Adhesion barriers applicable by minimally invasive surgery and methods of use thereof

• US 7,347,850 B2
• Filed: 12/13/2002
• Issued: 03/25/2008
• Est. Priority Date: 08/14/1998
• Status: Expired due to Term

• Current Assignee: Incept LLC
• Original Assignee: Incept LLC
• Inventors: Sawhney, Amarpreet S.
• Primary Examiner(s): Lucchesi; Nicholas D.
• Assistant Examiner(s): Koharski; Christopher
• Application Number:
  US10/319,308
• Publication Number:
  US 20030108511A1
• Time in Patent Office: 1,929 Days
• Field of Search: 604/191, 604/82, 604/83, 604/197, 604/240, 604/500, 604/506, 604/507, 424/78, 424/484, 424/423, 424/425, 424/426, 514/772.3
• US Class Current: 604/500
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 2017/00495 for two-component glue
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61M 25/0071 Multiple separate lumens multiple separate lumens throughout the catheter A61M25/0026
• CPC Class Codes: C08G 63/08 Lactones or lactides
• CPC Class Codes: C08G 63/912 derived from hydroxycarboxylic acids

Abstract

Biocompatible crosslinked polymers, and methods for their preparation and use with minimally invasive surgery applicators are disclosed. The disclosure includes compositions and methods for in situ formation of hydrogels using minimally invasive surgical techniques.

Claims

1. A method of coating a patient'"'"'s abdominopelvic tissue comprising:

delivering to the abdominopelvic tissue, using minimally invasive surgical techniques, a first synthetic reactive precursor species and a second reactive precursor species and

mixing the reactive precursor species to interact with each other to form a biocompatible, covalently crosslinked, synthetic hydrogel in situ within about one minute of the mixing that adheres to the abdominopelvic tissue, is hydrolytically biodegraded, and is effective in humans to reduce the risk of patient injury caused by adhesions,

wherein the first reactive precursor species comprises nucleophilic functional groups and the second reactive precursor species comprises electrophilic functional groups and the mixing of the reactive precursor species causes the electrophilic functional groups and the nucleophilic functional groups to form covalent bonds with each other to form the hydrogel wherein the hydrogel is hydrolytically biodegraded in less than about 30 days and wherein the reactive precursor species are delivered to the tissue using a spray applicator.

2. A hydrogel composition adapted for use with a tissue of a patient, the composition being made by the process of claim 1.

3. The method of claim 1 wherein the second reactive precursor species further comprises at least two polyethylene oxide repeating groups.

4. The method of claim 1 wherein the hydrogel further comprises a biologically active agent.

5. The method of claim 1 wherein the first reactive precursor species comprises between about 3 and about 8 of the nucleophilic functional groups.

6. The method of claim 1 wherein the second reactive precursor species has a molecular weight between about 5,000 and about 50,000.

7. The method of claim 1 wherein the second reactive precursor species is synthetic.

8. The method of claim 1 wherein the first reactive precursor species consists essentially of dilysine, trilysine, or tetralysine.

9. The method of claim 1 wherein the biocompatible, covalently crosslinked, synthetic hydrogel is formed within about 4 seconds.

10. The method of claim 1 wherein a concentration of the first reactive precursor species and the second reactive precursor species are combined to form a total solids concentration of solids in the hydrogel of about 8 to about 20 percent.

11. The method of claim 1 wherein the hydrolytic biodegradation occurs by degradation of esters.

12. A method of coating a patient'"'"'s abdominopelvic tissue comprising:

delivering to the abdominopelvic tissue, using minimally invasive surgical techniques, a first synthetic reactive precursor species and a second reactive precursor species and

mixing the reactive precursor species to interact with each other to form a biocompatible, covalently crosslinked, synthetic hydrogel in situ within about one minute of the mixing that adheres to the abdominopelvic tissue, is hydrolytically biodegraded, and is effective in humans to reduce the risk of patient injury caused by adhesions,

wherein the second reactive precursor species comprises electrophilic functional groups and the mixing of the reactive precursor species causes the electrophilic functional groups to react with nucleophilic functional groups in the first reactive precursor species to form covalent bonds to form the hydrogel, wherein the first reactive species consists essentially of dilysine, trilysine, tetralysine, or a combination thereof and wherein the reactive precursor species are delivered to the tissue using a spray applicator.

13. The method of claim 12 wherein the hydrogel further comprises a biologically active agent.

14. The method of claim 12 wherein the second reactive precursor species has a molecular weight between about 5,000 and about 50,000.

15. The method of claim 12 wherein the hydrogel is hydrolytically biodegraded in less than about 30 days.

16. The method of claim 12 wherein the biocompatible, covalently crosslinked, synthetic hydrogel is formed within about 4 seconds.

17. The method of claim 12 wherein a concentration of the first reactive precursor species and the second reactive precursor species are combined to form a total solids concentration of solids in the hydrogel of about 8 to about 20 percent.

18. The method of claim 12 wherein the hydrolytic biodegradation occurs by degradation of esters.