Biodegradable polyesteramide copolymers for drug delivery
The present invention relates to a poly (ester amide) (PEA) having a chemical formula described by structural formula (IV), wherein m+p varies from 0.9-0.1 and q varies from 0.1 to 0.9 m+p+q=1 whereby m or p could be 0 n is about 5 to about 300; (pref. 50-200) R 1 is independently selected from the group consisting of (C 2 -C 20 ) alkylene, (C 2 -C 20 ) alkenylene, —(R 9 —CO—O—R 10 —O—CO—R 9 )—, —CHR 11 —O—CO—R 12 —COOCR 11 — and combinations thereof; R 3 and R 4 in a single backbone unit m or p, respectively, are independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 10 )aryl, (C 1 -C 6 )alkyl, —(CH 2 )SH, —(CH 2 ) 2 S(CH 3 ), —CH 2 OH, —CH(OH)CH 3 , —(CH 2 ) 4 NH 3 +, —(CH 2 ) 3 NHC(═NH 2 +)NH 2 , —CH 2 COOH, —(CH 2 )COOH, —CH 2 —CO—NH 2 , —CH 2 CH 2 —CO—NH 2 , —CH 2 CH 2 COOH, CH 3 —CH 2 —CH(CH 3 )—, (CH 3 ) 2 —CH—CH 2 —, H 2 N—(CH 2 ) 4 —, Ph-CH 2 —, CH═C—CH 2 —, HO-p-Ph-CH 2 —, (CH 3 ) 2 —CH—, Ph-NH—, NH—(CH 2 ) 3 —C—, NH—CH═N—CH═C—CH 2 —. R 5 is selected from the group consisting of (C 2 -C 20 )alkylene, (C 2 -C 20 )alkenylene, alkyloxy or oligoethyleneglycol R 6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III); R 7 is selected from the group consisting of (C 6 -C 10 )aryl (C 1 -C 6 )alkyl R 8 is —(CH2)4-; R 9 or R 10 are independently selected from C 2 -C 12 alkylene or C 2 -C 12 alkenylene. R 11 or R 12 are independently selected from H, methyl, C 2 -C 12 alkylene or C 2 -C 12 alkenylene whereby a is at least 0.05 and b is at least 0.05 and a+b=1.
1. An article or device comprising a bioactive agent and a biodegradable polyesteramide copolymer (PEA) according to the following formula:
wherein
m+p is from 0.9-0.1 and q is from 0.1 to 0.9;
m+p+q=1 whereby one of m or p could be 0;
n is about 5 to about 300;
a is at least 0.05, b is at least 0.05, a+b=1, qa=q*a, and qb=q*b; wherein units of m (if present), units of p (if present), units of a, and units of b are all randomly distributed throughout the copolymer;
R 1 is independently selected from the group consisting of (C 2 -C 20 ) alkylene, (C 2 -C 20 ) alkenylene, —(R 9 —CO—O—R 10 —O—CO—R 9 )—, —CHR 11 —O—CO—R 12 —COOCR 11 — and combinations thereof;
R 3 and R 4 in a single backbone unit m or p, respectively, are independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 10 )aryl, (C 1 -C 6 )alkyl, —(CH 2 )SH, —(CH 2 ) 2 S(CH 3 ), —CH 2 OH, —CH(OH)CH 3 , —(CH 2 ) 4 NH 3 +, —(CH 2 ) 3 NHC(═NH 2 +)NH 2 , —CH 2 COOH, —(CH 2 )COOH, —CH 2 —CO—NH 2 , —CH 2 CH 2 —CO—NH 2 , —CH 2 CH 2 COOH, CH 3 —CH 2 —CH(CH 3 )—, (CH 3 ) 2 —CH—CH 2 —, H 2 N—(CH 2 ) 4 —, Ph-CH 2 —, CH═C—CH 2 —, HO-p-Ph-CH 2 —, (CH 3 ) 2 —CH—, Ph-NH—, NH—(CH 2 ) 3 —C—, NH—CH═N—CH═C—CH 2 —;
R 5 is selected from the group consisting of (C 2 -C 20 )alkylene, (C 2 -C 20 )alkenylene, alkyloxy or oligoethyleneglycol;
R 6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III);
R 7 is selected from the group consisting of (C 6 -C 10 ) aryl (C 1 -C 6 )alkyl;
R 8 is —(CH 2 ) 4 —;
R 9 or R 10 are independently selected from C 2 -C 12 alkylene or C 2 -C 12 alkenylene;
R 11 or R 12 are independently selected from H, methyl, C 2 -C 12 alkylene or C 2 -C 12 alkenylene.
2. The article or device according to claim 1 , wherein a is at least 0.15.
3. The article or device according to claim 1 , wherein a is at least 0.5.
4. The article or device according to claim 1 , wherein a is at least 0.8.
5. The article or device according to claim 1 , wherein
p=0, m=0.75, and a=0.5;
wherein the m, qa, and qb units are randomly distributed;
R 1 is —(CH 2 ) 8 —, R 3 is (CH 3 ) 2 —CH—CH 2 —, R 5 is hexyl, and R 7 is benzyl.
6. The article or device according to claim 1 , wherein
q=0.25, p=0.45, m=0.3, and a=0.5;
wherein the m, p, qa, and qb units are randomly distributed;
R 1 is —(CH 2 ) 8 —; R 3 and R 4 respectively, are (CH 3 ) 2 —CH—CH 2 —; R 5 is (C 2 -C 20 )alkylene; and R 7 is benzyl.
7. The article or device according to claim 1 , wherein
q=0.25, p=0.45, m=0.3, and a=0.75;
wherein the m, p, qa, and qb units are randomly distributed;
R 1 is —(CH 2 ) 8 —; R 4 is (CH 3 ) 2 —CH—CH 2 —; and R 7 is benzyl.
8. The article or device according to claim 1 , wherein
q=0.1, p=0.30, m=0.6, and a=0.5;
wherein the m, p, qa, and qb units are randomly distributed;
R 1 —(CH 2 ) 4 —; R 3 and R 4 respectively, are (CH 3 ) 2 —CH—CH 2 —; R 7 benzyl;
and R 5 is (C 2 -C 20 )alkylene.
9. The article or device according to claim 1 , wherein R 1 is independently selected from (C 2 -C 20 )alkylene.
10. The article or device according to claim 1 , wherein R 5 is (C 2 -C 20 )alkylene.
11. The article or device according to claim 10 , wherein R 5 is (C 2 -C 20 )alkylene.
12. The article or device according to claim 1 , wherein the biodegradable polyesteramide copolymer has an Mn of about 15,000 to about 100,000 Daltons, as measured via GPC in THF with polystyrene as standard.
13. The article or device according to claim 1 , wherein the biodegradable polyesteramide copolymer has an Mn of about 30,000 to about 80,000 Daltons, as measured via GPC in THF with polystyrene as standard.
14. The article or device according to claim 11 , wherein the biodegradable polyesteramide copolymer has an Mn of about 15,000 to about 100,000 Daltons, as measured via GPC in THF with polystyrene as standard.
15. The article or device according to claim 11 , wherein the biodegradable polyesteramide copolymer has an Mn of about 30,000 to about 80,000 Daltons, as measured via GPC in THF with polystyrene as standard.
16. The article or device according to claim 7 , wherein R 5 is (C 2 -C 20 )alkylene.
17. The article or device according to claim 16 , wherein the biodegradable polyesteramide copolymer has an Mn of about 15,000 to about 100,000 Daltons, as measured via GPC in THF with polystyrene as standard.
18. The article or device according to claim 16 , wherein the biodegradable polyesteramide copolymer has an Mn of about 30,000 to about 80,000 Daltons, as measured via GPC in THF with polystyrene as standard.
19. The article or device according to claim 1 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
20. The article or device according to claim 2 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
21. The article or device according to claim 3 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
22. The article or device according to claim 11 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
23. The article or device according to claim 14 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
24. The article or device according to claim 15 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
25. The article or device according to claim 16 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
26. The article or device according to claim 17 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
27. The article or device according to claim 18 , wherein the article or the device is a film, a coating, a micelle, a catheter, a stent, a rod, a microparticle, a nanoparticle, or an implant.
28. The article or device according to claim 1 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
29. The article or device according to claim 2 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
30. The article or device according to claim 3 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
31. The article or device according to claim 11 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
32. The article or device according to claim 14 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
33. The article or device according to claim 15 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
34. The article or device according to claim 16 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
35. The article or device according to claim 17 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.
36. The article or device according to claim 18 , wherein the article or device is a drug delivery device for ophthalmology applications and the bioactive agent is a small molecule ophthalmic drug, or prodrug or metabolite thereof.