US20140287061A1 - In-situ cross-linkable polymeric compositions and methods thereof - Google Patents

In-situ cross-linkable polymeric compositions and methods thereof Download PDF

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US20140287061A1
US20140287061A1 US14/357,342 US201214357342A US2014287061A1 US 20140287061 A1 US20140287061 A1 US 20140287061A1 US 201214357342 A US201214357342 A US 201214357342A US 2014287061 A1 US2014287061 A1 US 2014287061A1
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polymer
polymeric composition
weight
biocompatible polymeric
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Joseph A. Landolina
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Cresilon Inc
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Suneris Inc
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Assigned to Suneris, Inc. reassignment Suneris, Inc. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LANDOLINA, JOSEPH A.
Publication of US20140287061A1 publication Critical patent/US20140287061A1/en
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Assigned to CRESILON, INC. reassignment CRESILON, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: Suneris, Inc.
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0052Mixtures of macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001Use of materials characterised by their function or physical properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0014Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/0066Medicaments; Biocides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08FMACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F283/00Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/04Alginic acid; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding

Definitions

  • the present invention relates generally to a composition using a biocompatible polymeric formulation and, in particular, to a hemophilic polymeric matrix for use in wound healing, blood coagulation, and cosmetic use.
  • Wound healing is an intricate, orchestrated process involving the interactions of various cells and matrix components to first establish a provisional tissue and then remodel this while forming the mature replacement.
  • the hemostatic platelet plug reestablishes the infection-limiting and desiccation-limiting barrier, and elicits the first wave of cellular infiltrates.
  • This consists mainly of leukocytes that provide both innate and acquired immunity. These cells produce enzymes and biocidal molecules to eliminate microbial contamination; however, these same defense mechanisms are detrimental to the keratinocytes, fibroblasts and endothelial cells required to regenerate the lost tissue.
  • the events and processes of the inflammatory phase need to regress.
  • a particular challenge is offered in the case of skin wound repair, which occurs at a contaminated surface. If a wound becomes infected, the normal healing is disrupted as the inflammatory phase becomes chronic, suppressing the regenerative phase. Further, the enzymes liberated by both the microbes and leukocytes break down the wound tissue as well as surrounding skin. Thus, it is critical to ensure proper healing to prevent infections being established by normal skin wound contaminants.
  • Fibronectin has been reported to be involved in each stage of the wound healing process, particularly by creating a scaffold to which the invading cells will adhere. Initially, there is a release of many mediators to the wound site, such as fibronectin and fibrinogen. Fibronectin promotes inflammatory cell migration into the wound and debris phagocytosis by monocytes. Thereafter, angiogenesis and reepithelialization take place. At this stage, fibronectin exerts chemotactic activity on endothelial cells, and promotes epithelial cell and fibroblast migration onto the basal membrane. Fibronectin also appears to be essential in the remodeling phase where it plays a major role in the organization of collagen fibrils. The fibrillar collagen ultimately forms fibrous bundles that enhance the tissue tensile strength, leading to would closure.
  • Hydrogels have typically been utilized as topical formulations for promoting the wound healing process.
  • the gel compositions have been selected for their properties of swelling degree, biocompatibility, permeability, and swelling kinetics. Examples of such compounds have included vinyl polymers (e.g. polyacrylic acid), cellulose, and cellulose derivatives.
  • vinyl polymers e.g. polyacrylic acid
  • cellulose e.g. cellulose
  • cellulose derivatives e.g. polyacrylic acid
  • Polyacrylic acid polymer also referred to as carbomer, has been used because of its superiority in delivering fibronectin to skin wounds.
  • Naturally occurring biopolymers have applications in tissue engineering, regenerative medicine, drug delivery, medical implant, plastic surgery, and others.
  • Such products have components including hyaluronic acid (HA), chitosan, heparin, chondroitin sulfate, alginate and other glucosamine and glycosaminoglycans, other polysaccharides, and derivatives thereof.
  • HA hyaluronic acid
  • chitosan chitosan
  • heparin chondroitin sulfate
  • alginate and other glucosamine and glycosaminoglycans other polysaccharides, and derivatives thereof.
  • fibronectin and similar proteins
  • alginate salt concentrations of fibronectin (and similar proteins) have been utilized with alginate salt to treat chronic ulcers.
  • the dressing system has been solidified, converting the gel into fibers, by a process of freeze-drying. This procedure creates a sponge-like structure with hydrophilic properties.
  • the dressings can return to a gel-like state, absorbing up to 20 times their weight in wound exudate.
  • the dressing is easily removed after the wound treatment because of its sponge-like structure and moisture retention.
  • the fibronectin-cellulose dressing does not provide the desired fibrous protective film on the surface of the deepithelialized human skin. Debridement is then performed upon removal of the dressing to remove any necrotic material.
  • Chronic wounds which would assist healing, decrease inflammation, reduce pain, and prevent scar formation with both acute and chronic wounds.
  • acute wounds that could be treated include burns, abrasions, dry skin, post-op surgical incisions, cuts, puncture wounds, blisters, insect bites, and other severe tissue injury.
  • Chronic wound treatment might encompass slow to heal wounds including pressure ulcers, venous ulcers, diabetic foot ulcers, decubitus ulcers, and non-healing tissue injuries.
  • composition that will be easily applied, forming a matrix conducive to the healing of a tissue, and having anti-microbial properties.
  • the composition may be biocompatible or quickly reacted to avoid possibilities of cytotoxicity. Further, the composition will stimulate and maximize wound healing while providing a controlled method for providing thin and thick layers of a solidified wound dressing, as desired.
  • Indirect effects may include reduced need for medical procedures such as debridement, decreased hospitalization time, reduced postoperative recovery times, shortened return interval to daily functions and work, and reduced overall treatment costs. Desirably, these improvements to wound healing, including application and method of use, will be valuable in treating and repairing various tissue(s).
  • the following invention is a biocompatible polymeric composition that is a gelatinous wound healing and hemostatic matrix able to be formed and solidified both internally and externally.
  • the biocompatible polymeric composition comprises 1) one or more than one polyanionic polymer and 2) one or more than one polycationic polymer.
  • the one or more than one polyanionic polymer includes at least one cross-linkable polyanionic polymer.
  • the one or more than one polyanionic polymer includes at least one cross-linkable polyanionic polymer and at least one non-cross-linkable polyanionic polymer.
  • the biocompatible polymeric composition comprises a mixture of 1) one or more than one polyanionic polymer able to be formed on the surface of a wound and 2) one or more than one polycationic polymer that assists in the solidification process as well as speeds up blood clotting.
  • the biocompatible polymeric composition comprises a mixture of 1) one or more than one polyanionic polymer able to be formed on the surface of a wound; 2) one or more than one polycationic polymer that assists in the solidification process as well as speeds up blood clotting; and 3) a cross-linking mist that cross-links the gel in the wound while disinfecting the surrounding area.
  • the one or more than one polyanionic polymer comprises alginates or hyaluronates. In one embodiment of the invention, the one or more than one polycationic polymer comprises chitosan. In one embodiment of the invention, the cross-linking mist may be aqueous calcium chloride.
  • One or more methods of using the medical gel of the invention are also disclosed, including rapidly achieving hemostasis without the need to apply pressure, and providing a biocompatible wound healing matrix.
  • Various embodiments of the invention allow the formulation to be adjusted and implemented for varying the desired viscosity and pre-determined characteristic functions.
  • the ratio of the polycationic polymer to the polyanionic polymer may be improved, having varying degrees of efficiency in wound healing.
  • therapeutics can be added to integrate drug formulations for drug delivery options.
  • other features may encompass controlling temperature(s) and/or pressure(s) during the preparation of the medical gel, during application of the gel, and implementing a control for the elasticity or rigidity of the solidified matrix.
  • the matrix formulation, both liquid and solidified structures, may also be dependent on anatomical and physiological measurements and conditions.
  • compositions allow the composition to be adjusted and implemented at a first tissue site or a second tissue site, and such modification deemed obvious may be integrated and combined in varying quantities to provide for a structural matrix of any size, shape, and configuration.
  • FIG. 1 is a side view of an embodiment of the present invention.
  • FIG. 2 is a microscopic depiction of how the present invention interacts with blood and itself.
  • FIGS. 3A to 3I show various polymeric subunits that can be used to make up the polycationic or polyanionic polymers.
  • FIG. 4 shows the benefits of the present invention as compared to existing technology.
  • Biocompatible polymeric compositions of the present invention may be used to treat external wounds as well as internal wounds.
  • the biocompatible polymeric composition may be applied to a variety of wounds.
  • wounds include, but are not limited to: an external laceration, an abrasion, a burn, an ocular laceration, damage to a parenchymal organ, an internal laceration, a laceration in the gastrointestinal tract, superficial cuts and scrapes, internal bleeding, an arterial bleed, a venous bleed, dental or oral bleeds and incisions.
  • Subjects who can benefit from such wound treatment include a variety of animals including humans, mammals such as horses, sheep, cattle, hogs, dogs, cats, and marine animals such as whales, dolphins, seals, otters, fish, and reptiles such as turtles.
  • FIG. 1 An illustration of a structural matrix in accordance with one embodiment of the invention is shown in FIG. 1 .
  • a damaged section of tissue, wound ( 112 ) has vasculature ( 116 ) protruding throughout.
  • a biocompatible polymeric composition ( 114 ) has been applied to the wound ( 112 ), which has been coated with protective coat ( 110 ).
  • FIG. 2 shows a magnified view of one embodiment of biocompatible polymeric composition ( 114 ), which comprises structural polymer ( 226 ) and hemophilic polymer ( 224 ).
  • Structural polymer ( 226 ) comprises about 0.1% to 95% by total composition weight of a cross-linkable polyanionic polymer and 0% to 95% by total composition weight of a non-cross-linkable polyanionic polymer.
  • Hemophilic polymer ( 224 ) comprises about 1% to 90% by total composition weight of a polycationic polymer.
  • Red blood cell ( 210 ) is shown in relation to the cationic function groups ( 212 ) via a red blood cell-cationic group linkage ( 216 ).
  • FIGS. 3A to 3I show various polymers that can be chosen as structural polymer ( 226 ) or hemophilic polymer ( 224 ). Polymers can be modified through the addition of carboxymethyl (CM) groups to gain anionic functional groups ( 218 ).
  • FIG. 3E shows carboxymethyl cellulose. Alginate ( 3 A), sodium hyaluronate ( 3 F), ⁇ -carrageenan ( 3 G), ⁇ -carrageenan ( 3 H), and sodium polyacrylate ( 3 I) are examples of polymers that would function as structural polymer ( 226 ).
  • chitin ( 3 B) and chitosan ( 3 C) are examples of polymers that would function as hemophilic polymer ( 224 ).
  • FIG. 3D shows how any polymer ( 340 ) can be modified with a diethylaminoethyl (DEAE) group to gain cationic functional groups ( 212 ).
  • DEAE diethylaminoethyl
  • Biocompatible polymeric composition ( 114 ) contains about 0.1% to 99.8% by total composition weight of a solvent.
  • the solvent is ethanol.
  • the solvent is a 5% aqueous solution of ethanol in water.
  • Non-limiting examples of solvents include water, ethanol, amyl acetate, acetone, methyl ethyl ketone, isopropanol, and tetrahydrofuran.
  • structural polymer ( 226 ) and hemophilic polymer ( 224 ) experience intermolecular interactions which bind them together.
  • hemophilic polymer ( 224 ) attract anionic functional groups ( 218 ) on structural polymer ( 226 ) and result in ionic cross-linking ( 214 ). Additionally, hemophilic polymer ( 224 ) and structural polymer ( 226 ) can be covalently cross-linked ( 228 ), similar to a Schiff base or azomethine linkage.
  • Protective coat ( 110 ) comprises 0.1% to 30% by weight of a di- or higher valent cation ( 220 ), 0% to 90% by weight of a hydrophobic polymer, and 5% to 99.9% by weight of a solvent.
  • Protective coat ( 110 ) cross-links composition ( 114 ) by diffusing divalent cation ( 220 ) inwards, which results in divalent cation cross-linking ( 222 ) of structural polymer ( 226 ). This increases the rigidity of composition ( 114 ) and allows for better stability.
  • Protective coat ( 110 ) can also contain hydrophobic polymers, which limit the water loss from composition ( 114 ) and improve durability.
  • the hydrophobic polymer may be a polyurethane, nitrocellulose, a cyanoacrylate, a styrene, a polytetrafluoroethane, and a silicone, and combinations thereof.
  • the solvent may be water, amyl acetate, acetone, methyl ethyl ketone, isopropanol, and tetrahydrofuran, and combinations thereof.
  • the di- or higher valent cation may be Ca2+, Fe2+, Fe3+, Ag2+, Ag3+, Au2+, Au3+, Mg2+, Cu2+, Cu3+, and Zn2+. In one embodiment of the invention, the cation is Ca2+.
  • structural polymer ( 226 ) comprises 0.1% to 5% by weight of sodium alginate and 1% to 5% by weight of sodium hyaluronate
  • hemophilic polymer ( 224 ) comprises 2% to 25% by weight of chitosan chloride
  • the solvent comprises 65% to 96.9% by weight of a 5% aqueous solution of ethanol in water.
  • the composition functions as a wound healing matrix to facilitate faster tissue regeneration.
  • structural polymer ( 226 ) comprises 2% to 5% by weight of sodium alginate and 0% to 2% by weight of sodium hyaluronate
  • hemophilic polymer ( 224 ) comprises 5% to 20% by weight of chitosan chloride
  • the solvent comprises 73% to 93% by weight of a 5% aqueous solution of ethanol in water.
  • the composition functions as a thick gel for rapidly achieving hemostasis without the need to apply pressure.
  • the composition can be delivered topically to the compromised blood vessel.
  • structural polymer ( 226 ) comprises 0.1% to 4% by weight of sodium alginate and 1% to 5% by weight of a lysine-rich polypeptide
  • hemophilic polymer ( 224 ) comprises 5% to 25% by weight of diethylaminoethyl-dextran (DEAE-Dextran)
  • the solvent comprises 65% to 93% by weight of a 5% aqueous solution of ethanol in water.
  • the biocompatible polymeric composite ( 114 ) is then cross-linked in situ by applying an aerosol mist comprising 0.1% to 1% by weight of calcium chloride, 1% to 5% by weight of nitrocellulose, and 94% to 98.9% by weight of amyl acetate.
  • the composition functions as a protective covering for cuts and scrapes that is durable and limits water loss from the wound.
  • the biocompatible polymeric composition comprises about 3.6% by weight of sodium alginate, about 7% by weight of chitosan chloride, and about 89.4% by weight of a 5% aqueous solution of ethanol in water.
  • This embodiment may function as a composition to treat arterial bleeds.
  • the protective coat comprises a solution comprising about 0.1% to about 30% by weight of a di- or higher valent cation; 0% to about 90% by weight of a hydrophobic polymer; and about 5% to about 99.9% by weight of a solvent.
  • the protective coat comprises a solution comprising about 0.1% to about 1% by weight of a di-valent cation; about 1 to about 5% by weight of a hydrophobic polymer; and about 94% to about 98.9% by weight of a solvent.
  • composition ( 114 ) is used as a carrier for a therapeutic agent such as a drug or biologic molecule.
  • a therapeutic agent such as a drug or biologic molecule.
  • protective coat ( 110 ) is prepared with a salt of silver, increasing the antimicrobial properties of the gel.
  • the therapeutic agent is selected from the group consisting of: antimicrobial agents, antibiotics, hormones, proteins (such as calreticulin, thrombin, prothrombin, Factor VIII), and iodine, and combinations thereof.
  • the therapeutic agent is preferably iodine.
  • the therapeutic agent is a protein.
  • the cross-linkable polyanionic polymer may be a polystyrene sulfonate (such as sodium polystyrene sulfonate), a polyacrylate (such as sodium polyacrylate), a polymethacrylate (such as sodium polymethacrylate), a polyvinyl sulphate (such as sodium polyvinyl sulphate), a polyphosphate (such as sodium polyphosphate), Iota carrageenan, Kappa carrageenan, gellan gum, carboxyl methyl cellulose, carboxyl methyl agarose, carboxyl methyl dextran, carboxyl methyl chitin, carboxyl methyl chitosan, a polymer modified with a carboxyl methyl group, an alginate (such as sodium alginate), a polymer containing a plurality of carboxylate groups, a xanthan gum, and combinations thereof.
  • the crosslinkable polyanionic polymer is an alginate (such as sodium alg
  • the cross-linkable polyanionic polymer comprises about 1% to about 95% by weight of the biocompatible polymeric composition; preferably the cross-linkable polyanionic polymer comprises about 5% to about 40% by weight of the biocompatible polymeric composition; preferably the cross-linkable polyanionic polymer comprises about 10% to about 30% by weight of the biocompatible polymeric composition.
  • the non-cross-linkable polyanionic polymer may be a hyaluronate (such as sodium hyaluronate), a polynucleotide (such as RNA), a polypeptide chain having an average residue isoelectric point below 7, a glucosaminoglycan, and a proteoglycan, and combinations thereof.
  • a hyaluronate such as sodium hyaluronate
  • RNA polynucleotide
  • a polypeptide chain having an average residue isoelectric point below 7 a glucosaminoglycan
  • proteoglycan and combinations thereof.
  • the non-cross-linkable polyanionic polymer is a hyaluronate, more preferably sodium hyaluronate.
  • the non-cross-linkable polyanionic polymer comprises about 0 to about 95% by weight of the biocompatible polymeric composition; preferably the non-cross-linkable polyanionic polymer comprises about 5 to about 25% by weight of the biocompatible polymeric composition; preferably the non-cross-linkable polyanionic polymer comprises about 0 to about 5% by weight of the biocompatible polymeric composition; preferably the non-cross-linkable polyanionic polymer comprises about 0 to about 2% by weight of the biocompatible polymeric composition; preferably the non-cross-linkable polyanionic polymer comprises about 1 to about 5% by weight of the biocompatible polymeric composition.
  • the polycationic polymer may be a chitosan (such as chitosan chloride), chitin, diethylaminoethyl-dextran, diethylaminoethyl-cellulose, diethylaminoethyl-agarose, diethylaminoethyl-alginate, a polymer modified with a diethylaminoethyl group, a polymer containing a plurality of protonated amino groups, and a polypeptide having an average residue isoelectric point above 7, and combinations thereof.
  • the polycationic polymer is a chitosan, more preferably chitosan chloride.
  • the polycationic polymer is diethylaminoethyl-dextran (DEAE-Dextran).
  • the polycationic polymer comprises about 1% to about 90% by weight of the biocompatible polymeric composition; preferably the polycationic polymer comprises about 2% to about 80% by weight of the biocompatible polymeric composition; preferably the polycationic polymer comprises about 2% to about 25% by weight of the biocompatible polymeric composition.
  • the individual components of the biocompatible polymeric composition may be stored in a variety of different containers for a variety of different applications, including for example, packets, sachets, tubes, tubs, pumps, syringes, bottles, bags, and aerosol-based spray cans.
  • the components may be stored in containers made of a variety of materials, including for example, plastic, metal, or glass.
  • the components may be provided in operably connected configurations, or as separate components for a user to set up prior to use.
  • compositions and systems described herein may be included in a kit or article of manufacture for forming a biocompatible polymeric composition
  • a biocompatible polymeric composition comprising one or more of: a solution comprising a polyanionic polymer; a solution comprising a polycationic polymer; a solvent; and a solution comprising a di- or higher valent cation, a hydrophobic polymer, and solvent.
  • the kit or article of manufacture may further contain gauze, bandages, tape, brushes, spatulas, and sponges.
  • the studies described may utilize one embodiment of the composition to form a rigid matrix while another composition may be designed with an increased elasticity, alone or in combination. Further, the methods of mixing and formulating the composition may be performed in any order and combination so as to achieve the same or similar effects of the embedded solidified matrix, the matrix integrating the formation of naturally restructuring tissue.
  • the one or more than one polyanionic polymer is first applied to a wound and then the one or more than one polycationic polymer is applied to the said one or more than one polymeric polymer at the wound site.
  • the one or more than one polyanionic polymer is mixed with the one or more than one polycationic polymer and then the mixture is then applied to the wound.
  • the one or more than one polyanionic polymer is applied to a wound at the same time, or about the same time, that the one or more than one polycationic polymer is applied to a wound.
  • a method of treating a wound comprises applying one or more than one polyanionic polymer to a wound and then applying one or more than one polycationic polymer to the said one or more than one polymeric polymer at the wound site.
  • a method of treating a wound comprises mixing one or more than one polyanionic polymer with one or more than one polycationic polymer and then applying the mixture to the wound.
  • a method of treating a wound comprises applying one or more than one polyanionic polymer to the wound at the same time, or about the same time, as one or more than one polycationic polymer is applied to a wound.

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MX366366B (es) 2019-07-05
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US9687584B1 (en) 2017-06-27
SG11201402279SA (en) 2014-06-27
HK1201734A1 (en) 2015-09-11
BR112014011442A2 (pt) 2017-05-16
IL232330A0 (en) 2014-06-30
JP2018183611A (ja) 2018-11-22
IN2014CN03524A (https=) 2015-10-09
EP2776068A1 (en) 2014-09-17
AU2017219007A1 (en) 2017-09-07
SG10201610469QA (en) 2017-02-27
WO2013071235A1 (en) 2013-05-16
RU2014124157A (ru) 2015-12-27
AU2012334982A1 (en) 2014-05-22
KR20140090670A (ko) 2014-07-17
JP2014533181A (ja) 2014-12-11
CN109602944A (zh) 2019-04-12
ZA201403166B (en) 2015-11-25
JP7013336B2 (ja) 2022-01-31
US20210290817A1 (en) 2021-09-23
CN103930133A (zh) 2014-07-16
US10850003B2 (en) 2020-12-01
WO2013071235A9 (en) 2013-07-18
JP2021007754A (ja) 2021-01-28
US20170266339A1 (en) 2017-09-21
IL232330B (en) 2019-06-30
US20170157286A1 (en) 2017-06-08
BR112014011442A8 (pt) 2018-01-09
CA2855347C (en) 2019-03-05
MX2019008051A (es) 2019-09-09
MX2014005738A (es) 2014-07-09
RU2017144044A (ru) 2019-02-15
RU2640084C2 (ru) 2017-12-26
US11383005B2 (en) 2022-07-12

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