Local polymeric gel cellular therapy

• US 5,843,156 A
• Filed: 05/06/1994
• Issued: 12/01/1998
• Est. Priority Date: 08/24/1988
• Status: Expired due to Term

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Endoluminal Therapeutics Incorporated
• Inventors: Slepian, Marvin, Massia, Stephen P.
• Primary Examiner(s): BRITTINGHAM, DEBRA
• Application Number:
  US08/238,931
• Time in Patent Office: 1,670 Days
• Field of Search: 673/1, 673/11, 673/12, 673/16, 604/96
• US Class Current: 128/898
• 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 altering cellular interactions on a surface, the method comprising applying a biocompatible polymeric material to a cellular or tissue surface, wherein the polymeric material is applied in a first fluent state and converted in situ to a second non-fluent state, and wherein the material in the second non-fluent state has a controlled porosity and permeability for passage therethrough of macromolecules, microorganisms, and cells, wherein the polymeric material has incorporated therein a bioactive agent which is a modulator of cellular interactions.

2. The method of claim 1 wherein the polymeric material is capable of controlled delivery of the bioactive agent.

3. The method of claim 1 wherein the polymeric material is selected from the group consisting of biodegradable and bioerodible materials.

4. The method of claim 1 wherein the polymeric material is selected from the group consisting of an organogel and a hydrogel.

5. The method of claim 1 wherein the polymer is applied to a tissue lumen surface.

6. The method of claim 1 wherein the bioactive agent is a modulator of cell-extracellular matrix interactions.

9. The method of claim 1 wherein the bioactive agent is selected from the group consisting of chemotactic agents, haptotactic agents, and contact guidance agents.

10. The method of claim 9 wherein the haptotactic agent is an extracellular matrix protein.

11. The method of claim 9 wherein the haptotactic agent is selected from the group consisting of peptides comprising the sequence RGD and peptides comprising the sequence YIGSR.

12. The method of claim 11 wherein the haptotactic peptide is a cyclic peptide containing the RGD sequence.

13. The method of claim 12 wherein the peptide is applied in the polymeric material to a blood vessel.

14. The method of claim 11 wherein the haptotactic peptide contains the sequence YIGSR.

15. The method of claim 14 wherein the peptide is applied in the polymeric material to a blood vessel.

16. The method of claim 1, in which the bioactive agent is selected from the group of 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.

17. The method of claim 6 wherein the bioactive agent is an antiproliferative and wherein the polymeric material is applied to a cancerous area.

18. The method of claim 6 wherein the polymeric material is applied to a blood vessel to provide hemocompatibility.

19. The method of claim 18 wherein the polymer is selected from the group consisting of polyoxyalkylene polymers and copolymers, copolymers and blends of polyoxyalkylenes with poly(alpha-hydroxy acids), hydroxypropyl cellulose, purified konjac glucomannan gum, agarose, agar, furcellaran, beta-carrageenan, beta-1,3-glucans, hyaluronic acid, alginates and derivatized alginates and kappa, lambda, and iota carrageenans, heparin, carboxymethyl cellulose, cellulose sulfate, xanthan gum, pectin, chitosan, and polymers of monomers containing acrylic, allylic or vinyl groups, and dimeric or oligomeric forms of these compounds such as methylene bisacrylamide.

7. A method for altering cellular interactions, the method comprising applying a polymeric material to a substrate selected from the group consisting of a prosthesis, implant, and unstable plaque;

wherein the polymeric material is applied in a first fluent state and converted in situ to a second non-fluent state; and

wherein the material in the second non-fluent state has a controlled porosity and permeability for passage therethrough of macromolecules, microorganisms, and cells; and

wherein the polymeric material has incorporated therein a bioactive agent which is a modulator of cellular interactions.

8. The method of claim 7 wherein the polymeric material is a trophic layer on the surface.