Amphiphilic polymers for medical applications
View Patent ↗The present invention is directed to medical devices or pharmaceutical compositions, each containing a synthetic, bioabsorbable, biocompatible polymer that is the reaction product of a polybasic acid or derivative thereof, a monoglyceride, and a polyether.
1. A medical device, comprising an effective amount of a bioactive agent and: a synthetic, bioabsorbable, biocompatible polymer comprising the condensation reaction product of a) a polybasic acid or derivative thereof, b) a monoglyceride selected from the group consisting of monostearoyl glycerol, monopalmitoyl glycerol, monomyrisitoyl glycerol, monocaproyl glycerol, monodecanoyl glycerol, monolauroyl glycerol, monolinoleoyl glycerol and monooleoyl glycerol, and c) an aliphatic polyhydric alcohol.
2. The medical device of claim 1 wherein said polybasic acid or derivative thereof is selected from the group consisting of succinic acid, guccinic anhydride, malic acid, tartaric acid, citric acid, diglycolic acid, diglycolic anhydride, glutaric acid, glutaric anhydride, adipic acid, pimelic acid, suberic acid, sebacic acid, fumaric acid, maleic acid, maleic anhydride, and mixed anhydrides.
3. The medical device of claim 2 wherein said polybasic acid derivative is succinic anhydride.
4. The medical device of claim 2 wherein said polybasic acid is succinic acid.
5. The medical device of claim 1 wherein said aliphatic polyhydric alcohol is poly(ethylene glycol).
6. The medical device of claim 1 wherein said polymer is branched.
7. The medical device of claim 1 wherein said polymer comprises a copolymer.
8. The medical device of claim 7 wherein said copolymer comprises the reaction product of said monoglyceride, said aliphatic polyhydric alcohol, and at least two of said polybasic acids or derivatives thereof selected from the group consisting of succinic acid, succinic anhydride, malic acid, tartaric acid, citric acid, diglycolic acid and diglycolic anhydride.
9. The medical device of claim 7 wherein said copolymer comprises the reaction product of said polybasic acid or derivative thereof, said aliphatic polyhydric alcohol, and at least two monoglycerides selected from the group consisting of monostearoyl glycerol, monopalmitoyl glycerol, monomyrisitoyl glycerol, monocaproyl glycerol, monodecanoyl glycerol, monolauroyl glycerol, monolinoleoyl glycerol and monodecanoyl glycerol.
10. The medical device of claim 1 further comprising end capping moieties selected from the group consisting of alkyls, alkenyls, alkynyls, acrylates, methacrylates, nines, isocyanates and isothiocyanates.
11. The medical device of claim 1 further comprising an aliphatic polyester prepared from monomers selected from the group consisting of glycolide, L-lactide, D-lactide, meso-lactide, rac-lactide, ε-caprolactone, trimethylene carbonate, p-dioxanone, 1,4-dioxanone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and substituted derivatives thereof.
12. The medical device of claim 1 comprising a coating of said polymer.
13. The medical device of claim 12 further comprising an aliphatic polyester prepared from the group of monomers selected from the group consisting of glycolide, L-lactide, D-lactide, meso-lactide, rac-lactide, ε-caprolactone, trimethylene carbonate, p-dioxanone, 1,4-dioxanone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and substituted derivatives thereof.
14. The medical device of claim 1 comprising a bone replacement material comprising said polymer and an inorganic filler.
15. The medical device of claim 14 wherein said inorganic filler is selected from the group consisting of alpha-tricalcium phosphate, beta-tricalcium phosphate, calcium carbonate, barium carbonate, calcium sulfate, barium sulfate and hydroxyapatite.
16. The medical device of claim 14 wherein said inorganic filler comprises a polymorph of calcium phosphate.
17. The medical device of claim 14 further comprising an effective amount of a bioactive agent.
18. The medical device of claim 1 selected from the group consisting of sutures, stents, vascular grafts, stent-graft combinations, meshes, tissue engineering scaffolds, pins, clips, staples, films, sheets, foams, anchors, screws and plates.
19. A composition, comprising: an effective amount of a bioactive agent, and a polymer comprising the condensation reaction product of a) a polybasic acid or derivative thereof, b) a monoglyceride selected from the group consisting of monostearoyl glycerol, monopalmitoyl glycerol, monomyrisitoyl glycerol, monocaproyl glycerol, monodecanoyl, monolauroyl glycerol, monolinoleoyl glycerol and monooleoyl glycerol, and c) an aliphatic polyhydric alcohol.
20. The composition of claim 19 wherein said polybasic acid or derivative thereof is selected from the group consisting of succinic acid, succinic anhydride, malic acid, tartaric acid, citric acid, diglycolic acid, diglycolic anhydride, glutaric acid, glutaric anhydride, adipic acid, pimelic acid, suberic acid, sebacic acid and derivatives thereof.
21. The composition of claim 20 wherein said polybasic acid derivative is succinic anhydride.
22. The composition of claim 20 wherein said polybasic acid is succinic acid.
23. The composition of claim 19 wherein said polymer is branched.
24. The composition of claim 19 wherein said polymer comprises a copolymer.
25. The composition of claim 24 wherein said copolymer comprises the reaction product of said monoglyceride, said aliphatic polyhydric alcohol, and at least two of said polybasic acids or derivatives thereof selected from the group consisting of succinic acid, succinic anhydride, malic acid, tartaric acid, citric acid, diglycolic acid and diglycolic anhydride.
26. The composition of claim 24 wherein said copolymer comprises the reaction product of said polybasic acid or derivative thereof, said aliphatic polyhydric alcohol, and at least two monoglycerides selected from the group consisting of monostearoyl glycerol, monopalmitoyl glycerol, monomyrisitoyl glycerol, monocaproyl glycerol, monodecanoyl glycerol, monolauroyl glycerol, monolinoleoyl glycerol and monooleoyl glycerol.
27. The composition of claim 19 wherein said bioactive agent is selected from the group consisting of antiinfectives, analgesics, anorexics, antihelmintics, antiarthritics, antiasthmatics, anticonvulsants, antidepressants, antidiuretics, antidiarrheals, antihistamines, anti-inflammatory agents, antimigraine preparations, antinauseants, antineoplastics, antiparkinsonism drugs, antipruritics, antipsychotics, antipyretics, antispasmodics, anticholinergics, sympathomimetics, xanthine derivatives, calcium channel blockers, beta-blockers, antiarrhythmics, antihypertensives, diuretics, vasodilators, central nervous system stimulants, decongestants, hormones, steroids, hypnotics, immunosuppressives, muscle relaxants, parasympatholytics, psychostimulants, sedatives, tranquilizers, naturally derived or genetically engineered proteins, growth factors, polysaccharides, glycoproteins, or lipoproteins, oligonucleotides, antibodies, antigens, cholinergics, chemotherapeutics, hemostatics, clot dissolving agents, radioactive agents and cystostatics.
28. The composition of claim 19 further comprising an aliphatic polyester prepared from the group of monomers selected from the group consisting of glycolide, L-lactide, D-lactide, meso-lactide, rac-lactide, ε-caprolactone, trimethylene carbonate, p-dioxanone, 1,4-dioxanone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and substituted derivatives thereof.
29. The device of claim 1 wherein said polymer is a polymeric wax having a melting point between about 25° C. and about 70° C.
30. The device of claim 1 wherein said polymer is a liquid polymer having a melting point below about 25° C.
31. The composition of claim 19 wherein said polymer is a polymeric wax having a melting point between about 25° C. and about 70° C.
32. The device of claim 19 wherein said polymer is a liquid polymer having a melting point below about 25°.
33. A microdispersion comprising: a blend of a polymeric wax and a liquid polymer, wherein said polymeric wax and said liquid polymer comprise the condensation reaction product of a) a polybasic acid or derivative thereof, b) a monoglyceride selected from the group consisting of monostearoyl glycerol, monopalmitoyl glycerol, monomyrisitoyl glycerol, monocaproyl glycerol, monodecanoyl glycerol, monolauroyl glycerol, monolinoleoyl glycerol and monooleoyl glycerol, and c) an aliphatic polyhydric alcohol; wherein said polymeric wax has a melting point between about 25° C. and about 70° C., and wherein said liquid polymer has a melting point below about 25° C.
34. The microdispersion of claim 33 wherein said polybasic acid or derivative thereof is selected from the group consisting of succinic acid, succinic anhydride, malic acid, tartaric acid, citric acid, diglycolic acid, diglycolic anhydride, glutaric acid, glutaric anhydride, adipic acid, pimelic acid, suberic acid, sebacic acid, fumaric acid, maleic acid, maleic anhydride, and mixed anhydrides.
35. The microdispersion of claim 34 wherein said polybasic acid derivative is succinic anhydride.
36. The microdispersion of claim 34 wherein said polybasic acid is succinic acid.
37. The microdispersion of claim 33 wherein said aliphatic polyhydric alcohol is polyethylene glycol.
38. The microdispersion of claim 33 further comprising an effective amount of a bioactive agent.