H-DL-Ser-DL-Val-DL-Ser-DL-Glu-DL-xiIle-DL-Gln-DL-Leu-DL-Met-DL-His-DL-Asn-DL-Leu-Gly-DL-Lys-DL-His-DL-Leu-DL-Asn-DL-Ser-DL-Met-DL-Glu-DL-Arg-DL-Val-DL-Glu-DL-Trp-DL-Leu-DL-Arg-DL-Lys-DL-Lys-DL-Leu-DL-Gln-DL-Asp-DL-Val-DL-His-DL-Asn-DL-Phe-OH.CH3CO2H.H2O | 52232-67-4

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 其他保护氨基酸
• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: H-DL-Ser-DL-Val-DL-Ser-DL-Glu-DL-xiIle-DL-Gln-DL-Leu-DL-Met-DL-His-DL-Asn-DL-Leu-Gly-DL-Lys-DL-His-DL-Leu-DL-Asn-DL-Ser-DL-Met-DL-Glu-DL-Arg-DL-Val-DL-Glu-DL-Trp-DL-Leu-DL-Arg-DL-Lys-DL-Lys-DL-Leu-DL-Gln-DL-Asp-DL-Val-DL-His-DL-Asn-DL-Phe-OH.CH3CO2H.H2O
• 英文别名: acetic acid;4-[[2-[[2-[[4-amino-2-[[2-[[2-[[6-amino-2-[[2-[[2-[[4-amino-2-[[2-[[2-[[2-[[5-amino-2-[[2-[[2-[[2-[[2-[(2-amino-3-hydroxypropanoyl)amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[1-[[1-[[1-[[1-[[1-[[1-[[6-amino-1-[[6-amino-1-[[1-[[5-amino-1-[[1-[[1-[[1-[[4-amino-1-[(1-carboxy-2-phenylethyl)amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-oxopentanoic acid;hydrate
• CAS: 52232-67-4
• 化学式: C183H297N55O54S2
• 分子量: 4196.0
• InChiKey: QCVZCKSPTMFSSY-UHFFFAOYSA-N

物化性质

• 熔点：
  >205oC (dec.)
• 溶解度：
  DMSO（少许）、水（少许）

安全信息

• WGK Germany：
  3
• 海关编码：
  2937190000

制备方法与用途

分子结构

特立帕肽是一种合成的34肽，为人甲状旁腺素PTH的1-34氨基酸片段，该片段是含有84个氨基酸的内源性甲状旁腺素PTH具有生物活性的N-末端区域。本品的免疫学和生物学特性与内源性甲状旁腺素PTH以及牛甲状旁腺素PTH(bPTH)完全相同。

药代动力学

特立帕肽皮下注射后吸收及消除速度都很快，皮下注射本品20 μg，达峰时间(tmax)为30 min，半衰期(t1/2 )为60 min，静脉注射血清半衰期为5 min，绝对生物利用度95%。90%药物经肾脏清除。

不良反应与安全性

特立帕肽注射后常见不良反应包括头晕、背痛、恶心和下肢痉挛等，多为一过性；少见的不良反应包括心律失常、耳聋等。目前认为不良反应发生与患者年龄和给药剂量之间无明显关系。

作用机制

特立帕肽可通过抑制成骨细胞凋亡、激活骨衬细胞和增强成骨细胞分化来介导骨代谢。通过调节腺苷酸环化酶-环磷酸腺苷-蛋白激酶A传导通路间歇性刺激成骨细胞、骨衬细胞和骨髓基质干细胞表面PHT-Ⅰ受体，促进成骨细胞的分化、延长成骨细胞寿命；通过磷酸酯C-胞浆钙离子-蛋白激酶C信号传导通路，刺激成骨细胞系增殖；通过抑制PPARγ的反式激活活性，减少基质细胞向脂肪细胞系分化，使成骨细胞数量增加；通过调节细胞因子间接调节骨的成长，例如可以诱导iGF-1与成骨细胞结合，从而促进骨的形成；通过Wnt信号通路调节骨形成的过程，从而增加骨的形成。

多肽类药物

礼来公司甲状旁腺激素复泰奥（特立帕肽）最早批准用于绝经后妇女骨质疏松 症，初期或性腺机能减退的男性骨质疏松症患者，后来再次增加新适应症用于 在具有骨折高风险的治疗与持久性、全身性糖皮质激素治疗有关的骨质疏松。
2011年复泰奥（特立帕肽）在全球销售额达到9.51亿美元。在中国市场，2011 年由礼来（法国）公司开始进口。

生物活性

Teriparatide (Human parathyroid hormone-(1-34)) 是 PHT 的激动剂，其在 HEK293 细胞中的 IC50 值为 2 nM。

靶点

IC50: 2 nM (PTH).

体内研究

Trabecular bone calcium and dry weight of the distal femur increased significantly in Teriparatide-treated animals. The increase in trabecular calcium compared with vehicle control occurred as early as 1 week after initiation of treatment with a 35% and 45% increase, respectively, for 10 μg/kg and 40 μg/kg Teriparatide. Similar results were observed for trabecular dry weight. After 4 weeks of treatment with 10 mg/kg or 40 mg/kg Teriparatide, trabecular calcium increased significantly by 70% and 123%, respectively, compared with the vehicle and by 73%.
The 4-week Teriparatide administration increase the pore ratio, number, and density as well as the cortical area, thickness, and bone mineral content (BMC), without significant influencing the volumetric bone mineral density (BMD). The 4-week Teriparatide administration + 8-week vehicle administration decrease the pore ratio, number, and density as well as the cortical area and thickness, compared with the 4-week Teriparatide administration, but the pore ratio, cortical area, and thickness are still higher compared with the 12-week vehicle administration. The 4-week Teriparatide administration + 8-week higherdose IBN administration increase the cortical area, thickness, BMC, and volumetric BMD and decrease the pore ratio, but not the pore number or density, compared with the 4-week Teriparatide administration + 8-week vehicle administration.

参考质量标准

外观?白色粉末纯度(HPLC) ≥95.0%
单杂≤1.0%
醋酸根含量5.0%～12.0%
水分含量≤10.0%
肽含量≥80.0%
内毒素≤5EU/mg