(480mmol),搅拌加热至回流，反应2h.用4mol/L的NaOH溶液调至PH>=10,析出白色固体019,用乙醇重结晶得精品019 24.7g,以红霉素A计总收率达49.5%,mp222~225 ºC .

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克拉霉素海关

[ 海关编码 ]: 29419000

克拉霉素文献

Environmental friendly method for urban wastewater monitoring of micropollutants defined in the Directive 2013/39/EU and Decision 2015/495/EU.

J. Chromatogr. A. 1418 , 140-9, (2015)

The fate and removal of organic micropollutants in the environment is a demanding issue evidenced by the recent European policy. This work presents an analytical method for the trace quantification of...

Dissolution enhancement and in vitro performance of clarithromycin nanocrystals produced by precipitation-lyophilization-homogenization method.

Eur. J. Pharm. Biopharm. 88(3) , 886-96, (2014)

The gastroduodenal diseases caused by Helicobacter pylori were commonly treated with antibiotic clarithromycin as a standard regimen. According to the poorly water-soluble of clarithromycin, the nanoc...

Simple and accurate quantitative analysis of 20 anti-tuberculosis drugs in human plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry.

J. Pharm. Biomed. Anal. 102 , 9-16, (2014)

A simple and accurate liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method for the quantitation of 20 anti-tuberculosis (anti-TB) drugs in human plasma, was developed as a tool for thera...

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克拉霉素相关知识

克拉霉素片说明书-克拉霉素副作用

2019-01-09 16:41:56

导读：克拉霉素又名甲红霉素，是红霉素的衍生物，上世纪90年代初由日本大正公司开发成功，并以商品名Clarith注册。尔后，大正公司首先将其技术转让给美国雅培公司生产；1990年在爱尔兰、意大利上市，1991年10月获FDA批准定为IB类新药上市，商品名Biaxin，1993年以Klacid在中国香...

克拉霉素

克拉霉素用途

克拉霉素作用

克拉霉素名称

克拉霉素生物活性

克拉霉素物理化学性质

克拉霉素MSDS

详细MSDS(安全技术说明书)

克拉霉素毒性和生态

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

克拉霉素安全信息

克拉霉素合成路线

详细合成路线

克拉霉素上下游产品

克拉霉素上游产品

克拉霉素下游产品

克拉霉素制备

克拉霉素海关

克拉霉素文献

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