WO2001037660A1 - Sustained-release preparation of aqueous dispersion type and process for producing the same - Google Patents
Sustained-release preparation of aqueous dispersion type and process for producing the same Download PDFInfo
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- WO2001037660A1 WO2001037660A1 PCT/JP2000/008102 JP0008102W WO0137660A1 WO 2001037660 A1 WO2001037660 A1 WO 2001037660A1 JP 0008102 W JP0008102 W JP 0008102W WO 0137660 A1 WO0137660 A1 WO 0137660A1
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
- A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
- A01N25/10—Macromolecular compounds
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
- A01N35/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aliphatically bound aldehyde or keto groups, or thio analogues thereof; Derivatives thereof, e.g. acetals
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/20—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom three- or four-membered rings
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- 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
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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
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
- C08F220/1802—C2-(meth)acrylate, e.g. ethyl (meth)acrylate
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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
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
- C08F220/1804—C4-(meth)acrylate, e.g. butyl (meth)acrylate, isobutyl (meth)acrylate or tert-butyl (meth)acrylate
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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
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
- C08F220/1812—C12-(meth)acrylate, e.g. lauryl (meth)acrylate
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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
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
- C08F220/1808—C8-(meth)acrylate, e.g. isooctyl (meth)acrylate or 2-ethylhexyl (meth)acrylate
Definitions
- the present invention can release almost all of the functional substance contained in the interpenetrating polymer network (hereinafter abbreviated as IPN) at a constant volatilization rate over a long period of time, and can be easily sprayed or sprayed.
- IPN interpenetrating polymer network
- the present invention relates to a water-dispersed sustained-release preparation capable of imparting functions such as adhesion performance and a method for producing the same.
- sustained-release preparations containing functional substances such as pheromones, pharmaceuticals, pesticides, and fragrances. So far, sustained-release preparations in which a functional substance is micro-encapsulated with a cellulose derivative (JP-A-58-186601), a pellet of a synthetic resin having compatibility with the functional substance. The product is impregnated with a functional substance and pulverized, and the surface is coated with an inorganic powder or a synthetic resin that is incompatible with the functional substance.
- Japanese Patent Application Laid-Open No. Hei 7-213 743 discloses a suspension prepared by mixing and suspending a synthetic resin pellet containing a functional substance with an OZW-type acryl-based adhesive Emulsion. Many methods have been proposed.
- microencapsulated sustained-release preparation disclosed in Japanese Patent Application Laid-Open No. 58-183601 is difficult to control the release rate of the functional substance, and the capsule covering the surface is difficult to control. Had poor mechanical strength and was not sufficient as a sustained-release preparation.
- the sustained-release preparation disclosed in Japanese Patent Application Laid-Open No. 6-192024 prevents blocking, but requires secondary processing of coating the surface, so that the process for production is inevitable. There was a problem that the number increased.
- the sustained-release preparation disclosed in Japanese Patent Application Laid-Open No. 7-231374 has a high possibility that unevenness occurs during spraying or spraying due to poor water dispersibility of the preparation.
- problems such as necessity.
- a first invention for solving the above-mentioned problems is a microgel A formed from a monomer component having a high affinity with a functional substance, and a microgel B formed from a monomer component having a low affinity with a functional substance.
- This is a water-dispersed sustained-release preparation characterized by containing a functional substance in an interpenetrating polymer network consisting of:
- the second invention is the water-dispersed sustained-release preparation according to the first invention, wherein the microgel A and the microgel B in the interpenetrating polymer network are chemically bonded. .
- the microgel A and the microgel B in the interpenetrating polymer network each contain a photoinitiating group-containing (meth) acrylate monomer (component al) or a radical polymerizable organic peroxide (component a).
- a photoinitiating group-containing (meth) acrylate monomer component al
- a radical polymerizable organic peroxide component a
- the microgel A is one type selected from the group consisting of a photoinitiating group-containing (meth) acrylate monomer (component al) and a radical polymerizable organic peroxide (component a2);
- a photoinitiating group-containing (meth) acrylate monomer component al
- a radical polymerizable organic peroxide component a2
- the invention according to any one of the first to third inventions, which is formed from a monomer component containing an acrylate monomer (component b) and a polyfunctional (meth) acrylate monomer (component c). This is a water-dispersed sustained-release preparation.
- a fifth invention is directed to any one of the first invention to the fourth invention, wherein the microgel A is further formed from a monomer component containing a hydrophilic monomer (component d). It is a water-dispersed sustained-release preparation.
- the microgel B contains a (meth) acrylate monomer (component e) and a polyfunctional (meth) acrylate monomer (component f).
- component e a (meth) acrylate monomer
- component f a polyfunctional (meth) acrylate monomer
- a seventh invention is characterized in that the functional substance is a pheromone, and that the (meth) acrylate monomer (component b) of the microgel A has an alkyl chain having 6 to 20 carbon atoms.
- the water-dispersed sustained-release preparation according to any one of the first to sixth inventions.
- An eighth invention is characterized in that the functional substance is a pheromone, and the (meth) acrylate monomer (component e) of the microgel B has an alkyl chain having 1 to 8 carbon atoms.
- the water-dispersed sustained-release preparation according to any one of the first to seventh inventions.
- a ninth invention is the aqueous dispersion of any one of the first to eighth inventions, wherein the pH value of the emulsion of the water-dispersed sustained-release preparation is 2 to 9. Is a sustained-release preparation.
- the tenth invention is directed to a (meth) acrylic acid ester monomer selected from a photoinitiating group-containing (meth) acrylic acid ester monomer (component a 1) and a radical polymerizable organic peroxide (component a 2)
- a monomer component containing (component b), a polyfunctional (meth) acrylate monomer (component c) and, if necessary, a hydrophilic monomer (component d), as well as functional substances, surfactants, and polymerization A first step in which an emulsion is obtained by emulsion copolymerization using an initiator and water; and (meth) an acrylic acid ester monomer (component e) and a plurality of emulsions in the emulsion obtained in the first step.
- FIG. 1 and FIG. 2 are graphs showing a volatile state of a functional substance in a preparation of an example.
- IPN is a substance in which two polymers are entangled when a new polymer is polymerized or cross-linked while a polymer network is present. A microcell is formed in the gap where the two polymers are entangled.
- the water-dispersed sustained-release preparation of the present invention is one in which microgel A and microgel B have an IPN structure and a functional material is dispersed in microcells therein.
- the functional substance is released from the microcells at a constant volatilization rate from the microcells.
- microgel A contains functional substances, monomers with high affinity for functional substances, and polyfunctional monomers
- microgel B contains monomers and polyfunctional monomers with low affinity for functional substances. Is an essential component, and the unit composed of these monomers controls the sustained release.
- the monomer having a high affinity for the functional substance constituting the microgel A has a role of stably retaining the functional substance in the microgel.
- a stable emulsion cannot be obtained.
- a polymer component weight average molecular weight: 500 or more is used obtained by ordinary solution polymerization of the monomer component to be used and the functional substance are weighed. Mix at a ratio of 1: 9, and you can judge by the dispersion state of the mixed solution at that time. For example, if the polymer component is easily dissolved in the functional substance, the affinity is high, and if it is not dissolved, the affinity is low.
- any monomer having a high affinity for the functional substance can be used.
- a (meth) acrylate monomer (component b) is used, a stable emulsion can be easily obtained, and It is preferable from the viewpoint of the conversion.
- other monomer components may be contained in the monomer component forming the microgel A as long as the function of the microgel II is not impaired.
- component b examples include (meth) acrylic acid ester monomers having an alkyl chain having 1 to 24 carbon atoms, such as methyl (meth) acrylate, ethyl (meth) acrylate, and propyl (meth) acrylate. , Butyl (meth) acrylate U, pentyl (meth) acrylate, hexyl (meth) acrylate, n-octyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, lauryl (meth) acrylate, cetyl (meth) acrylate, Stearyl (meth) acrylate, behenyl (meth) acrylate, and the like.
- acrylic acid ester monomers having an alkyl chain having 1 to 24 carbon atoms such as methyl (meth) acrylate, ethyl (meth) acrylate, and propyl (meth) acrylate.
- a (meth) acrylate monomer having an alkyl chain having 6 to 20 carbon atoms is preferable in order to have an affinity with the pheromone.
- Specific examples include hexyl (meth) acrylate, n-methylhexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, lauryl (meth) acrylate, cetyl (meth) acrylate, stearyl ( Meth) acrylate and the like.
- (meth) acrylic acid ester monomers having an alkyl chain having 8 to 20 carbon atoms More preferred are (meth) acrylic acid ester monomers having an alkyl chain having 8 to 20 carbon atoms, and specific examples thereof include, for example, n-butyl octyl (meth) acrylate, 2-ethylhexyl (Meth) acrylate, lauryl (meth) acrylate, cetyl (meth) acrylate, stearyl (meth) acrylate, and the like.
- the monomer having low affinity for the functional substance constituting the microgel B is a component used for the purpose of releasing the functional substance and for imparting the adhesion of the particles. Therefore, a monomer different from the above high affinity monomer is used. Furthermore, it is necessary to select a monomer that swells the microgel A for the monomer having a low affinity. If the microgel A cannot be swollen, the polymerization proceeds outside the microgel A, and it becomes impossible to form IPN.
- the criterion when using a monomer having a low affinity is determined based on the criterion for determining the affinity with the above-mentioned functional substance, and a polymer component (eg, a polymer component obtained by solution polymerization of a monomer having a high affinity) is used.
- a polymer component eg, a polymer component obtained by solution polymerization of a monomer having a high affinity
- low affinity monomer are mixed at a weight ratio of 1: 9
- the dispersion state of the mixed solution at that time is judged.
- the polymer component can be dissolved or dispersed, it can be used as a monomer constituting microgel B, but if it cannot be dissolved at all, it cannot be used because it cannot form IPN. .
- any monomer having a low affinity for the functional substance can be used.
- (meth) acrylic acid ester monomer (component e) when used, particle attachment may occur. It is preferable from the viewpoint of easy control of the adhesion and the polymerization conversion rate.
- one monomer component forming the microgel B may contain other monomer components as long as the function of the microgel B is not impaired.
- component e examples include a (meth) acrylate monomer having an alkyl chain having 1 to 24 carbon atoms, such as methyl (meth) acrylate, ethyl (meth) acrylate, and propyl (meth) acrylate.
- a (meth) acrylate monomer having an alkyl chain having 1 to 24 carbon atoms such as methyl (meth) acrylate, ethyl (meth) acrylate, and propyl (meth) acrylate.
- a substance having an alkyl chain having 1 to 8 carbon atoms is preferable.
- Specific examples include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, pentyl (meth) acrylate, hexyl (meth) acrylate, n-octyl (meth) acrylate, 2-ethylhexyl (meth) acrylate and the like. More preferably, it has an alkyl chain having 1 to 6 carbon atoms.
- a polyfunctional monomer is an essential component constituting the microgels A and B. Any monomer having two or more radically polymerizable functional groups, for example, a vinyl group, can be used.
- a polyfunctional (meth) acrylate monomer component c: used for microgel A, component: microphone
- Used for oral gel B makes it possible to control good sustained release.
- This monomer forms a gel by cross-linking a monomer with high affinity or a monomer with low affinity with the functional substance, and forms a microcell upon IPN conversion. Therefore, it is possible to control the sustained release property by the amount of the polyfunctional monomer used. Basically, as the amount of the polyfunctional monomer used increases, the microcells tend to be denser and the sustained release tends to be slower, and as the amount used decreases, the microcells become coarser and the sustained release tends to be faster. There is a tendency to be.
- component c and component f include, for example, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene dimethyl alcohol (meth) acrylate, polyethylene glycol di (meth) acrylate, 1, 3-butylene glycol di (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,6-hexanediol di (meth) acrylate, neopentyldarichol di (meth) acrylate, diacrylphthalate, aryl (Meth) acrylate, 2-hydroxy-1-, 3-di (meth) acryloxypropane, 2,2bis (4 ((meth) acryloxyethoxy) phenyl) propane, trimethylolpropanetri (meth) acrylate, tetra Ramethylol methane Meth) Akurireto, pen evening erythritol!
- component C and the component f only one type of monomer may be used, or two or more types of monomers may be used in combination.
- the number of microcells increases because the ratio of IPN in the particles increases, as compared with the IPN without chemical bonding. For this reason, the functional substance is uniformly dispersed in the microcell. Therefore, the aqueous dispersion stability of the particles is improved, and the sustained release rate tends to be more easily controlled.
- the reason for the increase in the ratio of IPN is that the radical generation source for forming microgel B is present in microgel A, so that IPN is formed efficiently.
- a photoinitiator-containing (meth) acrylate monomer that functions as a photopolymerization initiator in microgel A or radical polymerization that functions as an organic peroxide Organic peroxide (component a 2) is essential.
- component a1 which is a (meth) acrylate monomer containing a photoinitiating group
- component a1 which is a (meth) acrylate monomer containing a photoinitiating group
- CH 2 C (CH 3 ) -C-0- (CH2) 2 -0-C-0- (CI3 ⁇ 4) 2 -0- ⁇ -CC (CH3) 2 -OH
- radical polymerizable organic peroxide for example, t-butylperoxyacryloyloxyshethyl carbonate, t-butylperoxy Methacryloyloxyl carbonate, t-butylperoxyaryl carbonate, t-butylperoxymethacrylic carbonate, and the like.
- t-butyl peroxyacryloyloxyshethyl carbonate t-butyl peroxymethacryloyloxyshethyl carbonate, etc. is important in terms of IPN formation and the initiation of decomposition of peroxide bonds. It is preferable because the temperature is high.
- hydrophilic monomer (component d) that dissolves in water at an arbitrary ratio can be copolymerized with the microgel A in order to improve the stability of the emulsion.
- the hydrophilic component is oriented on the surface of the polymer (particle), so that the water dispersibility can be enhanced.
- component d include, for example, (meth) acrylic acid, itaconic acid, crotonic acid, fumaric acid, maleic acid, mesaconic acid, citraconic acid, and 3- (meth) acryloyloxicetyl hydrogen Unsaturated monocarboxylic acid monomers such as succinate, or unsaturated acids such as maleic anhydride, itaconic anhydride, citraconic anhydride, 4 methacryloxyshethyl trimellitate anhydride Anhydrous monomer, or hydroxyphenoxy polyethylene glycol (methyl) acrylate with 2 to 90 moles of added hydroxyphenoxyethyl (meth) acrylate and ethylene oxide, 2 moles of added mole of propylene oxide ⁇ 90 hydroxy phenoxy polypropylene glycol (meth) acrylate, vinyl phenol, hydro A phenolic group-containing monomer such as cyphenyl maleimide, or a sulfonic acid group-containing monomer such as
- (Meth) A quaternary ammonium base-containing (meth) acrylate monomer such as hydroxypropyltrimethylammonium ammonium acrylate, or an arylglycol or polyethylene oxide monomer having an added mole number of 3 to 32 of ethylene oxide.
- aryl compound monomers such as (meth) aryl ether and methoxypolyethylene glycol monoallyl ether; or cyclic heterocycle-containing compound monomers such as N-vinylpiperidone and N-vinylcaprolactam; And vinyl cyanide monomers such as acrylonitrile, methacrylonitrile, and vinylidene cyanide.
- unsaturated monocarboxylic acid monomers such as hydroxysuccinyl hydrogen succinate, or hydroxyphenoxyl (meth) acrylate, or hydroxyphenol polyethylene glyco
- styrene Sulfonic acid acrylamide-t-butyl sulfonic acid, sulfonic acid group-containing monomers such as (meth) aryl sulfonic acid, or N, N-dimethyl (meth) acryl amide, N, N-getyl (meth) acryl amide, (Meth) acrylamide monomers such as N-isopropyl (meth) acrylamide, acryloylmorpholine, N, N-dimethylaminopropyl (methyl) acrylamide, (meth) acrylamide, and N-methylol (meth) acrylamide Or 2-hydroxyethyl
- Hydroxyalkyl (meth) acrylate monomers such as (meth) acrylate, 2-hydroxypropyl (meth) acrylate, and 2,3-dihydroxypropyl (meth) acrylate, or the number of moles of added ethylene oxide is 2 to 9 8
- Polyethylene glycol mono (meth) acrylate, nonylphenol monoethoxylate (meth) acrylate having 1 to 4 moles of added ethylene oxide (meth) acrylate, methoxyl acrylate, ethoxydiethylene glycol (meth) acrylate, and other polyoxyethylene monomers Includes (meth) acrylate monomer or quaternary ammonium base such as (meth) acrylic acid hydroxyethyltrimethylam
- the water-dispersed sustained-release preparation containing the functional substance of the present invention can be used in any form of an aqueous dispersion in the form of an emulsified liquid, a dried powder thereof, and a film thereof. It is.
- a method for obtaining a sustained-release preparation in a dry state from a water-dispersed state all the usual means for removing water can be used.
- the preparation is produced by vacuum drying, freeze-drying and the like.
- the solid content in the water-dispersed state (total amount of microgel A and microgel B) is usually 1 to 60 wt%, preferably 10 to 50 wt%, and the sustained-release property dispersed in water.
- the average particle size of the preparation is usually from 10 nm to 100 nm, preferably from 50 nm to 70 nm.
- the pH value of the emulsified liquid may be adjusted with an alkaline substance such as aqueous ammonia or sodium hydroxide to improve the water dispersibility of the sustained-release preparation and prevent denaturation of the functional substance. It may be prepared.
- the range of the pH value is usually 2 to 9, preferably 3 to 8, and more preferably 3.5 to 7.5. If the pH value deviates from the above range, the stability of the emulsion will be impaired.
- the monomer component forming the microgel A only one monomer may be used in each component, or two or more monomers may be used in combination.
- the monomer component forming the microgel A includes, besides the monomer, other monomer components such as styrene, 0! -Methylstyrene, and vinyltoluene as long as the function of the microgel A is not impaired.
- a vinyl ester monomer such as an aromatic vinyl monomer, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl vivalate, vinyl laurate, and vinyl versatate may be used.
- the type and ratio of the above components used when forming the microgel A by emulsion copolymerization can be appropriately changed according to the functional substance to be contained.
- the use ratio of the component a1 or the component a2 based on the total amount of the monomer components of the microgel A is usually 0 to 20% by weight, preferably 0.05 to 15% by weight. If it exceeds 20% by weight, the photoinitiating group or peroxidation bond introduced into the obtained microgel may cause radical collapse or extreme gelation during the reaction.
- the use ratio of the component b is usually 45 to 99.5% by weight, preferably 50 to 95% by weight, based on the total amount of the monomer components of the microphone mouth gel A. If the amount is less than 45% by weight, the functional substance cannot be stably retained in the sustained-release preparation, and if the amount exceeds 99% by weight, the emulsification tends to be unstable and agglomerates tend to be easily generated.
- the proportion of component c used is based on the total amount of the monomer components of Mike mouth gel A, Usually 0.05 to 15% by weight, preferably 0.2 to: L 0% by weight. If the content is less than 0.05% by weight, the sustained release speed is too fast, and if it exceeds 15% by weight, the sustained release performance tends to be lost.
- the use ratio of the component d is usually 0 to 45% by weight, preferably 5 to 40% by weight, based on the total amount of the monomer components of the microgel A. If the content exceeds 45% by weight, the functional substance tends to be unable to be stably retained in the sustained-release preparation.
- the proportion of the component e based on the total amount of the monomer components forming the microgel B is usually 60 to 99.9% by weight, preferably 70 to 99% by weight.
- Component f is used in an amount of usually 0.1 to 40% by weight, preferably 1 to 30% by weight, based on the total amount of components e and f.
- the ratio of microgel B to microgel A is usually 10 to 500 parts by weight, preferably 20 to 400 parts by weight, based on 100 parts by weight of microgel A. If the amount is out of the range of 10 to 500 parts by weight, it becomes difficult for the IPN to have a uniform and dense interpenetrating network structure, which is not preferable as a sustained-release preparation.
- sustained-release products of the IPN type formed by microgel A and microgel B must maintain the release amount of the functional substance in the late stage at the same level as the initial release amount It shows excellent sustained release performance.
- Examples of the functional substance include the following. That is, 14-methyl-11-year-old kutadecene, Z9-trichocene, E4-tridecenyl acetate, dodecyl acetate, Z7-dodecenyl acetate, Z8-dodecenyl acetate, Z9-dodecenyl acetate , E 7, E 9-dodecadienyl acetate, Z 9-tetradecyl acetate, E 11-tetradecenyl acetate, Z 11-tetradecenyl acetate, Z 9, E 11- Tetradecadienyl acetate, Z 9, E 12—Tetradecadienyl acetate, Z 11—Hexadecenyl acetate, Z 7, ZZE 11—Hexadecadienyl acetate, Z 13—Hexadecatrienyl Acetate, Z 13—Deceenyl acetate, E
- the content of these functional substances is usually 0.1 to 150 parts by weight, preferably 5 to 100 parts by weight, based on 100 parts by weight of the microgel A. If the amount is less than 0.1 part by weight I, the sustained release performance will be insufficient, and if it exceeds 150 parts by weight, the water dispersibility of the microgel tends to decrease.
- a method for producing a water-dispersed sustained-release preparation containing a functional substance in IPN synthesized from the two steps will be described.
- the manufacturing method can be performed in three ways.
- the monomer shown here describes the case where a typical monomer is used, it is not limited to these monomers.
- a method of synthesizing without using the component a1 or the component a2 will be described.
- microgel A is obtained by emulsion copolymerization.
- the functional substance, surfactant and water are pre-emulsified by using a stirrer having a high shearing force such as a homomixer to uniformly emulsify and disperse.
- a stirrer having a high shearing force such as a homomixer to uniformly emulsify and disperse.
- This pre-emulsion is dropped into water containing a polymerization initiator to carry out emulsion copolymerization.
- the functional material is incorporated into the microgel A as the polymerization proceeds.
- the polymerization initiator may be added in advance during the preparation of the pre-emulsion.
- the surfactant is not particularly limited.
- examples of the surfactant include an anionic surfactant, a nonionic surfactant, a cationic surfactant, an amphoteric surfactant, a polymer surfactant, and a reactive emulsifier. All surfactants can be used.
- the surfactants can be used alone or as a mixture of two or more kinds.
- the amount of the surfactants used is 0.1 to 25 parts by weight based on 100 parts by weight of the total amount of the monomers used in the first step. Parts, preferably 0.5 to 20 parts by weight. If the amount is less than 0.1 part by weight, the emulsification becomes unstable and agglomerates are formed. If the amount exceeds 25 parts by weight, the viscosity of the emulsion tends to increase.
- anionic surfactants in particular, anionic surfactants
- nonionic surfactant it is preferable to use a nonionic surfactant.
- the polymerization initiator is not particularly limited, and those described below can be used.
- the amount of the polymerization initiator to be used is generally 0.05 to 10 parts by weight, preferably 0.1 to 5 parts by weight, based on 100 parts by weight of the total amount of the monomers used in the first step. If the amount is less than 0.05 part by weight, the polymerization initiating ability tends to decrease, and if it exceeds 10 parts by weight, the polymerization stability tends to decrease.
- the polymerization temperature during the emulsion polymerization is usually 40 to 120 ° (: preferably 60 to 100 ° C, and the polymerization time is usually 2 to 12 hours, preferably 4 to 10 hours.
- the microgel A is formed into the microgel B. That is, the (meth) acrylate monomer is contained in the emulsion of the microgel A containing the functional substance obtained in the first step. (Component e), and a polyfunctional (meth) acrylic acid ester monomer (component) are added dropwise, and a polymerization initiator is added and polymerized. You can use the one described in.
- the amount of the polymerization initiator to be used is generally 0.05 to 10 parts by weight, preferably 0.1 to 5 parts by weight, based on 100 parts by weight of the total amount of the monomers used in the second step. If the amount is less than 0.05 parts by weight, the polymerization initiating ability tends to decrease, and if it exceeds 10 parts by weight, the polymerization stability tends to decrease.
- the polymerization temperature is usually 40 to 120, preferably 60 to 100 ° C, and the polymerization time is usually 2 to 12 hours, preferably 4 to 10 hours.
- microgel A containing a photoinitiating group is obtained by emulsion copolymerization. That is, a photoinitiating group-containing (meth) acrylate monomer (component al), a (meth) acrylate monomer (component), and a polyfunctional (meth) acrylate monomer (component c), if necessary.
- Emulsion copolymerization is carried out using a monomer component containing a hydrophilic monomer (component d), a functional substance, a surfactant, a polymerization initiator and water to obtain an emulsion.
- a preferred process as the first step will be described more specifically.
- a (meth) acrylate monomer containing a photoinitiating group component al
- a (meth) acrylate monomer component b
- a polyfunctional (meth) acrylate monomer component c
- Pre-emulsification of a monomer component containing a hydrophilic monomer component d
- a functional substance a surfactant
- water using a stirrer with a strong shearing force such as a homomixer to uniformly emulsify and disperse.
- This pre-emulsion is dropped into water containing a polymerization initiator to carry out emulsion copolymerization.
- the functional substance is taken into the microgel A as the polymerization proceeds.
- the polymerization initiator may be added in advance during the preparation of the pre-emulsion liquid.
- the surfactant is not particularly limited, and all surfactants can be used.
- the surfactants can be used alone or as a mixture of two or more kinds.
- the amount of the surfactants is from 0.1 to 25 parts per 100 parts by weight of the total amount of the monomers used in the first step. Parts by weight, preferably 0.5 to 20 parts by weight. If the amount is less than 0.1 part by weight, the emulsification becomes unstable and agglomerates are formed. If the amount exceeds 25 parts by weight, the viscosity of the emulsion tends to increase.
- the surfactants it is particularly preferable to use an anionic surfactant or a nonionic surfactant.
- the polymerization initiator is not particularly limited, and those described below can be used.
- the amount of these polymerization initiators to be used is usually 0.05 to 10 parts by weight, preferably 0.1 to 5 parts by weight, based on 100 parts by weight of the total amount of the monomers used in the first step. is there.
- the amount is less than 0.05 part by weight, the polymerization initiation ability tends to decrease, and if it exceeds 10 parts by weight, the polymerization stability tends to decrease.
- the polymerization temperature during the emulsion polymerization is usually 40 to 120 ° C., preferably 60 to 100 ° C., and the polymerization time is usually 2 to 12 hours, preferably 4 to 10 hours. Time.
- microgel B is bonded to microgel B. That is, in the emulsion of the microgel A containing the functional substance obtained in the first step, the (meth) acrylate monomer (component e), and the polyfunctional (meth) acrylic acid The ester monomer (component f) is added dropwise while adding the active energy ray. Polymerize by irradiation.
- a microgel A containing a peroxide bond is obtained by emulsion copolymerization. That is, a radically polymerizable organic peroxide (component a2), a (meth) acrylate monomer (component b), a polyfunctional (meth) acrylate monomer (component c), and, if necessary, hydrophilic.
- Emulsion copolymerization is carried out using a monomer component containing a functional monomer (component d), a functional substance, a surfactant, a polymerization initiator and water to obtain an emulsion.
- a radical polymerizable organic peroxide component a2
- a (meth) acrylate monomer component b
- a polyfunctional (meth) acrylate monomer component c
- Pre-emulsification of monomer components including hydrophilic monomers (component d), functional substances, surfactants, and water using a homo-mixer or other high-shearing stirrer to uniformly emulsify and disperse Let it.
- This pre-emulsion liquid is dropped into water containing a polymerization initiator to carry out emulsion copolymerization.
- the functional substance is incorporated into the microgel A as the polymerization proceeds.
- the polymerization initiator may be added in advance at the time of preparing the pre-emulsion.
- the surfactant is not particularly limited, and all surfactants can be used. These surfactants can be used alone or as a mixture of two or more kinds.
- the amount of the surfactant used is 0.1 to 2 parts by weight based on 100 parts by weight of the total amount of monomers used in the first step. It is 5 parts by weight, preferably 0.5 to 20 parts by weight. If the amount is less than 0.1 part by weight, the emulsification becomes unstable and aggregates are formed. If the amount exceeds 25 parts by weight, the viscosity of the emulsion tends to increase.
- the polymerization initiator is not particularly limited, and those described below can be used.
- the amount of these polymerization initiators to be used is usually 0.05 to 10 parts by weight, preferably 0.1 to 5 parts by weight, based on 100 parts by weight of the total amount of the monomers used in the first step. is there. If the amount is less than 0.05 parts by weight, the ability to initiate polymerization is reduced, and if the amount exceeds 10 parts by weight, The polymerization stability tends to decrease.
- the polymerization temperature during the emulsion polymerization is usually 40 to 90 ° C, preferably 60 ° (: to 80 ° C, and the polymerization time is usually 2 to 12 hours, preferably 4 to 10 hours. It is.
- microgel B is bonded to microgel B. That is, in the emulsion of the microgel A containing the functional substance obtained in the first step, the (meth) acrylate monomer (component e), and the polyfunctional (meth) acrylic acid The ester monomer (component f) is added dropwise and polymerized using the peroxide bond in microgel A. Since the 10-hour half-life temperature of the peroxide bond is 90 ° C. or higher, most of the peroxide bond remains when the microgel A is synthesized.
- the reaction condition in the second step is a polymerization temperature of 80 to 180, preferably 110 to 150 ° C., using a pressurizable reactor such as an autoclave.
- the polymerization time is usually 2 to 12 hours, preferably 4 to 10 hours.
- anionic surfactants include alkali metal alkyl sulfates such as sodium dodecyl sulfate and potassium dodecyl sulfate, ammonium alkyl sulfates such as ammonium dodecyl sulfate, sodium dodecyl polydalichol ether ether sulfate, and the like.
- Alkylsulfonates such as sodium sulfolisinoate, alkali metal salts of sulfonated paraffins or ammonium salts of sulfonated paraffins, sodium laurate or triethanolamine oleate or triethanolamine aviate Alkyl salts such as sodium dodecylbenzenesulfonate or alkali metal phenol hydroxyethylene metal salt sulphate, etc.
- Dialkyl sulfosuccinates such as kilnafylene sulfonic acid salt, naphthalene sulfonic acid formalin condensate, sodium octyl sulfosuccinate, polyoxyethylene alkyl ether sulfate salt, polyoxyethylene alkyl ether sulfate Examples thereof include monosalts and polyoxyethylene alkylarylsulfate salts.
- Non-ionic surfactants include polyoxyethylene alkyl ether, poly Condensation of fatty acid monoglycerides, such as fatty ethers, sorbitan fatty acid esters, polio fatty acid esters, glycerol monolaurate, polyoxyethyleneoxypropylene copolymers, or ethylene oxide with fatty acid amines or amides or acids Products and the like are mentioned as examples.
- cationic surfactant examples include octadecylamine acetate, dodecyltrimethylammonium chloride, hexadecyltrimethylammonium chloride, benzylammonium chloride, and dioleyldimethylammonium chloride. It is listed as.
- amphoteric surfactant examples include dimethyl lauryl benzoin, sodium lauryl diaminoethyl glycine, amido benzoin type, and imidazoline type.
- Polymer surfactants include polyvinyl alcohol, or sodium poly (meth) acrylate, potassium poly (meth) acrylate, ammonium poly (meth) acrylate, hydroxyethyl ethyl poly (meth) acrylate, poly ( Examples thereof include water-soluble polymers such as hydroxypropyl (meth) acrylate.
- Examples of the reactive emulsifier include Lamtell S-180 or S-180A manufactured by Kao Corporation, Aqualon RN series or HS Series or New Frontier A-229E or N-177E manufactured by Daiichi Kogyo Seiyaku Co., Ltd. Antox MS-60, MS-2N or RA-1120 or RA-2614 or RM A-564 or RMA-568 or RM Al 114 manufactured by Nippon Emulsifier Co., Ltd., Adeka manufactured by Asahi Denka Kogyo Co., Ltd. Rear soap NE-10 or NE-1 20 or NE-40, or NK ester M20G or M-40G or M-90G or M-230G manufactured by Shin-Nakamura Chemical Co., Ltd. is an example.
- the polymerization initiator is not particularly restricted but includes sodium persulfate, potassium persulfate, ammonium persulfate, acetyl chloride, isobutyl peroxide, octyl peroxide, decanol.
- sodium persulfate, potassium persulfate, ammonium persulfate, acetyl peroxide, isobutyl peroxide, 3,3,5-trimethylhexanoyl baroxide are preferred.
- Example 1 After charging 60 parts by weight of ion-exchanged water into a flask equipped with a stirrer, thermometer, cooler, dropping device, and nitrogen gas inlet tube, the temperature was raised to 80 ° C with stirring while blowing in nitrogen gas. did. Thereafter, 0.4 part by weight of potassium persulfate was added as a polymerization initiator.
- the pre-emulsion was dropped into the flask over 3 hours while maintaining the temperature condition of 80 ° C, and then polymerized for another 4 hours to obtain the emulsion (water containing Z11-hexadecenyl acetate). A dispersed microgel A) was obtained.
- the obtained water-dispersed sustained-release preparation was dried to obtain a powdered Z-11-hexadecenyl acetate-containing sustained-release preparation.
- the sustained-release preparation containing Z 11 -hexadecenyl acetate was placed under the conditions of 40 ° C. and a wind speed of 0.5 mZ seconds.
- the release rate of Z111-hexadecenyl acetate from the drug product by weight change it showed good sustained-release performance, and the remaining amount of Z111-hexadecenyl acetate after 40 days The rate was 15%.
- Examples 2 to 6 After charging 60 parts by weight of exchanged water into a flask equipped with a stirrer, a thermometer, a cooler, a dropping device, and a nitrogen gas inlet tube, the temperature was raised to 65 ° C. with stirring while blowing nitrogen gas. Thereafter, 0.4 parts by weight of 2,2-azobis (2-amidinopropane) dihydrochloride was added as a polymerization initiator.
- the pre-emulsion was dropped into the flask over 3 hours while maintaining the temperature condition of 65 ° C, and polymerization was further performed for 4 hours to obtain an emulsion (water-dispersible emulsion containing E MOD). Microgel A) was obtained.
- the average particle size of the obtained microgel was 200 nm as measured by dynamic light scattering (DLS).
- the obtained water-dispersed sustained release preparation was dried to obtain a film-form EMOD-containing sustained release preparation.
- the EMOD-containing sustained-release preparation was placed under the conditions of 35 ° C and a wind speed of 1.5 mZ seconds, and the release rate of EMOD from the preparation was measured by weight change.
- the results are shown in FIG. As can be seen from FIG. 1, the release amount of EMOD of these sustained-release preparations was almost constant over 40 days, indicating good sustained-release performance.
- Example 7> Using a monomer component having the same composition ratio as in Example 3, using Z 11 —hexadecenyl acetate (sex pheromone of Konaga) instead of EM ⁇ D as the functional substance, Emulsion copolymerization and radical polymerization were performed by the same operation. By the same method as in Example 1, it was confirmed that the polymerization was completed. The obtained emulsion did not precipitate aggregates and the like even when left for a long period of time, and showed stable water dispersibility. Further, the pH value of the emulsion was 5.4.
- the water-dispersed sustained-release preparation containing the synthesized Z11-hexadecenyl acetate was dried to obtain a film-form sustained-release preparation containing Z11-hexadecenyl acetate. .
- the sustained-release preparation containing Z11-hexadecenyl acetate was placed under the conditions of 35 ° C and a wind speed of 1.5 m / sec.
- the release rate of Z11-hexadecenyl acetate from the preparation by weight change it showed good sustained release performance, and the remaining amount of Z11-hexadecenyl acetate after 40 days The rate was 13%.
- the pre-emulsion was dropped into the flask over 3 hours while maintaining the temperature condition of 65 ° C, and then polymerized for another 4 hours to obtain the emulsion (water-dispersed type containing EMOD). Microgel A) was obtained. By the same method as in Example 1, it was confirmed that the polymerization was completed.
- Monomer component e which was previously mixed at the composition ratio described in Table 2 with the obtained emulsion, f A total of 8 parts by weight was added dropwise at room temperature over 1 hour, and the mixture was further stirred for 1 hour to impregnate the microgel A with the monomer. Thereafter, 0.2 parts by weight of 2,2-azobis (2-amidinopropane) dihydrochloride was added, and the mixture was polymerized for 4 hours while maintaining the temperature condition at 65 ° C. A water-dispersed sustained-release preparation containing EMOD was obtained. By the same method as in Example 1, it was confirmed that the polymerization was completed.
- the average particle size of the obtained microgel was measured by dynamic light scattering (DLS) and found to be 230 nm.
- the obtained water-dispersed sustained release preparation was dried to obtain a film-like EMOD-containing sustained release preparation.
- the EMOD-containing sustained-release preparation was placed under the conditions of 35 ° C and a wind speed of 1.5 mZ seconds, and the release rate of EMOD from the preparation was measured by weight change.
- the results are shown in FIG.
- the release amount of EMOD of these sustained-release preparations showed a relatively good sustained-release performance although the release amount slightly decreased from 30 days to 40 days.
- E MOD 7,8-epoxy-12-methyloxydecane
- a monomer component composition ratio is described in Table 1
- polyoxy Add 1 part by weight of ethylene alkyl ether sulfate (Persoft EL (manufactured by NOF CORPORATION), anionic surfactant) and 19 parts by weight of ion-exchanged water. The mixture was stirred to prepare a pre-emulsion.
- the emulsified liquid obtained in the autoclave was charged, and a total of 8 parts by weight of the monomer components e and f mixed in the composition ratio shown in Table 2 was added dropwise over 1 hour at room temperature, and further stirred for 1 hour to obtain a microgel. A was impregnated with the monomer. Thereafter, polymerization was carried out for 4 hours while maintaining the temperature condition of 120 ° C. to obtain a water-dispersed sustained-release preparation containing EMOD in IPN. By the same method as in Example 1, it was confirmed that the polymerization was completed.
- the average particle size of the obtained microgel was measured by dynamic light scattering (DLS) and found to be 210 nm.
- the obtained water-dispersed sustained release preparation was dried to obtain a film-like EMOD-containing sustained release preparation.
- 351 The EMOD-containing sustained-release preparation was placed under conditions of wind speed of 1.5 mZ seconds, and the release rate of EMOD from the preparation was measured by weight change. The results are shown in FIG. As can be seen from FIG. 1, the release amount of EMOD of these sustained-release preparations was almost constant over 40 days, indicating good sustained-release performance.
- Example 3 A monomer component having the same composition ratio as in Example 3 was used, and instead of EM OD, Zl 1-hexadecenal (a sex pheromone of the tobacco moth) was used as a functional substance. Emulsion copolymerization and radical polymerization were performed. By the same method as in Example 1, it was confirmed that the polymerization was completed. The obtained emulsion did not precipitate aggregates and the like even when left for a long period of time, and showed stable water dispersibility. Further, the pH value of the emulsion was 5.6.
- aqueous dispersion-type sustained-release preparation containing the synthesized Z11-hexadecenal The resin content was adjusted to 10% with exchange water.
- the sustained release formulations, nylon fabric using a spray one (size: 2 0 0 X 2 0 0 mm) to to be about 5 g / m 2 as an adhesion amount of the resin component uniformly sprayed also dry was And evaluated for sustained release.
- a sustained-release formulation containing Z11-hexadecenal attached to a nylon cloth was installed under the condition of 25 ° (wind speed: 2.0 m / sec. Z11-hexadecenena from the formulation.
- the release rate was measured by GC analysis and the results are shown in Fig. 2. As can be seen from Fig. 2, the release of Z11-hexadecenal from these sustained-release preparations was almost unchanged over 40 days. It was constant and showed good sustained release performance.
- Example 3 The water-dispersed sustained release preparation containing EMOD described in Example 3 was evaluated for sustained release in the same manner as in Example 10. The results are shown in FIG. As can be seen from FIG. 2, the release of EMOD from these sustained-release preparations was almost constant over 40 days, indicating good sustained-release performance.
- Emulsion copolymerization was carried out in the same manner as in the above Examples, using monomer components a, c, and d having the same composition ratio as in Examples 3, 4, and 6, and replacing monomer component b with styrene.
- the ratio is shown in Table 1).
- a large amount of aggregates were generated during the polymerization in the first step, and a sustained-release preparation having good aqueous dispersion stability could not be obtained.
- CH 2 C (CH 3 ) -C-0- (CH 2 ) 2 -0-C-0- (CH 2 ) 2 -0- _C-C (CH 3 ) r OH
- the water-dispersed sustained-release preparation of the present invention can release almost all of the contained functional substances such as pheromone, pharmaceuticals, agricultural chemicals, and flavors at a constant volatilization rate over a long period of time, and can be sprayed or sprayed. It is a sustained-release preparation that is easy to apply and can also provide functions such as adhesion performance. Therefore, the water-dispersed sustained-release preparation of the present invention can be expected to be used in a wide range of fields.
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Priority Applications (3)
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EP00976305A EP1230855B1 (en) | 1999-11-19 | 2000-11-16 | Sustained-release preparation of aqueous dispersion type and process for producing the same |
AU14144/01A AU1414401A (en) | 1999-11-19 | 2000-11-16 | Sustained-release preparation of aqueous dispersion type and process for producing the same |
DE60040411T DE60040411D1 (de) | 1999-11-19 | 2000-11-16 | Gerter freigabe und verfahren zu ihrer herstellung |
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JP11-329827 | 1999-11-19 | ||
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JP2000182127 | 2000-06-16 |
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EP (1) | EP1230855B1 (ja) |
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WO2005023877A1 (ja) * | 2003-09-03 | 2005-03-17 | Hokkaido Technology Licensing Office Co., Ltd. | 吸水性樹脂及びその製造方法 |
JP2006035210A (ja) * | 2004-06-21 | 2006-02-09 | Nisshin Chem Ind Co Ltd | マイクロカプセルエマルジョン及びその製造方法 |
JP2008508344A (ja) * | 2004-08-04 | 2008-03-21 | ビーエーエスエフ ソシエタス・ヨーロピア | 水に難溶性である活性物質の水性活性物質組成物の製造方法 |
JP2008532978A (ja) * | 2005-03-10 | 2008-08-21 | ビーエーエスエフ ソシエタス・ヨーロピア | 農薬を含む水性ポリマー分散液の製造方法およびその使用 |
WO2012124598A1 (ja) * | 2011-03-11 | 2012-09-20 | 日本エンバイロケミカルズ株式会社 | 徐放性粒子 |
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CA2562347C (en) | 2004-04-26 | 2013-04-16 | Basf Aktiengesellschaft | Aqueous fungicidal composition and use thereof for combating harmful micro organisms |
US20050282011A1 (en) * | 2004-06-21 | 2005-12-22 | Nissin Chemical Industry Co., Ltd. | Microcapsule emulsion and method for producing the same |
CA2599507A1 (en) * | 2005-03-09 | 2006-09-14 | Patrick Amrhein | Aqueous insecticidal compositions and the use thereof for protecting lignocellulose-containing materials |
AU2008281829B9 (en) | 2007-08-02 | 2014-05-29 | Basf Se | Polymer networks comprising active ingredients, process for their production, and their use |
EP2282632B1 (de) | 2008-05-21 | 2021-05-05 | Bayer CropScience Aktiengesellschaft | Insektizide formulierungen mit verbesserter langzeitwirkung auf oberflächen |
WO2011003240A1 (en) * | 2009-07-10 | 2011-01-13 | Basf (China) Company Limited | Formulation comprising terpolymer and active substance, and preparation thereof |
CN102939010B (zh) | 2010-06-16 | 2014-06-11 | 巴斯夫欧洲公司 | 含水活性成分组合物 |
FR3041503B1 (fr) * | 2015-09-25 | 2017-10-20 | Melchior Mat And Life Science France | Projectiles oxodegradables contenant des pheromones |
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- 2000-11-16 EP EP00976305A patent/EP1230855B1/en not_active Expired - Lifetime
- 2000-11-16 AU AU14144/01A patent/AU1414401A/en not_active Abandoned
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Cited By (7)
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WO2005023877A1 (ja) * | 2003-09-03 | 2005-03-17 | Hokkaido Technology Licensing Office Co., Ltd. | 吸水性樹脂及びその製造方法 |
JP2006035210A (ja) * | 2004-06-21 | 2006-02-09 | Nisshin Chem Ind Co Ltd | マイクロカプセルエマルジョン及びその製造方法 |
JP2008508344A (ja) * | 2004-08-04 | 2008-03-21 | ビーエーエスエフ ソシエタス・ヨーロピア | 水に難溶性である活性物質の水性活性物質組成物の製造方法 |
JP2008532978A (ja) * | 2005-03-10 | 2008-08-21 | ビーエーエスエフ ソシエタス・ヨーロピア | 農薬を含む水性ポリマー分散液の製造方法およびその使用 |
WO2012124598A1 (ja) * | 2011-03-11 | 2012-09-20 | 日本エンバイロケミカルズ株式会社 | 徐放性粒子 |
JP2012207012A (ja) * | 2011-03-11 | 2012-10-25 | Japan Enviro Chemicals Ltd | 徐放性粒子 |
US9511030B2 (en) | 2011-03-11 | 2016-12-06 | Osaka Gas Chemicals Co., Ltd. | Controlled release particles |
Also Published As
Publication number | Publication date |
---|---|
DE60040411D1 (de) | 2008-11-13 |
EP1230855A4 (en) | 2005-01-12 |
EP1230855A1 (en) | 2002-08-14 |
EP1230855B1 (en) | 2008-10-01 |
AU1414401A (en) | 2001-06-04 |
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