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WO2017034027A1 - Patch adhésif - Google Patents

Patch adhésif Download PDF

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Publication number
WO2017034027A1
WO2017034027A1 PCT/JP2016/075041 JP2016075041W WO2017034027A1 WO 2017034027 A1 WO2017034027 A1 WO 2017034027A1 JP 2016075041 W JP2016075041 W JP 2016075041W WO 2017034027 A1 WO2017034027 A1 WO 2017034027A1
Authority
WO
WIPO (PCT)
Prior art keywords
sensitive adhesive
pressure
polyisobutylene
adhesive layer
acrylate
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.)
Ceased
Application number
PCT/JP2016/075041
Other languages
English (en)
Japanese (ja)
Inventor
薦田　俊一
久美 小端
河盛　唯夫
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.)
Artience Co Ltd
Original Assignee
Toyo Ink SC Holdings 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
Application filed by Toyo Ink SC Holdings Co Ltd filed Critical Toyo Ink SC Holdings Co Ltd
Priority to JP2017536492A priority Critical patent/JP6304457B2/ja
Priority to CN201680049133.5A priority patent/CN107921141A/zh
Publication of WO2017034027A1 publication Critical patent/WO2017034027A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine

Definitions

  • the present invention relates to a patch for transdermal administration of a drug.
  • the patch generally includes a support and an adhesive layer containing an adhesive and a drug.
  • an acrylic pressure-sensitive adhesive As the pressure-sensitive adhesive, an acrylic pressure-sensitive adhesive, a rubber pressure-sensitive adhesive, a silicone pressure-sensitive adhesive, and the like are used. Among these, since the function and the transdermal absorption performance can be selected depending on the combination of the monomers, an acrylic pressure-sensitive adhesive is often used (for example, Patent Document 1).
  • Patent Document 2 includes a support and a pressure-sensitive adhesive layer disposed on the support and containing a pressure-sensitive adhesive base and a drug.
  • the pressure-sensitive adhesive base has a carboxyl group and a hydroxyl group in the molecule.
  • An acrylic polymer substantially free of rubber and a rubber polymer are contained, the acrylic polymer is 2-ethylhexyl acrylate / vinyl acetate copolymer, and the rubber polymer is styrene-
  • a patch is proposed in which the isoprene-styrene block copolymer and polyisobutylene are at least one selected from the group consisting of basic drugs and pharmacologically acceptable salts thereof. ing.
  • the patch according to Patent Document 2 can exhibit sufficient tack when applied to the skin.
  • the patch applied to the skin easily peels from the skin. Therefore, a patch that can be stably applied to the skin for a long period of time regardless of the movement of the human body is desired.
  • An object of the present invention is to provide a patch that can exhibit an excellent tack when applied to the skin and that has reduced peeling from the skin during application. Therefore, the patch of the present invention can be stably applied to the skin over a long period of time, and the drug can be stably percutaneously absorbed into the body.
  • the patch of the present invention comprises a support, laminated and integrated on one surface of the support, and contains an acrylic pressure-sensitive adhesive, a polyisobutylene having a weight average molecular weight of 40,000 to 400,000, and a drug, and the polyisobutylene and And a pressure-sensitive adhesive layer having a content ratio of the acrylic pressure-sensitive adhesive (polyisobutylene / acrylic pressure-sensitive adhesive) of 0.4 to 0.8.
  • the present invention it is possible to provide a patch that can exhibit an excellent tack to the skin at the time of application and has reduced peeling from the skin during application.
  • the patch of the present invention includes a support and a pressure-sensitive adhesive layer laminated and integrated on one surface of the support.
  • the pressure-sensitive adhesive layer contains an acrylic pressure-sensitive adhesive, polyisobutylene and a drug.
  • the acrylic pressure-sensitive adhesive is not particularly limited as long as it is a pressure-sensitive adhesive conventionally used in patches.
  • an acrylic adhesive the acrylic polymer formed by polymerizing the monomer containing an alkyl (meth) acrylate is mentioned.
  • the alkyl (meth) acrylate preferably does not have a functional group other than an ethylenically unsaturated double bond and an ester bond (—COO—).
  • the hydrogen atom of the alkyl group of alkyl (meth) acrylate is not substituted by the functional group. Examples of such a functional group include a hydroxyl group, an amino group, a carboxy group (—COOH), and a halogen atom.
  • (meth) acrylate means an acrylate or a methacrylate.
  • An acrylic polymer may be used independently or may use 2 or more types together.
  • polyisobutylene is incompatible with the acrylic adhesive, the acrylic adhesive and polyisobutylene do not form a single phase in the adhesive layer, but each phase is separated and exists as an independent phase. .
  • the acrylic pressure-sensitive adhesive contains an acrylic polymer obtained by polymerizing a monomer containing an alkyl (meth) acrylate, and the alkyl (meth) acrylate contains an ethylenically unsaturated double bond and an ester bond (—COO).
  • the acrylic pressure-sensitive adhesive and the polyisobutylene have a micro phase separation structure. Mix well while removing.
  • the micro-dispersed polyisobutylene aggregates and breaks down over the entire surface of the adhesive layer. While pulling the thread against the skin.
  • the polyisobutylene in the form of a thread prevents the pressure-sensitive adhesive layer from peeling off from the skin surface, and returns the pressure-sensitive adhesive layer to the state of being stuck to the skin surface by elastic restoring force. Therefore, the patch can maintain a state of being stably adhered over a long period of time regardless of the movement of the human body.
  • the number of carbon atoms in the alkyl group of the alkyl (meth) acrylate is preferably 1 to 16, more preferably 1 to 14, particularly preferably 2 to 14, and most preferably 2 to 12.
  • alkyl (meth) acrylate having an alkyl group having 1 to 16 carbon atoms examples include methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, isopropyl (meth) acrylate, n-butyl ( (Meth) acrylate, isobutyl (meth) acrylate, hexyl (meth) acrylate, n-octyl (meth) acrylate, isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, decyl (meth) acrylate, dodecyl (meth) acrylate, Tridecyl (meth) acrylate, hexadecyl (meth) acrylate, cyclododecyl (meth) acrylate, cyclohexyl (meth) acrylate, hydroxy
  • alkyl (meth) acrylate having 1 to 16 carbon atoms in the alkyl group dodecyl (meth) acrylate, n-octyl (meth) acrylate, and 2-ethylhexyl (meth) acrylate are preferable, and dodecyl (meth) acrylate and 2 -Ethylhexyl (meth) acrylate is more preferred, dodecyl methacrylate and 2-ethylhexyl (meth) acrylate are particularly preferred, dodecyl methacrylate, 2-ethylhexyl acrylate and 2-ethylhexyl methacrylate are particularly preferred.
  • Alkyl (meth) acrylate may be used independently or may use 2 or more types together.
  • the acrylic polymer is an acrylic polymer obtained by copolymerizing the alkyl (meth) acrylate having 1 to 16 carbon atoms in the alkyl group and the alkyl (meth) acrylate having 3 to 16 carbon atoms in the alkyl group.
  • a copolymer is preferred. It is necessary that the alkyl (meth) acrylate having 1 to 16 carbon atoms in the alkyl group is different from the alkyl (meth) acrylate having 3 to 16 carbon atoms in the alkyl group.
  • alkyl (meth) acrylate having 3 to 16 carbon atoms in the alkyl group examples include n-propyl (meth) acrylate, n-butyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylbutyl (meth) acrylate, Examples include isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, decyl (meth) acrylate, dodecyl (meth) acrylate, and tridecyl (meth) acrylate. Of these, dodecyl (meth) acrylate is preferable.
  • acrylic copolymer an acrylic copolymer obtained by copolymerizing a monomer containing n-octyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, and dodecyl (meth) acrylate is preferable.
  • An acrylic copolymer obtained by copolymerizing a monomer containing ethylhexyl (meth) acrylate and dodecyl (meth) acrylate is more preferable, and a single amount containing dodecyl methacrylate, 2-ethylhexyl acrylate, and 2-ethylhexyl methacrylate
  • An acrylic copolymer obtained by copolymerizing the body is particularly preferred.
  • the content of the alkyl (meth) acrylate component having 1 to 16 carbon atoms of the alkyl group in the acrylic copolymer is preferably 40% by mass or more, more preferably 45 to 100% by mass, and 45 to 95% by mass. Particularly preferred.
  • the content of the alkyl (meth) acrylate having 3 to 16 carbon atoms of the alkyl group in the acrylic copolymer is preferably less than 60% by mass, more preferably 1 to 55% by mass, and particularly preferably 5 to 55% by mass. preferable.
  • the monomer of the acrylic copolymer may contain other monomers other than alkyl (meth) acrylate.
  • examples of other monomers include 1-vinyl-2-pyrrolidone, acrylamide, dimethylacrylamide, acrylonitrile, dimethylaminoethyl (meth) acrylate, t-butylaminoethyl (meth) acrylate, vinyl acetate, and vinyl propionate.
  • (meth) acrylic acid means acrylic acid or methacrylic acid.
  • the acrylic polymer may be polymerized by a conventionally known method.
  • a method of polymerizing the above-described monomer in the presence of a polymerization initiator can be mentioned. Specifically, a predetermined amount of a monomer, a polymerization initiator, a polymerization solvent, and, if necessary, a crosslinking agent are supplied to the reactor and heated at a temperature of 60 to 80 ° C. for 4 to 48 hours. The monomer is radically polymerized.
  • polymerization initiator examples include 2,2′-azobisisobutyronitrile (AIBN), 1,1′-azobis (cyclohexane-1-carbonitrile), 2,2′-azobis- (2,4 ′ Azobis-based polymerization initiators such as -dimethylvaleronitrile); peroxide-based polymerization initiators such as benzoyl peroxide (BPO), lauroyl peroxide (LPO), and di-tert-butyl peroxide.
  • polymerization solvent examples include ethyl acetate and toluene.
  • the polymerization reaction is preferably performed in a nitrogen gas atmosphere.
  • the content of the acrylic pressure-sensitive adhesive in the pressure-sensitive adhesive layer is preferably 35% by mass or more, more preferably 40% by mass or more, and particularly preferably 45% by mass or more. 65 mass% or less is preferable, as for content of the acrylic adhesive in an adhesive layer, 60 mass% or less is more preferable, and 55 mass% or less is especially preferable.
  • the content of the acrylic pressure-sensitive adhesive is 35% by mass or more, the pressure-sensitive adhesive layer can exhibit more excellent tack on the skin.
  • the content of the acrylic pressure-sensitive adhesive is 65% by mass or less, a necessary amount of drug can be easily added to the pressure-sensitive adhesive layer.
  • the solubility parameter of the acrylic pressure-sensitive adhesive is preferably 8.5 to 10 (cal / cm 3 ) 1/2, more preferably 8.7 to 9.5 (cal / cm 3 ) 1/2. .
  • the solubility parameter of the acrylic pressure-sensitive adhesive is 8.5 (cal / cm 3 ) 1/2 or more
  • the acrylic pressure-sensitive adhesive and polyisobutylene form a micro phase separation structure.
  • the solubility parameter of the acrylic pressure-sensitive adhesive is 10 (cal / cm 3 ) 1/2 or less
  • the acrylic pressure-sensitive adhesive and polyisobutylene are mixed well in the pressure-sensitive adhesive layer while taking a micro phase separation structure. is doing. Therefore, even when a force for peeling the patch from the skin is applied to the patch, the polyisobutylene pulls the thread on the entire surface of the pressure-sensitive adhesive layer, and the patch is well prevented from peeling from the skin surface.
  • a solubility parameter is the square root of density (cal / cm 3 ) per unit volume (cm 3 ) of cohesive energy (cal) between molecules, as defined by J. H. Hildebrand.
  • solubility parameter for example, refer to the values described in “Solubility Parameter Application Examples” (Akitoshi Taniguchi, Information Organization Co., Ltd., March 15, 2007, p.276-282). You can also.
  • the solubility parameter of the acrylic pressure-sensitive adhesive is the square root of the sum of the values obtained by multiplying the weight percentage of each monomer by the square of the solubility parameter of each monomer. Specifically, it is calculated
  • ⁇ A [( ⁇ 1 ⁇ ⁇ 1 2 + ⁇ 2 ⁇ ⁇ 2 2 +... + ⁇ n ⁇ ⁇ n 2 ) / 100] 1/2 (2)
  • ⁇ A is the solubility parameter [(cal / cm 3 ) 1/2 ] of the acrylic pressure-sensitive adhesive.
  • ⁇ n is the weight percentage (mass%) of the n-th monomer among all monomers.
  • ⁇ n is the solubility parameter [(cal / cm 3 ) 1/2 ] of the n-th monomer, where n is an integer representing the number of types of monomers.)
  • the pressure-sensitive adhesive layer contains polyisobutylene.
  • polyisobutylene does not form a single phase with the acrylic pressure-sensitive adhesive without being compatible with the acrylic pressure-sensitive adhesive, and exists as an independent phase.
  • polyisobutylene has rubber elasticity.
  • the skin surface changes with the movement of the human body. Due to the movement of the human body, a peeling force for peeling the patch from the skin surface may be applied to the patch stuck to the skin surface. Even if the pressure-sensitive adhesive layer tends to float from the skin surface due to this peeling force, the polyisobutylene is in a state where a thread is pulled between the pressure-sensitive adhesive layer and the skin surface.
  • the thread-like polyisobutylene functions to prevent the pressure-sensitive adhesive layer from detaching from the skin surface and to return the pressure-sensitive adhesive layer that is about to leave the skin surface by elastic restoring force to the skin surface.
  • the pressure-sensitive adhesive layer maintains a state adhered to the skin surface. Therefore, the pressure-sensitive adhesive layer reliably maintains the state of sticking to the skin surface regardless of the movement of the human body, and the patch maintains the state of being securely applied to the skin surface regardless of the movement of the skin after application. To do.
  • the weight average molecular weight Mw of polyisobutylene is 40,000 to 400,000, preferably 60000 to 150,000, and more preferably 65,000 to 100,000.
  • the weight average molecular weight of the polyisobutylene is 40000 or more, even if the pressure-sensitive adhesive layer tends to float from the skin surface, it becomes a thread between the pressure-sensitive adhesive layer and the skin surface, and the patch is attached to the skin surface. Make sure to maintain the state.
  • the weight average molecular weight of the polyisobutylene is 400000 or less, the thread-like polyisobutylene temporarily formed between the pressure-sensitive adhesive layer and the skin surface has elasticity necessary for returning the pressure-sensitive adhesive layer to the skin surface. Since it expresses, it is preferable.
  • the weight average molecular weight of polyisobutylene says the polystyrene conversion value measured by a gel permeation chromatography (GPC) method.
  • the weight average molecular weight Mw of the polyisobutylene refers to a value calculated based on the following formula (3).
  • Mw [M 1 ⁇ W 1 + M 2 ⁇ W 2 +... + Mn ⁇ Wn] / 100 (3)
  • Mw is the weight average molecular weight of polyisobutylene
  • Mn is the weight average molecular weight of the nth polyisobutylene in the total polyisobutylene
  • Wn is the weight percentage of the nth polyisobutylene in the total polyisobutylene ( N is an integer representing the number of types of polyisobutylene.)
  • the solubility parameter of polyisobutylene is preferably 7.1 to 8.3 (cal / cm 3 ) 1/2 .
  • the solubility parameter of polyisobutylene is 7.1 to 8.3 (cal / cm 3 ) 1/2
  • the acrylic adhesive and polyisobutylene take a micro phase separation structure in the adhesive layer. Mix well. Therefore, even when a force for peeling the patch from the skin is applied to the patch, the polyisobutylene pulls the thread on the entire surface of the pressure-sensitive adhesive layer, and the patch is well prevented from peeling from the skin surface.
  • the solubility parameter of polyisobutylene can be measured by the same method as the case of an acrylic adhesive.
  • the absolute value of the difference between the solubility parameter of the acrylic adhesive and the solubility parameter of polyisobutylene is preferably 0.9 to 2.5 (cal / cm 3 ) 1/2 , 1.1 to 1.9 ( cal / cm 3 ) 1/2 is more preferable.
  • the absolute value of the difference between the solubility parameter of the acrylic adhesive and the solubility parameter of polyisobutylene is 0.9 to 2.5 (cal / cm 3 ) 1/2 .
  • the content ratio of polyisobutylene and acrylic pressure-sensitive adhesive is 0.4 to 0.8, preferably 0.5 to 0.7, 0.55 to 0.65 is more preferable.
  • the content ratio of the polyisobutylene and the acrylic pressure-sensitive adhesive is 0.4 or more, the patch can be stably adhered to the skin surface regardless of the movement of the human body.
  • the content ratio of the polyisobutylene and the acrylic pressure-sensitive adhesive is 0.8 or less, the pressure-sensitive adhesive layer can exhibit more excellent tack to the skin.
  • the content of polyisobutylene in the pressure-sensitive adhesive layer is preferably 15 to 40% by mass, more preferably 20 to 38% by mass, and particularly preferably 25 to 36% by mass.
  • the patch can be stably adhered to the skin surface regardless of the movement of the human body.
  • the content of polyisobutylene in the pressure-sensitive adhesive layer is 40% by mass or less, the pressure-sensitive adhesive layer can exhibit more excellent tack to the skin.
  • the pressure-sensitive adhesive layer preferably contains a plasticizer. It is preferable that the plasticizer is compatible with both the acrylic pressure-sensitive adhesive and the polyisobutylene because the pressure-sensitive adhesive layer exhibits a better tack with respect to the skin. When polyisobutylene is contained in the pressure-sensitive adhesive layer, the tackiness of the pressure-sensitive adhesive layer with respect to the skin is reduced as compared with the case where polyisobutylene is not contained in the pressure-sensitive adhesive layer. By including a plasticizer in the pressure-sensitive adhesive layer, the acrylic pressure-sensitive adhesive can be plasticized and the anchoring property of the pressure-sensitive adhesive layer to the skin surface can be improved.
  • the adhesive layer can exhibit an excellent tack to the skin, and the patch can be reliably stuck to the skin. Therefore, by using a combination of polyisobutylene and a plasticizer, the patch can be firmly attached to the skin surface, and the patch can be stably applied after the application regardless of the movement of the human body. Can be attached to the skin surface.
  • plasticizer examples include esters such as isopropyl myristate, decyl oleate, isopropyl adipate, glyceryl tricaprylate, glyceryl tricaprate, glyceryl tri (caprylate / caprate); myristyl alcohol, cetanol, octyldodecanol, Examples include monohydric alcohols such as isostearyl alcohol and stearyl alcohol; dihydric alcohols such as octanediol; acids such as oleic acid and stearic acid; and liquid paraffin.
  • esters such as isopropyl myristate, decyl oleate, isopropyl adipate, glyceryl tricaprylate, glyceryl tricaprate, glyceryl tri (caprylate / caprate); myristyl alcohol, cetanol, octyldodecanol, Examples include monohydr
  • esters and liquid paraffin are preferable, and esters of monovalent carboxylic acid and monohydric alcohol and liquid paraffin are more preferable.
  • the monovalent carboxylic acid include myristic acid and oleic acid.
  • the monohydric alcohol include isopropyl alcohol, decyl alcohol, myristyl alcohol, cetanol, octyldodecanol, isostearyl alcohol, stearyl alcohol and the like.
  • a plasticizer may be used independently or may use 2 or more types together.
  • the content ratio (plasticizer mass / polyisobutylene mass) of the plasticizer and polyisobutylene is preferably 2 or less, more preferably 0.4 or less, and particularly preferably 0.35 or less.
  • the content ratio of the plasticizer and polyisobutylene is 2 or less, the filamentous polyisobutylene that is temporarily formed between the adhesive layer and the skin surface is necessary to restore the adhesive layer to the skin surface. It is preferable because it exhibits excellent elasticity.
  • the content ratio of the plasticizer to the polyisobutylene (the mass of the plasticizer / the mass of the polyisobutylene) is preferably 0.1 or more, and more preferably 0.15 or more.
  • the content ratio of the plasticizer and polyisobutylene is 0.1 or more, even if the distance between the adhesive layer and the skin surface increases, the polyisobutylene pulls the thread, and the adhesive layer is more securely attached to the skin surface.
  • the content of the plasticizer in the pressure-sensitive adhesive layer is preferably 0.1 to 35% by mass, more preferably 1 to 15% by mass, and particularly preferably 2 to 10% by mass.
  • the content of the plasticizer is 0.1% by mass or more, the pressure-sensitive adhesive layer can exhibit excellent tack to the skin. It is preferable for the content of the plasticizer to be 35% by mass or less because cold flow of the pressure-sensitive adhesive layer during storage can be suppressed.
  • the solubility parameter of the plasticizer is preferably 6.5 to 9.2 (cal / cm 3 ) 1/2, more preferably 6.5 to 8.4 (cal / cm 3 ) 1/2 , and 6.7 ⁇ 8.2 (cal / cm 3 ) 1/2 is particularly preferred, and 7.0 to 8.0 (cal / cm 3 ) 1/2 is most preferred.
  • the solubility parameter of the plasticizer is 6.5 to 9.2 (cal / cm 3 ) 1/2
  • the plasticizer is well compatible with both the acrylic adhesive and polyisobutylene,
  • the pressure-sensitive adhesive layer can exhibit better tack.
  • the solubility parameter of a plasticizer means the value measured in the same way as the solubility parameter of an acrylic adhesive.
  • the pressure-sensitive adhesive layer contains a drug. Any drug may be used as long as it can be absorbed transdermally.
  • a drug such as donepezil, rivastigmine, galantamine, tacrine, and memantine; Parkinson's disease drugs such as selegiline and rotigotine; Anti-inflammatory drugs such as diclofenac, indomethacin, and ethyl salicylate.
  • the drug is preferably a liquid drug that is liquid at 30 ° C. and has a plasticizing effect.
  • liquid drugs include rivastigmine, selegiline, memantine, and ethyl salicylate.
  • the acrylic adhesive can be plasticized to further improve the anchoring property of the adhesive layer to the skin surface. Thereby, when sticking a patch, the adhesive layer can exhibit the tack which was more excellent with respect to skin.
  • the content of the drug in the pressure-sensitive adhesive layer is preferably 1 to 40 parts by weight, more preferably 1 to 30 parts by weight, and particularly preferably 5 to 25 parts by weight with respect to 100 parts by weight of the acrylic pressure-sensitive adhesive. If the drug content is low, the drug blood concentration may not be improved to the desired range. In addition, if the content of the drug is high, excessive drug may be wasted.
  • the pressure-sensitive adhesive layer may contain other additives in addition to the above-mentioned acrylic pressure-sensitive adhesive, polyisobutylene and plasticizer.
  • other additives include absorption promoters, stabilizers, fillers, and the like.
  • the filler is used to adjust the shape retention of the pressure-sensitive adhesive layer.
  • the filler include inorganic fillers such as silicic anhydride, titanium oxide, and zinc oxide; organometallic salts such as calcium carbonate and magnesium stearate; cellulose such as lactose, crystalline cellulose, ethyl cellulose, and low-substituted hydroxypropyl cellulose. Derivatives and the like.
  • the content of the filler in the pressure-sensitive adhesive layer is preferably 5 parts by mass or less and more preferably 2 parts by mass or less with respect to 100 parts by mass of the acrylic pressure-sensitive adhesive.
  • the tackiness of the pressure-sensitive adhesive layer may be lowered.
  • the thickness of the pressure-sensitive adhesive layer is not particularly limited, but is preferably 10 to 250 ⁇ m, more preferably 20 to 200 ⁇ m, and particularly preferably 40 to 150 ⁇ m.
  • a thin adhesive layer may not contain a sufficient amount of drug.
  • a thick adhesive layer may reduce the cohesive force.
  • the above-mentioned pressure-sensitive adhesive layer is laminated and integrated on one surface of the support.
  • the support is required to have strength for preventing loss of the drug in the pressure-sensitive adhesive layer and imparting self-holding property to the patch.
  • Examples of such a support include a resin film, a nonwoven fabric, a woven fabric, a knitted fabric, and an aluminum sheet.
  • Examples of the resin constituting the resin film include cellulose acetate, rayon, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyethylene, Examples thereof include polypropylene and polyvinylidene chloride.
  • polyethylene terephthalate is particularly preferable because it can prevent loss of the drug from the pressure-sensitive adhesive layer even if it is a volatile drug.
  • Examples of the material constituting the nonwoven fabric include polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ethylene-methyl (meth) acrylate copolymer, nylon, polyester, vinylon, styrene-isoprene-styrene block copolymer, Examples thereof include styrene-ethylene / butylene-styrene block copolymers, rayon and cotton, and polyester is preferred. In addition, these materials may be used independently or 2 or more types may be used together.
  • the support may be a single layer or a laminated sheet in which a plurality of layers are laminated and integrated.
  • the laminated sheet include a laminated sheet in which a polyethylene terephthalate sheet and a nonwoven fabric or a flexible resin sheet are laminated and integrated.
  • the thickness of the support is not particularly limited, but is preferably 2 to 200 ⁇ m, more preferably 2 to 100 ⁇ m.
  • a release liner may be laminated and integrated on one surface of the pressure-sensitive adhesive layer so as to be peeled off.
  • the release liner is used for preventing loss of the drug in the pressure-sensitive adhesive layer and protecting the pressure-sensitive adhesive layer.
  • Examples of the release liner include paper and resin film.
  • Examples of the resin constituting the resin film include polyethylene terephthalate, polyethylene, polypropylene, polyvinyl chloride, and polyvinylidene chloride. It is preferable that the surface of the release liner facing the pressure-sensitive adhesive layer is subjected to a mold release treatment.
  • a pressure-sensitive adhesive layer solution containing an acrylic pressure-sensitive adhesive and polyisobutylene, a drug and a solvent is applied to one surface of the support and then dried.
  • a pressure-sensitive adhesive layer is laminated and integrated on one surface of the body, and if necessary, a release liner is laminated on the pressure-sensitive adhesive layer so that the surface where the release treatment of the release liner is performed faces the pressure-sensitive adhesive layer.
  • Method (2) The pressure-sensitive adhesive layer solution is applied onto the release liner surface, and dried to form a pressure-sensitive adhesive layer on the release liner, which is then supported by the pressure-sensitive adhesive layer. Examples include a method of stacking and integrating the body.
  • the pressure-sensitive adhesive layer solution can be obtained by uniformly stirring an acrylic pressure-sensitive adhesive, polyisobutylene, drug and solvent.
  • the solvent is not limited as long as it can dissolve the acrylic pressure-sensitive adhesive and polyisobutylene.
  • toluene, normal hexane, cyclohexane, normal heptane, and ethyl acetate are preferable.
  • Acrylic adhesive A was prepared as follows. A monomer containing 13 parts by weight of dodecyl methacrylate, 78 parts by weight of 2-ethylhexyl methacrylate and 9 parts by weight of 2-ethylhexyl acrylate was added to 50 parts by weight of ethyl acetate, and these were stirred to obtain a reaction solution. . Next, the reaction solution was supplied to a 40 liter polymerization machine, and the inside of the polymerization machine was set to a nitrogen atmosphere at 80 ° C. On the other hand, 0.5 parts by mass of benzoyl peroxide was dissolved in 50 parts by mass of cyclohexane to obtain a polymerization initiator solution.
  • the monomer is copolymerized while adding the polymerization initiator solution to the reaction solution over 24 hours, and after completion of the polymerization, ethyl acetate is further added to the reaction solution, and the content of the acrylic pressure-sensitive adhesive A is 35% by mass. A solution was obtained.
  • the solubility parameter of the acrylic pressure-sensitive adhesive A was 9.0 (cal / cm 3 ) 1/2 .
  • Acrylic pressure-sensitive adhesive A ethyl cellulose (coagulation modifier, solubility parameter: 10.3 (cal / cm 3 ) 1/2 , trade name “Etocel” manufactured by Dow Chemical Co.), polyisobutylene A (weight average molecular weight: 340000, Solubility parameter: 7.6 (cal / cm 3 ) 1/2 , product name “Oppanol B50” manufactured by BASF), polyisobutylene B (weight average molecular weight: 200000, solubility parameter: 7.6 (cal / cm 3) ) 1/2 , a product name “OPPANOL B30” manufactured by BASF), polyisobutylene C (weight average molecular weight: 75000, solubility parameter: 7.6 (cal / cm 3 ) 1/2 , a product name “OPPANOL” manufactured by BASF B15 "), polyisobutylene D (weight average molecular weight: 51000, solubility parameter: 7.6 ( al
  • Tri (caprylic acid / capric acid) glyceryl is a triester of glycerin and carboxylic acid containing caprylic acid and capric acid.
  • a polyethylene terephthalate film (thickness 38 ⁇ m) subjected to silicone release treatment was prepared as a release liner.
  • a polyethylene terephthalate film (thickness 25 ⁇ m) was prepared as a support.
  • the support and the laminate were overlapped so that the support and the pressure-sensitive adhesive layer faced each other, and the adhesive layer of the laminate was laminated and integrated on one surface of the support to obtain a patch.
  • a patch (after use) in which the content of rivastigmine in the pressure-sensitive adhesive layer was 2 parts by mass was prepared.
  • a patch (after use) in which the content of rivastigmine in the pressure-sensitive adhesive layer was 3 parts by mass was prepared.
  • a patch (after use) in which the content of rivastigmine in the pressure-sensitive adhesive layer was 3 parts by mass was prepared.
  • the patch (after use) was subjected to a 180 ° peel test, a ball tack test, and a probe tack test in the following manner, and the obtained results are shown in the “API low concentration” column of Tables 1 to 3.
  • Test tack test Three test pieces (area 3 cm 2 ) were obtained by cutting an arbitrary part of the patch. About each test piece, the probe was press-bonded to the surface of the pressure-sensitive adhesive layer of the test piece with a pressure of 1000 g for 3 seconds using a probe tack tester (trade name “TA-500” manufactured by UBM). Next, the probe was pulled away from the pressure-sensitive adhesive layer at a speed of 0.01 mm / s, and the tensile force was continuously measured until the pressure-sensitive adhesive layer of the test piece and the probe were completely peeled to obtain a tensile peak. The area of the measured tensile peak is shown in Tables 1-3.
  • the patch of the present invention can exhibit an excellent tack to the skin at the time of application, and the peeling from the skin during the application is reduced, so that various drugs can be stably percutaneously absorbed and the drug administration effect can be obtained. It can be obtained stably.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un patch adhésif qui est susceptible de présenter une excellente adhérence lorsqu'il adhère à la peau et réduit l'exfoliation de la peau une fois qu'il adhère à celle-ci. Ce patch adhésif est caractérisé en ce qu'il comprend : un corps de support; et une couche adhésive qui est stratifiée d'un seul tenant sur une surface du corps de support et comprend un adhésif acrylique, du polyisobutylène ayant une masse moléculaire moyenne en poids de 40 000 à 400 000, et un médicament, le rapport des teneurs en polyisobutylène et en adhésif acrylique (masse de polyisobutylène / masse d'adhésif acrylique) étant de 0,4 à 0,8.
PCT/JP2016/075041 2015-08-27 2016-08-26 Patch adhésif Ceased WO2017034027A1 (fr)

Priority Applications (2)

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JP2017536492A JP6304457B2 (ja) 2015-08-27 2016-08-26 貼付剤
CN201680049133.5A CN107921141A (zh) 2015-08-27 2016-08-26 贴剂

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JP2015168095 2015-08-27
JP2015-168095 2015-08-27

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WO2017034027A1 true WO2017034027A1 (fr) 2017-03-02

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PCT/JP2016/075041 Ceased WO2017034027A1 (fr) 2015-08-27 2016-08-26 Patch adhésif

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CN (1) CN107921141A (fr)
WO (1) WO2017034027A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019017266A1 (fr) * 2017-07-19 2019-01-24 帝國製薬株式会社 Préparation de type à absorption percutanée contenant de la rivastigmine
WO2022039195A1 (fr) * 2020-08-19 2022-02-24 東洋インキＳｃホールディングス株式会社 Timbre adhésif

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210065931A (ko) * 2018-09-26 2021-06-04 니찌방 가부시기가이샤 함수계 첩부제

Citations (5)

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JPH06510279A (ja) * 1991-06-27 1994-11-17 ノーヴェン ファーマシューティカルズ インコーポレイテッド 溶解パラメーターに基く薬剤送出系及び薬剤飽和濃度を変化させる方法
JPH09511987A (ja) * 1994-01-07 1997-12-02 ノーヴェン ファーマシューティカルズ インコーポレイテッド 溶解度増強剤としてポリビニルピロリドンを含む経皮部材
WO2001005381A1 (fr) * 1999-07-15 2001-01-25 Hisamitsu Pharmaceutical Co., Inc. Preparations a absorption percutanee
WO2002069942A1 (fr) * 2001-03-07 2002-09-12 Hisamitsu Pharmaceutical Co., Inc. Timbre adhesif
WO2002098396A1 (fr) * 2001-05-31 2002-12-12 Hisamitsu Pharmaceutical Co., Inc. Timbres a absorption par voie percutanee

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JPH0696529B2 (ja) * 1987-03-31 1994-11-30 積水化学工業株式会社 ニトログリセリン貼付剤およびその製造方法
US9333182B2 (en) * 2011-08-31 2016-05-10 Sekisui Medical Co., Ltd. Adhesive patch

Patent Citations (5)

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Publication number Priority date Publication date Assignee Title
JPH06510279A (ja) * 1991-06-27 1994-11-17 ノーヴェン ファーマシューティカルズ インコーポレイテッド 溶解パラメーターに基く薬剤送出系及び薬剤飽和濃度を変化させる方法
JPH09511987A (ja) * 1994-01-07 1997-12-02 ノーヴェン ファーマシューティカルズ インコーポレイテッド 溶解度増強剤としてポリビニルピロリドンを含む経皮部材
WO2001005381A1 (fr) * 1999-07-15 2001-01-25 Hisamitsu Pharmaceutical Co., Inc. Preparations a absorption percutanee
WO2002069942A1 (fr) * 2001-03-07 2002-09-12 Hisamitsu Pharmaceutical Co., Inc. Timbre adhesif
WO2002098396A1 (fr) * 2001-05-31 2002-12-12 Hisamitsu Pharmaceutical Co., Inc. Timbres a absorption par voie percutanee

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019017266A1 (fr) * 2017-07-19 2019-01-24 帝國製薬株式会社 Préparation de type à absorption percutanée contenant de la rivastigmine
JPWO2019017266A1 (ja) * 2017-07-19 2020-05-28 帝國製薬株式会社 リバスチグミン含有経皮吸収型製剤
EP3656383A4 (fr) * 2017-07-19 2021-05-19 Teikoku Seiyaku Co., Ltd. Préparation de type à absorption percutanée contenant de la rivastigmine
JP7193863B2 (ja) 2017-07-19 2022-12-21 帝國製薬株式会社 リバスチグミン含有経皮吸収型製剤
US12290501B2 (en) 2017-07-19 2025-05-06 Teikoku Seiyaku Co., Ltd. Rivastigmine-containing transdermal absorption preparation
WO2022039195A1 (fr) * 2020-08-19 2022-02-24 東洋インキＳｃホールディングス株式会社 Timbre adhésif

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JP6304457B2 (ja) 2018-04-04
JPWO2017034027A1 (ja) 2018-02-22

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