WO2023276951A1 - Matériau de traitement médical et procédé de fabrication de celui-ci - Google Patents

Matériau de traitement médical et procédé de fabrication de celui-ci Download PDF

Info

Publication number
WO2023276951A1
WO2023276951A1 PCT/JP2022/025566 JP2022025566W WO2023276951A1 WO 2023276951 A1 WO2023276951 A1 WO 2023276951A1 JP 2022025566 W JP2022025566 W JP 2022025566W WO 2023276951 A1 WO2023276951 A1 WO 2023276951A1
Authority
WO
WIPO (PCT)
Prior art keywords
polymer
medical treatment
treatment material
mass
meth
Prior art date
Application number
PCT/JP2022/025566
Other languages
English (en)
Japanese (ja)
Inventor
義之 小山
智子 伊藤
賢一 中村
彩歌 大内
Original Assignee
東亞合成株式会社
義之 小山
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 東亞合成株式会社, 義之 小山 filed Critical 東亞合成株式会社
Priority to JP2023531939A priority Critical patent/JPWO2023276951A1/ja
Publication of WO2023276951A1 publication Critical patent/WO2023276951A1/fr

Links

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
    • A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L101/00—Compositions of unspecified macromolecular compounds
    • C08L101/02—Compositions of unspecified macromolecular compounds characterised by the presence of specified groups, e.g. terminal or pendant functional groups
    • C08L101/06—Compositions of unspecified macromolecular compounds characterised by the presence of specified groups, e.g. terminal or pendant functional groups containing oxygen atoms
    • C08L101/08—Carboxyl groups

Definitions

  • TECHNICAL FIELD The present disclosure relates to a medical treatment material and its manufacturing method, and more particularly to a medical treatment material that forms a hydrogel upon contact with water and its manufacturing method.
  • Patent Document 1 proposes a hydrogel-forming material as a medical treatment material that forms a hydrogel through hydrogen bonding between polyacrylic acid and polyvinylpyrrolidone.
  • an aqueous solution of either polyacrylic acid or polyvinylpyrrolidone is dried into a film, and the film is brought into contact with the other aqueous solution and then dried to form a hydrogel.
  • dry films and sponges that can form hydrogels by absorbing water are obtained.
  • the films and sponges thus obtained have the function of rapidly absorbing moisture such as blood and interstitial fluid on wet biological tissues such as wounds and hemostatic sites, swelling, and adhering to the biological tissues. .
  • the present disclosure has been made in view of the above circumstances, and its purpose is to provide a medical treatment material that has excellent adhesiveness to living tissue.
  • a medical treatment material containing a specific carboxyl group-containing polymer and a polymer capable of forming a hydrogen bond with this polymer can be used as a pseudo body fluid. It was found that by swelling moderately without dissolving, it exhibits high adhesiveness to living tissue. Specifically, the present disclosure provides the following means.
  • a medical treatment material that forms a hydrogel upon contact with water which is a polymer (A ) and a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymer (A)).
  • the polymer (A) is poly(meth)acrylic acid.
  • a method for producing a medical treatment material that forms a hydrogel upon contact with water comprising the following polymer (A) and polymer (B): Polymer (A): A polymer having a carboxyl group and having a viscosity of 500 mPa ⁇ s or more at 25° C. in a 1% by mass aqueous solution Polymer (B): A functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymer (A)) having a step of obtaining a film-like solid containing one of the polymers, and bringing a solution containing the other polymer out of the polymer (A) and the polymer (B) into contact with the film-like solid and drying after washing.
  • a polymer component of a medical treatment material that forms a hydrogel a polymer (A ) in combination with the polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group, a medical treatment material having excellent adhesiveness to living tissue can be obtained.
  • (meth)acryl means acryl and/or methacryl.
  • (Meth)acrylate means acrylate and/or methacrylate.
  • the medical treatment material of the present disclosure is a medical treatment material that forms hydrogel upon contact with water.
  • the medical treatment material is a hydrogel-forming article that can be used as an anti-adhesion material, a hemostatic material, a wound dressing material, etc., and is, for example, a film-like, sponge-like, sheet-like or powdery hydrogel-forming material.
  • the medical treatment material of the present disclosure contains the following polymer (A) and polymer (B).
  • polymer (A) a polymer mainly composed of structural units derived from an ethylenically unsaturated monomer having a carboxyl group (hereinafter also referred to as "unsaturated monomer (ma)”) can be preferably used. .
  • unsaturated monomers (ma) include (meth)acrylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid, citraconic acid, cinnamic acid, monohydroxyethyl succinate (meth)acrylate, ⁇ - carboxy-caprolactone mono(meth)acrylate, ⁇ -carboxyethyl(meth)acrylate, 4-carboxystyrene and the like.
  • (meth)acrylic acid can be preferably used as the unsaturated monomer (ma) in that the adhesiveness to living tissue can be increased.
  • the content of structural units derived from the unsaturated monomer (ma) is preferably 40% by mass or more, more preferably 50% by mass, based on the total structural units constituting the polymer (A).
  • the above is more preferable, 60% by mass or more is still more preferable, 70% by mass or more is still more preferable, 80% by mass or more is still more preferable, and 90% by mass or more is even more preferable.
  • the structural unit derived from the unsaturated monomer (ma) in the polymer (A) is within the above range, it is preferable in that a hydrogel having higher adhesiveness to living tissue can be obtained.
  • the unsaturated monomers (ma) constituting the polymer (A) may be of one type or two or more types.
  • the method for obtaining the polymer (A) is not limited to the above.
  • the polymer (A) may be obtained by polymerizing (meth)acrylic acid ester monomers and then hydrolyzing them.
  • the polymer (A) is obtained by a method of treating with a strong alkali, a method of reacting a polymer having a hydroxyl group with an acid anhydride, or the like. You may get
  • the aqueous solution has a viscosity of 500 mPa ⁇ s or more at 25°C.
  • a relatively high-viscosity polymer it is possible to obtain a hydrogel-forming material that is highly swellable when brought into contact with water and has excellent adhesiveness to living tissue.
  • high molecular weight polymer includes a crosslinked polymer or a polymer having a weight average molecular weight of 1,800,000 or more (hereinafter referred to as “high molecular weight polymer (AH) ”) can be preferably used.
  • a crosslinked polymer as the polymer (A) because of its superior swelling property upon contact with moisture and adhesiveness to living tissue.
  • the viscosity at 25° C. of an aqueous solution containing 1% by mass of the polymer (A) is 600 mPa s from the viewpoint of obtaining a hydrogel that has high swelling property upon contact with water and excellent adhesiveness to living tissue. or more, more preferably 800 mPa s or more, still more preferably 900 mPa s or more, even more preferably 1,500 mPa s or more, and 5,000 mPa s or more. More preferably.
  • an aqueous solution containing 1% by mass of the polymer (A) is preferably 30,000 mPa s or less, more preferably 25,000 mPa s or less, from the viewpoint of improving handleability. preferable.
  • the viscosity of the aqueous solution containing the polymer (A) is a value measured at 25°C using a Brookfield viscometer. The details of the measurement method follow the method described in the examples below.
  • the method for producing the crosslinked polymer is not particularly limited.
  • Examples of the method for producing the crosslinked polymer include the following method (1) and method (2).
  • mc ethylenically unsaturated monomer
  • ma unsaturated monomer
  • a method of synthesizing a polymer having a reactive functional group and cross-linking by adding a cross-linking agent if necessary. ) is preferred.
  • the unsaturated monomer (mc) includes a polyfunctional polymerizable monomer having two or more ethylenically unsaturated groups, and a self-crosslinkable functional group having a self-crosslinkable functional group (e.g., hydrolyzable silyl group). and the like.
  • polyfunctional polymerizable monomers include polyfunctional (meth)acrylate compounds, polyfunctional alkenyl compounds, compounds having both a (meth)acryloyl group and an alkenyl group, and the like.
  • the unsaturated monomer (mc) is preferably a polyfunctional alkenyl compound because a uniform crosslinked structure can be easily obtained.
  • polyfunctional alkenyl compounds include polyfunctional allyl ether compounds such as trimethylolpropane diallyl ether, trimethylolpropane triallyl ether, pentaerythritol diallyl ether, pentaerythritol triallyl ether, tetraallyloxyethane, and polyallyl saccharose; Polyfunctional allyl compounds such as diallyl phthalate; Polyfunctional vinyl compounds such as divinylbenzene; Allyl (meth)acrylate, isopropenyl (meth)acrylate, butenyl (meth)acrylate, pentenyl (meth)acrylate, (meth)acrylate Examples include alkenyl group-containing (meth)acrylic acid compounds such as 2-(2-vinyloxyethoxy)ethyl acrylate. Among these polyfunctional alkenyl compounds, polyfunctional allyl ether compounds having a plurality of allyl ether groups in the molecule are particularly preferred.
  • self-crosslinking monomers include hydrolyzable silyl group-containing vinyl monomers.
  • hydrolyzable silyl group-containing vinyl monomers include vinylsilanes such as vinyltrimethoxysilane, vinyltriethoxysilane, vinylmethyldimethoxysilane, and vinyldimethylmethoxysilane; trimethoxysilylpropyl (meth)acrylate; Silyl group-containing (meth)acrylic acid esters such as triethoxysilylpropyl (meth)acrylate and methyldimethoxysilylpropyl (meth)acrylate; trimethoxysilylpropyl vinyl ether, vinyl trimethoxysilylundecanoate and the like.
  • the amount of the structural unit (mc) contained in the polymer (A) is 0.01 with respect to all structural units constituting the polymer (A). % by mass or more is preferable, and 0.1% by mass or more is more preferable. Further, the amount of the structural unit (mc) contained in the polymer (A) is preferably 5% by mass or less, more preferably 2% by mass or less, based on the total structural units constituting the polymer (A). % by mass or less is more preferable.
  • the structural unit (mc) contained in the polymer (A) may be of one type or two or more types.
  • the polymer (A) is a monomer different from the unsaturated monomer (ma) and the unsaturated monomer (mc) (hereinafter referred to as "other monomer (md)”) may further have a structural unit derived from it.
  • other monomers (md) include (meth)acrylic acid alkyl esters, (meth)acrylic acid aliphatic cyclic esters, (meth)acrylic acid aromatic esters, and (meth)acrylic acid alkoxyalkyl esters. , (meth)acrylic acid hydroxyalkyl ester, polyalkylene glycol mono(meth)acrylate, and the like.
  • (meth)acrylic acid alkyl esters such as methyl (meth)acrylate, ethyl (meth)acrylate, isopropyl (meth)acrylate, n-propyl (meth)acrylate, and (meth)acrylic acid.
  • examples include n-butyl acid, isobutyl (meth)acrylate, tert-butyl (meth)acrylate, hexyl (meth)acrylate and 2-ethylhexyl (meth)acrylate.
  • aliphatic cyclic esters of (meth)acrylic acid include cyclohexyl (meth)acrylate, methylcyclohexyl (meth)acrylate, tert-butylcyclohexyl (meth)acrylate, cyclododecyl (meth)acrylate, Examples include isobornyl (meth)acrylate, adamantyl (meth)acrylate, dicyclopentenyl (meth)acrylate and dicyclopentanyl (meth)acrylate.
  • aromatic esters of (meth)acrylic acid include phenyl (meth)acrylate, benzyl (meth)acrylate, phenoxymethyl (meth)acrylate, 2-phenoxyethyl (meth)acrylate and (meth)acrylate. and 3-phenoxypropyl acrylate.
  • (meth)acrylic acid alkoxyalkyl esters include methoxymethyl (meth)acrylate, methoxyethyl (meth)acrylate, ethoxyethyl (meth)acrylate, n-propoxyethyl (meth)acrylate, (meth) ) n-butoxyethyl acrylate, methoxypropyl (meth)acrylate, ethoxypropyl (meth)acrylate, n-propoxypropyl (meth)acrylate, n-butoxypropyl (meth)acrylate, methoxy(meth)acrylate butyl, ethoxybutyl (meth)acrylate, n-propoxybutyl (meth)acrylate and n-butoxybutyl (meth)acrylate.
  • (meth)acrylic acid hydroxyalkyl esters include 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, and 2-hydroxypropyl (meth)acrylate. -hydroxybutyl, 3-hydroxybutyl (meth)acrylate, and 4-hydroxybutyl (meth)acrylate.
  • Polyalkylene glycol mono(meth)acrylates include polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate and polyethylene glycol-polypropylene glycol mono(meth)acrylate.
  • the content of structural units derived from other monomers (md) is preferably 5% by mass or less, more preferably 2% by mass, based on the total structural units constituting the polymer (A). The following are more preferable, and 1% by mass or less is even more preferable.
  • Other monomers constituting the polymer (A) may be of one type or two or more types.
  • the weight-average molecular weight (Mw) of the high-molecular-weight polymer (AH) is preferably 1.0 from the viewpoint of sufficiently increasing adhesiveness to living tissue. 8 ⁇ 10 6 or more. Further, from the viewpoint of handleability, Mw of the high molecular weight polymer (AH) is preferably 5 ⁇ 10 7 or less, more preferably 3 ⁇ 10 7 or less, and still more preferably 1 ⁇ 10 7 or less. .
  • the molecular weight of the high-molecular-weight polymer (AH) is a polystyrene-equivalent value measured by gel permeation chromatography (GPC) using tetrahydrofuran as an eluent after the carboxyl group is methylated with trimethylsilyldiazomethane.
  • a commercial product can also be used as the polymer (A).
  • Such commercially available products include, for example, the trade names of Jurimer (registered trademark) AC-10SHP, Junron (registered trademark) PW-120, Junron PW-121, and Junron PW-312S (manufactured by Toagosei Co., Ltd.). is mentioned.
  • the polymer (B) has a functional group capable of forming a hydrogen bond with the carboxyl group of the polymer (A) (hereinafter also referred to as "functional group E"), and has a polymer different from that of the polymer (A). There is no particular limitation as long as it is coalescence.
  • the functional group E include an amide group, a cyano group, a carbonyl group, an amino group, and a hydroxyl group.
  • the functional group E possessed by the polymer (B) may be of one type or two or more types.
  • the functional group E is, among others, an amide group and/or Alternatively, a hydroxyl group is preferred, and an amide group is particularly preferred.
  • the polymer (B) having an amide group can be produced, for example, by polymerizing an ethylenically unsaturated monomer having an amide group.
  • Ethylenically unsaturated monomers having an amide group include, for example, (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-dimethylaminopropyl(meth)acrylamide, N-methyl(meth)acrylamide , N-vinyl-2-pyrrolidone, 1-vinyl-4-methyl-2-pyrrolidone, and the like.
  • polymer (B) having a hydroxyl group examples include polyethylene glycol (commercially available, such as Macrogol 4000, Macrogol 6000 and Macrogol 20000 manufactured by NOF Corporation), polyoxyethylene hydrogenated castor oil (commercially available, such as BASF Cremophor RH40 manufactured by Nikko Chemical Co., Ltd.; HCO-40 and HCO-60 manufactured by Nikko Chemical Co., Ltd.); be done.
  • polyethylene glycol commercially available, such as Macrogol 4000, Macrogol 6000 and Macrogol 20000 manufactured by NOF Corporation
  • polyoxyethylene hydrogenated castor oil commercially available, such as BASF Cremophor RH40 manufactured by Nikko Chemical Co., Ltd.; HCO-40 and HCO-60 manufactured by Nikko Chemical Co., Ltd.
  • the polymer (B) having a hydroxyl group is preferably polyethylene glycol.
  • the content of the structural units derived from the ethylenically unsaturated monomer having the functional group E is 70% by mass or more with respect to the total structural units constituting the polymer (B). is preferably 80% by mass or more, more preferably 90% by mass or more, and even more preferably 97% by mass or more.
  • a crosslinked polymer or a polymer having a weight average molecular weight of 10,000 or more (hereinafter also referred to as "high molecular weight polymer (BH)") can be preferably used.
  • BH can be used more preferably.
  • the polymer (B) is at least one selected from the group consisting of polyvinylpyrrolidone, polyacrylamide and polymethacrylamide. More preferably at least one selected from the group consisting of polyvinylpyrrolidone and polyacrylamide in terms of excellent polymerizability of the constituent monomers and easy production of the polymer (B). .
  • Polyvinylpyrrolidone is typically a polymer composed of N-vinyl-2-pyrrolidone. However, it may contain a structural unit derived from a monomer different from N-vinyl-2-pyrrolidone as long as it does not impair the effects of the present disclosure. Specific examples of the monomer different from N-vinyl-2-pyrrolidone include the compounds exemplified as other monomers that may constitute the polymer (A). In polyvinylpyrrolidone, the content of structural units derived from a monomer different from N-vinyl-2-pyrrolidone is preferably 3% by mass or less, and 1% by mass or less, based on the total structural units constituting polyvinylpyrrolidone. is more preferable, and 0.5% by mass or less is even more preferable.
  • polyacrylamide is typically a polymer composed of acrylamide. However, it may contain a structural unit derived from a monomer different from acrylamide as long as the effect of the present disclosure is not impaired. Specific examples of the monomer different from acrylamide include the compounds exemplified as other monomers that may constitute the polymer (A).
  • the content of structural units derived from a monomer different from acrylamide is preferably 3% by mass or less, more preferably 1% by mass or less, based on the total structural units constituting polyacrylamide. 5% by mass or less is more preferable.
  • Polymethacrylamide is typically a polymer composed of methacrylamide. However, it may contain a structural unit derived from a monomer different from methacrylamide as long as the effect of the present disclosure is not impaired. Specific examples of the monomer different from methacrylamide include the compounds exemplified as other monomers that may constitute the polymer (A). In polymethacrylamide, the content of structural units derived from a monomer different from methacrylamide is preferably 3% by mass or less, more preferably 1% by mass or less, based on the total structural units constituting polymethacrylamide. , 0.5% by mass or less is more preferable.
  • the weight average molecular weight (Mw) of the high molecular weight polymer (BH) is not particularly limited, but from the viewpoint of ensuring mechanical strength and thickening effect. , preferably 1 ⁇ 10 4 or more, more preferably 3 ⁇ 10 4 or more, and still more preferably 5 ⁇ 10 4 or more. From the viewpoint of handleability, Mw of the high molecular weight polymer (BH) is preferably 1 ⁇ 10 8 or less, more preferably 5 ⁇ 10 7 or less, and still more preferably 3 ⁇ 10 7 or less. .
  • the molecular weight of the polymer (B) is a polystyrene conversion value measured by GPC.
  • the total amount of the polymer (A) and the polymer (B) contained in the medical treatment material of the present disclosure is a medical treatment material that can form a hydrogel with excellent adhesiveness to living tissue and has excellent mechanical strength. From the viewpoint of obtaining the treatment material, it is preferably 70% by mass or more, more preferably 80% by mass or more, still more preferably 90% by mass or more, and even more preferably 95% by mass or more, relative to the total amount of the medical treatment material.
  • the content of polymer (A) and polymer (B) is 20 to 500 parts by mass of polymer (B) per 100 parts by mass of polymer (A). It is preferable to adjust When the content of the polymer (A) and the polymer (B) is within the above range, the effect of improving the mechanical strength is high, and it is preferable in that a hydrogel exhibiting excellent adhesiveness to living tissue can be formed. is. From such a viewpoint, the content of the polymer (A) and the polymer (B) is such that the polymer (B) is 30 to 400 parts by mass with respect to 100 parts by mass of the polymer (A). More preferably, the amount is 50 to 300 parts by mass.
  • the polymerization method for producing polymer (A) and polymer (B) is not particularly limited.
  • Polymer (A) and polymer (B) are prepared by polymerizing monomers by employing known radical polymerization methods such as solution polymerization, suspension polymerization, emulsion polymerization, and bulk polymerization. Obtainable.
  • a polymerization initiator eg, an azo compound
  • the desired product is polymerized by heating to 40 to 250 ° C. A polymer can be obtained.
  • the medical treatment material of the present disclosure further contains components different from the polymer (A) and the polymer (B) (hereinafter also referred to as “other components”) depending on the purpose of use. good too.
  • Other components include, for example, antibacterial agents, anti-inflammatory agents, blood coagulants, anticoagulants, local anesthetics, various drugs such as vasoconstrictors and vasodilators, as well as polymer (A) and polymer (B ) and a water-soluble polymer (C) different from ).
  • one or more can be contained.
  • the content of other components can be appropriately selected according to each component within a range that does not impair the effects of the present disclosure.
  • the water-soluble polymer (C) includes water-soluble polymers that can be generally used as thickeners, and specific examples include polysaccharides.
  • polysaccharides include cellulose derivatives such as hydroxyethylcellulose, carboxymethylcellulose and hydroxypropylmethylcellulose; mucopolysaccharides such as hyaluronic acid and chondroitin sulfate; water-soluble natural products such as carrageenan, pectin, locust bean gum, guar gum, xanthan gum and welan gum.
  • Polymeric polysaccharides and salts thereof (eg, sodium salts) and the like are included.
  • the water-soluble polymer (C) is preferably hyaluronic acid or a salt thereof.
  • the number average molecular weight of the water-soluble polymer (C) is, for example, 200,000 or more.
  • the molecular weight of the water-soluble polymer (C) is a polystyrene conversion value measured by GPC.
  • the content of the water-soluble polymer (C) is 100 parts by mass of the total amount of the polymer (A) and the polymer (B). On the other hand, it is preferably 0.01 to 50 parts by mass.
  • the content of the water-soluble polymer (C) is more preferably 0.1 parts by mass or more with respect to 100 parts by mass of the total amount of the polymer (A) and the polymer (B), and 0.5 parts by mass. Part by mass or more is more preferable.
  • the upper limit of the content of the water-soluble polymer (C) is more preferably 20 parts by mass or less, and 15 parts by mass or less with respect to 100 parts by mass of the total amount of the polymer (A) and the polymer (B). is more preferred.
  • the water-soluble polymer (C) one type may be used alone, or two or more types may be used in combination.
  • Method [1] A method [2] in which a solid film containing one of polymer (A) and polymer (B) is brought into contact with a solution containing the other polymer and then dried.
  • the aqueous solution of the polymer (A) and the aqueous solution of the polymer (B) are simply mixed, the carboxyl group of the polymer (A) and the functional group E of the polymer (B) Hydrogen bonds form hydrogels very quickly.
  • the hydrogel thus obtained has insufficient water solubility and swelling properties, and is inferior in adhesiveness to living tissue.
  • a medical treatment material exhibiting excellent water solubility and water swellability can be produced.
  • a film-like solid material containing one of the polymer (A) and the polymer (B) (hereinafter also referred to as "first polymer”) is prepared.
  • first polymer a film-like solid material containing one of the polymer (A) and the polymer (B)
  • first polymer for preparing the film-like solid, for example, a solution drying method, a heat press method, and the like can be used. Among these, the solution drying method is preferable because it can suppress the generation of air bubbles and can produce a smooth film.
  • a polymer solution (hereinafter also referred to as "first polymer solution”) is prepared by dissolving the first polymer in a solvent, and then the first polymer is Preferably, the solution is applied to the support and dried.
  • the first polymer that constitutes the film-like solid may be the polymer (A) or the polymer (B).
  • Examples of the solvent for dissolving the first polymer include water, a mixture of a water-soluble organic solvent and water, and a water-soluble organic solvent.
  • Examples of water-soluble organic solvents include methanol, ethanol, and acetone.
  • As the solvent for dissolving the first polymer among these, water, ethanol, or a mixture of water and ethanol is preferable.
  • the polymer concentration in the first polymer solution is not particularly limited, but is, for example, 0.01 to 10% by mass, preferably 0.1 to 5% by mass.
  • a method for forming a film-like solid on a support is not particularly limited, and a known film-forming method can be employed.
  • a solid film containing the first polymer can be formed on the support by coating the support with the first polymer solution and preferably heating to remove the solvent.
  • the heating temperature is, for example, 50 to 120° C.
  • the heating time is, for example, 0.1 to 5 hours.
  • the heat treatment may be performed under reduced pressure or under ventilation.
  • the thickness of the solid film formed on the support is, for example, 1 to 5,000 ⁇ m.
  • the water content of the solid film is, for example, 10% by mass or less.
  • a film-like solid material formed on the support and a polymer different from the first polymer (hereinafter also referred to as "second polymer”) among the polymer (A) and the polymer (B) is dissolved in a solvent (hereinafter also referred to as "second polymer solution").
  • the solvent for dissolving the second polymer include the same solvents as those exemplified as the solvent for dissolving the first polymer.
  • the polymer concentration in the second polymer solution is, for example, 0.1 to 30 mass %, preferably 1 to 20 mass %.
  • the method of bringing the solid film containing the first polymer into contact with the second polymer solution is not particularly limited.
  • Examples of the method of bringing the solid film into contact with the polymer solution include a method of applying, dropping, or spraying the second polymer solution on the surface of the solid film, and a method of applying the solid film to the second polymer solution.
  • a method of immersion and the like can be mentioned.
  • a liquid layer comprising the second polymer solution is formed on the film-like solid by dripping the second polymer solution onto the surface of the film-like solid, and the liquid layer is formed on the film-like solid for a predetermined time (for example, 10 minutes). ⁇ 180 minutes) Let stand.
  • the thickness of the liquid layer is not particularly limited, it is, for example, 0.1 to 50,000 ⁇ m.
  • the first polymer in the solid film is gradually dissolved in the second polymer solution to form a hydrogel.
  • the amount of the second polymer solution brought into contact with the film-like solid is such that a crosslinked structure is appropriately formed in the resulting hydrogel.
  • the number of moles of the functional group E possessed by the polymer (B) is preferably 0.1 to 10 mol, more preferably 0.2 to 1 mol, per 1 mol of the carboxyl group possessed by the polymer (A). It is preferable to adjust the amounts of the solid film and the second polymer solution and the polymer concentration so that the amount is 8 mol, more preferably 0.5 to 2 mol.
  • the water-soluble polymer (C) may contain a film-like solid substance, and the second polymer solution may contain the water-soluble polymer (C). good too.
  • the second polymer solution contains the water-soluble polymer (C)
  • the water-soluble polymer (C) is blended in advance with the second polymer solution, and the second polymer containing the water-soluble polymer (C) is prepared.
  • the solution may be brought into contact with the film-like solid, or the water-soluble polymer (C) may be added to the second polymer solution after contacting the film-like solid with the second polymer solution. good.
  • the second polymer solution contains the water-soluble polymer (C), and the second polymer solution containing the water-soluble polymer (C) in advance is more preferably brought into contact with the solid film.
  • the content of the water-soluble polymer (C) in the second polymer solution is 100 mass of the second polymer. It is preferably 0.01 to 50 parts by mass, more preferably 0.1 to 20 parts by mass, even more preferably 0.5 to 15 parts by mass.
  • the resulting hydrogel is dried to obtain the desired dry product.
  • a method for drying the hydrogel is not particularly limited, and a known drying treatment method can be appropriately employed.
  • the freezing temperature is, for example, -70°C to -5°C, preferably -60°C to -5°C.
  • Drying treatment by freeze-drying is preferably carried out at room temperature under reduced pressure.
  • the pressure during freeze-drying is, for example, 50 Pa or less, preferably 20 Pa or less, and more preferably 10 Pa or less.
  • dry means a state in which water is completely removed as well as a state in which water remains in the drying process.
  • the moisture content of the dried body obtained by the drying treatment is, for example, 10% by mass or less, preferably 5% by mass or less.
  • the thickness of the dried body is, for example, 0.1 to 50,000 ⁇ m.
  • a solid film containing one of polymer (A) and polymer (B) is brought into contact with a solution containing the other polymer and then dried to form a solid film. It is possible to obtain a dried body having
  • a solvent that dissolves the polymer in the solution containing the polymer (A) (hereinafter also referred to as “polymer solution A”) and the solution containing the polymer (B) (hereinafter also referred to as “polymer solution B”)
  • the solvent include the same solvents as those exemplified as the solvent for dissolving the first polymer. Among these, from the viewpoint of efficiently performing the drying process, it is preferable to use water alone.
  • the polymer concentration is, for example, 0.001 to 5% by mass, preferably 0.01 to 1% by mass.
  • the content of each of the polymer (A) and the polymer (B) is 20 parts by mass of the polymer (B) per 100 parts by mass of the polymer (A). It is preferable to adjust the amount and concentration of the polymer solution A and the polymer solution B so as to be 500 parts by mass.
  • the amount of the polymer (A) and the polymer (B) is more preferably 30 to 400 parts by mass of the polymer (B) with respect to 100 parts by mass of the polymer (A). It is more preferable to set the amount to 300 parts by mass.
  • the same specific examples as the water-soluble polymer (C) exemplified above can be mentioned.
  • hyaluronic acid or a salt thereof can be preferably used.
  • the amount of the water-soluble polymer (C) used is preferably 0.01 to 50 parts by mass, more preferably 0.1 to 20 parts by mass, relative to 100 parts by mass of the polymer (A). , more preferably 0.5 to 15 parts by mass.
  • the water-soluble polymer (C) is preferably used as an aqueous solution.
  • the mixed liquid containing the polymer (A), the polymer (B) and the water-soluble polymer (C) obtained above is subjected to a drying treatment to obtain the desired dried product.
  • the drying treatment is preferably freeze-drying. Freeze-drying can be performed according to a conventional method. For example, the mixed solution is placed in a mold, frozen, and the molded frozen product is freeze-dried to obtain a target product (dry body) having a desired shape.
  • the moisture content of the dried product is, for example, 10% by mass or less, preferably 5% by mass or less.
  • the medical treatment material obtained as described above does not dissolve in ion buffer solutions such as body fluids, and swells moderately upon contact with water.
  • the medical treatment material of the present disclosure preferably has a water swelling degree (hereinafter also referred to as “water swelling degree ⁇ ”) represented by the following formula (1) of 20 to 60.
  • Water swelling degree ⁇ W 2 /W 1 (1)
  • W 1 Mass (g) after drying at 150°C for 60 minutes in a windless dryer
  • W 2 mass (g) after swelling with ionic buffer for 1 hour
  • the water swelling degree ⁇ of the medical treatment material is 20 or more, a hydrogel having excellent adhesiveness to living tissue can be obtained. Further, when the water swelling degree ⁇ is 60 or less, the volume of the medical treatment material (that is, hydrogel) after absorbing water does not become excessively large, and pressure on living tissue can be suppressed. From this point of view, the water swelling degree ⁇ of the medical treatment material is more preferably 30 or more, still more preferably 40 or more, and even more preferably 44 or more. Further, the upper limit of the water swelling degree ⁇ is more preferably 55 or less, and even more preferably 50 or less.
  • the medical treatment material of the present disclosure is a solid substance in a dry state (that is, a dry substance) before use, and when it comes into contact with water, it absorbs water and swells to become a hydrogel (that is, a swollen substance).
  • the medical treatment material of the present disclosure is a dry body having flexibility before contact with water, and changes from a dry body to a swollen body upon contact with water, thereby exhibiting adhesiveness to living tissue.
  • water includes water, water-soluble organic solvents (ethanol, etc.), body fluids (blood, interstitial fluid, etc.), and mixtures thereof.
  • the medical treatment material of the present disclosure does not have bioabsorbability and is gradually decomposed and solubilized under physiological conditions, so it is highly safe and can be left in the body.
  • a medical treatment material of the present disclosure is particularly suitable as various medical treatment materials such as an anti-adhesion material, a hemostatic material, and a wound dressing.
  • the shape of the medical treatment material of the present disclosure is not particularly limited, and can be used in the form of film, sponge, sheet, powder, and the like. Further, the medical treatment material of the present disclosure may be provided in a state of being held on a support, or may be provided in a state of being included in a package such as a film.
  • the shape and material of the support are not particularly limited, but examples thereof include fabrics such as woven fabrics and non-woven fabrics; Since the medical treatment material of the present disclosure has high mechanical strength and excellent flexibility, it can be preferably used as a hydrogel-forming film or a hydrogel-forming sponge.
  • Example 1 A silicon rubber sheet (thickness 10 mm) having an opening of 25 mm ⁇ 7 mm was placed on a polypropylene base material of 50 mm ⁇ 50 mm, and uncrosslinked polyacrylic acid (manufactured by Toagosei Co., Ltd., Jurimer AC-10SHP, hereinafter "PAA1" 1.5 mL of an aqueous solution containing 1.2% of (also called) was cast and dried at 70° C. for 20 hours to prepare a PAA1 film.
  • PAA1 uncrosslinked polyacrylic acid
  • Examples 2 to 4 and Comparative Example 1 A hydrogel-forming sponge was obtained as a medical treatment material by performing the same operation as in Example 1, except that the types of raw materials were as described in Table 1.
  • Viscosity of 1% Aqueous Solution of Carboxyl Group-Containing Polymer A carboxyl group-containing polymer was dissolved in pure water to prepare an aqueous solution having a polymer concentration of 1%. After storing the prepared aqueous solution at a liquid temperature of 25 ⁇ 1° C. for 1 hour, the aqueous solution viscosity was measured at 25° C. with a Brookfield viscometer at 6 rpm (measurement time: 90 seconds).
  • PAA1 uncrosslinked polyacrylic acid [manufactured by Toagosei Co., Ltd., Jurimer AC-10SHP]
  • PAA2 Medium cross-linked polyacrylic acid [Junron PW-121 manufactured by Toagosei Co., Ltd.]
  • PAA3 Highly crosslinked polyacrylic acid [Junron PW-120, manufactured by Toagosei Co., Ltd.]
  • PAA4 Uncrosslinked polyacrylic acid [manufactured by Toagosei Co., Ltd., Jurimer AC-10LHPK, weight average molecular weight 1,500,000]
  • HA Sodium hyaluronate [Kewpie Co., Ltd., Hy
  • the hydrogel-forming sponges of Examples 1 to 4 containing the polymer (A) and the polymer (B) have an adhesive force to the skin of 2.5 N/cm 2 or more. It was high and easy to use.
  • Examples 1, 2, and 4 using PAA1 as the carboxyl group-containing polymer which has a sufficiently high viscosity of 900 mPa ⁇ s or more at 25° C. when made into a 1% by mass aqueous solution, have an adhesive force to the skin of 3.0%. It was excellent, being as high as 0 N/cm 2 or more.
  • Examples 2 and 4 in which a crosslinked polymer was used as the carboxyl group-containing polymer exhibited even higher adhesion to the skin of 3.5 N/cm 2 or more.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un matériau de traitement médical formant un hydrogel par contact avec de l'eau. Plus précisément, l'invention concerne un matériau de traitement médical qui comprend : un polymère (A) qui possède un groupe carboxyle, et dont la viscosité à 25°C, lorsqu'il consiste en une solution aqueuse à 1% en masse, est supérieure ou égale à ５００ｍＰａ・ｓ ; et un polymère (B) possédant un groupe fonctionnel capable de former une liaison hydrogène avec le groupe carboxyle (le polymère (A) étant exclu).
PCT/JP2022/025566 2021-06-29 2022-06-27 Matériau de traitement médical et procédé de fabrication de celui-ci WO2023276951A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2023531939A JPWO2023276951A1 (fr) 2021-06-29 2022-06-27

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021-108067 2021-06-29
JP2021108067 2021-06-29

Publications (1)

Publication Number Publication Date
WO2023276951A1 true WO2023276951A1 (fr) 2023-01-05

Family

ID=84689925

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2022/025566 WO2023276951A1 (fr) 2021-06-29 2022-06-27 Matériau de traitement médical et procédé de fabrication de celui-ci

Country Status (2)

Country Link
JP (1) JPWO2023276951A1 (fr)
WO (1) WO2023276951A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011122524A1 (fr) * 2010-03-29 2011-10-06 アステラス製薬株式会社 Composition pharmaceutique à libération contrôlée
WO2014065291A1 (fr) * 2012-10-23 2014-05-01 Koyama Yoshiyuki Matière de formation d'hydrogel
WO2021059689A1 (fr) * 2019-09-27 2021-04-01 積水化成品工業株式会社 Hydrogel

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011122524A1 (fr) * 2010-03-29 2011-10-06 アステラス製薬株式会社 Composition pharmaceutique à libération contrôlée
WO2014065291A1 (fr) * 2012-10-23 2014-05-01 Koyama Yoshiyuki Matière de formation d'hydrogel
WO2021059689A1 (fr) * 2019-09-27 2021-04-01 積水化成品工業株式会社 Hydrogel

Also Published As

Publication number Publication date
JPWO2023276951A1 (fr) 2023-01-05

Similar Documents

Publication Publication Date Title
RU2326893C2 (ru) Ковалентное и нековалентное сшивание гидрофильных полимеров и адгезивные композиции, полученные с ними
AU648536B2 (en) Composite of a dispersed gel in an adhesive matrix and method for preparing same
KR100725024B1 (ko) 고흡수성 하이드로콜로이드의 제조방법
JP3717952B2 (ja) 医療用粘着剤及びこれを有する医療用ドレッシング材
Wang et al. Asymmetric composite wound dressing with hydrophobic flexible bandage and tissue-adhesive hydrogel for joints skin wound healing
JP2002542962A (ja) 多孔性基材を被覆する方法
WO2005033198A1 (fr) Composition utilisee en tant qu'adhesif et son utilisation
Zhang et al. Fabrication of adhesive hydrogels based on poly (acrylic acid) and modified hyaluronic acid
Mert et al. A novel wound dressing material: Pullulan grafted copolymer hydrogel via UV copolymerization and crosslinking
CN113893386B (zh) 一种喷涂干粉凝胶敷料及其制备方法
CA3136635A1 (fr) Hydrogels superporeux, leurs procedes de fabrication et articles les incorporant
RU2588628C2 (ru) Амфифильный клей, склеивающий при надавливании, для склеивания кожи человека
CN112646082A (zh) 丙烯酸酯聚合物微球聚集体及其制备方法
CN115746388A (zh) 一种含多尺度孔道网络的自粘附型止血修复凝胶、其制备方法及应用
JP4685301B2 (ja) 湿潤粘着性接着剤
Pulat et al. Swelling behavior and morphological properties of semi-IPN hydrogels based on ionic and non-ionic components
WO2023276951A1 (fr) Matériau de traitement médical et procédé de fabrication de celui-ci
JP5688578B2 (ja) 粘着性ゲル
WO2023276950A1 (fr) Matériau de traitement médical, et procédé de fabrication de celui-ci
JP2023005852A (ja) 医療用処置材及びその製造方法
WO2023022021A1 (fr) Éponge et son procédé de production
JP2024089234A (ja) ハイドロゲル形成材の製造方法
JP2006271927A (ja) 創傷被覆用組成物、及び創傷シート状創傷被覆材
JP2024089233A (ja) ハイドロゲル形成材
JP2023029055A (ja) 医療用処置材の製造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22833098

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2023531939

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22833098

Country of ref document: EP

Kind code of ref document: A1