US20070098766A1 - Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same - Google Patents

Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same Download PDF

Info

Publication number
US20070098766A1
US20070098766A1 US10561751 US56175104A US2007098766A1 US 20070098766 A1 US20070098766 A1 US 20070098766A1 US 10561751 US10561751 US 10561751 US 56175104 A US56175104 A US 56175104A US 2007098766 A1 US2007098766 A1 US 2007098766A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
sensitive adhesive
pressure
percutaneous absorption
dimethacrylate
tape preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10561751
Inventor
Naohisa Kawamura
Hidenori Sawada
Takayuki Kobayashi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nipro Patch Co Ltd
Original Assignee
Saitama Daiichi Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/046Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal 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
    • A61K9/7038Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053Transdermal 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
    • A61K9/7061Polyacrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F2013/00361Plasters
    • A61F2013/00655Plasters adhesive
    • A61F2013/00659Plasters adhesive polymeric base
    • A61F2013/00663Plasters adhesive polymeric base acrylic
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T156/00Adhesive bonding and miscellaneous chemical manufacture
    • Y10T156/10Methods of surface bonding and/or assembly therefor
    • Y10T156/1052Methods of surface bonding and/or assembly therefor with cutting, punching, tearing or severing

Abstract

A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption comprising (a) a support, (b) a pressure-sensitive adhesive layer containing a drug and a nonaqueous pressure-sensitive adhesive and (c) a release film laminated in that order, and a medicinal tape preparation for percutaneous absorption comprising the adhesive. The nonaqueous pressure-sensitive adhesive may comprise a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers from among other (meth)acrylic monomers without acetoacetyl groups and copolymerizable vinyl monomers, in a nonaqueous solvent. Suitable (meth)acrylic monomers having an acetoacetyl group in the molecule are acetoacetoxyalkyl methacrylates, and especially 2-acetoacetoxyethyl methacrylate. The copolymer nonaqueous pressure-sensitive adhesive of the invention, comprising a (meth)acrylic monomer having an acetoacetyl group as a constituent monomer, is capable of containing large amounts of lipophilic oily substances in the pressure-sensitive adhesive layer, and during heat drying, the acetoacetyl groups undergo self-crosslinking to form a network structure as the solvent evaporates off, so that large amounts of oily substances such as the plasticizer can be included in the network structure. The pressure-sensitive adhesive of the invention uses no polyamine derivatives, isocyanate compounds, polyvalent metal chelate compounds, etc. as crosslinking agents, and therefore toxicity is not a concern and skin is not irritated. A medicinal tape preparation for percutaneous absorption of the invention has superior adhesive strength and cohesive strength, and is highly safe with low skin irritation. It also has excellent drug release and percutaneous absorption properties.

Description

    TECHNICAL FIELD
  • The present invention relates to a nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption, comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers selected from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent, as well as to a medicinal tape preparation for percutaneous absorption produced by coating a nonaqueous pressure-sensitive adhesive onto the top side of a support or release film, together with a drug and plasticizer, and heating to dryness to form a pressure-sensitive adhesive layer, and then further laminating a release film or support over the pressure-sensitive adhesive layer, and to a process for producing the same. The medicinal tape preparation for percutaneous absorption according to the invention is a highly stable tape preparation for percutaneous absorption which exhibits excellent drug release from the preparation and excellent drug skin permeability, with low skin irritation.
  • BACKGROUND ART
  • Paints, coatings and pressure-sensitive adhesives are known wherein copolymers obtained by copolymerization of acetoacetoxyalkyl methacrylates and other monomers are crosslinked with crosslinking agents such as polyamine compounds or isocyanate compounds. (See, for example, Patent document 1 and Patent document 2). However, no patent document or non-patent document can be found which describes the use of a nonaqueous pressure-sensitive adhesive comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group, and one or more monomers selected from among other (meth)acrylic monomers and copolymerizable vinyl monomers, as the pressure-sensitive adhesive used in a medicinal tape preparation for percutaneous absorption.
  • Tape preparations for percutaneous absorption have been known which comprise a drug and plasticizer in a pressure-sensitive adhesive layer, wherein a ketone group-containing pressure-sensitive adhesive is substantially crosslinked with a polyamine crosslinking agent. (See, for example, Patent document 3). However, no description is found of a tape preparation for percutaneous absorption having a pressure-sensitive adhesive comprising a copolymer with an acetoacetyl group.
  • There have also been known preparations for percutaneous absorption which contain an isosorbide dinitrate coronary vasodilator and a fatty acid ester in a crosslinked pressure-sensitive adhesive comprising an acrylic copolymer composed of an acrylic acid alkyl ester and a functional monomer as essential components. (See, for example, Patent document 4). However, this preparation for percutaneous absorption employs a crosslinking agent, and it is stated that without a crosslinking agent the pressure-sensitive adhesive layer lacks cohesive strength and cannot be used in a preparation for percutaneous absorption. In addition, Patent documents 3 and 4 do not provide examples of tape preparations for percutaneous absorption with pressure-sensitive adhesives comprising copolymers with acetoacetyl groups.
  • Patent document 1: Japanese Unexamined Patent Publication HEI No. 6-108033
  • Patent document 2: Japanese Unexamined Patent Publication HEI No. 7-238203
  • Patent document 3: Japanese Unexamined Patent Publication No. 2002-535475
  • Patent document 4: Japanese Unexamined Patent Publication HEI No. 8-81369
  • DISCLOSURE OF THE INVENTION
  • Problems to be Solved by the Invention
  • It is an object of the present invention to provide a medicinal tape preparation for percutaneous absorption having a drug-containing pressure-sensitive adhesive layer formed on a support and a release liner laminated thereover, wherein a large amount of a lipophilic oily substance can be included in the pressure-sensitive adhesive layer and the preparation has excellent adhesion, cohesive strength and stability, as well as a nonaqueous pressure-sensitive adhesive for the preparation.
  • The pressure-sensitive adhesive layer of the medicinal tape preparation for percutaneous absorption may also contain, in addition to a drug, also a solvent for dissolution of the drug, a percutaneous absorption accelerator to accelerate the percutaneous absorption rate of the drug, a plasticizer for improved plasticity of the pressure-sensitive adhesive or a tackifier for improved adhesive strength, and in some cases it may be necessary to include such components in significant amounts. The drug-dissolving solvent, percutaneous absorption accelerator, plasticizer and tackifier included with the drug in the pressure-sensitive adhesive layer will usually be lipophilic oily substances.
  • Problems have been encountered with conventional medicinal tape preparations for percutaneous absorption employing a non-crosslinked pressure-sensitive adhesive, in that it has not been possible to hold large amounts of oily substances, or when large amounts of oily substances are contained it has not been possible to form tape preparations and the oily substances have separated from the pressure-sensitive adhesive layers after formation of the preparations, and therefore the amounts of oily substances in pressure-sensitive adhesive layers have been limited.
  • In order to overcome these problems, there have also been studied tape preparations wherein a pressure-sensitive adhesive obtained by polymerizing a functional group-containing monomer is crosslinked with a crosslinking agent such as a polyamine compound, isocyanate compound or polyvalent metal chelate compound. However, such crosslinking agents are often toxic compounds or they have undesirable effects on certain drugs, while restrictions are necessary on their use or the amounts of their use.
  • Self-crosslinking pressure-sensitive adhesives employing no crosslinking agents are known, such as pressure-sensitive adhesives comprising N-methylolacrylamide as a constituent monomer, but such adhesives are not preferred for medicinal pressure-sensitive adhesive tapes due to gradually release of the harmful substance formaldehyde.
  • There are also known copolymers comprising acetoacetyl group-containing monomers as constituent monomers, for use as paints, coating agents and adhesives, but all such compounds are crosslinked using crosslinking agents such as polyamine derivatives, isocyanate compounds and polyvalent metal chelate compounds, and their use in medicinal tape preparations for percutaneous absorption is not known. In addition, these crosslinking agents are associated with such problems as toxicity and unsuitability for certain types of drugs.
  • Means for Solving the Problems
  • As a result of much research conducted with the aim of solving the problems described above, the present inventors discovered that it is possible to hold large amounts of oily substances such as plasticizers by using a nonaqueous pressure-sensitive adhesive comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers selected from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent.
  • The nonaqueous pressure-sensitive adhesive used in the medicinal tape preparation for percutaneous absorption of the invention, comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group and one or more vinyl monomers selected from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent, undergoes self-crosslinking of the acetoacetyl groups as the solvent evaporates during the step of coating onto a support or release film together with a drug and plasticizer followed by heating to dryness, thereby forming a network structure with the oily substances such as the plasticizer held in the network structure.
  • By adjusting the amount of acetoacetyl group-containing (meth)acrylic monomer in the starting material, it is possible to alter the degree of self-crosslinking of the pressure-sensitive adhesive. It was discovered that, as a result, it is possible to adjust the content of lipophilic oily substances such as plasticizers, percutaneous absorption accelerators, drug dissolving agents and the like in the pressure-sensitive adhesive layer, and that by modifying the content ratio of the pressure-sensitive adhesive and the plasticizer or percutaneous absorption accelerator it is possible to produce suitable adhesion and cohesive strength and obtain a stable tape preparation for percutaneous absorption; the present invention was completed on the basis of this discovery.
  • EFFECT OF THE INVENTION
  • In the step of heat drying the nonaqueous pressure-sensitive adhesive copolymer comprising a (meth)acrylic monomer having an acetoacetyl group as a constituent monomer according to the invention, a network structure is formed by self-crosslinking of the acetoacetyl groups as the solvent evaporates, so that large amounts of oily substances such as the plasticizer can be included in the network structure. The pressure-sensitive adhesive of the invention uses no polyamine derivatives, isocyanate compounds or polyvalent metal chelate compounds as crosslinking agents, and therefore since toxicity is not a concern and the skin is not irritated, the adhesive is suitable for medical use. The medicinal tape preparation for percutaneous absorption of the invention has excellent adhesive and cohesive strength, and is highly safe with low skin irritation. Its properties of drug release and percutaneous absorption are also excellent.
  • BEST MODE FOR CARRYING OUT THE INVENTION
  • The nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to the invention may be obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the same molecule and one or more monomers selected from among (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent.
  • As (meth)acrylic monomers having an acetoacetyl group there may be mentioned acetoacetoxyalkyl methacrylates or acetoacetoxyalkyl acrylates such as 2-acetoacetoxyethyl methacrylate, 2-acetoacetoxyethyl acrylate, 3-acetoacetoxypropyl methacrylate, 3-acetoacetoxypropyl acrylate, 4-acetoacetoxybutyl methacrylate and 4-acetoacetoxybutyl acrylate, among which any one or more may be used, although 2-acetoacetoxyethyl methacrylate and 2-acetoacetoxyethyl acrylate are preferred.
  • As other (meth)acrylic monomers having no acetoacetyl group there may be used any (meth)acrylic monomers having a copolymerizable double bond in the molecule, and one or more such (meth)acrylic monomers may be used. As specific examples there may be mentioned one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, diacetoneacrylamide, butyl acrylate, butyl methacrylate, ethyleneglycol dimethacrylate, diethyleneglycol dimethacrylate, triethyleneglycol methacrylate, tetraethyleneglycol diacrylate, tetraethyleneglycol dimethacrylate, hexaethyleneglycol dimethacrylate, hexaethyleneglycol diacrylate, methyl methacrylate, acrylamide, methacrylamide, 2-hydroxyethyl acrylate and acrylic acid, of which there are preferred one or more acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, diacetoneacrylamide, butyl acrylate, tetraethyleneglycol diacrylate, tetraethyleneglycol dimethacrylate and methyl methacrylate.
  • The other vinyl compound which is copolymerizable with the monomer having an acetoacetyl group need only have a copolymerizable vinyl group in the molecule, and as examples there may be mentioned vinyl derivatives such as N-vinyl-2-pyrrolidone and vinyl acetate.
  • The content of the acetoacetyl group-containing monomer in the copolymer used in the nonaqueous pressure-sensitive adhesive of the invention is preferably 1-40 wt % and more preferably 5-40 wt % with respect to the total weight of the copolymer. The proportion is preferably not smaller than 1 wt %, because the oily substance-holding power and the cohesive strength will be reduced, and it is preferably not greater than 40 wt % because the network structure will become too dense, reducing the holding power for the plasticizer and other components.
  • The solvent of the nonaqueous pressure-sensitive adhesive for the medicinal tape preparation for percutaneous absorption according to the invention may be any organic solvent which volatilizes in the heat drying step during the production process for the medicinal tape preparation for percutaneous absorption of the invention. Such a solvent may be any of various organic solvents including acetic acid esters such as methyl acetate, ethyl acetate, propyl acetate and butyl acetate, aliphatic hydrocarbons such as hexane, heptane, octane and cyclohexane, aromatic hydrocarbons such as benzene, toluene and xylene, ketones such as acetone and methyl ethyl ketone, and ethers such as isopropyl ether, tetrahydrofuran and dioxane, among which any may be used alone, or two or more may be used in combination.
  • The nonaqueous pressure-sensitive adhesive of the invention may be produced by a well-known method in the relevant technical field. A specific preferred method is dissolution of each of the monomers in an organic solvent and polymerization with a radical initiator.
  • Alternatives include dissolution of all of the monomers in a prescribed organic solvent beforehand, nitrogen substitution, and then heating for polymerization, or successive loading of the monomer in separate amounts into the solvent for polymerization. The monomer concentration in the organic solvent is preferably 10-80 wt %. The concentration is preferably not less than 10 wt % because it will be difficult to achieve a high polymerization degree, while it is preferably not greater than 80 wt % because control of the heat of polymerization during the reaction will become difficult. The organic solvent used for the polymerization may be any single solvent selected from the group consisting of organic solvents mentioned above, or a combination of two or more thereof. Also, the same type or different types of solvents may be added successively during the polymerization.
  • The radical initiator used for the invention may be a compound selected from among peroxides, azo initiators and the like, or a mixture thereof, and it is used in an amount of preferably 0.001-2.00 parts by weight and more preferably 0.005-0.1 part by weight to 100 parts by weight of the monomer.
  • As specific peroxides there may be mentioned benzoyl peroxide, lauroyl peroxide, tert-butyl hydroperoxide, di(2-ethylhexyl)peroxydicarbonate and 1,1′-di-tert-butyl-peroxy-2-methylcyclohexane. As specific azo initiators there may be mentioned 2,2′-azobisisobutyronitrile, 4,4′-azobis-4-cyanovaleric acid and 2,2′-azobis(2-amidinopropane) dihydrochloride.
  • The polymerization temperature may be a temperature at which the radical initiator generates a suitable level of radicals, and in most cases it is preferably 50-120° C.
  • The amount of residual monomer of the nonaqueous pressure-sensitive adhesive of the invention is preferably minimized for reduced skin irritation and improved drug stability, and preferably it is no greater than 20,000 ppm with respect to the solid portion of the pressure-sensitive adhesive. In order to reduce the residual monomer, for example, additional radical initiator may be added after completion of the polymerization, or high-temperature treatment may be carried out under pressurized conditions.
  • A greater molecular weight of the copolymer of the pressure-sensitive adhesive of the invention will result in inferior adhesion, while a smaller molecular weight will result in inferior cohesive strength. The molecular weight of the copolymer may be a weight-average molecular weight of between several tens of thousands to several million.
  • The glass transition temperature (hereinafter also referred to as “Tg”) of the copolymer of the pressure-sensitive adhesive of the invention also has a significant effect on the adhesive and cohesive strength of the pressure-sensitive adhesive, with a high Tg tending to result in a harder pressure-sensitive adhesive and a low Tg tending to results in a softer one, and therefore the Tg of the copolymer is preferably in the range of −60° C. to −5° C. The range is more preferably between −50° C. and −10° C. If it is below −60° C., the cohesive strength of the pressure-sensitive adhesive will tend to be too weak when the plasticizer is added, while a Tg of higher than −5° C. will tend to result in poor adhesive strength even with addition of a large amount of plasticizer.
  • The glass transition temperature can generally be determined by measurement with a DSC apparatus or measurement of the viscoelasticity. It can also be derived by calculation using the following formula 1, as the glass transition temperature of the homopolymer. 100 Tg = Wi Tgi ( 1 )
    (wherein Wi represents the weight fraction (%) of the monomer of component “i”, and Tgi represents the glass transition temperature (° K.) of the homopolymer of component
  • The plasticizer included in the pressure-sensitive adhesive layer of the medicinal tape preparation for percutaneous absorption of the invention may be an oily substance with a high boiling point in most cases. For example, there may be used fatty acid ester derivatives such as isopropyl myristate, diethyl sebacate, diisopropyl adipate, ethyl oleate, isopropyl palmitate, ethyl laurate, octyl palmitate, isotridecyl myristate and medium-chain fatty acid triglycerides; higher alcohol derivatives such as hexyldecanol and octyldodecanol; polyalkylene glycols such as polyethylene glycol and polypropylene glycol; and fats and oils such as olive oil, castor oil and the like. These may be used alone or in mixtures of two or more, but isopropyl myristate and isopropyl palmitate are most preferred because they function as plasticizers for the pressure-sensitive while also accelerating diffusion of the drug in the tape preparation and promoting skin permeability of the drug. The plasticizer content is preferably no greater than 50 wt % and more preferably 10-40 wt % with respect to the total weight of the pressure-sensitive adhesive layer. The plasticizer content is preferably not greater than 50 wt % because such an amount cannot be held in the pressure-sensitive adhesive layer, and the oily substances will tend to bleed from the pressure-sensitive adhesive layer.
  • The pressure-sensitive adhesive in the pressure-sensitive adhesive layer of the medicinal tape preparation for percutaneous absorption of the invention exhibits suitable adhesive strength even alone if it contains a percutaneous absorbing drug and a plasticizer in addition to the nonaqueous pressure-sensitive adhesive, but if even stronger adhesive strength is desired, a tackifier may be included in the pressure-sensitive adhesive layer to increase the adhesive strength, and examples of tackifiers that are suitable for use include alicyclic saturated hydrocarbon resins and rosin ester derivatives. Alicyclic saturated hydrocarbon resins include ALCON P-100 (trade name of Arakawa Chemical Industries Co., Ltd.) while rosin ester derivatives include ESTERGUM H (trade name of Arakawa Chemical Industries Co., Ltd.), and any one or mixtures of two or more may be used.
  • There are no particular restrictions on drugs to be formulated in the tape preparation for percutaneous absorption of the invention, and they may be selected to conform to the purpose of treatment; examples of suitable drugs include steroid hormones, non-steroidal anti-inflammatory drugs, tranquilizers, anti-hypertensive agents, ischemic heart disease drugs, anti-histamines, antiasthmatic drugs, anti-Parkinson drugs, cerebral circulation improvers, antiemetics, anti-depressants, anti-dementia drugs, Sjogren's syndrome treatments, anti-arrhythmia drugs, anticoagulants, gout suppressants, antifungal agents, narcotic analgesics, beta blockers, ⊕1 agonists, β2 agonists, antitumor agents, diuretics, antithrombotic agents, histamine Hi receptor antagonists, histamine H2 receptor antagonists, anti-allergic agents, serotonin receptor antagonists, anti-hypercholesteremic agents and smoking cessation aids, and any percutaneously absorbed drugs may be used which do not reside on the skin surface but penetrate to the subcutaneous layer or into the blood to exhibit a local or systemic effect. Two or more of such drugs may also be used together if necessary. Also, the contents of the drugs may be appropriately set depending on the type of drug, its effect and the purpose of administration.
  • If necessary, the pressure-sensitive adhesive layer of the tape preparation for percutaneous absorption of the invention may also include, in addition to the aforementioned drug, pressure-sensitive adhesive and plasticizer, also a drug solubilizer, percutaneous absorption accelerator and other excipients.
  • A drug solubilizer is a drug-dissolving solvent, and any solvent which is not skin-irritating may be used. Specifically, there may be used lower alcohols such as ethanol, propanol and isopropanol, medium alcohols such as hexanol and octanol, polyhydric alcohols such as glycerin, ethylene glycol and diethyleneglycol, fatty acid esters, polyvinyl alcohols, N-methylpyrrolidone, crotamiton and the like, any of which may be used alone or in combinations of two or more as drug-dissolving agents, although there is no limitation to these.
  • As drug percutaneous absorption accelerators there may be used any which are commonly utilized in tape preparations for percutaneous absorption, including fatty acid esters such as isopropyl myristate, isopropyl palmitate and diisopropyl adipate, fatty acid polyhydric alcohol esters such as caprylic monoglyceride, caprylic triglyceride and sorbitan fatty acid esters, and terpenes such as 1-menthol, peppermint oil and limonene.
  • Examples of excipients include silicon compounds such as silicic anhydride and light silicic anhydride, cellulose derivatives such as ethyl cellulose, methyl cellulose, carboxymethylcellulose sodium, hydroxypropyl cellulose and hydroxypropylmethyl cellulose, water-soluble polymers such as polyvinyl alcohol, antioxidants such as dibutylhydroxytoluene and powders such as kaolin and titanium oxide, as well as aromatics and coloring agents, and these may be added in medically acceptable ranges.
  • There are no particular restrictions on the support for the tape preparation for percutaneous absorption of the invention, and there may be used stretchable or non-stretchable woven or nonwoven fabric or knit textiles made of polyethylene, polypropylene, polyester or the like, plastic films made of polyethylene, polypropylene, polyester, ethylene-vinyl acetate copolymer, vinyl chloride or the like, or foam films made of polyurethane or the like, either alone or in laminated combinations, depending on the purpose of use.
  • The release liner on the tape preparation for percutaneous absorption of the invention serves to protect the pressure-sensitive adhesive layer during storage, and there may be used polyester, polyethylene, polypropylene, ethylene-vinyl acetate copolymer resin, polyurethane, a metal foil thin-film, a film having a laminated structure comprising a combination of such materials, a film which has been silicon-treated on the surface to be attached to the pressure-sensitive adhesive layer, or a film having a metal such as aluminum vapor-deposited on the surface. In addition, the release liner may be provided with a continuous or non-continuous straight or curved notch for easier release.
  • The tape preparation for percutaneous absorption of the invention may be produced by coating the surface of the release liner with a solution containing the drug, plasticizer and if necessary a drug-dissolving agent or percutaneous absorption accelerator, with the pressure-sensitive adhesive, and then heating to dryness at a temperature of 40-150° C. to form a pressure-sensitive adhesive layer, subsequently laminating a support on the surface of the pressure-sensitive adhesive layer opposite the side on which the release liner is attached, and cutting it to an appropriate size. When a non-water-permeable support is used as the support, a pressure-sensitive adhesive solution containing the drug, plasticizer, etc. may be applied onto the support and heated to dryness, and then the release liner laminated thereon. The temperature for heating to dryness may be a temperature above the volatilization temperature of the solvent. The temperature is preferably not too low because the solvent will not completely volatilize, and it is preferably not above 150° C. because an adverse effect may be produced on the drug, plasticizer and percutaneous absorption accelerator.
  • EXAMPLES
  • The nonaqueous pressure-sensitive adhesive for the medicinal tape preparation for percutaneous absorption of the invention and the medicinal tape preparation for percutaneous absorption will now be further explained through the following examples, with the understanding that the invention is in no way limited to these examples.
  • Example 1 Production of Nonaqueous Pressure-Sensitive Adhesive 1
  • After charging 157.5 g of 2-ethylhexyl acrylate (hereinafter abbreviated as 2EHA), 35 g of 2-acetoacetoxyethyl methacrylate (hereinafter abbreviated as AAEM), 80.5 g of diacetoneacrylamide (hereinafter abbreviated as DAAM) and 76 g of methyl methacrylate (hereinafter abbreviated as MMA) in a 2-liter four-necked flask equipped with a Dimroth condenser, thermometer, nitrogen gas blow-in tube and stirrer, 525 g of ethyl acetate was added as a solvent and the mixture was dissolved to uniformity. The temperature was raised to 75° C. while blowing in nitrogen gas at flow rate of 100 ml/min. After holding at 75° C. for 30 minutes, a solution of 0.21 g of benzoyl peroxide as an initiator in 5 g of ethyl acetate was added, and the external temperature was set to 85° C. Subsequently, 300 g of toluene was loaded in portions of 100 g at a time at 3, 5 and 7 hours after adding the initiator. During the polymerization, nitrogen gas was continuously blown in at a flow rate of 100 ml/min.
  • At 12 hours after the final toluene loading, 0.35 g of benzoyl peroxide was loaded as an additional catalyst, and then heat treatment for 12 hours at an external temperature of 95° C. was followed by cooling to obtain nonaqueous pressure-sensitive 1.
  • (Physical Properties of Solution of Nonaqueous Pressure-Sensitive Adhesive 1)
    • Solution viscosity (measured with Brookfield viscometer): 30,000 mPa·s
    • Solid portion (150° C.×1 hour treatment): 28.5%
    • Residual monomers: 300 ppm 2EHA, 20 ppm AAEM, 1000 ppm DAAM, 150 ppm MMA (measured by HPLC)
    Example 2 Production of Nonaqueous Pressure-Sensitive Adhesive 2
  • A monomer solution was prepared by uniformly pre-dissolving 78.8 g of 2EHA, 78.8 g of n-butyl acrylate (hereinafter abbreviated as BA), 105 g of AAEM, 87.5 g of MMA and 1.05 g of diethyleneglycol dimethacrylate (hereinafter abbreviated as DEGMA). After adding 100 g of the monomer solution in a 2-liter four-necked flask equipped with a Dimroth condenser, thermometer, nitrogen gas blow-in tube and stirrer, 350 g of ethyl acetate was added as a solvent. The temperature was raised to 75° C. while blowing in nitrogen gas at flow rate of 100 ml/min, and after holding at 75° C. for 30 minutes, a solution of 0.35 g of benzoyl peroxide as an initiator in 5 g of ethyl acetate was added, and the external temperature was set to 85° C. Upon confirming reflux of the solvent, the remaining monomer solution was loaded continuously for 3 hours. Next, one hour after the initial continuous loading of the monomer solution, 500 g of ethyl acetate was continuously loaded for 3 hours. After continuing to stir for 12 hours after loading the ethyl acetate, 0.5 g of benzoyl peroxide was loaded as additional catalyst and then heat treatment for 12 hours was followed by cooling to obtain nonaqueous pressure-sensitive 2. During the polymerization, nitrogen gas was continuously blown in at a flow rate of 100 ml/min.
  • (Physical Properties of Solution of Nonaqueous Pressure-Sensitive Adhesive 2)
    • Solution viscosity (measured with Brookfield viscometer): 25,000 mPa·s
    • Solid portion (150° C.×1 hour treatment): 27.5%
    • Residual monomers: 1000 ppm 2EHA, 200 ppm BA, 100 ppm AAEM, 250 ppm MMA, DEGMA below detection limit (measured by HPLC)
  • Nonaqueous pressure-sensitive adhesives 3-10 for Examples 3-10 shown in Table 1 were produced by the method described in Example 2.
  • Comparative Example 1 Production of Comparison Pressure-Sensitive Adhesive 1
  • Polymerization and synthesis were conducted by the same method as for pressure-sensitive adhesive 1 of Example 1 using a monomer composition of 90 g 2EHA, 90 g BA, 80.5 g DAAM, 87.5 g MMA and 1.0 g DEGMA, to produce comparison pressure-sensitive adhesive 1.
  • (Physical Properties of Solution of Comparison Pressure-Sensitive Adhesive 1)
    • Solution viscosity (measured with Brookfield viscometer): 38,000 mPa·s
    • Solid portion (150° C.×1 hour treatment): 28.5%
    • Residual monomers: 300 ppm 2EHA, 200 ppm BA, 1500 ppm DAAM, 100 ppm MMA, DEGMA below detection limit (measured by HPLC)
    Comparative Example 2 Preparation of Comparison Pressure-Sensitive Adhesive 2
  • Polymerization and synthesis were conducted by the same method as in Example 2 using a monomer composition of 130 g 2EHA, 130 g BA and 90 g MMA, to produce comparison pressure-sensitive adhesive 2.
  • (Physical Properties of Solution of Comparison Pressure-Sensitive Adhesive 2)
    • Solution viscosity (measured with Brookfield viscometer): 28,000 mPa·s
    • Solid portion (150° C.×1 hour treatment): 27.5%
    • Residual monomers: 500 ppm 2EHA, 300 ppm BA, 150 ppm MMA (measured by HPLC)
  • The monomer compositions, solvents and calculated Tg values for the nonaqueous pressure-sensitive adhesives of Examples 1-10 and Comparative Examples 1 and 2 are shown in Table 1.
    TABLE 1
    Nonaqueous pressure-sensitive adhesives
    Monomer Calculated
    Example AAEM DAAM MMA 2EHA BA DEGMA TEGMA Solvent Tg value
     1 10.0 23.1 21.8 45.1 EtOAc, −12.3
    toluene
     2 29.9 24.9 22.5 22.5 0.2 EtOAc, −15.0
    toluene
     3 0.1 28.9 35.4 35.4 0.2 EtOAc, −32.2
    toluene
     4 1.0 29.0 34.8 35.0 0.2 EtOAc, −31.6
    toluene
     5 5.0 25.0 34.8 35.0 0.2 EtOAc, −33.7
    toluene
     6 10.0 10.0 40.0 39.8 0.2 EtOAc, −47.6
    toluene
     7 10.0 22.9 21.8 45.0 0.3 EtOAc, −12.0
    toluene
     8 20.0 20.0 29.8 30.0 0.2 EtOAc, −29.3
    toluene
     9 30.0 25.0 22.4 22.4 0.2 EtOAc, −15.0
    toluene
    10 40.0 19.9 20.0 19.9 0.2 EtOAc, −27.5
    toluene
    Comp. 0 23.1 25.1 25.8 25.8 0.2 EtOAc, −9.2
    Ex. 1 toluene
    Comp. 0 25.8 37.1 37.1 EtOAc, −36
    Ex. 2 toluene

    AAEM: 2-acetoacetoxyethyl methacrylate; DAAM: diacetoneacrylamide; MMA: methyl methacrylate; 2EHA: 2-ethylhexyl acrylate; BA: n-butyl acrylate; DEGMA: diethyleneglycol dimethacrylate; TEGMA: tetraethyleneglycol dimethacrylate; EtOAc: ethyl acetate

    The values in the monomer columns are the weight percentages of each monomer with respect to 100 as the total dry copolymer weight.
  • Test Example 1
  • The nonaqueous pressure-sensitive adhesives 1-10 of the invention and the comparison pressure-sensitive adhesives 1 and 2 shown in Table 1, and the commercially available acrylic solvent-type (nonaqueous) pressure-sensitive adhesive S-3403 (ARONTACK S-3403, trade name of Toa Gosei Co., Ltd.) were used for coating and drying onto a support to produce tapes 2-1 to 2-21 and comparison tapes 3-5, and the compatibility of the pressure-sensitive adhesives and oily substances, the adhesive and cohesive strengths of the pressure-sensitive adhesives were evaluated.
  • 1) Tape Production Methods
  • Production of Tape 2-1
  • A 38.69 g portion of pressure-sensitive adhesive 1 was placed in a screw-cap bottle and stirred for more than an hour in the bottle. A coating tester (LTE-S, Wener Mathis AG) was used for coating and drying of the solution onto a support (polyester film) to a dried coating weight of 70 mg/10 cm2, and then a liner (silicon-treated polyester film) was used to cover it with the silicon side contacting the pressure-sensitive to obtain tape 2-1.
  • Production of Tape 2-2
  • A 38.69 g portion of pressure-sensitive adhesive 1, and then 1.2 g of isopropyl myristate (IPM), were placed in a screw-cap bottle and stirred for more than an hour in the bottle. A coating tester (LTE-S, Wener Mathis AG) was used for coating and drying of the solution onto a support (polyester film) to a dried coating weight of 70 mg/10 cm2, and then a liner (silicon-treated polyester film) was used to cover it with the silicon side contacting the pressure-sensitive to obtain tape 2-2.
  • Pressure-sensitive adhesives and corresponding plasticizers were used in the same method as the production method of tape 2-2 to produce tapes 2-3 to 2-21 and comparison tape 3-5.
  • 2) Evaluation of Compatibility Between Pressure-Sensitive Adhesives and Oily Substances
  • The preparation liners were released and an optical microscope was used to observe the condition of liquid substance adhering to the liner surface.
  • Evaluation:
  • ◯: No liquid substance on the liner surface
  • x: Liquid substance on the liner surface
  • 3) Evaluation of Tape Adhesive Strength
  • After releasing the liner of the preparation, the pressure-sensitive adhesive side was touched with a finger and evaluated based on the following evaluation scale.
  • ◯: (excellent) Adhesive strength comparable to MOHRUS TAPE (trade name of Hisamitsu Pharmaceutical) and YAKUBAN (trade name of Mikasa Seiyaku) which employ styrene-isoprene-styrene copolymer.
  • Δ: (good) Adhesive strength comparable to SERASTAR (trade name of Yamanouchi Pharmaceutical) and FALZY (trade name of Sawai Pharmaceutical) which employ natural rubber latex.
  • x: (poor) Adhesive strength below that of commercial products.
  • -: Evaluation impossible due to significantly low cohesive strength (semi-solid state).
  • 4) Evaluation of Tape Cohesive Strength (Hardness)
  • After releasing the liner of the tape, the pressure-sensitive adhesive side was touched with a finger and evaluated based on the following evaluation scale.
  • Evaluation:
  • ◯: (excellent) Cohesive strength comparable to SERASTAR (trade name of Yamanouchi Pharmaceutical) and FALZY (trade name of Sawai Pharmaceutical) which employ natural rubber latex.
  • Δ: (good) Cohesive strength comparable to MOHRUS TAPE (trade name of Hisamitsu Pharmaceutical) and YAKUBAN (trade name of Mikasa Seiyaku) which employ styrene-isoprene-styrene copolymer.
  • x: (poor) Cohesive strength below that of commercial products.
  • Tapes 2-1 to 2-21 and comparison tape 3-5 were used for evaluation of the compatibility of the pressure-sensitive adhesives and oily substances, the adhesive and cohesive strengths, giving the results shown in Table 2. The comparison tapes 3 and 4, and comparison tape 5 which employed a commercially available acrylic pressure-sensitive adhesive, all exhibited inadequate adhesive and cohesive strength, while tapes 2-1 to 2-21 which were prepared using nonaqueous pressure-sensitive adhesives of the invention exhibited adequate adhesive and cohesive strength.
    TABLE 2
    Compatibilities, adhesive strengths and cohesive strengths of nonaqueous pressure-sensitive adhesive tapes
    Tape Monomer Compati- Adhesive Cohesive
    No. AAEM DAAM MMA 2EHA BA DEGMA TEGMA Solvent Plasticizer bility strength strength
    2-1 10.0 23.1 21.8 45.1 EtOAc,
    toluene
    2-2 10.0 23.1 21.8 45.1 EtOAc, IPM 10
    toluene
    2-3 10.0 23.1 21.8 45.1 EtOAc, IPM 20
    toluene
    2-4 10.0 23.1 21.8 45.1 EtOAc, IPM 30
    toluene
    2-5 10.0 23.1 21.8 45.1 EtOAc, IPM 40
    toluene
    2-6 10.0 23.1 21.8 45.1 EtOAc, IPP 20
    toluene
    2-7 10.0 23.1 21.8 45.1 EtOAc, HD 20
    toluene
    2-8 10.0 23.1 21.8 45.1 EtOAc, DES 20
    toluene
    2-9 10.0 23.1 21.8 45.1 EtOAc, DPA 20
    toluene
    2-10 10.0 23.1 21.8 45.1 EtOAc, MFTG 20
    toluene
    2-11 10.0 23.1 21.8 45.1 EtOAc, PETA 20
    toluene
    2-12 10.0 23.1 21.8 45.1 EtOAc, Castor oil 20
    toluene
    2-13 29.9 24.9 22.5 22.5 0.2 EtOAc, IPM 20
    toluene
    2-14 0.1 28.9 35.4 35.4 0.2 EtOAc, IPM 20 Δ
    toluene
    2-15 1.0 29.0 34.8 35.0 0.2 EtOAc, IPM 20
    toluene
    2-16 5.0 25.0 34.8 35.0 0.2 EtOAc, IPM 20
    toluene
    2-17 10.0 10.0 40.0 39.8 0.2 EtOAc, IPM 20
    toluene
    2-18 10.0 22.9 21.8 45.0 0.3 EtOAc, IPM 20
    toluene
    2-19 20.0 20.0 29.8 30.0 0.2 EtOAc, IPM 20
    toluene
    2-20 30.0 25.0 22.4 22.4 0.2 EtOAc, IPM 20
    toluene
    2-21 40.0 19.9 20.0 19.9 0.2 EtOAc, IPM 20
    toluene
    Comp. Ex. 3 0 23.1 25.1 25.8 25.8 0.2 EtOAc, IPM 20 x
    toluenee
    Comp. Ex. 4 0 25.8 37.1 37.1 EtOAc, IPM 20 x
    toluene
    Comp. Ex. 5 Acrylic solvent-type pressure-sensitive adhesive: S-3403 IPM 20 x
    (ARONTACK S-3403 Toa Gosei Co., Ltd.)

    AAEM: 2-acetoacetoxyethyl methacrylate; DAAM: diacetoneacrylamide; MMA: methyl methacrylate; 2EHA: 2-ethylhexyl acrylate; BA: n-butyl acrylate; DEGMA: diethyleneglycol dimethacrylate; TEGMA: tetraethyleneglycol dimethacrylate; EtOAc: ethyl acetate; IPM: isopropyl myristate; IPP: isopropyl palmitate; HD: hexyldecanol; DBS: diethyl sebacate; DPA: diisopropyl adipate; MFTG: medium chain fatty acid triglyceride; PETA: polyester adipate.

    The values in the monomer columns are the weight percentages of each monomer with respect to 100 as the total dry copolymer weight. The values in the plasticizer column are the weight percentages of each plasticizer with respect to 100 as the total weight of the pressure-sensitive adhesive layer.
  • Example 11 Production of Tape Preparation for Percutaneous Absorption 11
  • A 36.2 g portion of pressure-sensitive adhesive 7, and then 1.5 g of ketoprofen, were placed in a screw-cap bottle and stirred for more than an hour in the bottle. A coating tester (LTE-S, Wener Mathis AG) was used for coating and drying of the solution onto a support (polyester film) to a dried coating weight of 140 mg/10 cm2, and then a liner (silicon-treated polyester film) was used to cover it with the silicon side contacting the pressure-sensitive to obtain tape preparation for percutaneous absorption 11. The ketoprofen content of the obtained preparation was 10 w/w %.
  • Example 12 Production of Tape Preparation for Percutaneous Absorption 12
  • A 35.69 g portion of pressure-sensitive adhesive 7, and then 3.0 g of IPM and 1.5 g of ketoprofen, were placed in a screw-cap bottle and stirred for more than an hour in the bottle. A coating tester (LTE-S, Wener Mathis AG) was used for coating and drying of the solution onto a support (polyester film) to a dried coating weight of 140 mg/10 cm2, and then a liner (silicon-treated polyester film) was used to cover it with the silicon side contacting the pressure-sensitive to obtain tape preparation for percutaneous absorption 12. The ketoprofen content of the obtained preparation was 10 w/w %.
  • Examples 13-16 Production of Tape Preparations for Percutaneous Absorption 13-16
  • Tape preparations for percutaneous absorption 13-16 were each produced by the same method as Example 11 or Example 12, using pressure-sensitive adhesive 7, a drug and if necessary IPM plasticizer.
  • Comparative Examples 6-9 Production of Comparison Tape Preparations for Percutaneous Absorption 6-9
  • Comparison tape preparations for percutaneous absorption 6-9 were produced by the same method as in Example 12, using a specific drug and plasticizer, with a commercially available solvent-type acrylic pressure-sensitive adhesive for Comparative Examples 8 and 9 and addition of an isocyanate crosslinking agent for Comparative Examples 6 and 7.
  • The compatibility evaluation and tape adhesive and cohesive strength evaluation described in Test Example 1 were conducted using the tape preparations for percutaneous absorption 11-16 obtained in Examples 11-16, and the comparison tape preparations for percutaneous absorption 6-9. The tape preparations for percutaneous absorption according to the invention exhibited satisfactory adhesive and cohesive strength, while the comparison tape preparations for percutaneous absorption exhibited inferior adhesive and cohesive strength. The results are shown in Table 3.
    TABLE 3
    Compatibilities, adhesive strengths and cohesive strengths of medicinal tapes for percutaneous absorption
    Pressure- Crosslinking
    sensitive agent Plasticizer Drug Adhesive Cohesive
    Example adhesive (amount) (amount) (amount) Compatibility strength strength
    11 Adhesive 7 ketoprofen 10
    12 Adhesive 7 IPM 20 ketoprofen 10
    13 Adhesive 7 indomethacin 10
    14 Adhesive 7 IPM 20 indomethacin 10
    15 Adhesive 7 tulobuterol 10
    16 Adhesive 7 IPM 20 tulobuterol 10
    Comp. Ex. 6 Nissetsu PE300 CK101 0.1 IPM 20 ketoprofen 10 x
    Comp. Ex. 7 Nissetsu PE300 CK101 0.1 IPM 20 indomethacin 10 x
    Comp. Ex. 8 Nissetsu PE300 tulobuterol 10 x
    Comp. Ex. 9 Nissetsu PE300 IPM 20 tulobuterol 10 x

    CK101: isocyanate crosslinking agent CK101 (Nippon Carbide Industries Co., Ltd.);

    Nissetsu PE300: Solvent-type acrylic pressure-sensitive adhesive, Nissetsu PE300 (Nippon Carbide Industries Co., Ltd.); IPM: isopropyl myristate.

    The values for the crosslinking agents, plasticizers and drugs are weight percentages with respect to 100 as the total dry weight of the pressure-sensitive adhesive layer.
  • Test Example 2 Drug Release Test
  • Each preparation was applied onto extracted skin of a Yucatan micropig (YMP) and allowed to stand under conditions of 32° C.-60% RH. After 24 hours, the preparation was peeled off and the residual drug content of the preparation was measured by HPLC. The residual drug content was used to calculate the drug release rate (%) from the preparation. (drug content before application−residual drug content)/drug content before application×100=drug release rate (%)
  • Test Example 3 Hairless Mouse Extracted Skin Permeability Test
  • After placing 0.05 mol/L McIlvaine Buffer (pH 7.4) on the cutis side (receiver side) of the extracted skin in a vertical diffusion cell, the preparation was applied to the horny layer side. The receiver solution was sampled at different time points, and then an equivalent amount of 0.05 mol/L McIlvaine Buffer was added. The drug concentration of the sampling solution was measured by HPLC, and the flux, lag time and 24 hr cumulative permeation were calculated.
    TABLE 4
    Drug release rates and skin permeabilities of medicinal tapes for percutaneous absorption
    Pressure- Cumulative
    sensitive Plasticizer Drug Release Lag Time FLUX permeation
    adhesive (amount) (concentration) rate (%) (hr) (μg/cm2/hr) (μg/cm2/24 hr)
    Example 15 Adhesive 7 tulobuterol 10 95.7 ± 0.8 2.31 ± 0.98 1.757 ± 0.398 17.71 ± 4.27
    Example 16 Adhesive 7 IPM 20 tulobuterol 10 96.1 ± 0.3 0.17 ± 0.17 3.620 ± 0.057 29.40 ± 1.23
    Comp. Ex. 8 Nissetsu PE-300 tulobuterol 10 88.9 ± 0.2 5.14 ± 1.93 0.335 ± 0.133  3.30 ± 1.12
    Comp. Ex. 9 Nissetsu PE-300 IPM 20 tulobuterol 10 83.0 ± 0.4 1.10 ± 0.28 2.238 ± 0.008 20.98 ± 2.24

    IPM: isopropyl myristate; Nissetsu PE300: Solvent-type acrylic pressure-sensitive adhesive Nissetsu PE300 (Nippon Carbide Industries Co., Ltd.).

    The values for the plasticizer and drug are the weight percentages with respect to 100 as the total weight of the pressure-sensitive adhesive layer.
  • A drug release test and skin permeability test were conducted for Test Examples 2 and 3, using the tape preparations for percutaneous absorption 15 and 16 of the examples and the tape preparations for percutaneous absorption 8 and 9 of the comparative examples. The results are shown in Table 4. The tape preparations for percutaneous absorption of the examples according to the invention had significantly superior drug release rates and skin permeabilities compared to the tape preparations for percutaneous absorption of the comparative examples.
  • Test Example 4 Cumulative Skin Irritation Test (Rabbit)
  • Rabbits used for the test were shaved on the back with an electric razor up to the day prior to the test.
  • The preparation was applied onto the back of a rabbit or guinea pig, impermeable oiled paper was laid thereover, a nonwoven fabric pressure-sensitive adhesive bandage (MESHPORE, Nichiban) was attached firmly over it, and the entire application site was covered with gauze and then covered with a pressure-sensitive adhesive elastic bandage (ELASTOPORE, Nichiban). After 6 hours, the test preparation was removed and the site of application was lightly scraped with absorbent cotton wetted with lukewarm water and allowed to stand for 30 minutes, after which the site of application was observed. After observation was complete, the test preparation was applied at the same site and the same procedure was repeated for 7 days. The application site was observed in the same manner at 48 and 72 hours after final removal of the preparation, and a rating was assigned based on the following evaluation scale of Draize et al.
  • Evaluation Scale of Draize et al.
  • A: Erythema and scab formation
  • No erythema: 0; Very mild erythema: 1; Apparent erythema: 2; Medium to severe erythema: 3; Severe erythema to slight scab formation: 4.
  • B: Edema formation
  • No edema: 0; Very mild edema: 1; Mild edema: 2; Moderate edema (approximately 1 mM protrusions): 3; Severe edema: 4.
  • The 7-day cumulative skin irritation test described in Test Example 4 was conducted using a Japanese Pharmacopeia bandage and tapes 2-18 of the invention shown in Table 2, and the rabbit skin cumulative skin irritation scores were determined. As a result, the score for tapes 2-18 using pressure-sensitive adhesives of the invention was 4.0 while the score for the Japanese Pharmacopeia bandage was 14.6, thus indicating that the pressure-sensitive adhesives of the invention are highly safe, with low irritation on rabbit skin.
    TABLE 5
    Rabbit 7-day cumulative skin irritation test
    Cumulative irritation (7 days)
    Japan Pharmacopeia bandage 14.6
    Invention tapes 2-18 4.0

    The average scores were calculated by the following formula. The 7-day cumulative irritation represents the cumulative total of the average scores from day 1 to day 9. Average score=[(total of erythema scores)+(total of edema scores)]/5
  • INDUSTRIAL APPLICABILITY
  • In the process of heat drying, the nonaqueous pressure-sensitive adhesive of the invention forms a network structure by self-crosslinking of the acetoacetyl groups, so that large amounts of oily substances such as the plasticizer can be included in the network structure. The pressure-sensitive adhesive of the invention uses no polyamine derivatives, isocyanate compounds, polyvalent metal chelate compounds or the like as crosslinking agents, and therefore since toxicity is not a concern and the skin is not irritated, the adhesive is suitable for medical use. The medicinal tape preparation for percutaneous absorption of the invention is superior from the standpoint of adhesive strength, cohesive strength, safety, drug release property and percutaneous absorption.

Claims (22)

  1. 1. A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption, characterized by comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent.
  2. 2. A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to claim 1, characterized in that the copolymer is a copolymer obtained by copolymerization of an acetoacetoxyalkyl acrylate or acetoacetoxyalkyl methacrylate and one or more monomers from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers.
  3. 3. A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to claim 1, characterized in that the copolymer is a copolymer obtained by copolymerization of an acetoacetoxyalkyl acrylate or acetoacetoxyalkyl methacrylate and one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate, diacetoneacrylamide, butyl acrylate, ethyleneglycol dimethacrylate, ethyleneglycol diacrylate, diethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, tetraethyleneglycol dimethacrylate, hexaethyleneglycol dimethacrylate and acrylamide.
  4. 4. A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to claim 1, characterized in that the copolymer is a copolymer obtained by copolymerization of 2-acetoacetoxyethyl methacrylate and one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate, diacetoneacrylamide, butyl acrylate, ethyleneglycol dimethacrylate, ethyleneglycol diacrylate, diethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, tetraethyleneglycol dimethacrylate, hexaethyleneglycol dimethacrylate and acrylamide.
  5. 5. A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to claim 1, characterized by comprising a copolymer obtained by copolymerization of 2- acetoacetoxyethyl methacrylate in an amount of 1-40 wt % of the total copolymer weight and one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate, diacetoneacrylamide, butyl acrylate, ethyleneglycol dimethacrylate, ethyleneglycol diacrylate, diethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, tetraethyleneglycol dimethacrylate, hexaethyleneglycol dimethacrylate and acrylamide.
  6. 6. A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to claim 1, characterized in that the copolymer is a copolymer obtained by copolymerization of 2-acetoacetoxyethyl methacrylate, diacetoneacrylamide, 2-ethylhexyl acrylate, methyl methacrylate and tetraethyleneglycol dimethacrylate.
  7. 7. A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to claim 1, characterized in that the copolymer has a calculated glass transition temperature (Tg) of between −60° C. and −5° C.
  8. 8. A medicinal tape preparation for percutaneous absorption comprising (a) a support, (b) a pressure-sensitive adhesive layer containing a drug and a nonaqueous pressure-sensitive adhesive and (c) a release film laminated in that order, the medicinal tape preparation for percutaneous absorption being characterized in that said pressure-sensitive adhesive layer is formed by coating a support or release film with a nonaqueous pressure-sensitive adhesive comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent, together with a drug, and heating to dryness.
  9. 9. A medicinal tape preparation for percutaneous absorption according to claim 8, characterized in that the copolymer is a copolymer obtained by copolymerization of an acetoacetoxyalkyl acrylate or acetoacetoxyalkyl methacrylate and one or more monomers from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers.
  10. 10. A medicinal tape preparation for percutaneous absorption according to claim 8, characterized in that the copolymer is a copolymer obtained by copolymerization of an acetoacetoxyalkyl acrylate or acetoacetoxyalkyl methacrylate and one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate, diacetoneacrylamide, butyl acrylate, ethyleneglycol dimethacrylate, ethyleneglycol diacrylate, diethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, tetraethyleneglycol dimethacrylate, hexaethyleneglycol dimethacrylate and acrylamide.
  11. 11. A medicinal tape preparation for percutaneous absorption according to claim 8, characterized in that the copolymer is a copolymer obtained by copolymerization of 2-acetoacetoxyethyl methacrylate and one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate, diacetoneacrylamide, butyl acrylate, ethyleneglycol dimethacrylate, ethyleneglycol diacrylate, diethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, tetraethyleneglycol dimethacrylate, hexaethyleneglycol dimethacrylate and acrylamide.
  12. 12. A medicinal tape preparation for percutaneous absorption according to claim 8, characterized by comprising a copolymer obtained by copolymerization of 2-acetoacetoxyethyl methacrylate in an amount of 1-40 wt % of the total copolymer weight and one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate, diacetoneacrylamide, butyl acrylate, ethyleneglycol dimethacrylate, ethyleneglycol diacrylate, diethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, tetraethyleneglycol dimethacrylate, hexaethyleneglycol dimethacrylate and acrylamide.
  13. 13. A medicinal tape preparation for percutaneous absorption according to claim 8, characterized in that the copolymer has a calculated glass transition temperature (Tg) of between −60° C. and −5° C.
  14. 14. A medicinal tape preparation for percutaneous absorption according to claim 8, characterized in that the pressure-sensitive adhesive layer further comprises a plasticizer.
  15. 15. A medicinal tape preparation for percutaneous absorption according to claim 14, characterized in that the plasticizer is one or more oils selected from the group consisting of fatty acid esters, higher alcohols and castor oil.
  16. 16. A medicinal tape preparation for percutaneous absorption according to claim 14, characterized in that the plasticizer content is no greater than 50 wt % of the total weight of said pressure-sensitive adhesive layer.
  17. 17. A medicinal tape preparation for percutaneous absorption according to claim 15, characterized in that the plasticizer is one or more fatty acid esters selected from the group consisting of isopropyl myristate, isopropyl palmitate, medium-chain fatty acid triglycerides, diethyl sebacate and diisopropyl adipate.
  18. 18. A medicinal tape preparation for percutaneous absorption according to claim 17, characterized in that the plasticizer is isopropyl myristate.
  19. 19. A medicinal tape preparation for percutaneous absorption according to claim 14, characterized in that the nonaqueous pressure-sensitive adhesive comprises a copolymer obtained by copolymerization of 2-acetoacetoxyethyl methacrylate, diacetoneacrylamide, 2-ethylhexyl acrylate, methyl methacrylate and tetraethyleneglycol dimethacrylate in a nonaqueous solvent, and the plasticizer is isopropyl myristate.
  20. 20. A medicinal tape preparation for percutaneous absorption according to claim 8, characterized in that the drug is a percutaneously absorbing drug selected from the group consisting of steroid hormones, non-steroidal anti-inflammatory drugs, tranquilizers, antihypertensive agents, ischemic heart disease drugs, anti-histamines, antiasthmatic drugs, anti-Parkinson drugs, cerebral circulation improvers, antiemetics, antidepressants, anti-dementia drugs, Sjogren's syndrome treatments, anti-arrhythmia drugs, anticoagulants, gout suppressants, antifungal agents, narcotic analgesics, beta blockers, β1 agonists, β2 agonists, antitumor agents, diuretics, antithrombotic agents, histamine H1 receptor antagonists, histamine H2 receptor antagonists, antiallergic agents, serotonin receptor antagonists, anti-hypercholesteremic agents and smoking cessation aids.
  21. 21. A process for production of a medicinal tape preparation for percutaneous absorption comprising (a) a support, (b) a pressure-sensitive adhesive layer containing a drug and a nonaqueous pressure-sensitive adhesive and (c) a release film laminated in that order, the process being characterized by coating the surface of a release film or support with a nonaqueous pressure-sensitive adhesive comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent, with a drug and if necessary with a plasticizer, heating to dryness to form a pressure-sensitive adhesive layer, and then laminating a release film or support thereon and cutting it to a desired size.
  22. 22. A process for production of a medicinal tape preparation for percutaneous absorption according to claim 21, characterized in that the pressure-sensitive adhesive layer is formed by heat drying at 40-150° C.
US10561751 2003-06-24 2004-06-17 Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same Abandoned US20070098766A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2003179162 2003-06-24
JP2003-179162 2003-06-24
PCT/JP2004/008544 WO2004112760A1 (en) 2003-06-24 2004-06-17 Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous absorption, and process for producing the same

Publications (1)

Publication Number Publication Date
US20070098766A1 true true US20070098766A1 (en) 2007-05-03

Family

ID=33535049

Family Applications (3)

Application Number Title Priority Date Filing Date
US10561751 Abandoned US20070098766A1 (en) 2003-06-24 2004-06-17 Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same
US12460146 Abandoned US20090274748A1 (en) 2003-06-24 2009-07-14 Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous absorption, and process for producing the same
US13750361 Active 2024-07-12 US8962012B2 (en) 2003-06-24 2013-01-25 Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous absorption, and process for producing the same

Family Applications After (2)

Application Number Title Priority Date Filing Date
US12460146 Abandoned US20090274748A1 (en) 2003-06-24 2009-07-14 Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous absorption, and process for producing the same
US13750361 Active 2024-07-12 US8962012B2 (en) 2003-06-24 2013-01-25 Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous absorption, and process for producing the same

Country Status (6)

Country Link
US (3) US20070098766A1 (en)
EP (1) EP1639999B1 (en)
JP (1) JP3809462B2 (en)
KR (1) KR101128317B1 (en)
CN (1) CN1812774B (en)
WO (1) WO2004112760A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120226245A1 (en) * 2009-09-07 2012-09-06 Nipro Patch Co., Ltd. Transdermally absorbable preparation
US20140018284A1 (en) * 2011-03-25 2014-01-16 Karine Coget Detergent compositions
US20160271074A1 (en) * 2010-07-21 2016-09-22 3M Innovative Properties Company Transdermal adhesive compositions, devices and methods

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1905866B (en) 2004-01-20 2011-01-05 尼普洛外用药品株式会社 Tulobuterol adhesive patch
CN101080244B (en) 2004-12-15 2011-06-08 尼普洛外用药品株式会社 Medical tape preparation
JP4832831B2 (en) * 2005-08-09 2011-12-07 日東電工株式会社 Percutaneous absorption type preparation
US9056061B2 (en) 2005-09-23 2015-06-16 Alza Corporation Transdermal nicotine salt delivery system
EP1948142B1 (en) 2005-09-23 2014-04-09 ALZA Corporation High enhancer-loading polyacrylate formulation for transdermal applications
JP4981402B2 (en) * 2005-10-13 2012-07-18 日東電工株式会社 Nicotine transdermal preparation and production method thereof
EP2010239A2 (en) * 2006-04-06 2009-01-07 Symyx Technologies, Inc. Water resistant film forming compositions incorporating hydrophilic activities
WO2011010556A1 (en) * 2009-07-23 2011-01-27 ニプロパッチ株式会社 Transdermal preparation
US8221994B2 (en) * 2009-09-30 2012-07-17 Cilag Gmbh International Adhesive composition for use in an immunosensor
US9346982B2 (en) 2010-08-16 2016-05-24 Convatec Technologies Inc. Amphiphilic pressure sensitive adhesives for human skin adhesion
JP2012219045A (en) * 2011-04-06 2012-11-12 Nitto Denko Corp Patch and patch preparation
JP2012219044A (en) * 2011-04-06 2012-11-12 Nitto Denko Corp Adhesive preparation
EP2893927A4 (en) * 2012-09-03 2016-03-09 Nipro Patch Co Ltd Adhesive skin patch
EP2939667A4 (en) * 2012-12-28 2016-06-15 Nipro Patch Co Ltd Packaging
US10053597B2 (en) 2013-01-18 2018-08-21 Basf Se Acrylic dispersion-based coating compositions
KR101465866B1 (en) * 2013-03-20 2014-12-01 서울대학교산학협력단 Nanocomposite of Biocompatible PHEMA derivatives/Ag having antibacterial and antifouling activity
CN105885741A (en) * 2016-05-17 2016-08-24 上海巍盛化工科技有限公司 Medical pressure-sensitive adhesive and medical dressing

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4751087A (en) * 1985-04-19 1988-06-14 Riker Laboratories, Inc. Transdermal nitroglycerin delivery system
US5435879A (en) * 1986-05-30 1995-07-25 Rohm And Haas Company Methods of using pressure-sensitive adhesives

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5185212A (en) * 1986-05-02 1993-02-09 Rohm And Haas Company Acetoacetoxy-alkyl acrylate-containing pressure sensitive adhesives manufactured articles
USH509H (en) * 1987-12-22 1988-08-02 Preparation of adhesives
US5362816A (en) * 1992-06-04 1994-11-08 Rohm And Haas Company High cohesive strength pressure-sensitive adhesives incorporating acetoacetate
JP3454564B2 (en) * 1994-03-01 2003-10-06 ダイセル化学工業株式会社 The aqueous emulsion composition and method of manufacturing
JP3604177B2 (en) * 1994-09-14 2004-12-22 トーアエイヨー株式会社 Percutaneous absorption preparation
US6417267B1 (en) * 1996-05-28 2002-07-09 Eastman Chemical Company Adhesive compositions containing stable amino-containing polymer latex blends
JPH1033657A (en) * 1996-07-23 1998-02-10 Dainippon Ink & Chem Inc In vivo decomposing material and its manufacture
US6818207B1 (en) * 1998-03-09 2004-11-16 Creative Nail Design, Inc. Artificial nail compositions and related method
DE60014604D1 (en) * 1999-01-29 2004-11-11 Strakan Ltd adhesives
JP5021124B2 (en) * 2001-08-29 2012-09-05 日東電工株式会社 Medical adhesive composition, medical adhesive tapes and percutaneous absorption tape preparation using the same
JP2004148221A (en) * 2002-10-31 2004-05-27 Nippon Synthetic Chem Ind Co Ltd:The Aldehyde adsorbent and its application

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4751087A (en) * 1985-04-19 1988-06-14 Riker Laboratories, Inc. Transdermal nitroglycerin delivery system
US4751087B1 (en) * 1985-04-19 1993-03-02 Riker Laboratories Inc
US5435879A (en) * 1986-05-30 1995-07-25 Rohm And Haas Company Methods of using pressure-sensitive adhesives

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120226245A1 (en) * 2009-09-07 2012-09-06 Nipro Patch Co., Ltd. Transdermally absorbable preparation
US9168232B2 (en) * 2009-09-07 2015-10-27 Nipro Patch Co., Ltd. Transdermally absorbable preparation
US20160271074A1 (en) * 2010-07-21 2016-09-22 3M Innovative Properties Company Transdermal adhesive compositions, devices and methods
US10034840B2 (en) * 2010-07-21 2018-07-31 3M Innovative Properties Company Transdermal adhesive compositions, devices and methods
US20140018284A1 (en) * 2011-03-25 2014-01-16 Karine Coget Detergent compositions
US20140017184A1 (en) * 2011-03-25 2014-01-16 Lamberti Spa Personal care compositions

Also Published As

Publication number Publication date Type
US20090274748A1 (en) 2009-11-05 application
CN1812774B (en) 2010-06-16 grant
WO2004112760A1 (en) 2004-12-29 application
US8962012B2 (en) 2015-02-24 grant
KR101128317B1 (en) 2012-03-23 grant
JPWO2004112760A1 (en) 2006-07-20 application
EP1639999B1 (en) 2016-01-20 grant
JP3809462B2 (en) 2006-08-16 grant
US20130138056A1 (en) 2013-05-30 application
CN1812774A (en) 2006-08-02 application
KR20060022652A (en) 2006-03-10 application
EP1639999A1 (en) 2006-03-29 application
KR20110019788A (en) 2011-02-28 application
EP1639999A4 (en) 2012-03-28 application

Similar Documents

Publication Publication Date Title
Tan et al. Pressure-sensitive adhesives for transdermal drug delivery systems
US6448303B1 (en) Hot melt adhesives for dermal application
US5830505A (en) Active ingredient patch
US20040057985A1 (en) Transdermal therapeutic system comprising the active ingredient oxybutynin
US20060240087A1 (en) Composition and methods for drug delivery
US20030170195A1 (en) Compositions and methods for drug delivery
US20040028726A1 (en) Transdermal systems for the delivery of clonidine
US6316022B1 (en) Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures
US6086911A (en) Drug delivery device
US5650165A (en) Percutaneous absorption preparation
US20020012695A1 (en) Transdermal preparation containing hydrophilic or salt-form drug
WO2012065740A1 (en) Transdermal therapeutic system comprising buprenorphine
EP0531938A1 (en) Acrylic gel material and gel-based medical preparation for percutaneous absorption employing the same
US20040033254A1 (en) Transdermal drug delivery system with improved water absorbability and adhesion properties
WO1999002141A1 (en) Block copolymer
US20060173124A1 (en) Solution pressure sensitive adhesives based on acrylic block copolymers
US6139867A (en) Medical adhesive sheet
EP0225005A1 (en) Anti-inflammatory analgesic adhesive preparation
WO1996040085A2 (en) Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures
US20070264319A1 (en) Transdermal Antiemesis Delivery System, Method and Composition Therefor
US20040234582A1 (en) Pressure-sensitive adhesive for the skin and tapes or sheets for the skin made by using the same
US4971799A (en) Percutaneous-administration-type pharmaceutical preparation of nitroglycerin
JP2008273865A (en) External cataplasm
JP2000026285A (en) Plaster
JP2003062058A (en) Medical adhesive composition, medical adhesive tape and percutaneous absorbing tape preparation using it

Legal Events

Date Code Title Description
AS Assignment

Owner name: SAITAMA DAIICHI PHARMACEUTICAL CO., LTD., JAPAN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KAWAMURA, NAOHISA;SAWADA, HIDENORI;KOBAYASHI, TAKAYUKI;REEL/FRAME:017403/0029

Effective date: 20051014

AS Assignment

Owner name: NIPRO PATCH CO., LTD., JAPAN

Free format text: CHANGE OF NAME;ASSIGNOR:SAITAMA DAIICHI PHARMACEUTICAL CO., LTD.;REEL/FRAME:021526/0166

Effective date: 20080701