Poly(ethylene glycol) aldehyde hydrates and related polymers and applications in modifying amines
AssigneeShearwater Polymers, Inc.
InventorsMichael D. Bentley, J. Milton Harris
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Abstract
The present invention provides a method of coupling PEG or related polymers to a substance by reductive amination. An activated PEG having an aldehyde hydrate moiety is prepared and is conveniently used as an intermediate for coupling PEG to a variety of biomolecules by reductive amination. The method of making PEG-conjugated biomolecules in accordance with the present invention avoids the condensation and oxidation reactions that are inherent in the coupling methods employed heretofore in the prior art using PEG aldehyde. As a result, high purity of PEG-conjugates can be achieved.
Claims23
A method for conjugating a water soluble polymer to a substance having an amine group, comprising:
- providing a polymer precursor by linking to said polymer a moiety having the formula of
- --(CH.sub.2).sub.n CH(XR).sub.2
- OR ##STR8## wherein n is a number of from 1 to 6, X is the atom of O or S, and R is an alkyl group;
- converting said polymer precursor to an activated polymer having an aldehyde hydrate moiety;
- and
- reacting said substance with the polymer having an aldehyde hydrate moiety and forming a linkage between the substance and the water soluble polymer.
A method of making a hydrogel from an amine-containing biomaterial and a water soluble polymer comprising:
- providing a polymer precursor by linking to said polymer at least two moieties each having the formula of
- --(CH.sub.2).sub.n CH(XR).sub.2
- OR ##STR10## wherein n is a number of from 1 to 6, X is the atom of O or S, and R is an alkyl group;
- converting said polymer precursor to an activated organic polymer having at least two active aldehyde hydrate moieties, wherein the linkage between the polymer and each aldehyde hydrate moiety is stable against hydrolysis;
- and
- reacting said biomaterial with the activated organic polymer having at least two active aldehyde hydrate moieties and forming a linkage between the substance and the water soluble polymer.
A method for preparing an aldehyde derivative of a water soluble polymer comprising:
- providing a polymer precursor by linking to said organic polymer a moiety having the formula of
- --(CH.sub.2).sub.n CH(XR).sub.2
- OR ##STR11## wherein n is a number of from 1 to 6, X is the atom of O or S, and R is an alkyl group;
- converting said polymer precursor to an activated organic polymer having an active aldehyde hydrate moiety, wherein the linkage between the polymer and the aldehyde hydrate moiety is stable against hydrolysis;
- extracting the activated polymer into an organic solvent;
- and
- removing said solvent by distillation in an inert atmosphere whereby the aldehyde derivative of the water soluble organic polymer is obtained.
An aldehyde derivative of a water soluble polymer selected from the group consisting of poly(alkylene oxides), poly(vinyl alcohol), poly(oxyethylated polyols), poly(olefinic alcohols), poly(acryloyl morpholine), poly(vinyl pyrrolidone), poly(oxazoline), poly(hydoxyethyl methacrylate, dextran and derivatives thereof, comprising a functional moiety linked to said water soluble polymer, said moiety having the formula of
- --(CH.sub.2).sub.n CH(XR).sub.2
- OR ##STR13## wherein n is a number of from 1 to 6, X is the atom of O or S, and R is an alkyl group.
Dependencies are inferred from the claim text.