Acylated derivative of human insulin or analogue thereof
AssigneeJiangsu Hengrui Medicine Co., Ltd.
InventorsDeyu LIU, Hongwei WANG, Liang ZHAO, Feifei WANG, Xiang ZENG, Tao WANG, Yali WANG, Yulu DAI
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Abstract
Provided is an acylated derivative of human insulin or an analogue thereof. Specifically disclosed is an acylated derivative of a human insulin analogue, or zinc complex thereof; said acylated derivative is longer-lasting than existing insulin analogues and acylated derivatives thereof, its blood glucose reduction is more steady, and it is more stable in storage.
Claims20
An acylated derivative of human insulin analogue or a zinc complex thereof, wherein the acylated derivative of human insulin analogue has a structure represented by the following formula:
- S—W—X—Y—Z (I)
- wherein S is human insulin in which threonine at amino acid 30 on B chain is absent;
- and
- —W—X—Y—Z is an acylated modifying group of insulin analogue;
- wherein W is a diacyl structure having —OC(CH2)nCO—, wherein n is an integer between 2 and 10, and an amide bond is formed by one of said diacyl structure's acyl groups with α-amino group of the amino acid residue at N-end of A-chain or B-chain of parent insulin or analogue thereof or with ε-amino group of lysine residue present on B-chain;
- X is a diamino compound containing carboxylic acid group, and an amide bond is formed by linking one of the amino groups of the compound to one of the acyl groups in W;
- Y is -A(CH2)m—, wherein m is an integer between 6 and 32, preferably an integer between 10 and 16, particularly preferably an integer between 12 and 14, and A is absent or CO—;
- and
- Z is —COOH.
Nα—(HOOC(CH2)14CO)—Nε—(OCCH2CH2CO—(NεB29-Des(B30) human insulin))-Lys-OH or a zinc complex thereof, preferably lysine B29 (Nε—(Nα-hexadecane diacid-L-lysine-M-oxobutyryl))des(B30) human insulin or a zinc complex thereof.
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Dependencies are inferred from the claim text.