Microporous articles comprising biodegradable medical polymers, method of preparation thereof and method of use thereof

• US 20070116737A1
• Filed: 04/02/2004
• Published: 05/24/2007
• Est. Priority Date: 04/03/2003
• Status: Active Grant

• Current Assignee: Corporation De L'Ecole Polytechnique De Montreal
• Original Assignee: Corporation De L'Ecole Polytechnique De Montreal
• Inventors: Sarazin, Pierre, Yuan, Zhenhua, Li, Jiangming, Favis, Basil
• Granted Patent: US 8,007,823 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention relates to a highly controlled method of preparation of a microporous biodegradable polymeric article. Firstly, at least one biodegradable polymer A, one polymer B, biodegradable or not, partially or totally immiscible with A, and a compatibilizer C for A and B are selected. Secondly, the selected polymers are melt-blended, thereby preparing a polymer blend; wherein said polymers A and B have an essentially continuous morphology. Thirdly, after cooling, polymer B and compatibilizer C are selectively extracted from the polymer blend by dissolution in a solvent that is a non-solvent of polymer A. The resulting polymeric article has an essentially continuous porosity with a void volume between 10 and 90% and a unimodal diameter distribution set to a predefined unimodal peak location. It can be used in tissue engineering, for controlled release applications or as an implantable medical device.

Claims

1. A microporous biodegradable polymeric article comprising an essentially continuous porosity with a void volume from 10 to 90%, wherein pore diameters show a unimodal distribution set to a predefined unimodal peak location corresponding to a chosen pore diameter, and wherein a majority of pores has a diameter within ±

50% of the chosen pore diameter.

2. The microporous biodegradable polymeric article according to claim 1, wherein the predefined unimodal peak location corresponds to a chosen pore diameter selected from 20 nm to 600 μ

m.

3. The microporous biodegradable polymeric article according to claim 2, wherein the predefined unimodal peak location corresponds to a chosen pore diameter selected from 1 to 72 μ

m.

4. The microporous biodegradable polymeric article according to claim 3, wherein the majority of pores has a diameter within ±

40% of the chosen pore diameter.

5. The microporous biodegradable polymeric article according to claim 1, wherein the predefined unimodal peak location corresponds to a chosen pore diameter selected from 1 to 3 μ

m, and wherein the majority of pores has a diameter within ±

25% of the chosen pore diameter,

6. The microporous biodegradable polymeric article according to claim 1, wherein the porosity is fully continuous.

7. The microporous biodegradable polymeric article according to claim 1, wherein the article has a symmetric morphology.

8. The microporous biodegradable polymeric article according to claim 1, wherein the article has an asymmetric morphology.

9. The microporous biodegradable polymeric article according to claim 8, wherein the article has a closed-cell skin.

10. The microporous biodegradable polymeric article according to claim 1, wherein at least 95% of said article is made of a biodegradable medical polymer selected from the group consisting of poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic), polyorthoesters, polycaprolactones, polyanhydrides and their copolymers.

11. The microporous biodegradable polymeric article according to claim 1, wherein at least 99% of said article is made of a biodegradable medical polymer selected from the group consisting of poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic), polyorthoesters, polycaprolactones, polyanhydrides and their copolymers.

12. The microporous biodegradable polymeric article according to claim 1, wherein said article is essentially made of a biocompatible, implantable polymer.

37. The use of a microporous biodegradable article according to claim 1 in tissue engineering.

39. The use of a microporous biodegradable article according to claim 1 as a substrate for controlled release applications.

13. A microporous biodegradable polymeric article comprising an essentially continuous porosity with a void volume from 10 to 90%, wherein pore diameters show a unimodal distribution set at a predefined unimodal peak location corresponding to a chosen pore diameter, and wherein a majority of pores has a diameter within ±

50% of the chosen pore diameter, prepared according to a method comprising the steps;

(a) selecting at least one biodegradable polymer A, one polymer B, biodegradable or not, at least partially immiscible with A, and a polymeric compatibilizer C for A and B;

(b) melt blending the selected polymers from step a) and the compatibilizer C, thereby preparing a compatibilized polymer blend, wherein said polymers A and B have an essentially continuous morphology;

(c) cooling said polymer blend to room temperature, thereby retaining its morphology; and

(d) extracting said polymer B and said compatibilizer C, at least partially, from the polymer blend by dissolving them in a solvent that is a non-solvent of polymer A,

14. A method of preparation of a microporous biodegradable polymeric article, comprising the steps:

(a) selecting at least one biodegradable polymer A, one polymer B, biodegradable or not, at least partially immiscible with A, and a polymeric compatibilizer C for A and B;

(b) melt blending the selected polymers from step a) and the compatibilizer C, thereby preparing a compatibilized polymer blend, wherein said polymers A and B have an essentially continuous morphology;

(c) cooling said polymer blend to room temperature, thereby retaining its morphology; and

(d) extracting said polymer B and said compatibilizer C, at feast partially, from the polymer blend by dissolving them in a solvent that is a non-solvent of polymer A,

wherein said polymeric article has an essentially continuous porosity with a void volume from 10 to 90%, wherein pore diameters show a unimodal distribution set to a predefined unimodal peak location corresponding to a chosen pore diameter, and wherein a majority of pore has a diameter within ±

50% of the chosen pore diameter.

15. The method according to claim 14, wherein said polymer A is a biodegradable medical polymer.

16. The method according to claim 15, wherein said polymer A is an aliphatic polyester.

17. The method according to claim 15, wherein said polymer A is selected from the group consisting of poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic), poly(hydroxyalkanoates), polyorthoesters, polycaprolactones, polydioanone, polyanhydrides and their copolymers.

18. The method according to claim 14, wherein said polymer B is a non-biodegradable polymer.

19. The method according to claim 14, wherein said polymer B is a biodegradable medical polymer.

20. The method according to claim 19, wherein said polymer B is selected from a group consisting of poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic), poly(hydroxyalkanoates), polyorthoesters, polycaprolactonest polyanhydrides and their copolymers.

21. The method according to claim 14, wherein said compatibilizer C is a polymeric compatibilizer.

22. The method according to claim 21, wherein said compatibilizer C is a copolymer of A and B.

23. The method according to claim 14, wherein said polymers A and 8 are fully immiscible.

24. The method according to claim 14, wherein said polymer blend is co-continuous at more than 90%.

25. The method according to claim 14, wherein said polymer blend may contain one or more additives.

26. The method according to claim 14, wherein said polymer blend is submitted to a further step of controlled annealing between steps b) and. c), thereby increasing the pore size of the porous article.

27. The method according to claim 14, wherein said polymer blend is submitted to controlled cooling rates in step c).

28. The method according to claim 14, wherein said polymer blend is further shaped into a geometrical form between steps b) and c).

29. The method according to claim 28, wherein said polymer blend is further shaped in a mold or die, between steps b) and c).

30. The method according to claim 28, wherein said polymer blend is shaped by injection molding, between steps b) and c).

31. The method according to claim 28, wherein said polymer blend is formed by extrusion, between steps b) and c).

32. The method according to claim 28, wherein said polymer blend is formed by melt spinning between steps b) and c).

33. The method according to claim 14, wherein said polymer blend is submitted to a mechanical stress that orients the porosity in at least one specific direction, between steps b) and c).

34. The method according to claim 14, wherein said polymer blend is submitted to a mechanical stress that orients the porosity in at least one specific direction, during step c).

35. The method according to claim 14, wherein said polymeric article is further submitted to a controlled immersion in a solvent for its polymer A after step d), thereby creating a closed-cell skin.

36. The method according to claim 14, wherein said polymer blend is further submitted to a controlled immersion in a common solvent for A and B between steps c) and d), thereby creating an asymmetric open-cell morphology in the porous article.

38. The use of a microporous biodegradable article obtained by the method according to claim 14 in tissue engineering.

40. The use of a microporous biodegradable article obtained by the method according to claim 14 as a substrate for controlled release applications.

42. The use of a microporous biodegradable article obtained by the method according to claim 14 as an implantable medical device.

41. The use of a microporous biodegradable article according to 1 as an implantable medical device.