Method for preparing branched functionalized polymers using branched polyol cores

• US 8,901,246 B2
• Filed: 10/10/2013
• Issued: 12/02/2014
• Est. Priority Date: 07/18/2005
• Status: Active Grant

• Current Assignee: Nektar Therapeutics
• Original Assignee: Nektar Therapeutics
• Inventors: McManus, Samuel P., Kozlowski, Antoni
• Primary Examiner(s): LISTVOYB, GREGORY
• Application Number:
  US14/051,246
• Publication Number:
  US 20140039205A1
• Time in Patent Office: 418 Days
• Field of Search: 424/78.08, 424/78.37, 525/56, 525/123, 525/410, 549/370
• US Class Current: 525/56
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/34 from hydroxy compounds or their metallic derivatives C08G65/26 takes precedence
• CPC Class Codes: C08G 65/48 Polymers modified by chemical after-treatment
• CPC Class Codes: C08G 71/04 Polyurethanes
• CPC Class Codes: C08L 2203/02 for biomedical use
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

A method of preparing a multiarm polymer includes reacting a branched polyol with one or more functionalizing reagents to effect substitution of an ionizable functional group or a protected ionizable functional group, Y, to form a mixture comprising (i) unsubstituted branched polyol containing no Y groups; (ii) a monosubstituted polyol comprising one Y group, and (iii) a multisubstituted polyol (e.g., a disubstituted polyol comprising two Y groups); followed by purifying the mixture to separate the monosubstituted polyol from other species Thereafter, a water-soluble and non-peptidic polymer segment is attached to the monosubstituted branched polyol at the site of at least one of the hydroxyl groups. The invention also provides purified monosubstituted branched polyols and multiarm polymers prepared by the method and polyol precursors for use in the method.

Claims

1. A chromatographically purified branched polyol having the structure Y—

R(—

OH)_p, wherein R is a branched hydrocarbon, Y is an ionizable functional group selected from the group consisting of amine and carboxylic acid, and p is at least 2, and further wherein (i) the branched polyol has a single ionizable functional group, optionally in protected form, (ii) the polyol has a purity of at least about 83%, and (iii) the R group includes a poly(alkylene glycol) chain of 1 to about 25 monomer subunits attached to each terminal hydroxyl group.

2. The branched polyol of claim 1, wherein the polyol has a purity of at least about 91%.

3. The branched polyol of claim 2, wherein the polyol has a purity of at least about 97%.

4. The branched polyol of claim 3, wherein the polyol has a purity of about 100%.

5. The branched polyol of claim 1, wherein p is 3 to about 25.

6. The branched polyol of claim 1, wherein p is 3 to about 10.