79517-01-4

• 常用中文名：奥曲肽
• 常用英文名：Octreotide acetate salt
• CAS号：79517-01-4
• 分子式：C₅₁H₇₀N₁₀O₁₂S₂
• 分子量：1079.29
• 相关类别： 原料药 激素及调节内分泌功能类药 其它
• 发布时间：2018-03-11 08:00:00
• 更新时间：2024-01-02 10:04:12
• Octreotide acetate是长效的天然生长抑素合成类似物,是比生长抑素更有效的生长激素,胰高血糖素和胰岛素的抑制剂。
• 体外活性：与盐水组相比，奥曲肽治疗组显示肿瘤体积显着减少。 奥曲肽-PPSG（1.4mg / kg，腹膜内）显示出比奥曲肽溶液（100μg/ kg，腹膜内注射）更强的抗肿瘤效果。 与盐水组相比，奥曲肽处理对携带原代HCC的大鼠中SSTR2和SSTR5的表达水平具有显着的抑制作用。 奥曲肽-PPSG似乎比奥曲肽 - 溶液治疗组更能抑制SSTR2和SSTR5的表达。 醋酸奥曲肽的测试剂量在2小时内将血清胃泌素水平显着降低至基线的约三分之一，并且效果持续约6小时。 在第21天，开始用缓释制剂醋酸奥曲肽（5mg肌肉注射，q 4周）治疗。

名称

• 中文名: 奥曲肽
• 英文名: acetic acid,10-(4-aminobutyl)-19-[(2-amino-3-phenylpropanoyl)amino]-16-benzyl-N-(1,3-dihydroxybutan-2-yl)-7-(1-hydroxyethyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide
• 英文别名: Sandostatin (TN); Octreotide acetate (USAN); 1,2-Dithia-5,8,11,14,17-pentaazacycloeicosane-4-carboxamide, 10-(4-aminobutyl)-19-[[(2R)-2-amino-1-oxo-3-phenylpropyl]amino]-7-(1-hydroxyethyl)-N-[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-16-(phenylmethyl)-, (4R,7S,10S,13R,16S,19R)-, acetate (1:1) (salt); Octreotide (acetate); (4R,7S,10S,13R,16S,19R)-10-(4-Aminobutyl)-16-benzyl-N-[(2R,3R)-1,3-dihydroxy-2-butanyl]-7-(1-hydroxyethyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-19-(D-phenylalanylamino)-1,2-dithia-5,8,11,14,17-pentaazacycloicosane-4-carboxamide acetate (1:1); Octreotide; Octreotide Acetate; SMS 201-995; 1,2-Dithia-5,8,11,14,17-pentaazacycloeicosane-4-carboxamide, 10-(4-aminobutyl)-19-[[(2R)-2-amino-1-oxo-3-phenylpropyl]amino]-7-[(1R)-1-hydroxyethyl]-N-[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-16-(phenylmethyl)-, (4R,7S,10S,13R,16S,19R)-; Sandostatin LAR; (4R,7S,10S,13R,16S,19R)-10-(4-Aminobutyl)-16-benzyl-N-[(2R,3R)-1,3-dihydroxy-2-butanyl]-7-[(1R)-1-hydroxyethyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-19-(D-phenylalanylamino)-1,2-dithia-5,8,11,14,17-pentaazacycloicosane-4-carboxamide; Sandostatin; (4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-16-benzyl-N-[(2R,3R)-1,3-dihydroxybutan-2-yl]-7-(1-hydroxyethyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-19-(D-phenylalanylamino)-1,2-dithia-5,8,11,14,17-pentaazacycloicosane-4-carboxamide acetate (1:1); zacycloicosane-4-carboxamide acetate

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 1447.2±65.0 °C at 760 mmHg
• 熔点: 153-156ºC
• 分子式: C₅₁H₇₀N₁₀O₁₂S₂
• 分子量: 1079.29
• 闪点: 829.1±34.3 °C
• PSA: 382.82000
• LogP: 0.77
• 外观性状: 无色至灰白色冻干的固体
• 蒸汽压: 0.0±0.3 mmHg at 25°C
• 折射率: 1.673
• 储存条件: 库房低温,通风,干燥,与食品原料分开存放
• 稳定性:

  是迄今惟一成功地应用于治疗的胃肠激素类似物，是一个含有环状结构的合成八肽，部分氨基酸序列与生长抑素类似，具备生长抑素的几乎全部生物作用，如抑制多种垂体和胃肠胰激素释放，抑制胃酸、胰液和胆汁分泌，抑制胃肠道运动和分泌等，但半衰期为生长抑素的30倍。

生物活性

• 描述: Octreotide acetate是长效的天然生长抑素合成类似物,是比生长抑素更有效的生长激素,胰高血糖素和胰岛素的抑制剂。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 生长抑素受体
  多肽产品
  研究领域 >> 心血管疾病
  研究领域 >> 炎症/免疫
  多肽产品
• 体内研究: 与盐水组相比,奥曲肽治疗组显示肿瘤体积显着减少。奥曲肽-PPSG(1.4mg/kg,ip)显示出比奥曲肽溶液(100μg/ kg,ip)更强的抗肿瘤效果。与盐水组相比,奥曲肽处理对携带原代HCC的大鼠中SSTR2和SSTR5的表达水平具有显着的抑制作用。与Octreotide-soln治疗组相比,奥曲肽-PPSG似乎更能抑制SSTR2和SSTR5的表达[1]。醋酸奥曲肽的测试剂量在2小时内将血清胃泌素水平显着降低至基线的约三分之一,并且效果持续约6小时。在第21天,开始用缓释制剂醋酸奥曲肽(5mg肌内,q 4周)治疗[2]。
• 动物实验: 小鼠[1]将30只HCC异种移植物小鼠随机分成三组：（A）奥曲肽 - 溶质组，（B）奥曲肽 - PPSG组和（C）对照组。奥曲肽 - 溶质组每天一次腹膜内注射100μg/ kg奥曲肽 - 溶液，连续14天。奥曲肽-PPSG组单次皮下注射1.4 mg / kg奥曲肽-PPSG，注射量约为0.2 mL。对照组每天一次腹腔注射盐水，连续14天。在注射H22肝细胞瘤细胞悬液后第二天开始治疗并维持14天。通过在接种后第7天和第14天的定期测径器测量来监测肿瘤生长。肿瘤体积（V）基于肿瘤的长度和宽度通过等式计算。大鼠[1]将12只雄性SD大鼠分成两组，并置于25℃的标准笼中，在实验前自由获取食物和水一周。给大鼠皮下注射奥曲肽 - 戊二酸溶液（奥曲肽 - 溶液）或奥曲肽 - PPSG，剂量相当于20mg / kg。剂量基于人体中奥曲肽 - soln的临床剂量确定。在给药前将大鼠禁食12小时，并在给药后约2小时返回食物。使用肝素化的Eppendorf管在预定时间点收集血液样品。收集后立即将血液样品置于冰上，直至在1小时内以3000g离心10分钟。收集血浆并储存在-20℃直至分析。
• 参考文献:

  [1]. Wang M, et al. Pharmacokinetic and pharmacodynamic study of a phospholipid-based phase separation gel for once a month administration of octreotide. J Control Release. 2016 May 28;230:45-56.

  [2]. Kim S, et al. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog. J Am Anim Hosp Assoc. 2015 Nov-Dec;51(6):407-12.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : HA1000000 CHEMICAL NAME : L-Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophy l-L-lysyl-L-threonyl- N- (2-hydroxy-1-(hydroxymethyl)propyl)-, cyclic(2-7)-disulfide, (R-(R*,R*))-, acetate (salt) CAS REGISTRY NUMBER : 79517-01-4 LAST UPDATED : 199709 DATA ITEMS CITED : 8 MOLECULAR FORMULA : C49-H66-N10-O10-S2.2C2-H4-O2 MOLECULAR WEIGHT : 1139.49 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Human - man DOSE/DURATION : 2587 ug/kg TOXIC EFFECTS : Gastrointestinal - changes in structure or function of endocrine pancreas Liver - liver function tests impaired REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 348,1668,1996 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Human - man DOSE/DURATION : 1429 ug/kg TOXIC EFFECTS : Gastrointestinal - changes in structure or function of endocrine pancreas Liver - liver function tests impaired REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 348,1668,1996 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >50 mg/kg TOXIC EFFECTS : Skin and Appendages - dermatitis, allergic (after topical exposure) Skin and Appendages - hair 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: 21,5151,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18100 ug/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: 22,967,1991 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >100 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - somnolence (general depressed activity) Behavioral - ataxia 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: 21,5151,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 72300 ug/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: 22,967,1991 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >20 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,240,1990 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18200 ug/kg/13W-C TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes Blood - other changes Biochemical - Metabolism (Intermediary) - Plasma proteins not involving coagulation 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: 21,5151,1987

安全

• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3