Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device

• US 7,758,881 B2
• Filed: 03/24/2005
• Issued: 07/20/2010
• Est. Priority Date: 06/30/2004
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Dugan, Stephen
• Primary Examiner(s): Azpuru; Carlos A
• Application Number:
  US11/090,507
• Publication Number:
  US 20060002977A1
• Time in Patent Office: 1,944 Days
• Field of Search: 424/1
• US Class Current: 424/423
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 31/4745 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• 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 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• 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 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• 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

Drug-delivery systems such as drug-delivery stents having an anti-proliferative agent such as everolimus and an anti-inflammatory agent such as clobetasol are provided. Also disclosed are methods of treating a vascular impairment such as restenosis or vulnerable plaque

Claims

1. A drug-delivery system, comprising:

an effective amount of an anti-proliferative agent;

a body structure of an implantable medical device; and

an effective amount of a steroidal anti-inflammatory agent or a non steroidal anti-inflammatory agent within the body structure of the device for the treatment of a vascular disorder or a related disorder;

wherein the anti-proliferative agent is everolimus and the steroidal or non-steroidal anti-inflammatory agent is clobetasol,

and wherein the ratio of the dose of everolimus to the dose of clobetasol is 1;

1 to 3;

1 on a molar basis.

2. A method of treating restenosis or vulnerable plaque of a blood vessel comprising:

administering to a patient an effective amount of an anti-proliferative agent; and

allowing an effective amount of a steroidal anti-inflammatory agent or a non steroidal anti-inflammatory agent to elute to a vessel from within a body structure of an implantable medical device, wherein the combination of the anti-proliferative and anti-inflammatory agents is for treatment of restenosis or vulnerable plaque;

wherein the anti-proliferative agent is everolimus and the steroidal or non-steroidal anti-inflammatory agent is clobetasol,

and wherein the ratio of the dose of everolimus to the dose of clobetasol is 1;

1 to 3;

1 on a molar basis.

3. A drug-delivery system, comprising:

an effective amount of everolimus;

a biodegradable body structure of an implantable medical device;

an effective amount of clobetasol mixed or dispersed within the biodegradable body structure of the implantable medical device for the treatment of a vascular disorder or a related disorder, wherein the clobetasol is released based on the degradation of the body structure in a patient;

a coating completely surrounding the exterior surface of a structural element of the biodegradable body structure, wherein the coating contains at least a portion of the everolimus;

wherein the ratio of the dose of everolimus to the dose of clobetasol is 1;

1 to 3;

1 on a molar basis.

4. A method of treating restenosis or vulnerable plaque of a blood vessel comprising:

administering to a patient an effective amount of everolimus; and

allowing an effective amount of clobetasol mixed or dispersed within a bioabsorbable polymer body structure of an implantable medical device to release to a vessel from the implantable medical device, wherein the combination of everolimus and clobetasol is for treating restenosis or vulnerable plaque,

a coating completely surrounding the exterior surface of a structural element of the bioabsorbable body structure, wherein the coating contains at least a portion of the everolimus which is administered by eluting from the coating; and

wherein the ratio of the dose of everolimus to the dose of clobetasol is 1;

1 to 3;

1 on a molar basis.