Non-adhesive elastic gelatin matrices

Inventors

DiTizio, ValerioDiCosmo, FrankXiao, Yuehua

Assignees

Covalon Technologies Ltd

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Publication Number

US-8361501-B2

Patent

Publication Date

2013-01-29

Expiration Date


Abstract

The present invention is a substantially non-adhesive elastic gelatin matrix. The matrix is both non-adhesive to wounds, tissues and organs and is also elastic such that it is flexible. The matrix is a lyophilized mixture of protein(s), polymer(s), cross-linking agent(s) and optional plasticizer(s). The invention also provides methods for making the non-adhesive elastic gelatin matrix.

Core Innovation

The invention provides an elastic non-adhesive protein matrix comprising about 50-90% by wgt of one or more proteins selected from collagen and denatured collagen and mixtures thereof, about 10-40% by wgt of one or more biocompatible polymers selected from polyetheylene glycol, poly-L-lysine, alginate, chitosan, hyaluronic acid, and chondroitin sulfate and mixtures thereof, and about 0.5-5% by wgt of diglycidyl ether.

The matrix is lyophilized after addition of diglycidyl ether to result in a matrix that is non-adherent to wounds tissues, and organs and can be removed after 24 hours. The lyophilized matrix maintains an elastic, non-adhesive character associated with the defined collagen/biocompatible polymer composition and diglycidyl ether content.

Methods are provided for making a non-adhesive elastic protein matrix by mixing collagen and/or denatured collagen in a solution and heating, adding selected biocompatible polymers, and adding selected cross-linking agents under conditions that induce protein cross-linking while maintaining a solution. The process forms a pourable gel, then cools the gel, and lyophilizes the cooled gel to form the non-adhesive elastic protein matrix.

Claims Coverage

The independent claims define 2 main inventive features: an elastic non-adhesive lyophilized protein matrix composition, and methods for making such a matrix with specified component sets, cross-linking agents, gel formation, cooling, and lyophilization.

Elastic non-adhesive lyophilized protein matrix with collagen, biocompatible polymers and diglycidyl ether

An elastic non-adhesive protein matrix comprising about 50-90% by wgt of one or more proteins selected from collagen and denatured collagen and mixtures thereof; about 10-40% by wgt of one or more biocompatible polymers selected from polyetheylene glycol, poly-L-lysine, alginate, chitosan, hyaluronic acid, and chondroitin sulfate and mixtures thereof; and about 0.5-5% by wgt of diglycidyl ether, wherein the matrix is lyophilized after addition of diglycidyl ether to result in a matrix that is non-adherent to wounds tissues, and organs and can be removed after 24 hours.

Method producing a non-adhesive elastic lyophilized protein matrix removable after 24 hours

A method for making a non-adhesive elastic protein matrix comprising mixing collagen, denatured collagen, or a combination thereof in a solution and heating said solution; adding polyethylene glycol, poly-L-lysine, alginate, chitosan, hyaluronic acid, or chondroitin sulfate or any combination thereof; adding cross-linking agents including EDC, NHS, formaldehyde, glutaraldehyde, a polyaziridine, or a diglycidyl ether or any combination thereof under conditions that induce protein cross-linking while maintaining a solution; forming a pourable gel; cooling the gel; and lyophilizing the cooled gel to form the non-adhesive elastic protein matrix removable after 24 hours.

Method with specified component percentages and lyophilization for a removable non-adhesive elastic matrix

A method for making a non-adhesive elastic protein matrix comprising mixing collagen or denatured collagen, one or more biocompatible polymers, one or more cross-linking agents, solvent, and optionally plasticizer until a pourable gel is formed; cooling the gel; and lyophilizing the cooled gel to form the non-adhesive elastic protein matrix that is removable after 24 hours.

Overall, the independent claims cover an elastic, non-adhesive, lyophilized protein matrix built from collagen or denatured collagen with defined biocompatible polymer fractions and specified cross-linking agents, including diglycidyl ether, and methods that use mixing, heating, gel formation, cooling, and lyophilization to produce the matrix.

Stated Advantages

The matrix is non-adherent to wounds tissues and organs.

The matrix can be removed after 24 hours.

The matrix is elastic.

Documented Applications

Wound barriers, dressings, wraps, and vascular coverings for wounds involving wounds tissues and organs.

Drug loading and release from gelatin wraps, including pharmaceuticals and agents such as sirolimus (rapamycin).

Evaluation of biodegradation, water uptake, solubility/stability for removability, mechanical properties, and drug release.

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