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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:||Sep 18, 1992|
|Claims:||1. A polyanhydride for the controlled delivery of substances prepared by polymerization of a dicarboxylic acid and a compound selected from the group consisting of a tricarboxylic acid and a polycarboxylic acid branching agent further comprising a substance to be delivered. |
2. The polyanhydride of claim 1, 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.
3. The polyanhydride of claim 1, 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).
4. 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 (ocetanedioic acid), itaconic acid, biphenyl-4,.sup.1 -dicarboxylic acid, and benzophenone-4, 4.sup.1 -dicarboxylic acid.
5. The polyanhydride of claim 1, wherein the substance s a bioactive compound.
6. The polyanhydride of claim 5, wherein the bioactive compound is selected from the group consisting of morphine, tetracyline, ibuprofen, marcaine, methotrexate, dexamethazone and triamcinolone.
7. The polyanhydride of claim 1, wherein the substance is incorporated by swell fabrication.