Active agent eluting matrices with particulates

• US 20080038354A1
• Filed: 06/28/2007
• Published: 02/14/2008
• Est. Priority Date: 06/28/2006
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Anderson, Aron, Slager, Joram
• Granted Patent: US 7,638,344 B2
• Time in Patent Office: Days
• US Class Current: 424/487
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/129 containing macromolecular fillers
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 31/04 Homopolymers or copolymers of vinyl acetate
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

The present invention is directed to polymeric matrices for the controlled release of a hydrophilic bioactive agent. Generally, the elution control matrix includes a polymeric matrix having a first polymer and a plurality of microparticles that include the hydrophilic bioactive agent. In one embodiment, the matrix includes a polymer comprising hydrophilic and hydrophobic portions. In another embodiment, the microparticles include a crosslinked hydrophilic polymer.

Claims

1. An elution control matrix for the controlled release of a hydrophilic bioactive agent, comprising:

a first polymer that is hydrophobic, wherein a portion or all of the polymeric matrix is formed from the first polymer;

a second polymer that comprises hydrophobic and hydrophilic portions; and

a plurality of microparticles dispersed within the matrix;

wherein the microparticles comprise a hydrophilic bioactive agent.

2. The elution control matrix of claim 1 wherein the microparticles comprise a polypeptide.

3. The elution control matrix of claim 1, wherein the microparticles comprises a polypeptide that is an antibody or fragment thereof.

4. The elution control matrix of claim 1, wherein the microparticles comprises a Fab fragment.

5. The elution control matrix of claim 1, wherein the microparticles are formed predominantly of the hydrophilic bioactive agent.

6. The elution control matrix of claim 1 wherein the first polymer is a biostable polymer.

7. The elution control matrix of claim 6 wherein the first polymer is selected from the group consisting of poly(alkyl(meth)acrylates) and poly(aromatic(meth)acrylates).

8. The elution control matrix of claim 7 wherein the first polymer comprises poly(n-butyl methacrylate).

9. The elution control matrix of claim 1 wherein the second polymer is biodegradable.

10. The elution control matrix of claim 1 wherein the second polymer comprises a polyethylene glycol block copolymer.

11. The elution control matrix of claim 1 wherein the second polymer comprises a polyether ester copolymer.

12. The elution control matrix of claim 1 wherein the second polymer comprises PEGT/PBT.

13. The elution control matrix of claim 1 wherein the weight ratio of the second polymer to the microparticles in the matrix is in the range of 0.5:

1 to 1;

1.

14. The elution control matrix of claim 1 wherein the microparticles are present in the matrix in an amount in the range of 30% to 70% by weight solids.

15. The elution control matrix of claim 1 wherein the microparticles are present in the matrix in an amount in the range of 30% to 40% by weight solids.

16. The elution control matrix of claim 1 which is in the form of a coating on an implantable medical device.

17. The elution control matrix of claim 1 which is in the form of a coating on an implantable intraocular device.

18. The elution control matrix of claim 1 comprising a third polymer that is blendable with the first polymer.

19. The elution control matrix of claim 18, wherein the third polymer comprises poly(ethylene-co-vinyl acetate).

20. The elution control matrix of claim 1 comprising a fourth polymer that is present within and/or on the surface of the microparticles.

21. The elution control matrix of claim 20 wherein the fourth polymer comprises a natural biodegradable polysaccharide.

22. The elution control matrix of claim 1 wherein the first polymer is selected from the group consisting of poly(glycolic acid), poly(lactic acid), poly(lactic-co-glycolic acid), and poly(caprolactone).

23. The elution control matrix of claim 1 which is in the form of an implant.

24. A method for preparing an elution control matrix for the controlled release of a hydrophilic bioactive agent, comprising the steps of:

providing a composition comprising

a first polymer that is hydrophobic;

a second polymer comprising hydrophobic and hydrophilic portions; and

a plurality of microparticles, wherein the microparticles comprise a hydrophilic bioactive agent; and

disposing the composition on the surface of a substrate.

25. The method of claim 24, wherein the step of disposing comprises spraying the composition on the surface.

26. An elution control matrix for the controlled release of a hydrophilic bioactive agent, comprising:

a first polymer that is hydrophobic, wherein a portion or all of the polymeric matrix is formed from the first polymer; and

a plurality of microparticles dispersed within the matrix;

wherein the microparticles comprise a hydrophilic bioactive agent and crosslinked hydrophilic polymer.