Bioerodable poly(etheresteramides) and medical article uses
Bioerodable poly(etheresteramides) and matrices formed therefrom, such as medical device coatings, are described. The matrices show desirable erosion properties desirable for therapeutic use. The matrices can include a bioactive agent which can be used to treat medical conditions.
1. A bioerodable polymeric matrix comprising a bioerodable polymer comprising units of:
wherein R 1 , R 3 , R 5 , and R 7 are independently selected from: —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —(CH 2 ) 3 CH 3 , —CH 2 C 6 H 5 , —(CH 2 ) 2 SCH 3 , —CH 3 , —CH 2 SH, —CH 2 CO 2 H, —(CH 2 ) 2 CO 2 H, —H, —CH 2 —imidazole, —(CH 2 ) 4 NH 2 , —CH 2 CONH 2 , —(CH 3 ) 3 —N a (cyclic), —(CH 2 ) 2 CONH 2 , —(CH 2 ) 3 NHC(NH 2 ) 2 + , —CH 2 OH, —CH(CH 3 )OH, —CH 2 —indole, and —CH 2 —C 6 H 4 —OH;
R 2 and R 6 are independently selected from divalent alkane, alkene (hydrocarbylene), and alkoxy (oxyalkylene), wherein the alkoxy is selected from —CH 2 OCH 2 —and —CH 2 OCH 2 CH 2 —, wherein (R 2 ) n , is different than and has a higher hydrophilic-lipophilic ratio than (R 6 ) s ; n is 1 or greater; s is 1 or greater; and
R 4 and R 8 are independently selected from divalent, linear or branched, saturated or unsaturated, C1-C12 fragments
wherein at least 50% (w/v) of the bioerodable polymeric matrix is capable of either (a) eroding within 6 months following providing the matrix in a subject
wherein the internal environment of said subject causes eroding of the matrix, or (b) eroding within 120 days of incubation of the matrix in phosphate buffered-saline at 37° C.,
wherein the matrix optionally comprises a bioactive agent.
2. The bioerodable polymeric matrix of claim 1 wherein R 1 , R 3 , R 5 , and R 7 are the same.
3. The bioerodable polymeric matrix of claim 1 wherein one or more of R 1 , R 3 , R 5 , and R 7 is —CH 2 C 6 H 5 .
4. The bioerodable polymeric matrix of claim 1 wherein R 2 is —CH 2 OCH 2 —.
5. The bioerodable polymeric matrix of claim 1 wherein n is in the range of 2 to 150.
6. The bioerodable polymeric matrix of claim 1 wherein R 6 is a divalent, linear or branched, saturated or unsaturated, C1-C12 fragment.
7. The bioerodable polymeric matrix of claim 6 wherein R 6 is —(CH 2 )—; and s is 6.
8. The bioerodable polymeric matrix of claim 1 wherein the bioerodable polymer of is formed from a composition comprising at least the following monomers:
where R 1 and R 3 are independently selected from: —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , — CH(CH 3 )CH 2 CH 3 , —(CH 2 ) 3 CH 3 , —CH 2 C 6 H 5 , —(CH 2 ) 2 SCH 3 , —CH 3 , —CH 2 SH, —CH 2 CO 2 H, —(CH 2 ) 2 CO 2 H, —H, —CH 2 —imidazole, —(CH 2 ) 4 NH 2 , —CH 2 CONH 2 , —(CH 3 ) 3 —N a (cyclic), —(CH 2 ) 2 CONH 2 , —(CH 2 ) 3 NHC(NH 2 ) 2 + , —CH 2 OH, —CH(CH 3 )OH, —CH 2 —indole, and —CH 2 —C 6 H 4 —OH; R 2 is independently selected from divalent alkane, alkene (hydrocarbylene), and alkoxy (oxyalkylene), wherein the alkoxy is selected from —CH 2 OCH 2 —and —CH 2 OCH 2 CH 2 —; and n is 1 or greater; and R 9 and R 10 are independently selected from: —NH 2 and —NH 3 + X − , wherein X is a monovalent atomic or molecular cation;
where R 4 is divalent, linear or branched, saturated or unsaturated, C1-C12 fragment; and
where R 5 and R 7 are independently selected from: —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , — CH(CH 3 )CH 2 CH 3 , —(CH 2 ) 3 CH 3 , —CH 2 C 6 H 5 , —(CH 2 ) 2 SCH 3 , —CH 3 , —CH 2 SH, —CH 2 CO 2 H, —(CH 2 ) 2 CO 2 H, —H, —CH 2 —imidazole, —(CH 2 ) 4 NH 2 , —CH 2 CONH 2 , —(CH 3 ) 3 —N a (cyclic), —(CH 2 ) 2 CONH 2 , —(CH 2 ) 3 NHC(NH 2 ) 2 + , —CH 2 OH, —CH(CH 3 )OH, —CH 2 —indole, and —CH 2 —C 6 H 4 —OH; R 6 is selected from divalent alkane, alkene (hydrocarbylene), and alkoxy(oxyalkylene), wherein the alkoxy is selected from —CH 2 OCH 2 —and —CH 2 OCH 2 CH 2 —; s is 1 or greater; and R 9 and R 10 are independently selected from: —NH 2 and —NH 3 + X − , wherein X is a monovalent atomic or molecular cation; and
where, in the composition, (R 2 ), of monomer (a) has a higher hydrophilic-lipophilic ratio than (R 6 ) s , of monomer (c).
9. An implantable or injectable biomedical article, the article comprising the bioerodable polymeric matrix of claim 1 and a bioactive agent.
10. The implantable or injectable biomedical article of claim 9 , wherein the polymeric matrix is in the form of a coating.
11. The implantable or injectable biomedical article of claim 10 , wherein the coating is present on an intraluminal stent.
12. The implantable or injectable biomedical article of claim 10 , wherein 50% (w/v) of the bioerodable polymeric matrix is capable of eroding within 6 months in vivo following implantation in a subject.
13. The implantable or injectable biomedical article of claim 9 , wherein the bioerodable polymeric matrix is in the form of a hydrogel.
14. A method for delivering a bioactive agent to a subject comprising implanting the implantable or injectable biomedical article of claim 13 into a subject and allowing the bioactive agent to be released from the bioerodable polymeric matrix.
15. The bioerodable polymeric matrix of claim 5 wherein n is in the range of 2-6.
16. The bioerodable polymeric matrix of claim 1 wherein R 4 and R 8 are independently selected from the group consisting of: —CH 2 —, —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 —, —(CH 2 ) 5 —, —(CH 2 ) 6 —, —(CH 2 ) 7 —, —(CH 2 ) 8 —, —(CH 2 ) 9 —, —(CH 2 ) 10 —, —(CH 2 ) 11 —, and —(CH 2 ) 12 —.
17. The bioerodable polymeric matrix of claim 1 wherein R 2 is —CH 2 OCH 2 —, n is in the range of 2 to 25, and (R 6 ) s , is a divalent, linear or branched, saturated or unsaturated, C1-C8 fragment.
18. The bioerodable polymeric matrix of claim 17 wherein R 2 is —CH 2 OCH 2 —, n is in the range of 2 to 6, and (R 6 ) s , is a divalent, linear or branched, saturated or unsaturated, C1-C8 fragment.