Preparation for restenosis prevention

• US 8,389,043 B2
• Filed: 07/13/2010
• Issued: 03/05/2013
• Est. Priority Date: 03/26/2001
• Status: Expired due to Term

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Pharma AG (Bayer AG)
• Inventors: Speck, Ulrich, Scheller, Bruno
• Primary Examiner(s): Meeks, Timothy
• Assistant Examiner(s): SELLMAN, CACHET I
• Application Number:
  US12/835,420
• Publication Number:
  US 20100278997A1
• Time in Patent Office: 966 Days
• Field of Search: 427/2.1, 427/2.24, 427/2.25, 623/1.42, 623/1.44, 623/1.46, 604/103.8, 604/265, 604/266, 604/509
• US Class Current: 427/2.24
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/095 Sulfur, selenium, or tellurium compounds, e.g. thiols
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 49/0433 containing an organic halogenated X-ray contrast-enhancing agent
• CPC Class Codes: A61K 49/0438 Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
• CPC Class Codes: A61K 49/0447 Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
• CPC Class Codes: A61K 49/0452 Solutions, e.g. for injection
• CPC Class Codes: A61K 49/105 the metal complex being Gd-DTPA
• CPC Class Codes: A61K 49/106 the complex-forming compound being cyclic, e.g. DOTA
• CPC Class Codes: A61K 49/18 characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 29/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The invention relates to a preparation for restenosis prevention. The preparations for restenosis prevention known as yet do not reach sufficient active agent concentrations in the affected sections of the vascular walls as higher doses cause undesirable side effects. The present invention is a preparation to which at least one antihyperplastic agent is added that has a distribution ratio between butanol and water .gtoreq.0.5. The lipophilic active agent is absorbed by the vascular wall fast and in sufficient quantity. The preparation may be a liquid that can pass through capillaries and may contain a contrast agent so that the active agent is transferred into the vascular wall without any additional effort while the usually required contrast radiograms are taken. The preparation may also be applied to a catheter.

Claims

1. A method for making a drug-coated angioplasty catheter, comprising:

applying a solution of a lipophilic drug directly to a surface of a balloon wall of a balloon of an angioplasty catheter, and

drying the solution to form a coating of the lipophilic drug directly on the balloon wall to provide an outermost surface over the balloon,

wherein said solution comprises a solvent, said lipophilic drug, and a contrast agent, and said lipophilic drug is selected from azithromycin, roxithromycin, probucol, prostacyclins, corticoids, rapamycin, colchicine, paclitaxel, docetaxel, and 7-(2″

,3″

dihydroxypropyl oxycarbonyl)-paclitaxel.

2. The method of claim 1, wherein the lipophilic drug is paclitaxel.

3. The method of claim 2, wherein the solution consists of said solvent, paclitaxel, and said contrast agent.

4. The method of claim 1, wherein the solution consists of said solvent, said lipophilic drug, and said contrast agent.

5. The method of claim 1, also comprising processing said angioplasty catheter to be suitable for insertion into a patient with said coating providing said outermost surface.

6. The method of claim 1, wherein said solvent is ethanol.

7. A method of claim 1, wherein said solution consists of ethanol, paclitaxel, and a contrast agent, and said applying is by immersing said balloon surface into said solution.

8. The method of claim 1, wherein said contrast agent is selected from iodixanol, iopromide, iohexyl, iopamidol, gadolinium-DPTA, and Gd-DO3A-butrol.

9. The method of claim 8, wherein the lipophilic drug is paclitaxel.

10. The method of claim 8, wherein the lipophilic drug is rapamycin.

11. The method of claim 1, wherein said contrast agent is selected from iodixanol, iopromide, iohexyl, and iopamidol.

12. The method of claim 9, wherein the lipophilic drug is paclitaxel.

13. The method of claim 11, wherein the lipophilic drug is rapamycin.

14. A method for making a drug-coated angioplasty device, comprising:

applying a solution of a lipophilic drug directly to a surface of a balloon of an angioplasty device, said solution comprising a solvent, said lipophilic drug, and a contrast agent, and drying the solution to form a coating of the lipophilic drug directly on the surface of said balloon to provide an outermost surface over said balloon,

wherein said lipophilic drug is selected from azithromycin, roxithromycin, probucol, prostacyclins, corticoids, rapamycin, colchicine, paclitaxel, docetaxel, and 7-(2″

,3″

-dihydroxypropyl oxycarbonyl)-paclitaxel.

15. The method of claim 14, wherein the lipophilic drug is paclitaxel.

16. The method of claim 15, wherein the solution consists of said solvent, paclitaxel, and said contrast agent.

17. The method of claim 14, wherein the solution consists of said solvent, said lipophilic drug, and said contrast agent.

18. The method of claim 14, also comprising rendering said angioplasty device suitable for insertion into a patient with said coating providing said outermost surface.

19. The method of claim 14, wherein said surface is a balloon wall surface of the angioplasty device.

20. The method of claim 14, wherein said contrast agent is selected from iodixanol, iopromide, iohexyl, iopamidol, gadolinium-DPTA, and Gd-DO3A-butrol.

21. The method of claim 20, wherein the lipophilic drug is paclitaxel.

22. The method of claim 20, wherein the lipophilic drug is rapamycin.

23. The method of claim 14, wherein said contrast agent is selected from iodixanol, iopromide, iohexyl, and iopamidol.

24. The method of claim 23, wherein the lipophilic drug is paclitaxel.

25. The method of claim 23, wherein the lipophilic drug is rapamycin.

26. A method for making an angioplasty device useful for applying a lipophilic drug to a wall of a vascular vessel of a patient, the angioplasty device comprising a balloon having an outermost surface for contact with the wall of the vascular vessel, the method comprising:

processing an angioplasty device so as to be suitable for insertion into a patient to perform an angioplasty, wherein the processed angioplasty device comprises a balloon having an outermost coating comprising a lipophilic drug, the outermost coating positioned on a portion of the balloon that contacts the wall of the vascular vessel upon conduct of an angioplasty procedure with the angioplasty device;

wherein said processing includes applying an amount of a solution comprising a solvent, said lipophilic drug, and a contrast agent directly to the balloon to form said outermost coating, and

wherein said lipophilic drug is selected from azithromycin, roxithromycin, probucol, prostacyclins, corticoids, rapamycin, colchicine, paclitaxel, docetaxel, and 7-(2″

,3″

-dihydroxypropyl oxycarbonyl)-paclitaxel.

27. The method of claim 26, wherein said lipophilic drug is paclitaxel.

28. The method of claim 26, wherein the solution consists of said solvent, paclitaxel, and said contrast agent.

29. The method of claim 26, wherein the solution consists of said solvent, said lipophilic drug, and said contrast agent.

30. The method of claim 26, wherein said contrast agent is selected from iodixanol, iopromide, iohexyl, iopamidol, gadolinium-DPTA, and Gd-DO3A-butrol.

31. The method of claim 30, wherein the lipophilic drug is paclitaxel.

32. The method of claim 30, wherein the lipophilic drug is rapamycin.

33. The method of claim 26, wherein said contrast agent is selected from iodixanol, iopromide, iohexyl, and iopamidol.

34. The method of claim 33, wherein the lipophilic drug is paclitaxel.

35. The method of claim 33, wherein the lipophilic drug is rapamycin.

36. A method for making a drug-coated angioplasty catheter, comprising:

applying a solution of a lipophilic drug directly to a surface of a balloon wall of a balloon of the angioplasty catheter and drying the solution to form a coating comprising the lipophilic drug directly on the balloon wall to provide an outermost surface over the balloon,

wherein said solution comprises a solvent, said lipophilic drug, and a contrast agent, and said lipophilic drug is selected from azithromycin, roxithromycin, probucol, prostacyclins, corticoids, rapamycin, colchicine, paclitaxel, docetaxel, and 7-(2″

,3″

-dihydroxypropyl oxycarbonyl)-paclitaxel.

37. A method for making a drug-coated angioplasty device, comprising:

applying a solution of a lipophilic drug directly to a surface of a polymeric balloon wall of a balloon of an angioplasty device and drying the solution to form a coating of the lipophilic drug directly on the polymeric balloon wall to provide an outermost surface over the balloon,

wherein said solution comprises a solvent, said lipophilic drug, and a contrast agent, and said lipophilic drug is selected from azithromycin, roxithromycin, probucol, prostacyclins, corticoids, rapamycin, colchicine, paclitaxel, docetaxel, and 7-(2″

,3″

-dihydroxypropyl oxycarbonyl)-paclitaxel.