FIELD

The present invention relates to matrices. More specifically, the present invention is, in aspects, concerned with foamed matrices, and related compositions, methods of making and using same.

BACKGROUND

Gelatin- and collagen-based materials have hemostatic ability and as such, gelatin and collagen sponges have been used as effective tools to control wound bleeds. Typically, gelatin-based materials are stabilized in some way so that they are durable when applied to human skin or tissue. Methods of stabilizing gelatin-based materials include chemical treatments, heat treatments and crosslinking methods.

U.S. Pat. No. 2,465,357 describes a liquid-permeable, water-insoluble, gelatin sponge having the general physical characteristics of a sponge but being absorbable by animal bodies.

U.S. Pat. No. 4,703,108 describes a process for preparing biodegradable collagen-based matrices in sponge or sheet form wherein a collagen-based material is freeze dried to form a collagen-based sponge which is contacted with a cross-linking agent to form an intermediate collagen-based matrix which is subsequently subjected to conditions of severe dehydration to form the collagen-based matrix in sponge or sheet form.

U.S. Pat. No. 8,361,501 describes 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). Methods for making the non-adhesive elastic gelatin matrix are also described.

There is a need for alternative matrices and compositions to overcome or mitigate at least some of the deficiencies of the prior art, or to provide a useful alternative.

SUMMARY

In accordance with an aspect, there is provided a matrix comprising: a biomolecule; wherein the matrix is a dried, cross-linked foam.

In aspects, the matrix is non-lyophilized.

In aspects, the biomolecule is selected from the group consisting of gelatin, collagen, elastin, and combinations thereof.

In aspects, the biomolecule is present at about 40% to about 80% (w/w).

In aspects, the matrix described herein further comprises at least two layers.

In aspects, the at least two layers are substantially identical with respect to the biomolecule content and/or an amount of crosslinking relative to an adjacent foam layer.

In aspects, the at least two layers are different with respect to the biomolecule content and/or an amount of crosslinking relative to an adjacent foam layer.

In aspects, the matrix is free of a hardened “skin” and/or a compacted “skin” on a surface of the matrix.

In aspects, the matrix described herein further comprises at least one biocompatible polymer.

In aspects, the biocompatible polymer is selected from the group consisting of polyethylene glycol, poly-L-lysine, alginate, chitosan, hyaluronic acid, chondroitin sulfate, pectin, cellulose, carboxymethylcellulose and mixtures thereof.

In aspects, the biocompatible polymer is present in about 0.4% to about 25% (w/w).

In aspects, the matrix has a pore size ranging from about 100 μm to about 750 μm.

In aspects, the matrix has an absorption capacity of about 20 times to about 50 times a dry weight of the dried, crosslinked foam matrix.

In aspects, the matrix has a thickness of at least 1 mm.

In aspects, the matrix further comprises an active agent.

In aspects, the active agent is selected from the group consisting of an antimicrobial agent, an analgesic agent, an anti-adhesion compound, an anti-tumor drug, an anti-proliferative drug, a chelator and combinations thereof.

In aspects, the antimicrobial agent is selected from the group consisting of chlorhexidine, octenidine, benzalkonium chloride, benzethonium chloride, polyhexamethylene biguanide, copper, zinc, silver, chlorine, an active chlorine compound, fluoroquinolones, b-lactams, macrolides, aminoglycosides, tetracyclines, and combinations thereof.

In aspects, the antimicrobial agent comprises silver ions.

In aspects, the silver ions are derived from a silver salt selected from the group consisting of silver phosphate, silver sulfate, silver citrate, silver lactate, silver acetate, silver benzoate, silver chloride, silver carbonate, silver iodide, silver iodate, silver nitrate, silver laurate, silver sulfadiazine, silver palmitate, and mixtures thereof.

In aspects, the active agent is present at about 0.1% to 30% (w/w).

In aspects, the active agent is present in and/or on one of the at least two layers.

In aspects, the active agent is present in and/or on both of the at least two layers.

In aspects, the active agent, the biomolecule and/or the biocompatible polymer is evenly distributed through and/or on both of the at least two layers.

In aspects, the active agent, the biomolecule and/or the biocompatible polymer is non-uniformly distributed through and/or on both of the at least two layers.

In aspects, the matrix is cross-linked using a crosslinking agent.

In aspects, the crosslinking agent is selected from the group consisting of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), N-hydroxysuccinimide (NHS) and mixtures thereof.

In aspects, the crosslinking agent is present in about 0.5% to about 5% (w/w).

In aspects, the matrix is fabricated as a covering.

In aspects, the covering is selected from the group consisting of a wound barrier, a wound dressing, a hemostatic dressing, a vascular wrap, a sponge, a gauze, a bandage, a film, a sheet, a tube and combinations thereof.

In aspects, the matrix is for use as a wound barrier, a wound dressing, a hemostatic dressing, a vascular wrap, a sponge, a gauze, a bandage, a film, a sheet, a tube and combinations thereof.

In aspects, the matrix is for use in delivery of an active agent to a surface.

In aspects, the matrix is for use in treating in a wound.

In accordance with another aspect, there is provided a composition for forming a foamed, cross-linked and non-lyophilized matrix, the composition comprising: a biomolecule, wherein the composition is foamable and the biomolecule is crosslinkable.

In aspects, the composition described herein further comprises a pharmaceutically acceptable excipient.

In aspects, the pharmaceutically acceptable excipient is selected from the group consisting of a diluent, a disintegrant, a glidant, a binder, a lubricant, an antioxidant, a preservative, a coloring agent, a flavoring agent, an emulsifying agent, a suspending agent, a pharmaceutical solvent and combinations thereof.

In aspects, the biomolecule is selected from the group consisting of gelatin, collagen, elastin, and combinations thereof.

In aspects, the biomolecule is present at about 40% to about 80% (w/w).

In aspects, the composition described herein further comprises an active agent.

In aspects, the active agent is selected from the group consisting of an antimicrobial agent, an analgesic agent, an anti-adhesion compound, an anti-tumor drug, an anti-proliferative drug, a chelator and combinations thereof.

In aspects, the antimicrobial agent is selected from the group consisting of chlorhexidine, octenidine, benzalkonium chloride, benzethonium chloride, polyhexamethylene biguanide, copper, zinc, silver, chlorine, an active chlorine compound, fluoroquinolones, b-lactams, macrolides, aminoglycosides, tetracyclines, and combinations thereof.

In aspects, the antimicrobial agent comprises silver ions.

In aspects, the silver ions are derived from a silver salt selected from the group consisting of silver phosphate, silver sulfate, silver citrate, silver lactate, silver acetate, silver benzoate, silver chloride, silver carbonate, silver iodide, silver iodate, silver nitrate, silver laurate, silver sulfadiazine, silver palmitate, and mixtures thereof.

In aspects, the active agent is present at about 0.1% to 30% (w/w).

In aspects, the composition further comprises a crosslinking agent.

In aspects, the crosslinking agent is selected from the group consisting of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), N-hydroxysuccinimide (NHS) and mixtures thereof.

In aspects, the crosslinking agent is present in about 0.5% to about 5% (w/w).

In aspects, the composition further comprises at least one biocompatible polymer.

In aspects, the biocompatible polymer is selected from the group consisting of polyethylene glycol, poly-L-lysine, alginate, chitosan, hyaluronic acid, chondroitin sulfate, pectin, cellulose, carboxymethyl cellulose and mixtures thereof.

In aspects, the biocompatible polymer is present in about 0.4% to about 25% (w/w).

In accordance with another aspect, there is provided a use of the matrix described herein for reducing microorganism growth on a surface.

In aspects, the microorganism is selected from the group consisting ofCandida albicans, Escherichia coli, and antibiotic-resistantEnterococcus.

In aspects, the surface is skin or a medical device.

In accordance with another aspect, there is provided a use of the matrix described herein as a wound dressing, a bandage, or a sponge.

In accordance with yet another aspect, there is provided a use of the composition described herein for forming a foamed, crosslinked, non-lyophilized matrix for reducing microorganism growth on a surface.

In aspects, the microorganism is selected from the group consisting ofCandida albicans, Escherichia coli, and antibiotic-resistantEnterococcus.

In aspects, the surface is skin or a medical device.

In accordance with yet another aspect, there is provided a method of treating a wound comprising applying the matrix described herein to the wound.

In accordance with a further aspect, there is provided a use of the matrix described herein to treat a wound.

In accordance with still a further aspect, there is provided a method for making a matrix comprising: foaming a composition comprising a biomolecule; crosslinking the composition; and drying the composition.

In aspects, the composition described herein further comprises a pharmaceutically acceptable excipient.

In aspects, the pharmaceutically acceptable excipient is selected from the group consisting of a diluent, a disintegrant, a glidant, a binder, a lubricant, an antioxidant, a preservative, a coloring agent, a flavoring agent, an emulsifying agent, a suspending agent, a pharmaceutical solvent and combinations thereof.

In aspects, the biomolecule is selected from the group consisting of gelatin, elastin, collagen, and combinations thereof.

In aspects, the crosslinking is carried out after foaming.

In aspects, the crosslinking is carried out while foaming.

In aspects, the crosslinking comprises adding a crosslinking agent.

In aspects, the crosslinking agent is selected from the group consisting of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), N-hydroxysuccinimide (NHS) and mixtures thereof.

In aspects, the adding is done in a dropwise manner.

In aspects, the composition described herein further comprises at least one biocompatible polymer.

In aspects, the at least one biocompatible polymer is selected from the group consisting of polyethylene glycol, poly-L-lysine, alginate, chitosan, hyaluronic acid, chondroitin sulfate, pectin, cellulose, carboxymethylcellulose and mixtures thereof.

In aspects, the composition described herein further comprises an active agent.

In aspects, the active agent does not substantially affect the foaming.

In aspects, the method described herein further comprises layering an active agent onto the matrix.

In aspects, the active agent is in a powdered or concentrated liquid form.

In aspects, the active agent is selected from the group consisting of an antimicrobial agent, an analgesic agent, an anti-adhesion compound, an anti-tumor drug, an anti-proliferative drug, a chelator and combinations thereof.

In aspects, the antimicrobial agent is selected from the group consisting of chlorhexidine, octenidine, benzalkonium chloride, benzethonium chloride, an active chlorine compound, polyhexamethylene biguanide, copper, zinc, silver, chlorine, fluoroquinolones, b-lactams, macrolides, aminoglycosides, tetracyclines, and combinations thereof.

In aspects, the antimicrobial agent comprises silver ions.

In aspects, the silver ions are derived from a silver salt selected from the group consisting of silver phosphate, silver sulfate, silver citrate, silver lactate, silver acetate, silver benzoate, silver chloride, silver carbonate, silver iodide, silver iodate, silver nitrate, silver laurate, silver sulfadiazine, silver palmitate, and mixtures thereof.

In aspects, the method described herein further comprises heating the composition.

In aspects, the heating is carried out prior to foaming.

In aspects, the heating takes place at about 50° C.

In aspects, the method described herein further comprises cooling the composition.

In aspects, the cooling is carried out prior to foaming.

In aspects, the cooling takes place at about 25° C. to about 28° C.

In aspects, the cooling takes place at about 26° C.

In aspects, the cooling is carried out with continuous stirring of the composition.

In aspects, the method described herein further comprises transferring the matrix to a tray or mold.

In aspects, the transferring is carried out prior to drying.

In aspects, the tray or mold is lined with a hydrophobic film.

In aspects, the transferring step comprises spreading the matrix in the tray or mold.

In aspects, the drying step comprises air-drying.

In aspects, the air-drying is carried out at ambient pressure and temperature.

In aspects, the air-drying is carried out at about 40° C.

In aspects, the drying ensures efficient air circulation around the matrix.

In aspects, the drying is up to 48 hours.

In aspects, the drying is not freeze drying.

In aspects, the matrix is free of a hardened skin and/or a compacted skin on a surface of the matrix.

In accordance with still yet another aspect, there is provided a wound dressing comprising the matrix described herein.

In accordance with still yet another aspect, there is provided a matrix made by the method described herein.

Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from said detailed description.

