Preparation for the prophylaxis of restenosis

• US 20050101522A1
• Filed: 12/20/2001
• Published: 05/12/2005
• Est. Priority Date: 03/26/2001
• Status: Active Grant

• Current Assignee: Brunn Scheller, Ulrich Speck
• Original Assignee: Bayer Schering Pharma AG (Bayer AG)
• Inventors: Scheller, Brunn, Speck, Ulrich
• Granted Patent: US 7,750,041 B2
• Time in Patent Office: Days
• US Class Current: 514/1
• 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 ≧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 composition of matter comprising a pharmaceutically effective amount of taxol or a tumor-active analog thereof, solubilized in a pharmaceutically acceptable carrier comprising an oil having a dipole moment of between about 0.5 Debyes and about 2.0 Debyes.

2. The composition of claim 1 wherein said oil comprises an ether lipid as a major component.

3. The composition of claim 1 wherein said oil is a marine oil having an ether lipid as a major component thereof.

4. The composition of claim 1 wherein said oil comprises a terpene hydrocarbon as a major component.

5. The composition of claim 1 which comprises taxol.

6. An emulsion comprising the composition of claim 1.

7. The emulsion of claim 6 that is an oil-in-water emulsion.

18. A pharmaceutical dosage form comprising the composition of claim 1.

8. A composition of matter comprising a pharmaceutically effective amount of taxol solubilized in an oil selected from the group consisting of orange roughy oil, shark liver oil, squalane and squalene.

9. The composition of claim 8 wherein said oil is squalane or squalene.

10. A composition of matter comprising an oil having a dipole moment of between about 0.5 Debyes and about 2.0 Debyes in which taxol or a tumor-active analog thereof is solubilized in said oil at a level greater than or equal to 1 mg/ml.

11. The composition of matter of claim 10 wherein said taxol or tumor-active analog thereof is solubilized in said oil at a level greater than or equal to 5 mg/ml.

12. The composition of matter of claim 11 wherein said oil is squalane or squalene.

13. A method for solubilizing taxol or a tumor-active taxol analog in a pharmaceutically acceptable carrier comprising:

(a) solubilizing taxol or said taxol analog in an anhydrous alcohol;

(b) mixing the solution of (a) with a sufficient amount of a pharmaceutically acceptable carrier comprising an oil having a dipole moment of between about 0.5 Debyes and about 2.0 Debyes, to solubilize said solution.

14. The method of claim 13 further comprising removing said anhydrous alcohol from the solution of step (b).

15. A pharmaceutical composition comprising the solution prepared by the method of claim 14.

16. The method of claim 14 further comprising preparing an oil-in-water emulsion with the solution from which said anhydrous alcohol has been removed.

17. An emulsion prepared by the method of claim 16.