US20180185543A1 - Highly efficacious hemostatic adhesive polymer scaffold - Google Patents

Highly efficacious hemostatic adhesive polymer scaffold Download PDF

Info

Publication number
US20180185543A1
US20180185543A1 US15/739,095 US201515739095A US2018185543A1 US 20180185543 A1 US20180185543 A1 US 20180185543A1 US 201515739095 A US201515739095 A US 201515739095A US 2018185543 A1 US2018185543 A1 US 2018185543A1
Authority
US
United States
Prior art keywords
polymeric composition
chitosan
sodium alginate
kda
deacetylation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US15/739,095
Other languages
English (en)
Inventor
Joseph A. Landolina
Omar M. Ahmad
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cresilon Inc
Original Assignee
Cresilon Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cresilon Inc filed Critical Cresilon Inc
Publication of US20180185543A1 publication Critical patent/US20180185543A1/en
Assigned to CRESILON, INC. reassignment CRESILON, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AHMAD, OMAR M., LANDOLINA, JOSEPH A.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/225—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/043—Mixtures of macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0052—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28—Polysaccharides or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/58—Adhesives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0036—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/08—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0066—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/008—Hydrogels or hydrocolloids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/04—Alginic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/04—Alginic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Definitions

  • Hemostasis is a complex, multi-stage mechanism involving an orchestrated effort on the part of many cell types and scaffold formations to begin production of an initial platelet plug at the site of a wound and then develop a fully mature clot capable of arresting blood flow. Hemostasis is usually divided into three phases: primary hemostasis, the coagulation cascade, and fibrinolysis. Initially, a platelet plug is formed as a response to exposed endothelial cells at a compromised surface, after platelets adhere to collagen fibers surrounding said surface. Exposure to collagen “activates” the platelets, prompting them to release coagulation factors that allow for the coagulation cascade to progress. The process ends in the cleavage of fibrinogen by thrombin to form the foundational material for a clot, known as fibrin.
  • a notable challenge in the treatment of bleeding wound surfaces is presented by the adhesive properties of the physical barrier component of a given hemostatic device. If sustained blood flow is particularly strong, hemostasis can be disrupted as premature platelet plugs and fibrin clots may be ruptured in the process. This difficulty can be exacerbated if a hemostatic device lacks sufficient adhesion and a partially formed plug or clot disengages prematurely from a wound site.
  • Various hemostatic devices seek to increase adhesive strength by utilizing dry devices to dehydrate the wound site. Such devices retard epithelialization and, in turn, slow wound healing substantially.
  • the invention is a class of biocompatible polymer compositions useful in facilitating and maintaining hemostasis.
  • the biocompatible polymeric composition comprises (a) one or more than one polyanionic polymer, (b) one or more than one polycationic polymer, and (c) a solvent.
  • one polyanionic polymer comprises sodium alginate; in one embodiment of the invention, one polycationic polymer comprises chitosan; in one embodiment of the invention, a solvent comprises water.
  • the biocompatible polymeric composition comprises sodium alginate, chitosan, and water.
  • properties associated with each component of the biocompatible polymeric compositions may impact the properties of the final product.
  • Properties associated with the selection of a particular polyanionic polymer include chain length, molecular weight, viscosity in solution, particle size, and morphology.
  • Properties associated with the selection of a particular polycationic polymer include chain length, molecular weight, degree of deacetylation, viscosity in solution, particle size, and morphology.
  • Properties associated with the solvent include pH and polarity.
  • Final biocompatible polymer composition properties include viscosity, hemostatic efficiency, fracture strength, and pH.
  • Factors impacting the properties of the final product include the amount of each component as well as the method of manufacturing.
  • FIG. 1 schematically illustrates a Fourier Transform Infrared spectrum of sodium alginate.
  • FIG. 2 schematically illustrates a Fourier Transform Infrared spectrum of chitosan.
  • FIG. 3 schematically illustrates a Fourier Transform Infrared spectrum of an inventive biocompatible polymeric composition.
  • the invention disclosed herein is a class of biocompatible polymer gel compositions useful in facilitating and maintaining hemostasis.
  • the biocompatible polymeric gel composition generally comprises (a) a polyanionic polymer, (b) a polycationic polymer, and (c) a solvent.
  • the polymeric gel composition comprises about 0.10% to about 5.00% by weight of a polyanionic polymer (or more than one polyanionic polymer).
  • the polymeric gel composition comprises about 1.00% to about 4.00% by weight of a polyanionic polymer; preferably the polymeric gel composition comprises about 2.00% to about 3.00% by weight of a polyanionic polymer.
  • the polymeric gel composition may comprise about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.55%, about 0.60%, about 0.65%, about 0.70%, about 0.75%, about 0.80%, about 0.85%, about 0.90%, about 0.95%, about 1.00%, about 1.05%, about 1.10%, about 1.15%, about 1.20%, about 1.25%, about 1.30%, about 1.35%, about 1.40%, about 1.45%, about 1.50%, about 1.55%, about 1.60%, about 1.65%, about 1.70%, about 1.75%, about 1.80%, about 1.85%, about 1.90%, about 1.95%, about 2.00%, about 2.05%, about 2.10%, about 2.15%, about 2.20%, about 2.25%, about 2.30%, about 2.35%, about 2.40%, about 2.45%, about 2.50%, about 2.55%, about 2.60%, about 2.65%, about 2.7
  • the 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 polyanionic polymer is an alginate, more preferably sodium
  • the polyanionic polymer has a chain length of between about 1,000 nm and about 3,000 nm.
  • the increased chain length of a particular polyanionic polymer aids in the increased ability of the composition—when applied to a wound—to adhere to tissue.
  • Short-chain polyanionic polymers may yield a biocompatible polymeric gel composition having difficult or poor adhesion to a wound.
  • the polyanionic polymer may have a chain length of about 1,000, about 1,100, about 1,200, about 1,300, about 1,400, about 1,500, about 1,600, about 1,700, about 1,800, about 1,900, about 2,000, about 2,100, about 2,200, about 2,300, about 2,400, about 2,500, about 2,600, about 2,700, about 2,800, about 2,900, or about 3,000 nm.
  • the polyanionic polymer comprises particles having an average particle size of between 10 mesh and 300 mesh. As the particle size of the polyanionic polymer increases, the amount of cell adhesion to the polymer increases. However as the particle size of the polyanionic polymer increases this may decrease surface area of wound coverage.
  • the polyanionic polymer comprises particles having an average particle size of between 100 mesh and 270 mesh.
  • the polyanionic polymer comprises particles having an average particle size of between 120 mesh and 250 mesh.
  • the polyanionic polymer comprises particles having an average particle size of between 150 mesh and 200 mesh.
  • the polyanionic polymer comprises particles having an average particle size of about 180 mesh.
  • the polyanionic polymer may have an average particle size of about 80, about 100, about 120, about 150, about 180, about 200, about 250, or about 270 mesh.
  • the polyanionic polymer has a number average molecular weight (Mn) of between 100 kDa to about 1,000 kDa.
  • Mn number average molecular weight
  • the polyanionic polymer has a molecular weight of between about 500 kDa to about 900 kDa.
  • the polyanionic polymer has a molecular weight of about 800 kDa.
  • Higher molecular weight polyanionic polymers will increase the viscosity of the polymeric gel composition and will maintain its flowability to resist fracture and prevent or reduce blood passage through it.
  • the polyanionic polymer may have a molecular weight of about 100 kDa, about 150 kDa, about 200 kDa, about 250 kDa, about 300 kDa, about 350 kDa, about 400 kDa, about 450 kDa, about 500 kDa, about 550 kDa, about 600 kDa, about 650 kDa, about 700 kDa, about 750 kDa, about 800 kDa, about 850 kDa, about 900 kDa, about 950 kDa, or about 1,000 kDa.
  • the polyanionic polymer has a viscosity of between about 100 centipoise (cP) to about 2,000 cP in a 1% weight per volume (w/v) solution of water at about 25° C.
  • the polyanionic polymer has a viscosity of between about 100 cP to about 1,000 cP in a 1% w/v solution of water at about 25° C.
  • the polyanionic polymer may have a viscosity of about 100 cP, about 200 cP, about 300 cP, about 400 cP, about 500 cP, about 600 cP, about 700 cP, about 800 cP, about 900 cP, about 1,000 cP, about 1,100 cP, about 1,200 cP, about 1,300 cP, about 1,400 cP, about 1,500 cP, about 1,600 cP, about 1,700 cP, about 1,800 cP, about 1,900 cP, or about 2,000 cP in a 1% w/v solution of water at about 25° C.
  • the polyanionic polymer has a viscosity of about 1,000 cP in a 1% w/v solution of water at about 25° C.
  • the polyanionic polymer present in the polymeric gel composition comprises the scaffold onto which fibrin adheres.
  • the morphology of polyanionic polymer particles is preferably a mesh or combination of fibrous particles onto which fibrin can easily bind and form a patch at the wound bed.
  • the polyanionic polymer particles may have a morphology that is fibrous, crystalline, amorphous, spherical, cuboidal, or a combination thereof.
  • Polyanionic polymers may be obtained from various commercial suppliers. However, the source of polyanionic polymer can impact the potential for foreign contaminants, such as prions, to be present in raw materials.
  • the polyanionic polymer is obtained from an organic source.
  • the polyanionic polymer is sodium alginate.
  • the sodium alginate is obtained from marine algae such as Macrocystis pyrifera (kelp).
  • the polymeric gel composition comprises about 5% to about 40% by weight of a polycationic polymer (or more than one polycationic polymer).
  • the polymeric gel composition comprises about 8% by weight of a polycationic polymer; preferably the polymeric gel composition comprises about 22% by weight of a polycationic polymer.
  • the polymeric gel composition may comprise about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40% by weight of a polycationic polymer.
  • 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; preferably the polycationic polymer is chitosan chloride.
  • the polycationic polymer is diethylaminoethyl-dextran (DEAE-Dextran).
  • the polycationic polymer has a chain length of between about 2,000 nm and about 4,000 nm. In a preferred embodiment the polycationic polymer has a chain length of between about 2,800 nm and about 2,900 nm. In a preferred embodiment the polycationic polymer has a chain length of between about 2,850 nm. In a preferred embodiment the polycationic polymer has a chain length of between about 2,849 nm.
  • the polyanionic polymer may have a chain length of about 2,000, about 2,100, about 2,200, about 2,300, about 2,400, about 2,500, about 2,600, about 2,700, about 2,800, about 2,900, about 3,000, about 3,100, about 3,200, about 3,300, about 3,400, about 3,500, about 3,600, about 3,700, about 3,800, about 3,900, or about 4,000 nm.
  • the polycationic polymer comprises particles having an average particle size of between 50 mesh and 500 mesh. As the particle size of the polycationic polymer increases, the amount of cell adhesion to the polymer increases. However as the particle size of the polycationic polymer increases this may decrease surface area of wound coverage.
  • the polycationic polymer comprises particles having an average particle size of between 60 mesh and 400 mesh.
  • the polycationic polymer comprises particles having an average particle size of between 80 mesh and 325 mesh.
  • the polycationic polymer comprises particles having an average particle size of between 80 mesh and 120 mesh.
  • the polycationic polymer comprises particles having an average particle size of about 100 mesh.
  • the polycationic polymer may have an average particle size of about 50, about 60, about 80, about 100, about 120, about 150, about 180, about 200, about 250, about 270, about 325, about 400, or about 500 mesh.
  • the polycationic polymer has a number average molecular weight (Mn) of between about 1 kDa to about 2,000 kDa.
  • Mn number average molecular weight
  • the polycationic polymer has a molecular weight of between about 1 kDa to about 1,000 kDa.
  • the polycationic polymer has a molecular weight of between about 800 kDa to about 1,200 kDa.
  • the polycationic polymer has a molecular weight of between about 900 kDa to about 1,100 kDa.
  • the polycationic polymer has a molecular weight of about 1,000 kDa.
  • the polycationic polymer may have a molecular weight of about 100 kDa, about 200 kDa, about 300 kDa, about 400 kDa, about 500 kDa, about 600 kDa, about 700 kDa, about 800 kDa, about 900 kDa, about 1,000 kDa, about 1,100 kDa, about 1,200 kDa, about 1,300 kDa, about 1,400 kDa, about 1,500 kDa, about 1,600 kDa, about 1,700 kDa, about 1,800 kDa, about 1,900 kDa, or about 2,000 kDa.
  • the polycationic polymer has a viscosity of between about 10 cP to about 1,000 cP in a 1% weight per volume (w/v) solution of 5% acetic acid at about 25° C.
  • the polycationic polymer has a viscosity of between about 50 cP to about 1,000 cP in a 1% w/v solution of 5% acetic acid at about 25° C.
  • the polycationic polymer may have a viscosity of about 10 cP, about 20 cP, about 30 cP, about 40 cP, about 50 cP, about 60 cP, about 70 cP, about 80 cP, about 90 cP, about 100 cP, about 110 cP, about 120 cP, about 130 cP, about 140 cP, about 150 cP, about 160 cP, about 170 cP, about 180 cP, about 190 cP, about 200 cP, about 210 cP, about 220 cP, about 230 cP, about 240 cP, about 250 cP, about 260 cP, about 270 cP, about 280 cP, about 290 cP, about 300 cP, about 310 cP, about 320 cP, about 330 cP, about 340 cP, about 350 cP, about 360 cP, about 370 cP, about
  • the polycationic polymer particles present in the polymeric gel composition comprise a surface onto which cells may adhere to permit platelet aggregation. A greater surface area of polycationic polymer particles may accelerate hemostasis.
  • the morphology of polycationic polymer particles is preferably spherical with pores and allows for aggregation both inside the particle as well as outside.
  • the polycationic polymer particles may have a morphology that is fibrous, crystalline, amorphous, spherical, cuboidal, or a combination thereof.
  • the polycationic polymer may also be bound or functionalized to a core of a different material such as a polymeric substance.
  • the core is an inert core.
  • the core is poly-L-lactic acid. Binding the polycationic polymer to a core may, for example, reduce the amount of polycationic polymer needed to achieve a given surface area compared with a solid particle of a given polycationic polymer. Binding the polycationic polymer to a core may also allow for a geometries that would otherwise be impossible or impractical absent the core.
  • a cuboidal core is coated in chitosan to yield a cuboidal geometry for chitosan—where chitosan on its own will not form cuboidal geometries under ordinary conditions. Binding the polycationic polymer to a core may also permit a polycationic polymer to exist in a crystalline form within the biocompatible polymer gel composition when such polymer would not otherwise be able to exist as a crystal based on the conditions in the composition.
  • a core of poly-L-lactic acid is bound to diethylaminoethyl-dextran (DEAE-Dextran) and used in a stable biocompatible polymer gel composition comprising alginate—where DEAE-Dextran cannot form a crystal on its own under ordinary conditions and may not form a stable gel when used with alginate alone.
  • the one or more than one polycationic polymer comprises diethylaminoethyl-dextran bound as a coating to a core of poly-L-lactic acid; the one or more than one polycationic polymer comprises diethylaminoethyl-dextran covalently linked to a core of poly-L-lactic acid.
  • Polycationic polymers may be obtained from various commercial suppliers. However, the source of polycationic polymer can impact the potential for foreign contaminants, such as prions, to be present in raw materials.
  • the polycationic polymer is obtained from an organic source.
  • the polycationic polymer is chitosan, it may be obtained from crustaceans, fungi, insects, and other organisms. Chitosan may also be obtained from plant sources.
  • the chitosan is obtained from algae.
  • the polycationic polymer is chitosan and it is obtained from fungi such as the genus Pleurotus .
  • the polycationic polymer is chitosan and it is obtained from marine invertebrates.
  • the polycationic polymer is chitosan and it is obtained from Aspergillus niger.
  • the degree of deacetylation is a factor that impacts the properties of the polymeric gel composition.
  • Chitosan is an analog to the commonly known chitin, and the degree of deacetylation of chitin coincides with hemostatic efficacy.
  • the chitosan has an average degree of deacetylation of between about 75.0% to about 99.5%.
  • the chitosan has an average degree of deacetylation of between about 75.0% to about 85.0%.
  • the chitosan has an average degree of deacetylation of between about 78.0% to about 83.0%.
  • the chitosan has an average degree of deacetylation of between about 80.0% to about 81.0%.
  • the chitosan has an average degree of deacetylation of 80.5%.
  • the chitosan may have an average degree of deacetylation of about 75.0%, about 75.5%, about 76.0%, about 76.5%, about 77.0%, about 77.5%, about 78.0%, about 78.5%, about 79.0%, about 79.5%, about 80.0%, about 80.5%, about 81.0%, about 81.5%, about 82.0%, about 82.5%, about 83.0%, about 83.5%, about 84.0%, about 84.5%, about 85.0%, about 85.5%, about 86.0%, about 86.5%, about 87.0%, about 87.5%, about 88.0%, about 88.5%, about 89.0%, about 90.0%, about 90.0%, about 90.
  • Biocompatible polymeric compositions of the invention contain between about 50.0% to about 90.0% weight of a solvent.
  • the compositions comprise between about 50.0% to about 90.0% solvent; preferably the compositions comprise between about 60.0% and about 90.0% solvent; preferably the compositions comprise between about 75.0% and about 90.0% solvent.
  • the solvent may be present in the biocompatible polymeric composition in an amount of about 50.0%, about 50.5%, about 51.0%, about 51.5%, about 52.0%, about 52.5%, about 53.0%, about 53.5%, about 54.0%, about 54.5%, about 55.0%, about 55.5%, about 56.0%, about 56.5%, about 57.0%, about 57.5%, about 58.0%, about 58.5%, about 59.0%, about 59.5%, about 60.0%, about 60.5%, about 61.0%, about 61.5%, about 62.0%, about 62.5%, about 63.0%, about 63.5%, about 64.0%, about 64.5%, about 65.0%, about 65.5%, about 66.0%, about 66.5%, about 67.0%, about 67.5%, about 68.0%, about 68.5%, about 69.0%, about 69.0%, about 69.0%, about 69.0%, about 69.0%,
  • Non-limiting examples of solvents include water, ethanol, amyl acetate, acetone, methyl ethyl ketone, isopropanol, tetrahydrofuran, and combinations thereof.
  • the solvent is polar.
  • the solvent is pH neutral (about 7.0).
  • the solvent is water.
  • the solvent is present in the biocompatible polymeric composition in an amount of about 89.5%.
  • the solvent is present in the biocompatible polymeric composition in an amount of between about 77.0% and about 78.0%.
  • the biocompatible polymeric composition may be a gel that comprises between about 0.1% to about 5% by weight of one or more than one polyanionic polymer, between about 10% to about 40% by weight of one of more than one polycationic polymer; and between about 50% to 99.9% by weight solvent.
  • the biocompatible polymeric gel composition comprises (a) between about 0.0200 g/mL and about 0.0230 g/mL of one or more than one polyanionic polymer and (b) between about 0.185 g/mL and about 0.210 g/mL of one of more than one polycationic polymer.
  • the biocompatible polymeric gel composition comprises (a) between about 0.0200 g/mL and about 0.0230 g/mL of sodium alginate and (b) between about 0.185 g/mL and about 0.210 g/mL of chitosan.
  • the biocompatible polymeric gel composition comprises about 0.02247 g/mL of one or more than one polyanionic polymer and about 0.200 g/mL of one of more than one polycationic polymer.
  • the biocompatible polymeric gel composition comprises about 0.02247 g/mL of sodium alginate and about 0.200 g/mL of chitosan measured as anhydrous powders.
  • the biocompatible polymeric gel composition comprises about 0.0225 g/mL of sodium alginate and about 0.200 g/mL of chitosan measured as anhydrous powders.
  • the biocompatible polymeric gel composition comprises about 0.0212 g/mL of one or more than one polyanionic polymer and about 0.1887 g/mL of one of more than one polycationic polymer.
  • the biocompatible polymeric gel composition comprises about 0.0212 g/mL of sodium alginate and about 0.1887 g/mL of chitosan measured as anhydrous powders.
  • the biocompatible polymeric gel composition comprises about 0.021 g/mL of sodium alginate and about 0.190 g/mL of chitosan measured as anhydrous powders.
  • a preferred solvent is water.
  • the inventive biocompatible polymeric gel composition is able to clot blood rapidly while maintaining a strong clot.
  • Clot strength is a primary metric of the utility of a biocompatible polymeric composition.
  • a Sonoclot coagulation analyzer (marketed by Sienco as Sonoclot Analyzer) is recognized as a suitable method for testing efficacy of hemostatic devices.
  • Clot strength of a formed clot increases over time, depending upon the activator it is exposed to.
  • the clot strength of a clot on a wound exposed to an inventive biocompatible polymeric compositions may be 50% higher than the strength of a clot formed without exposure to the inventive composition.
  • CSU clot strength units
  • Time to clot is another primary metric of the utility of a biocompatible polymeric composition.
  • Clot strength and clot strength units
  • the biocompatible polymeric composition facilitates hemostasis when applied to a wound, and preferably time to clot is achieved in 120 seconds or less, preferably in 90 seconds or less, preferably in 60 seconds or less, preferably 30 seconds or less, preferably 15 seconds or less.
  • the time to clot of a wound exposed to the inventive biocompatible polymeric compositions is about 190% faster than the time to clot of a wound without exposure to the inventive composition.
  • the biocompatible polymeric composition can preferably clot blood in vitro in 120 seconds or less, preferably in 90 seconds or less, preferably in 60 seconds or less, preferably 30 seconds or less, preferably 15 seconds or less.
  • the time to clot blood exposed to the inventive biocompatible polymeric composition (in vitro) is about 190% faster than the time to clot without exposure to the inventive composition (in vitro).
  • about 13 mg or more of the inventive composition coagulates about 0.34 mL of blood in vitro.
  • Adhesive strength is yet another metric of the utility of a biocompatible polymeric gel composition.
  • the inventive compositions should demonstrate sufficient adhesion to a wound to keep the composition at the site of the wound but without the permanence of adhesives such as cyanoacrylate glues.
  • the biocompatible polymeric composition preferably withstands a vertical strain of up to 0.5 Newtons per square millimeter without fracture between two samples of tissue.
  • 1 mL of a biocompatible polymeric gel is placed between two pieces of chicken liver (20 mm ⁇ 20 mm ⁇ 5 mm) and compressed, and the gel withstands a vertical strain of about 0.5 Newtons per square millimeter without fracture when then the tissue samples are pulled apart vertically.
  • the biocompatible polymeric gel composition may be characterized by various methods including viscosity, pH, Fourier Transform Infrared (FTIR) spectroscopy, and chemical analysis.
  • FTIR Fourier Transform Infrared
  • the inventive biocompatible polymeric composition preferably has a viscosity between about 145,000 (centipoise) cP and about 250,000 cP at about 25° C. In a preferred embodiment the biocompatible polymeric composition has a viscosity of between about 165,000 cP and about 174,000 cP at about 25° C. In a preferred embodiment the biocompatible polymeric composition has a viscosity of between about 169,000 cP and about 170,000 cP at about 25° C. In a preferred embodiment the biocompatible polymeric composition has a viscosity of about 169,500 cP at about 25° C. A preferred viscosity allows for maximum adhesion capabilities which, in turn, affects performance.
  • the biocompatible polymeric composition may have a viscosity of about 145,000 cP, about 145,500 cP, about 146,000 cP, about 146,500 cP, about 147,000 cP, about 147,500 cP, about 148,000 cP, about 148,500 cP, about 149,000 cP, about 149,500 cP, about 150,000 cP, about 150,500 cP, about 151,000 cP, about 151,500 cP, about 152,000 cP, about 152,500 cP, about 153,000 cP, about 153,500 cP, about 154,000 cP, about 154,500 cP, 155,000 cP, about 155,500 cP, about 156,000 cP, about 156,500 cP, about 157,000 cP, about 157,500 cP, about 158,000 cP, about 158,500 c
  • the polyanionic polymer is sodium alginate having a chain length of between about 1,000 nm and about 3,000 nm, a molecular weight of about 800 kDa, a viscosity of about 1,000 cP in a 1% w/v solution of water at about 25° C., is comprised of particles having an average particle size of about 180 mesh with an amorphous morphology, and is sourced from marine algae.
  • the polycationic polymer is chitosan having an average degree of deacetylation of about 80.5%, a chain length of between about 2,850 nm, a molecular weight of about 1,000 kDa, a viscosity of between about 80 cP in a 1% w/v solution of 5% acetic acid at about 25° C., is comprised of particles having an average particle size of about 100 mesh with a porous and spherical morphology, and is sourced from marine invertebrates.
  • the solvent is water.
  • the inventive biocompatible polymeric composition preferably has a pH between about 6.0 and about 8.0, preferably between about 6.5 and about 7.5, preferably between about 6.8 and about 7.2, preferably about 7.0.
  • the FTIR spectra of preferred component alginate and chitosan are shown in FIGS. 1 and 2 , respectively.
  • the FTIR spectrum of a preferred biocompatible polymeric gel composition is shown in FIG. 3 .
  • FIG. 1 schematically illustrates a Fourier Transform Infrared spectrum of a preferred sodium alginate.
  • Major absorption peaks appear as follows: a broad peak at from about 3,600 cm ⁇ 1 to about 3,000 cm ⁇ 1 for —OH stretching vibration, at about 2,900 cm ⁇ 1 for C—H stretching vibration, at about 1,600 cm ⁇ 1 for C ⁇ O of carboxyl group stretching vibration, at about 1,400 cm ⁇ 1 for carboxyl group stretching vibration overlapped with C—H deformation, and multiple peaks around 1,000 cm ⁇ 1 for C—O vibration corresponding to a polysaccharide structure.
  • FIG. 2 schematically illustrates a Fourier Transform Infrared spectrum of a preferred chitosan.
  • Absorption peaks appear as follows: a broad peak at from about 3,600 cm ⁇ 1 to about 3,000 cm ⁇ 1 for O—H stretching vibration overlapped to N—H stretching vibration, at about 2,910 cm ⁇ 1 and at about 2,870 cm ⁇ 1 for C—H stretching vibration, at about 1,650 cm ⁇ 1 for C ⁇ O of amide stretching vibration, at about 1,580 cm ⁇ 1 for N—H deformation, multiple peaks around 1,400 cm ⁇ 1 for C—H deformation, and multiple peaks around 1,000 cm ⁇ 1 for C—O vibration corresponding to a polysaccharide structure.
  • FIG. 3 schematically illustrates a Fourier Transform Infrared spectrum of a preferred biocompatible polymeric composition.
  • Absorption peaks appear as follows: a broad peak at from about 3,600 cm ⁇ 1 to about 3,000 cm ⁇ 1 for O—H stretching vibration overlapped to N—H stretching vibration, at about 2,900 cm ⁇ 1 for C—H stretching vibration, at about 1,640 cm ⁇ 1 for C ⁇ O stretching vibration, at about 1,590 cm ⁇ 1 for N—H deformation, multiple peaks around 1,400 cm ⁇ 1 for C—H deformation, and multiple peaks around 1,000 cm ⁇ 1 for C—O vibration corresponding to a polysaccharide structure.
  • the inventive biocompatible polymeric compositions are intended to be stored at about 25° C.
  • the biocompatible polymeric compositions have a density of between about 1.00 and 1.40 g/mL at about 25° C.
  • the biocompatible polymeric compositions have a density of between about 1.10 and 1.30 g/mL at about 25° C.
  • the biocompatible polymeric compositions have a density of between about 1.20 and 1.22 g/mL at about 25° C.
  • a preferred biocompatible polymeric composition gel has a density of about 1.21 g/mL at about 25° C.
  • the biocompatible polymeric composition may have density of about 1.00 g/mL, about 1.01 g/mL, about 1.02 g/mL, about 1.03 g/mL, about 1.04 g/mL, about 1.05 g/mL, about 1.06 g/mL, about 1.07 g/mL, about 1.08 g/mL, about 1.09 g/mL, about 1.10 g/mL, about 1.11 g/mL, about 1.12 g/mL, about 1.13 g/mL, about 1.14 g/mL, about 1.15 g/mL, about 1.16 g/mL, about 1.17 g/mL, about 1.18 g/mL, about 1.19 g/mL, about 1.20 g/mL, about 1.21 g/mL, about 1.22 g/mL, about 1.23 g/mL, about 1.24 g/mL, about 1.25 g/mL, about 1.26 g/mL, about
  • the inventive biocompatible polymeric composition has a modulus of elasticity of between about 6 kPa to about 23 kPa. In one embodiment the biocompatible polymeric composition has a modulus of elasticity of about 16 kPa.
  • the biocompatible polymeric composition may have a modulus of elasticity of about 6 kPa, about 7 kPa, about 8 kPa, about 9 kPa, about 10 kPa, about 11 kPa, about 12 kPa, about 13 kPa, about 14 kPa, about 15 kPa, about 16 kPa, about 17 kPa, about 18 kPa, about 19 kPa, about 20 kPa, about 21 kPa, about 22 kPa, or about 23 kPa.
  • Preferred storage media containers for the biocompatible polymeric composition include syringes, packets, sachets, tubes, tubs, pumps, bottles, and bags.
  • the polymeric composition is sterile and suitable for application to humans and animals.
  • One preferred storage media is a 5 mL syringe (sterile); one preferred storage media is a 10 mL syringe (sterile).
  • the biocompatible polymeric composition may further include optional components such as antimicrobial, preservative, or therapeutic agents.
  • the composition may include silver salts, metal or carbon nanoparticles, antibiotics, hormones, proteins (such as calreticulin, thrombin, prothrombin, Factor VIII), methylparaben, chlorocresol, cetrimide, and iodine, and combinations thereof.
  • the composition further includes iodine.
  • the composition further includes silver nitrate.
  • the composition further includes methylparaben.
  • Production of the biocompatible polymeric composition generally proceeds as follows. First the one or more polyanionic polymer is mixed with a solvent for a period of time to reach a desired viscosity at about 25° C. The polyanionic mixing may occur between approximately 20 revolutions per minute (RPM) to about 80 RPM, preferably about 48 RPM. Following this first mixing step, the one or more polycationic polymer is added to the mixture and the components are mixed for a period of time to reach a final desired viscosity at about 25° C.; this mixing may occur between approximately 40 RPM to about 100 RPM, preferably about 62 RPM. In a preferred embodiment the mixing in the first mixing period is performed at a lower speed than the mixing in the second mixing period.
  • RPM revolutions per minute
  • sodium alginate is mixed into a vessel with water to reach a desired viscosity at about 25° C. This mixing is performed for about six hours under low-shear mixing, at about 48 RPM. After the sodium alginate and water are mixed, chitosan is added. The mixture including chitosan is mixed under faster mixing than the sodium alginate/water mixing for about one hour at about 25° C. Preferably, upon incorporation of chitosan, the mixing is performed at about 62 RPM.
  • chitosan should not be incorporated simultaneously with the sodium alginate and water as the chitosan particles are porous and tend to pull water out of solution. Simultaneous mixing of all three components (as opposed to first mixing the water and sodium alginate) results in a less efficacious gel that is thicker than desired and may include undissolved sodium alginate. Such gel may comprise a compressible colloid of sodium alginate and wetted chitosan which may exhibit crosslinking issues and poor tissue adherence.
  • the biocompatible polymeric composition is a colloidal gel with solid particles dispersed in a solution. It is believed that the fluidity of the gel allows for aided wound surface area coverage as it conforms to the site of injury better than solids (such as gauzes or sponges) while the solid particles allow for weight to mechanically prevent bleeding through the fluid, as well as aiding in better cell adhesion/aggregation.
  • the packaging of the inventive biocompatible polymeric composition into, for example, a kit or article of manufacture, and application device for any embodiment of the disclosure is chosen and manufactured by persons skilled in the art on the basis of their general knowledge, and adapted according to the nature of the composition to be packaged.
  • the type of device to be used may be in particular linked to the consistency of the composition, in particular to its viscosity; it may also depend on the nature of the constituents present in the composition.
  • the kit or article of manufacture may include, but is not limited to, the inventive composition, a device for the application of the inventive composition, instructions for the use and application of the inventive composition, one or more than one additional solution, a listing of ingredients and/or warnings, and the like.
  • the kit includes a 5 mL syringe filled with an inventive biocompatible polymeric gel along with a separate syringe containing 10% w/v calcium chloride solution in water.
  • the gel is applied to a wound including, for example, 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.
  • the inventive polymeric gel is useful for treating various wounds including those caused unintentionally (such as accidents or unforeseen injuries) as well as those caused intentionally (such as in surgery).
  • the gel is applied directly to a bleeding wound surface.
  • the gel When applied to a volume of blood, the gel will aid in the clotting of blood at the gel-blood interface.
  • efficacy may decrease if gel is not directly in contact with a bleeding wound surface, though is relatively close to the wound site.
  • the operator may preferentially employ a large-bore syringe in order to rapidly apply a substantial amount of gel, due to the gel's viscous nature.
  • the gel may be dispensed via catheter (such as a 16 gauge or larger) during laparoscopic procedures.
  • the inventive polymeric gel may be dispensed across a gauze pad to increase the surface area of exposed gel for treatment of large surface bleeds.
  • Subjects that can benefit from wound treatment using the polymeric compositions of the invention 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.
  • the composition may be cross-linked by addition of a di- or higher valent cation. Addition of the di- or higher valent cation may assist with removal of the product from the wound site.
  • the di- or higher valent cation may be one or more of Ca2+, Fe2+, Fe3+, Ag2+, Ag3+, Au2+, Au3+, Mg2+, Cu2+, Cu3+, and Zn2+.
  • the cation is Ca2+.
  • the di- or higher valent cation is delivered in a solution.
  • the di- or higher valent cation may be present in solution from about 0.1% to about 30% w/v.
  • the solvent is water. In a preferred embodiment a 10% w/v calcium chloride solution in water may be used.
  • an operator received a beaker, a stirring rod, 106 mL of water, 2.247 g of sodium alginate, and 20 g of chitosan.
  • the 106 mL of water was added to the beaker.
  • the operator added up to 50 mg at a time of sodium alginate, followed by 2 minutes of aggressive hand-stirring. This occurred until all sodium alginate was incorporated and was dissolved into the water.
  • the sodium alginate and water solution was left to sit for less than 6 hours to ensure full dissolving.
  • the operator slowly added up to 50 mg at a time of chitosan, followed by 2 minutes of aggressive hand-stirring. This occurred until all chitosan was incorporated and the solution was evenly mixed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Materials For Medical Uses (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Processes Of Treating Macromolecular Substances (AREA)
US15/739,095 2015-06-22 2015-06-22 Highly efficacious hemostatic adhesive polymer scaffold Abandoned US20180185543A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2015/036894 WO2016209198A1 (en) 2015-06-22 2015-06-22 Highly efficacious hemostatic adhesive polymer scaffold

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2015/036894 A-371-Of-International WO2016209198A1 (en) 2015-06-22 2015-06-22 Highly efficacious hemostatic adhesive polymer scaffold

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US17/133,089 Continuation US12016968B2 (en) 2015-06-22 2020-12-23 Highly efficacious hemostatic adhesive polymer scaffold

Publications (1)

Publication Number Publication Date
US20180185543A1 true US20180185543A1 (en) 2018-07-05

Family

ID=57585881

Family Applications (2)

Application Number Title Priority Date Filing Date
US15/739,095 Abandoned US20180185543A1 (en) 2015-06-22 2015-06-22 Highly efficacious hemostatic adhesive polymer scaffold
US17/133,089 Active US12016968B2 (en) 2015-06-22 2020-12-23 Highly efficacious hemostatic adhesive polymer scaffold

Family Applications After (1)

Application Number Title Priority Date Filing Date
US17/133,089 Active US12016968B2 (en) 2015-06-22 2020-12-23 Highly efficacious hemostatic adhesive polymer scaffold

Country Status (17)

Country Link
US (2) US20180185543A1 (zh)
EP (1) EP3310402B1 (zh)
JP (1) JP2018522101A (zh)
KR (1) KR102518121B1 (zh)
CN (2) CN107708750A (zh)
AR (1) AR105098A1 (zh)
AU (1) AU2015399459B2 (zh)
BR (1) BR112017027625A2 (zh)
CA (1) CA2990589C (zh)
ES (1) ES2875098T3 (zh)
HK (1) HK1244720A1 (zh)
IL (1) IL256361B (zh)
MX (1) MX2017016865A (zh)
NZ (1) NZ739244A (zh)
RU (1) RU2750648C2 (zh)
WO (1) WO2016209198A1 (zh)
ZA (1) ZA201800419B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10850003B2 (en) 2011-11-13 2020-12-01 Cresilon, Inc. In-situ cross-linkable polymeric compositions and methods thereof
US12016968B2 (en) 2015-06-22 2024-06-25 Cresilon, Inc. Highly efficacious hemostatic adhesive polymer scaffold

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018119320A1 (en) * 2016-12-21 2018-06-28 Cresilon, Inc. Hemostatic compositions with antifibrinolytic agents
WO2019098560A1 (ko) 2017-11-20 2019-05-23 주식회사 엘지화학 회전식 디스크 시스템을 활용한 중금속 정성 및 정량 분석 디바이스 및 분석 방법
CN108969791B (zh) * 2018-08-23 2021-05-14 大连大学 一种负载纳米银的复合伤口敷料及其制备方法
US12091471B2 (en) 2018-11-19 2024-09-17 Endomedix, Inc. Methods and compositions for achieving hemostasis and stable blood clot formation
US10517988B1 (en) 2018-11-19 2019-12-31 Endomedix, Inc. Methods and compositions for achieving hemostasis and stable blood clot formation
CN115531596A (zh) * 2021-06-30 2022-12-30 苏州美创医疗科技有限公司 止血凝胶组合物及其制备方法

Family Cites Families (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58206751A (ja) * 1982-05-26 1983-12-02 日石三菱株式会社 創傷被覆材
JPS59139310A (ja) * 1983-01-31 1984-08-10 Shiseido Co Ltd 乳化組成物
JPH0612993B2 (ja) * 1987-08-10 1994-02-23 株式会社クラレ 球状の微生物固定化成形物の製造法
US4956350A (en) 1988-08-18 1990-09-11 Minnesota Mining And Manufacturing Company Wound filling compositions
FI95207C (fi) * 1992-09-14 1996-01-10 Novasso Oy Haavansuojaside
JP3411602B2 (ja) 1992-10-22 2003-06-03 グンゼ株式会社 キトサンの溶解方法
DE4337152A1 (de) 1993-10-30 1995-05-04 Merck Patent Gmbh Verfahren zur Herstellung von wäßrigen Chitosan-Lösungen und -Gelen
US5670169A (en) * 1993-12-20 1997-09-23 E.R. Squibb & Sons, Inc. Wound hydrating gel with novel preservative system and low cytotoxicity
US20020032488A1 (en) 1994-05-13 2002-03-14 Brekke John H. Device for regeneration of articular cartilage and other tissue
US6150581A (en) 1995-06-07 2000-11-21 United States Surgical Corporation Chitosan/alginate anti-adhesion barrier
US5836970A (en) 1996-08-02 1998-11-17 The Kendall Company Hemostatic wound dressing
GB2328443B (en) 1997-08-21 2001-09-05 Reckitt & Colmann Prod Ltd In situ formation of pharmaceutically acceptable polymeric material
EP1049424A4 (en) 1998-01-06 2001-11-28 Nicholas A Sceusa MEDICINE DOSAGE BASED ON THE TEORELL MAYER GRADIENT
US6200595B1 (en) 1998-04-24 2001-03-13 Kuraray Co., Ltd. Medical adhesive
JPH11318407A (ja) 1998-05-19 1999-11-24 Lion Corp 加工食品
WO2000012144A1 (en) 1998-08-31 2000-03-09 Coloplast A/S A composition capable of absorbing fluid
JP4267106B2 (ja) 1998-10-15 2009-05-27 株式会社クラレ 癒着防止用材料
JP4159682B2 (ja) * 1998-12-22 2008-10-01 株式会社クラレ 止血材
JP4149098B2 (ja) * 1999-09-13 2008-09-10 株式会社クラレ 水膨潤性医療用高分子ゲルの製造法及び水膨潤性医療用高分子ゲル
US20030206958A1 (en) * 2000-12-22 2003-11-06 Cattaneo Maurizio V. Chitosan biopolymer for the topical delivery of active agents
US7217426B1 (en) 2002-06-21 2007-05-15 Advanced Cardiovascular Systems, Inc. Coatings containing polycationic peptides for cardiovascular therapy
JP2004041586A (ja) 2002-07-15 2004-02-12 Fujimori Kogyo Co Ltd 生体適合性材料およびその製造方法
EP1452167A1 (de) * 2003-02-28 2004-09-01 Cognis France S.A. Kosmetische, pharmazeutische und/oder dermatologische Zubereitungen enthaltend einen Extrakt aus Eperua falcata
US7112713B2 (en) 2003-03-12 2006-09-26 Gelsus Research And Consulting, Inc. Dressing based on the Teorell-Meyer gradient
US8383158B2 (en) 2003-04-15 2013-02-26 Abbott Cardiovascular Systems Inc. Methods and compositions to treat myocardial conditions
ES2384519T3 (es) 2004-02-23 2012-07-06 Loma Linda University Medical Center Agente hemostático para uso tópico e interno
WO2005087280A1 (en) * 2004-03-11 2005-09-22 Medtrade Products Limited Compositions of alpha and beta chitosan and methods of preparing them
RU2369408C2 (ru) 2004-07-09 2009-10-10 Ферросан А/С Гемостатическая композиция, включающая гиалуроновую кислоту
WO2006012541A2 (en) 2004-07-22 2006-02-02 Henry Eisenson Compositions and methods for treating excessive bleeding
RU2403069C2 (ru) 2005-07-21 2010-11-10 ФМС БиоПолимер АС Медицинские устройства, покрытые быстро растворяющимся биосовместимым покрытием
CN100411690C (zh) 2006-01-17 2008-08-20 武汉理工大学 一种抑菌聚电解质多孔材料的制备方法
WO2007112446A2 (en) * 2006-03-28 2007-10-04 University Of Washington Alginate-based nanofibers and related scaffolds
ITPD20060203A1 (it) 2006-05-22 2007-11-23 Univ Degli Studi Trieste Idrogeli di miscele di polisaccaridi per l'ingegneria tissutale e la veicolazione di composti attivi
US7935363B2 (en) 2006-12-12 2011-05-03 Synthasome, Inc. Composite material for tissue repair
WO2008103345A2 (en) * 2007-02-19 2008-08-28 Marine Polymer Technologies, Inc. Hemostatic compositions and therapeutic regimens
WO2008152955A1 (ja) 2007-06-11 2008-12-18 National University Corporation Kyoto Institute Of Technology 植物の加工方法
US20090041858A1 (en) * 2007-08-06 2009-02-12 Cao Group, Inc. Haemostatic Compositions Thickened by Polymers Containing Nitrogen Moieties
US20090123509A1 (en) * 2007-11-08 2009-05-14 Cory Berkland Biodegradable Colloidal Gels as Moldable Tissue Engineering Scaffolds
US8283384B2 (en) 2008-01-24 2012-10-09 University Of Utah Research Foundation Adhesive complex coacervates and methods of making and using thereof
WO2010022132A2 (en) 2008-08-19 2010-02-25 The Regents Of The University Of Michigan Biocompatible coatings, and methods of making and using the same
CN101463144B (zh) 2009-01-12 2010-12-29 武汉理工大学 羟丙基壳聚糖/氧化海藻酸钠自交联抗菌水凝胶材料的制备方法
CN101463145A (zh) 2009-01-12 2009-06-24 武汉理工大学 羧甲基壳聚糖/氧化海藻酸钠自交联抗菌水凝胶材料
EP2416741B1 (en) 2009-04-06 2015-03-11 Bender Analytical Holding B.V. In situ gelling alginate systems
CN102844053B (zh) * 2009-11-25 2015-08-05 洛马林达大学医学中心 基于壳聚糖的止血织物
EP2512588A4 (en) 2009-12-16 2014-06-04 Univ Columbia METHODS, DEVICES, AND SYSTEMS FOR DELIVERY OF ULTRASOUND-DEMARTED MEDICATION
US8389498B2 (en) 2010-03-26 2013-03-05 Taiwan Textile Research Institute Spinning solution and method for manufacturing biomaterial fibers
US8968362B2 (en) 2010-04-08 2015-03-03 Covidien Lp Coated looped suture
CA2799818A1 (en) 2010-05-24 2011-12-01 University Of Utah Research Foundation Reinforced adhesive complex coacervates and methods of making and using thereof
CN102475691B (zh) * 2010-11-30 2014-04-16 中国科学院大连化学物理研究所 海藻酸盐-壳聚糖酰基衍生物微胶囊及其制备和应用
WO2012125994A2 (en) * 2011-03-17 2012-09-20 Perma-Fix Environmental Services, Inc. Preparation of chitosan-based microporous composite material and its applications
JP5835751B2 (ja) * 2011-04-01 2015-12-24 珠海奥托沙医薬科技有限公司 医療用吸収性骨創傷止血材及びその調製方法
GB2499359B (en) * 2011-10-05 2016-12-28 Univ Of Bolton Polysaccharide fibres for wound dressings
RU2640084C2 (ru) * 2011-11-13 2017-12-26 Крезилон, Инк. Сшиваемые in situ полимерные композиции и способы для них
US8895304B2 (en) * 2011-12-09 2014-11-25 Acell, Inc. Hemostatic device
CA2894448C (en) * 2012-12-10 2019-09-17 Regenics As Use of cellular extracts for skin rejuvenation
EP2983718A4 (en) * 2013-04-11 2016-12-07 Univ Of Vermont And State Agricultural College DECELLULARIZATION AND RECELLULARIZATION OF WHOLE ORGANS
EP3310402B1 (en) 2015-06-22 2021-04-07 Cresilon, Inc. Highly efficacious hemostatic adhesive polymer scaffold

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10850003B2 (en) 2011-11-13 2020-12-01 Cresilon, Inc. In-situ cross-linkable polymeric compositions and methods thereof
US11383005B2 (en) 2011-11-13 2022-07-12 Cresilon, Inc. In-situ cross-linkable polymeric compositions and methods thereof
US12016968B2 (en) 2015-06-22 2024-06-25 Cresilon, Inc. Highly efficacious hemostatic adhesive polymer scaffold

Also Published As

Publication number Publication date
CA2990589C (en) 2023-10-10
BR112017027625A2 (pt) 2018-08-28
KR20180053636A (ko) 2018-05-23
NZ765579A (en) 2023-12-22
NZ739244A (en) 2023-07-28
US12016968B2 (en) 2024-06-25
HK1244720A1 (zh) 2018-08-17
ES2875098T3 (es) 2021-11-08
JP2018522101A (ja) 2018-08-09
EP3310402A4 (en) 2019-02-27
AU2015399459A1 (en) 2018-02-15
AU2015399459B2 (en) 2021-02-18
US20210322630A1 (en) 2021-10-21
IL256361A (en) 2018-02-28
RU2018102112A3 (zh) 2019-07-24
CN107708750A (zh) 2018-02-16
IL256361B (en) 2021-10-31
ZA201800419B (en) 2022-04-28
EP3310402A1 (en) 2018-04-25
RU2750648C2 (ru) 2021-06-30
AU2015399459A8 (en) 2018-02-22
WO2016209198A1 (en) 2016-12-29
EP3310402B1 (en) 2021-04-07
RU2018102112A (ru) 2019-07-22
MX2017016865A (es) 2018-09-06
CA2990589A1 (en) 2016-12-29
KR102518121B1 (ko) 2023-04-05
AR105098A1 (es) 2017-09-06
CN115463248A (zh) 2022-12-13

Similar Documents

Publication Publication Date Title
US12016968B2 (en) Highly efficacious hemostatic adhesive polymer scaffold
US10179145B2 (en) Advanced functional biocompatible polymeric matrix used as a hemostatic agent and system for damaged tissues and cells
JP2021007754A (ja) インサイチュー架橋性ポリマー組成物およびその方法
CN104399109B (zh) 一种凝胶止血材料组合物及其制备方法
US20180036338A1 (en) Flowable hemostatic composition
US12091471B2 (en) Methods and compositions for achieving hemostasis and stable blood clot formation
CN114949334A (zh) 可降解的止血剂组合物
JP2023024742A (ja) 高度に有用な止血用接着性ポリマー足場
WO2018119320A1 (en) Hemostatic compositions with antifibrinolytic agents
TWI769136B (zh) 高效用止血黏著性聚合物支架
Sanyal et al. The next frontier in hemorrhagic management: A comprehensive review on development of natural polymer-based injectable hydrogels as promising hemostatic dressings
BR102014014009A2 (pt) Hydrogel based on natural polycarkarides, processes and uses
CN106955375A (zh) 一种用于微创手术止血的包含植物多聚糖的医疗装置

Legal Events

Date Code Title Description
STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

AS Assignment

Owner name: CRESILON, INC., NEW YORK

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LANDOLINA, JOSEPH A.;AHMAD, OMAR M.;REEL/FRAME:049465/0244

Effective date: 20190214

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION