Solution formulations of sirolimus and its analogs for CAD treatment

• US 7,846,940 B2
• Filed: 03/31/2004
• Issued: 12/07/2010
• Est. Priority Date: 03/31/2004
• Status: Active Grant

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Zhao, Jonathon Z., Falotico, Robert
• Primary Examiner(s): Kim; Jennifer M
• Application Number:
  US10/813,965
• Publication Number:
  US 20050222191A1
• Time in Patent Office: 2,442 Days
• Field of Search: 514/183, 514/291
• US Class Current: 514/291
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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 9/12 Antihypertensives
• 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. 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.

Claims

1. An aqueous formulation of a therapeutic agent comprising:

rapamycin in a pharmaceutically effective dosage;

ethanol in a residual concentration of about 1.57 percent by weight;

vitamin E TPGS in an amount of about 6.55 percent by weight; and

water in an amount of about 90.51 percent by weight, the rapamycin, vitamin E TPGS and water forming a stable aqueous solution, thereby remaining a solution without precipitation, the stable aqueous formulation comprising a final solution of rapamycin in the range from about 4 mg/ml to about 15 mg/ml.

2. The aqueous formulation according to claim 1, wherein the rapamycin is sirolimus.

3. The aqueous formulation according to claim 1, wherein the rapamycin is CCI-779.