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|Abstract:||Branched polyanhydrides that have superior properties for use in the controlled delivery of substances, prepared by the polymerization of a dicarboxylic acid monomer and a branching agent. The branching agent is a polycarboxylic acid monomer such as 1,3,5-benzenetricarboxylic acid ("BTC"), or an oligomerized fatty acid trimer. Alternatively, the branching agent is a polycarboxylic acid polymer such as poly(acrylic acid) ("PAA"). These branched polymers have significantly higher molecular weights and lower specific viscosity than linear polymers prepared under similar conditions. A major advantage of branched polyanhydrides is that the degradation and release kinetics can be substantially altered without significantly changing the physical properties of the polymer relative to the corresponding linear polymer. By manipulating both the diacid and the branching agent, a wide variety of biodegradable controlled delivery devices for diverse applications can be prepared.|
|Inventor(s):||Domb; Abraham J. (Baltimore, MD), Maniar; Manoj (Baltimore, MD)|
|Assignee:||Nova Pharmaceutical Corporation (Baltimore, MD)|
|Filing Date:||Jun 04, 1990|
|Claims:||1. A polyanhydride for the controlled delivery of substances prepared by the polymerization of a dicarboxylic acid and a compound selected from the group consisting of a tricarboxylic acid and a polycarboxylic acid branching agent. |
2. The polyanhydride of claim 1, wherein the branching agent is a polycarboxylic acid monomer.
3. The polyanhydride of claim 1, wherein the branching agent is a polycarboxylic acid polymer.
4. The polyanhydride of claim 2, wherein the branching agent is selected from the group consisting of 1,3,5-benzenetricarboxylic acid, butane-1,1,4-tricarboxylic acid, tricarballylic acid (propane-1,2,3-tricarboxylic acid), butane-1,2,3,4-tetracarboxylic acid, and oligomerized fatty acid trimers.
5. The polyanhydride of claim 3, wherein the branching agent is selected from the group consisting of poly(acrylic acid), poly(.alpha.-methacrylic acid), poly(.beta.-methacrylic acid), and poly(maleic acid).
6. The polyanhydride of claim 1, wherein the dicarboxylic acid is selected from the group consisting of sebacic acid, adipic acid, isophthalic acid, p-carboxyphenoxyalkanoic acid, terephthalic acid, fumaric acid, dodecanedicarboxylic acid, azeleic acid, pimelic acid, suberic acid (octanedioic acid), itaconic acid, biphenyl-4,4'-dicarboxylic acid, and benzophenone-4,4'-dicarboxylic acid.
7. The polyanhydride of claim 1, wherein mixtures of dicarboxylic acids are polymerized.
8. The polyanhydride of claim 1, wherein mixtures of branching agents are polymerized.
9. The polyanhydride of claim 1, wherein the polymerization is stopped before the gel point.
10. The polyanhydride of claim 1, wherein the polymerization is stopped after the gel point.
11. The polyanhydride of claim 1 of molecular weight greater than 140,000 M.sub.w.
12. The polyanhydride of claim 1, wherein the ratio of dicarboxylic acid to branching agent is between 0.1 and 15%.
13. The polyanhydride of claim 1 that is a random copolymer.
14. The polyanhydride of claim 1 that is a graft copolymer.
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