Therapeutic inhibitor of vascular smooth muscle cells

• US 6,569,441 B2
• Filed: 11/27/2001
• Issued: 05/27/2003
• Est. Priority Date: 01/28/1993
• Status: Expired due to Fees

• Current Assignee: UAB Research Foundation (University of Alabama System)
• Original Assignee: NeoRx Corporation
• Inventors: Kunz, Lawrence L., Reno, John M.
• Primary Examiner(s): BARTS, SAMUEL A
• Application Number:
  US09/995,490
• Publication Number:
  US 20030039675A1
• Time in Patent Office: 546 Days
• Field of Search: 606/159, 606/191, 606/108, 604/890.1, 604/891.1, 604/104, 604/96.01, 604/507, 604/508, 514/411, 424/423
• US Class Current: 424/423
• CPC Class Codes: A61K 31/04 Nitro compounds
• CPC Class Codes: A61K 31/131 acyclic
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/4035 Isoindoles, e.g. phthalimide
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/51 the non-active ingredient being a modifying agent
• CPC Class Codes: A61K 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/6809 Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
• CPC Class Codes: A61K 47/6817 Toxins
• CPC Class Codes: A61K 47/6831 : Fungal toxins, e.g. alpha sarcine, mitogillin, zinniol or restrictocin
• CPC Class Codes: A61K 47/6843 : the antibody targeting a material from animals or humans
• CPC Class Codes: A61K 47/6927 : the form being a solid microparticle having no hollow or gas-filled cores
• CPC Class Codes: A61K 9/0024 : Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• 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 2300/602 : Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 : Coatings
• CPC Class Codes: A61L 31/148 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: G01N 2800/323 : Arteriosclerosis, Stenosis
• CPC Class Codes: Y10S 435/975 : Kit

Abstract

Methods are provided for inhibiting stenosis or restenosis following vascular trauma in a mammalian host, comprising administering to the host a therapeutically effective dosage of a cytostatic agent and/or cytoskeletal inhibitor so as to biologically stent the traumatized vessel. Also provided is a method to inhibit or reduce vascular remodeling following vascular trauma, comprising administering an effective amount of a cytoskeletal inhibitor. Further provided are pharmaceutical compositions and kits comprising the therapeutic agents of the invention.

Claims

1. A method of preparing a therapeutic device suitable for delivery of a therapeutic agent to a mammalian blood vessel traumatized by a surgical procedure, comprising introducing to a device an amount of a cytoskeletal inhibitor effective to inhibit or reduce stenosis or restenosis of the traumatized mammalian blood vessel following placement of the device, wherein the device comprises an artificial graft, a shunt or an adventitial wrap.

2. The method of claim 1 wherein the device is a stent overlayed with an artificial graft.

3. The method of claim 2 wherein the artificial graft comprises the cytoskeletal inhibitor.

4. The method of claim 1 wherein the device comprises a pharmaceutically acceptable release carrier matrix comprising the cytoskeletal inhibitor.

5. The method of claim 4 wherein the carrier matrix is a gel, paste or permeable membrane.

6. The method of claim 1 wherein the cytoskeletal inhibitor comprises a cytochalasin, taxol, or an analog thereof.

7. The method of claim 1 wherein the cytoskeletal inhibitor is coated on the device.

8. The method of claim 1 wherein the device is an artificial graft and wherein the cytoskeletal inhibitor is a cytochalasin or an analog thereof.

9. The method of claim 1 wherein the device is an adventitial wrap.

10. The method of claim 1 wherein the cytoskeletal inhibitor is a cytochalasin or an analog thereof.