ANDRESEN, Lene,HANSEN, Rosa Rebecca Erritzøe,JEPPESEN, Per
申请号：
ES11718398
公开号：
ES2612468T3
申请日:
2011.05.09
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
A process for preparing a pharmaceutical formulation containing an insulin derivative, where the procedure comprises dissolving an insulin derivative in water, adjusting the pH of the solution to a pH greater than 7.2, adding a zinc solution for a longer period. seven minutes while continuously stirring and adjusting the pH to the desired pH of the formulation, and where the insulin derivative comprises an insulin molecule having a side chain attached to the ε-amino group of a Lys residue present in the chain B of the original insulin or an analogue thereof, where the side chain has the general formula: -WXYZ. where W is: * a residue of an α-amino acid having a carboxylic acid group in the side chain where the residue forms, with one of its carboxylic acid groups, an amide group together with the ε-amino group of a Lys residue present in the B chain of the original insulin； * a chain composed of two, three or four α-amino acid residues linked together through carbonylamide bonds, where the chain, through an amide bond, is attached to a ε-amino group of a Lys residue present in the original insulin B chain, where W amino acid residues are chosen from the group of amino acid residues that have a neutral side chain and amino acid residues that have a carboxylic acid group in the side chain so that W has at least one amino acid residue with a carboxylic acid group in the side chain； or * a covalent bond between X and a ε-amino group of a Lys residue present in the B chain of the original insulin； X is: - -CO-； - -CH (COOH) CO-； - -CO-N (CH2COOH) CH2CO-； - -CO-N (CH2COOH) CH2CON (CH2COOH) CH2CO-； - -CO-N (CH2CH2COOH) CH2CH2CO-； - -CO-N (CH2CH2COOH) CH2CH2CON (CH2CH2COOH) CH2CH2CO-； - -CO-NHCH (COOH) (CH2) 4NHCO-； - -CO-N (CH2CH2COOH) CH2CO-； or - -CO-N (CH2COOH) CH2CH2CO-. that a) when W is an amino acid residue or a chain of amino acid residues, through a bond from the underlined carbon it forms an amide bond with an amino group of W, or b) when W is a covalent bond, th
