Cured oil-hydrogel biomaterial compositions for controlled drug delivery

• US 9,867,880 B2
• Filed: 03/15/2013
• Issued: 01/16/2018
• Est. Priority Date: 06/13/2012
• Status: Active Grant

• Current Assignee: Atrium Medical Corporation (Getinge AB)
• Original Assignee: Atrium Medical Corporation (Getinge AB)
• Inventors: Faucher, Keith M., Conroy, Suzanne, Albergo, Theresa K., Bienkiewicz, Joseph
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): AL-AWADI, DANAH J
• Application Number:
  US13/843,068
• Publication Number:
  US 20130337029A1
• Time in Patent Office: 1,768 Days
• Field of Search: None
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/14 Macromolecular materials
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/04 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The present invention is generally directed to materials, gels, coatings and films prepared using a biomaterial (e.g., a fatty acid-based material comprising a network of cross-linked fatty acids) and a fixating material, layer or film (e.g., a fixating material comprising Na—CMC). The materials, gels, coatings and films disclosed herein can be used to facilitate the delivery of one or more therapeutic agents to a targeted tissue and a desired rate of release.

Claims

1. A coating material coating a medical device, comprising:

a biomaterial layer comprising a biomaterial, wherein the biomaterial comprises fatty acids cross-linked to each other; and

a fixating material layer comprising a fixating material, wherein the fixating material comprises material selected from the group consisting of sodium carboxymethylcellulose (Na—

CMC), poly(ethylene glycol), poly(ethylene oxide), poly(HEMA), poly(N-vinyl pyrrolidone), poly(acrylic acid), carboxymethyl cellulose (CMC), and chitosan, and wherein the fixating material layer is disposed on an outer surface of the biomaterial layer relative to the medical device, and the biomaterial protonates the fixating material so as to alter a drug eluting property of the fixating material;

wherein the fixating material layer comprises one or more therapeutic agents; and

wherein the coating material effects controlled delivery in a patient of the one or more therapeutic agents from the coating material based on at least the altered drug eluting property of the fixating material.

2. The coating material of claim 1, wherein the biomaterial layer comprises one or more therapeutic agents and wherein the rate of release of the one or more therapeutic agents from the fixating material layer is extended at least in part by the protonation of the fixating material caused by a relative amount of fatty acids in the biomaterial.

3. The coating material of claim 1, wherein the biomaterial layer comprises a first therapeutic agent, wherein the fixating material layer comprises a second therapeutic agent, wherein the biomaterial layer releases the first therapeutic agent at a first rate, and wherein the fixating material layer releases the second therapeutic agent at a second rate.

4. The coating material of claim 3, wherein the second rate is influenced by a composition of the biomaterial.

5. The coating material of claim 3, wherein the biomaterial has a high fatty acid density and wherein the high fatty acid density delays the second rate.

6. The coating material of claim 3, wherein the biomaterial has a low fatty acid density of about 13.8 mg/in² and wherein the low fatty acid density accelerates the second rate.

7. The coating material of claim 2, wherein the fixating material is sodium carboxymethylcellulose (Na—

CMC).

8. The coating material of claim 1, wherein the biomaterial further comprises alpha-tocopherol.

9. The coating material of claim 1, wherein the biomaterial further comprises fish oil.

10. The coating material of claim 1, wherein the fatty acids are omega-3 fatty acids.

11. The coating material of claim 1, wherein the fatty acids are selected from the group consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and combinations thereof.

12. The coating material of claim 1, wherein the coating is on the medical device.

13. The coating material of claim 12, wherein the medical device is selected from the group consisting of a surgical mesh, a graft, a catheter balloon, a stand-alone film and a stent.

14. The coating material of claim 1, further comprising a plasticizing agent.

15. The coating material of claim 14, wherein the plasticizing agent is selected from the group consisting of glycerin, propylene glycol, poly ethylene glycol, triacetin citrate, triacetin and combinations thereof.

16. The coating material of claim 1, wherein the coating material is bioabsorbable.

17. The coating material of claim 1, wherein the fixating material fixates the coating material to tissue in vivo for a duration of greater than 10 days.

18. The coating material of claim 1, wherein the fixating material layer comprises one or more therapeutic agents and wherein the one or more therapeutic agents is released from the fixating material layer for a duration of greater than 10 days.

19. The coating material of claim 1, wherein the biomaterial further comprises ethyl esters of one or more fatty acids selected from the group consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

20. A film, comprising:

a biomaterial, wherein the biomaterial comprises fatty acids cross-linked to each other; and

a fixating material, wherein the fixating material is disposed as a layer on an outer surface of the biomaterial, and the biomaterial protonates the fixating material so as to alter a drug eluting property of the fixating material;

wherein the fixating material comprises sodium carboxymethylcellulose and one or more therapeutic agents; and

wherein the film is implantable in a patient to effect controlled delivery of the one or more therapeutic agents to the patient based on at least the altered drug eluting property of the fixating material.

21. The film of claim 20, wherein the biomaterial comprises the one or more therapeutic agents and wherein the rate of release of the one or more therapeutic agents from the fixating material is extended at least in part by the protonation of the fixating material caused by a relative amount of fatty acids in the biomaterial.

22. A film, comprising:

a biomaterial, wherein the biomaterial comprises fatty acids cross-linked to each other; and

a fixating material, wherein the fixating material is disposed as a layer on an outer surface of the biomaterial, and the biomaterial protonates the fixating material so as to alter a drug eluting property of the fixating material;

wherein the fixating material is sodium carboxymethylcellulose; and

one or more therapeutic agents carried by the biomaterial, or carried by the fixating material, or carried by both the biomaterial and the fixating material;

wherein the film is implantable in a patient to effect controlled delivery of the one or more therapeutic agents to the patient based on at least the altered drug eluting property of the fixating material.

23. The film of claim 22, wherein the protonation of the fixating material alters water solubility of the fixating material so as to extend delivery of the one or more therapeutic agents from the film.