Compositions and methods for altering the rate of hydrolysis of cured oil-based materials

• US 10,322,213 B2
• Filed: 07/16/2011
• Issued: 06/18/2019
• Est. Priority Date: 07/16/2010
• Status: Active Grant

• Current Assignee: Atrium Medical Corporation (Getinge AB)
• Original Assignee: Atrium Medical Corporation (Getinge AB)
• Inventors: Faucher, Keith M., Albergo, Theresa K., Martakos, Paul
• Primary Examiner(s): Stevens, Mark V
• Application Number:
  US13/184,512
• Publication Number:
  US 20120016038A1
• Time in Patent Office: 2,894 Days
• CPC Class Codes: A61L 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08L 91/00 Compositions of oils, fats or waxes; Compositions of derivatives thereof
• CPC Class Codes: C09D 191/00 Coating compositions based on oils, fats or waxes; Coating compositions based on derivatives thereof polishing compositions, ski waxes C09G

Abstract

Disclosed herein is the correlation of chemical properties of oils with the physical properties of a resulting cured oil composition. Also disclosed are biocompatible materials and coatings for medical devices prepared using enriched oils and methods for enhancing or modifying the physical and chemical characteristics of cured oils by enriching such oils with fatty acid alkyl esters. Methods of tailoring the properties of biocompatible materials and coatings to deliver one or more therapeutic agents are also provided.

Claims

1. A method of increasing the in vivo hydrolysis rate of a cured oil coating having cross-linked fatty acids, wherein the method comprises the steps of (i) enriching one or more oils used to form the cured oil coating by adding one or more fatty acid ethyl esters to form an enriched oil, wherein the enriched oil comprises about 75% w/w or more of the one or more fatty acid ethyl esters, and wherein the enriched oil comprises at least 50% w/w polyunsaturated fatty acids and (ii) exposing the enriched oil to curing conditions to form the cured oil coating so that a number of polar hydroxyl functional groups are formed in the cured oil coating during curing that increases the polarity of the cured oil coating compared to what is formed during curing when the one or more oils are cured without the enriching step, thereby increasing the in vivo hydrolysis rate of the cured oil coating and providing the coating with a contact angle of less than 90°

.

2. The method of claim 1, wherein the fatty acid ethyl esters comprise an ethyl ester of eicosapentaenoic acid (EPA).

3. The method of claim 1, wherein the fatty acid ethyl esters comprise an ethyl ester of docosahexaenoic acid (DHA).

4. The method of claim 1, wherein the fatty acid ethyl esters comprise ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

5. The method of claim 1, wherein the one or more oils are selected from the group consisting of fish oil, flaxseed oil, grapeseed oil, safflower oil, soybean oil, corn oil, echium oil, hempseed oil, walnut oil, olive oil and combinations thereof.

6. The method of claim 1, wherein the enriched oil comprises flaxseed oil and ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

7. The method of claim 6, wherein the enriched oil comprises about 10% or more w/w flaxseed oil.

8. The method of claim 1, wherein the one or more oils are marine oils.

9. The method of claim 1, wherein the enriched oil comprises fish oil and ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

10. The method of claim 1, wherein the enriched oil comprises about 10% or more w/w fish oil.

11. The method of claim 1, wherein the enriched oil comprises at least 60% polyunsaturated fatty acids.

12. The method of claim 1, wherein the coating has a contact angle of less than 70°

.

13. The method of claim 1, wherein the coating completely hydrolyzes in vivo in less than about 60 days.

14. The method of claim 1, wherein the coating completely hydrolyzes in vivo in less than about 90 days.

15. The method of claim 1, wherein the coating completely hydrolyzes in vivo into substantially non-inflammatory compounds.

16. The method of claim 1, wherein the coating has one or more polar hydroxyl groups as indicated by an infrared absorption spectrum having a peak at approximately 3300-3600 cm⁻

1.

17. The method of claim 1, wherein the coating further comprises one or more therapeutic agents.

18. The method of claim 17, wherein the one or more therapeutic agents are selected from the group consisting of an anti-proliferative agent, an anti-inflammatory agent, an antimicrobial agent, an antibiotic agent and combinations thereof.

19. The method of claim 17, wherein the one or more therapeutic agents are eluted from the coating over an extended period of time.

20. The method of claim 19, wherein the extended period of time is at least seven days.

21. The method of claim 19, wherein the extended period of time is at least fourteen days.

22. The method of claim 19, wherein the extended period of time is at least about thirty days.

23. The method of claim 19, wherein the extended period of time is at least sixty days.

24. The method of claim 1, wherein the curing conditions comprise heat.

25. The method of claim 1, wherein the cured oil coating forms a coating on a medical device.

26. A method of increasing the in vivo hydrolysis rate of a cured oil coating having cross-linked fatty acids, wherein the method comprises the steps of:

enriching one or more oils used to form the cured oil coating by blending in one or more fatty acid alkyl esters to form an enriched oil, wherein the enriched oil comprises about 75% w/w or more of the one or more fatty acid alkyl esters, and

exposing the enriched oil to curing conditions to form the cured oil coating so that a number of polar hydroxyl functional groups are formed in the cured oil coating during curing that increases the polarity of the cured oil coating compared to what is formed during curing when the one or more oils are cured without the enriching step, thereby increasing the in vivo hydrolysis rate of the cured oil coating,

wherein the coating has a contact angle of less than 90° and

wherein the coating has substantially more polar hydroxyl groups than a coating formed by exposing non-enriched forms of the one or more oils to the curing conditions as indicated by an infrared absorption spectrum having a broad substantial peak at approximately 3300-3600 cm¹.

27. The method of claim 26, wherein the fatty acid alkyl esters comprise lower alkyl esters of fatty acids, wherein the lower alkyl esters of fatty acids are selected from the group consisting of a linear C1-C6 alkyl ester and a branched C1-C6 alkyl ester.

28. The method of claim 26, wherein the fatty acid alkyl esters are ethyl esters of fatty acids.

29. The method of claim 26, wherein the alkyl esters of fatty acids are selected from the group consisting of a linear C1-C22 alkyl ester and a branched C1-C22 alkyl ester.

30. A method of increasing the in vivo hydrolysis rate of a cured oil coating having cross-linked fatty acids, wherein the method comprises the steps of (i) enriching one or more oils used to form the cured oil coating by adding one or more fatty acid ethyl esters to form an enriched oil, wherein the enriched oil comprises about 50% w/w or more of the one or more fatty acid ethyl esters, and wherein the enriched oil comprises at least 50% w/w polyunsaturated fatty acids and (ii) exposing the enriched oil to curing conditions to form the cured oil coating so that a number of polar hydroxyl functional groups are formed in the cured oil coating during curing that increases the polarity of the cured oil coating compared to what is formed during curing when the one or more oils are cured without the enriching step, thereby increasing the in vivo hydrolysis rate of the cured oil coating.