Medical treatment material and its manufacturing method

Abstract

To provide a medical treatment material having excellent adhesion to biological tissue and mechanical strength.SOLUTION: A medical treatment material forms a hydrogel by contact with moisture, the medical treatment material containing polymethyl methacrylate (A), and a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymethyl methacrylate (A)).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a medical treatment material and a method for producing the same, and more particularly to a medical treatment material that forms a hydrogel upon contact with water, and a method for producing the same. [Background technology]

[0002] Hydrogels that adhere to biological tissues can be used as adhesion inhibitors, hemostatic materials, wound dressings, and the like, and various studies have been conducted on them (see, for example, Patent Document 1). 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. The technology described in Patent Document 1 involves drying an aqueous solution of either polyacrylic acid or polyvinylpyrrolidone into a film, contacting this film with the other aqueous solution, and then drying the film to obtain a dried film or sponge that can form a hydrogel by absorbing water, serving as a hydrogel-forming material. The films and sponges obtained in this manner rapidly absorb water, such as blood or tissue fluid, and swell when placed on wet biological tissue, such as a wound or a site where bleeding is desired, thereby adhering to the biological tissue. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-100462 Summary of the Invention [Problem to be solved by the invention]

[0004] As a result of investigations by the present inventors, it has been found that the hydrogel-forming material described in Patent Document 1 does not have sufficient adhesiveness to biological tissue and mechanical strength, and is not necessarily a user-friendly medical treatment material.

[0005] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a medical treatment material that has excellent adhesiveness to biological tissue and mechanical strength. [Means for solving the problem]

[0006] The present inventors have conducted extensive research to solve the above problems and have discovered that by using a specific carboxyl group-containing polymer as a polymer component of a medical treatment material that forms a hydrogel through hydrogen bonding, it is possible to obtain a medical treatment material that has excellent adhesiveness to biological tissue and mechanical strength, and have completed the present invention. Specifically, the present invention provides the following means.

[0007] [1] A medical treatment material that forms a hydrogel upon contact with water, comprising polymethacrylic acid (A) and a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymethacrylic acid (A)). [2] The medical treatment material according to the above [1], wherein the polymer (B) has an amide group. [3] The medical treatment material according to [1] or [2] above, wherein the polymer (B) is at least one of polyvinylpyrrolidone, polyacrylamide, and polymethacrylamide.

[0008] [4] The medical treatment material according to any one of the above [1] to [3], wherein the proportion of structural units derived from methacrylic acid in the polymethacrylic acid (A) is 80 mass% or more based on the total structural units constituting the polymethacrylic acid (A). [5] The medical treatment material according to any one of the above [1] to [4], which is formed by contacting a film-like solid material containing one of the polymethacrylic acid (A) and the polymer (B) with a solution containing the other polymer and drying the resulting material, which forms a hydrogel upon absorbing water, and which has adhesive properties to biological tissue.

[0009] [6] A method for producing a medical treatment material that forms a hydrogel upon contact with water, comprising the steps of obtaining a film-like solid material containing one of polymethacrylic acid (A) and a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymethacrylic acid (A)), and bringing the film-like solid material into contact with a solution containing the other polymer, followed by drying. [Effects of the Invention]

[0010] According to the present invention, by using a combination of polymethacrylic acid (A) and a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group as the polymer component of a medical treatment material that forms a hydrogel, a medical treatment material that has high mechanical strength and excellent adhesiveness to biological tissue can be obtained. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention will be described in detail below. In this specification, "(meth)acrylic" means acrylic and / or methacrylic, and "(meth)acrylate" means acrylate and / or methacrylate.

[0012] <Medical treatment materials> The medical treatment material of the present invention is a medical treatment material that forms a hydrogel upon contact with water. The medical treatment material is a hydrogel-forming article that can be used as an adhesion barrier, hemostatic material, wound dressing, etc., and is, for example, a film-, sponge-, sheet-, or powder-like hydrogel-forming material. The medical treatment material of the present invention contains polymethacrylic acid (A) and a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding polymethacrylic acid (A)).

[0013] <Polymethacrylic acid (A)> The polymethacrylic acid (A) is a carboxyl group-containing polymer mainly composed of structural units derived from methacrylic acid (CH═C(CH)—COOH). Specifically, the proportion of structural units derived from methacrylic acid in the polymethacrylic acid (A) is preferably 70% by mass or more, more preferably 80% by mass or more, even more preferably 90% by mass or more, and still more preferably 95% by mass or more, based on the total structural units constituting the polymethacrylic acid (A).

[0014] As the polymethacrylic acid (A), a crosslinked polymer or a polymer having a weight-average molecular weight of 100,000 or more (hereinafter also referred to as a "high molecular weight polymer (AH)") can be preferably used. Among these, it is preferable to use a crosslinked polymer as the polymethacrylic acid (A) because it has superior swelling properties when in contact with water and adhesive properties to biological tissues.

[0015] The polymethacrylic acid (A) may be a polymer consisting of only methacrylic acid, or may be a polymer further containing structural units derived from a monomer other than methacrylic acid (hereinafter also referred to as "other monomers"), provided that the effects of the present invention are not impaired. The other monomers are not particularly limited as long as they are monomers copolymerizable with methacrylic acid. When a crosslinked polymer is used as the polymethacrylic acid (A), the polymethacrylic acid (A) preferably contains structural units derived from an ethylenically unsaturated monomer having a crosslinkable functional group (hereinafter also referred to as "structural unit (c1)").

[0016] Examples of the ethylenically unsaturated monomer having a crosslinkable functional group include a polyfunctional polymerizable monomer having two or more polymerizable unsaturated groups, and a self-crosslinkable monomer having a self-crosslinkable crosslinkable functional group (e.g., a hydrolyzable silyl group). Specific examples of the polyfunctional polymerizable monomer include a polyfunctional (meth)acrylate compound, a polyfunctional alkenyl compound, and a compound having both a (meth)acryloyl group and an alkenyl group. Of these, the ethylenically unsaturated monomer having a crosslinkable functional group is preferably a polyfunctional alkenyl compound, since it is easy to obtain a uniform crosslinked structure.

[0017] Specific examples of polyfunctional alkenyl compounds include polyfunctional allyl ether compounds such as trimethylolpropane diallyl ether, trimethylolpropane triallyl ether, pentaerythritol diallyl ether, pentaerythritol triallyl ether, tetraallyloxyethane, and polyallylsucrose; polyfunctional allyl compounds such as diallyl phthalate; polyfunctional vinyl compounds such as divinylbenzene; and alkenyl group-containing (meth)acrylic acid compounds such as allyl (meth)acrylate, isopropenyl (meth)acrylate, butenyl (meth)acrylate, pentenyl (meth)acrylate, and 2-(2-vinyloxyethoxy)ethyl (meth)acrylate. Among these polyfunctional alkenyl compounds, polyfunctional allyl ether compounds having multiple allyl ether groups in the molecule are particularly preferred.

[0018] Specific examples of the self-crosslinking monomer include hydrolyzable silyl group-containing vinyl monomers, etc. Examples of the hydrolyzable silyl group-containing vinyl monomers include vinyl silanes such as vinyltrimethoxysilane, vinyltriethoxysilane, vinylmethyldimethoxysilane, and vinyldimethylmethoxysilane; silyl group-containing (meth)acrylic acid esters such as trimethoxysilylpropyl (meth)acrylate, triethoxysilylpropyl (meth)acrylate, and methyldimethoxysilylpropyl (meth)acrylate; trimethoxysilylpropyl vinyl ether; and vinyl trimethoxysilylundecanoate.

[0019] When polymethacrylic acid (A) contains structural units (c1), the amount of structural units (c1) contained in polymethacrylic acid (A) is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, based on all structural units constituting polymethacrylic acid (A). Furthermore, the amount of structural units (c1) contained in polymethacrylic acid (A) is preferably 5% by mass or less, more preferably 2% by mass or less, and even more preferably 1% by mass or less, based on all structural units constituting polymethacrylic acid (A). Polymethacrylic acid (A) may contain only one type of structural unit (c1), or two or more types.

[0020] Other monomers constituting the polymethacrylic acid (A) include, in addition to the above, for example, (meth)acrylic acid alkyl esters, aliphatic cyclic esters of (meth)acrylic acid, aromatic esters of (meth)acrylic acid, (meth)acrylic acid alkoxyalkyl esters, (meth)acrylic acid hydroxyalkyl esters, polyalkylene glycol mono(meth)acrylates, etc.

[0021] Specific examples of these include (meth)acrylic acid alkyl esters such as methyl (meth)acrylate, ethyl (meth)acrylate, isopropyl (meth)acrylate, n-propyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, tert-butyl (meth)acrylate, hexyl (meth)acrylate, and 2-ethylhexyl (meth)acrylate.

[0022] Specific examples of the aliphatic cyclic esters of (meth)acrylic acid include cyclohexyl (meth)acrylate, methylcyclohexyl (meth)acrylate, tert-butylcyclohexyl (meth)acrylate, cyclododecyl (meth)acrylate, isobornyl (meth)acrylate, adamantyl (meth)acrylate, dicyclopentenyl (meth)acrylate, and dicyclopentanyl (meth)acrylate, etc. Specific examples of the aromatic esters of (meth)acrylic acid include phenyl (meth)acrylate, benzyl (meth)acrylate, phenoxymethyl (meth)acrylate, 2-phenoxyethyl (meth)acrylate, and 3-phenoxypropyl (meth)acrylate, etc.

[0023] Specific examples of (meth)acrylic acid alkoxyalkyl esters include methoxymethyl (meth)acrylate, methoxyethyl (meth)acrylate, ethoxyethyl (meth)acrylate, n-propoxyethyl (meth)acrylate, n-butoxyethyl (meth)acrylate, methoxypropyl (meth)acrylate, ethoxypropyl (meth)acrylate, n-propoxypropyl (meth)acrylate, n-butoxypropyl (meth)acrylate, methoxybutyl (meth)acrylate, ethoxybutyl (meth)acrylate, n-propoxybutyl (meth)acrylate, and n-butoxybutyl (meth)acrylate.

[0024] Specific examples of the (meth)acrylic acid hydroxyalkyl ester include 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, and 4-hydroxybutyl (meth)acrylate, etc. Examples of the polyalkylene glycol mono(meth)acrylate include polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, and polyethylene glycol-polypropylene glycol mono(meth)acrylate, etc.

[0025] In the polymethacrylic acid (A), the content of structural units derived from other monomers is preferably 5% by mass or less, more preferably 2% by mass or less, and even more preferably 1% by mass or less, based on the total structural units constituting the polymethacrylic acid (A). The other monomers constituting the polymethacrylic acid (A) may be one type or two or more types.

[0026] When a high molecular weight polymer (AH) is used as the polymethacrylic acid (A), the high molecular weight polymer (AH) is preferably a polymer that does not have the structural unit (c1). The weight-average molecular weight (Mw) of the high molecular weight polymer (AH) is not particularly limited, but from the viewpoint of ensuring mechanical strength and thickening effect, it is preferably 500,000 or more, more preferably 1,000,000 or more, and even more preferably 1,800,000 or more. From the viewpoint of handleability, the Mw of the high molecular weight polymer (AH) is preferably 10,000,000 or less, more preferably 8,000,000 or less, and even more preferably 5,000,000 or less. The molecular weight of the high molecular weight polymer (AH) is a polystyrene-equivalent value measured by gel permeation chromatography (GPC) using a tetrahydrofuran eluent after methylating the carboxyl groups with trimethylsilyldiazomethane.

[0027] <Polymer (B)> The polymer (B) is not particularly limited as long as it has a functional group (hereinafter also referred to as "functional group E") capable of forming a hydrogen bond with a carboxyl group of the polymethacrylic acid (A) and is a polymer different from the polymethacrylic acid (A). Examples of 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 of the polymer (B) may be one type or two or more types.

[0028] Among these, the functional group E is preferably an amide group and / or a hydroxyl group, and particularly preferably an amide group, since a hydrogel-forming material with excellent water-swelling properties can be obtained by forming a hydrogen bond between the carboxyl group of the polymethacrylic acid (A) and the functional group E.

[0029] The polymer (B) having an amide group can be produced, for example, by polymerizing an ethylenically unsaturated monomer having an amide group. Examples of the ethylenically unsaturated monomer having an amide group include (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-dimethylaminopropyl(meth)acrylamide, N-methyl(meth)acrylamide, N-vinyl-2-pyrrolidone, and 1-vinyl-4-methyl-2-pyrrolidone.

[0030] Examples of the polymer (B) having hydroxyl groups include polyethylene glycol (commercially available products such as Macrogol 4000, Macrogol 6000, and Macrogol 20000 manufactured by NOF Corporation), polyoxyethylene hydrogenated castor oil (commercially available products such as Cremophor RH40 manufactured by BASF and HCO-40 and HCO-60 manufactured by Nikko Chemicals), polyoxyethylene polyoxypropylene glycol (commercially available products such as Pluronic (registered trademark) F68 manufactured by ADEKA Corporation), and polyvinyl alcohol. Of these, polyethylene glycol is preferred as the polymer (B) having hydroxyl groups.

[0031] In the polymer (B), the content of structural units derived from ethylenically unsaturated monomers having a functional group E is preferably 70% by mass or more, more preferably 80% by mass or more, even more preferably 90% by mass or more, and even more preferably 97% by mass or more, based on all structural units constituting the polymer (B).

[0032] As the polymer (B), a crosslinked polymer or a polymer having a weight average molecular weight of 10,000 or more (hereinafter also referred to as a "high molecular weight polymer (BH)") can be preferably used.

[0033] From the viewpoint of obtaining a medical treatment material that forms a highly swellable hydrogel upon contact with water, the polymer (B) is preferably at least one selected from the group consisting of polyvinylpyrrolidone, polyacrylamide, and polymethacrylamide, and more preferably at least one selected from the group consisting of polyvinylpyrrolidone and polyacrylamide, in view of the excellent polymerizability of the constituent monomers and the ease of production of the polymer (B).

[0034] Polyvinylpyrrolidone is typically a polymer made of N-vinyl-2-pyrrolidone. However, it may contain structural units derived from a monomer other than N-vinyl-2-pyrrolidone, provided that the effects of the present invention are not impaired. Specific examples of monomers other than N-vinyl-2-pyrrolidone include the compounds exemplified as other monomers that may constitute polymethacrylic acid (A). In polyvinylpyrrolidone, the content of structural units derived from monomers other than N-vinyl-2-pyrrolidone is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less, based on the total structural units constituting polyvinylpyrrolidone.

[0035] Similarly, polyacrylamide is typically a polymer made of acrylamide. However, it may contain structural units derived from monomers other than acrylamide, provided that the effects of the present invention are not impaired. Specific examples of monomers other than acrylamide include the compounds exemplified as other monomers that may constitute polymethacrylic acid (A). In polyacrylamide, the content of structural units derived from monomers other than acrylamide is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less, based on the total structural units constituting the polyacrylamide.

[0036] Polymethacrylamide is typically a polymer made of methacrylamide. However, it may contain structural units derived from a monomer other than methacrylamide, provided that the effects of the present invention are not impaired. Specific examples of monomers other than methacrylamide include the compounds exemplified as other monomers that may constitute polymethacrylic acid (A). In polymethacrylamide, the content of structural units derived from monomers other than methacrylamide is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less, based on the total structural units constituting the polymethacrylamide.

[0037] When a high molecular weight polymer (BH) is used as the polymer (B), 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, it is preferably 10,000 or more, more preferably 30,000 or more, and even more preferably 50,000 or more. Furthermore, from the viewpoint of handleability, the Mw of the high molecular weight polymer (BH) is preferably 100 million or less, more preferably 50 million or less, and even more preferably 30 million or less. The molecular weight of the polymer (B) is a polystyrene-equivalent value measured by GPC.

[0038] The total amount of polymethacrylic acid (A) and polymer (B) contained in the medical treatment material of the present invention is preferably 70% by mass or more, more preferably 80% by mass or more, even more preferably 90% by mass or more, and even more preferably 95% by mass or more, based on the total amount of the medical treatment material, from the viewpoint of being able to form a hydrogel that has excellent adhesiveness to biological tissue and obtaining a medical treatment material that has excellent mechanical strength.

[0039] In the medical treatment material of the present invention, the content of polymethacrylic acid (A) and polymer (B) is preferably adjusted so that the amount of polymer (B) is 20 to 500 parts by mass per 100 parts by mass of polymethacrylic acid (A). The content of polymethacrylic acid (A) and polymer (B) within the above ranges is advantageous in that it is highly effective in improving mechanical strength and can form a hydrogel that exhibits excellent adhesiveness to biological tissue. From this perspective, the content of polymethacrylic acid (A) and polymer (B) is more preferably adjusted so that the amount of polymer (B) is 30 to 400 parts by mass, and even more preferably 50 to 300 parts by mass, per 100 parts by mass of polymethacrylic acid (A).

[0040] The polymerization method for producing polymethacrylic acid (A) and polymer (B) is not particularly limited. Polymethacrylic acid (A) and polymer (B) can be obtained by polymerizing monomers using known radical polymerization methods such as solution polymerization, suspension polymerization, emulsion polymerization, and bulk polymerization. In the case of solution polymerization, for example, an organic solvent and monomers are charged into a reactor, a polymerization initiator (e.g., an azo compound) is added, and the mixture is heated to 40 to 250°C to polymerize, thereby obtaining the desired polymer.

[0041] <Other ingredients> The medical treatment material of the present invention may further contain components other than polymethacrylic acid (A) and polymer (B) (hereinafter also referred to as "other components") depending on the purpose of use, etc. Examples of other components include various drugs such as antibacterial agents, anti-inflammatory agents, blood coagulants, anticoagulants, local anesthetics, vasoconstrictors and vasodilators, as well as water-soluble polymers (C) other than polymethacrylic acid (A) and polymer (B). One or more other components may be contained. The content of the other components may be selected appropriately depending on each component, as long as it does not impair the effects of the present invention.

[0042] Examples of the water-soluble polymer (C) include water-soluble polymers that can be commonly used as thickeners, specifically, polysaccharides. Examples of polysaccharides include cellulose derivatives such as hydroxyethyl cellulose, carboxymethyl cellulose, and hydroxypropyl methyl cellulose; mucopolysaccharides such as hyaluronic acid and chondroitin sulfate; water-soluble natural polymeric polysaccharides such as carrageenan, pectin, locust bean gum, guar gum, xanthan gum, and welan gum, as well as salts thereof (e.g., sodium salts). Among these, hyaluronic acid or its salts are preferred as the water-soluble polymer (C). 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-equivalent value measured by GPC.

[0043] When the medical treatment material of the present invention contains a water-soluble polymer (C), the content of the water-soluble polymer (C) is preferably 0.01 to 50 parts by mass per 100 parts by mass of the total amount of polymethacrylic acid (A) and polymer (B). By setting the content of the water-soluble polymer (C) within the above range, it is possible to improve the water retention of the hydrogel. From this perspective, the content of the water-soluble polymer (C) is more preferably 0.1 parts by mass or more, and even more preferably 0.5 parts by mass or more, per 100 parts by mass of the total amount of polymethacrylic acid (A) and polymer (B). Furthermore, the upper limit of the content of the water-soluble polymer (C) is more preferably 20 parts by mass or less, and even more preferably 15 parts by mass or less, per 100 parts by mass of the total amount of polymethacrylic acid (A) and polymer (B). As the water-soluble polymer (C), one type may be used alone, or two or more types may be used in combination.

[0044] <Method for manufacturing medical treatment materials> Although there are no particular limitations on the method for producing the medical treatment material of the present invention, it is preferable to use the following method [1] or method [2]. Method [1]: A method in which a film-like solid containing one of polymethacrylic acid (A) and polymer (B) is brought into contact with a solution containing the other polymer, and then dried. Method [2]: A method of mixing a solution containing polymethacrylic acid (A) and a solution containing polymer (B) in the presence of a water-soluble polymer (C) and drying the mixture.

[0045] Here, if an aqueous solution of polymethacrylic acid (A) and an aqueous solution of polymer (B) are simply mixed, a hydrogel is formed very quickly due to hydrogen bonding between the carboxyl groups of polymethacrylic acid (A) and the functional group E of polymer (B). However, the hydrogel obtained in this manner has insufficient solubility and swelling in water and poor adhesion to biological tissue. In contrast, the above-mentioned methods [1] and [2] make it possible to produce a medical treatment material that exhibits excellent water solubility and water swelling.

[0046] (Regarding Method 1) In method [1], first, a film-like solid material containing one of polymethacrylic acid (A) and polymer (B) (hereinafter also referred to as "first polymer") is prepared. Methods for preparing the film-like solid material include, for example, solution drying and heat pressing. Among these, solution drying is preferred because it can suppress the generation of bubbles and produce a smooth film. When producing a film-like solid material by solution drying, it is preferable to prepare a polymer solution (hereinafter also referred to as "first polymer solution") by dissolving the first polymer in a solvent, and then coat the first polymer solution on a support and dry it. The first polymer constituting the film-like solid material may be polymethacrylic acid (A) or polymer (B).

[0047] Examples of the solvent for dissolving the first polymer include water, a mixture of a water-soluble organic solvent and water, and an organic solvent that is soluble in water. Examples of the organic solvent that is soluble in water include methanol, ethanol, and acetone. Of these, the solvent for dissolving the first polymer is preferably water, ethanol, or a mixture of water and ethanol. The polymer concentration in the first polymer solution is not particularly limited, but is, for example, 0.01 to 10% by mass, and preferably 0.1 to 5% by mass.

[0048] The method for forming a film-like solid on a support is not particularly limited, and known film-forming methods can be used. For example, a film-like solid containing the first polymer can be formed on a support by applying a first polymer solution to the support and preferably heating it to remove the solvent. When heat treatment is performed, the heating temperature is, for example, 50 to 120°C, and the heating time is, for example, 0.1 to 5 hours. The heat treatment may be performed under reduced pressure or under airflow. The thickness of the film-like solid formed on the support is, for example, 1 to 5,000 μm. The moisture content of the film-like solid is, for example, 10% by mass or less.

[0049] Subsequently, the film-like solid formed on the support is brought into contact with a polymer solution (hereinafter also referred to as "second polymer solution") obtained by dissolving a polymer (hereinafter also referred to as "second polymer") different from the first polymer out of polymethacrylic acid (A) and polymer (B) in a solvent. Examples of 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% by mass, and preferably 1 to 20% by mass.

[0050] The method for contacting the film-like solid material containing the first polymer with the second polymer solution is not particularly limited. Examples of methods for contacting the film-like solid material with the polymer solution include applying, dripping, or spraying the second polymer solution onto the surface of the film-like solid material, and immersing the film-like solid material in the second polymer solution. In a preferred embodiment, the second polymer solution is dripped onto the surface of the film-like solid material to form a liquid layer of the second polymer solution on the film-like solid material, and the solid material is then allowed to stand for a predetermined period of time (e.g., 10 to 180 minutes). The thickness of the liquid layer is not particularly limited, but is, for example, 0.1 to 50,000 μm. This allows the first polymer in the film-like solid material to gradually dissolve in the second polymer solution, forming a hydrogel.

[0051] When a film-like solid containing a first polymer is contacted with a second polymer solution, the amount of the second polymer solution to be contacted with the film-like solid is preferably selected so that a crosslinked structure is appropriately formed in the resulting hydrogel. Specifically, the amounts of the film-like solid and the second polymer solution and the polymer concentrations are preferably adjusted so that the number of moles of functional group E in polymer (B) is preferably 0.1 to 10 moles, more preferably 0.2 to 8 moles, and even more preferably 0.5 to 2 moles per mole of carboxyl group in polymethacrylic acid (A).

[0052] When a dried product containing the water-soluble polymer (C) is obtained as a medical treatment material, the water-soluble polymer (C) may be contained in the film-like solid or the second polymer solution. When the water-soluble polymer (C) is contained in the second polymer solution, the water-soluble polymer (C) may be blended in advance with the second polymer solution, and the second polymer solution containing the water-soluble polymer (C) may be brought into contact with the film-like solid. Alternatively, the film-like solid and the second polymer solution may be brought into contact with each other, and then the water-soluble polymer (C) may be added to the second polymer solution. From the viewpoint of optimally forming a hydrogel, it is preferable that the second polymer solution contains the water-soluble polymer (C), and it is more preferable that the second polymer solution containing the water-soluble polymer (C) is brought into contact with the film-like solid.

[0053] When the second polymer solution containing the water-soluble polymer (C) is brought into contact with a film-like solid, the content of the water-soluble polymer (C) in the second polymer solution is preferably 0.01 to 50 parts by mass, more preferably 0.1 to 20 parts by mass, and even more preferably 0.5 to 15 parts by mass, per 100 parts by mass of the second polymer.

[0054] The resulting hydrogel is then dried to obtain the desired dried product. There are no particular limitations on the method for drying the hydrogel, and any known drying method can be used as appropriate.

[0055] When drying a hydrogel by the solution drying method, freeze-drying is preferred. In the freeze-drying process, the freezing temperature is, for example, -70°C to -5°C, preferably -60°C to -5°C. The freeze-drying process 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. In this specification, the term "dry" refers to a state in which moisture is completely removed, as well as a state in which moisture remains during the drying process. The moisture content of the dried product obtained by the drying process is, for example, 10 mass % or less, preferably 5 mass % or less. When the obtained dried product is in the form of a film, the thickness of the dried product is, for example, 0.1 to 50,000 μm. This allows for the production of a dried product formed by contacting a film-like solid containing one of the polymers (polymethacrylic acid (A) and polymer (B) with a solution containing the other polymer, and then drying the resulting product.

[0056] (Regarding Method 2) In method [2], a solution containing polymethacrylic acid (A) and a solution containing polymer (B) are mixed in the presence of water-soluble polymer (C), and the mixture is then dried to produce a dried product as a medical treatment material.

[0057] In the solution containing polymethacrylic acid (A) (hereinafter also referred to as "polymer solution A") and the solution containing polymer (B) (hereinafter also referred to as "polymer solution B"), examples of the solvent for dissolving the polymer include the same solvents as those exemplified as the solvent for dissolving the first polymer. Of these, it is preferable to use water alone from the viewpoint of efficiently performing the drying step. In polymer solution A and polymer solution B, the polymer concentration is, for example, 0.001 to 5% by mass, and preferably 0.01 to 1% by mass.

[0058] In addition, the amounts and concentrations of the polymethacrylic acid (A) and polymer (B) in the polymer solutions A and B are preferably adjusted so that the content of the polymer (B) is 20 to 500 parts by mass per 100 parts by mass of the polymethacrylic acid (A). The amounts of the polymethacrylic acid (A) and polymer (B) are more preferably 30 to 400 parts by mass, and even more preferably 50 to 300 parts by mass, per 100 parts by mass of the polymethacrylic acid (A).

[0059] The water-soluble polymer (C) used in the method [2] can be the same as the specific examples of the water-soluble polymer (C) exemplified above. Among these, 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, and even more preferably 0.5 to 15 parts by mass, relative to 100 parts by mass of the polymethacrylic acid (A). The water-soluble polymer (C) is preferably used as an aqueous solution.

[0060] Subsequently, the mixed solution containing the polymethacrylic acid (A), polymer (B), and water-soluble polymer (C) obtained as described above is subjected to a drying treatment to obtain the target dried product. The drying treatment is preferably freeze-drying. Freeze-drying can be carried out according to a conventional method. For example, the mixed solution is placed in a mold and frozen, and the formed frozen product is freeze-dried to obtain the target product (dried product) having the desired shape. The moisture content of the dried product is, for example, 10% by mass or less, preferably 5% by mass or less.

[0061] <Usage of medical treatment materials> The medical treatment material of the present invention is a dry solid (i.e., a dried body) before use, and upon contact with water, absorbs water and swells to become a hydrogel (i.e., a swollen body). The medical treatment material of the present invention is a flexible dry body before contact with water, and upon contact with water, it changes from a dry body to a swollen body, thereby exhibiting adhesive properties to biological tissue. Here, water includes water, water-soluble organic solvents (e.g., ethanol), body fluids (e.g., blood, tissue fluid), and mixtures thereof. Furthermore, the medical treatment material of the present invention is not bioabsorbable and gradually decomposes and solubilizes under physiological conditions, making it highly safe and allowing it to be left in the body. The medical treatment material of the present invention is particularly suitable as a variety of medical treatment materials, such as adhesion barriers, hemostatic materials, and wound dressings.

[0062] The shape of the medical treatment material of the present invention is not particularly limited, and it can be used in the form of, for example, a film, a sponge, a sheet, or a powder. The medical treatment material of the present invention may be provided in a state where it is held on a support, or in a state where it is enclosed in a package such as a film. The shape and material of the support are not particularly limited, and examples include fabrics such as woven fabrics and nonwoven fabrics; and resin substrates such as polystyrene, polypropylene, and polyethylene. Because the medical treatment material of the present invention has high mechanical strength and excellent flexibility, it can be preferably used as a hydrogel-forming film or a hydrogel-forming sponge. [Example]

[0063] The present invention will be specifically described below based on examples, but the present invention is not limited to these examples. In the following, "parts" and "%" mean "parts by mass" and "% by mass", respectively, unless otherwise specified.

[0064] <Production of polymers> [Synthesis Example 1] A 1-liter four-neck flask was charged with 85 parts by mass of methacrylic acid, 0.4 parts by mass of pentaerythritol triallyl ether, 200 parts by mass of n-hexane, and 200 parts by mass of ethyl acetate to prepare a mixed solution. This mixed solution was thoroughly degassed by bubbling nitrogen gas, and the internal temperature of the mixed solution was raised to 60°C. 0.06 parts by mass of 2,2'-azobis(2,4-dimethylvaleronitrile) was added to initiate polymerization. Cooling of the polymerization reaction solution began 10 hours after the initiation of polymerization, and after the internal temperature had dropped to 25°C, a reaction solution containing a polymer was obtained. This reaction solution was dried under reduced pressure at 100°C for 24 hours to remove volatiles, yielding a carboxyl group-containing polymer (hereinafter also referred to as "PMAA").

[0065] <Production of sponge for hydrogel formation> [Example 1] A 10 mm thick silicone rubber sheet with a 25 mm x 7 mm opening was placed on a 50 mm x 50 mm polypropylene substrate. 1.5 mL of a 1.2% PMAA aqueous solution was cast onto the substrate and dried at 70 °C for 20 hours to produce a PMAA film. Next, a mixed solution of 0.6 mL of a 4.6% polyvinylpyrrolidone (polymer (B), hereafter also referred to as "PVP") aqueous solution and 0.9 mL of a 0.4% sodium hyaluronate (water-soluble polymer (C), hereafter also referred to as "HA") aqueous solution was dripped onto the surface of the PMAA film, allowed to stand for 60 minutes, and then frozen at -50 °C. The frozen product was freeze-dried at room temperature under reduced pressure (5 Pa) to obtain a hydrogel-forming sponge (25 mm x 7 mm x 7 mm) for use as a medical treatment material. The mixing ratio was PMAA:PVP:HA = 1:1.53:0.2 (mass ratio).

[0066] [Example 2 and Comparative Example 1] The same procedure as in Example 1 was carried out except that the types of raw materials were as shown in Table 1, to obtain a hydrogel-forming sponge as a medical treatment material.

[0067] <Evaluation method> The following measurements and evaluations were carried out on the hydrogel-forming sponges of Examples 1 and 2 and Comparative Example 1. The results are shown in Table 1. Measurement and evaluation of adhesive strength to biological tissue (skin) Protein leather (Protein Leather PBZ13001-BK, manufactured by Ideatex Japan Co., Ltd.) was used as a simulated skin, and the surface adhesive strength of the hydrogel-forming sponge to the protein leather was measured. First, two 3 cm square pieces of protein leather were attached to the lids of 50 mL centrifuge tubes using instant adhesive (Aron Alpha (registered trademark), manufactured by Toagosei Co., Ltd.). An appropriate amount of water was applied to each protein leather with a cotton swab, and the hydrogel-forming sponge was sandwiched between them. A 300 g weight was then placed on top and left for 1 minute. One minute after the weight was removed, the maximum stress (N / cm) generated when the tubes were pulled at 25°C and 120 mm / min using a tensile tester was measured. 2 ) was measured.

[0068] Measurement and evaluation of mechanical strength The tensile strength of the hydrogel-forming sponge (25 mm × 7 mm × 7 mm) was measured. Specifically, the top and bottom of the hydrogel-forming sponge were fixed to a tensile tester, and the maximum stress (N / cm) generated when the sponge was pulled at 25°C and 70 mm / min was measured. 2 ) was measured.

[0069] [Table 1]

[0070] Details of the compounds used in Table 1 are shown below. PMAA: Polymethacrylic acid produced in Synthesis Example 1 PAA: Cross-linked polyacrylic acid (Lubrizol, Carbopol 934P NF) PVP: Polyvinylpyrrolidone (BASF, Kollidon 90F, polystyrene equivalent weight average molecular weight = 320,000 (dimethylformamide eluent)) PAAm: Polyacrylamide (MT Aquapolymer, Acofloc N-100, polystyrene equivalent weight average molecular weight = 17 million (dimethylformamide eluent)) HA: Sodium hyaluronate (Kewpie Corporation, Hyaluronsan HA-LQH)

[0071] <Evaluation results> As is clear from the results in Table 1, the hydrogel-forming sponges of Examples 1 and 2, which contain polymethacrylic acid (A) and polymer (B), have an adhesive strength to the skin of 3.0 N / cm 2 Ultra-high mechanical strength of 3.0N / cm 2 On the other hand, when polyacrylic acid was used as the carboxyl group-containing polymer, both the adhesive strength to the skin and the mechanical strength were low, and were inferior to Examples 1 and 2 (Comparative Example 1).

Claims

1. A medical treatment material that forms a hydrogel upon contact with water, Polymethacrylic acid (A), a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymethacrylic acid (A)); Contains The medical treatment material, wherein the polymethacrylic acid (A) is a crosslinked polymer.

2. 2. The medical treatment material according to claim 1, wherein the polymer (B) has an amide group.

3. 3. The medical treatment material according to claim 1, wherein the polymer (B) is at least one of polyvinylpyrrolidone, polyacrylamide, and polymethacrylamide.

4. The medical treatment material according to any one of claims 1 to 3, wherein the proportion of structural units derived from methacrylic acid in the polymethacrylic acid (A) is 80 mass% or more relative to all structural units constituting the polymethacrylic acid (A).

5. a film-like solid material containing one of the polymethacrylic acid (A) and the polymer (B) that has been brought into contact with a solution containing the other polymer, and the resulting product is dried; 5. The medical treatment material according to claim 1, which forms a hydrogel when it absorbs water, and the hydrogel has adhesive properties to biological tissue.

6. A method for producing a medical treatment material that forms a hydrogel upon contact with water, comprising: obtaining a film-like solid material containing one of polymethacrylic acid (A) and a polymer (B) having a functional group capable of forming a hydrogen bond with a carboxyl group (excluding the polymethacrylic acid (A)); a step of contacting the film-like solid with a solution containing the other polymer and then drying the film-like solid; Including, The method for producing a medical treatment material, wherein the polymethacrylic acid (A) is a crosslinked polymer.

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