Fatty-acid based particles

• US 9,427,423 B2
• Filed: 03/10/2009
• Issued: 08/30/2016
• Est. Priority Date: 03/10/2009
• Status: Active Grant

• Current Assignee: Atrium Medical Corporation (Getinge AB)
• Original Assignee: Atrium Medical Corporation (Getinge AB)
• Inventors: Swanick, Thomas M., Ferraro, Joseph, Rogers, Lisa, Martakos, Paul
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): HELM, CARALYNNE E
• Application Number:
  US12/401,243
• Publication Number:
  US 20100233232A1
• Time in Patent Office: 2,730 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/4353 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/7028 Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 35/60 Fish, e.g. seahorses; Fish eggs
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• 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]

Abstract

The present invention is directed toward fatty acid-based particles, and methods of making such particles. The particles can be associated with an additional, therapeutic agent. Also provided herein is a method of forming fatty acid particles, comprising associating a cross-linked, fatty acid-derived biomaterial with a cryogenic liquid; and fragmenting the bio material/cryogenic liquid composition, such that fatty acid particles are formed. The particles can be used for a variety of therapeutic applications.

Claims

1. A method of forming therapeutic fatty acid particles, comprising:

(a) curing a fish oil combined with a therapeutic agent to form a bioabsorbable material comprising fatty acids cross-linked directly to each other by bonds formed during the curing process, wherein the bioabsorbable material is hydrolyzable by tissue into non-inflammatory components;

(b) associating the bioabsorbable material with a cryogenic liquid; and

(c) fragmenting the material/cryogenic liquid composition, such that therapeutic fatty acid particles are formed.

2. The method of claim 1, wherein the material is a cross-linked gel.

3. The method of claim 1, wherein the step of associating the material with a cryogenic liquid comprises at least one of suspending, submerging, and surrounding the material with a cryogenic liquid.

4. The method of claim 1, wherein the cryogenic liquid comprises liquid nitrogen.

5. The method of claim 1, wherein the material/cryogenic liquid composition is fragmented using one or more of grinding, shearing, shocking, shattering, granulating, pulverizing, shredding, crushing, homogenizing, sonicating, vibrating, and/or milling.

6. The method of claim 1, wherein the cryogenic liquid is substantially removed by evaporation, either before fragmentation or after the particles are formed.

7. The method of claim 1, wherein the material is in the form of a film.

8. The method of claim 7, wherein the film is ground prior to association with a cryogenic liquid.

9. The method of claim 1, wherein the mean particle size of the particles is in the range of about 1 micron to about 50 microns.

10. The method of claim 1, wherein the oil further comprises vitamin E.

11. The method of claim 7, wherein the film is coated with a therapeutic agent/solvent mixture.

12. The method of claim 11, wherein the therapeutic agent is dissolved in a solvent, and the therapeutic agent/solvent mixture is applied to the film.

13. The method of claim 12, wherein the therapeutic agent/solvent mixture is applied to the film by dipping or spraying.

14. The method of claim 1, wherein the fatty acid particles are further soaked in a therapeutic agent dissolved in solvent.

15. The method of claims 11 or 14 wherein the solvent is methanol or ethanol.

16. The method of claims 11 or 14 wherein the solvent is hexane, isopar, water, ethanol, methanol, proglyme, methylene chloride, acetonitrile, acetone, or MEK.

17. The method of claim 1, wherein the therapeutic agent comprises one or more of an antioxidant, anti-inflammatory agent, anti-coagulant agent, drug to alter lipid metabolism, anti-proliferative, anti-neoplastic, tissue growth stimulant, functional protein/factor delivery agent, anti-infective agent, imaging agent, anesthetic agent, chemotherapeutic agent, tissue absorption enhancer, anti-adhesion agent, germicide, analgesic, antiseptic, or pharmaceutically acceptable salts, esters, or prodrugs thereof.

18. The method of claim 1, wherein the therapeutic agent is selected from the group consisting of rapamycin, marcaine, CSA, ISA and gentamycin, and rifampicin.

19. A method of forming therapeutic fatty acid particles comprising:

(a) curing a fish oil to form a bioabsorbable material comprising fatty acids cross-linked directly to each other by bonds formed during the curing process, wherein the bioabsorbable material is hydrolyzable by tissue into non-inflammatory components;

(b) combining the material and a therapeutic agent to form a composition;

(c) submerging, surrounding, or suspending the composition in a cryogenic liquid; and

(d) fragmenting the composition to form therapeutic fatty acid particles comprising cross-linked fatty acids and the therapeutic agent.

20. The method of claim 19, wherein the cryogenic liquid is removed.

21. The method of claim 19, wherein the material is in the form of a film.

22. The method of claim 21, wherein the film is ground into particles before association with the therapeutic agent.

23. A method of forming therapeutic fatty acid particles, comprising the steps of:

curing a fish oil to form a bioabsorbable material comprising fatty acids cross-linked directly to each other, wherein the bioabsorbable material is hydrolyzable by tissue into non-inflammatory components;

loading the material with a therapeutic agent before associating the material with a cryogenic liquid; and

fragmenting the material/cryogenic liquid composition, such that therapeutic fatty acid particles are formed.

24. A method of forming therapeutic fatty acid particles pressed into a film or three dimensional article, the method comprising the steps of:

curing a fish oil to form a bioabsorbable material comprising fatty acids cross-linked directly to each other, wherein the bioabsorbable material is hydrolyzable by tissue into non-inflammatory components;

combining the material and a therapeutic agent to form a composition;

submerging, surrounding, or suspending the composition in a cryogenic liquid;

fragmenting the composition to form therapeutic fatty acid particles comprising cross-linked fatty acids and the therapeutic agent; and

pressing the therapeutic fatty acid particles into the film or three dimensional article.