奈替米星

奈替米星用途

为氨基糖苷类抗生素西梭霉素的衍生物。抗菌谱和庆大霉素、妥布霉素、西梭霉素、丁胺卡那霉素相似,但对金黄色葡萄球菌、肠道细菌更为有效,抑制绿脓杆菌、普罗威斯登菌则稍差。其最大的优点是对听觉神经及肾脏的毒性比临床常用的氨基糖苷类抗生素为小,对耐庆大霉素的肠道细菌及绿脓杆菌有高效。用于呼吸系统感染、皮肤软组织感染、泌尿系统感染、创面感染、骨关节感染、产后感染、胃肠道及胆道感染、败血症等。

奈替米星作用

本品属半合成氨基糖甙类抗生素,其抗菌谱广,对大肠肝菌、克霉伯菌属、肠肝菌属、沙雷菌属、枸橼酸杆菌属、变形杆菌属、沙门菌属、志贺菌属、嗜血质流感杆菌等具有高度抗菌活性;对缘脓杆菌等假单胞菌、普鲁威登菌和不动杆菌属等的某些菌株亦具有抗菌活性;对葡萄球菌属,包括甲氧西林敏感菌株和部分甲氧西林耐药菌株也具抗菌作用,对肺炎球菌、溶血性链球菌、粪肠球菌的抗菌作用较差。性状:本品为无色或几乎无色的澄明液体。

奈替米星名称

[ CAS 号 ]:
56391-56-1

[ 中文名 ]:
奈替米星

[ 英文名 ]:
NETILMICIN

[中文别名 ]:

[英文别名 ]:

奈替米星物理化学性质

[ 密度 ]:
1.32g/cm3

[ 沸点 ]:
684.3ºC at 760mmHg

[ 分子式 ]:
C21H41N5O7

[ 分子量 ]:
475.58000

[ 闪点 ]:
367.7ºC

[ 精确质量 ]:
475.30100

[ PSA ]:
199.73000

[ 折射率 ]:
1.597

奈替米星毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :
WK2285000
CHEMICAL NAME :
D-Streptamine, O-3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopy ranosyl(1-6)-O-(2,6- diamino-2,3,4,6-tetradeoxy-alpha-D-glycero-hex-4-enop yranosyl(1-4))-2-deox y-N(sup 1)-ethyl-
CAS REGISTRY NUMBER :
56391-56-1
LAST UPDATED :
199612
DATA ITEMS CITED :
17
MOLECULAR FORMULA :
C21-H41-N5-O7
MOLECULAR WEIGHT :
475.67

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Human
DOSE/DURATION :
52 mg/kg/7D-C
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes
REFERENCE :
CMAJAX Canadian Medical Association Journal. (Canadian Medical Assoc., POB 8650, Ottawa, ON K1G 0G8, Canada) V.1- 1911- Volume(issue)/page/year: 120,161,1979
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
25200 ug/kg
TOXIC EFFECTS :
Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Blood - hemorrhage
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
40 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
AMACCQ Antimicrobial Agents and Chemotherapy. (American Soc. for Microbiology, 1913 I St., NW, Washington, DC 20006) V.1- 1972- Volume(issue)/page/year: 29,543,1986
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
500 mg/kg
TOXIC EFFECTS :
Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Blood - hemorrhage
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intramuscular
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
125 mg/kg
TOXIC EFFECTS :
Brain and Coverings - changes in circulation (hemorrhage, thrombosis, etc.) Lungs, Thorax, or Respiration - chronic pulmonary edema Blood - hemorrhage
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
207 mg/kg
TOXIC EFFECTS :
Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Blood - hemorrhage
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intramuscular
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
181 mg/kg
TOXIC EFFECTS :
Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Blood - hemorrhage
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981 ** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
1350 mg/kg/15D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Metabolism (Intermediary) - other proteins
REFERENCE :
AMACCQ Antimicrobial Agents and Chemotherapy. (American Soc. for Microbiology, 1913 I St., NW, Washington, DC 20006) V.1- 1972- Volume(issue)/page/year: 10,845,1976
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
322 mg/kg/2W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - changes in bladder weight Related to Chronic Data - death
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
560 mg/kg/14D-I
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
REFERENCE :
CLREAS Clinical Research. (Slack Inc., 6900 Grove Rd., Thorofare, NJ 08086) V.6- 1958- Volume(issue)/page/year: 26,141A,1978
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
700 mg/kg/2W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in bladder weight
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Primate - monkey
DOSE/DURATION :
2100 mg/kg/21D-I
TOXIC EFFECTS :
Behavioral - ataxia Related to Chronic Data - death
REFERENCE :
JIDIAQ Journal of Infectious Diseases. (Univ. of Chicago Press, Journals Div., POB 37005, Chicago, IL 60637) V.1- 1904- Volume(issue)/page/year: 137,476,1978
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Mammal - cat
DOSE/DURATION :
4200 mg/kg/30W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 77,479,1985
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
31500 mg/kg/21D-I
TOXIC EFFECTS :
Related to Chronic Data - death
REFERENCE :
APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 53,230,1983 ** REPRODUCTIVE DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
2720 mg/kg
SEX/DURATION :
female 14 day(s) pre-mating female 1-20 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - other effects to embryo
REFERENCE :
APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 45,145,1979
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
3040 mg/kg
SEX/DURATION :
female 6-22 day(s) after conception lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)
REFERENCE :
APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 45,145,1979
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
250 mg/kg
SEX/DURATION :
female 6-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,816,1981

奈替米星合成路线

奈替米星上下游产品

奈替米星制备

方法1:发酵法,产生菌为Micromonospora inyoensis 155OF-1G,由N-乙基-α-去氧-D-链霉胺发酵,提纯而得。


方法2:以西梭霉素为原料,调节Ph值为5,乙醛烷化再氰基氢硼化钠还原即得奈替米星。


方法3:部分氨上乙酰化的西梭霉素,用乙醛和氰基硼氢化钠引入乙基后,经碱性树脂脱去乙酰基,即得奈替米星。

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