Bioerodable poly(etheresteramides) and medical article uses
View Patent ↗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.