WO2024162149A1 - Polymère à base d'acide (méth)acrylique ou sel de celui-ci, agent de base pour timbre adhésif transdermique et timbre adhésif transdermique, et leurs procédés de production - Google Patents

Polymère à base d'acide (méth)acrylique ou sel de celui-ci, agent de base pour timbre adhésif transdermique et timbre adhésif transdermique, et leurs procédés de production Download PDF

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WO2024162149A1
WO2024162149A1 PCT/JP2024/002124 JP2024002124W WO2024162149A1 WO 2024162149 A1 WO2024162149 A1 WO 2024162149A1 JP 2024002124 W JP2024002124 W JP 2024002124W WO 2024162149 A1 WO2024162149 A1 WO 2024162149A1
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meth
acrylic acid
salt
acid polymer
producing
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Japanese (ja)
Inventor
智文 近藤
慎哉 神戸
賢司 伊藤
知崇 水野
秀紀 榊原
涼輔 山内
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Toagosei Co Ltd
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Toagosei Co Ltd
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Priority to JP2024574499A priority Critical patent/JPWO2024162149A1/ja
Priority to KR1020257021316A priority patent/KR20250138172A/ko
Priority to CN202480006588.3A priority patent/CN120569416A/zh
Publication of WO2024162149A1 publication Critical patent/WO2024162149A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/04—Acids; Metal salts or ammonium salts thereof
    • C08F220/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2/00—Processes of polymerisation
    • C08F2/38—Polymerisation using regulators, e.g. chain terminating agents, e.g. telomerisation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/04—Acids, Metal salts or ammonium salts thereof
    • C08F20/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2438/00—Living radical polymerisation
    • C08F2438/03—Use of a di- or tri-thiocarbonylthio compound, e.g. di- or tri-thioester, di- or tri-thiocarbamate, or a xanthate as chain transfer agent, e.g . Reversible Addition Fragmentation chain Transfer [RAFT] or Macromolecular Design via Interchange of Xanthates [MADIX]

Definitions

  • the present invention relates to a (meth)acrylic acid polymer or its salt, a base for a skin patch, a skin patch, and a method for producing the same.
  • (Meth)acrylic acid polymers or their salts are useful as dispersants for various pigments, scale inhibitors, cleaning builders, thickeners, binders, and bases for skin patches such as medicinal poultices and poultices, and are used in a wide variety of fields.
  • (meth)acrylic acid-based polymers or salts thereof used as bases for skin patches include, for example, (meth)acrylic acid (salts) with a weight-average molecular weight of 600,000 or more and a degree of dispersion of 5 to 60 (Patent Document 1).
  • the present invention has been made in consideration of the above circumstances, and its purpose is to provide a (meth)acrylic acid-based polymer or a salt thereof, which, when used as a base for a skin patch such as a cataplasm, allows the paste to exhibit an appropriate curing speed and appropriate hardness, thereby preventing the paste from bleeding out and enabling the production of a skin patch with stable paste properties, and a method for producing the same.
  • the present invention also provides a skin patch base containing the above (meth)acrylic acid-based polymer or a salt thereof, a method for producing the same, and a skin patch.
  • the present invention is as follows. [1] A (meth)acrylic acid polymer or a salt thereof, in which the ratio (X) of the peak area of a molecular weight component in the range represented by the mathematical formula (1) to the total area of detected peaks measured by gel permeation chromatography (GPC) is 20% or less. 3 ⁇ logM ⁇ 5.6 (1) (Note that the standard substance in the GPC measurement is sodium polyacrylate, and the eluent is an aqueous sodium nitrate solution.
  • M is the molecular weight of the (meth)acrylic acid polymer or a salt thereof obtained by the GPC measurement, and logM is the common logarithm of M.
  • [2] The (meth)acrylic acid polymer or salt thereof according to [1], wherein the viscosity of a 0.2% by mass aqueous solution at 20° C. is 400 to 650 mPa ⁇ s.
  • [3] The (meth)acrylic acid polymer or a salt thereof according to [1] or [2], wherein the content of insoluble matter in a 0.2% by mass aqueous solution is 1.0% by mass or less.
  • [4] The (meth)acrylic acid polymer or a salt thereof according to any one of [1] to [3], wherein the ratio (M1/M2) of the structural unit M1 derived from (meth)acrylic acid to the structural unit M2 derived from a (meth)acrylic acid salt is 40/60 to 70/30 (molar ratio).
  • a base for a skin patch comprising the (meth)acrylic acid polymer or its salt according to any one of [1] to [4].
  • [6] A skin patch comprising the substrate described in [5].
  • a method for producing a (meth)acrylic acid-based polymer or a salt thereof comprising the step of polymerizing a monomer component containing (meth)acrylic acid and/or a salt thereof by active energy rays in the presence of a chain exchange transfer mechanism type regulator to produce a (meth)acrylic acid-based polymer.
  • a chain exchange transfer mechanism type regulator to produce a (meth)acrylic acid-based polymer.
  • the RAFT agent has the formula (2): (wherein R3 and R4 represent an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aralkyl group).
  • R3 and R4 represent an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aralkyl group.
  • the (meth)acrylic acid-based polymer or salt thereof of the present invention when used as a base for a cataplasm or the like, makes it possible to produce a skin patch that is excellent in quality and has stable paste properties without oozing out of the paste.
  • (meth)acrylic acid polymer or a salt thereof the process for producing the same, and the base for a skin patch of the present invention will each be described in detail below.
  • (meth)acrylic means acrylic and/or methacrylic. 1.
  • the (meth)acrylic acid polymer or salt thereof of the present invention (hereinafter also collectively referred to as "the polymer") has a structural unit derived from (meth)acrylic acid (hereinafter also referred to as “structural unit M1”) and/or a structural unit derived from a (meth)acrylic acid salt (hereinafter also referred to as "structural unit M2”), and the ratio (X) of the peak area of a molecular weight component in the range represented by formula (1) to the total area of detected peaks measured by gel permeation chromatography (GPC) is 20% or less.
  • structural unit M1 structural unit derived from (meth)acrylic acid
  • structural unit M2 structural unit derived from a (meth)acrylic acid salt
  • the ratio (X) of the peak area of a molecular weight component in the range represented by formula (1) to the total area of detected peaks measured by gel permeation chromatography (GPC) is 20% or less.
  • the above ratio (X) is preferably 15% or less, more preferably 13% or less, and even more preferably 0% or less, from the viewpoint that the paste properties can be further stabilized when used as a base for a skin patch.
  • the (meth)acrylate salt means a neutralized product of (meth)acrylic acid, which is a neutralized product of (meth)acrylic acid neutralized with an alkali metal, ammonia, an organic amine, or the like.
  • Specific examples include sodium (meth)acrylate, potassium (meth)acrylate, calcium (meth)acrylate, magnesium (meth)acrylate, and ammonium (meth)acrylate, and these may be used alone or in combination of two or more.
  • sodium (meth)acrylate is preferred because it is useful as a base for skin patches.
  • the acid portion of (meth)acrylic acid may be neutralized with an alkali metal or the like in advance to prepare a (meth)acrylic acid salt as a raw material for polymerization, or (meth)acrylic acid may be polymerized to obtain a (meth)acrylic acid-based polymer, which may then be neutralized with an alkali metal or the like.
  • the viscosity of a 0.2% by mass aqueous solution of the present polymer at 20° C. is preferably 400 to 650 mPa ⁇ s, and more preferably 450 to 600 mPa ⁇ s. If the viscosity of a 0.2% by mass aqueous solution is less than 400 mPa ⁇ s or exceeds 650 mPa ⁇ s, the workability of the present polymer when used as an aqueous solution is significantly reduced.
  • the viscosity of a 0.2% by mass aqueous solution is a value measured using a BM type viscometer at 20° C. and 30 rpm.
  • the content of insoluble matters in a 0.2% by mass aqueous solution of the present polymer is preferably 1.0% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.1% by mass or less. If the content of insoluble matters exceeds 1.0% by mass, the solubility and dispersibility will decrease when used in an aqueous solution, which may result in poor workability and poor physical properties in various applications.
  • the insoluble content was determined by preparing a 0.2% by mass aqueous solution of the present polymer, filtering the aqueous solution by suction through a 140-mesh filter cloth, measuring the mass of the residue on the filter cloth, and calculating the proportion (mass%) of the residue to the total amount of the aqueous solution as the content of the insoluble content.
  • the ratio of structural unit M1 to structural unit M2 (M1/M2) in this polymer is preferably 40/60 to 70/30 in molar ratio, and more preferably 45/55 to 65/35, in order to further stabilize the paste properties when used as a base for a skin patch.
  • the weight average molecular weight (Mw) of the present polymer is preferably from 1 million to 8 million, more preferably from 2 million to 7 million, and even more preferably from 3 million to 6 million, in terms of being able to further stabilize the properties of the paste when used as a base for a skin patch.
  • the number average molecular weight (Mn) of the present polymer, as measured by the GPC measurement is preferably from 100,000 to 3,000,000, more preferably from 300,000 to 2,500,000, and even more preferably from 500,000 to 2,000,000, from the viewpoint that the paste properties can be further stabilized when used as a base for a skin patch.
  • the dispersity (Mw/Mn) of the present polymer is preferably 1.0 to 7.0, more preferably 1.0 to 6.5, and even more preferably 1.0 to 6.0, in order to further stabilize the paste properties when used as a base for a skin patch.
  • the polymer may have structural units derived from monomers other than (meth)acrylic acid, so long as the effects of the present invention are achieved.
  • monomers include unsaturated carboxylic acids such as ⁇ -hydroxyacrylic acid, crotonic acid, maleic acid, itaconic acid, and fumaric acid, and their salts, and unsaturated sulfonic acids such as 2-(meth)acrylamido-2-methylpropanesulfonic acid, (meth)allylsulfonic acid, and styrenesulfonic acid, and their salts. If necessary, one or more of these can be used in an amount of 20 mol % or less based on the total amount of (meth)acrylic acid and (meth)acrylate salts.
  • the present polymer can be obtained by radical polymerization of a monomer component containing (meth)acrylic acid and/or a (meth)acrylate salt. It is also possible to polymerize a mixture of a monomer component containing (meth)acrylic acid and a compound that neutralizes the acid, such as an alkali metal hydroxide or ammonia.
  • the polymerization method include known polymerization methods such as aqueous solution polymerization, slurry polymerization, suspension polymerization, and emulsion polymerization. However, aqueous solution polymerization is preferred in that it can solve problems such as solvent removal, solvent safety, and contamination with surfactants.
  • the aqueous solution polymerization method is a method in which an aqueous solution of the monomer components is adjusted to a predetermined concentration, dissolved oxygen in the reaction system is sufficiently replaced with an inert gas, a radical polymerization initiator is added, and, if necessary, a polymerization reaction is carried out by heating or irradiating with active energy rays (ultraviolet rays, electron beams, etc.).
  • active energy rays ultraviolet rays, electron beams, etc.
  • the polymerization method is preferably a method in which an aqueous solution containing the monomer components and the exchange chain transfer mechanism type control agent is irradiated with active energy rays, and a radical polymerization initiator can be used in combination.
  • radical polymerization initiator examples include azo radical polymerization initiators and so-called photoradical polymerization initiators (excluding azo radical polymerization initiators).
  • the photopolymerization initiators are preferred in that they can further stabilize the paste properties when the polymer is used as a base for a skin patch.
  • azo radical polymerization initiators examples include 2,2'-azobisisobutyronitrile, 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile), dimethyl-2,2'-azobis(2-methylpropionate), 2,2'-azobis(2-methylbutyronitrile), 1,1'-azobis(cyclohexane-1-carbonitrile), 2,2'-azobis[N-(2-propenyl)-2-methylpropionamide], 2,2'-azobis( N-butyl-2-methylpropionamide), 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobis[2-(2-imidazolin-2-yl)propane], 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, 2,2'-azobis[2-(-imidazolin-2-yl)propane] dis
  • the radical polymerization initiator in the aqueous solution polymerization is preferably a water-soluble radical polymerization initiator, and examples thereof include a compound having a hydrophilic group (e.g., a carboxyl group) and/or a salt or hydrate thereof.
  • photoradical polymerization initiators examples include benzoin and its alkyl ethers, acetophenones, anthraquinones, thioxanthones, ketals, benzophenones, xanthones, acylphosphine oxides, ⁇ -diketones, ⁇ -hydroxyketones, etc.
  • acetophenones are preferred, and 2-hydroxy-2-methyl-1-phenyl-1-propanone is most preferred, since they can further stabilize the paste properties when the present polymer is used as a base for a skin patch.
  • a photosensitizer may be used in combination, if necessary.
  • the amount of radical polymerization initiator used is preferably 10 to 10,000 ppm, more preferably 10 to 5,000 ppm, based on the total amount of monomer. If the amount of radical polymerization initiator is less than 10 ppm, polymerization will not occur sufficiently, and if it exceeds 10,000 ppm, the degree of polymerization of the resulting polymer will decrease.
  • Chain transfer mechanism type control agent As the chain transfer mechanism type control agent, control agents used in various polymerization methods such as reversible addition-fragmentation chain transfer polymerization method (RAFT method), polymerization method using an organotellurium compound (TERP method), polymerization method using an organoantimony compound (SBRP method), polymerization method using an organobismuth compound (BIRP method), and iodine transfer polymerization method can be used.
  • RAFT method reversible addition-fragmentation chain transfer polymerization method
  • TRIP method polymerization method using an organotellurium compound
  • SBRP method organoantimony compound
  • BIRP method organobismuth compound
  • iodine transfer polymerization method iodine transfer polymerization method
  • RAFT agents reversible addition-fragmentation chain transfer agents in the RAFT method are preferred, in that the present polymer can be easily produced in an aqueous system, that structural units derived from ionic functional group-containing monomers such as (meth)acrylates can be easily introduced into the present polymer, and that the ratio (X) of the present polymer as measured by GPC can be easily controlled to 20% or less.
  • RAFT RAFT
  • polymerization proceeds via a reversible chain transfer reaction in the presence of a RAFT agent and a free radical polymerization initiator.
  • RAFT agent include a dithioester compound represented by formula (1) or a salt thereof, a trithiocarbonate compound represented by formula (2) or a salt thereof, a dithiocarbamate compound represented by formula (3) or a salt thereof, and a xanthate compound represented by formula (4) or a salt thereof.
  • R 1 to R 9 represent an alkyl group which may have a substituent, an aryl group which may have a substituent, a heteroaryl group which may have a substituent, or an aralkyl group which may have a substituent, and R 6 and R 7 may be bonded to each other to form a ring together with the adjacent nitrogen atom, and the ring may have a substituent.
  • alkyl group of the alkyl group which may have a substituent and is represented by R 1 to R 9 include linear or branched alkyl groups having 1 to 16 carbon atoms (preferably 1 to 12 carbon atoms, more preferably 1 to 6 carbon atoms, and particularly preferably 1 to 4 carbon atoms). Specific examples include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and the like.
  • examples of the substituent include a carboxyl group, an ester group (such as an alkoxycarbonyl group), a cyano group, a hydroxyl group, an alkoxy group, and the like.
  • the alkyl group may have 1 to 4 substituents selected from these substituents.
  • the "aryl group" of the aryl group which may have a substituent and is represented by R 1 to R 9 includes a monocyclic or bicyclic aryl group. Specific examples include a phenyl group, a toluyl group, a xylyl group, a naphthyl group, etc.
  • examples of the substituent include a carboxyl group, an ester group (such as an alkoxycarbonyl group), a cyano group, a hydroxyl group, an alkoxy group, a halogen atom, etc.
  • the aryl group may have 1 to 5 substituents selected from these substituents.
  • examples of the substituent include a carboxyl group, an ester group (such as an alkoxycarbonyl group), a cyano group, a hydroxyl group, an alkoxy group, and a halogen atom.
  • the heteroaryl group may have 1 to 4 substituents selected from these substituents.
  • the "aralkyl group" of the aralkyl group which may have a substituent and is represented by R 1 to R 9 means an alkyl group substituted with an aryl group, and examples thereof include a benzyl group and a phenethyl group.
  • examples of the substituent include a carboxyl group, an ester group (an alkoxycarbonyl group, etc.), a cyano group, a hydroxyl group, an alkoxy group, a halogen atom, etc.
  • the aryl group in the aralkyl group may have 1 to 5 substituents selected from these substituents.
  • R6 and R7 represented by formula (3) may be bonded to each other to form a ring together with the adjacent nitrogen atom, and the ring may have a substituent.
  • the ring include a pyrrolidine ring, a piperidine ring, and a morpholine ring.
  • the ring may have 1 to 3 substituents selected from these substituents.
  • the RAFT agent for aqueous solution polymerization is preferably a water-soluble RAFT agent, and examples thereof include compounds having a thiocarbonylthio group (-CS-S-) and a hydrophilic group (e.g., a carboxyl group) in the molecule and/or salts thereof.
  • Salts of the compounds represented by formulas (1) to (4) include, for example, alkali metal salts (sodium salt, potassium salt, etc.) and ammonium salts when the compound has an acidic group, and for example, inorganic acid salts such as hydrochloric acid and sulfuric acid; organic acid salts of carboxylates (acetate, etc.) and sulfonates (p-toluenesulfonate, etc.) when the compound has a basic group.
  • R3 and R4 are the same or different and are preferably an alkyl group which may have a substituent, more preferably an alkyl group having 1 to 12 carbon atoms (more preferably 1 to 6 carbon atoms) which may have at least one (particularly 1 to 3) substituent selected from the group consisting of a carboxyl group, an ester group (such as an alkoxycarbonyl group), a cyano group, a hydroxyl group, and an alkoxy group, and particularly preferably an alkyl group having 1 to 4 carbon atoms which may have one carboxyl group.
  • R3 and R4 are the same or different and are preferably an alkyl group which may have a substituent, more preferably an alkyl group having 1 to 12 carbon atoms (more preferably 1 to 6 carbon atoms) which may have at least one (particularly 1 to 3) substituent selected from the group consisting of a carboxyl group, an ester group (such as an alkoxycarbonyl group), a cyano group,
  • Examples of the compound represented by formula (2) include groups represented by formula (2A): (wherein R 3A and R 4A are the same or different and represent an alkylene group having 1 to 6 carbon atoms (particularly 1 to 4 carbon atoms) which may have at least one (particularly 1 to 3) substituent selected from the group consisting of an ester group (such as an alkoxycarbonyl group), a cyano group, a hydroxyl group, and an alkoxy group).
  • R 3A and R 4A are the same or different and represent an alkylene group having 1 to 6 carbon atoms (particularly 1 to 4 carbon atoms) which may have at least one (particularly 1 to 3) substituent selected from the group consisting of an ester group (such as an alkoxycarbonyl group), a cyano group, a hydroxyl group, and an alkoxy group).
  • R 3A and R 4A are preferably an alkylene group having 1 to 3 carbon atoms, and examples thereof include 2- ⁇ [(2-carboxyethyl)sulfanylthiocarbonyl]sulfanyl ⁇ propanoic acid and 4-[(2-carboxyethylsulfanylthiocarbonyl)sulfanyl]-4-cyanopentanoic acid.
  • a trithiocarbonate compound represented by formula (2) or a salt thereof is preferred, and a trithiocarbonate compound represented by formula (2A) or a salt thereof is more preferred.
  • the amount of the RAFT agent used is adjusted appropriately depending on the type of monomer and RAFT agent used, but from the viewpoint of reducing the amount of insoluble matter in the aqueous solution of this polymer and controlling the above ratio (X), it is preferably 1 to 500 ppm, and more preferably 3 to 100 ppm, based on the total amount of monomer. If it is less than 1 ppm, sufficient effect will not be obtained, and if it exceeds 500 ppm, the degree of polymerization will be low.
  • active energy rays examples include ultraviolet rays, visible light rays, electron beams, etc. Among these, ultraviolet rays and electron beams are preferred.
  • the wavelength is, for example, 250 to 400 nm.
  • ultraviolet ray irradiation devices include black light fluorescent lamps, fluorescent chemical lamps, high pressure mercury lamps, metal halide lamps, ultraviolet electrodeless lamps, and ultraviolet light emitting diodes (UV-LEDs). The intensity of the light irradiation is determined in consideration of the type of monomer, the type and concentration of the photopolymerization initiator, the viscosity of the target polymer, and the polymerization time.
  • the intensity of the light irradiation may be constant during the polymerization or may be changed during the polymerization .
  • the integrated light amount is preferably 500 mJ/ cm2 or more, more preferably 1,000 mJ/ cm2 or more, and even more preferably 1,500 mJ/cm2 or more. From the viewpoint of reducing energy, the upper limit of the integrated light amount is preferably 25,000 mJ/ cm2 or less, and more preferably 20,000 mJ/ cm2 or less.
  • the light irradiation atmosphere may be air or an inert gas such as nitrogen or carbon dioxide, but among these, a nitrogen atmosphere is preferred. Furthermore, during the polymerization reaction, it is preferable to keep the reaction liquid at 5 to 95°C, more preferably 15 to 80°C, and even more preferably 30 to 60°C. Cooling may be required to maintain the temperature, and although there are no particular limitations on the cooling method, the outer periphery of the reaction vessel is usually cooled with a refrigerant (e.g., cold water, cold methanol, etc.).
  • the photopolymerization reaction of the aqueous solution of the monomer mixture may be either batch-type or continuous-type. When the photopolymerization reaction is carried out in a batch-type manner, the light irradiation time (polymerization time) is preferably 1 to 240 minutes, more preferably 5 to 120 minutes, and even more preferably 15 to 60 minutes.
  • the electron beam irradiation device is not particularly limited, but examples include Cockcroft-Walton type, Van de Graaff type, and resonant transformer type devices.
  • the absorbed dose of the electron beam is preferably 1 to 200 kGy, more preferably 10 to 100 kGy.
  • the acceleration voltage of the electron beam may be appropriately set in the range of 80 to 300 kV depending on the thickness of the substrate or other object to be coated.
  • the oxygen concentration of the electron beam irradiation atmosphere is preferably 500 ppm or less, more preferably 300 ppm or less.
  • the production method of the present invention can be carried out either batchwise or continuously, but it is preferable to employ a continuous polymerization method because of its excellent productivity.
  • a continuous polymerization method various methods are adopted, and a method using an apparatus consisting of a movable belt having a liquid reservoir placed in an airtight chamber and an active energy ray source fixed to the upper part of the airtight chamber is preferred.
  • an aqueous solution of the monomer components is continuously supplied from one side of a movable belt so as to maintain the desired depth.
  • an inert gas such as nitrogen into the airtight chamber to prevent inhibition of polymerization of the monomer components by oxygen.
  • the belt moves continuously together with the aqueous solution of the monomer components, and the aqueous solution of the monomer components is supplied under a fixed active energy ray source.
  • the aqueous solution of the monomer components is polymerized by the active energy rays irradiated from the active energy ray source.
  • the active energy ray source is provided with a section that satisfies the first stage irradiation intensity, and a section that satisfies the second stage irradiation intensity and integrated light amount, and if necessary, the third stage irradiation intensity.
  • the sheet of (meth)acrylic acid polymer or its salt obtained by the above polymerization method can be cut, shredded, dried, and pulverized into a powder product in the usual manner.
  • the polymer is excellent as a base for skin patches such as poultices, and can be mixed with water, a polyvalent metal compound as a crosslinking agent, and a polyhydric alcohol as a water-retaining agent to form a gel-like paste.
  • additives such as inorganic powders and medicinal ingredients can be mixed into the above-mentioned paste, and the components are added and mixed all at once or successively so as to obtain a predetermined blend ratio, and then kneaded to obtain the paste.
  • the blending ratio is usually 5-20% by mass of the skin patch base, 1-50% by mass of a moisture retaining agent such as glycerin, 0.001-2% by mass of a polyvalent metal compound such as aluminum hydroxide, 1-10% by mass of an inorganic additive such as kaolin, 0.01-10% by mass of a medicinal ingredient, and 30-80% by mass of water, based on the total amount of the paste.
  • the skin patch base is less than 5% by mass of the total paste, the adhesiveness, thickening and formability will decrease, and if it exceeds 20% by mass, the viscosity will increase too much, making kneading difficult and making it impossible to achieve a uniform kneading. Therefore, it is usually 5-20% by mass, and preferably 7-12% by mass.
  • the polyvalent metal compound used in preparing the paste functions as a crosslinking agent, and specifically, there are no particular limitations on the polyvalent metal compound, so long as it is an aluminum compound typified by dihydroxyaluminum aminoacetate, aluminum hydroxide, aluminum chloride, aluminum sulfate, aluminum silicate, aluminum phosphate, aluminum magnesium hydroxide, aluminum glycinate, etc., calcium chloride, ferric sulfate, etc., or a compound containing a metal having a valence of two or more (polyvalent metal compound), but among the above-mentioned polyvalent metals, aluminum compounds are preferred. These polyvalent metals may be used alone or in combination, and may be used whether they are water-soluble or hydrophobic.
  • the amount of polyvalent metal compound to be added varies depending on the degree of polymerization and amount of the copolymer, the type of polyvalent metal compound, and the influence of other ingredients, but is usually preferably 0.001 to 2% by mass, and more preferably 0.01 to 1% by mass, based on the total amount of the paste.
  • additives generally used in topical preparations i.e., water-soluble polymers such as gelatin, polyvinyl alcohol, sodium carboxymethylcellulose, polyvinylpyrrolidone, and sodium alginate, may be blended as thickeners or tackifiers in order to further improve suitability during manufacturing and quality during use.
  • water-retaining agent for example, polyhydric alcohols such as glycerin, propylene glycol, sorbitol, and butylene glycol can be used.
  • polyhydric alcohols such as glycerin, propylene glycol, sorbitol, and butylene glycol
  • kaolin, titanium oxide, silicic anhydride, etc. can be used as powdered inorganic fillers, dibutylhydroxytoluene, butylhydroxyanisole, etc. as antioxidants, methyl parahydroxybenzoate, propyl parahydroxybenzoate, etc. as preservatives, etc., and one or more of these can be blended into the paste as necessary.
  • antihistamines such as methyl salicylate, glycol salicylate, menthol, camphor, thymol, peppermint oil, borneol, and glycyrrhizic acid
  • anti-inflammatory analgesics such as indomethacin and flurbiprofen
  • local anesthetics such as dibucaine hydrochloride and lidocaine.
  • the amount of such medicinal components is usually preferably 0.1 to 10% by weight based on the total weight of the paste.
  • the skin patch is made by spreading the gel-like paste prepared as described above on a support such as a nonwoven fabric, covering the applied surface with a peelable film to protect it, then cutting and packaging it.
  • Example 1 A stainless steel tray with a Teflon-coated inner surface was used as a reaction vessel, and an aqueous acrylic acid solution, an aqueous sodium acrylate solution, and ion-exchanged water were charged so that the monomer concentration was 36% by mass, the total amount was 1,160 g, and the compositions of acrylic acid and sodium acrylate were 51 mol % and 49 mol %, respectively. While maintaining the temperature of the mixture of these aqueous monomer solutions at 8° C., dissolved oxygen was expelled with nitrogen.
  • a black light fluorescent lamp manufactured by Toshiba Corporation which radiates light from 300 to 450 nm with a peak wavelength of 352 nm, was used through a 5 mm thick borosilicate glass (manufactured by Corning Incorporated, product name: Pyrex) as a light transmitting material, and was set so that the UV meter UIT-150 (UVD-S365) manufactured by Ushio Inc. was set to 0.40 mW/ cm2 , and polymerization of the monomer preparation solution was initiated by exposure.
  • UV meter UIT-150 UVD-S365
  • Examples 2 to 9, Comparative Examples 1 to 3 The same procedure as in Example 1 was repeated except that the composition ratio of acrylic acid and sodium acrylate, and the types and amounts of the polymerization initiator and chain transfer agent were changed, to obtain a powder sample of the target (meth)acrylic acid polymer salt.
  • ⁇ Molecular weight and peak area ratio (X)> The powder sample was dissolved in pure water to prepare an aqueous solution of a partially neutralized poly(meth)acrylic acid having a concentration of 0.05% by mass. The aqueous solution was subjected to gel permeation chromatography (GPC) to measure the number average molecular weight (Mn), weight average molecular weight (Mw) and dispersity (Mw/Mn) of the (meth)acrylic acid polymer salt based on a calibration curve previously prepared by measuring sodium polyacrylate as a standard substance.
  • GPC gel permeation chromatography
  • the ratio (X) of the peak area of the molecular weight components in the molecular weight range of M 1000 to 3.98 ⁇ 10 5 (3 ⁇ log M ⁇ 5.6) to the total area of the peaks detected by the GPC measurement was determined. Measurement conditions Column: 2 columns of TSKgel GMPW (Tosoh Corporation) Eluent: 0.1 mol/L aqueous sodium nitrate solution Column temperature: 40°C Detector: RI Flow rate: 500 ⁇ L/min
  • ⁇ Viscosity of 0.2% by mass aqueous solution 400 g of pure water was placed in a 500 ml conical beaker, and 0.8 g of an accurately weighed powder sample was added while stirring with a magnetic stirrer. After stirring for 1 hour, the mixture was left to stand sufficiently to dissolve, thereby preparing a (meth)acrylic acid-based polymer or a salt thereof with a concentration of 0.2% by mass. The viscosity was measured at 20° C. and 30 rpm using a BM-type viscometer manufactured by Tokyo Keiki Co., Ltd.
  • AA Acrylic acid
  • AANa Sodium acrylate
  • A1 2,2'-Azobis(2-methylpropionamidine) dihydrochloride
  • A2 2-Hydroxy-2-methyl-1-phenyl-1-propanone
  • B1 3-((((1-carboxyethyl)thio)carbonothioyl)thio)propanoic acid
  • B2 S,S-Dibenzyltrithiocarbonate
  • B3 4-Cyano-4-((dodecylsulfanylthiocarbonyl)sulfanyl)pentanoic acid
  • B4 Mercaptoethanol

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

La présente invention concerne : un polymère à base d'acide (méth)acrylique ou un sel de celui-ci qui, lorsqu'il est utilisé en tant qu'agent de base pour un timbre adhésif transdermique tel qu'un cataplasme, peut produire un timbre adhésif transdermique dans lequel un onguent présente une vitesse de durcissement appropriée et une dureté appropriée, et par conséquent, l'onguent ne suinte pas, et présente des propriétés d'onguent stables ; et un procédé de production du polymère à base d'acide (méth)acrylique ou d'un sel de celui-ci. De plus, l'invention concerne : un agent de base qui est destiné à un timbre adhésif transdermique et qui comprend le polymère à base d'acide (méth)acrylique ou un sel de celui-ci ; un procédé de production de l'agent de base ; et un timbre adhésif transdermique.　Dans le polymère à base d'acide (méth)acrylique ou un sel de celui-ci, la proportion (X) de la surface de pics de composants de masses moléculaires dans une plage exprimée par l'expression (1) à la surface totale de pics détectés par une mesure de chromatographie par perméation de gel (GPC) est d'au plus 20 %.　(1) : 3 ≤ logM ≤ 5,6 (la substance standard dans la mesure de GPC étant du polyacrylate de sodium, et l'éluant étant une solution aqueuse de nitrate de sodium. M représente la masse moléculaire du polymère à base d'acide (méth)acrylique ou un sel de celui-ci obtenue dans la mesure de GPC, et logM est le logarithme décimal de M). Ce procédé est destiné à produire un polymère à base d'acide (méth)acrylique ou un sel de celui-ci, et comprend une étape de production du polymère à base d'acide (méth)acrylique par polymérisation de composants monomères comprenant de l'acide (méth)acrylique et/ou un sel de celui-ci à l'aide d'un faisceau d'énergie actinique en présence d'un agent de régulation de type à mécanisme de transfert de chaîne dégénératif.
PCT/JP2024/002124 2023-01-31 2024-01-24 Polymère à base d'acide (méth)acrylique ou sel de celui-ci, agent de base pour timbre adhésif transdermique et timbre adhésif transdermique, et leurs procédés de production Ceased WO2024162149A1 (fr)

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JP2024574499A JPWO2024162149A1 (fr) 2023-01-31 2024-01-24
KR1020257021316A KR20250138172A (ko) 2023-01-31 2024-01-24 (메타)아크릴산계 중합체 또는 그의 염, 피부 첩부제용 기제 및 피부 첩부제, 및 이들의 제조 방법
CN202480006588.3A CN120569416A (zh) 2023-01-31 2024-01-24 (甲基)丙烯酸系聚合物或其盐、皮肤贴附剂用基剂和皮肤贴附剂、以及它们的制造方法

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008088290A (ja) * 2006-10-02 2008-04-17 Toagosei Co Ltd ポリ（メタ）アクリル酸部分中和物およびその製造方法
WO2019131845A1 (fr) * 2017-12-28 2019-07-04 株式会社 資生堂 Produit cosmétique
CN110156925A (zh) * 2019-05-13 2019-08-23 浙江大学 一种水分散型聚丙烯酰胺类聚合物的制备方法
JP2020117597A (ja) * 2019-01-22 2020-08-06 東亞合成株式会社 水溶性ポリマーの製造方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3804938B2 (ja) 2002-06-10 2006-08-02 株式会社日本触媒 （メタ）アクリル酸（塩）系重合体及びその用途

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008088290A (ja) * 2006-10-02 2008-04-17 Toagosei Co Ltd ポリ（メタ）アクリル酸部分中和物およびその製造方法
WO2019131845A1 (fr) * 2017-12-28 2019-07-04 株式会社 資生堂 Produit cosmétique
JP2020117597A (ja) * 2019-01-22 2020-08-06 東亞合成株式会社 水溶性ポリマーの製造方法
CN110156925A (zh) * 2019-05-13 2019-08-23 浙江大学 一种水分散型聚丙烯酰胺类聚合物的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HAN SHIWEI, QIU TENG, XIONG CHONGWEN, LI XIAOYU, GUO LONGHAI: "Tunable Nitrogen Defects on Graphitic Carbon Nitride toward the Visible-Light-Induced Reversible-Deactivation Radical Polymerization", MACROMOLECULES, AMERICAN CHEMICAL SOCIETY, US, vol. 55, no. 13, 12 July 2022 (2022-07-12), US , pages 5314 - 5325, XP093196105, ISSN: 0024-9297, DOI: 10.1021/acs.macromol.2c01099 *

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