Hydroxyalkyl starch derivatives
AssigneeFresenius Kabi Deutschland GmbH
InventorsNorbert Zander, Harald Conradt, Wolfram Eichner
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Abstract
The present invention relates to a method of producing a hydroxyalkyl starch derivative comprising reacting hydroxyalkyl starch of formula (I) at its reducing end which is not oxidized prior to said reaction, with a compound of formula (II) R′NH—R″ (II) wherein R1-R2 and R3 are independently hydrogen or a linear or branched hydroxyalkyl group, and wherein either R′ or R″ or R′ and R″ comprise at least one functional group X capable of being reacted with at least one other compound prior to or after the reaction of (I) and (II), as well as to the hydroxyalkyl starch derivative as such, obtainable by said method, and to a pharmaceutical composition comprising said hydroxyalkyl starch derivative.
Claims35
A method of producing a hydroxyethyl starch (HES) derivative, comprising contacting HES of formula (I)
- with O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxyl amine, having the structure
- wherein R1, R2 and R3 are independently hydrogen or a 2-hydroxyethyl group, and wherein said contacting is under conditions that result in a reaction product in which the O-[2-(2-aminooxyethoxy)-ethyl]-hydroxyl amine is conjugated via one —O—NH2 group to the HES of formula (I) at its reducing end which is not oxidized prior to said contacting.
A method for producing a HES derivative, comprising
- (i) first contacting O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxyl amine, having the structure
- with a further compound selected from the group consisting of a polypeptide, a crosslinking compound, and a preliminary reaction product of a crosslinking compound and a polypeptide, wherein said contacting is under conditions that result in a first reaction product in which the O-[2-(2-aminooxyethoxy)-ethyl]-hydroxyl amine is conjugated via one —O—NH2 group to the further compound, and
- (ii) then contacting the first reaction product with HES of formula (I)
- wherein R1, R2 and R3 are independently hydrogen or a 2-hydroxyethyl group, and wherein said contacting is under conditions that result in a further reaction product in which the O-[2-(2-aminooxyethoxy)-ethyl]-hydroxyl amine is conjugated via its remaining —O—NH2 group to the HES of formula (I) at its reducing end which is not oxidized prior to said contacting.
A method of producing a HES derivative, comprising contacting HES of formula (I)
- in an aqueous medium with O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxyl amine, having the structure
- or with a polypeptide-modified derivative thereof, wherein R1, R2 and R3 are independently hydrogen or a 2-hydroxyethyl group, and wherein said contacting is carried out under conditions that result in a reaction product in which the O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxyl amine is conjugated via one —O—NH2 group to the HES of formula (I) at its reducing end which is not oxidized prior to said contacting.
A method of producing a HES derivative, comprising contacting HES of formula (I)
- with O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxyl amine, having the structure
- wherein R1, R2 and R3 are independently hydrogen or a 2-hydroxyethyl group, wherein said contacting is in an aqueous medium at a pH from 4.5 to 6.5 and a temperature of 10° C. to 30° C. for two hours to 48 hours, and wherein said contacting results in a reaction product in which the O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxyl amine is conjugated via one —O—NH2 group to the HES of formula (I) at its reducing end which is not oxidized prior to said contacting.
Dependencies are inferred from the claim text.