Drug/drug delivery systems for the prevention and treatment of vascular disease

• US 20040260268A1
• Filed: 04/21/2004
• Published: 12/23/2004
• Est. Priority Date: 05/12/2000
• Status: Active Grant

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Falotico, Robert, Kopia, Gregory A., Llanos, Gerard H.
• Granted Patent: US 7,300,662 B2
• Time in Patent Office: Days
• US Class Current: 604/500
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61F 2310/0097 Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics
• 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 31/436 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 31/727 Heparin; Heparan
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• 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 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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 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

Abstract

A drug and drug delivery system may be utilized in the treatment of vascular disease. A local delivery system is coated with rapamycin or other suitable drug, agent or compound and delivered intraluminally for the treatment and prevention of neointimal hyperplasia following percutaneous transluminal coronary angiography. The local delivery of the drugs or agents provides for increased effectiveness and lower systemic toxicity.

Claims

1. A method for preventing constrictive vascular remodeling comprising a controlled delivery, by release from a stent, of a compound having anti-proliferative and anti-inflammatory properties in therapeutic dosage amounts in the range from about thirty-five micrograms per fifteen to eighteen millimeters of stent to about four hundred thirty micrograms per fifteen to eighteen millimeters of stent, the compound substantially reducing in-lesion lumen loss both proximate and distal to the stent, the compound being incorporated in a polymeric matrix comprising first and second layers wherein the compound is substantially in the first layer and the second layer acts as a diffusion barrier for the controlled release of the compound, and having a thickness in the range from about one micron to about 20 microns with the first layer having a thickness in the range from about 8 microns to about 12 microns and the second layer having a thickness in the range from about 1 micron to about 2 microns.

2. The method for preventing constrictive remodeling according to claim 1, further includes utilizing the compound to block a proliferation of fibroblasts in a vascular wall in response to injury, thereby reducing a formation of vascular scar tissue.

3. The method for preventing constrictive remodeling according to claim 2, wherein the compound comprises rapamycin.

4. The method for preventing constrictive remodeling according to claim 2, wherein the compound comprises analogs and congeners that bind a high-affinity cytosolic protein, FKBP12, and possesses pharmacologic properties equivalent to rapamycin.

5. The method for preventing constrictive remodeling according to claim 1, further includes utilizing the compound to affect a translation of certain proteins involved in a collagen formation or metabolism.

6. The method for preventing constrictive remodeling according to claim 5, wherein the compound comprises rapamycin.

7. The method for preventing constrictive remodeling according to claim 5, wherein the compound comprises analogs and congeners that bind a high-affinity cytosolic protein, FKBP12, and possesses pharmacologic properties equivalent to rapamycin.

8. A drug delivery device for treating constrictive vascular remodeling comprising:

a stent; and

a therapeutic dosage, in the range from about thirty-five micrograms per fifteen to eighteen millimeters of stent to about four hundred thirty micrograms per fifteen to eighteen millimeters of stent, of an agent having anti-proliferative and anti-inflammatory properties releasably affixed to the stent for treatment of constrictive vascular remodeling, the agent substantially reducing in-lesion lumen loss both proximal and distal to the intraluminal medical device, the agent being incorporated in a polymeric matrix comprising first and second layers, the agent is substantially in the first layer and the second layer acts as a diffusion barrier for the controlled release of the agent, the polymeric matrix having a thickness in the range from about one micron to about 20 microns.

9. The drug delivery device according to claim 8, wherein the agent blocks a proliferation of fibroblasts in a vascular wall in response to injury, thereby reducing a formation of vascular scar tissue.

10. The drug delivery device according to claim 9, wherein the agent comprises rapamycin.

11. The drug delivery device according to claim 9, wherein the agent comprises analogs and congeners that bind a high-affinity cytosolic protein, FKBP12, and possesses pharmacologic properties equivalent to rapamycin.

12. The drug delivery device according to claim 8, wherein the agent affects the translation of certain proteins involved in collagen formation or metabolism.

13. The drug delivery device according to claim 12, wherein the agent comprises rapamycin.

14. The drug delivery device according to claim 12, wherein the agent comprises analogs and congeners that bind a high-affinity cytosolic protein, FKBP12, and possesses pharmacologic properties equivalent to rapamycin.