Preparation for the prophylaxis of restenosis

• US 20050250672A9
• Filed: 12/20/2001
• Published: 11/10/2005
• Est. Priority Date: 03/26/2001
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Schering Pharma AG (Bayer AG)
• Inventors: Speck, Ulrich, Scheller, Brunn
• 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 preparation containing at least one antihyperplastic agent with a distribution ratio between butanol and water of ≧

0.5 in liquid form suitable for passing through capillaries together with an agent for enhancing artery/vein imaging.

4. The preparation according to claims 1 through 3 wherein the antihyperplastic agent is a cytostatic, a corticoid, a prostacyclin, an antioxidant, an antibiotic, an agent inhibiting cell proliferation or an immunosuppressant.

5. The preparation according to claims 1 through 4 wherein the antihyperplastic agent is a taxoid.

6. The preparation according to claims 1 through 5 wherein the antihyperplastic agent is paclitaxel, docetaxel, probucol, a porphyrin derivative, colchicine or epithilone.

7. The preparation according to claims 1 through 6 wherein the agent for enhancing artery/vein imaging consists of solutions, suspensions or emulsions that the vessels can tolerate and that are used in X-raying, sonography, optical imaging, or magnetic resonance imaging for improved representation of the blood vessels or the bloodstream.

8. The preparation according to claims 1 through 7 wherein the agent for enhancing artery/vein imaging is an X-ray contrast medium.

9. The preparation according to claims 1 through 8 wherein the agent for enhancing artery/vein imaging is iodixanol (Visipaque), gadolinium-DTPA (Magnevist), Gd-DO3A-butrol (Gadovist), iopromide (Ultravist), iohexol (Omnipaque), or iopamidol (Solutrast).

10. The preparation according to claims 1 through 9, characterized in that the preparation additionally contains coagulation inhibitors and/or platelet aggregation inhibitors and/or enzyme inhibitors and/or calcium chelators.

11. The preparation according to claims 1 through 10 wherein the active agent irreversibly or reversibly binds to tissue at a minimum percentage of 10%.

12. The preparation according to claims 1 through 11 wherein the active agent or the component carrying the active agent comprises a specific affinity to vascular walls.

13. The preparation according to claims 1 through 12 wherein the preparation contains a solubility promoter that does not form micelles.

14. Use of the preparation according to claims 1 through 13 for restenosis prevention.

15. Use of the preparation according to claims 1 through 13 for treating tumor diseases.

2. A preparation containing at least one antihyperplastic agent with a distribution ratio between butanol and water of ≧

0.5 that is applied to a catheter.

3. A preparation in aqueous solution that may optionally contain additives as well as at least one antihyperplastic agent with a distribution ratio between butanol and water of ≧

0.5 at a concentration that exceeds the saturation concentration in the purely aqueous medium wherein the active agent is not enclosed in micelles.