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
  • A61L15/42—Use of materials characterised by their function or physical properties
  • A61L15/60—Liquid-swellable gel-forming materials, e.g. super-absorbents
• • 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
  • 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
  • A61L26/0014—Chemical 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
• • 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
  • A61L26/008—Hydrogels or hydrocolloids
• • 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
  • A61L26/009—Materials resorbable by the body
• • 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
  • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
  • A61L31/04—Macromolecular materials
  • A61L31/041—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
  • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
  • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
  • A61L31/145—Hydrogels or hydrocolloids
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
  • C08L39/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions of derivatives of such polymers
  • C08L39/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
  • C08L39/06—Homopolymers or copolymers of N-vinyl-pyrrolidones
• • 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

Definitions

• the present invention relates to a hydrogel-forming film or sponge that can be used as an adhesion-preventing material or a hemostatic material. More specifically, the present invention relates to a film or sponge that is provided as a flexible film or sponge in a dry state and can form a hydrogel by absorbing moisture or blood.
• Hydrogels that adhere to living tissues have been extensively studied for application to adhesion-preventing materials, hemostatic materials, wound dressings, drug release devices, etc., and have been partially put into practical use.
• Films and sponges that adhere to wet tissues such as mucous membranes and serosa and absorb surrounding water to form an adhesive gel are useful as anti-adhesion materials and hemostatic materials after surgery.
• Hydrogels are known to be derived from animal proteins, but there are dangers such as infections such as viruses and mad cow disease and immune responses to foreign proteins. Hydrogels cross-linked with natural polysaccharides have been developed as a means of avoiding these risks, but hydrogels cross-linked with natural polysaccharides are poorly flexible in the dry state and have a complicated use site. There is a problem that it cannot be sufficiently fitted to the site, and it is difficult to use it as an anti-adhesion material, and a chemically crosslinked gel has a problem that its bioabsorbability is low. In recent years, reports using synthetic polymer hydrogels are increasing, but synthetic polymers have a low risk of infection, but have low biocompatibility and are generally complicated to prepare. .
• hydrogels formed from synthetic polymers hydrogels formed by hydrogen bonding between polyacrylic acid and polyvinylpyrrolidone are known (Eur. Polym. J., 15, 223, 1979; Eur. Polym. J., 19, 923, 1983). Since this hydrogel is biocompatible and easy to prepare, it is expected to be applied as a hydrogel that avoids the above problems.
• polyacrylic acid and polyvinylpyrrolidone hydrogels are formed quickly by mixing aqueous solutions of both, but have the property of immediately forming hydrophobic aggregates and precipitating as fibrous aggregates. Therefore, there is a problem that a film-like or sponge-like hydrogel cannot be prepared simply by mixing these aqueous solutions.
• JP-A-60-215622 Japanese Patent Laid-Open No. 6-40890 JP-A-6-40889
• An object of the present invention is to provide a flexible film or sponge that can be used as an anti-adhesion material or a hemostatic material. More specifically, an object of the present invention is to provide a flexible dry film or sponge that can absorb water to form a hydrogel and can be used as an antiadhesive material or a hemostatic material. It is in.
• the present inventors have conducted research for the purpose of easily using a biocompatible hydrogel obtained from polyacrylic acid and polyvinylpyrrolidone as an anti-adhesion material or a hemostatic material, and in particular, polyacrylic acid and Provided is a means for preparing a soft dry gel by drying a hydrogel obtained from polyvinylpyrrolidone, and a means for forming a fully hydrated hydrogel by absorbing moisture into the dried gel.
• the present inventors previously dried an aqueous solution of either polyacrylic acid or polyvinyl pyrrolidone into a film, and obtained a flexible film when dried after contacting the other aqueous solution with this film. And the film was found to absorb water easily and form a hydrogel.
• the present inventors rapidly absorb moisture and blood to gel and strongly adhere to the applied site, thereby preventing adhesion of the organ and hemostasis. It was found to be extremely effective. Furthermore, it was also confirmed that the hydrogel produced from the applied film was slowly decomposed and solubilized under physiological conditions after application.
• the present inventor mixed a solution of polyacrylic acid and polyvinylpyrrolidone in the presence of a water-soluble polymer such as hyaluronic acid or a salt thereof, and obtained a soft and elastic solution obtained by freeze-drying the resulting solution. It has been found that a sponge-like solid can be used in the same manner as the above film. Furthermore, a sheet such as Japanese paper can be obtained by drying an aqueous solution of either polyacrylic acid or polyvinylpyrrolidone into a film, and then bringing the other aqueous solution into contact with this film and then freeze-drying it. It was found that it can be used in the same manner as films and sponges.
• a powder obtained by pulverizing a fragile solid obtained by adding a water-soluble polymer to a mixed solution of polyacrylic acid and polyvinylpyrrolidone and freeze-drying, and a solution of polyacrylic acid and polyvinylpyrrolidone simultaneously with mixing It has been found that the powder obtained by the spray drying method can be used as a hydrogel-forming agent in the same manner as the above film and sponge.
• the present invention has been completed based on these findings.
• a film for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone which is prepared from a solution of either polyacrylic acid or polyvinylpyrrolidone in a dry state, Provided is a film which can be obtained by bringing the remaining solid solution into contact with the obtained film-like solid and then drying it.
• a film-like solid in a dry state is prepared from a solution of polyacrylic acid, and the obtained film-like solid is contacted with a solution of polyvinylpyrrolidone and then dried.
• the film that can be obtained by bringing the remaining one solution into contact with the film-like solid containing polyacrylic acid or polyvinylpyrrolidone by dripping or spraying and then drying; and poly
• the acrylic acid solution and / or the polyvinylpyrrolidone solution comprises polyvinyl alcohol;
• the film is an aqueous solution, a solution of an organic solvent, or a mixture of water and an organic solvent.
• a method for producing a film for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone wherein a film-like solid in a dry state is obtained from a solution of either polyacrylic acid or polyvinylpyrrolidone.
• a method comprising the steps of preparing and drying the resulting film-like solid after contacting the remaining one solution.
• a sponge for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone comprising freezing a mixed solution of polyacrylic acid and polyvinylpyrrolidone in the presence of a water-soluble polymer.
• a sponge that can be obtained by drying is provided.
• the above sponge which is hyaluronic acid or a salt thereof is also provided.
• the solution is preferably an aqueous solution.
• a method for producing a sponge for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone comprising a step of freeze-drying a mixed solution of polyacrylic acid and polyvinylpyrrolidone in the presence of a water-soluble polymer A method is provided.
• a paper sheet for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone wherein the film is in a dry state from a solution of either polyacrylic acid or polyvinylpyrrolidone.
• the solid product is prepared, and the resulting solid film is brought into contact with a solution containing the remaining one and a water-soluble polymer, and then frozen, and the frozen product is freeze-dried.
• a paper sheet is provided.
• a film-like solid in a dry state is prepared from a solution of polyacrylic acid, and the obtained film-like solid is frozen after contacting with a solution containing polyvinylpyrrolidone and hyaluronic acid. Then, the above paper sheet that can be obtained by freeze-drying the frozen product is provided.
• a method for producing a paper-like sheet for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone which is a film-like solid in a dry state from a solution of either polyacrylic acid or polyvinylpyrrolidone.
• a method comprising freezing the solution containing the remaining one and the water-soluble polymer after contact with the obtained film-like solid, and lyophilizing the frozen product.
• a powder for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone which is obtained by a method of drying droplets of a solution of polyacrylic acid and polyvinylpyrrolidone.
• the powder can be obtained by spray drying the solution.
• it is a powder for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone, and can be obtained by freeze-drying a solution in which polyacrylic acid and polyvinylpyrrolidone are mixed in the presence of a water-soluble polymer.
• a powder obtained by grinding a solid is provided.
• a medical treatment material including the film, sponge, paper sheet, and powder is provided.
• the medical treatment material include an adhesion prevention material, a hemostatic material, and a wound dressing material.
• a film, sponge, paper sheet, and powder for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone This film, sponge, and paper-like sheet have sufficient flexibility and can be applied in close contact with the organ surface or bleeding site.
• it absorbs moisture, blood and the like to produce a hydrogel, and adheres firmly to the application site as a hydrogel to prevent adhesion of organs or to achieve treatment such as hemostasis.
• the above powder can absorb water and blood to form a hydrogel, and adhere firmly to the application site as a hydrogel to achieve treatment such as hemostasis.
• Polyacrylic acid and polyvinylpyrrolidone are safe synthetic polymers that are approved as pharmaceutical additives, respectively, and are highly biocompatible and safe substances. Therefore, the film, sponge, paper-like sheet, and The powder can be safely used as a medical treatment material. In addition, since it is gradually decomposed and solubilized under physiological conditions after application, it is safe to leave it in the body as an adhesion preventing material for internal organs during surgery.
• the film provided by the present invention is a film for forming a hydrogel containing polyacrylic acid and polyvinyl pyrrolidone, and a film-like solid in a dry state is obtained from one of the solutions of polyacrylic acid or polyvinyl pyrrolidone.
• the film-like solid prepared and obtained is brought into contact with the remaining one solution of polyacrylic acid or polyvinylpyrrolidone and then dried to obtain.
• the molecular weight of polyacrylic acid is not particularly limited, but a number average molecular weight of about 1,000 to 10,000,000 or a crosslinked polymer gel state can be used.
• the molecular weight of polyvinylpyrrolidone is not particularly limited, and those having a number average molecular weight of about 1,000 to 10,000,000 can be used.
• sodium polyacrylate can be used as the polyacrylic acid.
• a solvent for dissolving polyacrylic acid and polyvinylpyrrolidone it is possible to use a mixture of water, an aqueous organic solvent that mixes with water such as methanol, ethanol, and acetone at an arbitrary ratio, or an organic solvent. it can.
• water or ethanol, or a mixture of water and ethanol can be used, but is not limited thereto.
• a dry film-like solid is prepared from either one of polyacrylic acid or polyvinylpyrrolidone solution.
• concentration of the polyacrylic acid or polyvinylpyrrolidone solution is not particularly limited, but a solution having a concentration of about 0.01 to 10%, preferably about 0.1 to 1% can be used.
• a solution of polyacrylic acid or polyvinylpyrrolidone is placed on a support on a flat plate.
• the solution may be uniformly extended so as to have a thickness of 5 mm, and the solvent may be removed under blowing or heating.
• the thickness of the solution before drying on the support is not particularly limited, but can be selected, for example, from about 1 ⁇ m to 50 mm.
• the thickness of the solid film after drying is not particularly limited, but is generally about 0.1 ⁇ m to 5 mm.
• the drying can be performed, for example, at a temperature of about 50 to 100 ° C., but it may be desirable to perform the drying at a lower temperature under blowing or reduced pressure.
• the water content of the film-like solid after drying is not particularly limited, but is, for example, about 0.1% to 10%.
• the film of the present invention can be produced by bringing the remaining solid solution into contact with the dried film-like solid material containing either one of polyacrylic acid or polyvinylpyrrolidone and then drying.
• concentration of the polyacrylic acid or polyvinylpyrrolidone solution used for the contact is not particularly limited, but a solution having a concentration of about 0.01 to 10%, preferably about 0.1 to 1% can be used.
• the method of bringing the solution containing either polyacrylic acid or polyvinylpyrrolidone into contact with the film-like solid after drying is not particularly limited.
• means for dropping, coating, or spraying the solution on the surface of the film-like solid can be exemplified, but the invention is not limited to these means.
• the amount of the polyacrylic acid or polyvinylpyrrolidone solution to be brought into contact with the film-like solid after drying is not particularly limited, but the solution to be brought into contact with polyacrylic acid or polyvinylpyrrolidone contained in the film-like solid after drying.
• the concentration and amount of the solution to be contacted are adjusted so that the repeating unit molar ratio with polyacrylic acid or polyvinylpyrrolidone in the range is about 0.1 to 10, preferably the repeating unit molar ratio is about 0.5 to 2. It may be preferable.
• the drying of the film-like solid contacted with the above solution can be performed, for example, at a temperature of about 50 to 100 ° C., but it may be desirable to perform it at a lower temperature under air blowing or reduced pressure.
• drying must be interpreted in the broadest sense including the state where moisture is completely removed as well as the state where moisture remains in the drying process, and it has any meaning. It should not be interpreted in a limited way.
• the water content of the film of the present invention obtained after drying is not particularly limited, but is, for example, about 0.1% to 10%.
• the thickness of the film of the present invention after drying is not particularly limited, but is, for example, about 0.1 ⁇ m to 1 mm.
• Polyvinyl alcohol can be added to the solution for preparing the film-like solid and / or the solution for contacting the dried film-like solid, but this embodiment is excellent in strength in the present invention. This is a preferred embodiment for forming a thick film.
• the amount of polyvinyl alcohol added is not particularly limited, but can be selected, for example, to be about 0.01 to 50 mol, preferably about 0.1 to 10 mol, of polyvinyl alcohol repeating units with respect to 1 mol of polyacrylic acid repeating units.
• polyvinyl alcohol it may be preferable to add polyvinyl alcohol to the solution for contacting the film-like solid after drying.
• polyacrylic acid and polyvinylpyrrolidone in a repeating unit molar ratio of about 1: 1 and polyvinyl alcohol in a repeating unit molar ratio of about 5 to 20.
• polyethylene glycol may be added to the solution. By adding polyethylene glycol, the flexibility of the film is increased, and water absorption and swelling speed may be improved.
• polyethylene glycol 400 or polyethylene glycol 4000 can be used as the polyethylene glycol, but is not limited thereto.
• the sponge of the present invention is a sponge for forming a hydrogel containing polyacrylic acid and polyvinyl pyrrolidone, and is obtained by freeze-drying a mixed solution of polyacrylic acid and polyvinyl pyrrolidone in the presence of a water-soluble polymer. It is characterized by being able to.
• the sponge of the present invention has flexibility and also has elasticity because it contains air in the solid structure.
• a solvent for dissolving polyacrylic acid and polyvinylpyrrolidone it is possible to use a mixture of water, an aqueous organic solvent that mixes with water such as methanol, ethanol, and acetone at an arbitrary ratio, or an organic solvent. However, it is preferable to use water alone in order to efficiently perform the freezing process during freeze-drying.
• water-soluble polymers other than polyacrylic acid and polyvinylpyrrolidone such as polysaccharides and water-soluble synthetic polymers
• water-soluble polymers that can be used as thickeners are preferred.
• polysaccharides such as cellulose derivatives such as hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, mucopolysaccharides such as hyaluronic acid and chondroitin sulfate
• water-soluble natural polymers such as carrageenan, pectin, locust bean gum, guar gum, xanthan gum and welan gum
• water-soluble synthetic polymer polyvinyl alcohol or the like can be used.
• hyaluronic acid or a salt thereof is preferably used.
• hyaluronic acid or a salt thereof for example, sodium hyaluronate is preferably used.
• the molecular weight of hyaluronic acid is not particularly limited. For example, it may be preferable to use a hyaluronic acid having a number average molecular weight of 200,000 or more. Increasing the content of hyaluronic acid increases the strength of the sponge, which may make it possible to prepare a durable sponge.
• the sponge of the present invention can be produced by preparing a solution by mixing polyacrylic acid and polyvinylpyrrolidone in the presence of a water-soluble polymer, preferably hyaluronic acid or a salt thereof, and lyophilizing the solution. .
• a water-soluble polymer preferably hyaluronic acid or a salt thereof
• lyophilizing the solution preferably aqueous solution containing either one of polyacrylic acid or polyvinylpyrrolidone is prepared, a water-soluble polymer, preferably hyaluronic acid or a salt thereof, is added, and the remaining one aqueous solution is further added to add an aqueous solution.
• the method of preparing the solution for lyophilization is not limited to this method.
• the solution can be mixed at a temperature of about 0 ° C. to room temperature.
• Freeze-drying can be carried out according to a conventional method, but in the case of freeze-drying, a solution is put into a mold and frozen, and the molded frozen product is subjected to freeze-drying to prepare a desired three-dimensional sponge.
• the moisture content of the sponge after drying is not particularly limited, but is, for example, about 0.1% to 10%.
• the density of the sponge of the present invention after drying is not particularly limited, but is, for example, about 0.01 g to 0.9 g / cm 3 .
• the concentration of polyacrylic acid and polyvinylpyrrolidone in the solution subjected to lyophilization is not particularly limited, but can be, for example, a concentration of about 0.01 to 1%, each of which is a repeating unit with polyacrylic acid or polyvinylpyrrolidone in the solution
• the molar ratio is in the range of about 0.1 to 10, preferably the repeating unit molar ratio is in the range of about 0.5 to 2.
• the water-soluble polymer, preferably hyaluronic acid or a salt thereof, may be added so that the repeating unit is about 0.01 to 50 mol, preferably about 0.1 to 10 mol, per 1 mol of polyacrylic acid or polyvinylpyrrolidone repeating unit.
• a sponge is prepared using polyacrylic acid and polyvinylpyrrolidone in a repeating unit molar ratio of about 1: 1 and a water-soluble polymer, preferably sodium hyaluronate, in a repeating unit molar ratio of about 0.1 to 0.2. May be preferred.
• a water-soluble synthetic polymer preferably polyvinyl alcohol
• a water-soluble synthetic polymer preferably polyvinyl alcohol
• the addition amount of the water-soluble synthetic polymer, preferably polyvinyl alcohol is not particularly limited. For example, about 0.01 to 50 mol of polyvinyl alcohol repeating units per mol of polyacrylic acid repeating unit, preferably 0.1 to It can be selected to be about 10 moles.
• the paper-like sheet provided by the present invention is a paper-like sheet for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone, and is a film in a dry state from a solution of either polyacrylic acid or polyvinylpyrrolidone
• a solid-like solid was prepared, and the obtained film-like solid was frozen after contacting a solution containing the remaining one of polyacrylic acid and polyvinylpyrrolidone and a water-soluble polymer, and the frozen product was frozen. It can be obtained by drying.
• the term “paper-like” means a state in which a polymer made into a fiber like paper is converged to contain a large number of voids and is preferably an elastic, aerated solid. Preferably, it means the state of Japanese paper produced in Japan, but this term should not be interpreted in any way restrictively, but in the broadest sense.
• the means described above may be appropriately employed as a means for preparing a dry film-like solid from a solution of either polyacrylic acid or polyvinylpyrrolidone.
• general-purpose means such as coating, spraying, or dripping may be appropriately employed.
• the water-soluble polymer those described above can be used, but preferably hyaluronic acid can be used. It is preferable to bring the solution into contact with the film solid so that a uniform thin film is formed on the surface thereof.
• the paper-like sheet of the present invention can be prepared by freezing the film-like solid material in contact with the solution and then subjecting it to freeze-drying.
• the solution is preferably an aqueous solution. Freezing can be performed at a temperature of about ⁇ 20 ° C., for example, but is not particularly limited to the above temperature.
• the ratio of polyacrylic acid, polyvinyl pyrrolidone, and water-soluble polymer can be appropriately selected with reference to the ratio described above.
• the powder provided by the present invention is a powder for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone, and is obtained by drying a solution of polyacrylic acid and polyvinylpyrrolidone as droplets immediately after mixing. It is characterized by that.
• the powder of this embodiment can be obtained, for example, by spray drying the above solution using a spray dryer equipped with an appropriate nozzle. If necessary, a water-soluble polymer can be added to the solution.
• Another embodiment of the powder is a powder for forming a hydrogel containing polyacrylic acid and polyvinylpyrrolidone, and the solution obtained by mixing polyacrylic acid and polyvinylpyrrolidone in the presence of a water-soluble polymer is freeze-dried.
• the brittle solid can be prepared by the method described above.
• the pulverization can be easily performed by applying an appropriate physical impact.
• the particle size of the powder in each of the above embodiments is not particularly limited, but can be appropriately selected depending on the intended use within the range of several ⁇ m to several mm.
• the purpose of use of the film, sponge, paper sheet, and powder of the present invention is not particularly limited, it can be typically used as a medical treatment material, for example.
• it can be suitably used as an anti-adhesion material for organs during surgery, a hemostatic material against bleeding during surgery or injury, or a wound dressing for the purpose of protecting or promoting healing of wounds.
• a wound is generally an injury accompanied by skin failure, including cuts, lacerations, split wounds, abrasions, crush wounds, wounds, bruises, gun wounds, blasts, stab wounds, wounds, bites, etc. , Burns, pressure ulcers, etc., but are not limited to these. It can also be applied to minor wounds without skin rupture.
• the films, sponges, paper sheets, and powders of the present invention can be used as dressings for these wounds and at the same time a hemostatic material against bleeding from the wound site or lymph fluid leakage from the wound site. It can also be used as a body fluid absorbing material.
• Adhesion is a biological phenomenon in which tissues or organs that are originally separated medically are joined together to form scar tissue between them.
• gastroenterology, cardiology, orthopedics, gynecology, or ophthalmology May occur after surgery in various departments, or may occur in the form of adhesion between the intestinal walls or adhesion between the intestinal wall and the abdominal wall at the onset of inflammatory bowel disease.
• visceral adhesions include inflammatory bowel disease, irritable bowel syndrome, duodenal ulcer, acute enterocolitis, protein-losing enteropathy, colon cancer, appendicitis, hemorrhagic colitis, intestinal tuberculosis, intestine
• adhesive ileus intestinal obstruction
• colonic diverticulosis intraperitoneal adhesion by peritoneal dialysis
• uterine adhesion by Asherman syndrome As an anti-adhesion film, an anti-adhesion film (trade name: Sepra film) based on polysaccharides (such as hyaluronic acid) has been put to practical use. Is possible.
• an antibacterial agent for example, an antibacterial agent, an anti-inflammatory agent, a blood coagulant, an anticoagulant, a local anesthetic, a vasoconstrictor, or a vasodilator
• an antibacterial agent for example, an anti-inflammatory agent, a blood coagulant, an anticoagulant, a local anesthetic, a vasoconstrictor, or a vasodilator
• a drug such as an antibacterial agent, an anticoagulant, and / or an anti-inflammatory agent is blended.
• a local anesthetic can be added as necessary in addition to an antibacterial agent and the like. .
• the film, sponge, paper-like sheet and powder of the present invention are provided in a dry state, but are provided on a support as necessary or in a form including a support in the film. Also good.
• the film, sponge, and paper-like sheet of the present invention are, for example, woven fabrics and non-woven fabrics such as cotton and suf, as well as films and foam sheets such as soft vinyl chloride, polyethylene, and polyurethane, or supports such as gauze. It is also preferable to be provided in a state of being held on the body, or including a support in the film.
• the powder of the present invention can be adhered to gauze or the like.
• the film, sponge, paper sheet and powder of the present invention are desirably provided in an aseptic state, but are preferably stored in a sealed state in a packaging container after sterilization by ordinary means such as gas sterilization.
• Example 1 The following materials were used for the experiment.
• Polyacrylic acid PAA, Carbopol (registered trademark) 940, 934, Lubrizol Advanced Materials Inc., or Carbopol 934P NF Polymer, Kobayashi Inc.
• Polyvinylpyrrolidone PVP, polyvinylpyrrolidone K30, Wako Pure Chemical Industries, Ltd., or Kollidon 30, Kollidon 90F, BASF Japan Ltd.
• Polyvinyl alcohol PVA, polyvinyl alcohol 2800, partially hydrolysed, Wako Pure Chemical Industries, Ltd., or polyvinyl alcohol (partially saponified product) PE-05JPS, Nippon Vinegar Pover Co., Ltd.
• Sodium hyaluronate HA, derived from microorganisms, Nacalai Tesque Corporation, or Japanese Pharmacopoeia Sodium Hy
• a solution of 100 ⁇ L of 7.7% PVP (Kollidon 30 or 90F) ethanol solution, 200 ⁇ L of 3.06% PVA aqueous solution, 100 ⁇ L of 3.06% PEG400 or 4000 ethanol solution, 100 ⁇ L of 1% aqueous chitosan aqueous solution on the surface of PAA / PVA film after drying was added dropwise and dried at 75 ° C. to obtain a flexible water-soluble chitosan-containing PAA / PVP / PVA / PEG film.
• PAA / PVP powder A 0.05% PAA (934P NF) aqueous solution and 0.077% PVP (Kollidon 30) aqueous solution were spray-dried while being mixed using a spray dryer (manufactured by Fujisaki Electric) equipped with a four-fluid nozzle. PAA / PVP powder was obtained.
• the gel was strongly adhered to the burn site while gelling, and no adhesion to the organ or abdominal wall of the burn site was observed. From this result, it was confirmed that the film of the present invention has a high adhesion preventing effect.
• Example 4 Evaluation of hemostasis in mice
• Example 5 Pressure resistance evaluation of the hemostatic effect of a film
• Example 6 Evaluation of hemostasis in heparinized mice
• the skin inside the thigh of the right leg of male ddY mice (6-8 weeks old) was dissected under Nembutal anesthesia.
• the lower limb vein is cut and the film of the present invention described in (a) to (c), (e), (g) to (n), and (u), or (d), (f), (o) , (P), (s) and (t) of the present invention sponge, or (q), (r) of the present invention powder, or (q), (r) of the present invention.
• a mixture of powder of chitosan 10 and powder was applied to the incision site and observed for 1 hour, and the hemostatic effect was evaluated.
• the film, sponge or powder rapidly absorbed blood and gelled, strongly adhering to the incision site. As a result, a sufficient hemostatic effect was achieved efficiently. In particular, the hemostatic effect was greatly improved in films, sponges and powders containing chitosan.
• Example 7 Evaluation of hemostasis in clinical studies (1) After blood collection from a patient taking warfarin, the film of the present invention described in (c) was placed on the puncture part. The film adhered to the puncture part while gelling, and rapid hemostasis was achieved.
• Example 8 Evaluation of hemostasis in clinical studies (2) After extraction of a patient taking warfarin, the tooth was placed on the extraction socket and the sponge of the present invention described in (d). The sponge adhered while gelling, and rapid hemostasis was achieved.

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• 2013
  • 2013-05-24 JP JP2013109515A patent/JP6183831B2/ja active Active
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