Intraluminal device with a coating containing a therapeutic agent

• US 20050158361A1
• Filed: 11/08/2002
• Published: 07/21/2005
• Est. Priority Date: 11/08/2001
• Status: Active Grant

• Current Assignee: Atrium Medical Corporation (Getinge AB)
• Original Assignee: Atrium Medical Corporation (Getinge AB)
• Inventors: Dhondt, Maria, Martens, Johan, Jacobs, Pierre, De Scheerder, Ivan
• Granted Patent: US 8,460,693 B2
• Time in Patent Office: Days
• US Class Current: 424/425
• 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: A61L 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• 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 invention relates to an intraluminal device, in particular an intraluminal prosthesis, shunt, catheter or local drug delivery device. In order to increase the bio-compatibility of this device, it is provided with at least one coating. The coating contains a therapeutic agent which is comprised in a matrix that sticks to the intraluminal device. Instead of being formed by a little bio-compatible polymer, the matrix is formed by a bio-compatible oil or fat, such as cod-liver oil or olive oil. Preferably, the bio-compatible oil or fat further comprises alfa-tocopherol.

Claims

1. A device, comprising:

at least one coating containing a therapeutic agent comprised in a therapeutic matrix which covers at least a portion of the device, said therapeutic matrix disposed to deliver the therapeutic agent to tissue of a patient upon implantation in said patient, and

said therapeutic matrix formed by a bio-compatible oil or fat.

2. The device according to claim 1, wherein said therapeutic agent is dissolved in said oil or fat.

3. The device according to claim 1, wherein said therapeutic agent is dispersed, more particularly one of emulsified and suspended, in said oil or fat.

4. The device according to claim 1, wherein said therapeutic agent is chemically bonded to said oil or fat, said therapeutic agent is a component of said oil or fat, or said oil or fat substantially consists of said therapeutic agent.

5. The device according to claim 1, wherein said therapeutic agent comprises at least one of alfa-tocopherol, and a derivative thereof, which forms at least a portion of said oil or fat.

6. The device according to claim 1, wherein said oil or fat comprises at least one of fatty acids and a derivative thereof, in particular one or more triglycerides composed of glycerol and one or more fatty acids, said oil or fat comprising preferably triglycerides, more preferably in an amount of more than 20% by weight, and most preferably in an amount of more than 70% by weight.

7. The device according to claim 6, wherein said fatty acids comprise one or more fatty acids, in particular omega-3 fatty acids, the fatty acids comprising preferably more than 5%, more preferably more than 10%, and most preferably more than 15% by weight of unsaturated fatty acids.

8. The device according to claim 7, wherein said unsaturated fatty acids comprise at least one of eicosapentaenoic acid and decosahexaenoic acid.

9. The device according to claim 8, wherein said oil or fat further comprises at least one of alfa-tocopherol, and a derivative thereof, the oil or fat comprising the alfa-tocopherol, and/or the derivative thereof, preferably in an amount of between 20% and 80% by weight, more preferably in an amount of between 30 and 70% by weight.

10. The device according to claim 6, wherein said oil or fat comprises less than 50% by weight, preferably less than 10% by weight of free fatty acids.

11. The device according claim 1, wherein said oil or fat comprises a chemically modified, in particular one of partially hydrogenated and chemically hardened, one of animal, vegetable, and naturally occurring oil, in particular one of fish oil, olive oil, linseed oil, sunflower oil, corn oil, palm oil and palmnut oil, the oil comprising preferably fish oil, in particular cod-liver oil and more particularly purified cod-liver oil containing more than 90% by weight of triglycerides.

12. The device according to claim 1, wherein said coating comprises at least 50% by weight, preferably at least 70% by weight, more preferably at least 80% by weight and most preferably at least 90% by weight of said oil or fat.

13. The device according to claim 1, wherein said coating comprises at least 70% by weight, preferably at least 85% by weight and most preferably at least 95% by weight of said oil or fat and said therapeutic agent.

14. The device according to claim 1, wherein said device is an endovascular prosthesis.

15. The device according to claim 1, wherein said oil or fat has a melting point lower than 100°

C., preferably lower than 80°

C., more preferably lower than 60°

C., most preferably lower than 40°

C., in particular lower than or equal to 37°

C.

16. The device according to claim 1, wherein said oil or fat has a melting point higher than 10°

C., preferably higher than 15°

C. and more preferably higher than 20°

C., in particular higher than 30°

C.

17. The device according to claim 1, wherein said oil or fat is an oil which is liquid at room temperature, in particular at 20°

C.

18. The device according to claim 1, wherein said oil or fat is a chemically hardened oil or fat, in particular a hydrogenated oil or fat.

19. The device according to claim 18, wherein said chemically modified oil or fat comprises unsaturated fatty acid chains and is substantially free of trans isomers of unsaturated fatty acid chains.

20. The device according to claim 1, wherein said device is provided with a top coat applied on top of said coating.

21. The device according to claim 20, wherein said top coat comprises at least one of alfa-tocopherol, and a derivative thereof, in an amount of at least 80% by weight, preferably in an amount of at least 90% by weight and most preferably in an mount of at least 95% by weight.

22. The device according to claim 1, wherein said therapeutic agent comprises at least one therapeutic agent selected from the group consisting of vinblastine, sirolimus, mitoxantrone, tacrolimus, paclitaxel, cytochalasin, latrunculin, and everolimus.

23. The device according to claim 1, wherein said therapeutic agent comprises at least one therapeutic agent selected from the group consisting of deferoxamine, geldanamycin, nigericin, penitrem, paxilline, verruculogen, KT5720, KT5823, Anisomycin, chelerythrine chloride, genistein, parthenolide, trichostatin A, T2 toxin, Zearalenone, Interferon, epithalon-D, Caionophore, 4 bromo Ca Ionophore, Aflatoxins, aphidicolin, brefeldin A, cerulenin, chromomycin A3, citrinin, cyclopiazonic acid, forsokolin, fumagillin, fumonisins B 1, B2, hypericin, K252, mycophenolic acid, ochratoxin A, and oligomycin.

24. The device according to claim 1, wherein said therapeutic agent comprises at least one therapeutic agent selected from the group consisting of immunosuppressants, anti-inflammatories, anti-proliferatives, anti-migratory agents, anti-fibrotic agents, proapoptotics, calcium channel blockers, anti-neoplastics, antibodies, anti-thrombotics, anti-platelet agents, IIb/IIIa blockers, antiviral agents, anti-cancer agents, chemotherapeutics, thrombolytics, vasodilators, antibiotics, growth factor antagonists, free radical scavengers, radiopaque agents, anti-angiogenesis agents, angiogenesis drugs, cyclooxygenase inhibitors, phosphodiesterase inhibitors, cytokine inhibitors, nitrogen oxide donors, cytokine activators, anti-oxidants, radioactive compounds, steroids, and non-steroidal anti-inflammatory drugs.

25. The device according to claim 1, wherein said therapeutic agent comprises at least one therapeutic agent selected from the group consisting of mycophenolic acid, mycophenolate mofetil, mizoribine, methylprednisolone, dexamethasone and other corticosteriods, certican™

, tritolide™

, methotrexate™

, benidipine™

, ascomycin™

, wortmannin™

, LY 294002, Camptothecin™

, Topotecan™

, hydroxyurea, cyclophosphamide, cyclosporin, daclizumab, azathioprine, gemcitabine™

, and derivatives and analogues thereof.

29. The device according to claim 1, wherein said prosthesis is porous and said at least one coating is applied within pores of the prosthesis.

30. The device according to claim 1, wherein said oil or fat comprises at least one of fatty acids and one or more derivatives thereof, in particular one or more trihydroxy or polyhydroxy compounds and one or more fatty acids.

31. The device according to claim 1, wherein said matrix is formed of oils or fats comprised of at least one of a free fatty acid and a fatty acid derivative, and is preferably comprised of at least one of methyl esters and ethyl esters of fatty acids.

32. The device according to claim 1, wherein said oil or fat comprises a synthetic oil.

33. The device according to claim 1, wherein said therapeutic agent comprises at least one of a gene including a polynucleotide, an oligonucleotide, a recombinant nucleic acid, gene/vector system, and a nucleic acid.

34. The device according to claim 1, wherein said at least one coating comprises a local coating separate from a top coating.

35. The device according to claim 34, wherein said top coating comprises one of a polymeric substance, a binder, and a thickening agent to stabilize the therapeutic mixture.

36. The device according to claim 34, wherein said top coating comprises fish oil.

37. The device according to claim 1, wherein said matrix provides sufficient lubrication for device deployment without addition of a separate lubricant component.

38. The device according to claim 1, wherein said matrix comprises a mixture of hydrogenated and non-hydrogenated oil, fat or fatty acids.

39. The device according to claim 1, wherein said device comprises at least one of an intraluminal prosthesis, shunt, catheter and local drug delivery device.

26. A method for providing a device, comprising:

providing said device with at least one coating containing a therapeutic agent comprised in a therapeutic matrix which covers at least a portion of the device, and

applying a bio-compatible oil or fat, which comprises said therapeutic agent, in a flowable state onto the device to form said therapeutic matrix comprising the therapeutic agent.

27. The method according to claim 26, wherein said oil or fat is applied in a molten state onto the device.

28. The method according to claim 26, wherein said oil or fat is mixed with a solvent before applying it onto the device and, after having applied the mixture of solvent and oil or fat onto the device, the solvent is allowed to evaporate.