Dihydroxybenzoate polymers and uses thereof
View Patent ↗The present invention is directed to polyphenolic polymers formed from dihydroxybenzoic acid (DHB) derivatives or from resorcinol derivatives, monomers which form such polymers, blends of the polymers with drugs and/or additional polymers, as well as medical devices formed from, coated with, impregnated by or coverings made with any of the foregoing polymers (with or without drugs) or blends (with or without drugs).
1. A biocompatible, biodegradable polymer comprising one or more monomer units represented by the formula
wherein A is C(═NH) or C(S); W is O, NH or S; R is hydrogen, an ester or amide protecting group, a leaving group, a linear or branched, substituted or unsubstituted, alkyl, alkenyl, alkynyl, aryl, alkylaryl, alkoxyether, heteroaryl, heteroalkyl or cycloalkyl group having from 1 to 30 carbon atoms, (R 2 ) r O((CR 3 R 4 ) a O) s (R 2 ) r , a sugar, a pharmaceutically-active compound, or a biologically active compound, wherein each a is independently 1-4, r is independently 1-4, and each s is independently 1-5000; where each a is independently 1 to 4, each r is independently 1 to 4 and s is 1 to 5000; each R 2 is independently linear or branched lower alkyl; and each R 3 and R 4 is independently hydrogen, or linear or branched lower alkyl.
2. The polymer of claim 1 , wherein W is O; and R is hydrogen, a linear or branched, substituted or unsubstituted, alkyl, alkenyl, alkynyl, aryl, alkylaryl or alkoxyether group having from 1 to 30 carbon atoms, or (R 2 ) r O((CR 3 R 4 ) a O) s (R 2 ).
3. The polymer of claim 2 , wherein R is hydrogen, methyl, ethyl, phenyl or benzyl.
4. The polymer of claim 2 , wherein R is alkyl in about 50% to about 99% of the monomer units of the polymer, and R in the remaining monomer units is benzyl.
5. The polymer of claim 2 , wherein R is alkyl in about 50% to about 99% of the monomer units of the polymer, and R in the remaining monomer units is hydrogen.
6. The polymer of claim 4 wherein R is methyl in about 80% to about 95% of the monomer units, and R is benzyl in about 5% to about 80% of the monomer units.
7. The polymer of claim 5 wherein R is methyl in about 80% to about 95% of the monomer units, and R is hydrogen in about 5% to about 80% of the monomer units.
8. A biocompatible, biodegradable polymer comprising one or more monomer units represented by the formula
wherein A is C(═NH); W is O, NH or S; R is linear or branched, substituted or unsubstituted alkyl, aryl or alkylaryl having from 1 to 20 carbon atoms, a heteroatom-containing alkyl or aryl group, alkylcycloalkyl, alkoxy, alkyloxyamine, nitro, alkylether, —C(O)—R 2 , —(R 9 ) b C(O)—YR 10 , X, a protected hydroxyl group, a protected amino group and a protected carboxylic acid group, where b is zero or one; R 2 is linear or branched lower alkyl; R 3 and R 4 is independently hydrogen, or linear or branched lower alkyl; R 9 is lower alkylene or alkenylene; R 10 is hydrogen, alkyl, aryl or alkylaryl having from 1 to 20 carbon atoms, or —(R 2 ) b C(O)OR 2 , or (R 2 ) r O((CR 3 R 4 ) a O) s (R 2 ) r where r is 1-4, a is 1-4 and s is 1-5000; X is F or Cl; and Y is O or NH.
9. The polymer of claim 8 , wherein W is O.
10. The polymer of claim 9 , wherein R is —C(O)—R 2 .
11. The polymer of claim 10 , wherein R 2 is methyl or ethyl.
12. The polymer of claim 8 , wherein R is —C(O)—R 2 , and R 2 is methyl or ethyl.
13. A biocompatible, biodegradable polymer comprising one or more monomer units represented by the formula
wherein A is C(═NH) or C(S); W is O, NH or S; R is linear or branched, substituted or unsubstituted alkyl, aryl or alkylaryi having from 1 to 20 carbon atoms, a heteroatom-containing alkyl or aryl group, alkylcycloalkyl, alkoxy, alkyloxyamine, nitro, alkylether, —C(O)—R 2 , —(R 9 ) b C(O)—YR 10 , X, a protected hydroxyl group, a protected amino group and a protected carboxylic acid group, where b is zero or one; R 2 is linear or branched lower alkyl; R 9 is lower alkylene or alkenylene; R 10 is hydrogen, alkyl, aryl or alkylaryl having from 1 to 20 carbon atoms, or —(R 2 ) b C(O)OR 2 , or (R 2 ) r O((CR 3 R 4 ) a O) s (R 2 ) r where r is 1-4, a is 1-4 and s is 1-5000; X is F or Cl; and Y is O or NH.
14. The polymer of claim 13 , wherein R is —C(O)—R 2 .
15. The polymer of claim 14 , wherein R 2 is methyl.
16. The polymer of claim 14 , wherein R 2 is ethyl.