Cross-linked fatty acid-based biomaterials

• US 9,827,352 B2
• Filed: 04/06/2015
• Issued: 11/28/2017
• Est. Priority Date: 09/28/2004
• Status: Active Grant

• Current Assignee: Atrium Medical Corporation (Getinge AB)
• Original Assignee: Atrium Medical Corporation (Getinge AB)
• Inventors: Faucher, Keith M., Tang, Hui, Martakos, Paul, Karwoski, Theodore, Sullivan, Allison, Melville, Greg, Corbeil, Scott E.
• Primary Examiner(s): Thomas, Timothy
• Assistant Examiner(s): Rosenthal, Andrew S
• Application Number:
  US14/679,368
• Publication Number:
  US 20150209482A1
• Time in Patent Office: 967 Days
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 31/4353 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2430/00 Materials or treatment for tissue regeneration
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Fatty acid-based, pre-cure-derived biomaterials, methods of making the biomaterials, and methods of using them as drug delivery carriers are described. The fatty acid-derived biomaterials can be utilized alone or in combination with a medical device for the release and local delivery of one or more therapeutic agents. Methods of forming and tailoring the properties of said biomaterials and methods of using said biomaterials for treating injury in a mammal are also provided.

Claims

1. A solidified gel biomaterial comprising:

a thermally cured fatty acid based material having fatty acids cross-linked to other fatty acids via cross-linking bridges formed at unsaturated (C═

C) sites of a fish oil from which the thermally cured fatty acid based material is derived; and

a therapeutic agent loaded within the thermally cured fatty acid based material, wherein the therapeutic agent is not stable when subjected to thermal curing that thermally cures the fish oil;

wherein the biomaterial is derived from a pre-cure of the fish oil in combination with the therapeutic agent that are, following combination, additionally thermally cured to form the biomaterial, and wherein viscosity of the pre-cure is in the range of 1×

10⁵ cps at 22°

C. to 1×

10⁷ cps at 22°

C. and the viscosity of the biomaterial is greater than that of the pre-cure; and

wherein the therapeutic agent exhibits less degradation in the biomaterial than observed when cured with the fish oil by a thermal curing process that starts with uncured fish oil and ends with the thermally cured fatty acid based material.

2. The biomaterial of claim 1, wherein the biomaterial is hydrolysable by human tissue.

3. The biomaterial of claim 1, further comprising alpha-tocopherol disposed within the thermally cured fatty acid based material.

4. A method of creating a cured biomaterial comprising the solidified gel biomaterial according to claim 1, the method comprising the steps of:

curing a fish oil-containing starting material for a first curing time to create a pre-cure material by cross-linking fatty acids of the fish oil-containing starting material;

mixing a therapeutic agent with the pre-cure material to create a mixed preparation;

then curing the mixed preparation for a second curing time to create the cured biomaterial.

5. The method of claim 4, wherein a higher percentage of the therapeutic agent remains in the cured biomaterial after curing for the second curing time than would have remained in the biomaterial if the therapeutic had been subjected to curing conditions for both the first curing time and the second curing time.

6. The method of claim 5, wherein the second curing time is shorter than the first curing time.

7. The method of claim 6, wherein the second curing time is at least twice as long as the first curing time.

8. The method of claim 4, wherein the viscosity of the pre-cure material after curing for the first curing time has a viscosity of about 1.0×

10⁵ cps to 1.0×

10⁷ cps as measured at 22°

C.

9. The method of claim 4, further comprising mixing alpha-tocopherol with the fish oil-containing starting material or the pre-cure material.

10. The method of claim 9, wherein the alpha-tocopherol is mixed with the therapeutic agent and the pre-cure material to form the mixed preparation.

11. The biomaterial of claim 1, wherein the cross-linking bridges include ester bridges.

12. The biomaterial of claim 1, wherein the cross-linking bridges include a combination of peroxide bridges, ether bridges and hydrocarbon bridges.

14. The biomaterial of claim 1, wherein the cross-linking bridges include lactone bridges.

13. A solidified gel biomaterial comprising:

a UV cured cured fatty acid based material having fatty acids cross-linked to other fatty acids via cross-linking bridges formed at unsaturated (C═

C) sites of a fish oil from which the UV cured fatty acid based material is derived; and

a therapeutic agent loaded within the UV cured fatty acid based material, wherein the therapeutic agent is not stable when subjected to UV curing that UV cures the fish oil;

wherein the biomaterial is derived from a pre-cure of the fish oil in combination with the therapeutic agent that are, following combination, additionally UV cured to form the biomaterial, and wherein viscosity of the pre-cure is in the range of 1×

10⁵ cps at 22°

C. to 1×

10⁷ cps at 22°

C. and the viscosity of the biomaterial is greater than that of the pre-cure; and

wherein the therapeutic agent exhibits less degradation in the biomaterial than observed when cured with the fish oil by a UV curing process that starts with uncured fish oil and ends with the UV cured fatty acid based material.