INSULIN-OLIGOMER CONJUGATES, PREPARATIONS AND APPLICATIONS THEREOF Russian patent published in 2014 - IPC C07K14/62 A61K38/28 A61P3/10 

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to biotechnology and can be used in producing insulin preparations for therapeutic applications. What is presented is a complex of a conjugate of insulin with a bivalent cation of a group II metal or a transient metal, wherein insulin is conjugated with a modifying group: -X-R¹-Y-PAG-Z-R² (IV), wherein: X, Y and Z represents independently the chosen binding groups and each of them optionally presents, and X, if presents, is bound to the compound insulin by a covalent bond, wherein X, Y, Z can be independently specified in -S-, -O-, -NH- and -C(O)-; at least one of R¹ or R² presents and represents lower alkyl optionally containing a carbonyl group, and provide R¹ represents lower alkyl, then R² represents a blocking group specified in -CH₃, -H, tosylate or -C(O)OH; PAG represents a linear or branched carbon chain containing one or more PEG groups containing 2 to 10 of (CH₂CH₂O)-subunits, and optionally containing one or more additional groups specified in-S-, -O-, -NH- and -C(O)-; and wherein the modifying group has the maximum number of 3 to 25 heavy atoms specified in C, S, N and O, and bound to lysine in a position specified in a group consisting of the positions B26, B27, B28, B29 and B30 insulin within 5 amino acids of C-terminal of B-chain, thereby producing a monoconjugate. The conjugate of insulin is the same or more soluble than the respective non-conjugated insulin, and water solubility of the conjugate of insulin is reduced by adding zinc. The inventions also involve a method for preparing these complexes, pharmaceutical compositions for treating insulin deficiency in a human, containing these complexes and using them in preparing a drug for treating diabetes.

EFFECT: prepared complexes show improved chemical stability as compared to the conjugates of insulin not in the complex.

51 cl, 42 dwg, 40 tbl, 86 ex