Gelling hydrophobic injectable polymer compositions
Biodegradable carriers synthesized from ricinoleic acid oligoesters and aliphatic molecules having at least one carboxylic acid and at least one hydroxy or carboxylic acid group that are liquids or pastes at temperatures below 37° C. and methods of making and using thereof are described herein. The polymers described herein significantly increase their viscosity upon immersion in aqueous medium. These polymers can be used as hydrophobic biomedical sealants, temporary barriers to prevent adhesions, such as organ to organ adhesion, cell supports, carriers for drug delivery, and coatings on implantable medical devices, such as stents. The polymers made from ricinoleic acid oligoesters are less viscous and easier to inject compared to polymers of similar composition and molecular weight prepared from ricinoleic acid monomers, possess a higher molecular weight, retain an incorporated drug for longer periods, and degrade into soft degradation products at a slower rate compared with polymers synthesized from ricinoleic acid monomers. Pharmaceutically active agents can be incorporated into the liquid or pastes without the use of organic solvents.
1. A hydrophobic polymer composition comprising a polyester or a poly(ester-anhydride) composed of ricinoleic acid ester oligomer units and units of aliphatic molecules having at least one carboxylic acid and at least one hydroxyl group or one additional carboxylic acid group, the composition being a liquid or a paste at a temperature below 37° C. and forming a gel in aqueous solution.
2. The composition of claim 1 , wherein said poly(ester-anhydride) comprises alkanedioic acid monomer units having at least 4 carbon atoms.
3. The composition of claim 2 , wherein said alkanedioic acid monomer units are selected from the group consisting of linear dicarboxylic acid of the structure HOOC(CH 2 ) x COOH where x is an integer between 2 and 16, fumaric acid and maleic acid.
4. The composition of claim 3 , wherein said alkanedioic acid is sebacic acid.
5. The composition of claim 4 , wherein said poly(ester-anhydride) is composed of ricinoleic acid ester oligomer units and monomer units of sebacic acid.
6. The composition of claim 1 , wherein said polyester or said poly(ester-anhydride) comprises one or more hydroxyalkanoic acid monomer units having from 2 to 6 carbon atoms.
7. The composition of claim 6 , wherein the hydroxyalkanoic acid monomer units are selected from the group consisting of lactic acid, glycolic acid, 4-hydroxybutanoic acid, and 5-hydroxypentanoic acid.
8. The composition of claim 1 , wherein said ricinoleic acid ester oligomer units have at least an average of 1.5 ricinoleic acid units linked by an ester bond.
9. The composition of claim 1 , further comprising one or more excipients.
10. The composition of claim 1 , wherein said polyester or poly(ester-anhydride) has a weight-average molecular weight of 10,000 Da or higher.
11. The composition of claim 1 , where said polyester or poly(ester-anhydride) has a degree of polymerization of 40 or higher.
12. The composition of claim 1 , wherein said polyester or poly(ester-anhydride) biodegrades in about 12 weeks.
13. The composition of claim 1 , further comprising at least one active agent.
14. The composition of claim 13 , wherein said active agent is selected from the group consisting of therapeutic, diagnostic, and prophylactic agents.
15. The composition of claim 14 , wherein said active agent is selected from the group consisting of small drug molecules, peptides, proteins, oligo and polynucleotides, herbicides, and pesticides.
16. The composition of claim 14 , wherein said active agent is selected from the group consisting of analgesics, local anesthetics, anti-infectives, antinflammatory agents, antibiotics, growth hormones, anticancer agents, and combinations thereof.
17. The composition of claim 13 , wherein said at least one active agent comprises an anticancer agent, the composition being identified for use in treating solid tumors.
18. The composition of claim 13 , wherein said at least one active agent comprises an agent selected from the group consisting of an ant-infective agent, an antibiotic, and an antiviral agent, the composition being identified for use in treating a bone infection and/or a soft tissue infection.
19. The composition of claim 1 , being identified for use as a surgical sealant.
20. The composition of claim 1 , being identified for use as a barrier for reduction of organ to organ adhesion.
21. The composition of claim 1 , being identified for use as a coating.
22. The composition of claim 21 , wherein said composition is applied as a coating of a medical device.
23. The composition of claim 1 , being identified for use by injection or implantation thereof.