STABLE AQUEOUS PARENTERAL PHARMACEUTICAL COMPOSITIONS OF INSULINOTROPIC PEPTIDES

摘要

Disclosed herein is an insulinotropic peptide multi-dose aqueous parenteral pharmaceutical composition and use thereof. A long-term storage formulation of the insulinotropic peptide can be obtained via the method of the present disclosure. The pharmaceutical composition of the present disclosure comprises: insulinotropic peptide, insulinotropic peptide analogue and derivative; pharmaceutically acceptable tonicity modifier (stabilizer); pharmaceutically acceptable preservative; and pharmaceutically acceptable dissolution enhancer and pharmaceutically acceptable buffer solution. The pharmaceutical composition of the insulinotropic peptide is used in the preparation of drugs for treating diabetes and adiposis.

主权项

1. An aqueous parenteral pharmaceutical composition comprising an insulinotropic peptide, a pharmaceutically acceptable osmotic agent, a pharmaceutically acceptable preservative, a pharmaceutically acceptable dissolution enhancer, and a pharmaceutically acceptable buffer salt solution, wherein:
the aqueous parenteral pharmaceutical composition has a pH of 3.0 to 5.0; the insulinotropic peptide has a concentration of 0.1 mg/mL to 20 mg/mL; the insulinotropic peptide is GLP-1, Exendin-4, a GLP-1 analogue, an Exendin-4 analogue, a GLP-1 derivative or an Exendin-4 derivative; GLP-1 and the GLP-1 analogues have a sequence as follows:(SEQ ID NO: 1)6  10    20      30  37X6HX8EGTFTSD VSSYLEX22QAA X26EFIAWLVX34G X36X37 wherein, X6 is R or a deletion;X8 is A, G or V;X22 is G or E;X26 is K, R, Q or N;X34 is K, R, Q or N;X36 is R, R—NH2, K or K—NH2;X37 is G or a deletion; and Exendin-4 and the Exendin-4 analogue have a sequence as follows:(SEQ ID NO: 2)X1X2X3GTX6X7X8X9X10 SKQX14EEEAVX20 LX22X23X24X25LKNGGX31X32X33X34X35X36X37X38X39 wherein, X1 is H, R or Y; X2 is S, G, A or T; X3 is D or E; X6 is F or Y; X7 is T, Y or S; X8 is S or Y; X9 is D or E; X10 is L or I; X14 is L, I, V or M; X20 is R or K; X22 is F or Y; X23 is I, V, L or M; X24 is E or D; X25 is W, For Y; X31 is P or a deletion; X32 is S or a deletion; X33 is S or a deletion; X34 is G or a deletion; X35 is A or a deletion; X36 is P or a deletion; X37 is P or a deletion; X38 is P or a deletion; and X39 is S, R or a deletion.