含有甲硫氨酸的水性胰岛素制备物的制作方法_4

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Arg、Lys 或化学键;
[0306] B32是Arg-酰胺、Ly S-酰胺或氨基,
[0307] 其中,含有六5^15)18、8-1、80、81、82、83和财的组中的两个氨基酸残基同时且彼 此独立地为Asp或Glu。
[0308] 4.如项3中所要求保护的药物制剂,其中所述胰岛素类似物选自下组:
[0309] Arg(AO),His(A8),Glu(A5),Asp(A18),Gly(A21),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0310] Arg(AO),His(A8),Glu(A5),Asp(A18),Gly(A21),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0311 ] Arg(AO),His(A8),Glu(A15),Asp(A18),Gly(A21),Arg(B31),Arg(B32)-NH 2人胰 岛素、
[0312] Arg(AO),His(A8),Glu(A15),Asp(A18),Gly(A21),Arg(B31),Lys(B32)-NH 2人胰 岛素、
[0313] Arg(AO),His(A8),Glu(A5),Glu(A15),Gly(A21),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0314] Arg(AO),His(A8),Glu(A5),Glu(A15),Gly(A21),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0315] Arg(AO),His(A8),Glu(A5),Gly(A21),Asp(B3),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0316] Arg(AO),His(A8),Glu(A5),Gly(A21),Asp(B3),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0317] Arg(AO),His(A8),Glu(A15),Gly(A21),Asp(B3),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0318] Arg(AO),His(A8),Glu(A15),Gly(A21),Asp(B3),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0319] Arg(AO),His(A8),Asp(A18),Gly(A21),Asp(B3),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0320] Arg(AO),His(A8),Asp(A18),Gly(A21),Asp(B3),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0321 ] Arg(AO),His(A8),Gly(A21),Asp(B3),Glu(B4),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0322] Arg(AO),His(A8),Gly(A21),Asp(B3),Glu(B4),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0323] Arg(AO),His(A8),Glu(A5),Gly(A21),Glu(B4),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0324] Arg(AO),His(A8),Glu(A5),Gly(A21),Glu(B4),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0325] Arg(AO),His(A8),Glu(A15),Gly(A21),Glu(B4),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0326] Arg(AO),His(A8),Glu(A15),Gly(A21),Glu(B4),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0327] Arg(AO),His(A8),Asp(A18),Gly(A21),Glu(B4),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0328] Arg(AO),His(A8),Asp(A18),Gly(A21),Glu(B4),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0329] Arg(AO),His(A8),Glu(A5),Gly(A21) ,Glu(BO),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0330] Arg(AO),His(A8),Glu(A5),Gly(A21) ,Glu(BO),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0331 ] Arg(AO),His(A8),Glu(A15),Gly(A21) ,Glu(BO),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0332] Arg(AO),His(A8),Glu(A15),Gly(A21) ,Glu(BO),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0333] Arg(AO),His(A8),Asp(A18),Gly(A21) ,Glu(BO),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0334] Arg(AO),His(A8),Asp(A18),Gly(A21) ,Glu(BO),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0335] Arg(AO),His(A8),Glu(A5),Gly(A21) ,Asp(Bl),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0336] Arg(AO),His(A8),Glu(A5),Gly(A21) ,Asp(Bl),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0337] Arg(AO),His(A8),Glu(A15),Gly(A21) ,Asp(Bl),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0338] Arg(AO),His(A8),Glu(A15),Gly(A21) ,Asp(Bl),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0339] Arg(AO),His(A8),Asp(A18),Gly(A21) ,Asp(Bl),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0340] Arg(AO),His(A8),Asp(A18),Gly(A21) ,Asp(Bl),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0341] Arg(AO),His(A8),Gly(A21) ,Glu(BO) ,Asp(Bl),Arg(B31),Arg(B32)-NH2人胰岛 素、
[0342] Arg(AO),His(A8),Gly(A21) ,Glu(BO) ,Asp(Bl),Arg(B31),Lys(B32)-NH2人胰岛 素、
[0343] Arg(AO),His(A8),Asp(A18),Gly(A21),Asp(B3),Arg(B30),Arg(B31)-NH2人胰岛 素、
[0344] Arg(AO),His(A8),Asp(A18),Gly(A21),Asp(B3),Arg(B30),Lys(B31)-NH2人胰岛 素。
[0345] 5.如项I中所要求保护的药物制剂,所述胰岛素类似物选自含有式II的胰岛素类 似物的组,
[0347] 其中,
[0348] A-I 是 Lys、Arg 或氨基;
[0349] AO 是 Lys、Arg 或化学键;
[0350] Al 是 Arg 或 Gly;
[0351] A5 是 Asp、Glu 或 Gln;
[0352] A15 是 Asp、Glu 或 Gln;
[0353] A18 是 Asp、Glu 或 Asn;
[0354] A21是Ala、Ser、Thr或Gly;
[0355] B-I 是 Asp、Glu 或氨基;
[0356] BO 是 Asp、Glu 或化学键;
[0357] Bl 是 Asp、Glu、Phe 或化学键;
[0358] B3 是 Asp、Glu 或 Asn;
[0359] B4 是 Asp、Glu 或 Gln;
[0360] B29 是 Arg、Ly s 或选自含有氨基酸 Phe、Ala、Thr、Ser、Val、Leu、Glu 或 Asp的组的氨 基酸、或化学键;
[0361] B30是Thr或化学键;
[0362] B31 是 Arg、Lys 或化学键;
[0363] B32是Arg-酰胺或Lys-酰胺,
[0364] 其中,不多于一个选自含有45)15^18、8-1、80、81、82、83和财的组的氨基酸残基 同时且彼此独立地为Asp或Glu。
[0365] 6.如项5中所要求保护的药物制剂,其中所述胰岛素类似物选自下组:
[0366] Arg(A-I) ,Arg(AO),Glu(A5),His(A8),Gly(A21),Arg(B30)-NH2人胰岛素、
[0367] Arg(A-I) ,Arg(AO),Glu(A5),His(A8),Gly(A21),Lys(B30)-NH2人胰岛素、
[0368] Arg(A-I) ,Arg(AO),Glu(A15),His(A8),Gly(A21),Arg(B30)-NH2人胰岛素、
[0369] Arg(A-I) ,Arg(AO),Glu(A15),His(A8),Gly(A21),Lys(B30)-NH2人胰岛素、
[0370] Arg(A-I) ,Arg(AO),Asp(A18),His(A8),Gly(A21),Arg(B30)-NH2人胰岛素、
[0371] Arg(A-I) ,Arg(AO),Asp(A18),His(A8),Gly(A21),Arg(B30)-NH2人胰岛素、
[0372] Arg(A-I) ,Arg(AO),His(A8),Gly(A21) ,Glu(BO),Arg(B30)-NH2人胰岛素、
[0373] Arg(A-I) ,Arg(AO),His(A8),Gly(A21) ,Glu(BO),Lys(B30)-NH2人胰岛素、
[0374] Arg(A-I) ,Arg(AO),His(A8),Gly(A21),Asp(B3),Arg(B30)-NH2人胰岛素、
[0375] Arg(A-I) ,Arg(AO),His(A8),Gly(A21),Asp(B3),Lys(B30)-NH2人胰岛素、
[0376] Arg(A-I) ,Arg(AO),His(A8),Gly(A21),Glu(B4),Arg(B30)-NH2人胰岛素、
[0377] Arg(A-I) ,Arg(AO),His(A8),Gly(A21),Glu(B4),Lys(B30)-NH2人胰岛素、
[0378] Arg(AO),His(A8),Gly(A21),Arg(B31),Arg(B32)-NH2人胰岛素、
[0379] Arg(AO),His(A8),Gly(A21),Arg(B31),Lys(B32)-NH2人胰岛素、
[0380] Arg(AO),Glu(A5),His(A8),Gly(A21),Arg(B31),Arg(B32)-NH2人胰岛素、
[0381] Arg(AO)
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