WO2012105621A1 - 貼付製剤の製造方法 - Google Patents
貼付製剤の製造方法 Download PDFInfo
- Publication number
- WO2012105621A1 WO2012105621A1 PCT/JP2012/052309 JP2012052309W WO2012105621A1 WO 2012105621 A1 WO2012105621 A1 WO 2012105621A1 JP 2012052309 W JP2012052309 W JP 2012052309W WO 2012105621 A1 WO2012105621 A1 WO 2012105621A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- adhesive layer
- pressure
- sensitive adhesive
- lactic acid
- drug
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides 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
Definitions
- the present invention relates to a drug (provided that 2- (4-ethyl-1-piperazinyl) -4- (4-fluorophenyl) -5,6,7,8,9,10-hexahydrocycloocta [b Except pyridine and physiologically acceptable salts thereof) and a method for producing a patch preparation containing lactic acid.
- transdermal administration of the drug can directly absorb the drug from the capillary blood vessels on the skin surface, thereby avoiding the first-pass effect in the liver. Further, since transdermal administration releases a drug continuously, side effects due to absorption of a large amount of drug in a short time can be reduced. For this reason, transdermal administration is one of the effective means of drug administration.
- Drug percutaneous absorption preparations are already known (Patent Document 1). Patent Document 1 also discloses that lactic acid enhances the transdermal absorbability of a drug.
- Patent Document 2 describes a patch preparation containing lactic acid and describes that lactic acid enhances the transdermal absorbability of the drug.
- Patent Documents 1 and 2 mentions the influence of lactic acid on the physical properties of the pressure-sensitive adhesive layer.
- the subject of this invention is providing the manufacturing method of the patch preparation which can obtain the patch preparation which minimizes the influence which it has on the physical property of the adhesive layer of lactic acid, and is excellent in the physical property of an adhesive layer.
- the inventors of the present invention have made extensive studies to solve the above-mentioned problems. After forming a pressure-sensitive adhesive layer containing a drug but not containing lactic acid, the pressure-sensitive adhesive is obtained by attaching lactic acid to the pressure-sensitive adhesive surface of the pressure-sensitive adhesive layer. Lactic acid can be contained in the layer, and even in the preparation obtained in this way, it is found that the effect of promoting transdermal absorption of a drug by lactic acid can be sufficiently obtained, and further research is advanced based on this knowledge The present invention has been completed.
- the adhesive layer contains a drug (provided that 2- (4-ethyl-1-piperazinyl) -4- (4-fluorophenyl) -5,6,7,8,9,10-hexahydroxycroocta [ b) excluding pyridine and physiologically acceptable acid addition salts thereof) and a method for producing a patch preparation containing lactic acid, (A): a step of forming a pressure-sensitive adhesive layer containing a drug, an acrylic polymer and an organic liquid component compatible with the acrylic polymer, and not containing lactic acid; and (b): lactic acid in the pressure-sensitive adhesive layer.
- a method for producing a patch preparation comprising a step of containing.
- step (a) The method according to [1] above, wherein in step (a), a crosslinked pressure-sensitive adhesive layer is formed.
- step (a) The method according to [1] or [2] above, wherein in the step (a), an adhesive layer is formed on one side of the support or release liner.
- the pressure-sensitive adhesive layer contains lactic acid by impregnating the pressure-sensitive adhesive layer with a lactic acid solution in which lactic acid is dissolved in an organic solvent. The method described in one.
- the lactic acid solution is applied to the surface of the pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer is allowed to stand at a temperature of 5 to 40 ° C.
- the lactic acid is later contained in the pressure-sensitive adhesive layer not containing lactic acid, the influence of lactic acid on the physical properties of the pressure-sensitive adhesive layer can be reduced.
- the adverse effect of lactic acid on the cross-linking reaction of the adhesive layer can be suppressed.
- a patch preparation with improved holding power after application to the skin that is, cohesive strength of the adhesive layer after application
- the drug according to the present invention includes 2- (4-ethyl-1-piperazinyl) -4- (4-fluorophenyl) -5,6,7,8,9,10-hexahydrocycloocta [b] pyridine and its There is no particular limitation except that physiologically acceptable salts are removed, and a drug that can be administered through the skin to a mammal such as a human, that is, a transdermally absorbable drug is preferable.
- drugs include general anesthetics, hypnotics / sedatives, antiepileptics, antipyretic analgesic / anti-inflammatory drugs, antipruritics, neuropsychiatric drugs, central nervous system drugs, anti-dementia drugs, topical drugs Anesthetics, skeletal muscle relaxants, autonomic drugs, antispasmodics, antiparkinson drugs, antihistamines, cardiotonic drugs, arrhythmic drugs, diuretics, antihypertensive drugs, vasoconstrictors, coronary vasodilators, peripheral vasodilators Drugs, arteriosclerotic drugs, cardiovascular drugs, respiratory stimulants, antitussive expectorants, hormonal drugs, suppurative diseases topical drugs, analgesic / antipruritic / convergence / anti-inflammatory drugs, parasitic skin disease drugs, hemostatic drugs, Drugs for treating gout, drugs for diabetes, drugs for antineoplastic, antibiotics, chemotherapeutic drugs, n
- the drug according to the present invention includes not only a drug that is a free base but also a physiologically acceptable salt thereof.
- Such salts are not particularly limited, and examples thereof include formate, acetate, lactate, adipate, citrate, tartrate, methanesulfonate, fumarate, maleate and the like, and inorganic Examples of acid addition salts include hydrochlorides, sulfates, nitrates, phosphates and the like.
- the drug may be a solvate, a hydrate or a non-hydrate.
- the present invention is particularly advantageous for the production of a patch preparation containing a basic drug having a basic group.
- basic drugs having basic groups include alcoholic hydroxyl groups, thiol groups, phenolic hydroxyl groups, amine groups (for example, primary (—NH 2 ), secondary (—NRH), tertiary (— NRR ′)) and a drug having one or more functional groups selected from the group. That is, when the basic drug and the acidic additive lactic acid coexist in the pressure-sensitive adhesive layer, they may react to produce a salt, which may reduce the transdermal absorbability of the drug. As described later, after forming the pressure-sensitive adhesive layer containing the drug, lactic acid is contained in the pressure-sensitive adhesive layer, so that the opportunity for such a salt to be generated can be reduced.
- a solid drug means a drug that is solid at room temperature (25 ° C.), that is, a drug having a melting point higher than 25 ° C.
- fusing point here is a value by differential scanning calorimetry (DSC).
- the pressure-sensitive adhesive layer containing a drug is generally formed by applying a mixed solution obtained by mixing a pressure-sensitive polymer, drug, etc. in a solvent and drying the coating film. There is a possibility of forming crystal nuclei in the drying process. However, even if such crystal nuclei are formed, it is possible to dissolve the crystal nuclei by maintaining the pressure-sensitive adhesive layer in the lactic acid solution described later, and maintain the transdermal absorbability of the drug. it can.
- the production method of the present invention includes at least the following steps (a) and (b), and the patch preparation obtained thereby has a pressure-sensitive adhesive layer, and contains a drug, lactic acid and an organic liquid component therein. It is. Hereinafter, each process is explained in full detail.
- Step (a) In the production method of the present invention, first, a pressure-sensitive adhesive layer containing a pressure-sensitive adhesive such as a drug and an acrylic polymer and an organic liquid component is formed.
- the pressure-sensitive adhesive layer does not contain lactic acid.
- the pressure-sensitive adhesive layer is preferably formed on one side of the support or one side of the release liner.
- the one in which the pressure-sensitive adhesive layer is formed on one side of the support or the one side of the release liner is also referred to as “pressure-sensitive adhesive sheet”.
- the pressure-sensitive adhesive sheet is produced by preparing a laminate in which a support, a pressure-sensitive adhesive layer, and a release liner are laminated in this order, and then removing the release liner from the laminate or removing the support. It is particularly preferable that the release liner is easily removed, and therefore, it is particularly preferable to manufacture the laminate by removing the release liner.
- the content of each component in the pressure-sensitive adhesive layer in the following pressure-sensitive adhesive sheet is assumed to be a pressure-sensitive adhesive layer containing lactic acid, that is, the pressure-sensitive adhesive layer of the patch preparation, and the ratio to the total weight of the pressure-sensitive adhesive layer ( % By weight).
- the amount of the drug to be contained in the adhesive layer needs to be set according to the age, symptoms, etc. of the patient to be administered, and is not particularly limited, but a desired result in the treatment of a disease, condition or disorder, for example, It can be present in the adhesive layer in an amount, also referred to herein as an effective amount, sufficient to provide the desired therapeutic result.
- An effective amount of drug means, for example, an amount of the drug that is non-toxic but sufficient to produce a selected effect over a specified period of time.
- the effective amount depends on the area of the patch preparation, but is preferably about 0.1% by weight or more, more preferably about 0.5% by weight or more, particularly preferably about 0.00% by weight based on the total weight of the pressure-sensitive adhesive layer. 8% by weight or more.
- the upper limit thereof is preferably about 50% by weight or less, more preferably about 40% by weight or less, particularly preferably based on the total weight of the pressure-sensitive adhesive layer. Is about 30% by weight or less.
- ⁇ Acrylic polymer is used for the adhesive in the adhesive layer.
- the acrylic polymer is preferably contained in an amount of 30 to 80% by weight, more preferably 40 to 70% by weight, based on the total weight of the pressure-sensitive adhesive layer.
- an acrylic polymer having a main structural unit of a unit of (meth) acrylic acid alkyl ester is preferable.
- the acrylic polymer having (meth) acrylic acid alkyl ester as the main structural unit include alkyl (meth) acrylic acid from the viewpoints of ease of cross-linking treatment, adhesion to human skin, drug solubility, and the like.
- a copolymer of an ester (first monomer component) and a vinyl monomer having a functional group capable of participating in a crosslinking reaction (second monomer component), or another monomer other than these (third monomer component) is further co-polymerized. Polymerized copolymers are preferred.
- Examples of the (meth) acrylic acid alkyl ester (first monomer component) include linear, branched or cyclic alkyl groups having an alkyl group of 1 to 18 carbon atoms (for example, methyl, ethyl, n-propyl, Isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclohexyl, 3-methylpentyl, n-heptyl, cycloheptyl, n-octyl, 2- (Meth) acrylic acid alkyl esters composed of ethylhexyl, cyclooctyl, n-nonyl, cyclononyl, n-decyl, cyclodecyl, n-undecyl, n
- the alkyl group is a linear, branched or cyclic alkyl having 4 to 8 carbon atoms.
- a group for example, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclohexyl, 3-methylpentyl, n-heptyl, cycloheptyl, n-octyl, More preferred are (meth) acrylic acid alkyl esters comprising 2-ethylhexyl, cyclooctyl, etc., and particularly preferred are (meth) acrylic acid alkyl esters comprising an alkyl group consisting of n-butyl, 2-ethylhexyl or cyclohexyl.
- (meth) acrylic acid alkyl ester (first monomer component)
- first monomer component include butyl acrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, cyclohexyl acrylate, and cyclohexane methacrylate.
- Hexyl is mentioned, among which 2-ethylhexyl acrylate is most preferred.
- These (meth) acrylic acid alkyl esters (first monomer component) can be used alone or in combination of two or more.
- examples of the functional group that can participate in the crosslinking reaction include a hydroxy group, a carboxy group, and a vinyl group. And a carboxy group are preferred.
- Specific examples of the monomer (second monomer component) include (meth) acrylic acid hydroxyethyl ester, (meth) acrylic acid hydroxypropyl ester, (meth) acrylic acid, itaconic acid, maleic acid, maleic anhydride, and mesaconic acid. Citraconic acid, glutaconic acid and the like. Of these, acrylic acid, methacrylic acid, and hydroxyethyl acrylate are preferable, and acrylic acid is most preferable from the viewpoint of availability.
- These monomers (second monomer component) can be used alone or in combination of two or more.
- the other monomer (third monomer component) is mainly used for adjusting the cohesive force of the pressure-sensitive adhesive layer and adjusting the solubility and release properties of the drug.
- the monomer (third monomer component) include vinyl esters such as vinyl acetate and vinyl propionate; vinyl ethers such as methyl vinyl ether and ethyl vinyl ether; vinyl amides such as N-vinyl-2-pyrrolidone and N-vinylcaprolactam. (Meth) acrylic acid methoxyethyl ester, (meth) acrylic acid ethoxyethyl ester, (meth) acrylic acid tetrahydrofurfuryl ester, etc.
- vinyl esters and vinyl amides are preferable.
- Vinyl esters are preferably vinyl acetate, and vinyl amides are preferably N-vinyl-2-pyrrolidone.
- These monomers (third monomer component) can be used alone or in combination of two or more.
- the acrylic polymer is a copolymer of (meth) acrylic acid alkyl ester (first monomer component) and a vinyl monomer (second monomer component) having a functional group capable of participating in a crosslinking reaction
- the copolymer The ratio (first monomer component / second monomer component) is preferably 85 to 99% by weight / 1 to 15% by weight, more preferably 90 to 99% by weight / 1 to 10% by weight.
- the acrylic polymer includes (meth) acrylic acid alkyl ester (first monomer component), a vinyl monomer having a functional group capable of participating in a crosslinking reaction (second monomer component), and other monomers (first monomer component).
- the copolymerization ratio (first monomer component / second monomer component / third monomer component) is 40 to 94% by weight / 1 to 15% by weight / 5 to 50% by weight. %, Preferably 50 to 89% by weight / 1 to 10% by weight / 10 to 40% by weight.
- the polymerization reaction may be carried out by a method known per se, and is not particularly limited.
- the above-mentioned monomer is used in a solvent (eg, ethyl acetate) in a polymerization initiator (eg, benzoyl peroxide, azobisisobutyro).
- a method of reacting at 50 to 70 ° C. for 5 to 48 hours in the presence of nitrile or the like.
- acrylic polymers in the present invention are acrylic acid 2-ethylhexyl ester / acrylic acid / N-vinyl-2-pyrrolidone copolymer, acrylic acid 2-ethylhexyl ester / acrylic acid 2-hydroxyethyl ester / Vinyl acetate copolymer, 2-ethylhexyl acrylate / acrylic acid copolymer, and the like, more preferably 2-ethylhexyl acrylate / acrylic acid / N-vinyl-2-pyrrolidone copolymer It is.
- the glass transition temperature of the acrylic polymer in the present invention varies depending on the copolymer composition, it is usually preferably from ⁇ 100 ° C. to ⁇ 10 ° C., more preferably from the viewpoint of adhesiveness as a patch preparation. 90 ° C to -20 ° C.
- the organic layer is included in the adhesive layer.
- Such an organic liquid component can be used without particular limitation as long as it is a liquid at room temperature (25 ° C.) and exhibits a plasticizing action and is compatible with the acrylic polymer.
- the organic liquid component softens the adhesive layer and reduces physical irritation to the skin of the patch preparation.
- Specific examples of the organic liquid component include isopropyl myristate, ethyl laurate, isopropyl palmitate, ethyl oleate, isostearyl laurate, isotridecyl myristate, octyl palmitate, etc. (preferably 12 to 16 carbon atoms).
- Fatty acid ester of a monohydric alcohol having 1 to 18 carbon atoms (hereinafter also abbreviated as “C8-18 (12-16) -C1-18 fatty acid ester”); fatty acid having 8 to 9 carbon atoms [For example, caprylic acid (octanoic acid, C8), pelargonic acid (nonanoic acid, C9), etc.]; fatty acid glycerin ester; ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, 1,3-propanediol, polypropylene glycol, etc.
- Glycols olive oil, Fats and oils such as castor oil and squalene; organic solvents such as dimethylsulfoxide, dimethylformamide, dimethylacetamide, dimethyllaurylamide, dodecylpyrrolidone, isosorbitol, oleyl alcohol, lauric acid, N-methyl-2-pyrrolidone; polyoxyethylene alkyl Sodium ether sulfate, sodium polyoxyethylene lauryl ether sulfate, sodium alkylnaphthalene sulfonate, polyoxyethylene oleylamine, polyoxyethylene oleyl ether sodium phosphate, polyoxyl stearate, decaglyceryl laurate, polyoxyethylene sorbitan monolaurate, poly Oxyethylene sorbitan monostearate, sorbitan monolaurate, sorbitan trioleate, tetraolein Liquid surfactants such as polyoxyethylene sorbite, glycerol monoole
- the content of the organic liquid component in the pressure-sensitive adhesive layer is preferably 5 to 60% by weight, more preferably 10 to 50% by weight, based on the total weight of the pressure-sensitive adhesive layer.
- the content is less than 5% by weight, the softening of the pressure-sensitive adhesive layer may be insufficient, and a good soft feeling may not be obtained, or the skin irritation reduction effect may not be sufficiently obtained.
- the content exceeds 60% by weight, the organic liquid component cannot be retained in the pressure-sensitive adhesive even by the cohesive force of the pressure-sensitive adhesive, and blooms on the surface of the pressure-sensitive adhesive layer and becomes too weak. The product may fall off the skin surface.
- the pressure-sensitive adhesive layer may be subjected to physical crosslinking by irradiation with radiation such as ultraviolet irradiation or electron beam irradiation, or may be subjected to chemical crosslinking treatment using various crosslinking agents.
- a so-called gel-like pressure-sensitive adhesive layer obtained by crosslinking a pressure-sensitive adhesive layer in which the acrylic polymer and the organic liquid component are blended is preferable because it has appropriate adhesiveness and cohesive strength while giving a soft feeling to the skin.
- the crosslinking agent for performing the crosslinking treatment on the pressure-sensitive adhesive layer of the pressure-sensitive adhesive sheet is not particularly limited.
- an isocyanate compound for example, an organic metal compound (for example, zirconium and zinc alaninate, zinc acetate, glycine ammonium zinc, etc.), metal alcoholate (for example, tetraethyl titanate, tetraisopropyl titanate, aluminum isopropylate, aluminum sec-butyrate, etc.), metal chelate compounds (eg, dipropoxybis (acetylacetonato) titanium, tetraoctylene glycol titanium, aluminum isopropylate, ethyl acetoacetate aluminum diisopropylate) Rate, aluminum tris (ethyl acetoacetate), aluminum tris (acetylacetonate) and the like).
- organic metal compound for example, zirconium and zinc alaninate, zinc acetate, glycine ammonium zinc, etc.
- metal alcoholate for example, tetraethyl titanate, tetraisopropyl titanate, aluminum
- the pressure-sensitive adhesive layer of the pressure-sensitive adhesive sheet contains an isocyanate compound, so that the decrease in the cohesive force of the pressure-sensitive adhesive layer is reduced in the state where the patch preparation is applied to human skin, and the agglomeration when the pressure-sensitive adhesive layer is peeled Isocyanate compounds are preferred from the viewpoint of preventing destruction.
- lactic acid that adversely affects the cross-linking reaction is not present in the pressure-sensitive adhesive layer, a sufficiently high cross-linked structure can be formed, and a patch preparation with high holding power can be produced.
- the pressure-sensitive adhesive layer cross-linked with an isocyanate compound exhibits particularly high holding power (cohesive force after being applied to the skin).
- the isocyanate compound examples include aliphatic diisocyanates such as tetramethylene diisocyanate and hexamethylene diisocyanate, isophorone diisocyanate, hydrogenated xylylene diisocyanate, hydrogenated toluene diisocyanate, and hydrogenated diphenylmethane diisocyanate. And aromatic diisocyanates such as aromatic aliphatic diisocyanate, tolylene diisocyanate, and 4,4′-diphenylmethane diisocyanate. Moreover, the said isocyanate type compound may be used independently or may be used in combination with another crosslinking agent.
- the above crosslinking agents may be used alone or in combination of two or more.
- the blending amount of the cross-linking agent varies depending on the type of the cross-linking agent and the pressure-sensitive adhesive (acrylic polymer), but is generally preferably 0.01 to 10% by weight based on the total weight of the pressure-sensitive adhesive layer of the patch preparation. More preferably, it is 0.05 to 5% by weight, particularly preferably 0.1 to 0.3% by weight. If it is less than 0.01% by weight, there are too few crosslinking points, so that sufficient cohesive force cannot be imparted to the pressure-sensitive adhesive layer, and when the preparation is peeled from the skin, adhesive residue or strong skin irritation resulting from cohesive failure appears. There is a fear.
- the cohesive force is large, but sufficient skin adhesive force may not be obtained. Moreover, there is a possibility that skin irritation may occur due to residual unreacted crosslinking agent.
- the amount is preferably 0.03 to 0.6 parts by weight, more preferably 0.05 to 0.5 parts by weight, and still more preferably 0.15 to 0.5 parts by weight per 100 parts by weight of the acrylic polymer in the agent layer. Parts, most preferably 0.15 to 0.35 parts by weight.
- the chemical cross-linking treatment can be carried out, for example, by performing a process of heating and storing at a temperature higher than the cross-linking reaction temperature after addition of the cross-linking agent to the pressure-sensitive adhesive layer, that is, an aging process.
- the heating time is preferably 12 to 96 hours, more preferably 24 to 72 hours.
- the pressure-sensitive adhesive layer may be formed on one side of the support, or may be formed on one side of the release liner.
- the pressure-sensitive adhesive layer contains a drug, an acrylic polymer, an organic liquid component, a cross-linking agent, etc. (the cross-linking agent is used when forming a cross-linked pressure-sensitive adhesive layer), as well as a fragrance, a colorant, and other additives. Can be contained.
- the pressure-sensitive adhesive layer is preferably a non-hydrated pressure-sensitive adhesive layer.
- the non-water-containing pressure-sensitive adhesive layer as used herein is not necessarily limited to one that does not completely contain moisture, but some amount of moisture derived from air humidity, skin, etc. (for example, the total weight of the pressure-sensitive adhesive layer) Containing less than 1% by weight).
- the support in the pressure-sensitive adhesive sheet is not particularly limited, but the drug and the organic liquid component in the pressure-sensitive adhesive layer are lost from the back through the support and their ratio does not decrease (that is, the organic liquid component and Materials that are impermeable to drugs) are preferred.
- polyester eg, polyethylene terephthalate, etc.
- nylon polyvinyl chloride
- polyethylene polypropylene
- ethylene-vinyl acetate copolymer polytetrafluoroethylene
- ionomer resin polytetrafluoroethylene
- ionomer resin polytetrafluoroethylene
- the support is a laminate film of a nonporous film made of the above material and the following porous film, and the porous film side It is preferable to form an adhesive layer.
- the thickness of the nonporous film is preferably 2 to 100 ⁇ m, more preferably 2 to 50 ⁇ m.
- the porous film is not particularly limited as long as the anchoring property with the pressure-sensitive adhesive layer is improved.
- paper, woven fabric, nonwoven fabric for example, polyester (for example, polyethylene terephthalate) nonwoven fabric
- the above film for example, polyester, nylon, saran (trade name), polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, ethylene-ethyl acrylate copolymer, polytetrafluoroethylene, single films such as metal foil, And a film obtained by mechanically perforating a laminate film obtained by laminating one or two or more of these films), particularly paper, woven fabric, and non-woven fabric (for example, polyester (for example, polyethylene terephthalate) non-woven fabric).
- Etc. is preferable from the viewpoint of the flexibility of the support.
- the porous film is paper, woven fabric, non-woven fabric, etc.
- the basis weight thereof is preferably 5 to 30 g / m 2 from the viewpoint of improving the anchoring force.
- the laminate film on the support is produced by a known laminate film production method such as dry lamination method, wet lamination method, extrusion (extrusion) lamination method, hot melt lamination method, co-extrusion (coextrusion) lamination method, etc.
- a known laminate film production method such as dry lamination method, wet lamination method, extrusion (extrusion) lamination method, hot melt lamination method, co-extrusion (coextrusion) lamination method, etc.
- the thickness of the support in the pressure-sensitive adhesive sheet is not particularly limited, but is preferably 2 to 200 ⁇ m, more preferably 10 to 50 ⁇ m. When the thickness is less than 2 ⁇ m, the handling properties such as self-supporting properties tend to be lowered, and when it exceeds 200 ⁇ m, a sense of incongruity (stiff feeling) is caused and the followability tends to be lowered.
- the release liner in the pressure-sensitive adhesive sheet is not particularly limited, and a known release liner can be used.
- the release liner includes a release liner in which a release treatment agent layer made of a release treatment agent is formed on the surface of the release liner substrate, a plastic film having high releasability itself, or a release liner base. Examples thereof include a release liner in which a release layer made of a plastic film material having a high peelability is formed on the surface of the material.
- the release surface of the release liner may be only one side of the substrate or both sides.
- the release treatment agent is not particularly limited, and examples thereof include release agents such as long-chain alkyl group-containing polymers, silicone polymers (silicone release agents), and fluorine polymers (fluorine release agents). Can be mentioned.
- a plastic film such as a polyester (for example, polyethylene terephthalate) film, a polyimide film, a polypropylene film, a polyethylene film, a polycarbonate film, or a metal-deposited plastic film obtained by depositing a metal on these films; Papers such as Japanese paper, western paper, kraft paper, glassine paper, and high-quality paper; base materials made of fibrous materials such as nonwoven fabric and cloth; metal foils and the like.
- an ethylene- ⁇ -olefin copolymer such as polyethylene (low density polyethylene, linear low density polyethylene, etc.), polypropylene, or ethylene-propylene copolymer is used.
- block copolymer such as polyethylene (low density polyethylene, linear low density polyethylene, etc.), polypropylene, or ethylene-propylene copolymer is used.
- Polymer or random copolymer a polyolefin film made of a mixture of two or more selected from these; a film made of polytetrafluoroethylene (Teflon (registered trademark)), or the like.
- the release liner having a release layer made of a highly peelable plastic film material may be formed by laminating or coating the highly peelable plastic film material on the substrate for the release liner. it can.
- the thickness (overall thickness) of the release liner in the pressure-sensitive adhesive sheet is not particularly limited, but is usually 200 ⁇ m or less, preferably 25 to 100 ⁇ m.
- the method for producing the pressure-sensitive adhesive sheet is not particularly limited, but the following method is suitable.
- Adhesive polymer, drug, and organic liquid component are added to an appropriate solvent together with other additives to be blended as necessary, and mixed well until uniform.
- the solvent include ethyl acetate, toluene, hexane, 2-propanol, methanol, ethanol and the like.
- the obtained mixed solution is applied to one side of the support or the release treatment surface of the release liner, and dried to form an adhesive layer.
- the application can be performed by, for example, casting, printing, or other techniques known to those skilled in the art.
- a release liner or a support is bonded to the pressure-sensitive adhesive layer to form a laminate.
- the release liner or the support is bonded onto the pressure-sensitive adhesive layer, and then allowed to stand at 60 to 90 ° C., preferably 60 to 70 ° C. for 24 to 48 hours to promote the crosslinking reaction.
- a pressure-sensitive adhesive layer is formed on one side of the support or on one side of the release liner. An adhesive sheet is obtained.
- the release liner is easier to remove than the support, it is preferable to remove the release liner from the viewpoint of workability to obtain an adhesive sheet having an adhesive layer formed on one side of the support.
- the thickness of the pressure-sensitive adhesive layer is not particularly limited, but is preferably 20 to 300 ⁇ m, more preferably 30 to 300 ⁇ m, and most preferably 50 to 300 ⁇ m. If the thickness of the pressure-sensitive adhesive layer is less than 20 ⁇ m, it may be difficult to obtain sufficient adhesive strength and contain an effective amount of drug. If the thickness of the pressure-sensitive adhesive layer exceeds 300 ⁇ m, the pressure-sensitive adhesive layer is formed. May cause trouble (coating difficulty).
- Step (b) This step is a step of adding lactic acid to the pressure-sensitive adhesive layer containing a pressure-sensitive adhesive such as a drug or an acrylic polymer and an organic liquid component, which is formed in the step (a).
- a pressure-sensitive adhesive such as a drug or an acrylic polymer and an organic liquid component
- the lactic acid used in the present invention may be a racemic DL-lactic acid, or an optically active L-lactic acid or D-lactic acid. From the viewpoint of fluidity, DL-lactic acid is preferred.
- the method for containing lactic acid in the pressure-sensitive adhesive layer is not particularly limited, but a method in which a lactic acid solution in which lactic acid is dissolved in an organic solvent is prepared and the pressure-sensitive adhesive layer is impregnated with the lactic acid solution is suitable.
- the impregnation of the adhesive layer with the lactic acid solution is performed by casting the lactic acid solution onto the adhesive surface of the adhesive layer, or by applying a known application method (application such as spin coating, spray coating, brush coating, slot die coating, ink jet coating). It can carry out by apply
- coating of the lactic acid solution to the adhesive surface of this adhesive layer is normally performed under room temperature.
- the organic solvent used in the lactic acid solution is not particularly limited as long as it can dissolve lactic acid.
- lactic acid permeability into the pressure-sensitive adhesive layer for example, carbonyl group [—C (O) —], ester 2 to 4 carbon atoms having a polar group such as a group [—C (O) —O—], a carboxy group [—COOH] and a hydroxy group [—OH] (total carbon number including carbon atoms of the polar group)
- An organic solvent is preferable, and preferable specific examples include ethyl acetate, ethyl alcohol, acetone, acetaldehyde, and the like. Among them, ethyl acetate is particularly preferable.
- the lactic acid concentration in the lactic acid solution is not particularly limited, but is preferably about 5 to 50% by weight.
- the lactic acid solution can be allowed to penetrate into the pressure-sensitive adhesive layer basically by leaving it as it is, but the temperature of the leaving environment is preferably 5 to 40 ° C.
- the temperature is preferably set within a range of 15 to 30 ° C., and the temperature is preferably maintained for about 10 seconds to 10 minutes (preferably 30 seconds to 5 minutes).
- step (c) After the pressure-sensitive adhesive layer is impregnated with the lactic acid solution, the organic solvent derived from the lactic acid solution in the pressure-sensitive adhesive layer is evaporated to produce the final patch preparation (step (c)).
- the evaporation of the organic solvent is to evaporate the organic solvent under heating.
- the heating temperature has a lower limit of more than 40 ° C. and an upper limit of 100 ° C. or less, preferably 60 to 90 ° C.
- the time is preferably about 30 seconds to 5 minutes.
- the adhesive sheet is a laminate of the adhesive layer and the support
- a new release liner is laminated on the adhesive surface of the adhesive layer, and the adhesive sheet is released from the adhesive layer.
- a support is newly laminated on the adhesive surface of the adhesive layer to complete the patch preparation.
- stacked here it is the same as the specific example of the support body and release liner which were illustrated in the description of the above-mentioned [process (a)]. Things.
- the content of lactic acid in the pressure-sensitive adhesive layer is preferably 0.1 to 13% by weight, more preferably 1 to 10% by weight, based on the total weight of the pressure-sensitive adhesive layer. Most preferably, it is 1 to 8% by weight. Therefore, the concentration and application amount of the lactic acid solution applied to the surface of the pressure-sensitive adhesive layer are determined so that the lactic acid content is obtained. If the content of lactic acid in the adhesive layer of the patch preparation is too small, the effect of promoting the penetration of the drug into the skin (percutaneous absorption promotion effect) cannot be fully exerted, and if too much, the skin irritation may be strengthened. There is.
- the organic liquid component contained in the pressure-sensitive adhesive layer in the step (a) may partially evaporate in the step (c).
- a large amount of the organic liquid component corresponding to the amount of evaporation can be previously contained in the pressure-sensitive adhesive layer.
- Example 1 A solution prepared by dissolving 53.8 parts of acrylic polymer A, 6.0 parts of lidocaine (hereinafter also referred to as “LDC”) and 30.0 parts of isopropyl myristate (hereinafter also referred to as “IPM”) with an appropriate amount of ethyl acetate. After sufficiently mixing until uniform, 0.2 part of trifunctional isocyanate, Coronate HL (manufactured by Nippon Polyurethane Industry), was added as a cross-linking agent, and sufficiently mixed and stirred until uniform to obtain a coating solution. .
- LDC lidocaine
- IPM isopropyl myristate
- the obtained coating solution was applied to the surface subjected to the release treatment of the release liner which is a 75 ⁇ m-thick PET film subjected to the release treatment on one side so that the paste thickness after drying is about 60 ⁇ m, Drying was performed to form an adhesive layer.
- the pressure-sensitive adhesive surface of the formed pressure-sensitive adhesive layer was bonded to the nonwoven fabric side of a laminated film of a PET film having a thickness of 3.5 ⁇ m and a PET nonwoven fabric having a basis weight of 12 g / m 2 to prepare a laminate. Then, it was left to stand at 70 degreeC for 48 hours, and the crosslinked adhesive layer was prepared.
- Lidocaine has a melting point of 66 to 69 ° C. The melting point was measured with a DSC apparatus (Seiko Instruments (SII), model number DSC6220).
- the release liner was peeled off to obtain an adhesive sheet having a cross-linked adhesive layer on one side of the support.
- a release liner subjected to a release treatment was separately prepared, and the adhesive surface of the pressure-sensitive adhesive layer was bonded to the surface subjected to the release treatment of the release liner to obtain a patch preparation of Example 1.
- Examples 2 to 4 The patch preparations of Examples 2 to 4 were obtained in the same manner as in Example 1 except that the composition shown in Table 1 below was adopted.
- the pressure-sensitive adhesive surface of the formed pressure-sensitive adhesive layer was bonded to the nonwoven fabric side of a laminated film of a PET film having a thickness of 3.5 ⁇ m and a PET nonwoven fabric having a basis weight of 12 g / m 2 to prepare a laminate. Thereafter, it was allowed to stand at 70 ° C. for 48 hours to obtain a patch preparation of Comparative Example 1.
- Comparative Examples 2 to 4 The patch preparations of Comparative Examples 2 to 4 were obtained in the same manner as Comparative Example 1 except that the composition shown in Table 1 below was adopted.
- the effect of increasing the cohesive strength of the pressure-sensitive adhesive layer by adding lactic acid to the pressure-sensitive adhesive layer after the formation of the pressure-sensitive adhesive layer not containing lactic acid is that the lactic acid content in the pressure-sensitive adhesive layer is 3 to 6% by weight. It was particularly noticeable at times.
- the amount of the crosslinking agent was added in the range of 0.16 parts by weight to 0.32 parts by weight with respect to 100 parts by weight of the acrylic polymer.
- the effect of the present invention that is, the effect of increasing the cohesive force of the pressure-sensitive adhesive layer by adding lactic acid to the pressure-sensitive adhesive layer after the formation of the pressure-sensitive adhesive layer not containing lactic acid is remarkable.
- the lactic acid is later contained in the pressure-sensitive adhesive layer not containing lactic acid, the influence of lactic acid on the physical properties of the pressure-sensitive adhesive layer can be reduced.
- the adverse effect of lactic acid on the cross-linking reaction of the adhesive layer can be suppressed.
- a patch preparation with improved holding power after application to the skin that is, cohesive strength of the adhesive layer after application
- the present invention is based on Japanese Patent Application No. 2011-021203 filed in Japan, the contents of which are incorporated in full herein.
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Abstract
Description
薬物の経皮吸収製剤は、すでに知られている(特許文献1)。特許文献1はまた、乳酸が薬物の経皮吸収性を高めることを開示する。
[1] 粘着剤層に、薬物(但し、2-(4-エチル-1-ピペラジニル)-4-(4-フルオロフェニル)-5,6,7,8,9,10-ヘキサヒドロキシクロオクタ[b]ピリジン及びその生理学的に許容される酸付加塩を除く。)及び乳酸を含有する貼付製剤の製造方法であって、
(a):薬物、アクリル系ポリマーおよび該アクリル系ポリマーと相溶する有機液状成分を含有し、乳酸を含有しない粘着剤層を形成する工程、および
(b):前記粘着剤層中に乳酸を含有させる工程
を有することを特徴とする、貼付製剤の製造方法。
[2] 工程(a)において、架橋された粘着剤層を形成する、上記[1]記載の方法。
[3] 工程(a)において、支持体または剥離ライナーの片面に粘着剤層を形成する、上記[1]または[2]記載の方法。
[4] 工程(b)において、有機溶媒に乳酸を溶解させた乳酸溶液を粘着剤層に含浸させることによって粘着剤層中に乳酸を含有させる、上記[1]~[3]のいずれか一つに記載の方法。
[5] 乳酸溶液を粘着剤層の表面に塗布し、5~40℃の温度下に粘着剤層を所定時間放置することにより、乳酸溶液を粘着剤層に含浸させる、上記[4]記載の方法。
[6] 工程(b)の後に、(c):粘着剤層中に含まれる乳酸溶液由来の有機溶媒を蒸発させる工程をさらに有する、上記[4]または[5]記載の製造方法。
本発明の製造方法では、まず、薬物、アクリル系ポリマー等の粘着剤及び有機液状成分を含有する粘着剤層を形成する。ここで粘着剤層には乳酸は含有させない。
本工程は、上記の工程(a)で形成された、薬物、アクリル系ポリマー等の粘着剤及び有機液状成分を含有する粘着剤層に乳酸を含有させる工程である。
不活性ガス雰囲気下、75部のアクリル酸2-エチルヘキシル、22部のN-ビニル-2-ピロリドン、3部のアクリル酸および0.2部のアゾビスイソブチロニトリルを、酢酸エチル中60℃にて溶液重合させてアクリル系共重合体であるアクリル系ポリマーAの溶液を調製した。アクリル系共重合体(アクリル系ポリマーA)のガラス転移点は-45.2℃であった。
アクリル系ポリマーA53.8部、リドカイン(以下「LDC」とも称す。)6.0部、ミリスチン酸イソプロピル(以下「IPM」とも称す。)30.0部を、適量の酢酸エチルで溶解した溶液を均一になるまで十分に混合した後、架橋剤として三官能性イソシアネートであるコロネートHL(日本ポリウレタン工業製)を0.2部加え、均一になるまで十分に混合撹拌を行い塗工液を得た。得られた塗工液を片面に剥離処理を施した厚さ75μmのPETフィルムである剥離ライナーの剥離処理を施した面に、乾燥後の膏体厚が約60μmとなるように塗工し、乾燥を行い粘着剤層を形成した。形成した粘着剤層の粘着面を、厚さ3.5μmのPETフィルムと目付量12g/m2のPET不織布との積層フィルムの不織布側に貼り合わせて積層体を作製した。その後、70℃で48時間放置し、架橋粘着剤層を調製した。なお、リドカインの融点は66~69℃である。該融点はDSC装置(セイコーインスツルーメンツ(SII)製、型番DSC6220)で測定した。
後記表1の配合を採用した他は実施例1と同様にして実施例2~4の貼付製剤を得た。
アクリル系ポリマーA53.8部、リドカイン6.0部、IPM30.0部を、適量の酢酸エチルで溶解した溶液を均一になるまで十分に混合した後、架橋剤として三官能性イソシアネートであるコロネートHL(日本ポリウレタン工業製)を0.2部、及び乳酸10部を加え、均一になるまで十分に混合撹拌を行い塗工液を得た。得られた塗工液を片面に剥離処理を施した厚さ75μmのPETフィルムである剥離ライナーの剥離処理を施した面に、乾燥後の粘着剤層の厚みが約60μmとなるように塗工し、乾燥を行い粘着剤層を形成した。形成した粘着剤層の粘着面を、厚さ3.5μmのPETフィルムと目付量12g/m2のPET不織布との積層フィルムの不織布側に貼り合わせて積層体を作製した。その後、70℃で48時間放置し、比較例1の貼付製剤を得た。
後記表1の配合を採用した他は比較例1と同様にして比較例2~4の貼付製剤を得た。
<試験例>
[保持力]
幅10mm、長さ50mmに切断したサンプルの一端約25mmをベークライト(フェノール樹脂)板に重さ850gのローラーを一往復させて圧着し、逆の一端を補助紙で補強する。これを40±2℃の温度で安定した装置内のフックに取り付け30分放置した後、荷重(300g)を取り付け、自然落下するまで放置する。その際の保持時間を測定した。実験はn=3で行い、計3点を平均した。
貼付製剤を10cm2に裁断したサンプルの粘着剤層の重量(W1)を測定した。次に、そのサンプルをポリテトラフルオロエチレン(PTFE)多孔質膜(日東電工製のNTF膜)に貼り付け、そのサンプルを100mlの酢酸エチルに24時間浸漬した後、酢酸エチルを交換した。この操作を3回繰り返し溶剤可溶分を抽出した。その後サンプルを取出し、乾燥させた後の粘着剤層の重量(W2)を測定し、下記式によってゲル分率を算出した。
ゲル分率(%)=(W2×l00)/(W1×A/B)
A=(粘着剤+架橋剤)の重量
B=(粘着剤+有機液状成分+架橋剤)の重量
結果を表1に示す。
Claims (6)
- 粘着剤層に、薬物(但し、2-(4-エチル-1-ピペラジニル)-4-(4-フルオロフェニル)-5,6,7,8,9,10-ヘキサヒドロキシクロオクタ[b]ピリジン及びその生理学的に許容される塩を除く。)及び乳酸を含有する貼付製剤の製造方法であって、
(a):薬物、アクリル系ポリマーおよび該アクリル系ポリマーと相溶する有機液状成分を含有し、乳酸を含有しない粘着剤層を形成する工程、および
(b):前記粘着剤層中に乳酸を含有させる工程
を有することを特徴とする、貼付製剤の製造方法。 - 工程(a)において、架橋された粘着剤層を形成する、請求項1記載の方法。
- 工程(a)において、支持体または剥離ライナーの片面に粘着剤層を形成する、請求項1または2記載の方法。
- 工程(b)において、有機溶媒に乳酸を溶解させた乳酸溶液を粘着剤層に含浸させることによって粘着剤層中に乳酸を含有させる、請求項1~3のいずれか1項に記載の方法。
- 乳酸溶液を粘着剤層の表面に塗布し、5~40℃の温度下に粘着剤層を所定時間放置することにより、乳酸溶液を粘着剤層に含浸させる、請求項4記載の方法。
- 工程(b)の後に、(c):粘着剤層中に含まれる乳酸溶液由来の有機溶媒を蒸発させる工程をさらに有する、請求項4または5記載の製造方法。
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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EP12742503.1A EP2671594A4 (en) | 2011-02-02 | 2012-02-01 | PRODUCTION METHOD FOR ADHESIVE TRANSDERMAL STAMP |
KR1020137021789A KR20140033339A (ko) | 2011-02-02 | 2012-02-01 | 첩부 제제의 제조방법 |
US13/983,131 US20130302514A1 (en) | 2011-02-02 | 2012-02-01 | Production method for adhesive patch |
CN2012800075172A CN103347541A (zh) | 2011-02-02 | 2012-02-01 | 贴片制剂的制造方法 |
CA2825801A CA2825801A1 (en) | 2011-02-02 | 2012-02-01 | Production method for adhesive patch |
Applications Claiming Priority (2)
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JP2011021203A JP2012158572A (ja) | 2011-02-02 | 2011-02-02 | 貼付製剤の製造方法 |
JP2011-021203 | 2011-02-02 |
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PCT/JP2012/052309 WO2012105621A1 (ja) | 2011-02-02 | 2012-02-01 | 貼付製剤の製造方法 |
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US (1) | US20130302514A1 (ja) |
EP (1) | EP2671594A4 (ja) |
JP (1) | JP2012158572A (ja) |
KR (1) | KR20140033339A (ja) |
CN (1) | CN103347541A (ja) |
CA (1) | CA2825801A1 (ja) |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05132418A (ja) * | 1991-11-08 | 1993-05-28 | Lintec Corp | 揮発性剤担持体の製造方法 |
WO1996016642A1 (fr) * | 1994-11-29 | 1996-06-06 | Hisamitsu Pharmaceutical Co., Inc. | Composition de timbre transdermique du type matriciel |
WO2005115355A1 (ja) * | 2004-05-28 | 2005-12-08 | Hisamitsu Pharmaceutical Co., Inc. | 貼付製剤 |
WO2007142295A1 (ja) * | 2006-06-09 | 2007-12-13 | Dainippon Sumitomo Pharma Co., Ltd. | 新規テープ製剤 |
Family Cites Families (3)
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JP4659943B2 (ja) * | 2000-02-25 | 2011-03-30 | 帝三製薬株式会社 | 塩酸ブプレノルフィン含有貼付剤 |
CA2546200A1 (en) * | 2003-11-18 | 2005-06-02 | 3M Innovative Properties Company | Olanzapine containing transdermal drug delivery compositions |
WO2008069283A1 (ja) * | 2006-12-06 | 2008-06-12 | Nipro Patch Co., Ltd. | 外用医薬組成物及び貼付剤 |
-
2011
- 2011-02-02 JP JP2011021203A patent/JP2012158572A/ja active Pending
-
2012
- 2012-02-01 US US13/983,131 patent/US20130302514A1/en not_active Abandoned
- 2012-02-01 EP EP12742503.1A patent/EP2671594A4/en not_active Withdrawn
- 2012-02-01 CN CN2012800075172A patent/CN103347541A/zh active Pending
- 2012-02-01 KR KR1020137021789A patent/KR20140033339A/ko not_active Application Discontinuation
- 2012-02-01 CA CA2825801A patent/CA2825801A1/en not_active Abandoned
- 2012-02-01 WO PCT/JP2012/052309 patent/WO2012105621A1/ja active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05132418A (ja) * | 1991-11-08 | 1993-05-28 | Lintec Corp | 揮発性剤担持体の製造方法 |
WO1996016642A1 (fr) * | 1994-11-29 | 1996-06-06 | Hisamitsu Pharmaceutical Co., Inc. | Composition de timbre transdermique du type matriciel |
WO2005115355A1 (ja) * | 2004-05-28 | 2005-12-08 | Hisamitsu Pharmaceutical Co., Inc. | 貼付製剤 |
WO2007142295A1 (ja) * | 2006-06-09 | 2007-12-13 | Dainippon Sumitomo Pharma Co., Ltd. | 新規テープ製剤 |
Non-Patent Citations (1)
Title |
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See also references of EP2671594A4 * |
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KR20140033339A (ko) | 2014-03-18 |
CA2825801A1 (en) | 2012-08-09 |
EP2671594A4 (en) | 2014-07-30 |
US20130302514A1 (en) | 2013-11-14 |
CN103347541A (zh) | 2013-10-09 |
EP2671594A1 (en) | 2013-12-11 |
JP2012158572A (ja) | 2012-08-23 |
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