Silane-functionalized hydrophobic α(1→4)glucopyranose polymers and polymeric matrices for implantation or injection
View Patent ↗Silane-functionalized hydrophobic α(1→4)glucopyranose polymers and polymeric matrices are described. Biodegradable matrices can be formed from hydrophobic α(1→4)glucopyranose polymers with reactive pendent silyl ether groups. Reaction of the silyl ether groups provides improved matrix formation through bonding to a device surface of a device, polymer-polymer crosslinking, or both. Biodegradable matrices can be used for the preparation of implantable and injectable medical devices, including those that release a bioactive agent.
1. An implantable or injectable biomedical article comprising a polymeric matrix formed from a composition comprising a hydrophobic derivative of a natural biodegradable polysaccharide comprising:
a poly-α(1→4)glucopyranose portion comprising a monomeric unit according formula IIa as follows:
wherein R 5 is —(CH 2 ) x CH 3 , and x is an integer in the range of 0-11; and
and wherein R 6 and/or R 7 is
wherein R 8 is S or O, R 9 is C, O, N, or a covalent bond, y is an integer in the range of 2-8, wherein R 1 , R 2 , and R 3 , are independently selected from R 4 or OR 4 , wherein R 4 is a C1-C6-containing hydrocarbon group, with the proviso that at least one of R 1 , R 2 , or R 3 is OR 4 , and if R 6 or R 7 is not as defined above, then R 6 or R 7 is H.
2. The article of claim 1 wherein R 1 , R 2 , and R 3 are independently selected from OR 4 , wherein R 4 is selected from the group consisting of —CH 3 and —CH 2 CH 3 .
3. The article of claim 1 wherein R 5 and
are present at a weight to molar ratio in the range of 50 mgram:1 mmol to 4830 mgram:1 mmol, respectively.
4. The article of claim 1 wherein the poly-α(1→4)glucopyranose portion and
are present at a weight to molar ratio in the range of 77 mgram:1 mmol to 4053 mgram:1mmol, respectively.
5. The article of claim 1 further comprising a monomeric unit according formula IIIa as follows:
wherein R 5 is —(CH 2 ) x CH 3 , and x is an integer in the range of 0-11.
6. An implantable or injectable biomedical article comprising a polymeric matrix formed from a composition comprising a hydrophobic derivative of a natural biodegradable polysaccharide comprising:
a poly-α(1→4) glucopyranose portion comprising a monomeric unit according formula IVa as follows:
wherein R 10 is
wherein R 11 is C, O, N, or a covalent bond, y is an integer in the range of 2-8, and wherein R 1 , R 2 , and R 3 are independently selected from R 4 or OR 4 , wherein R 4 is a C1-C6-containing hydrocarbon group, with the proviso that at least one of R 1 , R 2 , or R 3 is OR 4 .
7. The article of claim 1 wherein the polysaccharide has a molecular weight in the range of 5 kDa to 1000kDa.
8. A hydrophobic derivative of a natural biodegradable polysaccharide comprising:
a poly-α(1→4)glucopyranose portion;
first groups pendent from the poly-α(1→4)glucopyranose portion having the formula:
wherein R 8 is S or O, R 9 is C, O, N, or a covalent bond, y is an integer in the range of 2-8, wherein R 1 , R 2 , and R 3 , are independently selected from R 4 or OR 4 , wherein R 4 is a C1-C6-containing hydrocarbon group, with the proviso that at least one of R 1 , R 2 , or R 3 is OR 4 , and if R 6 or R 7 is not as defined above, then R 6 or R 7 is H; and
second groups pendent from the poly-α(→4)glucopyranose portion, the second groups having the formula
wherein R 5 is a C 2 -C 10 linear or branched hydrocarbon group, and wherein the ester group in the formula is formed by reaction of a hydroxyl group of the poly-α(1→4)glucopyranose portion.
9. The hydrophobic derivative of claim 8 , where R 5 is: (a)-(CH 2 ) m CH 3 , and m is an integer in the range of 1 to 5, or (b) selected from the group consisting of ethyl, propyl, isopropyl, n-butyl, isobutyl, and t-butyl, and hexyl.
10. The hydrophobic derivative of claim 8 , having a degree of substitution in the range of 0.9 -2.5.