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Compositions and methods for inhibiting adhesions

A composition and group technology, applied in botanical equipment and methods, pharmaceutical formulations, animal repellants, etc., can solve problems such as adhesion, insufficient flexibility, and incompatibility of laparoscopic procedures

Inactive Publication Date: 2009-06-03
MASSACHUSETTS INST OF TECH +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Prepared solid formulations of HA in the form of flakes, for example, alone or in combination with other materials, have deficiencies including: Difficulty applying the film (e.g. difficult to handle, sticking of dry film to gloves, insufficient flexibility, need to remove ), incompatibility with laparoscopic procedures and less than desired efficacy

Method used

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  • Compositions and methods for inhibiting adhesions
  • Compositions and methods for inhibiting adhesions
  • Compositions and methods for inhibiting adhesions

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0256] Example 1: Preparation and Characterization of Hyaluronic Acid Derivatives and Crosslinked Hydrogels

[0257] Materials and Methods

[0258] Hyaluronic acid: Hyaluronic acid (HA, nominally 1.36 MD: high MW and 490 kD: medium MW) was purchased from Genzyme Corporation (Cambridge, MA). HA (nominal 50 kD: low MW) was purchased from Lifecore Biomedical, Inc. (Chaska, MN). All other reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA).

[0259] Preparation of crosslinkable hyaluronic acid: In situ crosslinkable HA derivatives were synthesized following previously reported methods (JiaX, Colombo G, Padera R, Lang Langer R, Kohane DS. Prolongation of sciatic nerve blockade by in situ cross-linked hyaluronic acid. (Biomaterials) 2004; 25(19):4797-4804, which is incorporated herein by reference). Briefly, by reacting HA (medium MW unless otherwise stated) with a 30-fold molar excess of adipate dihydrazide in the presence of 1-ethyl-3-carbodioxide at pH 6.8 and r...

example 2

[0272] Example 2: Biocompatibility of HAX hydrogels in vitro

[0273] Materials and Methods

[0274] In vitro cell viability analysis: Human mesothelial cells (ATCC, CRL-9444) were cultured in a medium containing Earle's salt, L-glutamine and 2.2g / L sodium bicarbonate supplemented with 3.3nM In medium 199 of epidermal growth factor, 400 nM hydrocortisone, 870 nM insulin, 20 mM HEPES and 10% fetal bovine serum. Cells from passage 5 to passage 25 were used in the following studies. Mesothelial cells were seeded at a density of 50,000 cells per well in 1 ml of medium in 24-well culture plates. After overnight incubation, the medium was replaced with fresh medium or fresh medium with 10 U / ml hyaluronidase, and 100 μl of cylindrical (diameter: 5 mm, height: 5.1 mm) HAX gel (20 mg / ml) was aseptically prepared. ml) and added to each well. Cell viability was assessed using the MTT assay kit (Promega CellTiter 96 Non-Radioactive Cell Proliferation Assay) after incubation in the p...

example 3

[0277] Example 3: Prevention of peritoneal adhesions by in situ cross-linking of HAX gels

[0278] Materials and Methods

[0279] In vivo administration of HAX gel was performed according to protocols approved by the Massachusetts Institute of Technology Committee on Animal Care, following NIH guidance on the care and use of laboratory animals (NIH Bulletin #85-23, revised 1985 ) care for animals. Female albino rabbits (Oryctolagus cuniculus; New Zealand White, Covance, Hazleton, PA) (3±0.5 kg) were used as model animals . Anesthesia was induced with Ketamine (35 mg / kg, intramuscular) and Xylazine (5 mg / kg, intramuscular); with 1-3% isoflurane in oxygen administered via an endotracheal tube Alkanes (isoflurane) to achieve maintenance. Use aseptic technique throughout the procedure. Animals were given lactated Ringer's solution throughout the procedure and vital signs were continuously monitored. A 10 cm long midline incision was made along the linea alba on the abdomin...

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Abstract

The present invention provides compositions and methods for inhibiting adhesions. The methods involve administering solutions containing hydrogel precursors such as polysaccharide derivatives, e.g., derivatives of hyaluronic acid, cellulose, or dextran, to a subject at a site where adhesions may form, e.g., as a consequence of surgery, injury, or infection. The hydrogel precursors, e.g., polysaccharide derivatives, become crosslinked following their administration to form a hydrogel that maintains tissue separation. In certain embodiments of the invention one or both solutions contains particles, e.g., polymeric nanoparticles or microparticles, so that a composite hydrogel containing the particles is formed. The solution(s), particle(s), or both, may contain a biologically active agent such as an agent that contributes to inhibiting adhesions. The biologically active agent may be covalently attached to a hydrogel precursor.

Description

[0001] Related applications [0002] This application asserts U.S. provisional patent applications U.S.S.N. 60 / 791,362 filed April 12, 2006, U.S.S.N. 60 / 857,557 filed November 8, 2006, and February 13, 2007 under 35 U.S.C. Priority of U.S.S.N. 60 / 901,241, all of which are incorporated herein by reference. [0003] governmental support [0004] Work described herein was supported in part by a National Institutes of Health grant (GM073626). The US Government may have certain rights in this invention. technical field [0005] none Background technique [0006] Adhesions are connections between tissues, organs or other anatomical structures that are normally separated from each other. It is usually composed of fibrous bands of scar-like tissue and usually occurs after an irritant such as surgery, injury, or infection. Postoperative adhesions are a common and potentially serious event as they are associated with serious complications such as abdominal and pelvic pain, inf...

Claims

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Application Information

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IPC IPC(8): A61F13/00A61F2/00A01N43/04A61K31/715
Inventor 杨允伊都田一罗伯特·S·兰格丹尼尔·S·柯哈内乔治·凯沃尔克·科多基安
Owner MASSACHUSETTS INST OF TECH
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