Injectable formulations of taxanes for cad treatment

• US 20050272806A1
• Filed: 06/02/2004
• Published: 12/08/2005
• Est. Priority Date: 06/02/2004
• Status: Active Grant

• Current Assignee: Cardinal Health Switzerland 515 GmbH (Cardinal Health, Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Zhao, Jonathon Z., Falotico, Robert
• Granted Patent: US 7,989,490 B2
• Time in Patent Office: Days
• US Class Current: 514/449
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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

Medical devices, and in particular implantable medical devices, may be coated to minimize or substantially eliminate a biological organism'"'"'s reaction to the introduction of the medical device to the organism. The medical devices may be coated with any number of biocompatible materials. Therapeutic drugs, agents or compounds may be mixed with the biocompatible materials and affixed to at least a portion of the medical device. These therapeutic drugs, agents or compounds may also further reduce a biological organism'"'"'s reaction to the introduction of the medical device to the organism. In addition, these therapeutic drugs, agents and/or compounds may be utilized to promote healing, including the formation of blood clots. The drugs, agents, and/or compounds may also be utilized to treat specific diseases, including vulnerable plaque. Therapeutic agents may also be delivered to the region of a disease site. In regional delivery, liquid formulations may be desirable to increase the efficacy and deliverability of the particular drug. Also, the devices may be modified to promote endothelialization. Various materials and coating methodologies may be utilized to maintain the drugs, agents or compounds on the medical device until delivered and positioned. In addition, the devices utilized to deliver the implantable medical devices may be modified to reduce the potential for damaging the implantable medical device during deployment. Medical devices include stents, grafts, anastomotic devices, perivascular wraps, sutures and staples. In addition, various polymer combinations may be utilized to control the elution rates of the therapeutic drugs, agents and/or compounds from the implantable medical devices. Liquid formulations, including solutions and suspensions of the various drugs, agents and/or compounds, may be locally or regionally delivered. In each of these instances, antioxidants are utilized to prolong product integrity.

Claims

1. A liquid formulation of a therapeutic agent comprising:

a taxane in a pharmaceutically effective dosage; and

one or more pharmaceutically acceptable solubility enhancers.

2. The liquid formulation according to claim 1, further comprising one or more pharmaceutically acceptable stabilizers.

3. The liquid formulation according to claim 2, wherein the concentration of the taxane in solution is in the range from about 0.05 mg/ml to about 5 mg/ml.

4. The liquid formulation according to claim 3, wherein the taxane comprises paclitaxel.

5. The liquid formulation according to claim 2, wherein the one or more pharmaceutically acceptable stabilizer and solubility enhancers comprises a polyethylene glycol.

6. The liquid formulation according to claim 2, wherein the one or more pharmaceutically acceptable stabilizer and solubility enhancers comprises Vitamin E TPGS.

7. The liquid formulation according to claim 1, further comprising water.

8. A method for the treatment of vascular disease comprising the administration of a liquid formulation of a taxane proximate the disease site.

9. The method for the treatment of vascular disease according to claim 8, wherein the liquid formulation of the taxane comprises paclitaxel in a pharmaceutically effective dosage and one or more pharmaceutically acceptable solubility enhancers.

10. An injectable formulation of a therapeutic agent comprising:

a taxane in a pharmaceutically effective dosage; and

one or more pharmaceutically acceptable solubility enhancers.

11. The injectable formulation according to claim 10, further comprising one or more pharmaceutically acceptable stabilizers.

12. The injectable formulation according to claim 11, wherein the concentration of the taxane in suspension is in the range from about 1 mg/ml to about 15 mg/ml.