Local polymeric gel cellular therapy

• US 6,290,729 B1
• Filed: 12/03/1997
• Issued: 09/18/2001
• Est. Priority Date: 03/25/1992
• Status: Expired due to Fees

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Endoluminal Therapeutics Incorporated
• Inventors: Massia, Stephen P., Slepian, Marvin J.
• Primary Examiner(s): Milano, Michael J.
• Application Number:
  US08/984,614
• Time in Patent Office: 1,385 Days
• Field of Search: 623/1, 623/11, 623/12, 623/66, 623/11.11, 623/16.11, 623/23.72, 623/23.73, 623/23.76, 600/36, 604/36, 604/48, 604/52, 604/82, 604/83, 604/96, 604/890.1, 604/891.1, 606/194, 606/195, 424/422, 424/423-426, 424/486
• US Class Current: 623/23.72
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/062 Apparatus for the production of blood vessels made from natural tissue or with layers of living cells prostheses made from natural tissue or living cells A61L27/507
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/88 the wire-like elements formed as helical or spiral coils forming a net-like or mesh-like structure A61F2/90
• CPC Class Codes: A61F 2/95 Instruments specially adapted for placement or removal of stents or stent-grafts
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/40 characterised by a specific therapeutic activity or mode of action
• 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 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 24/06 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043, A61L24/046 take precedence
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61L 31/145 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/1052 : for temporarily occluding a vessel for isolating a sector
• CPC Class Codes: A61M 2025/1095 : with perfusion means for enabling blood circulation while the balloon is in an inflated state or in a deflated state, e.g. permanent by-pass within catheter shaft
• CPC Class Codes: A61M 25/0043 : characterised by structural features
• CPC Class Codes: A61M 25/1011 : Multiple balloon catheters
• CPC Class Codes: A61M 25/104 : used for angioplasty
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: Y10S 623/916 : Blood vessel

Abstract

A method for providing a synthetic barrier made of biocompatible polymeric materials in vivo which involves application of a material to a tissue or cellular surface such as the interior surface of a blood vessel, tissue lumen or other hollow space, is disclosed herein. The material may also be applied to tissue contacting surfaces of implantable medical devices. The polymeric materials are characterized by a fluent state which allows application to and, preferably adhesion to, tissue lumen surfaces, which can be increased or altered to a second less fluent state in situ; controlled permeability and degradability; and, in the preferred embodiments, incorporation of bioactive materials for release in vivo, either to the tissue lumen surface or to the interior of the lumen, which alter cell to cell interactions.

Claims

1. A method for controlling tissue repair or ingrowth comprising applying a polymeric material, at a site where tissue growth may occur, wherein the polymeric material is applied in a first fluent state and converted in situ to a second non-fluent state, wherein the material includes a modulator of local cellular interaction, in combination with cells incorporated into the polymeric material as a suspension which forms a gel at the site where the polymeric material is applied.

2. The method of claim 1 wherein the polymeric material is applied adjacent to injured organs to enhance organ regrowth after disease or surgery.

3. The method of claim 1 wherein the cells are of the same type of cells as are present in the tissue at the site where the polymeric material is applied.

4. The method of claim 1 wherein the chemotactic factor is selected from the group consisting of PDGF, extracellular matrix proteins, heparin, macrophage chemotactic factor, basic FGF, EGF, and tumor angiogenesis factor.

5. The method of claim 1 for treating a patient with unstable angina, myocardial infarction, or during or post thrombolytic therapy comprising coating or stabilizing an unstable plaque.

6. The method of claim 1 for treating a patient with abrupt reclosure, thrombotic closure, threatened closure, dissection, perforation, or suboptimal angioplasty result, comprising coating or stabilizing a damaged portion of arterial surface.

7. The method of claim 1 for stabilizing or regressing an atherosclerotic plaque comprising coating the plaque with the polymeric material.

8. The method of claim 1 further comprising incorporating into the polymeric material chelator or ion exchange to remove calcium ions or lipids.

9. The method of claim 1 further comprising providing a compound selected from the group consisting of growth factors, antibiotics, antivirals, antiinflammatories, antineoplastics, anti-spasmodics, anticoagulants, nucleotide molecules, and vasodilating agents.

10. The method of claim 9 wherein the compound is selected from the group consisting of macrophage chemotactic factor, basic transformation growth factor, tumor angiogenesis factor, fibroblast growth factor and epidermal growth factor, insulin-like growth factor, platelet derived growth factor, and interleukins.

11. The method of claim 1 wherein the polymeric material is applied to a device selected from the group consisting of a prosthesis, stent, catheter, graft and implant.

12. The method of claim 1 wherein the modulator of local cellular interaction is selected from the group consisting of antiangiogenic factors, anitiproliferative factors, antisecretory factors, and haptotactic factors.

13. A kit for controlling tissue repair or ingrowth comprising:

a polymeric material that is in a first fluent state and can be converted in situ to a second non-fluent state, including at least one modulator of local cellular interaction selected from the group consisting of chemotactic factors, antiangiogenic factors, antiproliferative factors, antisecretory factors, and haptotactic factors;

cells incorporated into the polymeric material as a suspension which forms a gel at the site where the polymeric material is applied; and

a catheter for application of the polymeric material in a first fluid state at a site where tissue growth may occur.

14. The kit of claim 13 further comprising providing a compound selected from the group consisting of growth factors, antibiotics, antivirals, antiinflammatories, antineoplastics, anti-spasmodics, anticoagulants, nucleotide molecules, and vasodilating agents.