用于药物输送装置的驱动组件和药物输送装置的制造方法_2

文档序号:9528650阅读:来源:国知局
9_N_肉?蔑醜人膜岛素;Β29_Ν_掠桐醜人膜岛素;Β28_Ν_肉豆蔻酰LysB28ProB29人胰岛素;Β28_Ν_棕榈酰_LysB28ProB29人胰岛素;B30_N_肉豆蔻酰-ThrB29LysB30 人胰岛素;B30_N_ 棕榈酰 _ThrB29LysB30 人胰岛素;B29_N_ (N-棕榈酰-T -谷氨酰)-des (B30)人膜岛素;B29_N_ (N-石胆酰-T -谷氨酰)-des (B30)人膜岛素;B29_N_ (ω -竣基十七醜)_des (B30)人膜岛素和B29-N- (ω -竣基十七醜)人膜岛素。
[0037]毒蜥'外泌肽-4指例如毒蜥'外泌肽_4 (1_39),其是具有下述序列的肽:H-His_Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-1le-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser_NH20
[0038]毒蜥外泌肽-4衍生物例如选自下述化合物列表:
[0039]H- (Lys)4-des Pro36, des Pro37 毒蜥外泌肽 _4 (1-39) _NH2,
[0040]H- (Lys)5-des Pro36, des Pro37 毒蜥外泌肽 _4 (1-39)-NH2,
[0041 ] des Pro36 毒蜥'外泌妝 _4 (1-39),
[0042]des Pro36[Asp28]毒蜥外泌肽-4(1-39),
[0043]des Pro36 [IsoAsp28]毒蜥'外泌妝-4 (1-39),
[0044]des Pro36 [Met (0) 14,Asp28]毒蜥外泌肽 _4 (1-39),
[0045]des Pro36 [Met (0) 14, IsoAsp28]毒蜥'外泌妝-4 (1-39),
[0046]des Pro36 [Trp (02) 25,Asp28]毒蜥外泌肽 _4 (1-39),
[0047]des Pro36 [Trp (02) 25,IsoAsp28]毒蜥外泌肽 _4 (1-39),
[0048]des Pro36 [Met (0) 14 Trp (02) 25,Asp28]毒蜥外泌肽-4 (1-39),
[0049]des Pro36[Met(0) 14 Trp (02)25, IsoAsp28]毒蜥外泌肽 _4 (1-39);或
[0050]des Pro36 [Asp28]毒蜥'外泌妝-4 (1-39),
[0051]des Pro36 [IsoAsp28]毒蜥'外泌妝-4 (1-39),
[0052]des Pro36 [Met (0) 14,Asp28]毒蜥外泌肽 _4 (1-39),
[0053]des Pro36 [Met (0) 14, IsoAsp28]毒蜥'外泌妝-4 (1-39),
[0054]des Pro36 [Trp (02) 25,Asp28]毒蜥外泌肽 _4 (1-39),
[0055]des Pro36 [Trp (02) 25,IsoAsp28]毒蜥外泌肽 _4 (1-39),
[0056]des Pro36 [Met (0) 14 Trp (02) 25,Asp28]毒蜥外泌肽-4 (1-39),
[0057]des Pro36 [Met (0) 14 Trp (02) 25,IsoAsp28]毒蜥外泌肽-4 (1-39),
[0058]其中-Lys6-NH2基团可以结合于毒蜥外泌肽_4衍生物的C端;
[0059]或下述序列的毒蜥外泌肽-4衍生物
[0060]des Pro36 毒蜥外泌肽 _4 (1-39) -Lys6_NH2 (AVE0010),
[0061]Η- (Lys)6-des Pro36 [Asp28]毒蜥外泌肽 _4 (1-39)-Lys6_NH2,
[0062]des Asp28 Pro36, Pro37, Pro38 毒蜥外泌肽 _4 (1-39) -NH2,
[0063]H- (Lys)6-des Pro36, Pro38 [Asp28]毒蜥外泌肽 _4 (1-39)-NH2,
[0064]H-Asn- (Glu)5des Pro36, Pro37, Pro38[Asp28]毒蜥外泌肽-4 (1-39)-NH2,
[0065]des Pro36, Pro37, Pro38[Asp28]毒蜥外泌肽-4 (1-39) - (Lys) 6-NH2,
[0066]H- (Lys) 6_des Pro36, Pro37, Pro38 [Asp28]毒蜥外泌肽 _4 (1-39) - (Lys) 6-NH2,
[0067]H-Asn - (Glu) 5~des Pro36, Pro37, Pro38 [Asp28]毒撕外泌肽-4 (1-39)-(Lys)6-NH2,
[0068]H- (Lys) 6_des Pro36 [Trp (02) 25,Asp28]毒蜥外泌肽 _4 (1-39) -Lys6_NH2,
[0069]H-des Asp28 Pro36, Pro37, Pro38 [Trp (02) 25]毒蜥外泌肽 _4 (1-39) -NH2,
[0070]H- (Lys) 6~des Pro36, Pro37, Pro38 [Trp (02) 25, Asp28]毒蜥' 外泌肽-4(1-39)-ΝΗ2,
[0071]H-Asn-(Glu) 5_des Pro36, Pro37, Pro38 [Trp (02) 25, Asp28]毒蜥' 外泌肽-4(1-39)-ΝΗ2,
[0072]des Pro36, Pro37, Pro38 [Trp (02) 25,Asp28]毒蜥外泌肽 _4 (1-39) - (Lys) 6-NH2,
[0073]H- (Lys) 6~des Pro36, Pro37, Pro38 [Trp (02) 25, Asp28]毒蜥' 外泌肽-4 (1-39)-(Lys)6-NH2,
[0074]H-Asn-(Glu) 5_des Pro36, Pro37, Pro38 [Trp (02) 25, Asp28]毒蜥' 外泌肽-4 (1-39)-(Lys)6-NH2,
[0075]H- (Lys) 6_des Pro36 [Met (0) 14,Asp28]毒蜥外泌肽 _4 (1-39) -Lys6_NH2,
[0076]des Met (0) 14 Asp28 Pro36, Pro37, Pro38 毒蜥外泌肽 _4 (1-39) -NH2,
[0077]H- (Lys) 6-desPro36, Pro37, Pro38 [Met (0) 14,Asp28]毒蜥外泌肽 _4 (1-39) -NH2,
[0078]H-Asn-(Glu) 5-des Pro36, Pro37, Pro38 [Met (0) 14, Asp28]毒蜥外泌肽-4(1-39)-ΝΗ2,
[0079]des Pro36, Pro37, Pro38 [Met (0) 14,Asp28]毒蜥外泌肽 _4 (1-39) - (Lys) 6-NH2,
[0080]H- (Lys) 6~des Pro36, Pro37, Pro38 [Met (0) 14, Asp28]毒蜥' 外泌肽-4 (1-39)-(Lys)6-NH2,
[0081]H-Asn-(Glu) 5 des Pro36, Pro37, Pro38 [Met (0) 14, Asp28]毒蜥外泌肽-4 (1-39)-(Lys)6-NH2,
[0082]H-Lys6-des Pro36 [Met (0) 1 4, Trp (02) 25, Asp28]毒蜥外泌月太-4(l-39)-Lys6-NH2,
[0083]H-des Asp28 Pro36, Pro37, Pro38 [Met (0) 14, Trp (02) 25]毒蜥外泌肽-4(1-39)-ΝΗ2,
[0084]H- (Lys)6-des Pro36, Pro37, Pro38 [Met (0) 14, Asp28]毒蜥外泌肽 _4 (1-39)-NH2,
[0085]H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Met (0) 14, Trp (02) 25, Asp28]毒蜥外泌肽-4(1-39)-ΝΗ2,
[0086]des Pro36, Pro37, Pro38 [Met (0) 14, Trp (02) 25, Asp28]毒蜥' 外泌肽-4 (1-39)-(Lys)6-NH2,
[0087]H- (Lys)6-des Pro36, Pro37, Pro38 [Met (0) 14, Trp (02) 25, Asp28]毒蜥外泌月太-4(Sl-39)-(Lys)6-NH2,
[0088]H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Met (0) 14, Trp (02) 25, Asp28]毒蜥外泌肽-4 (1-39)-(Lys)6-NH2 ;
[0089]或前述任一种毒蜥外泌肽-4衍生物的药学可接受盐或溶剂合物。
[0090]激素例如在Rote Liste, ed.2008,第50章中列出的垂体激素(hypophysishormones)或下丘脑激素(hypothalamus hormones)或调节性活性月太(regulatoryactive peptides)和它们的措抗剂,诸如促性腺激素(促滤泡素(Follitropin)、促黄体激素(Lutropin)、绒毛膜促性腺激素(Chor1ngonadotropin)、绝经促性素(Menotropin))、Somatropine (生长激素(Somatropin))、去氨加压素(Desmopressin)、特利加压素(Terlipressin)、戈那瑞林(Gonadorelin)、曲普瑞林(Triptorelin)、亮丙瑞林(Leuprorelin)、布舍瑞林(Buserelin)、那法瑞林(Nafarelin)、戈舍瑞林(Goserelin)。
[0091]多糖例如葡糖胺聚糖(glucosaminoglycane)、透明质酸(hyaluronicacid)、肝素、低分子量肝素或超低分子量肝素或其衍生物,或前述多糖的硫酸化,例如多硫酸化的形式,和/或其药学可接受的盐。多硫酸化低分子量肝素的药学可接受盐的一个实例是依诺月干素钠(enoxaparin sodium)。
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