Polyesters and methods of use thereof
View Patent ↗The invention provides polymers and methods for the treatment of pain and inflammation.
1. A polyester comprising one or more groups of formula (I):
—C(═O)-A-C(═O)—O-L-O— (I)
wherein A is a C 2 -C 8 methylene chain that is covalently linked to two or more residues of a non-steroidal anti-inflammatory; and L is a C 2 -C 10 branched or straight chain alkyl.
2. The polyester of claim 1 , wherein the C 2 -C 8 methylene chain that is covalently linked to two or more residues of the non-steroidal anti-inflammatory through an ester or amide linkage.
3. The polyester of claim 1 which comprises one or more groups of formula (Ia):
—C(═O)—[CH(B)] 2-8 —C(═O)—O-L-O— (Ia)
wherein each B is independently a residue of a non-steroidal anti-inflammatory.
4. A polyester according to claim 1 , which comprises one or more groups of formula (II):
wherein each D is independently a direct bond, or an ester or amide linkage; each E is independently a residue that will release a non-steroidal anti-inflammatory agent upon hydrolysis of the polymer; n is 2, 3, 4, 5, 6, 7, or 8; and L is a C 2 -C 10 branched or straight chain alkyl.
5. The polyester of claim 4 wherein D is —O—.
6. The polyester of claim 5 which comprises one or more groups of formula (IIa):
wherein n is 2, 3, 4, 5, 6, 7, or 8.
7. The polyester of claim 5 which comprises one or more groups of formula (IIb):
wherein n is 2, 3, 4, 5, 6, 7, or 8.
8. A polyester accordingly to claim 1 , which comprises two or more repeating groups of formula (II):
wherein each D is independently a direct bond, or an ester or amide linkage; each E is independently a residue that will release a non-steroidal anti-inflammatory agent upon hydrolysis of the polymer; n 2, 3, 4, 5, 6, 7, or 8; and L is a C 2 -C 10 branched or straight chain alkyl.
9. The polyester of claim 8 which comprises 2-200 repeating groups of formula (II).
10. The polyester of claim 8 which comprises at least 2, 3, 4, 5, 6, 7, 8, or 9 repeating groups of formula (II).
11. The polyester of claim 8 which comprises two or more repeating groups of formula (IIa):
wherein n is 2, 3, 4, 5, 6, 7, or 8.
12. The polyester of claim 8 which comprises two or more repeating groups of formula (IIb):
wherein n is 2, 3, 4, 5, 6, 7, or 8.
13. The polyester of claim 1 wherein each non-steroidal anti-inflammatory agent is selected from ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, suprofen, benoxaprofen, indoprofen, pirprofen, carprofen, loxoprofen, pranoprofen, alminoprofen, salicylic acid, diflunisal, salsalate, oxaprozin, indomethacin, sulindac, etodolac, ketorolac, diclofenac, piroxicam, meloxicam, tenoxican, lornoxicam, isoxicam, mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, lumiracoxib and licofelone.
14. The polyester of claim 1 , wherein L is a C 2 -C 10 straight chain alkyl.
15. The polyester of claim 14 , wherein L is a C 4 -C 8 straight chain alkyl.
16. The polyester of claim 15 , wherein L is a C 6 straight chain alkyl.
17. The polyester of claim 1 , wherein L is a C 2 -C 10 branched chain alkyl.
18. A pharmaceutical composition comprising a polyester as described in claim 1 and a pharmaceutically acceptable carrier.
19. A method to treat pain or inflammation in a mammal, comprising administering a polyester as described in claim 1 to the mammal.