WO2011136330A1 - Adhesive patch and use thereof - Google Patents

Adhesive patch and use thereof Download PDF

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Publication number
WO2011136330A1
WO2011136330A1 PCT/JP2011/060373 JP2011060373W WO2011136330A1 WO 2011136330 A1 WO2011136330 A1 WO 2011136330A1 JP 2011060373 W JP2011060373 W JP 2011060373W WO 2011136330 A1 WO2011136330 A1 WO 2011136330A1
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WO
WIPO (PCT)
Prior art keywords
patch
adhesive layer
sensitive adhesive
skin
pressure
Prior art date
Application number
PCT/JP2011/060373
Other languages
French (fr)
Japanese (ja)
Inventor
川原康慈
石倉庸子
Original Assignee
ニチバン株式会社
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Publication date
Application filed by ニチバン株式会社 filed Critical ニチバン株式会社
Priority to JP2012512907A priority Critical patent/JPWO2011136330A1/en
Publication of WO2011136330A1 publication Critical patent/WO2011136330A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/58—Adhesives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/22—Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/428—Vitamins, e.g. tocopherol, riboflavin

Definitions

  • the present invention relates to a patch that can be used to cover and protect the affected skin area caused by various skin diseases such as atopic dermatitis, and to improve and treat various symptoms caused by the skin disease.
  • the patch of the present invention can reduce itch caused by inflammation and drying by covering the affected skin area where dermatitis or the like occurs, and also suppress the spread of itch caused by scratching the inflammatory site and the spread of inflammation. Can do.
  • the patch of the present invention can be applied to uses such as pharmaceuticals or quasi drugs by containing a pharmacologically active substance in the adhesive layer.
  • the patch of the present invention is suitable as a medical patch, but is not limited thereto and can be applied to other uses.
  • a layer structure in which a pressure-sensitive adhesive layer is provided on a support (base material layer), and a release liner is bonded to the pressure-sensitive adhesive layer.
  • a form of the patch a form wound in a roll shape is common, but there is also a sheet form. Since the patch is required to have various functions such as adhesion to the skin surface, peel resistance, and moisture permeability, for example, a patch using a thick material such as a nonwoven fabric as a support. There are many.
  • a thick patch has a defect that a sticking part is conspicuous. In order to relieve the sticking part from being noticeable, a patch is known in which the support is colored in a color close to the skin color, but it is difficult to sufficiently eliminate the difference in color tone from the actual skin.
  • Transparent products are also sold as patches used as medical dressings, but for the purpose of fixing infusion tubes, liquid injection needles, gauze, etc., the thickness of the support and adhesive layer is relatively large. The affixed part is easily noticeable. Moreover, since the adhesive has a strong adhesive force in the adhesive layer, the keratinocytes are easily detached when the adhesive is peeled from the skin surface. As a result, the patch may cause inflammation, rash, etc., or may increase inflammation due to skin irritation.
  • Patent Document 1 discloses a patch in which a drug-containing adhesive layer is provided on one side of a polyurethane film support, and the support has a 100% modulus of 60 to 110 kg /
  • a patch that is a non-self-adhesive polyurethane film having a thickness of 4 to 150 ⁇ m at cm 2 and having a moisture permeability of 300 to 500 g / m 2 ⁇ 24 hr has been proposed.
  • this patch has insufficient moisture permeability because its moisture permeability is kept as low as 300 to 500 g / m 2 ⁇ 24 hr.
  • Patent Document 2 describes an acrylic system in which a thermoplastic polyester polyurethane film having a thickness of 5 to 50 ⁇ m is used as a support and pyrrolidone having a thickness of 1 to 20 ⁇ m is copolymerized on one side of the support.
  • a patch with guide film having a layer structure provided with an adhesive layer has been proposed.
  • Patent Document 2 describes that the patch does not cause pain and does not cause redness of the skin due to sufficient moisture permeability and appropriate adhesive strength. The relaxation of keratinocyte detachment is not considered.
  • Patent Document 3 As a non-adhesive patch, an adhesive patch in which an adhesive layer having a thickness of 1 to 15 ⁇ m is provided on one side of a base material layer made of an elastomer film having a thickness of 1 to 10 ⁇ m is disclosed.
  • Patent Document 3 shows an experimental example using an acrylic pressure-sensitive adhesive as the pressure-sensitive adhesive layer.
  • a patch having an acrylic pressure-sensitive adhesive layer does not take into consideration the amount of keratinocyte peeling at the time of peeling.
  • Patent Document 4 discloses a patch comprising a base film having a thickness of 10 to 80 ⁇ m and a moisture-permeable base material, which is directly or indirectly formed with an adhesive layer for adhering to the skin.
  • a patch for treating dermatitis in which the moisture permeability as a patch is adjusted in the range of 300 to 1500 g / m 2 ⁇ 24 hr is disclosed.
  • the patch for dermatitis treatment is used for protecting the affected area of atopic dermatitis.
  • the patch for treating dermatitis moderately suppresses the transpiration of water from the skin of atopic dermatitis by selecting the base film and the pressure-sensitive adhesive so that the moisture permeability is in the above range.
  • Patent Document 4 describes that it is preferable to form the adhesive layer for skin application with an acrylic adhesive from the viewpoint of stability of quality, adhesive properties, and ease of adjustment of moisture permeability.
  • a patch having an acrylic pressure-sensitive adhesive layer has a defect that the amount of keratinocyte peeling attached to the pressure-sensitive adhesive layer is large when the patch is peeled off.
  • Patent Document 5 discloses a pressure-sensitive adhesive layer comprising a mutual condensation product of a mixture containing an organopolysiloxane resin and at least one alkylaryl polysiloxane raw rubber on the surface of an ultrathin polyurethane film.
  • An ultra-thin pressure-sensitive adhesive tape is disclosed.
  • the pressure-sensitive adhesive tape described in Patent Document 5 since the pressure-sensitive adhesive layer does not sufficiently adhere to the base material, the pressure-sensitive adhesive tends to remain on the skin surface when peeling from the skin surface.
  • Patent Document 6 discloses a body comprising a base material mainly composed of a polyester elastomer and an adhesive layer containing an addition reaction type silicone formed on at least one surface thereof. A surface patch is disclosed.
  • Patent Document 6 describes that the thickness of the base material composed mainly of a polyester elastomer is preferably 15 to 150 ⁇ m, and the thickness of the pressure-sensitive adhesive layer is preferably 10 to 2000 ⁇ m. Comparative Examples 1 and 2 of Patent Document 6 show that a patch using a polyurethane film as a base material instead of a polyester elastomer film tends to peel off the adhesive layer from the base material. It is described that the water vapor transmission rate is as small as 641 to 678 g / m 2 ⁇ 24 hr.
  • the patch not only prevents the invasion of various external factors such as pathogenic bacteria by covering the damaged skin such as inflammation and damage, but also supports the moisture retention function of the stratum corneum on the skin surface. Fulfill. For this reason, the patch acts as a substitute for the stratum corneum for skin with impaired original skin function, such as atopic dermatitis, and prevents the affected area from deteriorating by directly scratching strong itching. It is expected to play a role in promoting the natural recovery of the affected area.
  • the patch has an appropriate moisture retention function, it has a defect that sweat tends to accumulate between the skin surface and the adhesive layer. For this reason, it is desirable for the patch to be able to exhibit an appropriate moisture retention function while preventing sweat from accumulating between the skin surface and the pressure-sensitive adhesive layer by being excellent in moisture permeability.
  • the applied area may be unnoticeable because the applied area becomes larger or the applied area increases and the applied area is often exposed from clothing. desirable.
  • the patch contains a pharmacologically active substance in the adhesive layer, it is desirable that the pharmacologically active substance can be efficiently released even with a small content.
  • An object of the present invention is to provide a patch that is excellent in moisture permeability, in which the applied part is not conspicuous and the amount of keratinocyte peeling is suppressed.
  • Another subject of the present invention is excellent in the above-mentioned various characteristics, and when a pharmacologically active substance is contained in the pressure-sensitive adhesive layer, the release efficiency of the pharmacologically active substance is high even when the content is small, and the skin inflammation site It is to provide an effective patch for the treatment of cerebral palsy.
  • the present inventor has conducted intensive research in order to achieve the above problems. As a result, it is a patch having a layer structure in which a pressure-sensitive adhesive layer is provided on one side of a support, and a polyurethane film having a specific range of thickness is used as the support, and a specific range of thickness is used as the pressure-sensitive adhesive layer.
  • the release efficiency is high and a small amount of pharmacologically active substance is contained. It is possible to obtain a patch that can exhibit excellent medicinal effects even in an amount.
  • the present invention has been completed based on these findings.
  • the support is a polyurethane film having a thickness in the range of 1 to 10 ⁇ m
  • the adhesive layer is an addition reaction type silicone pressure-sensitive adhesive layer made of polyorganosiloxane having a thickness in the range of 5 to 50 ⁇ m and having no vinyl group in the side chain, and the moisture permeability of the patch is 1500 g.
  • a patch is provided that is more than / m 2 ⁇ 24 hr.
  • the adhesive patch wherein the adhesive layer contains a pharmacologically active substance in a proportion of 0.01 to 7% by weight based on the total amount of the adhesive.
  • the pharmacologically active substance contains at least one pharmacologically active substance selected from lipids or derivatives thereof present in the skin stratum corneum.
  • the pharmacologically active substance contains at least one pharmacologically active substance selected from the group consisting of fat-soluble vitamins, water-soluble vitamins and derivatives thereof.
  • the patch of the present invention is excellent in moisture permeability, it is difficult to cause rash and peeling due to the retention of sweat at the applied site.
  • the patch of the present invention is a polyurethane film with a very thin support, the entire layer thickness is relatively thin and excellent in transparency, so that it adheres to fine wrinkles and irregularities on the skin surface, and the application site is conspicuous Absent.
  • the addition reaction type silicone pressure-sensitive adhesive made of polyorganosiloxane having no vinyl group in the side chain used in the present invention is not excessively cured and becomes a gel because the crosslinking reaction is carried out only at the end of the molecule.
  • the silicone-based pressure-sensitive adhesive does not need to contain additives such as a silicone resin, a plasticizer (for example, an oily component), and a filler. For this reason, the patch of the present invention provided with the silicone-based pressure-sensitive adhesive layer has no adverse effect on the physical properties of the support and skin irritation caused by the additive component, and it is difficult to exfoliate keratinocytes on the skin surface at the time of exfoliation.
  • additives such as a silicone resin, a plasticizer (for example, an oily component), and a filler.
  • the patch of the present invention can contain a pharmacologically active substance suitable for improving various skin symptoms in the silicone pressure-sensitive adhesive layer.
  • the pharmacologically active substance exhibits a high release property with a small content.
  • the patch of the present invention covers and protects skin affected areas caused by various skin diseases such as atopic dermatitis, and is suitable for use in improving and treating various symptoms caused by skin diseases.
  • the patch of the present invention is a patch having a layer structure in which an adhesive layer is provided on one side of a support.
  • the entire shape is usually wound in a roll shape, but may be a sheet shape.
  • the support is a polyurethane film having a thickness in the range of 1 to 10 ⁇ m.
  • the pressure-sensitive adhesive layer is an addition reaction type silicone pressure-sensitive adhesive layer made of polyorganosiloxane having a thickness in the range of 5 to 50 ⁇ m and having no vinyl group in the side chain.
  • the moisture permeability of the patch is over 1500 g / m 2 ⁇ 24 hr.
  • the patch of the present invention may have a carrier film and / or a release liner in addition to the support and the pressure-sensitive adhesive layer.
  • the patch of the present invention preferably includes a carrier film, a support, and an adhesive layer in this order, and more preferably includes a carrier film, a support, an adhesive layer, and a release liner in this order.
  • the patch of the present invention has a layer configuration in which an adhesive layer is provided on one side of a support.
  • the patch of the present invention can be provided with additional layers such as a carrier film and a release liner.
  • the additional layer is peeled off when the patch is applied to the skin surface.
  • the characteristic of the patch such as moisture permeability means a characteristic relating to a multilayer structure composed of two layers of a support and an adhesive layer.
  • a release liner can be disposed to protect the surface of the pressure-sensitive adhesive layer.
  • a method of forming a pressure-sensitive adhesive layer on the release liner Since the polyurethane film of the support is extremely thin, it is preferable to use a multilayer film in which the polyurethane film is disposed on the carrier film.
  • the patch of the present invention usually preferably has a multilayer structure of “carrier film / support / adhesive layer / release liner” including a release liner and a carrier film.
  • the release liner is peeled and removed from the pressure-sensitive adhesive layer, and then applied to the skin surface, and then the carrier film on the support is peeled and removed.
  • the patch of the present invention has a layer structure of “support / adhesive layer” at the time of sticking to the skin surface.
  • the polyurethane film as a support of the patch of the present invention can be formed by any molding method such as a solution casting method or an extrusion molding method. Since the support of the patch of the present invention is an extremely thin polyurethane film having a thickness in the range of 1 to 10 ⁇ m, solution casting is required for stable and continuous production while suppressing the occurrence of tearing.
  • the method (solution coating method) or the extrusion lamination method is preferably employed, and the solution casting method is more preferably employed.
  • a method of applying an organic solvent solution of polyurethane onto a carrier film and drying is preferably employed.
  • a polyurethane solution is coated on the carrier film and dried, whereby a polyurethane film can be continuously formed.
  • the thickness of the polyurethane film can be accurately controlled, and the anisotropy of physical properties depending on the direction of the film can be reduced.
  • the pressure-sensitive adhesive layer is formed by (1) a method of directly forming a pressure-sensitive adhesive layer on a polyurethane film as a support; and (2) a pressure-sensitive adhesive layer on a release liner. After forming, the method of bonding so that the surface of this adhesive layer and the surface of a support body closely_contact
  • the silicone pressure-sensitive adhesive layer can be formed by applying a material for forming the addition reaction type silicone pressure-sensitive adhesive layer on one side of the support.
  • an organic solvent such as hexane or heptane may be used in the case of blending another solvent-based silicone pressure-sensitive adhesive obtained by a condensation reaction or the like with an addition-reactive silicone-based pressure-sensitive adhesive layer.
  • a bar coater such as a comma coater, a reverse coater, a comma reverse coater, a lip coater, a knife coater, and a Mayer bar can be employed.
  • the method (2) as a method for forming the pressure-sensitive adhesive layer on the release liner, a method of applying the material for forming the pressure-sensitive adhesive layer on the release liner and drying it while running the release liner in one direction.
  • the silicone-based pressure-sensitive adhesive may be applied on the release liner as a melt or a solution.
  • the patch of the present invention is non-aqueous, and water is not intentionally contained intentionally in the adhesive layer of the finally obtained patch.
  • the support of the patch of the present invention is a polyurethane film having a thickness in the range of 1 to 10 ⁇ m.
  • the polyurethane is not particularly limited as long as it is a polyurethane produced by polyaddition reaction of a polyisocyanate component and a polyol component. However, since a pharmacologically active substance can be added in a small amount, a polyether is used as a polyol component. The polyether-based polyurethane used is preferable.
  • Polyethers that are polyol components include polyethylene glycol, modified polyethylene glycol, polypropylene glycol, polytrimethylene ether glycol, polytetramethylene ether glycol, tetrahydrofuran, and modified polytetramethylene ether glycol that is a copolymer of 3-methyl-tetrahydrofuran. Etc. These polyol components can be used alone or in combination of two or more.
  • polyisocyanate components include diphenylmethane diisocyanate, tolylene diisocyanate, 1,4-diisocyanate benzene, xylylene diisocyanate, 2,6-naphthalene diisocyanate, methylenebiscyclohexyl isocyanate, isophorone diisocyanate, cyclohexane-1,4-diisocyanate, hexahydroxylylene. And diisocyanates such as diisocyanate and hexahydrotolylene diisocyanate. These diisocyanate components can be used alone or in combination of two or more.
  • polyester polyurethane using polyester as a polyol component in addition to polyether polyurethane, polyester polyurethane using polyester as a polyol component can be used.
  • the polyisocyanate component the diisocyanates listed above can be used.
  • the polyol component a polyester obtained from a dibasic acid such as adipic acid or phthalic acid and a diol such as ethylene glycol or propylene glycol is used.
  • the amount of the pharmacologically active substance contained in the silicone pressure-sensitive adhesive layer transferred to the support is relatively large, so that a sufficient pharmacological effect can be obtained. Needs to be added in relatively large amounts.
  • the pharmacologically active substance transferred to the support may impair properties such as strength and stretchability of the support. For this reason, polyether polyurethane is more preferable as polyurethane.
  • the thickness of the support is in the range of 1 to 10 ⁇ m, preferably 3 to 7 ⁇ m, particularly preferably 4 to 6 ⁇ m, from the viewpoint of being well adapted to the skin and not noticeable. If the thickness of the support is too thin, it is difficult to form a film, and the strength as a support is insufficient, so that the patch is applied to the adherend or the adhesive is peeled off from the adherend. In some cases, the support may be cut off. If the thickness of the support is too large, even if the thickness of the entire patch is reduced, the patch is less likely to adhere to the skin surface with fine irregularities such as skin grooves, making the applied state conspicuous and uncomfortable. It tends to grow.
  • the patch of the present invention can be used for the purpose of preventing skin scratching in humans and the like having dermatitis such as atopic dermatitis (hereinafter sometimes simply referred to as “atopy use”).
  • atopy use When the patch of the present invention is applied to atopy, the patch on the skin functions as a barrier to prevent direct scratching of the skin even when the skin is scratched, and the film does not easily break. It is preferable to have only strength.
  • the 10% tensile load in the longitudinal direction and the transverse direction of the polyurethane film measured according to JIS Z0237 of Japanese Industrial Standard is usually 0.01 to 1.2 N / 10 mm, preferably 0.05 to 1. It is desirable to be within the range of 0N / 10mm.
  • the 10% tensile load value of the polyurethane film is too small, the strength is so weak that the film-forming property and the handleability are lowered.
  • the 10% tensile load value of the polyurethane film is too large, the rigidity becomes strong and the stretchability and flexibility are insufficient. Therefore, the patch using the polyurethane film as a support is used for skin with fine irregularities such as skin grooves. It becomes difficult to adhere along the surface, and the attached state is easily noticeable.
  • the polyurethane film used for the support may contain a colorant such as a pigment or a dye, if desired. If necessary, the polyurethane film may further contain various additives such as a stabilizer, an ultraviolet absorber, and a lubricant.
  • the surface of the polyurethane film used for the support is subjected to surface treatment or primer treatment on the surface in contact with the pressure-sensitive adhesive layer of the support. It can be performed.
  • the surface treatment of the support include embossing, corona treatment, and alkali treatment.
  • a silane primer for example, FS XA-2869 manufactured by Dow Corning
  • the primer treatment agent can be applied directly to the surface of the support.
  • the thickness of the primer layer is preferably 0.05 to 3 ⁇ m, more preferably 0.05 to 1 ⁇ m.
  • the surface of the support opposite to the pressure-sensitive adhesive layer side ("support of the support"
  • a minute unevenness may be formed on the back surface.
  • the minute irregularities are particularly useful for suppressing the reflection of light on the back surface (support surface) of the support and making the application site inconspicuous, when the patch is difficult to notice. If minute irregularities are formed on the surface of the carrier film by embossing and a polyurethane film is formed on the minute irregularities, the minute irregularities can be transferred to the back surface of the support made of polyurethane film. .
  • the pressure sensitive adhesive layer of the patch of the present invention has an addition reaction type silicone pressure sensitive adhesive having a thickness in the range of 5 to 50 ⁇ m and comprising a polyorganosiloxane having no vinyl group in the side chain. Is a layer.
  • Acrylic adhesives that have been widely used as adhesives for patches have polar groups such as esters in the molecule, so the solubility of pharmacologically active substances is high, and when the amount of pharmacologically active substances added is small, There is a problem that the amount of release is reduced.
  • Rubber adhesives are composed of hydrocarbons, so the solubility of pharmacologically active substances is low, but they are poorly permeable to moisture, so sweat tends to accumulate on the application site and may be easily peeled off by external forces such as skin movements. There is a drawback.
  • Peroxide reaction type, condensation reaction type, and addition reaction type silicone pressure sensitive adhesives are known as general-purpose silicone pressure sensitive adhesives.
  • a peroxide-reactive silicone-based pressure-sensitive adhesive is benzoyl peroxide (BPO), which is a typical peroxide
  • BPO benzoyl peroxide
  • benzoic acid remains in the pressure-sensitive adhesive as a decomposition product, and is pressurized and sealed.
  • a large reactor is required.
  • the condensation reaction type silicone pressure-sensitive adhesive proceeds at room temperature, alcohols and carboxylic acids are generated as by-products, which is not preferable as a medical pressure-sensitive adhesive from the viewpoint of skin irritation.
  • Silicone pressure-sensitive adhesives generally used as medical pressure-sensitive adhesives are those in which one or more organometallic compounds are used to form a three-dimensional structure by cross-linking vinyl groups in the side chain in dimethylsiloxane.
  • a silicone resin having a three-dimensional structure is added to adjust the characteristics as an adhesive, moisture permeability, and the like.
  • the silicone-based pressure-sensitive adhesive having a general-purpose three-dimensional structure has a large number of functional groups involved in the crosslinking reaction in the molecule, so that the pressure-sensitive adhesive layer becomes hard. As a result, it was found that the amount of exfoliated keratinocytes is large and is not suitable particularly when used for atopic use.
  • the addition reaction type silicone pressure-sensitive adhesive used in the patch of the present invention is composed of a polyorganosiloxane having no vinyl group in the side chain as a main component, and the molecule has a linear structure due to the addition reaction using a catalyst. , Itself exhibits gel-like physical properties.
  • an addition reaction type silicone pressure-sensitive adhesive made of polyorganosiloxane having no vinyl group in the side chain is characterized by a lower cohesive force than a general pressure-sensitive adhesive, and as a result, is well adapted to the skin crevice. For this reason, it is useful as a pressure-sensitive adhesive for a patch where the patch site is less noticeable.
  • the patch using this addition reaction type silicone adhesive has a small amount of keratinocyte peeling when it is peeled off after being applied to the skin, and can efficiently release the added pharmacologically active substance. Therefore, an excellent function can be exhibited when combined with the polyurethane film support.
  • the addition reaction type silicone pressure-sensitive adhesive used in the patch of the present invention is prepared by adjusting the composition of a terminal vinyldimethylsiloxane, dimethylsiloxane, and dimethylsiloxane having a hydroxyl group at the terminal or side chain as a basic component within a suitable range. Further, it can be produced by a crosslinking reaction of a vinylsilyl group and a hydrosilyl group (Si—H) by adding a platinum catalyst or the like. Since the addition reaction can be cured at room temperature without using a solvent, it is friendly to the working environment, and no by-product is generated after the reaction. Therefore, the addition reaction is particularly useful as a medical adhesive.
  • the addition reaction type silicone pressure-sensitive adhesive layer of the present invention usually does not contain a silicone resin, a plasticizer, a filler or the like.
  • a silicone resin having a three-dimensional structure called MQ resin is a component that is usually blended in the silicone-based pressure-sensitive adhesive layer in order to increase skin adhesive force, but causes a large amount of keratinocyte peeling.
  • Silicone oils such as low molecular weight dimethylpolysiloxane that may be blended as a plasticizer (oil component) in the silicone pressure-sensitive adhesive layer may shift to the support and change its properties, or the silicone oil may remain on the skin after application. May feel uncomfortable.
  • the silicone-based pressure-sensitive adhesive layer contains a filler such as silica or aluminum silicate, the cohesive force is lowered and the skin adhesive ability is lowered.
  • the addition reaction type silicone pressure-sensitive adhesive layer of the present invention usually does not contain surfactants, powders, water-absorbing polymers, pH adjusters, preservatives, etc., but there are unavoidable circumstances due to the characteristic design of the pressure-sensitive adhesive. Sometimes, these additives can be blended to the extent that the object of the present invention is not impaired.
  • addition reaction type silicone pressure sensitive adhesive of the patch of the present invention it is possible to adjust the adhesive force by mixing other commonly used silicone pressure sensitive adhesives within the range of addition reaction type silicone as a main component. Can do. In particular, when pharmacologically active substances are added for the purpose of improving various skin symptoms, the adhesive properties generally decrease in many cases. For this reason, mixing with other silicone adhesives is useful. is there.
  • the content of the addition reaction type silicone in the pressure-sensitive adhesive is preferably in the range of 70 to 100% by weight, more preferably 80 to 100% by weight, and particularly preferably 90 to 100% by weight.
  • the pressure-sensitive adhesive component other than the silicone-based pressure-sensitive adhesive such as acrylic pressure-sensitive adhesive and rubber-based pressure-sensitive adhesive is usually in the range of 0 to 25% by weight, preferably 0 to 15% by weight, more preferably 0 to 10% by weight. You may contain in.
  • Additives such as fillers, pigments, and curing inhibitors can be added in the range of usually 0 to 30% by weight, preferably 0 to 20% by weight, more preferably 0 to 10% by weight.
  • the thickness of the addition reaction type silicone pressure-sensitive adhesive layer in the patch of the present invention is in the range of 5 to 50 ⁇ m, preferably 8 to 45 ⁇ m, more preferably 16 to 40 ⁇ m, and particularly preferably 20 to 35 ⁇ m.
  • the thickness of the pressure-sensitive adhesive layer is extremely thin, since the polyorganosiloxane having no vinyl group in the side chain has few functional groups, the crosslinking reaction does not proceed sufficiently.
  • crosslinking is easily inhibited, and it is important to ensure a certain thickness of the pressure-sensitive adhesive layer.
  • the total thickness of the support and the addition reaction type silicone pressure-sensitive adhesive layer is preferably 11 to 52 ⁇ m, in order to produce an effect that the followability to the skin surface is not impaired and the sticking site is not noticeable.
  • a range of 20 to 46 ⁇ m is more preferable, and a range of 25 to 40 ⁇ m is particularly preferable.
  • the patch of the present invention preferably exhibits an adhesive strength of 0.5 N / 10 mm or less, more preferably 0.2 N / 10 mm or less, particularly in a 90-degree peel test for a bakelite plate specified in JIS Z0237. Preferably, it is within the range of 0.01 to 0.1 N / 10 mm. If the adhesive strength of the pressure-sensitive adhesive layer is too large, the amount of keratinocyte peeling will increase. If the adhesive strength is too small, it may generally be easily peeled off by an external force such as skin movement. However, in the patch of the present invention, a combination of a thin and flexible support and a gel adhesive Thus, even if the adhesive force is small, it can follow the movement of the skin well.
  • the patch of the present invention preferably exhibits a holding force by which the weight falls within 30 minutes in a holding force test in which a load is applied with a weight of 200 g, and particularly preferably within a range of 5 to 25 minutes. That is, in the holding force test, a carton tape (manufactured by Nichiban Co., Ltd.) is attached to the support surface of the patch, backing, and cut into 12 mm ⁇ 50 mm, and this is pasted on a glass plate to be 12 mm ⁇ 20 mm. For a patch that was cut and applied with a weight of 200 g so that the patch hangs vertically, and the weight dropped within 30 minutes, the drop time is measured and the result of the holding force test is obtained.
  • a carton tape manufactured by Nichiban Co., Ltd.
  • the displacement distance after 30 minutes was measured with a microscope with a scale.
  • a patch in which the weight does not fall within 30 minutes has too much holding power for the pressure-sensitive adhesive layer and increases the amount of keratinocyte peeling. If the holding force is too small, it may be easily peeled off by an external force such as skin movement, but in the patch of the present invention, a combination of a thin and flexible support and a gel adhesive Thus, even if the holding force is small, the movement of the skin can be followed well.
  • the addition reaction type silicone pressure-sensitive adhesive layer preferably covers the entire surface of the support, but may be coated in a pattern if necessary.
  • a pattern for example, an arbitrary shape such as a wave shape, a lattice shape, a dot shape, a circular shape, or an arabesque pattern can be selected.
  • the patch of the present invention protects the skin surface while having appropriate moisture permeability without adding a pharmacologically active substance to the addition reaction type silicone pressure-sensitive adhesive layer. Since it is possible to prevent intrusion of an exogenous substance and prevent unintentional scratching, it is possible to prevent the affected part of dermatitis such as atopic dermatitis from getting worse.
  • the patch having the addition reaction type silicone pressure-sensitive adhesive layer of the present invention has a very small amount of exfoliated keratinocytes, and can suppress the exfoliation of the keratinocytes in the affected area to the minimum when exfoliating.
  • the patch of the present invention can enhance the function as a medical patch by containing a pharmacologically active substance in the addition reaction type silicone pressure-sensitive adhesive layer.
  • the skin of patients with atopic dermatitis is known to have glucosylceramide metabolism abnormality, and the amount of ceramide produced is small. Therefore, since the skin barrier function and moisturizing ability are lowered, it is effective to contain lipids or derivatives thereof existing in the skin stratum corneum such as ceramide in order to supplement the reduced production amount of ceramide.
  • ceramide and its precursor include ceramide 1, 2, 3, 4, 5, and 6, and keratinocyte lipids such as phytosphingosine.
  • vitamins that are effective against skin moisturizing and itching and blemishes; glycyrrhetin, glycyrrhizinate and menthol, which suppress skin inflammation; crotamiton, which suppresses skin itchiness; The drug lidocaine; and the like can be used.
  • the vitamins at least one selected from the group consisting of vitamin E, which is a fat-soluble vitamin, and esters thereof, vitamin B6, which is a water-soluble vitamin, vitamin C, esters thereof, and derivatives thereof is effective.
  • vitamin C derivative ascorbyl tetrahexyldecanoate (NIKKOL (registered trademark) VC-IP, Nikko Chemicals Co., Ltd.) has high permeability to the skin, relieves oxidative stress, and suppresses pigmentation.
  • pyridoxine tri-2-hexyldecanoate (NIKKOL (registered trademark) VB6-IP, Nikko Chemicals Co., Ltd.), which is a vitamin B6 derivative having a high moisturizing effect.
  • ceramide 1 which is considered to be remarkably reduced in affected areas of atopic dermatitis, phytosphingosine having ceramide synthesis promotion and bacteriostatic action is useful.
  • a humectant such as glycerin, propylene glycol, sorbitol, 1,3-butylene glycol, polyethylene glycol, urea, sodium lactate, peptide, heparin, and hyaluronic acid for maintaining the moisture retention can be appropriately added.
  • Ceramide or precursors of keratinocyte lipids lost in affected areas of dermatitis such as atopic dermatitis, and vitamins useful for alleviating skin symptoms are compatible with addition-reactive silicone adhesives. Since the solubility is moderately good, when it is added to an addition reaction type silicone pressure-sensitive adhesive, it exhibits a high release property with a small addition amount compared to the case of adding them to an acrylic pressure-sensitive adhesive. Therefore, the patch of the present invention containing a pharmacologically active substance in the pressure-sensitive adhesive layer is effective for treating and alleviating various symptoms of dermatitis.
  • Pharmacologically active substances can be used alone or in combination of two or more. These pharmacologically active substances are usually in the range of 0.01 to 7% by weight, preferably 0.05 to 6% by weight, more preferably 0.1 to 5% by weight in the addition reaction type silicone pressure-sensitive adhesive layer. It can be made to contain.
  • the thickness of the polyurethane film as the support in the patch of the present invention is 1 to 10 ⁇ m, more preferably 3 to 7 ⁇ m.
  • a carrier film is disposed on the surface (back surface) opposite to the addition-reactive silicone pressure-sensitive adhesive layer of the support for the purpose of improving handleability and usability at the time of application to the skin. It is desirable to have a layer structure.
  • the carrier film may cover the entire surface of the support, may cover only the edge of the patch, or may be covered with a pattern such as a lattice, but it covers the entire surface of the support. Preferably there is.
  • glassine paper using high-quality paper usually used for patches glassine paper using high-quality paper usually used for patches, polylaminated paper in which a plastic film is laminated on high-quality paper, or a film that has been subjected to a release treatment by applying a silicone resin to the surface of the plastic film, etc. Can be used.
  • plastic film used as the carrier film examples include various thermoplastic resins such as polyester, polyurethane, polyethylene, polypropylene, ionomer, polyamide, polyvinyl chloride, polyvinylidene chloride, ethylene vinyl acetate copolymer, and polytetrafluoroethylene. Can be used.
  • carrier film for example, polyhydroxybutyrate resin, polyhydroxyalkanoate, maltotriose, polylactic acid resin, polyethylene succinate resin, polybutylene succinate resin, polycaprolactone resin, polybutylene adipate Films formed from terephthalate, polytetramethylene adipate terephthalate, polyethylene terephthalate, polyvinyl alcohol, polyglycolic acid, starch fatty acid ester, starch processing resin, starch polyester, cellulose acetate, chitosan and the like can be used. Among these, a biodegradable plastic film is preferable. These various films may be laminated on paper.
  • the surface of the surface coated with silicone or the like can be removed.
  • a non-drug-adsorbing carrier film such as a polyester film is suitable because the pharmacologically active substance may migrate through the support polyurethane film. ing.
  • the patch having a low adhesive strength as in the present invention it is desirable that the patch is peeled off so that the carrier film can be easily peeled after being applied to the skin.
  • a polyester film that has been subjected to release treatment on both sides can be used for the carrier film.
  • the carrier film is desirably thicker or firmer than the support polyurethane film.
  • the thickness of the carrier film can be appropriately set, but is usually 10 ⁇ m or more, preferably 20 ⁇ m or more, and the upper limit is usually 500 ⁇ m, preferably 300 ⁇ m, more preferably 200 ⁇ m.
  • release liner In the patch of the present invention, a release liner (hereinafter sometimes referred to as “release film”) is provided on the surface of the addition reaction type silicone pressure-sensitive adhesive layer opposite to the side in contact with the support. Is preferred.
  • release liner polyolefin films such as untreated polyethylene film and polypropylene film; polyester film represented by polyethylene terephthalate; laminated paper of plastic film and paper (polylaminated paper); A release liner that is widely used in the above can be used.
  • the surface of the release liner (the surface on the pressure-sensitive adhesive layer side) can be subjected to a surface treatment (release treatment) with a fluororesin, a fluorosilicone resin, a silicone resin, or the like.
  • a surface treatment (release treatment) with a fluororesin, a fluorosilicone resin, a silicone resin, or the like is suitable.
  • the pharmacologically active substance may migrate to the release liner as in the case of the carrier film, it is preferable to perform a surface treatment (mold release treatment) on a non-drug adsorbing film such as a polyester film.
  • the thickness of the release liner can be appropriately set, but is usually 10 ⁇ m or more, preferably 20 ⁇ m or more, and the upper limit is usually 500 ⁇ m, preferably 300 ⁇ m, more preferably 200 ⁇ m.
  • the release liner may be formed by applying an addition reaction type silicone pressure-sensitive adhesive layer on a support and then pressing the release liner with the release liner, or the addition reaction type silicone pressure-sensitive adhesive layer on the release liner. After the coating, the addition reaction type silicone pressure-sensitive adhesive layer may be formed by a method of pressure-bonding to a support.
  • a patch comprising a carrier film, a support, a pressure-sensitive adhesive layer, and a release liner in this order is used to separate the support from the carrier film because of the peeling force required to peel the release liner from the pressure-sensitive adhesive layer. It is preferable to set so as to be larger than the required peeling force. By doing so, the surface of the addition reaction type silicone pressure-sensitive adhesive layer that appears after the release liner is peeled off can be applied to the skin, and then the carrier film can be peeled off, so that workability is improved.
  • the patch of the present invention is a patch having a layer structure in which an adhesive layer is provided on one side of a support, and the support is a polyurethane film having a thickness in the range of 1 to 10 ⁇ m.
  • the layer is an addition reaction type silicone pressure-sensitive adhesive layer made of polyorganosiloxane having a thickness in the range of 5 to 50 ⁇ m and having no vinyl group in the side chain, and the moisture permeability exceeds 1500 g / m 2 ⁇ 24 hr.
  • covering damaged skin not only prevents the invasion of various external factors, but also serves to help the moisture retention ability of the stratum corneum on the skin surface.
  • the patch of the present invention has a moisture permeability of more than 1500 g / m 2 ⁇ 24 hr, thereby preventing the skin that causes skin irritation from accumulating at the applied site, and causing the patch to peel from the skin by sweating. Therefore, the skin surface can be protected with appropriate moisture permeability.
  • the patch of the present invention can prevent the entry of exogenous substances, and can also serve as a substitute for the stratum corneum for skin in which the function of healthy skin such as atopic dermatitis is impaired. .
  • the moisture permeability is a value measured according to JIS Z0208.
  • the patch of the present invention covers the affected area of the skin, thereby avoiding deterioration of the affected area due to scratching and promoting natural recovery of the affected area of dermatitis such as atopic dermatitis.
  • the patch of the present invention prevents the entry of exogenous substances by protecting the skin surface while having an appropriate moisture permeability, even without adding a pharmacologically active substance to the addition reaction type silicone pressure-sensitive adhesive layer. Since it is possible to prevent a human having symptoms of dermatitis such as dermatitis from unintentionally scratching the skin, the affected area can be prevented from deteriorating.
  • the patch of the present invention functions as a barrier that prevents the skin patch from directly scratching even when a person with atopic skin inflammation or the like takes a skin scratching action. Therefore, the patch of the present invention can be suitably used as a patch for preventing skin scratches on humans with atopic skin inflammation.
  • the addition reaction type silicone pressure-sensitive adhesive layer may contain a pharmacologically active substance.
  • the patch of the present invention When the patch of the present invention is peeled off after being applied to the skin surface, the amount of exfoliated keratinocytes on the skin is extremely small.
  • the patch of the present invention When the patch of the present invention is affixed to the skin surface inside the human forearm for 6 hours and then peeled off, the keratinocyte peeling area relative to the sticking area can be 20% or less.
  • the keratinocyte peeling area is 20% or less, generation of skin irritation is suppressed, and the affected area is not deteriorated. Therefore, since the patch of the present invention has a particularly reduced keratin intercellular binding force, it does not exacerbate the human symptoms of atopic skin inflammation in which the keratinocytes are more easily detached.
  • a patch of a predetermined shape was applied to the inner side of the forearm of a healthy subject (subject with a healthy skin) for a predetermined time (6 hours). Thereafter, the patch was peeled off, and the keratinocytes peeled from the skin and transferred to the surface of the pressure-sensitive adhesive layer were observed using a staining solution, and the area stained with the peeled keratinocytes with respect to the entire area of the patch It means that the area ratio is 20% or less. If the keratinocyte peeling area after 6 hours of application is preferably 15% or less, more preferably 10% or less, still more preferably 5% or less, and particularly preferably 2% or less, the damage to the skin is minimized. be able to.
  • ⁇ Amount of exfoliated corneocytes> The amount of exfoliated keratinocytes is applied to the inside of the forearm of 6 healthy adult men and women in their 20s and 40s for 6 hours, and the patch cut into a size of 15mm x 50mm is applied for 6 hours.
  • the attached keratinocytes are stained by immersing them in a cationic dye solution (gentian violet B: 1%, brilliant green: 0.5%, distilled water: 98.5%) for 3 hours, and the keratinocytes are detached using an image processing apparatus. The area ratio (%) was measured, and an average value and a standard deviation were obtained.
  • ⁇ Moisture permeability> The moisture permeability was measured at a temperature of 40 ° C. and a relative humidity of 90% in accordance with the B condition of JIS Z0208. That is, one side of the sample is adjusted to a temperature of 40 ° C. and a relative humidity of 90%, and about 16 g of a hygroscopic agent (calcium chloride) is placed on the other side to absorb the moisture that has passed through the sample. The amount of change was converted to 1 m 2 per 24 hours, and the average value of the three patches was taken as moisture permeability.
  • a hygroscopic agent calcium chloride
  • the adhesive strength was measured according to the 90 degree peel test defined in JIS Z0237. Specifically, after the washed bakelite plate (phenol resin plate, manufactured by Sumitomo Bakelite Co., Ltd., PL-1102) is dried, a patch cut to a width of 10 mm is applied, and after pressing with a 2 kg load roll, 20 ⁇ Measure the stress (N) when peeling off at a pulling rate of 100 mm / min in the 90-degree direction with an Instron type tensile tester within 10 minutes to determine the adhesive strength and the average value and standard deviation of the three patches. Asked.
  • N stress
  • ⁇ Pharmacologically active substance release test> The amount of the pharmacologically active substance released was determined by mounting the patch on a horizontal diffusion cell having a substantial permeation area of 1.766 cm 2 (circular with a diameter of 1.5 cm) so that the adhesive layer surface was inside, and receiving the receiver liquid (PBS; pH 7 .4) A 20% PEG aqueous solution was added, and a release test was performed at 32 ° C. for measurement. Sampling the effluent of 1 hour after the start, by HPLC (Shimadzu high performance liquid chromatograph LC-2010), to quantify the concentration of the pharmacologically active substances of three patches, as emission amount per 1 cm 2 Average values and standard deviations were determined.
  • HPLC Shiadzu high performance liquid chromatograph LC-2010
  • Example 1 A polyether-based polyurethane elastomer solution (Lack Skin (registered trademark) US2268 manufactured by Seiko Kasei Co., Ltd.) is applied to the surface of a 75 ⁇ m-thick polyester (PET) film treated with silicone on one side so that the thickness after drying is 5 ⁇ m and dried. And it was set as the support body which consists of a polyurethane film. Next, an appropriate amount of a silane primer (FS XA-2869 manufactured by Dow Corning) was applied to the surface of the polyurethane film with a Mayer bar.
  • a silane primer FS XA-2869 manufactured by Dow Corning
  • the film was coated to a thickness of 30 ⁇ m, placed in a constant temperature bath at 170 ° C. for 1 minute, and cured.
  • the treated surface of a polyester (PET) film having a thickness of 75 ⁇ m treated with single-sided fluorosilicone is bonded to the addition reaction type silicone pressure-sensitive adhesive and cut to form a laminated structure of carrier film / support / adhesive layer / release liner.
  • a patch with the following was obtained.
  • Example 2 Polyester polyurethane elastomer solution (Nipporan (registered trademark) 5111 manufactured by Nippon Polyurethane Co., Ltd.) was applied to a 75 ⁇ m thick PET film surface treated with one side of silicone so that the thickness after drying was 5 ⁇ m, dried, and then a polyurethane film It was set as the support body which consists of.
  • the film was coated to a thickness of 30 ⁇ m, placed in a constant temperature bath at 170 ° C. for 1 minute, and cured.
  • the treated surface of a PET film having a thickness of 75 ⁇ m treated with single-sided fluorosilicone was bonded to the addition reaction type silicone pressure-sensitive adhesive and cut to obtain a patch.
  • Example 3 The polyurethane film produced in Example 1 was coated with the addition-reactive silicone pressure-sensitive adhesive used in Example 1 so that the thickness was 10 ⁇ m, and was similarly bonded with a single-sided fluorosilicone-treated PET film and cut. A patch was obtained.
  • Example 1 The polyurethane film produced in Example 1 was coated with the addition reaction type silicone pressure-sensitive adhesive used in Example 1 so as to have a thickness of 60 ⁇ m. A patch was obtained.
  • Example 2 instead of the addition reaction type silicone adhesive used in Example 1, a silicone adhesive (BIO-PSA (registered trademark) 4501 manufactured by Dow Corning) was dried on the polyurethane film produced in Example 1 after drying. was coated with a PET film treated with single-sided fluorosilicone and cut to obtain a patch.
  • BIO-PSA 4501 is a general-purpose three-dimensional crosslinking type condensation-type silicone adhesive.
  • Comparative Example 2-2 A patch was obtained in the same manner as in Comparative Example 2, except that a silicone adhesive (BIO-PSA (registered trademark) 4501 manufactured by Dow Corning) was applied so that the thickness after drying was 10 ⁇ m.
  • a silicone adhesive BIO-PSA (registered trademark) 4501 manufactured by Dow Corning
  • SIS styrene-isoprene-styrene block copolymer
  • Comparative Example 5 In the acrylic adhesive used in Comparative Example 3, 20% by weight of oily component isopropyl myristate (IPM manufactured by Nikko Chemicals Co., Ltd.) was mixed, and after stirring, a patch was prepared in the same manner as in Comparative Example 1. .
  • oily component isopropyl myristate IPM manufactured by Nikko Chemicals Co., Ltd.
  • Example 6 A patch was obtained in the same manner as in Example 1 except that the polyether-based polyurethane elastomer solution used in Example 1 was applied so that the thickness after drying was 20 ⁇ m.
  • Table 1 shows the measurement results for the patches of Examples 1 to 3 and Comparative Examples 1 to 6.
  • FIG. 1 shows an external appearance photograph when the patches of Example 1 and Comparative Examples 2, 3 and 5 were applied to the inner portion of the forearm for 20 minutes, and the gloss values of the respective gloss checkers.
  • the black numbers are the values of the affixed sites by the gloss checker
  • the white numbers are the values of the non-applied sites by the gloss checker.
  • FIG. 2 shows an enlarged photograph (100 times) of the skin at the site of application when the patches of Example 3, Comparative Example 1 and Comparative Example 3 were applied to the inner part of the forearm.
  • (1) in FIG. 2 is the skin surface at the site where the patch is not applied
  • (2) is the skin surface at the site where the patch of Example 3 is applied
  • (3) is the site where the patch of Comparative Example 1 is applied
  • (4) is the skin surface of the patch application site of Comparative Example 3.
  • the patch of Example 3 is in close contact with the skin groove.
  • the patch of Comparative Example 1 is in close contact with the skin groove, but since the adhesive layer is thick, the skin groove is hidden, and conversely, the appearance is conspicuous.
  • the patch of Comparative Example 3 has a high cohesive strength of the acrylic adhesive, and thus the adhesive patch does not adhere to the skin groove even though the thickness of the entire patch is thin (part that looks white). Therefore, the appearance is conspicuous in pasting for a short time (about 20 minutes).
  • the polyurethane film of the support has a thickness of 10 ⁇ m or less and the addition reaction type silicone pressure-sensitive adhesive layer has a thickness in the range of 5 to 50 ⁇ m.
  • a patch comprising an adhesive layer that falls within 30 minutes in a retention test and has an adhesive strength of 0.1 N / 10 mm or less is a patch with a less noticeable site and a small amount of exfoliated keratinocytes. It can be seen that it is.
  • Comparative Example 7 In the acrylic adhesive used in Comparative Example 3, 4% by weight of pyridoxine tri-2-hexyldecanoate (“NIKKOL (registered trademark) VB6-IP” manufactured by Nikko Chemicals Co., Ltd.) was mixed, and after stirring, the adhesive layer A patch was prepared in the same manner as in Comparative Example 3, except that the thickness was 10 ⁇ m.
  • NIKKOL registered trademark
  • VB6-IP pyridoxine tri-2-hexyldecanoate
  • Example 4 For each patch of Example 4 and Comparative Example 7, a release test of pyridoxine tri-2-hexyldecanoate, which is a pharmacologically active substance, was performed. The results are shown in FIG. Error bars in the figure indicate standard deviation.
  • FIG. 4 shows that the patch of Example 4 of the present invention shows sufficient release properties even when a pharmacologically active substance is contained at a low concentration.
  • the pharmacologically active substance concentration (4% by weight) in the adhesive layer was twice the concentration (2% by weight) in the patch of Example 4, It can be seen that there is only about half the amount of the patch of Example 4.
  • a patch was prepared in the same manner as in Example 1 except that the coating was applied so that the thickness of the agent layer was 30 ⁇ m. This patch was inconspicuous even when applied to the skin (hardness of conspicuity: AAA), the adhesive strength (N / 10 mm) was 0.13 (0.011), and the amount of keratinocyte detachment was small.
  • the patch of the present invention covers and protects skin affected areas caused by various skin diseases such as atopic dermatitis, and can be used for improvement and treatment of various symptoms caused by skin diseases.
  • the patch of the present invention can be applied to uses such as pharmaceuticals or quasi drugs by including a pharmacologically active substance in the adhesive layer.
  • the patch of the present invention is suitable as a medical patch, but is not limited thereto, and can be used for other purposes such as application to the skin surface requiring protection.

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Abstract

Disclosed is an adhesive patch which has a layer configuration wherein an adhesive layer is provided on one surface of a supporting body. The supporting body is formed of a polyurethane film that has a thickness within the range of 1-10 μm. The adhesive layer is formed of an addition-curable silicone adhesive layer that has a thickness within the range of 5-50 μm and is composed of a polyorganosiloxane that does not have a vinyl group in a side chain. The water vapor permeability of the adhesive patch is more than 1,500 g/m2·24 hr.

Description

貼付剤とその使用Patches and their use
　本発明は、アトピー性皮膚炎などの様々な皮膚疾患に起因する皮膚患部を覆って保護するほか、皮膚疾患による諸症状の改善や治療のために用いることができる貼付剤に関する。本発明の貼付剤は、皮膚炎などが生じている皮膚患部を覆うことにより、炎症や乾燥による痒みを緩和することができるうえ、炎症部位の掻破による痒みの拡散と炎症の拡大を抑制することができる。本発明の貼付剤は、粘着剤層に薬理活性物質を含有させることにより、医薬または医薬品部外品などの用途に適用することができる。本発明の貼付剤は、医療用貼付剤として好適であるが、それに限定されず、他の用途にも適用することができる。 The present invention relates to a patch that can be used to cover and protect the affected skin area caused by various skin diseases such as atopic dermatitis, and to improve and treat various symptoms caused by the skin disease. The patch of the present invention can reduce itch caused by inflammation and drying by covering the affected skin area where dermatitis or the like occurs, and also suppress the spread of itch caused by scratching the inflammatory site and the spread of inflammation. Can do. The patch of the present invention can be applied to uses such as pharmaceuticals or quasi drugs by containing a pharmacologically active substance in the adhesive layer. The patch of the present invention is suitable as a medical patch, but is not limited thereto and can be applied to other uses.
　皮膚への貼付剤として、皮膚疾患の治療のための医療用貼付剤、輸液チューブやガーゼなどの固定に用いられる医療用貼付剤などが知られている。これらの貼付剤は、支持体（基材層）上に粘着剤層を設け、該粘着剤層上に剥離ライナーを貼り合わせた層構成を有している。貼付剤の形態としては、ロール状に巻回した形状のものが一般的であるが、シート状のものもある。貼付剤には、皮膚表面への密着性、耐剥離性、透湿性など各種機能を有することが求められているため、例えば、支持体として不織布のような厚手のものを使用している貼付剤が多い。厚手の貼付剤は、貼付部分が目立つという欠陥がある。貼付部分が目立つのを緩和するために、支持体を肌色に近い色調に着色した貼付剤が知られているが、実際の肌との色調の差異を十分に解消することは困難である。 As skin patches, medical patches for the treatment of skin diseases, medical patches used for fixing infusion tubes, gauze and the like are known. These patches have a layer structure in which a pressure-sensitive adhesive layer is provided on a support (base material layer), and a release liner is bonded to the pressure-sensitive adhesive layer. As a form of the patch, a form wound in a roll shape is common, but there is also a sheet form. Since the patch is required to have various functions such as adhesion to the skin surface, peel resistance, and moisture permeability, for example, a patch using a thick material such as a nonwoven fabric as a support. There are many. A thick patch has a defect that a sticking part is conspicuous. In order to relieve the sticking part from being noticeable, a patch is known in which the support is colored in a color close to the skin color, but it is difficult to sufficiently eliminate the difference in color tone from the actual skin.
　医療用ドレッシングとして用いられる貼付剤として、透明な製品も販売されているが、輸液チューブや薬液注入針、ガーゼなどの固定を目的としているため、支持体や粘着剤層の厚みが比較的大きく、貼付部分が目立ちやすい。しかも、該貼付剤は、粘着剤層の粘着力が強いため、該貼付剤を皮膚表面から剥離するときに角質細胞を剥離しやすい。その結果、該貼付剤は、炎症やかぶれなどを発生させたり、皮膚刺激により炎症を亢進させたりすることがある。 Transparent products are also sold as patches used as medical dressings, but for the purpose of fixing infusion tubes, liquid injection needles, gauze, etc., the thickness of the support and adhesive layer is relatively large. The affixed part is easily noticeable. Moreover, since the adhesive has a strong adhesive force in the adhesive layer, the keratinocytes are easily detached when the adhesive is peeled from the skin surface. As a result, the patch may cause inflammation, rash, etc., or may increase inflammation due to skin irritation.
　特に、アトピー性皮膚炎の患者の場合、角質層での細胞間結合力が低下しているため、角質細胞が剥離しやすい状態にある。剥離時における角質細胞剥離量の多い貼付剤は、症状悪化の原因となる。角質細胞剥離量を低減する目的で、粘着剤層中に油状成分を多量に含有させる試みがされている。しかし、油状成分の支持体への移行により、支持体の物性が損なわれるおそれがある。粘着剤層への各種添加剤の含有は、添加剤の種類によっては、皮膚刺激を招く原因となる。 Especially, in the case of patients with atopic dermatitis, since the intercellular binding force in the stratum corneum is reduced, the stratum corneum is easily detached. A patch with a large amount of exfoliated keratinocytes at the time of detachment causes symptom deterioration. In order to reduce the amount of exfoliated corneocytes, attempts have been made to contain a large amount of oily components in the adhesive layer. However, there is a possibility that the physical properties of the support may be impaired due to the transfer of the oily component to the support. Inclusion of various additives in the pressure-sensitive adhesive layer may cause skin irritation depending on the type of the additive.
　これまで、皮膚への密着性を高めるために、柔軟な支持体を用いた各種貼付剤が提案されている。例えば、特公平７－１１６０２３号公報（特許文献１）には、ポリウレタンフィルム支持体の片面に薬物含有粘着剤層が設けられた貼付剤であって、該支持体が１００％モジュラス６０～１１０ｋｇ／ｃｍ２で厚み４～１５０μｍの非自己接着性ポリウレタンフィルムであり，該貼付剤の透湿度が３００～５００ｇ／ｍ２・２４ｈｒである貼付剤が提案されている。しかし、この貼付剤は、その透湿度が３００～５００ｇ／ｍ２・２４ｈｒと低く抑えられているため、透湿性が不十分である。 So far, various patches using a flexible support have been proposed in order to improve the adhesion to the skin. For example, Japanese Patent Publication No. 7-116023 (Patent Document 1) discloses a patch in which a drug-containing adhesive layer is provided on one side of a polyurethane film support, and the support has a 100% modulus of 60 to 110 kg / A patch that is a non-self-adhesive polyurethane film having a thickness of 4 to 150 μm at cm 2 and having a moisture permeability of 300 to 500 g / m 2 · 24 hr has been proposed. However, this patch has insufficient moisture permeability because its moisture permeability is kept as low as 300 to 500 g / m 2 · 24 hr.
　特開平７－１３２１３９号公報（特許文献２）には、厚さ５～５０μｍの熱可塑性ポリエステルポリウレタンフィルムを支持体とし、該支持体の片面に、厚み１～２０μｍのピロリドンを共重合したアクリル系粘着剤層を設けた層構成を有するガイドフィルム付貼付剤が提案されている。特許文献２には、該貼付剤が十分な透湿性と適度な粘着力により、剥離の際に痛みを与えず、皮膚の発赤を生じることがないと記載されているが、貼付剤を剥離するときの角質細胞剥離の緩和については考慮されていない。 Japanese Patent Application Laid-Open No. 7-132139 (Patent Document 2) describes an acrylic system in which a thermoplastic polyester polyurethane film having a thickness of 5 to 50 μm is used as a support and pyrrolidone having a thickness of 1 to 20 μm is copolymerized on one side of the support. A patch with guide film having a layer structure provided with an adhesive layer has been proposed. Patent Document 2 describes that the patch does not cause pain and does not cause redness of the skin due to sufficient moisture permeability and appropriate adhesive strength. The relaxation of keratinocyte detachment is not considered.
　国際公開第２００９／４１１２２号（特許文献３；米国特許出願公開第２０１０／０２１７１７１号及び欧州特許出願公開第２１９３７６９号対応）には、皺や肌の細かな凹凸にも適合し、貼付箇所が目立たない貼付剤として、厚さ１～１０μｍのエラストマーフィルムからなる基材層の片面に、厚み１～１５μｍの粘着剤層が設けられた貼付剤が開示されている。特許文献３には、該粘着剤層としてアクリル系粘着剤を用いた実験例が示されている。しかし、アクリル系粘着剤層を有する貼付剤は、剥離時の角質細胞の剥離量については考慮されていない。 International Publication No. 2009/41122 (patent document 3; corresponding to US Patent Application Publication No. 2010/0217171 and European Patent Application Publication No. 2193769) conforms to wrinkles and fine unevenness of skin, and the sticking part is conspicuous As a non-adhesive patch, an adhesive patch in which an adhesive layer having a thickness of 1 to 15 μm is provided on one side of a base material layer made of an elastomer film having a thickness of 1 to 10 μm is disclosed. Patent Document 3 shows an experimental example using an acrylic pressure-sensitive adhesive as the pressure-sensitive adhesive layer. However, a patch having an acrylic pressure-sensitive adhesive layer does not take into consideration the amount of keratinocyte peeling at the time of peeling.
　特開平１０－３３６５５号公報（特許文献４）には、厚み１０～８０μｍで透湿性を有する基材フィルムの片面に、直接的または間接的に皮膚貼着用粘着剤層を形成してなる貼付剤であって、貼付剤としての透湿度が３００～１５００ｇ／ｍ２・２４ｈｒの範囲に調整された皮膚炎処置用貼付剤が開示されている。該皮膚炎処置用貼付剤は、アトピー性皮膚炎の患部保護用に用いられるものである。該皮膚炎処置用貼付剤は、透湿度が上記範囲になるように、基材フィルムと粘着剤を選択することにより、アトピー性皮膚炎の皮膚からの水分の蒸散を適度に抑えている。特許文献４には、品質の安定性や粘着特性、透湿度の調整のしやすさの点から、皮膚貼着用粘着剤層をアクリル系粘着剤により形成することが好ましいと記載されている。しかし、一般にアクリル系粘着剤層を有する貼付剤は、該貼付剤を剥離するときに粘着剤層に付着する角質細胞剥離量が多いという欠陥を有している。さらに、夏場など皮膚から蒸散する水分量が多くなる季節においては、貼付剤としての透湿度が上記範囲では、皮膚表面と粘着剤層との間に汗が溜まりやすくなり、それによって、かぶれが生じたり、剥がれやすくなったりする。 Japanese Patent Application Laid-Open No. 10-33655 (Patent Document 4) discloses a patch comprising a base film having a thickness of 10 to 80 μm and a moisture-permeable base material, which is directly or indirectly formed with an adhesive layer for adhering to the skin. However, a patch for treating dermatitis in which the moisture permeability as a patch is adjusted in the range of 300 to 1500 g / m 2 · 24 hr is disclosed. The patch for dermatitis treatment is used for protecting the affected area of atopic dermatitis. The patch for treating dermatitis moderately suppresses the transpiration of water from the skin of atopic dermatitis by selecting the base film and the pressure-sensitive adhesive so that the moisture permeability is in the above range. Patent Document 4 describes that it is preferable to form the adhesive layer for skin application with an acrylic adhesive from the viewpoint of stability of quality, adhesive properties, and ease of adjustment of moisture permeability. However, in general, a patch having an acrylic pressure-sensitive adhesive layer has a defect that the amount of keratinocyte peeling attached to the pressure-sensitive adhesive layer is large when the patch is peeled off. In addition, in the summer season when the amount of moisture transpiration from the skin increases, when the moisture permeability as a patch is in the above range, sweat tends to accumulate between the skin surface and the adhesive layer, thereby causing rash. Or it becomes easy to peel off.
　特開昭６２－１７６８３９号公報（特許文献５）には、極薄ポリウレタンフィルム表面に、オルガノポリシロキサン樹脂及び少なくとも一種のアルキルアリールポリシロキサン生ゴムを含有する混合物の相互縮合生成物からなる粘着剤層を形成した極薄感圧粘着テープが開示されている。特許文献５に記載の粘着テープは、粘着剤層が基材に十分接着しないため、皮膚表面からの剥離時に、皮膚表面に粘着剤が残留しやすい。 Japanese Patent Application Laid-Open No. 62-176839 (Patent Document 5) discloses a pressure-sensitive adhesive layer comprising a mutual condensation product of a mixture containing an organopolysiloxane resin and at least one alkylaryl polysiloxane raw rubber on the surface of an ultrathin polyurethane film. An ultra-thin pressure-sensitive adhesive tape is disclosed. In the pressure-sensitive adhesive tape described in Patent Document 5, since the pressure-sensitive adhesive layer does not sufficiently adhere to the base material, the pressure-sensitive adhesive tends to remain on the skin surface when peeling from the skin surface.
　特開２００７－１３５６７３号公報（特許文献６）には、ポリエステルエラストマーを主成分とする基材とその少なくとも一方の面に形成された付加反応型シリコーンを含有してなる粘着剤層とからなる体表面用貼付剤が開示されている。特許文献６には、ポリエステルエラストマーを主成分とする基材の厚みが好ましくは１５～１５０μｍで、粘着剤層の厚みが好ましくは１０～２０００μｍであると記載されている。特許文献６の比較例１及び２には、基材として、ポリエステルエラストマーフィルムに代えてポリウレタンフィルムを使用した貼付剤は、粘着剤層が基材から剥がれやすくなることが示されており、貼付剤の透湿度も６４１～６７８ｇ／ｍ２・２４ｈｒと小さいことが記載されている。 Japanese Unexamined Patent Publication No. 2007-135673 (Patent Document 6) discloses a body comprising a base material mainly composed of a polyester elastomer and an adhesive layer containing an addition reaction type silicone formed on at least one surface thereof. A surface patch is disclosed. Patent Document 6 describes that the thickness of the base material composed mainly of a polyester elastomer is preferably 15 to 150 μm, and the thickness of the pressure-sensitive adhesive layer is preferably 10 to 2000 μm. Comparative Examples 1 and 2 of Patent Document 6 show that a patch using a polyurethane film as a base material instead of a polyester elastomer film tends to peel off the adhesive layer from the base material. It is described that the water vapor transmission rate is as small as 641 to 678 g / m 2 · 24 hr.
　貼付剤は、炎症や損傷などのダメージを負った皮膚を覆うことで、病原菌などの様々な外的因子の侵入を防ぐだけでなく、皮膚表面の角質層が持つ水分保持機能を補助する役割を果たす。このため、貼付剤は、アトピー性皮膚炎など本来の皮膚機能が損なわれた状態の皮膚に対して、角質層の代役を果たしたり、強い痒みを直接掻破することによる患部の悪化を防ぎ、皮膚患部が自然に回復するのを促進する役割を果たすことが期待されている。 The patch not only prevents the invasion of various external factors such as pathogenic bacteria by covering the damaged skin such as inflammation and damage, but also supports the moisture retention function of the stratum corneum on the skin surface. Fulfill. For this reason, the patch acts as a substitute for the stratum corneum for skin with impaired original skin function, such as atopic dermatitis, and prevents the affected area from deteriorating by directly scratching strong itching. It is expected to play a role in promoting the natural recovery of the affected area.
　貼付剤は、適度の水分保持機能を有することが望ましいが、その反面、皮膚表面と粘着剤層との間に汗が溜まりやすいという欠陥を有している。このため、貼付剤には、透湿性に優れることにより、皮膚表面と粘着剤層との間に汗が溜まるのを防ぎつつ、適度の水分保持機能を発揮し得ることが望ましい。貼付剤は、皮膚炎などの皮膚患部に貼付する場合、貼付面積が大きくなったり、貼付箇所が多くなったりして、貼付部位が衣類から露出することが多いため、貼付部位が目立たないことが望ましい。貼付剤は、粘着剤層に薬理活性物質を含有させた場合、少ない含有量でも効率的に薬理活性物質を放出できることが望ましい。 Although it is desirable that the patch has an appropriate moisture retention function, it has a defect that sweat tends to accumulate between the skin surface and the adhesive layer. For this reason, it is desirable for the patch to be able to exhibit an appropriate moisture retention function while preventing sweat from accumulating between the skin surface and the pressure-sensitive adhesive layer by being excellent in moisture permeability. When a patch is applied to an affected skin area such as dermatitis, the applied area may be unnoticeable because the applied area becomes larger or the applied area increases and the applied area is often exposed from clothing. desirable. When the patch contains a pharmacologically active substance in the adhesive layer, it is desirable that the pharmacologically active substance can be efficiently released even with a small content.
　しかし、透湿性に優れ、角質細胞を剥離しにくく、貼付部位が目立たず、薬理活性物質の放出性に優れるなどの諸特性が高度にバランスした貼付剤は、いまだ提案されておらず、解決すべき課題が残されている。 However, a patch with a high balance of various properties such as excellent moisture permeability, difficulty in exfoliating keratinocytes, inconspicuous application site, and excellent release of pharmacologically active substances has not yet been proposed and solved. Issues to be addressed remain.
特公平７－１１６０２３号公報Japanese Patent Publication No.7-116023 特開平７－１３２１３９号公報JP-A-7-132139 国際公開第２００９／４１１２２号International Publication No. 2009/41122 特開平１０－３３６５５号公報JP 10-33655 A 特開昭６２－１７６８３９号公報Japanese Patent Laid-Open No. 62-176839 特開２００７－１３５６７３号公報JP 2007-135673 A
　本発明の課題は、透湿性に優れ、貼付部分が目立たず、角質細胞剥離量が抑制された貼付剤を提供することにある。本発明の他の課題は、上記諸特性に優れる上、粘着剤層に薬理活性物質を含有させたとき、その含有量が少量であっても、薬理活性物質の放出効率が高く、皮膚炎症部位の治療などに効果的な貼付剤を提供することにある。 An object of the present invention is to provide a patch that is excellent in moisture permeability, in which the applied part is not conspicuous and the amount of keratinocyte peeling is suppressed. Another subject of the present invention is excellent in the above-mentioned various characteristics, and when a pharmacologically active substance is contained in the pressure-sensitive adhesive layer, the release efficiency of the pharmacologically active substance is high even when the content is small, and the skin inflammation site It is to provide an effective patch for the treatment of cerebral palsy.
　本発明者は、上記課題を達成するために鋭意研究を行った。その結果、支持体の片面に粘着剤層が設けられた層構成を有する貼付剤であって、支持体として、特定範囲の厚みを有するポリウレタンフィルムを用い、粘着剤層として、特定範囲の厚みを有し、凝集性が低く、側鎖にビニル基を持たない付加反応型シリコーン系粘着剤層を配置し、かつ、貼付剤の透湿性が高くなるように調整することにより、柔軟性に富み、よく肌に密着して目立たず、皮膚刺激が少なく、汗の滞留による剥離が生じにくく、その上、皮膚表面からの剥離時に角質細胞剥離量の少ない貼付剤が得られることを見出した。 The present inventor has conducted intensive research in order to achieve the above problems. As a result, it is a patch having a layer structure in which a pressure-sensitive adhesive layer is provided on one side of a support, and a polyurethane film having a specific range of thickness is used as the support, and a specific range of thickness is used as the pressure-sensitive adhesive layer. Having an addition reaction type silicone pressure-sensitive adhesive layer having a low cohesiveness and no vinyl group in the side chain, and being adjusted so that the moisture permeability of the patch is high, it is rich in flexibility, It has been found that a patch can be obtained that does not stand out in close contact with the skin well, has little skin irritation, does not easily peel off due to the retention of sweat, and has a small amount of keratinocyte peeling when peeled from the skin surface.
　さらに、上記特定のポリウレタンフィルムと特定のシリコーン系粘着剤層との選択された組み合わせによって、粘着剤層に薬理活性物質を含有させた場合に、その放出効率が高く、少量の薬理活性物質の含有量であっても優れた薬効を示すことができる貼付剤を得ることができる。本発明は、これらの知見に基づいて完成するに至ったものである。 Furthermore, when the pharmacologically active substance is contained in the pressure-sensitive adhesive layer by a selected combination of the specific polyurethane film and the specific silicone-based pressure-sensitive adhesive layer, the release efficiency is high and a small amount of pharmacologically active substance is contained. It is possible to obtain a patch that can exhibit excellent medicinal effects even in an amount. The present invention has been completed based on these findings.
　かくして、本発明によれば、支持体の片面に粘着剤層が設けられた層構成を有する貼付剤において、該支持体が、１～１０μｍの範囲内の厚みを持つポリウレタンフィルムであり、該粘着剤層が、５～５０μｍの範囲内の厚みを持つ、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤層であって、かつ、該貼付剤の透湿度が１５００ｇ／ｍ２・２４ｈｒ超過であることを特徴とする貼付剤が提供される。 Thus, according to the present invention, in a patch having a layer structure in which an adhesive layer is provided on one side of a support, the support is a polyurethane film having a thickness in the range of 1 to 10 μm, and the adhesive The adhesive layer is an addition reaction type silicone pressure-sensitive adhesive layer made of polyorganosiloxane having a thickness in the range of 5 to 50 μm and having no vinyl group in the side chain, and the moisture permeability of the patch is 1500 g. A patch is provided that is more than / m 2 · 24 hr.
　本発明によれば、以下の実施態様が提供される。
（１）該粘着剤層が、薬理活性物質を粘着剤全量基準で０．０１～７重量％の割合で含有する前記の貼付剤。
（２）該薬理活性物質が、皮膚角質層に存在する脂質またはその誘導体から選ばれる少なくとも一種の薬理活性物質を含有する前記の貼付剤。
（３）該薬理活性物質が、脂溶性ビタミン及び水溶性ビタミン並びにそれらの誘導体からなる群より選ばれる少なくとも一種の薬理活性物質を含有する前記の貼付剤。
（４）該支持体の粘着剤層に接する面に、シラン系プライマーの塗布層が配置されている前記の貼付剤。
（５）該支持体の粘着剤層と反対側の表面に、キャリアフィルムが配置されている前記の貼付剤。
（６）該キャリアフィルムが、離型処理されたポリエステルフィルムである前記の貼付剤。
（７）該粘着剤層の支持体と反対側の表面に、剥離ライナーが配置されている前記の貼付剤。
（８）該剥離ライナーが、離型処理されたポリエステルフィルムである前記の貼付剤。
（９）ヒト前腕内側の皮膚表面に６時間貼付後、剥離したときに、貼付面積に対する角質細胞剥離面積が２０％以下である貼付剤。
（１０）皮膚掻破防止用貼付剤である前記の貼付剤。 According to the present invention, the following embodiments are provided.
(1) The adhesive patch, wherein the adhesive layer contains a pharmacologically active substance in a proportion of 0.01 to 7% by weight based on the total amount of the adhesive.
(2) The above-mentioned patch, wherein the pharmacologically active substance contains at least one pharmacologically active substance selected from lipids or derivatives thereof present in the skin stratum corneum.
(3) The above-mentioned patch, wherein the pharmacologically active substance contains at least one pharmacologically active substance selected from the group consisting of fat-soluble vitamins, water-soluble vitamins and derivatives thereof.
(4) The above patch, wherein a coating layer of a silane primer is disposed on the surface of the support in contact with the pressure-sensitive adhesive layer.
(5) The patch, wherein a carrier film is disposed on the surface of the support opposite to the pressure-sensitive adhesive layer.
(6) The patch, wherein the carrier film is a release-treated polyester film.
(7) The patch, wherein a release liner is disposed on the surface of the pressure-sensitive adhesive layer opposite to the support.
(8) The patch, wherein the release liner is a release-treated polyester film.
(9) An adhesive patch having a keratinocyte release area of 20% or less with respect to the applied area when applied to the skin surface inside the human forearm for 6 hours and then released.
(10) The above patch, which is a patch for preventing skin scratching.
　さらに、本発明によれば、患部を含む皮膚表面に貼付して、皮膚患部の直接掻破を防止する前記貼付剤の使用が提供される。 Furthermore, according to the present invention, there is provided use of the above-mentioned patch which is applied to the skin surface including the affected part to prevent direct scratching of the affected part of the skin.
　本発明の貼付剤は、透湿性に優れるため、貼付部位に汗の滞留によるかぶれや剥離を生じにくい。本発明の貼付剤は、支持体が極薄のポリウレタンフィルムであり、全層厚みが比較的薄く、かつ、透明性に優れるため、皮膚表面の細かな皺や凹凸に密着し、貼付部位が目立たない。本発明で使用する側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤は、架橋反応が分子の末端のみで行われるため、過度に硬化せず、ゲル状となる。該シリコーン系粘着剤は、シリコーンレジン、可塑剤（例えば、油状成分）、充填材などの添加剤を含有させる必要がない。このため、該シリコーン系粘着剤層を設けた本発明の貼付剤は、添加剤成分による支持体物性への悪影響や皮膚刺激がなく、剥離時皮膚表面の角質細胞を剥離しにくい。 Since the patch of the present invention is excellent in moisture permeability, it is difficult to cause rash and peeling due to the retention of sweat at the applied site. The patch of the present invention is a polyurethane film with a very thin support, the entire layer thickness is relatively thin and excellent in transparency, so that it adheres to fine wrinkles and irregularities on the skin surface, and the application site is conspicuous Absent. The addition reaction type silicone pressure-sensitive adhesive made of polyorganosiloxane having no vinyl group in the side chain used in the present invention is not excessively cured and becomes a gel because the crosslinking reaction is carried out only at the end of the molecule. The silicone-based pressure-sensitive adhesive does not need to contain additives such as a silicone resin, a plasticizer (for example, an oily component), and a filler. For this reason, the patch of the present invention provided with the silicone-based pressure-sensitive adhesive layer has no adverse effect on the physical properties of the support and skin irritation caused by the additive component, and it is difficult to exfoliate keratinocytes on the skin surface at the time of exfoliation.
　本発明の貼付剤は、該シリコーン系粘着剤層に、皮膚の諸症状の改善に適した薬理活性物質を含有させることができる。薬理活性物質は、少ない含有量で高い放出性を示す。本発明の貼付剤は、アトピー性皮膚炎などの様々な皮膚疾患に起因する皮膚患部を覆って保護するほか、皮膚疾患による諸症状の改善や治療のために用いるのに適している。 The patch of the present invention can contain a pharmacologically active substance suitable for improving various skin symptoms in the silicone pressure-sensitive adhesive layer. The pharmacologically active substance exhibits a high release property with a small content. The patch of the present invention covers and protects skin affected areas caused by various skin diseases such as atopic dermatitis, and is suitable for use in improving and treating various symptoms caused by skin diseases.
貼付剤を貼付した前腕内側部の写真である。It is the photograph of the forearm inner side which stuck the patch. 前腕内側部に貼付した貼付剤の貼付部位の皮膚の拡大写真（１００倍）である。It is an enlarged photograph (100 times) of the skin of the application site | part of the patch stuck on the inner part of the forearm. 角質細胞剥離量の比較試験結果を示すグラフである。It is a graph which shows the comparative test result of keratinocyte peeling amount. 薬理活性物質の放出効果についての対比実験結果を示すグラフである。It is a graph which shows the comparison experiment result about the release effect of a pharmacologically active substance.
　本発明の貼付剤は、支持体の片面に粘着剤層が設けられた層構成を有する貼付剤である。その全体の形状は、通常、ロール状に巻回したものであるが、シート状であってもよい。該支持体は、１～１０μｍの範囲内の厚さを持つポリウレタンフィルムである。該粘着剤層は、５～５０μｍの範囲内の厚みを有する、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤層である。該貼付剤の透湿度は１５００ｇ／ｍ２・２４ｈｒ超過である。 The patch of the present invention is a patch having a layer structure in which an adhesive layer is provided on one side of a support. The entire shape is usually wound in a roll shape, but may be a sheet shape. The support is a polyurethane film having a thickness in the range of 1 to 10 μm. The pressure-sensitive adhesive layer is an addition reaction type silicone pressure-sensitive adhesive layer made of polyorganosiloxane having a thickness in the range of 5 to 50 μm and having no vinyl group in the side chain. The moisture permeability of the patch is over 1500 g / m 2 · 24 hr.
　本発明の貼付剤は、支持体及び粘着剤層に加えて、キャリアフィルム及び／または剥離ライナーを有していてもよい。本発明の貼付剤は、キャリアフィルム、支持体、及び粘着剤層をこの順序で備えることが好ましく、キャリアフィルム、支持体、粘着剤層、及び剥離ライナーをこの順序で備えることがより好ましい。 The patch of the present invention may have a carrier film and / or a release liner in addition to the support and the pressure-sensitive adhesive layer. The patch of the present invention preferably includes a carrier film, a support, and an adhesive layer in this order, and more preferably includes a carrier film, a support, an adhesive layer, and a release liner in this order.
１．貼付剤の層構成
　本発明の貼付剤は、支持体の片面に粘着剤層が設けられた層構成を有する。本発明の貼付剤は、これらの層に加えて、キャリアフィルムや剥離ライナーなどの付加的な層を設けることができる。付加的な層は、貼付剤の皮膚表面への貼付時に剥離される。本発明において、透湿度などの貼付剤の特性は、支持体と粘着剤層との２層からなる多層構造体に関する特性を意味する。 1. Layer configuration of patch The patch of the present invention has a layer configuration in which an adhesive layer is provided on one side of a support. In addition to these layers, the patch of the present invention can be provided with additional layers such as a carrier film and a release liner. The additional layer is peeled off when the patch is applied to the skin surface. In the present invention, the characteristic of the patch such as moisture permeability means a characteristic relating to a multilayer structure composed of two layers of a support and an adhesive layer.
　本発明の貼付剤は、粘着剤層の表面を保護するために、剥離ライナーを配置することができる。粘着剤層の保護の観点からだけではなく、厚みが薄く均一な粘着剤層を形成するには、該剥離ライナーの上に粘着剤層を形成する方法を採用することが望ましい。支持体のポリウレタンフィルムは、その厚みが極めて薄いので、キャリアフィルムの上にポリウレタンフィルムを配置した多層フィルムを用いることが好ましい。 In the patch of the present invention, a release liner can be disposed to protect the surface of the pressure-sensitive adhesive layer. In order to form a thin and uniform pressure-sensitive adhesive layer not only from the viewpoint of protecting the pressure-sensitive adhesive layer, it is desirable to employ a method of forming a pressure-sensitive adhesive layer on the release liner. Since the polyurethane film of the support is extremely thin, it is preferable to use a multilayer film in which the polyurethane film is disposed on the carrier film.
　したがって、本発明の貼付剤は、通常、剥離ライナーとキャリアフィルムとを含む「キャリアフィルム／支持体／粘着剤層／剥離ライナー」の多層構成を有することが好ましい。貼付剤の使用に際し、まず、粘着剤層から剥離ライナーを剥離・除去してから皮膚表面に貼付し、次いで、支持体上のキャリアフィルムを剥離・除去する。本発明の貼付剤は、皮膚表面への貼着時には、「支持体／粘着剤層」の層構成を有する。 Therefore, the patch of the present invention usually preferably has a multilayer structure of “carrier film / support / adhesive layer / release liner” including a release liner and a carrier film. When using the patch, first, the release liner is peeled and removed from the pressure-sensitive adhesive layer, and then applied to the skin surface, and then the carrier film on the support is peeled and removed. The patch of the present invention has a layer structure of “support / adhesive layer” at the time of sticking to the skin surface.
２．貼付剤の製造方法
　本発明の貼付剤の支持体であるポリウレタンフィルムは、溶液キャスティング法や押出成形法などの任意の成形方法によって形成することができる。本発明の貼付剤の支持体は、厚みが１～１０μｍの範囲内であり、極めて薄いポリウレタンフィルムであるため、破れの発生を抑制しながら、安定して連続的に製造するには、溶液キャスティング法（溶液コート法）または押出積層法を採用することが好ましく、溶液キャスティング法を採用することがより好ましい。 2. Manufacturing method of patch The polyurethane film as a support of the patch of the present invention can be formed by any molding method such as a solution casting method or an extrusion molding method. Since the support of the patch of the present invention is an extremely thin polyurethane film having a thickness in the range of 1 to 10 μm, solution casting is required for stable and continuous production while suppressing the occurrence of tearing. The method (solution coating method) or the extrusion lamination method is preferably employed, and the solution casting method is more preferably employed.
　溶液キャスティング法では、キャリアフィルム上にポリウレタンの有機溶剤溶液を塗工し、乾燥する方法が好ましく採用される。該キャリアフィルムを一方向に走行させながら、その上にポリウレタン溶液を塗工し、乾燥させると、連続的にポリウレタンフィルムを作成することができる。溶液キャスティング法によれば、ポリウレタンフィルムの厚みを正確に制御することができる上、フィルムの方向による物性の異方性を小さくすることができる。 In the solution casting method, a method of applying an organic solvent solution of polyurethane onto a carrier film and drying is preferably employed. When the carrier film is run in one direction, a polyurethane solution is coated on the carrier film and dried, whereby a polyurethane film can be continuously formed. According to the solution casting method, the thickness of the polyurethane film can be accurately controlled, and the anisotropy of physical properties depending on the direction of the film can be reduced.
　本発明の貼付剤において、粘着剤層を形成する方法としては、（１）支持体であるポリウレタンフィルム上に、粘着剤層を直接形成する方法；及び（２）剥離ライナー上に粘着剤層を形成した後、該粘着剤層の表面と支持体表面が密着するように貼り合わせる方法が、代表的なものである。 In the patch of the present invention, the pressure-sensitive adhesive layer is formed by (1) a method of directly forming a pressure-sensitive adhesive layer on a polyurethane film as a support; and (2) a pressure-sensitive adhesive layer on a release liner. After forming, the method of bonding so that the surface of this adhesive layer and the surface of a support body closely_contact | adhere is a typical thing.
　前記（１）の方法では、支持体の片面に付加反応型シリコーン系粘着剤層を形成する材料を塗布することにより、シリコーン系粘着剤層を形成することができる。その際、ヘキサン、ヘプタン等の有機溶媒は、縮合反応等によって得られた他の溶剤系シリコーン系粘着剤を付加反応型シリコーン系粘着剤層にブレンドする場合や、付加反応型シリコーン系粘着剤の希釈が必要な場合において使用することができるが、通常は作業環境の悪化となるため使用しない。粘着剤層の塗布方法は、通常行われている公知の塗布方式を採用することが可能である。塗布方式としては、例えば、コンマコーター、リバースコーター、コンマリバースコーター、リップコーター、ナイフコーター及びメイヤーバー等のバーコーターなどを採用することができる。 In the method (1), the silicone pressure-sensitive adhesive layer can be formed by applying a material for forming the addition reaction type silicone pressure-sensitive adhesive layer on one side of the support. At that time, an organic solvent such as hexane or heptane may be used in the case of blending another solvent-based silicone pressure-sensitive adhesive obtained by a condensation reaction or the like with an addition-reactive silicone-based pressure-sensitive adhesive layer. Although it can be used when dilution is necessary, it is usually not used because the working environment deteriorates. As a method for applying the pressure-sensitive adhesive layer, it is possible to adopt a publicly-known known application method. As a coating method, for example, a bar coater such as a comma coater, a reverse coater, a comma reverse coater, a lip coater, a knife coater, and a Mayer bar can be employed.
　前記（２）の方法において、剥離ライナー上に粘着剤層を形成する方法としては、剥離ライナーを一方向に走行させながら、その上に粘着剤層を形成する材料を塗布し、乾燥させる方法が好ましい。シリコーン系粘着剤は、溶融または溶液として剥離ライナー上に塗工してもよい。前記（２）の方法を採用することにより、貼付剤の作成が容易となる上、得られた貼付剤の取扱性が向上する。すなわちそれぞれ厚みが薄い支持体と粘着剤層とからなり、キャリアフィルムや剥離ライナーが配置されていない形態の貼付剤は、腰が弱くシワになりやすいため、取扱いが困難である。前記層構成を有する貼付剤は、貼付時に剥離ライナーを剥がして粘着剤層を露出させる。剥離ライナーを剥がしても、キャリアフィルムが存在するため、貼付剤の腰が強く、所望の貼付部位に粘着剤層の表面を当接させることができる。貼付後には、支持体上のキャリアフィルムも剥離する。なお、本発明の貼付剤は非水系であり、最終的に得られる貼付剤の粘着剤層において意図的に水分を含有させることは基本的に行わない。 In the method (2), as a method for forming the pressure-sensitive adhesive layer on the release liner, a method of applying the material for forming the pressure-sensitive adhesive layer on the release liner and drying it while running the release liner in one direction. preferable. The silicone-based pressure-sensitive adhesive may be applied on the release liner as a melt or a solution. By adopting the method (2), the preparation of the patch is facilitated and the handleability of the obtained patch is improved. That is, a patch comprising a support and a pressure-sensitive adhesive layer each having a small thickness and no carrier film or release liner disposed thereon is difficult to handle because it is weak and easily wrinkled. The patch having the layer structure peels off the release liner at the time of sticking to expose the pressure-sensitive adhesive layer. Even if the release liner is peeled off, since the carrier film is present, the patch is strong and the surface of the pressure-sensitive adhesive layer can be brought into contact with the desired application site. After pasting, the carrier film on the support is also peeled off. Note that the patch of the present invention is non-aqueous, and water is not intentionally contained intentionally in the adhesive layer of the finally obtained patch.
３．支持体
　本発明の貼付剤の支持体は、厚みが１～１０μｍの範囲内のポリウレタンフィルムである。ポリウレタンとしては、ポリイソシアネート成分とポリオール成分とを重付加反応させて生成するポリウレタンであれば、特に制限はないが、薬理活性物質の添加を少量とすることができるため、ポリオール成分としてポリエーテルを用いたポリエーテル系ポリウレタンであることが好ましい。 3. Support The support of the patch of the present invention is a polyurethane film having a thickness in the range of 1 to 10 μm. The polyurethane is not particularly limited as long as it is a polyurethane produced by polyaddition reaction of a polyisocyanate component and a polyol component. However, since a pharmacologically active substance can be added in a small amount, a polyether is used as a polyol component. The polyether-based polyurethane used is preferable.
　ポリオール成分であるポリエーテルとしては、ポリエチレングリコール、変性ポリエチレングリコール、ポリプロピレングリコール、ポリトリメチレンエーテルグリコール、ポリテトラメチレンエーテルグリコール、テトラヒドロフラン、３－メチル－テトラヒドロフランの共重合体である変性ポリテトラメチレンエーテルグリコール等が挙げられる。これらポリオール成分は、それぞれ単独で、または２種以上を組み合わせて使用することができる。 Polyethers that are polyol components include polyethylene glycol, modified polyethylene glycol, polypropylene glycol, polytrimethylene ether glycol, polytetramethylene ether glycol, tetrahydrofuran, and modified polytetramethylene ether glycol that is a copolymer of 3-methyl-tetrahydrofuran. Etc. These polyol components can be used alone or in combination of two or more.
　ポリイソシアネート成分としては、ジフェニルメタンジイソシアネート、トリレンジイソシアネート、１，４－ジイソシアネートベンゼン、キシリレンジイソシアネート、２，６－ナフタレンジイソシアネート、メチレンビスシクロヘキシルイソシアネート、イソホロンジイソシアネート、シクロヘキサン－１，４－ジイソシアネート、ヘキサヒドロキシリレンジイソシアネート、ヘキサヒドロトリレンジイソシアネート等のジイソシアネートが挙げられる。これらのジイソシアネート成分は、それぞれ単独で、または２種以上を組み合わせて使用することができる。 Examples of polyisocyanate components include diphenylmethane diisocyanate, tolylene diisocyanate, 1,4-diisocyanate benzene, xylylene diisocyanate, 2,6-naphthalene diisocyanate, methylenebiscyclohexyl isocyanate, isophorone diisocyanate, cyclohexane-1,4-diisocyanate, hexahydroxylylene. And diisocyanates such as diisocyanate and hexahydrotolylene diisocyanate. These diisocyanate components can be used alone or in combination of two or more.
　支持体に用いるポリウレタンフィルムとして、ポリエーテル系ポリウレタンのほか、ポリオール成分としてポリエステルを用いたポリエステル系ポリウレタンを使用することができる。ポリイソシアネート成分としては、上記に挙げたジイソシアネートを使用することができる。ポリオール成分としては、アジピン酸やフタル酸などの二塩基酸と、エチレングリコールやプロピレングリコールなどのジオールとから得られたポリエステルを用いる。支持体としてポリエステル系ポリウレタンフィルムを用いると、シリコーン系粘着剤層中に含有された薬理活性物質の支持体への移行量が相対的に多くなり、十分な薬理効果を得るために、薬理活性物質を比較的多量に添加する必要がある。支持体に移行した薬理活性物質は、支持体の強度や伸縮性などの特性を損なうことがある。このため、ポリウレタンとしては、ポリエーテル系ポリウレタンの方がより好ましい。 As the polyurethane film used for the support, in addition to polyether polyurethane, polyester polyurethane using polyester as a polyol component can be used. As the polyisocyanate component, the diisocyanates listed above can be used. As the polyol component, a polyester obtained from a dibasic acid such as adipic acid or phthalic acid and a diol such as ethylene glycol or propylene glycol is used. When a polyester-based polyurethane film is used as the support, the amount of the pharmacologically active substance contained in the silicone pressure-sensitive adhesive layer transferred to the support is relatively large, so that a sufficient pharmacological effect can be obtained. Needs to be added in relatively large amounts. The pharmacologically active substance transferred to the support may impair properties such as strength and stretchability of the support. For this reason, polyether polyurethane is more preferable as polyurethane.
　支持体の厚みは、皮膚によく馴染んで、目立たない観点から、１～１０μｍ、好ましくは３～７μｍ、特に好ましくは４～６μｍの範囲内である。支持体の厚みが薄くなりすぎると、製膜が困難であることに加えて、支持体としての強度が不十分となり、貼付剤を被着体に貼付したり、貼付剤を被着体から剥がしたりする作業の際に、支持体が切れてしまうことがある。支持体の厚みが大きすぎると、貼付剤全体の厚みを薄くしても、貼付剤が皮溝などの微細な凹凸のある皮膚表面に沿って密着しにくく、貼付状態が目立ちやすくなり、違和感も大きくなる傾向にある。 The thickness of the support is in the range of 1 to 10 μm, preferably 3 to 7 μm, particularly preferably 4 to 6 μm, from the viewpoint of being well adapted to the skin and not noticeable. If the thickness of the support is too thin, it is difficult to form a film, and the strength as a support is insufficient, so that the patch is applied to the adherend or the adhesive is peeled off from the adherend. In some cases, the support may be cut off. If the thickness of the support is too large, even if the thickness of the entire patch is reduced, the patch is less likely to adhere to the skin surface with fine irregularities such as skin grooves, making the applied state conspicuous and uncomfortable. It tends to grow.
　本発明の貼付剤は、アトピー性皮膚炎などの皮膚炎を有するヒトなどの皮膚掻破防止用の用途（以下、単に「アトピー用途」ということがある。）に用いることができる。本発明の貼付剤は、アトピー用途に適用する場合、皮膚掻破行動をとったときにも、皮膚上の貼付剤が皮膚の直接的な掻破を防止するバリアとして機能し、容易にフィルムが破断しないだけの強度を有することが好ましい。具体的には、日本工業規格のＪＩＳ　Ｚ０２３７に従って測定したポリウレタンフィルムの縦方向及び横方向の１０％引張荷重が、各々、通常０．０１～１．２Ｎ／１０ｍｍ、好ましくは０．０５～１．０Ｎ／１０ｍｍの範囲内であることが望ましい。ポリウレタンフィルムの１０％引張荷重値が小さすぎると、強度が弱く製膜性や取扱性が低下する。ポリウレタンフィルムの１０％引張荷重値が大きすぎると、剛性が強くなり、伸縮性や柔軟性が不足するため、該ポリウレタンフィルムを支持体とする貼付剤が、皮溝などの微細な凹凸のある皮膚表面に沿って密着しにくくなり、貼付状態が目立ちやすくなる。 The patch of the present invention can be used for the purpose of preventing skin scratching in humans and the like having dermatitis such as atopic dermatitis (hereinafter sometimes simply referred to as “atopy use”). When the patch of the present invention is applied to atopy, the patch on the skin functions as a barrier to prevent direct scratching of the skin even when the skin is scratched, and the film does not easily break. It is preferable to have only strength. Specifically, the 10% tensile load in the longitudinal direction and the transverse direction of the polyurethane film measured according to JIS Z0237 of Japanese Industrial Standard is usually 0.01 to 1.2 N / 10 mm, preferably 0.05 to 1. It is desirable to be within the range of 0N / 10mm. If the 10% tensile load value of the polyurethane film is too small, the strength is so weak that the film-forming property and the handleability are lowered. When the 10% tensile load value of the polyurethane film is too large, the rigidity becomes strong and the stretchability and flexibility are insufficient. Therefore, the patch using the polyurethane film as a support is used for skin with fine irregularities such as skin grooves. It becomes difficult to adhere along the surface, and the attached state is easily noticeable.
　支持体に用いるポリウレタンフィルムには、所望により、顔料や染料などの着色剤を含有させることができる。ポリウレタンフィルムには、所望により、さらに安定剤、紫外線吸収剤、滑剤などの各種添加剤を含有させることもできる。 The polyurethane film used for the support may contain a colorant such as a pigment or a dye, if desired. If necessary, the polyurethane film may further contain various additives such as a stabilizer, an ultraviolet absorber, and a lubricant.
　支持体に用いるポリウレタンフィルムの表面には、支持体と付加反応型シリコーン系粘着剤層との密着性を向上させるために、支持体の粘着剤層に接する側の表面に、表面処理やプライマー処理を行うことができる。支持体の表面処理としては、例えば、エンボス処理、コロナ処理、アルカリ処理等が挙げられる。プライマー処理としては、シラン系プライマー（例えば、ダウコーニング社製　ＦＳ　ＸＡ－２８６９）を用いることができる。プライマー処理剤は、直接支持体の表面に塗工することができる。プライマー処理剤を、ヘキサン等の有機溶媒で希釈して塗工することによってプライマー層を配置すると、好適な厚みのプライマー層が得られやすい。プライマー層の厚みは、好ましくは０．０５～３μｍ、より好ましくは０．０５～１μｍの範囲内である。 In order to improve the adhesion between the support and the addition-reactive silicone pressure-sensitive adhesive layer, the surface of the polyurethane film used for the support is subjected to surface treatment or primer treatment on the surface in contact with the pressure-sensitive adhesive layer of the support. It can be performed. Examples of the surface treatment of the support include embossing, corona treatment, and alkali treatment. As the primer treatment, a silane primer (for example, FS XA-2869 manufactured by Dow Corning) can be used. The primer treatment agent can be applied directly to the surface of the support. When the primer layer is arranged by diluting the primer treatment agent with an organic solvent such as hexane and coating it, a primer layer having a suitable thickness is easily obtained. The thickness of the primer layer is preferably 0.05 to 3 μm, more preferably 0.05 to 1 μm.
　本発明の貼付剤は、ヒトの皮膚表面に貼付したとき、貼付剤の手触り、滑り性、外観などを改善するために、支持体の粘着剤層側とは反対側の面（「支持体の背面」という。）に微小な凹凸を形成してもよい。微小な凹凸は、特に、目立ちにくい貼付剤とする場合、支持体の背面（支持体表面）の光の反射を抑え、貼付部位を目立たなくするためにも有用である。キャリアフィルムの表面にエンボス加工によって微小な凹凸を形成しておき、該微小な凹凸面上にポリウレタンフィルムを形成すれば、ポリウレタンフィルムからなる支持体の背面に該微小な凹凸を転写することができる。 When the patch of the present invention is applied to the surface of human skin, the surface of the support opposite to the pressure-sensitive adhesive layer side ("support of the support" A minute unevenness may be formed on the back surface. The minute irregularities are particularly useful for suppressing the reflection of light on the back surface (support surface) of the support and making the application site inconspicuous, when the patch is difficult to notice. If minute irregularities are formed on the surface of the carrier film by embossing and a polyurethane film is formed on the minute irregularities, the minute irregularities can be transferred to the back surface of the support made of polyurethane film. .
４．付加反応型シリコーン系粘着剤層
　本発明の貼付剤の粘着剤層は、５～５０μｍの範囲内の厚みを有する、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤層である。 4). Addition reaction type silicone pressure sensitive adhesive layer The pressure sensitive adhesive layer of the patch of the present invention has an addition reaction type silicone pressure sensitive adhesive having a thickness in the range of 5 to 50 μm and comprising a polyorganosiloxane having no vinyl group in the side chain. Is a layer.
　貼付剤の粘着剤として汎用されてきたアクリル系粘着剤は、分子内にエステルなどの極性基を有するため、薬理活性物質の溶解性が高く、薬理活性物質の添加量が少ない場合には、その放出量が少なくなるという問題がある。ゴム系粘着剤は、構成成分が炭化水素からなるため、薬理活性物質の溶解度は低いものの、透湿性に乏しいため貼付部位に汗が溜まりやすく、皮膚の動きなどの外力によって剥がれやすくなることがあるという欠点がある。 Acrylic adhesives that have been widely used as adhesives for patches have polar groups such as esters in the molecule, so the solubility of pharmacologically active substances is high, and when the amount of pharmacologically active substances added is small, There is a problem that the amount of release is reduced. Rubber adhesives are composed of hydrocarbons, so the solubility of pharmacologically active substances is low, but they are poorly permeable to moisture, so sweat tends to accumulate on the application site and may be easily peeled off by external forces such as skin movements. There is a drawback.
　汎用のシリコーン系粘着剤として、過酸化物反応型、縮合反応型、及び付加反応型のシリコーン系粘着剤が知られている。過酸化物反応型シリコーン系粘着剤は、例えば、代表的な過酸化物であるベンゾイルパーオキサイド（ＢＰＯ）を用いた場合、分解物として安息香酸が粘着剤中に残存する上、加圧・密閉系の大きな反応装置を必要とする。縮合反応型シリコーン系粘着剤は、常温で反応が進行するが、アルコール類やカルボン酸類が副生成物として発生するので、皮膚刺激性の観点から、医療用粘着剤としては好ましくない。一般に医療用粘着剤として用いられているシリコーン系粘着剤は、有機金属化合物の１種または２種以上を用いて、ジメチルシロキサンにおける側鎖のビニル基を架橋させて３次元構造を形成したものであって、さらに３次元構造を有するシリコーン樹脂を添加して粘着剤としての特性や透湿度等を調整している。しかし、この汎用の３次元構造を形成したシリコーン系粘着剤は、分子内に架橋反応に関与する官能基が多数存在するため、粘着剤層が硬くなる。その結果角質細胞剥離量が多く、特にアトピー用途で用いる場合には不適であることが判明した。 Peroxide reaction type, condensation reaction type, and addition reaction type silicone pressure sensitive adhesives are known as general-purpose silicone pressure sensitive adhesives. For example, when a peroxide-reactive silicone-based pressure-sensitive adhesive is benzoyl peroxide (BPO), which is a typical peroxide, benzoic acid remains in the pressure-sensitive adhesive as a decomposition product, and is pressurized and sealed. A large reactor is required. Although the condensation reaction type silicone pressure-sensitive adhesive proceeds at room temperature, alcohols and carboxylic acids are generated as by-products, which is not preferable as a medical pressure-sensitive adhesive from the viewpoint of skin irritation. Silicone pressure-sensitive adhesives generally used as medical pressure-sensitive adhesives are those in which one or more organometallic compounds are used to form a three-dimensional structure by cross-linking vinyl groups in the side chain in dimethylsiloxane. In addition, a silicone resin having a three-dimensional structure is added to adjust the characteristics as an adhesive, moisture permeability, and the like. However, the silicone-based pressure-sensitive adhesive having a general-purpose three-dimensional structure has a large number of functional groups involved in the crosslinking reaction in the molecule, so that the pressure-sensitive adhesive layer becomes hard. As a result, it was found that the amount of exfoliated keratinocytes is large and is not suitable particularly when used for atopic use.
　本発明の貼付剤において用いる付加反応型シリコーン系粘着剤は、側鎖にビニル基を持たないポリオルガノシロキサンを主成分として、触媒を使用する付加反応により、分子が直鎖状の構造となるため、それ自体がゲル状の物性を示すものである。このため、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤は、凝集力が一般の粘着剤に比べ低いことが特徴であり、結果として皮膚の皮溝によくなじむことから、貼付部位がより目立ちにくい貼付剤の粘着剤としては有用である。また、この付加反応型シリコーン系粘着剤を用いた貼付剤は、皮膚に貼付後、剥離するときの角質細胞剥離量が少なく、また、添加した薬理活性物質を効率的に放出することができるものであるため、上記ポリウレタンフィルム支持体と組み合わせたときに、優れた機能を発揮することができる。 The addition reaction type silicone pressure-sensitive adhesive used in the patch of the present invention is composed of a polyorganosiloxane having no vinyl group in the side chain as a main component, and the molecule has a linear structure due to the addition reaction using a catalyst. , Itself exhibits gel-like physical properties. For this reason, an addition reaction type silicone pressure-sensitive adhesive made of polyorganosiloxane having no vinyl group in the side chain is characterized by a lower cohesive force than a general pressure-sensitive adhesive, and as a result, is well adapted to the skin crevice. For this reason, it is useful as a pressure-sensitive adhesive for a patch where the patch site is less noticeable. In addition, the patch using this addition reaction type silicone adhesive has a small amount of keratinocyte peeling when it is peeled off after being applied to the skin, and can efficiently release the added pharmacologically active substance. Therefore, an excellent function can be exhibited when combined with the polyurethane film support.
　本発明の貼付剤に用いる付加反応型シリコーン系粘着剤は、基本的な成分として、末端ビニルジメチルシロキサン、ジメチルシロキサン、末端または側鎖に水酸基を有するジメチルシロキサンを、好適な範囲に組成を調整し、白金触媒などを加えてビニルシリル基とヒドロシリル基（Ｓｉ－Ｈ）との架橋反応により製造することができる。付加反応は、無溶剤で常温硬化することが可能であるため、作業環境に優しい上、反応後に副生成物が発生しないので、医療用粘着剤として特に有用である。 The addition reaction type silicone pressure-sensitive adhesive used in the patch of the present invention is prepared by adjusting the composition of a terminal vinyldimethylsiloxane, dimethylsiloxane, and dimethylsiloxane having a hydroxyl group at the terminal or side chain as a basic component within a suitable range. Further, it can be produced by a crosslinking reaction of a vinylsilyl group and a hydrosilyl group (Si—H) by adding a platinum catalyst or the like. Since the addition reaction can be cured at room temperature without using a solvent, it is friendly to the working environment, and no by-product is generated after the reaction. Therefore, the addition reaction is particularly useful as a medical adhesive.
　本発明の付加反応型シリコーン系粘着剤層は、通常、シリコーンレジン、可塑剤、充填材等を含まない。例えば、ＭＱレジンと呼ばれる３次元構造を有するシリコーンレジンは、皮膚粘着力を高めるために、シリコーン系粘着剤層に通常配合される成分であるが、角質細胞剥離量が多くなる原因となる。シリコーン系粘着剤層に可塑剤（油状成分）として配合されることがある低分子量ジメチルポリシロキサン等のシリコーンオイルは、支持体へ移行して特性を変えたり、貼付後に該シリコーンオイルが皮膚に残り不快に感じることがある。シリコーン系粘着剤層は、シリカ、ケイ酸アルミニウムなどの充填材を含有すると、凝集力が低下して、皮膚接着能が低下する。 The addition reaction type silicone pressure-sensitive adhesive layer of the present invention usually does not contain a silicone resin, a plasticizer, a filler or the like. For example, a silicone resin having a three-dimensional structure called MQ resin is a component that is usually blended in the silicone-based pressure-sensitive adhesive layer in order to increase skin adhesive force, but causes a large amount of keratinocyte peeling. Silicone oils such as low molecular weight dimethylpolysiloxane that may be blended as a plasticizer (oil component) in the silicone pressure-sensitive adhesive layer may shift to the support and change its properties, or the silicone oil may remain on the skin after application. May feel uncomfortable. When the silicone-based pressure-sensitive adhesive layer contains a filler such as silica or aluminum silicate, the cohesive force is lowered and the skin adhesive ability is lowered.
　本発明の付加反応型シリコーン系粘着剤層は、通常、界面活性剤、粉体、吸水性高分子、ｐＨ調整剤、防腐剤等も含まないが、粘着剤の特性設計上、やむをえない事情があるときに、本発明の目的を損なわない程度において、これらの添加剤を配合することができる。 The addition reaction type silicone pressure-sensitive adhesive layer of the present invention usually does not contain surfactants, powders, water-absorbing polymers, pH adjusters, preservatives, etc., but there are unavoidable circumstances due to the characteristic design of the pressure-sensitive adhesive. Sometimes, these additives can be blended to the extent that the object of the present invention is not impaired.
　本発明の貼付剤の付加反応型シリコーン系粘着剤としては、付加反応型シリコーンを主成分とする範囲で、一般的に使用されるその他のシリコーン系粘着剤を混合して粘着力を調整することができる。特に、皮膚の諸症状の改善を目的として薬理活性物質を添加する場合などは、一般的に粘着特性が低下する場合が多いので、その改善のためにその他のシリコーン系粘着剤の混合が有用である。粘着剤中の付加反応型シリコーンの含有量は、好ましくは７０～１００重量％、より好ましくは８０～１００重量％、特に好ましくは９０～１００重量％の範囲内である。このほか、アクリル系粘着剤、ゴム系粘着剤等のシリコーン系粘着剤以外の粘着剤成分を、通常０～２５重量％、好ましくは０～１５重量％、より好ましくは０～１０重量％の範囲内で含有してもよい。充填剤、顔料、硬化抑制剤などの添加剤を、通常０～３０重量％、好ましくは０～２０重量％、より好ましくは０～１０重量％の範囲内で添加することができる。 As an addition reaction type silicone pressure sensitive adhesive of the patch of the present invention, it is possible to adjust the adhesive force by mixing other commonly used silicone pressure sensitive adhesives within the range of addition reaction type silicone as a main component. Can do. In particular, when pharmacologically active substances are added for the purpose of improving various skin symptoms, the adhesive properties generally decrease in many cases. For this reason, mixing with other silicone adhesives is useful. is there. The content of the addition reaction type silicone in the pressure-sensitive adhesive is preferably in the range of 70 to 100% by weight, more preferably 80 to 100% by weight, and particularly preferably 90 to 100% by weight. In addition, the pressure-sensitive adhesive component other than the silicone-based pressure-sensitive adhesive such as acrylic pressure-sensitive adhesive and rubber-based pressure-sensitive adhesive is usually in the range of 0 to 25% by weight, preferably 0 to 15% by weight, more preferably 0 to 10% by weight. You may contain in. Additives such as fillers, pigments, and curing inhibitors can be added in the range of usually 0 to 30% by weight, preferably 0 to 20% by weight, more preferably 0 to 10% by weight.
　本発明の貼付剤における付加反応型シリコーン系粘着剤層の厚みは、５～５０μｍ、好ましくは８～４５μｍ、より好ましくは１６～４０μｍ、特に好ましくは２０～３５μｍの範囲内である。粘着剤層の厚みが極端に薄い場合は、側鎖にビニル基を持たないポリオルガノシロキサンは、官能基が少ないことから、架橋反応が十分に進まない。特に薬理活性物質を添加する場合には、架橋が阻害されやすく、ある程度の粘着剤層の厚みを確保することは重要である。粘着剤の厚みが大きすぎると、貼付部位が目立ってしまったり、角質細胞剥離量が多くなる傾向にあるため、好ましくない。粘着剤層の厚みが前記の範囲内にあることにより、皮膚表面に対する追従性を損なうことがなく、かつ、貼付部位が目立ちにくいという効果を得ることができる。支持体と付加反応型シリコーン系粘着剤層との合計の厚みは、皮膚表面に対する追従性を損なうことがなく、かつ、貼付部位が目立ちにくいとの効果を奏するために、好ましくは１１～５２μｍ、より好ましくは２０～４６μｍ、特に好ましくは２５～４０μｍの範囲であることが望ましい。 The thickness of the addition reaction type silicone pressure-sensitive adhesive layer in the patch of the present invention is in the range of 5 to 50 μm, preferably 8 to 45 μm, more preferably 16 to 40 μm, and particularly preferably 20 to 35 μm. When the thickness of the pressure-sensitive adhesive layer is extremely thin, since the polyorganosiloxane having no vinyl group in the side chain has few functional groups, the crosslinking reaction does not proceed sufficiently. In particular, when a pharmacologically active substance is added, crosslinking is easily inhibited, and it is important to ensure a certain thickness of the pressure-sensitive adhesive layer. If the thickness of the pressure-sensitive adhesive is too large, the applied site tends to be noticeable and the amount of keratinocyte peeling tends to increase, such being undesirable. When the thickness of the pressure-sensitive adhesive layer is within the above range, it is possible to obtain an effect that the followability with respect to the skin surface is not impaired and the sticking site is not noticeable. The total thickness of the support and the addition reaction type silicone pressure-sensitive adhesive layer is preferably 11 to 52 μm, in order to produce an effect that the followability to the skin surface is not impaired and the sticking site is not noticeable. A range of 20 to 46 μm is more preferable, and a range of 25 to 40 μm is particularly preferable.
　本発明の貼付剤は、ＪＩＳ　Ｚ０２３７に規定されている対ベークライト板の９０度剥離試験において、０．５Ｎ／１０ｍｍ以下の粘着力を示すことが好ましく、より好ましくは０．２Ｎ／１０ｍｍ以下、特に好ましくは０．０１～０．１Ｎ／１０ｍｍの範囲内である。粘着剤層の粘着力が大きすぎると、角質細胞剥離量が多くなってしまう。粘着力が小さすぎると、一般的には皮膚の動きなどの外力によって剥がれやすくなることがあるが、本発明の貼付剤においては、薄く柔軟性に富む支持体とゲル状の粘着剤との組合せにより、粘着力が小さくても皮膚の動きによく追従することができる。 The patch of the present invention preferably exhibits an adhesive strength of 0.5 N / 10 mm or less, more preferably 0.2 N / 10 mm or less, particularly in a 90-degree peel test for a bakelite plate specified in JIS Z0237. Preferably, it is within the range of 0.01 to 0.1 N / 10 mm. If the adhesive strength of the pressure-sensitive adhesive layer is too large, the amount of keratinocyte peeling will increase. If the adhesive strength is too small, it may generally be easily peeled off by an external force such as skin movement. However, in the patch of the present invention, a combination of a thin and flexible support and a gel adhesive Thus, even if the adhesive force is small, it can follow the movement of the skin well.
　本発明の貼付剤は、２００ｇの重りで荷重をかける保持力試験において、３０分間以内に重りが落下する保持力を示すことが好ましく、特に好ましくは５～２５分間の範囲内である。すなわち、保持力試験は、貼付剤の支持体面にカートンテープ（ニチバン株式会社製）を貼り合わせて裏打ちをし、１２ｍｍ×５０ｍｍに裁断し、これをガラス板に貼り付け、１２ｍｍ×２０ｍｍとなるよう裁断し、該貼付剤が垂直に垂れ下がるように２００ｇの重りで荷重をかけ、３０分間以内に重りが落下した貼付剤については、落下時間を測定して保持力試験の結果とする。３０分間以内に重りが落下しない貼付剤については、３０分間後のずれの距離を目盛付のマイクロスコープで測定した。３０分間以内に重りが落下しない貼付剤は、粘着剤層の保持力が大きすぎ、角質細胞剥離量が多くなってしまう。保持力が小さすぎると、一般的には皮膚の動きなどの外力によって剥がれやすくなることがあるが、本発明の貼付剤においては、薄く柔軟性に富む支持体とゲル状の粘着剤との組合せにより、保持力が小さくても皮膚の動きによく追従することができる。 The patch of the present invention preferably exhibits a holding force by which the weight falls within 30 minutes in a holding force test in which a load is applied with a weight of 200 g, and particularly preferably within a range of 5 to 25 minutes. That is, in the holding force test, a carton tape (manufactured by Nichiban Co., Ltd.) is attached to the support surface of the patch, backing, and cut into 12 mm × 50 mm, and this is pasted on a glass plate to be 12 mm × 20 mm. For a patch that was cut and applied with a weight of 200 g so that the patch hangs vertically, and the weight dropped within 30 minutes, the drop time is measured and the result of the holding force test is obtained. For the patch in which the weight did not fall within 30 minutes, the displacement distance after 30 minutes was measured with a microscope with a scale. A patch in which the weight does not fall within 30 minutes has too much holding power for the pressure-sensitive adhesive layer and increases the amount of keratinocyte peeling. If the holding force is too small, it may be easily peeled off by an external force such as skin movement, but in the patch of the present invention, a combination of a thin and flexible support and a gel adhesive Thus, even if the holding force is small, the movement of the skin can be followed well.
　付加反応型シリコーン系粘着剤層は、支持体の全面を被覆することが好ましいが、必要に応じてパターン状に被覆してもよい。パターンとしては、例えば、波状、格子状、点状、円状、唐草模様等の任意の形状を選択することができる。 The addition reaction type silicone pressure-sensitive adhesive layer preferably covers the entire surface of the support, but may be coated in a pattern if necessary. As the pattern, for example, an arbitrary shape such as a wave shape, a lattice shape, a dot shape, a circular shape, or an arabesque pattern can be selected.
５．薬理活性物質
　本発明の貼付剤は、付加反応型シリコーン系粘着剤層に薬理活性物質を添加しなくても、適度な透湿性を有しながら皮膚表面を保護することで、雑菌やアレルゲンなどの外因物質の侵入を防ぎ、かつ、無意識に掻破してしまうことを防ぐことができるので、アトピー性皮膚炎などの皮膚炎の患部が悪化するのを防ぐことができる。本発明の付加反応型シリコーン系粘着剤層を有する貼付剤は、角質細胞剥離量が極めて少なく、剥離するときに患部の角質細胞の剥離を最小限に抑制することができる。 5. Pharmacologically active substance The patch of the present invention protects the skin surface while having appropriate moisture permeability without adding a pharmacologically active substance to the addition reaction type silicone pressure-sensitive adhesive layer. Since it is possible to prevent intrusion of an exogenous substance and prevent unintentional scratching, it is possible to prevent the affected part of dermatitis such as atopic dermatitis from getting worse. The patch having the addition reaction type silicone pressure-sensitive adhesive layer of the present invention has a very small amount of exfoliated keratinocytes, and can suppress the exfoliation of the keratinocytes in the affected area to the minimum when exfoliating.
　本発明の貼付剤は、付加反応型シリコーン系粘着剤層に薬理活性物質を含有させることにより、医療用貼付剤としての機能を高めることができる。アトピー性皮膚炎の患者の皮膚では、グルコシルセラミドの代謝異常のあることが知られており、セラミドの生成量が少ない。そのため、皮膚のバリア機能や保湿能が低下していることから、減少したセラミドの生成量を補充するために、セラミドなどの皮膚角質層に存在する脂質またはその誘導体を含有させることが有効である。セラミド及びその前駆体としては、例えば、セラミド１、２、３、４、５、及び６、並びにフィトスフィンゴシンなどの角質細胞間脂質を挙げることができる。 The patch of the present invention can enhance the function as a medical patch by containing a pharmacologically active substance in the addition reaction type silicone pressure-sensitive adhesive layer. The skin of patients with atopic dermatitis is known to have glucosylceramide metabolism abnormality, and the amount of ceramide produced is small. Therefore, since the skin barrier function and moisturizing ability are lowered, it is effective to contain lipids or derivatives thereof existing in the skin stratum corneum such as ceramide in order to supplement the reduced production amount of ceramide. . Examples of ceramide and its precursor include ceramide 1, 2, 3, 4, 5, and 6, and keratinocyte lipids such as phytosphingosine.
　薬理活性物質として、セラミド類のほか、皮膚の保湿や皺やしみの発生などに対して効果を示すビタミン類；皮膚の炎症を抑えるグリチルレチン、グリチルリチン酸塩及びメントール；皮膚の痒みを抑えるクロタミトン；鎮痛薬のリドカイン；などを使用することができる。ビタミン類としては、脂溶性ビタミンであるビタミンＥやそのエステル、水溶性ビタミンであるビタミンＢ６、ビタミンＣやそのエステル、及びその誘導体からなる群より選ばれる少なくとも一種が有効である。特に好ましい薬理活性物質としては、皮膚に対する浸透性が高く、酸化ストレスを緩和し、色素沈着などを抑制するビタミンＣ誘導体のテトラヘキシルデカン酸アスコルビル（ＮＩＫＫＯＬ（登録商標）　ＶＣ－ＩＰ、日光ケミカルズ株式会社）や、保湿効果が高いビタミンＢ６誘導体であるトリ２－ヘキシルデカン酸ピリドキシン（ＮＩＫＫＯＬ（登録商標）　ＶＢ６－ＩＰ、日光ケミカルズ株式会社）などが挙げられる。またアトピー性皮膚炎の患部では減少が著しいとされるセラミド１や、セラミドの合成促進や静菌作用を持つフィトスフィンゴシンなどの添加が有用である。また適宜、保湿性を維持するためのグリセリン、プロピレングリコール、ソルビトール、１，３－ブチレングリコール、ポリエチレングリコール、尿素、乳酸ナトリウム、ポプチド、ヘパリン、ヒアルロン酸などの保湿剤の添加も可能である。その他、シミなどの皮膚の様々なトラブルに効果が期待される成分の添加も有用である。 As pharmacologically active substances, in addition to ceramides, vitamins that are effective against skin moisturizing and itching and blemishes; glycyrrhetin, glycyrrhizinate and menthol, which suppress skin inflammation; crotamiton, which suppresses skin itchiness; The drug lidocaine; and the like can be used. As the vitamins, at least one selected from the group consisting of vitamin E, which is a fat-soluble vitamin, and esters thereof, vitamin B6, which is a water-soluble vitamin, vitamin C, esters thereof, and derivatives thereof is effective. As a particularly preferred pharmacologically active substance, vitamin C derivative ascorbyl tetrahexyldecanoate (NIKKOL (registered trademark) VC-IP, Nikko Chemicals Co., Ltd.) has high permeability to the skin, relieves oxidative stress, and suppresses pigmentation. And pyridoxine tri-2-hexyldecanoate (NIKKOL (registered trademark) VB6-IP, Nikko Chemicals Co., Ltd.), which is a vitamin B6 derivative having a high moisturizing effect. In addition, addition of ceramide 1, which is considered to be remarkably reduced in affected areas of atopic dermatitis, phytosphingosine having ceramide synthesis promotion and bacteriostatic action is useful. In addition, a humectant such as glycerin, propylene glycol, sorbitol, 1,3-butylene glycol, polyethylene glycol, urea, sodium lactate, peptide, heparin, and hyaluronic acid for maintaining the moisture retention can be appropriately added. In addition, it is also useful to add ingredients that are expected to be effective for various skin problems such as spots.
　アトピー性皮膚炎などの皮膚炎の患部で失われている角質細胞間脂質のセラミドまたはその前駆体や、皮膚の諸症状の緩和に有用なビタミン類は、付加反応型シリコーン系粘着剤との相溶性が適度に良好であるため、付加反応型シリコーン系粘着剤に添加すると、これらをアクリル系粘着剤に添加する場合に比べて、少ない添加量で高い放出性を示す。このため、粘着剤層に薬理活性物質を含有する本発明の貼付剤は、皮膚炎の諸症状の治療・緩和に効果的である。 Ceramide or precursors of keratinocyte lipids lost in affected areas of dermatitis such as atopic dermatitis, and vitamins useful for alleviating skin symptoms are compatible with addition-reactive silicone adhesives. Since the solubility is moderately good, when it is added to an addition reaction type silicone pressure-sensitive adhesive, it exhibits a high release property with a small addition amount compared to the case of adding them to an acrylic pressure-sensitive adhesive. Therefore, the patch of the present invention containing a pharmacologically active substance in the pressure-sensitive adhesive layer is effective for treating and alleviating various symptoms of dermatitis.
　薬理活性物質は、それぞれ単独で、または２種以上を組み合わせて使用することができる。これらの薬理活性物質は、付加反応型シリコーン系粘着剤層中に、通常０．０１～７重量％、好ましくは０．０５～６重量％、より好ましくは０．１～５重量％の範囲内で含有させることができる。 Pharmacologically active substances can be used alone or in combination of two or more. These pharmacologically active substances are usually in the range of 0.01 to 7% by weight, preferably 0.05 to 6% by weight, more preferably 0.1 to 5% by weight in the addition reaction type silicone pressure-sensitive adhesive layer. It can be made to contain.
６．キャリアフィルム
　本発明の貼付剤における支持体であるポリウレタンフィルムの厚みは、先に述べたとおり、１～１０μｍであり、より好ましくは３～７μｍの範囲内である。本発明の貼付剤は、取扱性、皮膚への貼付時の使用性を向上させる目的で、該支持体の付加反応型シリコーン系粘着剤層と反対側の表面（背面）に、キャリアフィルムを配置した層構成を有するものであることが望ましい。キャリアフィルムは、支持体の全面を覆っていても、貼付剤の縁部のみを覆っていても、または、格子状などのパターン状に覆っていてもよいが、支持体の全面を覆うものであることが好ましい。 6). Carrier film As described above, the thickness of the polyurethane film as the support in the patch of the present invention is 1 to 10 μm, more preferably 3 to 7 μm. In the patch of the present invention, a carrier film is disposed on the surface (back surface) opposite to the addition-reactive silicone pressure-sensitive adhesive layer of the support for the purpose of improving handleability and usability at the time of application to the skin. It is desirable to have a layer structure. The carrier film may cover the entire surface of the support, may cover only the edge of the patch, or may be covered with a pattern such as a lattice, but it covers the entire surface of the support. Preferably there is.
　キャリアフィルムとしては、貼付剤に通常使用される上質紙を用いたグラシン紙や上質紙にプラスチックフィルムを積層したポリラミ紙、プラスチックフィルムなどの表面にシリコーン樹脂の塗布などにより剥離処理を施したものを使用することができる。 As carrier film, glassine paper using high-quality paper usually used for patches, polylaminated paper in which a plastic film is laminated on high-quality paper, or a film that has been subjected to a release treatment by applying a silicone resin to the surface of the plastic film, etc. Can be used.
　キャリアフィルムとして使用するプラスチックフィルムとしては、例えば、ポリエステル、ポリウレタン、ポリエチレン、ポリプロピレン、アイオノマー、ポリアミド、ポリ塩化ビニル、ポリ塩化ビニリデン、エチレン酢酸ビニル共重合体、ポリテトラフルオロエチレンなどの各種熱可塑性樹脂からなるフィルムを用いることができる。 Examples of the plastic film used as the carrier film include various thermoplastic resins such as polyester, polyurethane, polyethylene, polypropylene, ionomer, polyamide, polyvinyl chloride, polyvinylidene chloride, ethylene vinyl acetate copolymer, and polytetrafluoroethylene. Can be used.
　環境保全を目的として、キャリアフィルムとして、例えば、ポリヒドロキシブチレート樹脂、ポリヒドロキシアルカノエート、マルトトリオース、ポリ乳酸系樹脂、ポリエチレンサクシネート樹脂、ポリブチレンサクシネート樹脂、ポリカプロラクトン樹脂、ポリブチレンアジペートテレフタレート、ポリテトラメチレンアジペートテレフタレート、ポリエチレンテレフタレート、ポリビニルアルコール、ポリグリコール酸、デンプン脂肪酸エステル、デンプン加工樹脂、デンプンポリエステル、酢酸セルロース、キトサンなどから形成されたフィルムを使用することができる。これらの中でも、生分解性を有するプラスチックフィルムが好ましい。これら各種フィルムは、紙にラミネートされた状態のものでもよい。また必要に応じて表面にシリコーンなどを塗布して剥離処理したものを使うこともできる。特に、粘着剤中に薬理活性物質を含有させる場合には、支持体であるポリウレタンフィルムを介して薬理活性物質が移行するおそれがあることから、ポリエステルフィルムなどの薬物非吸着性のキャリアフィルムが適している。特に、本発明のような粘着力が小さい貼付剤では、皮膚に貼付後、容易にキャリアフィルムを剥離できるようにするため、剥離処理したものが望ましい。また、支持体製膜時にロール状に巻き取ることがある場合などでは、両面に剥離処理したポリエステルフィルムをキャリアフィルムに使用することもできる。 For the purpose of environmental conservation, as carrier film, for example, polyhydroxybutyrate resin, polyhydroxyalkanoate, maltotriose, polylactic acid resin, polyethylene succinate resin, polybutylene succinate resin, polycaprolactone resin, polybutylene adipate Films formed from terephthalate, polytetramethylene adipate terephthalate, polyethylene terephthalate, polyvinyl alcohol, polyglycolic acid, starch fatty acid ester, starch processing resin, starch polyester, cellulose acetate, chitosan and the like can be used. Among these, a biodegradable plastic film is preferable. These various films may be laminated on paper. Further, if necessary, the surface of the surface coated with silicone or the like can be removed. In particular, when a pharmacologically active substance is contained in the pressure-sensitive adhesive, a non-drug-adsorbing carrier film such as a polyester film is suitable because the pharmacologically active substance may migrate through the support polyurethane film. ing. In particular, in the patch having a low adhesive strength as in the present invention, it is desirable that the patch is peeled off so that the carrier film can be easily peeled after being applied to the skin. Moreover, when the roll may be wound up at the time of forming the support, a polyester film that has been subjected to release treatment on both sides can be used for the carrier film.
　キャリアフィルムは、支持体のポリウレタンフィルムに比べて、厚みが厚いか、腰の強いものであることが望ましい。キャリアフィルムの厚みは、適宜設定できるが、通常１０μｍ以上、好ましくは２０μｍ以上であり、その上限値は通常５００μｍ、好ましくは３００μｍ、より好ましくは２００μｍである。 The carrier film is desirably thicker or firmer than the support polyurethane film. The thickness of the carrier film can be appropriately set, but is usually 10 μm or more, preferably 20 μm or more, and the upper limit is usually 500 μm, preferably 300 μm, more preferably 200 μm.
７．剥離ライナー
　本発明の貼付剤においては、付加反応型シリコーン系粘着剤層の支持体に接する側と反対側の面に、剥離ライナー（以下、「離型フィルム」ということがある。）を設けることが好ましい。該剥離ライナーとしては、未処理のポリエチレンフィルム、ポリプロピレンフィルムなどのポリオレフィンフィルム；ポリエチレンテレフタレートに代表されるポリエステルフィルム；プラスチックフィルムと紙とのラミネート紙（ポリラミ紙）；など、通常、貼付剤の技術分野で汎用されている剥離ライナーが使用できる。軽度の剥離力が求められる場合には、剥離ライナーの表面（粘着剤層側の面）に、フッ素樹脂、フルオロシリコーン樹脂、シリコーン樹脂などによる表面処理（離型処理）を施すことができる。本発明では、粘着剤層にシリコーン系粘着剤を使用していることから、フッ素樹脂及びフルオロシリコーン樹脂による表面処理（離型処理）が適している。また、キャリアフィルムと同じく薬理活性物質が剥離ライナーに移行するおそれがあるので、ポリエステルフィルムなどの薬物非吸着性のフィルムに表面処理（離型処理）加工するのがよい。剥離ライナーの厚みは、適宜設定できるが、通常１０μｍ以上、好ましくは２０μｍ以上であり、その上限値は通常５００μｍ、好ましくは３００μｍ、より好ましくは２００μｍである。 7). Release liner In the patch of the present invention, a release liner (hereinafter sometimes referred to as “release film”) is provided on the surface of the addition reaction type silicone pressure-sensitive adhesive layer opposite to the side in contact with the support. Is preferred. As the release liner, polyolefin films such as untreated polyethylene film and polypropylene film; polyester film represented by polyethylene terephthalate; laminated paper of plastic film and paper (polylaminated paper); A release liner that is widely used in the above can be used. When a mild peeling force is required, the surface of the release liner (the surface on the pressure-sensitive adhesive layer side) can be subjected to a surface treatment (release treatment) with a fluororesin, a fluorosilicone resin, a silicone resin, or the like. In the present invention, since a silicone-based pressure-sensitive adhesive is used for the pressure-sensitive adhesive layer, surface treatment (release treatment) with a fluororesin and a fluorosilicone resin is suitable. Further, since the pharmacologically active substance may migrate to the release liner as in the case of the carrier film, it is preferable to perform a surface treatment (mold release treatment) on a non-drug adsorbing film such as a polyester film. The thickness of the release liner can be appropriately set, but is usually 10 μm or more, preferably 20 μm or more, and the upper limit is usually 500 μm, preferably 300 μm, more preferably 200 μm.
　剥離ライナーは、付加反応型シリコーン系粘着剤層を支持体上に塗布して形成した後、剥離ライナーと圧着することにより形成してもよいし、剥離ライナー上に付加反応型シリコーン系粘着剤層を塗布した後、該付加反応型シリコーン系粘着剤層を支持体と圧着する方法により形成してもよい。 The release liner may be formed by applying an addition reaction type silicone pressure-sensitive adhesive layer on a support and then pressing the release liner with the release liner, or the addition reaction type silicone pressure-sensitive adhesive layer on the release liner. After the coating, the addition reaction type silicone pressure-sensitive adhesive layer may be formed by a method of pressure-bonding to a support.
　キャリアフィルム、支持体、粘着剤層、及び剥離ライナーをこの順序で備えた貼付剤は、粘着剤層から剥離ライナーを剥離するのに必要な剥離力が、キャリアフィルムから支持体を分離するのに必要な剥離力よりも大きくなるように設定することが好ましい。こうすることで、剥離ライナーを剥離した後に現れる付加反応型シリコーン系粘着剤層の面を皮膚に貼付し、次いで、キャリアフィルムを剥離することができるので、作業性が向上する。 A patch comprising a carrier film, a support, a pressure-sensitive adhesive layer, and a release liner in this order is used to separate the support from the carrier film because of the peeling force required to peel the release liner from the pressure-sensitive adhesive layer. It is preferable to set so as to be larger than the required peeling force. By doing so, the surface of the addition reaction type silicone pressure-sensitive adhesive layer that appears after the release liner is peeled off can be applied to the skin, and then the carrier film can be peeled off, so that workability is improved.
８．貼付剤
　本発明の貼付剤は、支持体の片面に粘着剤層が設けられた層構成を有する貼付剤において、支持体が、１～１０μｍの範囲内の厚みを持つポリウレタンフィルムであり、粘着剤層が、５～５０μｍの範囲内の厚みを持つ、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤層であって、透湿度が１５００ｇ／ｍ２・２４ｈｒ超過であることによって、ダメージを負った皮膚を覆うことで、様々な外的因子の侵入を防ぐだけでなく、皮膚表面の角質層が持つ水分保持能を助ける役割も果たす。 8). Patch The patch of the present invention is a patch having a layer structure in which an adhesive layer is provided on one side of a support, and the support is a polyurethane film having a thickness in the range of 1 to 10 μm. The layer is an addition reaction type silicone pressure-sensitive adhesive layer made of polyorganosiloxane having a thickness in the range of 5 to 50 μm and having no vinyl group in the side chain, and the moisture permeability exceeds 1500 g / m 2 · 24 hr. In some cases, covering damaged skin not only prevents the invasion of various external factors, but also serves to help the moisture retention ability of the stratum corneum on the skin surface.
　本発明の貼付剤は、その透湿度が１５００ｇ/ｍ２・２４ｈｒ超過であることにより、貼付部位に皮膚刺激の原因となる汗が溜まることを防ぎ、貼付剤が発汗によって皮膚から剥離したりせず、適度な透湿性をもって皮膚表面を保護することができる。本発明の貼付剤は、外因物質の侵入を防ぐことができる上、例えば、アトピー性皮膚炎などの健常な皮膚の機能を損なった状態の皮膚に対して、角質層の代役を果たすことができる。透湿度は、ＪＩＳ Ｚ０２０８に従って測定した値である。 The patch of the present invention has a moisture permeability of more than 1500 g / m 2 · 24 hr, thereby preventing the skin that causes skin irritation from accumulating at the applied site, and causing the patch to peel from the skin by sweating. Therefore, the skin surface can be protected with appropriate moisture permeability. The patch of the present invention can prevent the entry of exogenous substances, and can also serve as a substitute for the stratum corneum for skin in which the function of healthy skin such as atopic dermatitis is impaired. . The moisture permeability is a value measured according to JIS Z0208.
　本発明の貼付剤は、皮膚患部を覆うことにより、掻破による患部の悪化を回避することができ、アトピー性皮膚炎などの皮膚炎の患部に対して自然の回復を促すことが可能となる。本発明の貼付剤は、付加反応型シリコーン系粘着剤層に薬理活性物質を含有させなくても、適度な透湿性を有しながら皮膚表面を保護することで、外因物質の侵入を防ぎ、アトピー性皮膚炎などの皮膚炎の症状を有するヒトが、無意識に皮膚を掻破してしまうことを防ぐことができるので、患部が悪化するのを防ぐことができる。本発明の貼付剤は、アトピー性皮膚炎症状のヒトなどが、皮膚掻破行動をとったときにも、皮膚上の貼付剤が皮膚の直接的な掻破を防止するバリアとして機能する。したがって、本発明の貼付剤は、アトピー性皮膚炎症状のヒトなどに対する皮膚掻破防止用の貼付剤として好適に使用することができる。先に述べたように付加反応型シリコーン系粘着剤層に薬理活性物質を含有させることは差し支えない。 The patch of the present invention covers the affected area of the skin, thereby avoiding deterioration of the affected area due to scratching and promoting natural recovery of the affected area of dermatitis such as atopic dermatitis. The patch of the present invention prevents the entry of exogenous substances by protecting the skin surface while having an appropriate moisture permeability, even without adding a pharmacologically active substance to the addition reaction type silicone pressure-sensitive adhesive layer. Since it is possible to prevent a human having symptoms of dermatitis such as dermatitis from unintentionally scratching the skin, the affected area can be prevented from deteriorating. The patch of the present invention functions as a barrier that prevents the skin patch from directly scratching even when a person with atopic skin inflammation or the like takes a skin scratching action. Therefore, the patch of the present invention can be suitably used as a patch for preventing skin scratches on humans with atopic skin inflammation. As described above, the addition reaction type silicone pressure-sensitive adhesive layer may contain a pharmacologically active substance.
　本発明の貼付剤は、皮膚表面に貼付後、剥離するときに、皮膚の角質細胞の剥離量が極めて少ない。本発明の貼付剤は、ヒト前腕内側の皮膚表面に６時間貼付後、剥離したときに、貼付面積に対する角質細胞剥離面積が２０％以下とすることができる。角質細胞剥離面積が２０％以下であると、皮膚刺激を発生させることが抑制され、患部を悪化させることがない。したがって、本発明の貼付剤は、特に角質の細胞間結合力が低下しているため、より角質細胞が剥離しやすい状態にあるアトピー性皮膚炎症状のヒトの症状を悪化させることがない。貼付６時間後の角質細胞剥離面積が２０％以下であるとは、健康な被験者（皮膚が健康な状態にある被験者）の前腕内側に、所定形状の貼付剤を所定時間（６時間）貼付した後、該貼付剤を剥離し、皮膚から剥離して粘着剤層の表面に移行した角質細胞を染色液を用いて観察し、貼付剤の全面積に対する、剥離した角質細胞によって染色された部分の面積の比率が２０％以下であることを意味する。貼付６時間後の角質細胞剥離面積は、好ましくは１５％以下、より好ましくは１０％以下、更に好ましくは５％以下、特に好ましくは２％以下であると、皮膚へのダメージを最小限に抑えることができる。 When the patch of the present invention is peeled off after being applied to the skin surface, the amount of exfoliated keratinocytes on the skin is extremely small. When the patch of the present invention is affixed to the skin surface inside the human forearm for 6 hours and then peeled off, the keratinocyte peeling area relative to the sticking area can be 20% or less. When the keratinocyte peeling area is 20% or less, generation of skin irritation is suppressed, and the affected area is not deteriorated. Therefore, since the patch of the present invention has a particularly reduced keratin intercellular binding force, it does not exacerbate the human symptoms of atopic skin inflammation in which the keratinocytes are more easily detached. When the keratinocyte exfoliation area 6 hours after application is 20% or less, a patch of a predetermined shape was applied to the inner side of the forearm of a healthy subject (subject with a healthy skin) for a predetermined time (6 hours). Thereafter, the patch was peeled off, and the keratinocytes peeled from the skin and transferred to the surface of the pressure-sensitive adhesive layer were observed using a staining solution, and the area stained with the peeled keratinocytes with respect to the entire area of the patch It means that the area ratio is 20% or less. If the keratinocyte peeling area after 6 hours of application is preferably 15% or less, more preferably 10% or less, still more preferably 5% or less, and particularly preferably 2% or less, the damage to the skin is minimized. be able to.
　以下、実施例及び比較例を挙げて、本発明についてより詳細に説明するが、本発明は、これらの実施例のみに限定されない。貼付剤の特性の測定方法は、以下のとおりである。 Hereinafter, although an example and a comparative example are given and the present invention is explained in detail, the present invention is not limited only to these examples. The method for measuring the characteristics of the patch is as follows.
＜目立ちにくさ＞
　貼付剤の目立ちにくさは、温度２５℃、相対湿度６５％の恒温室において、健康な３０歳代～４０歳代の成人男子３名の前腕内側部に、１５ｍｍ×５０ｍｍの大きさに裁断した貼付剤を貼付し、２０分後の外観から目立ちにくさを、各貼付剤ごとに以下の３段階で評価した。
Ａ：　目立たない
Ｂ：　若干気になる
Ｃ：　目立つ <Inconspicuous>
The inconspicuousness of the patch was cut to a size of 15 mm x 50 mm on the inner forearm of three healthy male adults in their 30s to 40s in a thermostatic chamber at a temperature of 25 ° C and a relative humidity of 65%. The patch was affixed, and the degree of inconspicuousness from the appearance after 20 minutes was evaluated for each patch in the following three stages.
A: Inconspicuous B: Slightly concerned C: Conspicuous
　またデジタルマイクロスコープ（ＶＨＸ－９００、株式会社キーエンス製）を用いて被験者の１名の貼付部位を１００倍に拡大した写真を撮影し、皮溝に対する密着度合いを調べた。参考としてグロスチェッカー（ＩＧ－３２０、株式会社堀場製作所製）を用いて、被験者１名の前腕内側部に２０分間貼付したときの支持体表面の光沢度を調べた。 Also, using a digital microscope (VHX-900, manufactured by Keyence Co., Ltd.), a photograph in which one subject's affixed site was magnified 100 times was taken to examine the degree of adhesion to the skin groove. As a reference, a gloss checker (IG-320, manufactured by HORIBA, Ltd.) was used to examine the glossiness of the support surface when applied to the inner side of the forearm of one subject for 20 minutes.
＜角質細胞剥離量＞
　角質細胞剥離量は、２０歳代から４０歳代の健康な成人男女６名の前腕内側部に、１５ｍｍ×５０ｍｍの大きさに裁断した貼付剤を６時間貼付し、剥離後の粘着剤表面に付着した角質細胞をカチオン染料液（ゲンチアナバイオレットＢ：１％、ブリリアントグリーン：０．５％、蒸留水：９８．５％）に３時間浸漬して染色し、画像処理装置を用いて角質細胞剥離面積の比率（％）を測定し、平均値と標準偏差を求めた。 <Amount of exfoliated corneocytes>
The amount of exfoliated keratinocytes is applied to the inside of the forearm of 6 healthy adult men and women in their 20s and 40s for 6 hours, and the patch cut into a size of 15mm x 50mm is applied for 6 hours. The attached keratinocytes are stained by immersing them in a cationic dye solution (gentian violet B: 1%, brilliant green: 0.5%, distilled water: 98.5%) for 3 hours, and the keratinocytes are detached using an image processing apparatus. The area ratio (%) was measured, and an average value and a standard deviation were obtained.
＜透湿度＞
　透湿度は、ＪＩＳ Ｚ０２０８のＢ条件に従って、温度４０℃、相対湿度９０％で測定した。すなわち、試料の片面側を温度４０℃、相対湿度９０％に調節し、他面側には約１６ｇの吸湿剤（塩化カルシウム）を置いて、試料を通過した水分を吸収させ、吸湿剤の重量変化量を１ｍ２、２４時間当りに換算して、３枚の貼付剤の平均値を透湿度とした。 <Moisture permeability>
The moisture permeability was measured at a temperature of 40 ° C. and a relative humidity of 90% in accordance with the B condition of JIS Z0208. That is, one side of the sample is adjusted to a temperature of 40 ° C. and a relative humidity of 90%, and about 16 g of a hygroscopic agent (calcium chloride) is placed on the other side to absorb the moisture that has passed through the sample. The amount of change was converted to 1 m 2 per 24 hours, and the average value of the three patches was taken as moisture permeability.
＜粘着力＞
　粘着力は、ＪＩＳ　Ｚ０２３７に規定されている９０度剥離試験に準じて行った。詳細には、洗浄したベークライト板（フェノール樹脂板、住友ベークライト株式会社製、ＰＬ－１１０２）を乾燥後、幅１０ｍｍに裁断した貼付剤を貼り付け、２ｋｇの荷重ロールを使って圧着後、２０±１０分間以内にインストロン型引張試験機で９０度方向に１００ｍｍ／ｍｉｎの引張速度で引き剥がす時の応力（Ｎ）を測定して粘着力とし、３枚の貼付剤の平均値と標準偏差を求めた。 <Adhesive strength>
The adhesive strength was measured according to the 90 degree peel test defined in JIS Z0237. Specifically, after the washed bakelite plate (phenol resin plate, manufactured by Sumitomo Bakelite Co., Ltd., PL-1102) is dried, a patch cut to a width of 10 mm is applied, and after pressing with a 2 kg load roll, 20 ± Measure the stress (N) when peeling off at a pulling rate of 100 mm / min in the 90-degree direction with an Instron type tensile tester within 10 minutes to determine the adhesive strength and the average value and standard deviation of the three patches. Asked.
＜保持力＞
　保持力は、貼付剤の支持体面にカートンテープ（ニチバン株式会社製）を貼り合わせて裏打ちをし、１２ｍｍ×５０ｍｍに裁断した。これをガラス板に貼り付け、１２ｍｍ×２０ｍｍとなるよう裁断し、該貼付剤が垂直に垂れ下がるように２００ｇの重りで荷重をかけ、３０分間後のずれの距離を目盛付のマイクロスコープで測定して保持力とし、３枚の貼付剤の平均値を求めた。なお、３０分間以内に重りが落下したものについては、落下時間の範囲を求めた。 <Retention force>
Holding force was bonded to the support surface of the patch with a carton tape (manufactured by Nichiban Co., Ltd.), lined, and cut into 12 mm × 50 mm. This is pasted on a glass plate, cut to 12 mm x 20 mm, a 200 g weight is applied so that the patch hangs vertically, and the distance of displacement after 30 minutes is measured with a microscope with a scale. The average value of the three patches was obtained. In addition, about the thing from which the weight fell within 30 minutes, the range of fall time was calculated | required.
＜薬理活性物質の放出試験＞
　薬理活性物質の放出量は、実質透過面積が１．７６６ｃｍ２（直径１．５ｃｍの円形）の横型拡散セルに貼付剤を粘着剤層面が内側になるように装着し、レシーバー液（ＰＢＳ；ｐＨ７．４）２０％ＰＥＧ水溶液を入れ、３２℃の条件で放出試験を行って測定した。開始１時間後の溶出液をサンプリングし、ＨＰＬＣ（株式会社島津製作所製高速液体クロマトグラフＬＣ－２０１０）で、３枚の貼付剤の薬理活性物質の濃度を定量し、１ｃｍ２あたりの放出量として平均値及び標準偏差を求めた。 <Pharmacologically active substance release test>
The amount of the pharmacologically active substance released was determined by mounting the patch on a horizontal diffusion cell having a substantial permeation area of 1.766 cm 2 (circular with a diameter of 1.5 cm) so that the adhesive layer surface was inside, and receiving the receiver liquid (PBS; pH 7 .4) A 20% PEG aqueous solution was added, and a release test was performed at 32 ° C. for measurement. Sampling the effluent of 1 hour after the start, by HPLC (Shimadzu high performance liquid chromatograph LC-2010), to quantify the concentration of the pharmacologically active substances of three patches, as emission amount per 1 cm 2 Average values and standard deviations were determined.
［実施例１］
　ポリエーテル系ポリウレタンエラストマー溶液（セイコー化成株式会社製　ラックスキン（登録商標）　ＵＳ２２６８）を、片面シリコーン処理した７５μｍ厚のポリエステル（ＰＥＴ）フィルム表面に、乾燥後の厚みが５μｍとなるよう塗布し、乾燥して、ポリウレタンフィルムからなる支持体とした。次にポリウレタンフィルムの表面にシラン系プライマー（ダウコーニング社製　ＦＳ　ＸＡ－２８６９）をメイヤーバーにて適量塗布した。 [Example 1]
A polyether-based polyurethane elastomer solution (Lack Skin (registered trademark) US2268 manufactured by Seiko Kasei Co., Ltd.) is applied to the surface of a 75 μm-thick polyester (PET) film treated with silicone on one side so that the thickness after drying is 5 μm and dried. And it was set as the support body which consists of a polyurethane film. Next, an appropriate amount of a silane primer (FS XA-2869 manufactured by Dow Corning) was applied to the surface of the polyurethane film with a Mayer bar.
　上記支持体のポリウレタンフィルム面に、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤（ダウコーニング社製　７－９８００　Ａ：Ｂ＝５０：５０）をベーカー式アプリケーターにて厚み３０μｍとなるように塗工し、１７０℃の恒温槽に１分入れ、硬化させた。次に片面フルオロシリコーン処理した厚み７５μｍのポリエステル（ＰＥＴ）フィルムの処理面を、前記付加反応型シリコーン系粘着剤と貼り合わせて裁断し、キャリアフィルム／支持体／粘着剤層／剥離ライナーの積層構成を持つ貼付剤を得た。 An addition reaction type silicone pressure sensitive adhesive (7-9800 A: B = 50: 50, manufactured by Dow Corning) made of polyorganosiloxane having no vinyl group in the side chain is applied to the baker type applicator on the polyurethane film surface of the support. The film was coated to a thickness of 30 μm, placed in a constant temperature bath at 170 ° C. for 1 minute, and cured. Next, the treated surface of a polyester (PET) film having a thickness of 75 μm treated with single-sided fluorosilicone is bonded to the addition reaction type silicone pressure-sensitive adhesive and cut to form a laminated structure of carrier film / support / adhesive layer / release liner. A patch with the following was obtained.
［実施例２］
　ポリエステル系ポリウレタンエラストマー溶液（日本ポリウレタン株式会社製　ニッポラン（登録商標）　５１１１）を、片面シリコーン処理した厚み７５μｍのＰＥＴフィルム表面に、乾燥後の厚みが５μｍとなるよう塗布し、乾燥して、ポリウレタンフィルムからなる支持体とした。 [Example 2]
Polyester polyurethane elastomer solution (Nipporan (registered trademark) 5111 manufactured by Nippon Polyurethane Co., Ltd.) was applied to a 75 μm thick PET film surface treated with one side of silicone so that the thickness after drying was 5 μm, dried, and then a polyurethane film It was set as the support body which consists of.
　上記支持体のポリウレタンフィルム面に、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤（ダウコーニング社製　７－９９００　Ａ：Ｂ＝５０：５０）をベーカー式アプリケーターにて厚み３０μｍとなるよう塗工し、１７０℃の恒温槽に１分入れ、硬化させた。次に片面フルオロシリコーン処理した厚み７５μｍのＰＥＴフィルムの処理面を、前記付加反応型シリコーン系粘着剤と貼り合わせて裁断し、貼付剤を得た。 Addition reaction type silicone adhesive (7-9900, A: B = 50: 50, manufactured by Dow Corning Co., Ltd.) made of polyorganosiloxane having no vinyl group in the side chain on the polyurethane film surface of the support as a baker type applicator. The film was coated to a thickness of 30 μm, placed in a constant temperature bath at 170 ° C. for 1 minute, and cured. Next, the treated surface of a PET film having a thickness of 75 μm treated with single-sided fluorosilicone was bonded to the addition reaction type silicone pressure-sensitive adhesive and cut to obtain a patch.
［実施例３］
　実施例１で作製したポリウレタンフィルムに、実施例１で使用した付加反応型シリコーン系粘着剤を厚みが１０μｍになるよう塗工し、同様に片面フルオロシリコーン処理したＰＥＴフィルムと貼り合わせて裁断し、貼付剤を得た。 [Example 3]
The polyurethane film produced in Example 1 was coated with the addition-reactive silicone pressure-sensitive adhesive used in Example 1 so that the thickness was 10 μm, and was similarly bonded with a single-sided fluorosilicone-treated PET film and cut. A patch was obtained.
［比較例１］
　実施例１で作製したポリウレタンフィルムに、実施例１で使用した付加反応型シリコーン系粘着剤を厚みが６０μｍになるよう塗工し、同様に片面フルオロシリコーン処理したＰＥＴフィルムと貼り合わせて裁断し、貼付剤を得た。 [Comparative Example 1]
The polyurethane film produced in Example 1 was coated with the addition reaction type silicone pressure-sensitive adhesive used in Example 1 so as to have a thickness of 60 μm. A patch was obtained.
［比較例２］
　実施例１で作製したポリウレタンフィルムに、実施例１で使用した付加反応型シリコーン系粘着剤に代えて、シリコーン系粘着剤（ダウコーニング社製　ＢＩＯ－ＰＳＡ（登録商標）　４５０１）を乾燥後の厚みが２０μｍとなるよう塗布し、片面フルオロシリコーン処理したＰＥＴフィルムと貼り合わせて裁断し、貼付剤を得た。ＢＩＯ－ＰＳＡ　４５０１は、汎用の３次元架橋タイプの縮合型シリコーン系粘着剤である。 [Comparative Example 2]
Instead of the addition reaction type silicone adhesive used in Example 1, a silicone adhesive (BIO-PSA (registered trademark) 4501 manufactured by Dow Corning) was dried on the polyurethane film produced in Example 1 after drying. Was coated with a PET film treated with single-sided fluorosilicone and cut to obtain a patch. BIO-PSA 4501 is a general-purpose three-dimensional crosslinking type condensation-type silicone adhesive.
［比較例２の２］
　シリコーン系粘着剤（ダウコーニング社製　ＢＩＯ－ＰＳＡ（登録商標）　４５０１）を乾燥後の厚みが１０μｍとなるよう塗布したこと以外は、比較例２と同様にして、貼付剤を得た。 [Comparative Example 2-2]
A patch was obtained in the same manner as in Comparative Example 2, except that a silicone adhesive (BIO-PSA (registered trademark) 4501 manufactured by Dow Corning) was applied so that the thickness after drying was 10 μm.
［比較例３］
　実施例１で作製したポリウレタンフィルムに、アクリル系粘着剤（アクリル酸２－エチルヘキシル／酢酸ビニル／アクリル酸＝８５／１１／４重量％の酢酸エチル溶液）を乾燥後の厚みが５μｍとなるよう塗布し、片面シリコーン処理したＰＥＴフィルムと貼り合わせて裁断し、貼付剤を得た。 [Comparative Example 3]
An acrylic pressure-sensitive adhesive (2-ethylhexyl acrylate / vinyl acetate / acrylic acid = 85/11/4 wt% ethyl acetate solution) was applied to the polyurethane film produced in Example 1 so that the thickness after drying was 5 μm. Then, it was bonded with a single-sided silicone-treated PET film and cut to obtain a patch.
［比較例４］
　実施例１で作製したポリウレタンフィルムに、スチレン－イソプレン－スチレンブロック共重合体（ＳＩＳ）系粘着剤（ＪＳＲ株式会社製　ＳＩＳ５２００／荒川化学社製ロジン樹脂　ＫＥ３１１＝１００／１００重量部のトルエン溶液）を乾燥後の厚みが５μｍとなるよう塗布し、片面シリコーン処理したＰＥＴフィルムと貼り合わせて裁断し、貼付剤を得た。 [Comparative Example 4]
A styrene-isoprene-styrene block copolymer (SIS) -based adhesive (SIS5200 manufactured by JSR Corporation / Rosin resin KE311 = 100/100 parts by weight toluene solution manufactured by Arakawa Chemical Co., Ltd.) was applied to the polyurethane film produced in Example 1. It was applied so as to have a thickness of 5 μm after drying, bonded to a single-sided silicone-treated PET film, and cut to obtain a patch.
［比較例５］
　比較例３で用いたアクリル系粘着剤中に、油状成分であるミリスチン酸イソプロピル（日光ケミカルズ株式会社製　ＩＰＭ）を２０重量％混合し、攪拌後、比較例１と同じ方法で貼付剤を作製した。 [Comparative Example 5]
In the acrylic adhesive used in Comparative Example 3, 20% by weight of oily component isopropyl myristate (IPM manufactured by Nikko Chemicals Co., Ltd.) was mixed, and after stirring, a patch was prepared in the same manner as in Comparative Example 1. .
［比較例６］
　実施例１で使用したポリエーテル系ポリウレタンエラストマー溶液を、乾燥後の厚みが２０μｍとなるよう塗布したこと以外は、実施例１と同様にして貼付剤を得た。 [Comparative Example 6]
A patch was obtained in the same manner as in Example 1 except that the polyether-based polyurethane elastomer solution used in Example 1 was applied so that the thickness after drying was 20 μm.
　実施例１～３及び比較例１～６の貼付剤について、各測定結果を表１に示す。 Table 1 shows the measurement results for the patches of Examples 1 to 3 and Comparative Examples 1 to 6.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　実施例１と、比較例２、３及び５の貼付剤を前腕内側部に２０分間貼付したときの外観写真と、それぞれのグロスチェッカーによる光沢度の値を図１に示す。図１において、黒数字はグロスチェッカーによる貼付部位の値であり、白数字はグロスチェッカーによる無貼付部位の値である。 FIG. 1 shows an external appearance photograph when the patches of Example 1 and Comparative Examples 2, 3 and 5 were applied to the inner portion of the forearm for 20 minutes, and the gloss values of the respective gloss checkers. In FIG. 1, the black numbers are the values of the affixed sites by the gloss checker, and the white numbers are the values of the non-applied sites by the gloss checker.
　実施例３と比較例１及び比較例３の貼付剤を、前腕内側部に貼付時の貼付部位の皮膚の拡大写真（１００倍）を図２に示す。図２の（１）は、貼付剤無貼付部位の皮膚表面、（２）は、実施例３の貼付剤の貼付部位の皮膚表面、（３）は、比較例１の貼付剤の貼付部位、（４）は、比較例３の貼付剤の貼付部位の皮膚表面である。実施例３の貼付剤は、皮溝によく密着している。比較例１の貼付剤は、皮溝に密着しているが、粘着剤層が厚いために、皮溝が隠れてしまい、逆に外観としては目立ってしまう。さらに、比較例３の貼付剤は、アクリル系粘着剤の凝集力が高いため、貼付剤全体の厚みが薄いにもかかわらず、皮溝に密着しきれずに浮いてしまっている（白く見える部分）ので、短時間（２０分程度）の貼付においては外観上目立ってしまう。 FIG. 2 shows an enlarged photograph (100 times) of the skin at the site of application when the patches of Example 3, Comparative Example 1 and Comparative Example 3 were applied to the inner part of the forearm. (1) in FIG. 2 is the skin surface at the site where the patch is not applied, (2) is the skin surface at the site where the patch of Example 3 is applied, (3) is the site where the patch of Comparative Example 1 is applied, (4) is the skin surface of the patch application site of Comparative Example 3. The patch of Example 3 is in close contact with the skin groove. The patch of Comparative Example 1 is in close contact with the skin groove, but since the adhesive layer is thick, the skin groove is hidden, and conversely, the appearance is conspicuous. Furthermore, the patch of Comparative Example 3 has a high cohesive strength of the acrylic adhesive, and thus the adhesive patch does not adhere to the skin groove even though the thickness of the entire patch is thin (part that looks white). Therefore, the appearance is conspicuous in pasting for a short time (about 20 minutes).
　また実施例１と比較例２、３及び５の貼付剤を、２０歳代～４０歳代の男女６名の前腕内側部に６時間貼付した後、剥離したときの角質細胞剥離量の値を図３に示す。なお、貼付剤を剥離して１時間後及び２４時間後の皮膚刺激は全例で認められず、汗の滞留による剥離も全例で認められなかった。図３中のエラーバーは標準偏差を示す。 In addition, the values of the amount of exfoliated keratinocytes when exfoliating after applying the patches of Example 1 and Comparative Examples 2, 3 and 5 to the inner forearm of 6 men and women in their 20s to 40s for 6 hours are shown. As shown in FIG. In addition, skin irritation 1 hour and 24 hours after peeling of the patch was not observed in all cases, and peeling due to retention of sweat was not observed in all cases. Error bars in FIG. 3 indicate standard deviation.
　図１～３及び表１から、実施例１～３の貼付剤は、皮膚に貼り付けても目立ちにくく、長時間（６時間）貼り付けても皮膚表面からの剥離を生じることなく、剥がすときの角質細胞剥離量が極めて少ないことがわかる。これに対して、付加反応型シリコーン系粘着剤層の厚みが厚すぎると、皮膚に貼り付けたときに目立ってしまう（比較例１）。粘着剤として、汎用のシリコーン系粘着剤である３次元架橋タイプのシリコーン系粘着剤（縮合型シリコーン系粘着剤）、アクリル系粘着剤、及びゴム系粘着剤を使用すると、粘着剤の凝集性が高いため、図１～２及び表１に示すとおり、皮溝に十分密着せず、その結果、皮溝と貼付剤との間に空間が生じ、斜めからみると貼付部位が、白く見え、目立ってしまうものであった（比較例２～５）。さらに図３及び表１に示すとおり、いずれの粘着剤も角質細胞剥離量が２０％を超え、極めて大きい（比較例２、２の２、３及び５）。 1 to 3 and Table 1 show that the patches of Examples 1 to 3 are not noticeable even when applied to the skin, and do not peel off from the skin surface even if applied for a long time (6 hours). It can be seen that the amount of exfoliated cells is extremely small. On the other hand, when the thickness of the addition reaction type silicone pressure-sensitive adhesive layer is too thick, it becomes conspicuous when affixed to the skin (Comparative Example 1). When a three-dimensional cross-linking type silicone pressure sensitive adhesive (condensation type silicone pressure sensitive adhesive), an acrylic pressure sensitive adhesive, or a rubber pressure sensitive adhesive, which is a general-purpose silicone pressure sensitive adhesive, is used as the pressure sensitive adhesive, the cohesiveness of the pressure sensitive adhesive is increased. As shown in FIGS. 1 and 2 and Table 1, it does not sufficiently adhere to the skin groove, resulting in a space between the skin groove and the patch. (Comparative Examples 2 to 5). Furthermore, as shown in FIG. 3 and Table 1, all the adhesives have an extremely large exfoliation amount exceeding 20% (Comparative Examples 2, 2, 2, 3 and 5).
　貼付部位が目立ちにくく、角質細胞剥離量が少ない貼付剤としては、支持体のポリウレタンフィルムが厚み１０μｍ以下で、付加反応型シリコーン系粘着剤層が厚み５～５０μｍの範囲にあることも重要であることがわかる。また、保持力の試験で３０分間以内に落下し、粘着力が０．１Ｎ／１０ｍｍ以下の値を示す粘着剤層を備える貼付剤は、貼付部位が目立ちにくく、角質細胞剥離量が少ない貼付剤であることがわかる。 It is also important for the patch where the applied site is not noticeable and the amount of exfoliated corneocytes is small, that the polyurethane film of the support has a thickness of 10 μm or less and the addition reaction type silicone pressure-sensitive adhesive layer has a thickness in the range of 5 to 50 μm. I understand that. In addition, a patch comprising an adhesive layer that falls within 30 minutes in a retention test and has an adhesive strength of 0.1 N / 10 mm or less is a patch with a less noticeable site and a small amount of exfoliated keratinocytes. It can be seen that it is.
［実施例４］
　付加反応型シリコーン系粘着剤（ダウコーニング社製「７－９８００」　Ａ：Ｂ＝５０：５０）中にビタミンＢ６（ピリドキシン）の２－ヘキシルデカン酸エステルであるトリ２－ヘキシルデカン酸ピリドキシン（日光ケミカルズ株式会社製「ＮＩＫＫＯＬ（登録商標）　ＶＢ６－ＩＰ」）を２重量％混合し、攪拌後、粘着剤層の厚みが２０μｍとなるように塗布したこと以外は、実施例１と同じ方法で貼付剤を作製した。この貼付剤は、皮膚に貼り付けても目立ちにくく（目立ちにくさ：ＡＡＢ）、粘着力（Ｎ／１０ｍｍ）が０．７９（０．０１０）と小さく、保持力が「１３～１７分で落下」であり、角質細胞剥離量（％）が０．２４（０．１４）と極めて少ないものだった。 [Example 4]
Pyridoxine tri-2-hexyldecanoate, a 2-hexyldecanoic acid ester of vitamin B6 (pyridoxine), in an addition reaction type silicone adhesive (“7-9800” manufactured by Dow Corning A: B = 50: 50) (Nikko Chemicals Co., Ltd.) (NIKKOL (registered trademark) VB6-IP) manufactured by the company was mixed at 2% by weight, and after stirring, the patch was applied in the same manner as in Example 1 except that the adhesive layer was applied to a thickness of 20 μm. Produced. This patch is inconspicuous even when applied to the skin (hardness of conspicuity: AAB), adhesive strength (N / 10 mm) is as small as 0.79 (0.010), and the holding power drops in “13-17 minutes” The amount of exfoliated corneocytes (%) was as extremely low as 0.24 (0.14).
［比較例７］
　比較例３で用いたアクリル系粘着剤中に、トリ２－ヘキシルデカン酸ピリドキシン（日光ケミカルズ株式会社製「ＮＩＫＫＯＬ（登録商標）　ＶＢ６－ＩＰ」）を４重量％混合し、攪拌後、粘着剤層の厚みが１０μｍとなるよう塗布したこと以外は、比較例３と同じ方法で貼付剤を作製した。 [Comparative Example 7]
In the acrylic adhesive used in Comparative Example 3, 4% by weight of pyridoxine tri-2-hexyldecanoate (“NIKKOL (registered trademark) VB6-IP” manufactured by Nikko Chemicals Co., Ltd.) was mixed, and after stirring, the adhesive layer A patch was prepared in the same manner as in Comparative Example 3, except that the thickness was 10 μm.
　実施例４及び比較例７の各貼付剤について、薬理活性物質であるトリ２－ヘキシルデカン酸ピリドキシンの放出試験を行った。結果を図４に示す。図中のエラーバーは標準偏差を示す。 For each patch of Example 4 and Comparative Example 7, a release test of pyridoxine tri-2-hexyldecanoate, which is a pharmacologically active substance, was performed. The results are shown in FIG. Error bars in the figure indicate standard deviation.
　図４から、本発明の実施例４の貼付剤では、薬理活性物質を低濃度で含有させても、十分な放出性が示されていることがわかる。これに対し、比較例７の貼付剤では、粘着剤層中の薬理活性物質濃度（４重量％）が実施例４の貼付剤における濃度（２重量％）の２倍であるにもかかわらず、実施例４の貼付剤の約半分程度の放出量しかないことがわかる。 FIG. 4 shows that the patch of Example 4 of the present invention shows sufficient release properties even when a pharmacologically active substance is contained at a low concentration. In contrast, in the patch of Comparative Example 7, the pharmacologically active substance concentration (4% by weight) in the adhesive layer was twice the concentration (2% by weight) in the patch of Example 4, It can be seen that there is only about half the amount of the patch of Example 4.
［実施例５］
　付加反応型シリコーン系粘着剤（ダウコーニング社製「７－９７００」　Ａ：Ｂ＝５０：５０）中にＣｅｒａｍｉｄｅ　ＩＩＩＢ（エボニック デグサ ジャパン 社製のセラミド３）を１重量％混合し、攪拌後、粘着剤層の厚みが３０μｍとなるように塗布したこと以外は、実施例１と同じ方法で貼付剤を作製した。この貼付剤は、皮膚に貼り付けても目立ちにくく（目立ちにくさ：ＡＡＡ）、粘着力（Ｎ／１０ｍｍ）が０．１３（０．０１１）であり、角質細胞剥離量も少なかった。 [Example 5]
1% by weight of Ceramide IIIB (ceramide 3 manufactured by Evonik Degussa Japan) was mixed in an addition reaction type silicone pressure-sensitive adhesive (“7-9700” manufactured by Dow Corning, A: B = 50: 50), stirred, and then adhered. A patch was prepared in the same manner as in Example 1 except that the coating was applied so that the thickness of the agent layer was 30 μm. This patch was inconspicuous even when applied to the skin (hardness of conspicuity: AAA), the adhesive strength (N / 10 mm) was 0.13 (0.011), and the amount of keratinocyte detachment was small.
　本発明の貼付剤は、アトピー性皮膚炎などの様々な皮膚疾患に起因する皮膚患部を覆って保護するほか、皮膚疾患による諸症状の改善や治療のために利用することができる。本発明の貼付剤は、粘着剤層に薬理活性物質を含有させることにより、医薬品または医薬部外品などの用途に適用することができる。本発明の貼付剤は、医療用貼付剤として好適であるが、それに限定されず、保護を必要とする皮膚表面への貼付など、他の用途にも利用することができる。 The patch of the present invention covers and protects skin affected areas caused by various skin diseases such as atopic dermatitis, and can be used for improvement and treatment of various symptoms caused by skin diseases. The patch of the present invention can be applied to uses such as pharmaceuticals or quasi drugs by including a pharmacologically active substance in the adhesive layer. The patch of the present invention is suitable as a medical patch, but is not limited thereto, and can be used for other purposes such as application to the skin surface requiring protection.

Claims (12)

  1. 　支持体の片面に粘着剤層が設けられた層構成を有する貼付剤において、該支持体が、１～１０μｍの範囲内の厚みを持つポリウレタンフィルムであり、該粘着剤層が、５～５０μｍの範囲内の厚みを持つ、側鎖にビニル基を持たないポリオルガノシロキサンからなる付加反応型シリコーン系粘着剤層であって、該貼付剤の透湿度が１５００ｇ／ｍ２・２４ｈｒ超過であることを特徴とする貼付剤。 In a patch having a layer structure in which a pressure-sensitive adhesive layer is provided on one side of a support, the support is a polyurethane film having a thickness in the range of 1 to 10 μm, and the pressure-sensitive adhesive layer has a thickness of 5 to 50 μm. An addition reaction type silicone pressure-sensitive adhesive layer comprising a polyorganosiloxane having a thickness within the range and having no vinyl group in the side chain, wherein the moisture permeability of the patch exceeds 1500 g / m 2 · 24 hr. A characteristic patch.
  2. 　該粘着剤層が、薬理活性物質を粘着剤全量基準で０．０１～７重量％の割合で含有する請求項１記載の貼付剤。 The patch according to claim 1, wherein the adhesive layer contains a pharmacologically active substance in a proportion of 0.01 to 7% by weight based on the total amount of the adhesive.
  3. 　該薬理活性物質が、皮膚角質層に存在する脂質またはその誘導体より選ばれる少なくとも一種の薬理活性物質を含有する請求項２記載の貼付剤。 The patch according to claim 2, wherein the pharmacologically active substance contains at least one pharmacologically active substance selected from lipids or derivatives thereof present in the skin stratum corneum.
  4. 　該薬理活性物質が、脂溶性ビタミン及び水溶性ビタミン並びにそれらの誘導体からなる群より選ばれる少なくとも一種の薬理活性物質を含有する請求項２記載の貼付剤。 The patch according to claim 2, wherein the pharmacologically active substance contains at least one pharmacologically active substance selected from the group consisting of fat-soluble vitamins, water-soluble vitamins and derivatives thereof.
  5. 　該支持体の粘着剤層に接する面に、シラン系プライマーの塗布層が配置されている請求項１記載の貼付剤。 The patch according to claim 1, wherein a coating layer of a silane primer is disposed on a surface of the support that contacts the pressure-sensitive adhesive layer.
  6. 　該支持体の粘着剤層と反対側の表面に、キャリアフィルムが配置されている請求項１記載の貼付剤。 The patch according to claim 1, wherein a carrier film is disposed on the surface of the support opposite to the pressure-sensitive adhesive layer.
  7. 　該キャリアフィルムが、離型処理されたポリエステルフィルムである請求項６記載の貼付剤。 The patch according to claim 6, wherein the carrier film is a release-treated polyester film.
  8. 　該粘着剤層の支持体と反対側の表面に、剥離ライナーが配置されている請求項１記載の貼付剤。 The patch according to claim 1, wherein a release liner is disposed on the surface of the pressure-sensitive adhesive layer opposite to the support.
  9. 　該剥離ライナーが、離型処理されたポリエステルフィルムである請求項８記載の貼付剤。 The patch according to claim 8, wherein the release liner is a polyester film subjected to a release treatment.
  10. 　ヒト前腕内側の皮膚表面に６時間貼付後、剥離したときに、貼付面積に対する角質細胞剥離面積が２０％以下である請求項１記載の貼付剤。 2. The patch according to claim 1, wherein when the skin is peeled after being applied to the skin surface inside the human forearm for 6 hours and then peeled, the keratinocyte peeling area relative to the sticking area is 20% or less.
  11. 　皮膚掻破防止用貼付剤である請求項１記載の貼付剤。 The patch according to claim 1, which is a patch for preventing skin scratching.
  12. 　患部を含む皮膚表面に貼付して、皮膚患部の直接掻破を防止する請求項１記載の貼付剤の使用。 The use of the patch according to claim 1, which is applied to the skin surface including the affected part to prevent direct scratching of the affected part of the skin.
PCT/JP2011/060373 2010-04-30 2011-04-28 Adhesive patch and use thereof WO2011136330A1 (en)

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JP7069042B2 (en) 2016-12-28 2022-05-17 久光製薬株式会社 Patch
JP7366166B2 (en) 2016-12-28 2023-10-20 久光製薬株式会社 patch
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