Hydrophobic polysaccharides with silyl ether linkages having enhanced degradation and medical articles made therefrom
View Patent ↗Hydrophobic α(1→4)glucopyranose polymers with enhanced degradation properties are described. Between the α(1→4)glucopyranose polymeric portion and the hydrophobic portion exists a linker portion having a silyl ether chemistry that facilitates degradation of the polymer. Biodegradable matrices can be formed from these polymers, and the matrices can be used for the preparation of implantable and injectable medical devices wherein the matrix is capable of degrading in vivo at an increased rate. Matrices including and capable of releasing a bioactive agent in vivo are also described.
1. An implantable or injectable medical article, the article comprising a bioactive agent releasable from the article and a biodegradable polymeric matrix or composition comprising a hydrophobic α(1→4)glucopyranose polymer, the polymer comprising:
(i) a poly-α(1→4)glucopyranose portion comprising glucopyranose monomeric units; and
(ii) a pendent group from the poly-α(1→4)glucopyranose portion comprising one or more hydrocarbon group(s) linked to a monomeric unit of the poly-α(1→4)glucopyranose portion via a linker segment comprising a silyl ether group.
2. The medical article of claim 1 wherein the pendent group is according to formula I:
wherein one or more of R 1 , R 2 , and/or R 3 comprise a C 1 -C 18 hydrocarbon group, with the proviso that the total number of carbon atoms among R 1 , R 2 , and R 3 is at three or more.
3. The medical article of claim 2 , wherein the total number of carbon atoms among R 1 , R 2 , and R 3 is in the range of 6-12.
4. The medical article of claim 2 , wherein two or more of R 1 , R 2 , and/or R 3 are selected from methyl and ethyl.
5. The medical article of claim 2 , wherein one of R 1 , R 2 , or R 3 is a C 4 -C 10 hydrocarbon group.
6. The medical article of claim 1 wherein the hydrophobic α(1→4)glucopyranose polymer has a degree of substitution in the range of 1.0 to 2.4 with the pendent groups.
7. The medical article of claim 1 wherein the hydrocarbon groups collectively represent a hydrophobic portion of the polymer, and the polymer has a weight ratio of the poly-α(1→4)glucopyranose portion to the hydrophobic portion in the range of 11:1 to 1:10.
8. The medical article of claim 1 wherein the polymer further comprises a second pendent group comprising a hydrocarbon group linked to the monomeric units of the poly-α(1→4)glucopyranose portion via a linker segment comprising a group that is not a silyl ether group.
9. The medical article of claim 8 wherein group that is not a silyl ether group is selected from the group consisting of ester, thioester, and carbonate.
10. The medical article of claim 8 wherein the second pendent group is pendent from the poly-α(1→4)glucopyranose portion at a degree of substitution less than the pendent group comprising the silyl ether group.
11. The medical article of claim 8 wherein the hydrophobic α(1→4)glucopyranose polymer has a degree of substitution in the range of 0.1 to 0.5 with the second pendent groups.
12. The implantable or injectable medical article of claim 1 , wherein the polymeric matrix or composition comprises at least 50% of the hydrophobic α(1→4)glucopyranose polymer.
13. The implantable or injectable medical article of claim 1 , wherein the polymeric matrix is in the form of a coating on an implantable medical device.
14. The implantable or injectable medical article of claim 1 , wherein the polymeric matrix is in the form of a topcoat on an implantable medical device.
15. The implantable or injectable medical article of claim 1 which is in the form of an in situ formed droplet.
16. The implantable or injectable medical article of claim 1 , wherein the polymeric matrix comprises the bioactive agent.
17. A method for treating a medical condition in a subject comprising a step of implanting or injecting a medical article in a subject, the article comprising a biodegradable polymeric matrix or composition comprising a hydrophobic α(1→4)glucopyranose polymer, the polymer comprising:
(i) a poly-α(1→4)glucopyranose portion comprising glucopyranose monomeric units; and
(ii) a pendent group from the poly-α(1→4)glucopyranose portion comprising one or more hydrocarbon group(s) linked to a monomeric unit of the poly-α(1→4)glucopyranose portion via a linker segment comprising a silyl ether group,
wherein the article (a) has a prosthetic, hemostatic, or anastomotic property useful for treating a medical condition at the site of implantation, (b) the article includes a bioactive agent which is released from the article and treats the medical condition, or (c) (a) and (b).
18. The medical article of claim 2 , wherein one of R 1 , R 2 , or R 3 is a C 3 -C 8 hydrocarbon group or a C 4 -C 10 hydrocarbon group.
19. The medical article of claim 2 , wherein one of R 1 , R 2 , or R 3 is an isopropyl or tert-butyl group.
20. The medical article of claim 2 , wherein one of R 1 , R 2 , or R 3 is a decyl group.
21. An implantable or injectable medical article, the article comprising a bioactive agent releasable from the article and a biodegradable polymeric matrix or composition comprising a hydrophobic α(1→4)glucopyranose polymer, the polymer comprising:
(i) a poly-α(1→4)glucopyranose portion comprising glucopyranose monomeric units; and
(ii) a pendent group from the poly-α(1→4)glucopyranose portion comprising one or more hydrocarbon group(s) linked to a monomeric unit of the poly-α(1→4)glucopyranose portion via a hydrolytically cleavable linker segment comprising a silyl ether group.
22. The method of claim 17 , where, following the step of implanting or injecting, the hydrophobic α(1→4)glucopyranose polymer has enhanced degradation via hydrolytic cleavage of the segment comprising a silyl ether group relative to a hydrophobic α(1→4)glucopyranose polymer that does not include the linker segment comprising a silyl ether group.
23. The method of claim 17 wherein the article that has a prosthetic, hemostatic, or anastomotic property is a vascular prosthesis, a wound dressing, a hemostatic barrier, a patch, or an anastomosis device.