WO2014200072A1 - 皮膚貼付用粘着シートおよびそれを用いた経皮吸収製剤 - Google Patents
皮膚貼付用粘着シートおよびそれを用いた経皮吸収製剤 Download PDFInfo
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- WO2014200072A1 WO2014200072A1 PCT/JP2014/065637 JP2014065637W WO2014200072A1 WO 2014200072 A1 WO2014200072 A1 WO 2014200072A1 JP 2014065637 W JP2014065637 W JP 2014065637W WO 2014200072 A1 WO2014200072 A1 WO 2014200072A1
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- sensitive adhesive
- adhesive sheet
- adhesive layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/325—Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
Definitions
- the present invention relates to a pressure-sensitive adhesive sheet for skin application having sufficient adhesiveness and low skin irritation, and a transdermal absorption preparation having low skin irritation and improved drug release.
- a drug When a drug is to be absorbed through the skin, the drug is mixed with an adhesive base to form a patch.
- an adhesive base As the adhesive base of this tape agent, a lipophilic adhesive base such as rubber, acrylic or silicone is used. Among them, rubber-based adhesive bases are widely used because additives can be easily blended as compared with other adhesive bases (Patent Documents 1 to 3).
- JP 2001-302502 A JP-A-9-291028 Japanese Patent Laid-Open No. 10-316559 WO2012 / 029325
- An object of the present invention is to provide an adhesive sheet for skin application having a sufficient variety of adhesive properties and low skin irritation, and further, transdermal absorption having low skin irritation, sufficient adhesive properties and sufficient drug release properties. It is to provide a formulation.
- the present inventors have obtained a mixture of a triblock copolymer and a diblock copolymer as an adhesive base, and the diblock copolymer in the mixture.
- a thermoplastic elastomer having a coalescence content of 20% by weight or more and a large amount of non-volatile hydrocarbon oil for the elastomer, it has sufficient various adhesive properties without containing a tackifier. It was found that an adhesive sheet for skin application having low skin irritation was obtained. Furthermore, it has been found that a transdermally absorbable preparation having sufficient drug releasability can be obtained by containing a drug or a pharmaceutically acceptable salt thereof in the pressure-sensitive adhesive sheet.
- a pressure-sensitive adhesive sheet for skin application wherein a pressure-sensitive adhesive layer is formed on a support,
- the pressure-sensitive adhesive layer At least a thermoplastic elastomer, and more than 50 parts by weight and less than 800 parts by weight of non-volatile hydrocarbon oil with respect to 100 parts by weight of the elastomer
- a pressure-sensitive adhesive sheet for skin application wherein the thermoplastic elastomer is a mixture of a triblock copolymer and a diblock copolymer, and the content of the diblock copolymer in the mixture is 20% by weight or more.
- the pressure-sensitive adhesive layer may further contain a tackifier, and the content of the tackifier in the pressure-sensitive adhesive layer is 20% by weight or less, and any one of the above [1] to [8] The adhesive sheet for skin sticking as described in one.
- the adhesive sheet for skin application of the present invention has sufficient adhesive properties when applied to the skin and has low skin irritation. Moreover, the transdermally absorbable preparation of the present invention has good drug release properties.
- the pressure-sensitive adhesive sheet for skin application and the transdermally absorbable preparation of the present invention have a pressure-sensitive adhesive layer provided on a support, and the pressure-sensitive adhesive layer contains 50 parts by weight of thermoplastic elastomer, 100 parts by weight of the elastomer. More than 800 parts by weight of non-volatile hydrocarbon oil and the thermoplastic elastomer is a mixture of a triblock copolymer and a diblock copolymer, and the content of the diblock copolymer in the mixture Is 20% by weight or more.
- thermoplastic elastomer used in the pressure-sensitive adhesive layer of the present invention is an elastomer that exhibits fluidity when softened and exhibits fluidity, and returns to a rubber-like elastic body when cooled.
- various thermoplastic elastomers such as styrene and olefin.
- the thermoplastic elastomer is a mixture of a triblock copolymer and a diblock copolymer, A mixture in which the content of the diblock copolymer in the mixture is 20% by weight or more is used.
- the mixing ratio of the diblock copolymer is preferably 20/80 to 75/25, more preferably 30/70 to 70/30, by weight.
- the solution viscosity at 25 ° C. of a 25 wt% toluene solution of a thermoplastic elastomer is 0.5 Pa ⁇ s or more. Preferably, it is 0.7 Pa ⁇ s or more, more preferably 0.9 Pa ⁇ s or more.
- the upper limit of the solution viscosity is not particularly limited, but is preferably 2.0 Pa ⁇ s or less, more preferably 1.8 Pa ⁇ s or less.
- toluene solution refers to the styrene / isoprene / styrene block copolymer described on page 375 of “Pharmaceutical Additive Standard 2003” (published by Yakuji Nippo). It is the value measured based on the viscosity measuring method.
- a styrene thermoplastic elastomer particularly a styrene block copolymer
- thermoplastic elastomer is preferably used as the thermoplastic elastomer.
- styrene block copolymers include styrene-butadiene block copolymers, styrene-butadiene-styrene block copolymers, styrene-isoprene block copolymers, styrene-isoprene-styrene block copolymers, and styrene.
- ethylene / butylene represents a copolymer block of ethylene and butylene
- ethylene / propylene represents a copolymer block of ethylene and propylene
- styrenic block copolymers may be used in combination of three or more as long as the mixing ratio of the above triblock copolymer and diblock copolymer. That is, one type or two or more types of triblock copolymers and diblock copolymers can be used.
- styrene-isoprene-styrene block copolymers and styrene are used from the viewpoints of sufficient skin adhesiveness and low skin irritation, as well as availability and handling properties of patch products.
- -Mixtures containing isoprene block copolymers are preferably used.
- the styrene-isoprene-styrene block copolymer preferably has a styrene content of 5 wt% to 60 wt% in the copolymer, and has a styrene content of 10 wt% to 50 wt%. More preferred. Further, those having a weight average molecular weight measured by gel filtration chromatography of 20,000 to 500,000 are preferred, and those having a weight average molecular weight of 30,000 to 300,000 are more preferred.
- the styrene-isoprene block copolymer preferably has a styrene content of 5 to 50% by weight, more preferably 10 to 40% by weight.
- styrene-isoprene-styrene block copolymer and styrene-isoprene block copolymer preferably has a weight average molecular weight of 20,000 to 500,000 as measured by gel filtration chromatography, and is 30,000. More preferred are those of up to 300,000.
- styrene-isoprene-styrene block copolymer and the styrene-isoprene block copolymer copolymers produced by a method known per se can be used.
- styrene-isoprene-styrene block copolymer and the styrene-isoprene block copolymer commercially available products that satisfy the above characteristics can be used.
- a mixture of a styrene-isoprene-styrene block copolymer and a styrene-isoprene block copolymer is also commercially available.
- a styrene-isoprene-styrene block copolymer and a styrene-isoprene block copolymer satisfying the above characteristics Can be suitably used as a commercial product of a mixture in which is mixed at the above mixing ratio.
- the thermoplastic elastomer content in the adhesive layer of the patch of the present invention is preferably 8% by weight or more, more preferably 10% by weight or more, still more preferably 12% by weight or more, and further preferably 15% by weight. More preferably, it is 18% by weight or more, particularly preferably 20% by weight or more, particularly preferably 24% by weight or more, and most preferably 28% by weight or more. Moreover, 66 weight% or less is preferable, More preferably, it is 65 weight% or less, More preferably, it is 64 weight% or less, More preferably, it is 49 weight% or less, More preferably, it is 39 weight% or less.
- thermoplastic elastomer content in the pressure-sensitive adhesive layer can be 8 wt% to 66 wt%, more preferably 10 wt% to 65 wt%, particularly preferably 12 wt%. % By weight to 64% by weight.
- the pressure-sensitive adhesive layer contains a nonvolatile hydrocarbon oil.
- the non-volatile hydrocarbon oil is preferably a chain saturated hydrocarbon having about 20 to 40 carbon atoms or a chain unsaturated hydrocarbon having about 20 to 40 carbon atoms, such as liquid paraffin, squalene, squalane, pristane, etc. Can be mentioned. Among these, liquid paraffin is more preferable from the viewpoint of easy availability.
- the liquid paraffin is a colorless and odorless liquid mixture of alkanes having 20 or more carbon atoms.
- a liquid paraffin that conforms to the standards prescribed in the Japanese Pharmacopoeia, the US Pharmacopoeia, and the like can be preferably used.
- the non-volatile hydrocarbon oil preferably has a high viscosity, and it is particularly preferable to use liquid paraffin having a high viscosity from the viewpoint of stickiness.
- the non-volatile hydrocarbon oil preferably has a kinematic viscosity at 40 ° C. of 60 mm 2 / s or more, more preferably 70 mm 2 / s or more, still more preferably 80 mm 2 / s or more, particularly preferably. 100 mm 2 / s or more.
- the upper limit of kinematic viscosity is not specifically limited, For example, 500 mm ⁇ 2 > / s or less is preferable and 250 mm ⁇ 2 > / s or less is more preferable from viewpoints of the ease of handling, availability, etc.
- “Kinematic viscosity” as used herein refers to “Method 2 rotational viscometer (2.12 single cylinder rotational viscometer (Brooks)” in “2.53 Viscosity measurement method” of the general test method of “16th revised Japanese Pharmacopoeia”. This is a value obtained by converting the viscosity (mPa ⁇ s) measured in accordance with “field type viscometer” (page 59) into kinematic viscosity.
- the pressure-sensitive adhesive sheet for skin application and the transdermally absorbable preparation of the present invention contain the above-described nonvolatile hydrocarbon oil in a weight ratio of more than 50 parts by weight and not more than 800 parts by weight with respect to 100 parts by weight of the thermoplastic elastomer. .
- the content of the non-volatile hydrocarbon oil with respect to 100 parts by weight of the thermoplastic elastomer exceeds 800 parts by weight, it becomes difficult to maintain the shape of the pressure-sensitive adhesive layer.
- the content of the non-volatile hydrocarbon oil is 50 parts by weight or less, there is a tendency that sufficient adhesiveness to the skin cannot be obtained due to the adhesive becoming too hard, particularly following the movement of the skin at the time of application.
- the content of the nonvolatile hydrocarbon oil in the pressure-sensitive adhesive layer is preferably 51 parts by weight to 800 parts by weight, more preferably 60 parts by weight to 600 parts by weight with respect to 100 parts by weight of the thermoplastic elastomer. Particularly preferred is 70 to 500 parts by weight.
- a non-volatile hydrocarbon oil having a low kinematic viscosity such as 40% by weight, for a thermoplastic elastomer having a low solution viscosity at 25 ° C. in a 25 wt% toluene solution, particularly less than 0.5 Pa ⁇ s.
- a material having a kinematic viscosity at 80 ° C. of less than 80 mm 2 / s if the content of the non-volatile hydrocarbon oil is large, the adhesive sticks out at the time of storage or sticking and adheres to the packaging material or clothes. It tends to come out.
- the content of the nonvolatile hydrocarbon oil in the pressure-sensitive adhesive layer is preferably 51 parts by weight to 300 parts by weight, more preferably 60 parts by weight to 250 parts by weight, with respect to 100 parts by weight of the thermoplastic elastomer. Particularly preferred is 70 to 200 parts by weight.
- the content of the non-volatile hydrocarbon oil in the pressure-sensitive adhesive layer is preferably 23.5% by weight or more, more preferably 25% by weight or more, still more preferably 26.5% by weight or more, and further preferably 35% by weight. % Or more, still more preferably 45% by weight or more, particularly preferably 50% by weight or more. Moreover, 88 weight% or less is preferable, More preferably, it is 85 weight% or less, More preferably, it is 83 weight% or less, More preferably, it is 70 weight% or less, More preferably, it is 68 weight% or less.
- the pressure-sensitive adhesive layer contains a thermoplastic elastomer and a non-volatile hydrocarbon oil in the content and content ratio as described above.
- the pressure-sensitive adhesive layer may contain a tackifier as necessary.
- the tackifier is a resin generally used for imparting skin adhesiveness in the field of patches, and includes, for example, rosin resins, polyterpene resins, coumarone-indene resins, petroleum resins, terpene-phenols. Examples thereof include resins and alicyclic saturated hydrocarbon resins, and one or more of them can be selected and used.
- the content of the tackifier in the pressure-sensitive adhesive layer is preferably 20% by weight or less from the viewpoint of reducing skin irritation.
- the content is preferably 10% by weight or less, more preferably 5% by weight or less, still more preferably 2% by weight or less, and most preferably no tackifier. That is, the content of the tackifier is related to the type, content, and content ratio of the thermoplastic elastomer and the non-volatile hydrocarbon oil, in relation to the skin adhesiveness of the adhesive sheet for skin application and the transdermally absorbable preparation. Accordingly, if sufficient skin adhesiveness can be obtained without containing a tackifier, the tackifier is unnecessary.
- a transdermally absorbable preparation can be obtained by further containing a drug or a pharmaceutically acceptable salt thereof in the adhesive layer of the adhesive sheet for skin application.
- drug or a pharmaceutically acceptable salt thereof refers to a drug or a salt thereof used for percutaneous absorption, and is not particularly limited.
- the drug include acetaminophen, phenacetin, mefenamic acid, diclofenac sodium, flufenamic acid, aspirin, sodium salicylate, methyl salicylate, glycol salicylate, aminopyrine, alclofenac, ibuprofen, naproxen, flurbiprofen, ketoprofen, sodium amfenac,
- Anti-inflammatory analgesics such as mepyrizole, indomethacin, piroxicam, felbinac; steroidal anti-inflammatory drugs such as hydrocortisone, triamcinolone, dexamethasone, prednisolone; diltiazem hydrochloride, pentaerythritol tetranitrate, isosorbide nitrate, taradipyl, nicor
- the content of the drug or pharmaceutically acceptable salt thereof in the transdermally absorbable preparation is not particularly limited, but preferably 1% by weight or more in the pressure-sensitive adhesive layer in view of dispersibility and drug release in the pressure-sensitive adhesive layer. 30% by weight, more preferably 2.5% by weight to 25% by weight, and most preferably 4% by weight to 20% by weight. In consideration of the peel resistance of the patch during bathing, it is preferably 15% by weight or less.
- the pressure-sensitive adhesive sheet for skin application and the transdermally absorbable preparation of the present invention are constituted by spreading a pressure-sensitive adhesive layer having the above-described structure on a support.
- the “support” in the present invention is not particularly limited, and a general-purpose one can be used.
- Examples thereof include stretchable or non-stretchable woven fabrics such as polyethylene and polypropylene, nonwoven fabrics, polyethylene, polypropylene, ethylene vinyl acetate copolymers, films such as vinyl chloride, and foamable supports such as urethane and polyurethane. These may be used alone, or may be used as a laminate of a plurality of types.
- a non-woven fabric or a woven fabric containing an antistatic agent can be used for preventing static electricity from accumulating on the support and for good anchoring properties with the adhesive layer.
- the percutaneous absorption preparation of the present invention may contain excipients, antioxidants, fragrances, coloring agents and the like as optional components.
- Excipients include, for example, silicon compounds such as silicic anhydride, light anhydrous silicic acid, hydrous silicic acid, cellulose derivatives such as ethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, water-soluble polymers such as polyvinyl alcohol, Examples include aluminum compounds such as dry aluminum hydroxide gel and hydrous aluminum silicate, kaolin, and titanium oxide.
- antioxidants examples include dibutylhydroxytoluene, ascorbic acid, tocopherol, tocopherol ester derivatives, butylhydroxyanisole, 2-mercaptobenzimidazole and the like.
- Liquid paraffin (“BENOL”, “KAYDOL”, “Hydrobrite 550PO”, “Hydrobrite HV” manufactured by Soneborn, Inc.) was added to the solution and mixed and stirred to prepare a coating solution for forming an adhesive layer.
- “D1111” is an abbreviation for “KRATON D1111”
- “D1119” is an abbreviation for “KRATON D1119”
- QTC3520” is an abbreviation for “Quintac3520”
- 5505 is an abbreviation for “JSR SIS5505”
- 5229 is Abbreviation for “JSR SIS 5229”.
- the coating solution was applied to a silicone-treated polyethylene terephthalate (PET) film (release liner), and the pressure-sensitive adhesive layer after drying was prepared to be about 300 ⁇ m. After drying in an oven at 80 ° C. for 1 hour, a PET film (support) was laminated on the surface of the pressure-sensitive adhesive layer, and cut into a size of 15 cm ⁇ 30 cm to obtain a target pressure-sensitive adhesive sheet.
- the SIS / SI ratio in the table is a weight ratio.
- each component constituting the pressure-sensitive adhesive layer was weighed and a sheet was prepared by the above method. However, for Comparative Example 3, sufficient tackiness was obtained. As for Comparative Example 4, the pressure-sensitive adhesive layer could not be maintained and could not be evaluated.
- Adhesive property test ⁇ Peel strength> The pressure-sensitive adhesive sheet cut to 25 mm ⁇ 100 mm was attached to a stainless steel (SUS304) plate, and the stress when peeled at a speed of 300 mm / min in the 180 ° direction was measured.
- ⁇ Ball tack> Roll the ball of 1/32 inch to 1 inch through the 100 mm runway on the slope with an inclination angle of 30 ° to which the adhesive sheet cut at 100 mm width is affixed. The nominal diameter was measured.
- ⁇ Evaluation criteria for skin irritation> [Formation of erythema and crust] No erythema; 0 points Very mild (barely discernable) erythema; 1 point Clear erythema; 2 points Moderate to high erythema; 3 points Marking erythema from high erythema 4 points [formation of edema] No edema; 0 points Very mild (barely discernable) edema; 1 point Mild edema (distinguishes distinct edges due to clear bulges); 2 points Moderate edema (about 1 point bulges); 3 points Advanced edema (bulges greater than 1 mm and spread beyond the exposure range); 4 points
- each pressure-sensitive adhesive sheet of the examples of the present invention exhibited moderate pressure-sensitive adhesive properties equal to or higher than those of commercially available patches, although the pressure-sensitive adhesive properties were low with respect to silicone pressure-sensitive adhesive sheets. .
- the skin irritation was low.
- high tackiness was exhibited.
- Liquid paraffin (“BENOL”, “KAYDOL”, “Hydrobrite 550PO”, “Hydrobrite HV” manufactured by Soneborn), various additives and chemicals are added to the solution, and the mixture is mixed and stirred. A liquid was prepared.
- “D1111” is an abbreviation for “KRATON D1111”
- “D1119” is an abbreviation for “KRATON D1119”
- “QTC3520” is an abbreviation for “Quintac3520”
- 5505 is an abbreviation for “JSR SIS5505”
- 5229 is Abbreviation for “JSR SIS 5229”.
- the coating solution was applied to a silicone-treated polyethylene terephthalate (PET) film (release liner) and prepared such that the rivastigmine content in the pressure-sensitive adhesive layer after drying was 1.8 mg / cm 2 .
- PET polyethylene terephthalate
- a PET film (support) was laminated on the surface of the pressure-sensitive adhesive layer and cut into a size of 15 cm ⁇ 30 cm to obtain the intended transdermally absorbable preparation.
- the SIS / SI ratio in the table is a weight ratio.
- Comparative Examples 6 and 7 according to the formulation shown in Table 4, each component constituting the pressure-sensitive adhesive layer was weighed and a percutaneous absorption preparation was prepared by the above-described method. In Comparative Example 7, the pressure-sensitive adhesive layer could not be maintained and could not be evaluated.
- each of the transdermally absorbable preparations of the examples of the present invention showed a drug release ability equivalent to or higher than that of a commercially available transdermally absorbable preparation, and had low skin irritation and excellent adhesive properties. It became clear to show.
- the pressure-sensitive adhesive sheet for skin application of the present invention has low skin irritation and moderate pressure-sensitive adhesiveness, and the transdermal absorption preparation using this has excellent drug release properties while maintaining this. There is a possibility that it can be used to improve the performance of existing transdermal absorption preparations and to develop new transdermal absorption preparations.
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Abstract
Description
このような状況下、本発明者らは、熱可塑性エラストマーと該エラストマーに対して多量の流動パラフィンを用いることで、粘着付与剤を含有しなくても、十分な粘着性を有しつつ皮膚刺激性が低い皮膚貼付用粘着シート、および、当該粘着シートに薬物又はその薬学的に許容し得る塩を含有させることで十分な経皮吸収性を有する経皮吸収製剤が得られることを見出した(特許文献4)。しかしながら、特に使用する熱可塑性エラストマーや流動パラフィンの限定がないため、処方によっては粘着物性が不足する場合があった。
[1] 支持体上に粘着剤層が形成された皮膚貼付用粘着シートであって、
該粘着剤層は、
少なくとも熱可塑性エラストマー、および
該エラストマー100重量部に対して50重量部を超え、800重量部以下の不揮発性炭化水素油を含み、
該熱可塑性エラストマーがトリブロック共重合体とジブロック共重合体との混合物であって、混合物中のジブロック共重合体の含有量が20重量%以上である、皮膚貼付用粘着シート。
[2] 熱可塑性エラストマーの25重量%トルエン溶液の25℃における溶液粘度が0.5Pa・s以上である、上記[1]に記載の皮膚貼付用粘着シート。
[3] 熱可塑性エラストマーがスチレン系ブロック共重合体である、上記[1]または[2]に記載の皮膚貼付用粘着シート。
[4] スチレン系ブロック共重合体がスチレン-イソプレン-スチレンブロック共重合体とスチレン-イソプレンブロック共重合体との混合物である、上記[3]に記載の皮膚貼付用粘着シート。
[5] 混合物中のジブロック共重合体の含有量が30重量%以上である、上記[1]~[4]のいずれか1つに記載の皮膚貼付用粘着シート。
[6] 熱可塑性エラストマーの25重量%トルエン溶液の25℃における溶液粘度が、0.7Pa・s以上である、上記[2]~[5]のいずれか1つに記載の皮膚貼付用粘着シート。
[7] 不揮発性炭化水素油の40℃における動粘度が80mm2/s以上である、上記[1]~[6]のいずれか1つに記載の皮膚貼付用粘着シート。
[8] 粘着剤層中の不揮発性炭化水素油の含有量が23.5重量%以上、88重量%以下である、上記[1]~[7]のいずれか1つに記載の皮膚貼付用粘着シート。
[9] 粘着剤層は、さらに粘着付与剤を含んでいてもよく、該粘着付与剤の粘着剤層中の含有量が20重量%以下である、上記[1]~[8]のいずれか1つに記載の皮膚貼付用粘着シート。
[10] 粘着剤層中の粘着付与剤の含有量が10重量%以下である、上記[9]に記載の皮膚貼付用粘着シート。
[11] 粘着剤層中に粘着付与剤を含まない、上記[1]~[8]のいずれか1つに記載の皮膚貼付用粘着シート。
[12] 上記[1]~[11]のいずれか一つに記載の粘着シートの粘着剤層に、薬物またはその薬学的に許容し得る塩を含有せしめてなる経皮吸収製剤。
なお、ここでいう、「25重量%トルエン溶液の25℃における溶液粘度」とは、「医薬品添加物規格2003」(薬事日報社発行)の375頁に記載のスチレン・イソプレン・スチレンブロック共重合体の粘度測定方法に基づいて測定された値である。
ここでいう「動粘度」とは、「第十六改正日本薬局方」の一般試験法の「2.53粘度測定法」における「第2法 回転粘度計法(2.12 単一円筒形回転粘度計(ブルックフィールド型粘度計)」(59頁)に準拠して測定した粘度(mPa・s)を動粘度に換算した値である。
表1に示す処方に従って、粘着剤層を構成する各成分を秤取した。まず、スチレン-イソプレン-スチレンブロック共重合体(SIS)/スチレン-イソプレンブロック共重合体(SI)混合物(KRATON POLYMERS社製「KRATON D1111」、「KRATON D1119」、日本ゼオン社製「Quintac3520」、JSR社製「JSR SIS5505」、「JSR SIS5229」)を、当該混合物100重量部に対し、230重量部のトルエンに溶解した。前記溶解液に、流動パラフィン(ソネボーン社製の「BENOL」「KAYDOL」、「Hydrobrite 550PO」、「Hydrobrite HV」)を加えて混合撹拌し、粘着剤層形成用の塗液を調製した。表中の「D1111」は「KRATON D1111」の略記、「D1119」は「KRATON D1119」の略記、「QTC3520」は「Quintac3520」の略記、「5505」は「JSR SIS5505」の略記、「5229」は「JSR SIS5229」の略記である。
上記塗液をシリコーン処理したポリエチレンテレフタレート(PET)製フィルム(剥離ライナー)に塗布し、乾燥後の粘着剤層が約300μmとなるように調製した。80℃のオーブンにて1時間乾燥後、該粘着剤層の表面にPET製フィルム(支持体)をラミネートし、15cm×30cmの大きさに裁断して、目的の粘着シートを得た。表中のSIS/SI比は重量比である。
なお、比較例3、4に関しては、表1に示す処方に従って、粘着剤層を構成する各成分を秤取し上記方法でシートを調製したが、比較例3に関しては、十分な粘着性が得られず、比較例4に関しては粘着剤層が維持できず、評価できなかった。
国際公開第2007/064407号公報の実施例の方法に準じて、乾燥後の組成が、シリコーン粘着剤(ダウコーニング製、「Bio-PSA Q7-4301」)98.9重量%、シリコーンオイル1.0重量%、ビタミンE0.1重量%となるように塗工液を調製し、乾燥後の単位面積当たりの重量が90g/m2となるように、テフロン処理したポリエチレンテレフタレート(PET)製フィルム(剥離ライナー)に塗工、乾燥した。
該粘着剤層の表面にPET製フィルム(支持体)をラミネートし、15cm×30cmの大きさに裁断して、目的の粘着シートを得た。
<剥離強度>
25mm×100mmに裁断した粘着シートをステンレス(SUS304)板に貼付し、180°方向に300mm/minのスピードで剥離した際の応力を測定した。
<ボールタック>
100mm幅で裁断した粘着シートを貼付した傾斜角30°の斜面において、100mmの助走路を経て1/32インチ~1インチのボールを転がして、粘着シート上で5秒以上留まった最大のボールの呼び径を測定した。
<保持力>
25mm×100mmに裁断した粘着シートをステンレス(SUS304)板に貼付し、90°方向に25gの荷重を60分間掛け、剥離した距離を測定した。
<はみ出し>
実施例および比較例で調製した粘着シートの端部を、支持体の上から指先で圧縮し、はみ出しの度合いを下記基準に従って評価した。
A:圧縮しても、粘着剤層は全くはみ出さない。
B:圧縮しても、粘着剤層がほとんどはみ出さない。
C:圧縮時、粘着剤層が変形して支持体からはみ出すが、圧縮を開放すると元に戻る。
D:圧縮時、粘着剤層が変形して支持体からはみ出し、圧縮を開放しても元に戻りにくい。
<入浴時剥離の程度>
実施例および比較例で調製した粘着シートを直径36mmの円形に打抜き、健常ボランティア5名の胸部に貼付し、入浴時の剥離の度合いを下記基準に従って評価した。
A:5名とも剥離しない。
B:1~2名に端部の剥離が見られるものの、脱落はしない。
C:1~2名で粘着シートが脱落。
D:3名以上で脱落。
貼付開始日の3日前にkbs:JW雌性家兎(17週齢)の背部被毛を電気バリカンで毛刈りし、実施例1の粘着シートと市販のリバスチグミン含有貼付剤をそれぞれ2.5cm角に裁断して皮膚に貼付した(n=3)。貼付場所を覆うように油紙を載せ、胸部から腹部全体にかけてアンダーラップテープ(ニチバン株式会社製)で覆うように巻き付け、さらに家兎用ジャケット(BJ03、バイオリサーチセンター株式会社製)を装着した。24時間固定後、試料を除去し、除去後1時間目、24時間目、48時間目、および72時間目にJ.Pharmacol.Exp.Ther.82,377-390(1944)に記載の方法に基き、皮膚刺激反応の程度を評価した。
[紅斑および痂皮の形成]
紅斑を認めない;0点
非常に軽度な(かろうじて識別できる程度の)紅斑を認める;1点
明確な紅斑を認める;2点
中等度ないし高度の紅斑を認める;3点
高度の紅斑から紅斑の採点を妨げる程度の痂皮の形成を認める;4点
[浮腫の形成]
浮腫を認めない;0点
非常に軽度な(かろうじて識別できる程度の)浮腫を認める;1点
軽度の浮腫を認める(はっきりした膨隆による明確な縁が識別できる);2点
中等度の浮腫(約1mmの膨隆)を認める;3点
高度の浮腫(1mm以上の膨隆と曝露範囲を超えた広がり)を認める;4点
表4に示す処方に従って、粘着剤層を構成する各成分を秤取した。まず、スチレン-イソプレン-スチレンブロック共重合体(SIS)/スチレン-イソプレンブロック共重合体(SI)混合物(KRATON POLYMERS社製「KRATON D1111」、「KRATON D1119」、日本ゼオン社製「Quintac3520」、JSR社製「JSR SIS5505」、「JSR SIS5229」)を、当該混合物100重量部に対し、230重量部のトルエンに溶解した。前記溶解液に、流動パラフィン(ソネボーン社製の「BENOL」、「KAYDOL」、「Hydrobrite 550PO」、「Hydrobrite HV」)、各種添加剤および薬剤を加えて混合撹拌し、粘着剤層形成用の塗液を調製した。表中の「D1111」は「KRATON D1111」の略記、「D1119」は「KRATON D1119」の略記、「QTC3520」は「Quintac3520」の略記、「5505」は「JSR SIS5505」の略記、「5229」は「JSR SIS5229」の略記である。
比較例6、7に関しては、表4に示す処方に従って、粘着剤層を構成する各成分を秤取し上記方法で経皮吸収製剤を調製したが、比較例6に関しては、十分な粘着性が得られず、比較例7に関しては粘着剤層が維持できず、評価できなかった。
国際公開第2006/093139号公報に記載された方法に準じて、Wister系雄性ラット(5週齢)の腹部抽出皮膚を縦型フランツ拡散セルに装着した。実施例9~21の各経皮吸収製剤および市販の経皮吸収製剤をそれぞれ面積1.0cm2の円形に打ち抜いて試料とし、拡散セルのラット皮膚上に貼付した(n=3)。レセプター側には10体積%エタノール生理食塩水を用いて、経時的にレセプター溶液中のリバスチグミン含有量を、高速液体クロマトグラフィー(HPLC)により定量した。
試料貼付後24時間にラット皮膚を透過した薬剤量を求めた。
Claims (12)
- 支持体上に粘着剤層が形成された皮膚貼付用粘着シートであって、
該粘着剤層は、
少なくとも熱可塑性エラストマー、および
該エラストマー100重量部に対して50重量部を超え、800重量部以下の不揮発性炭化水素油を含み、
該熱可塑性エラストマーがトリブロック共重合体とジブロック共重合体との混合物であって、混合物中のジブロック共重合体の含有量が20重量%以上である、皮膚貼付用粘着シート。 - 熱可塑性エラストマーの25重量%トルエン溶液の25℃における溶液粘度が0.5Pa・s以上である、請求項1に記載の皮膚貼付用粘着シート。
- 熱可塑性エラストマーがスチレン系ブロック共重合体である、請求項1または2に記載の皮膚貼付用粘着シート。
- スチレン系ブロック共重合体がスチレン-イソプレン-スチレンブロック共重合体とスチレン-イソプレンブロック共重合体との混合物である、請求項3に記載の皮膚貼付用粘着シート。
- 混合物中のジブロック共重合体の含有量が30重量%以上である、請求項1~4のいずれか1項に記載の皮膚貼付用粘着シート。
- 熱可塑性エラストマーの25重量%トルエン溶液の25℃における溶液粘度が、0.7Pa・s以上である、請求項2~5のいずれか1項に記載の皮膚貼付用粘着シート。
- 不揮発性炭化水素油の40℃における動粘度が80mm2/s以上である、請求項1~6のいずれか1項に記載の皮膚貼付用粘着シート。
- 粘着剤層中の不揮発性炭化水素油の含有量が23.5重量%以上、88重量%以下である、請求項1~7のいずれか1項に記載の皮膚貼付用粘着シート。
- 粘着剤層は、さらに粘着付与剤を含んでいてもよく、該粘着付与剤の粘着剤層中の含有量が20重量%以下である、請求項1~8のいずれか1項に記載の皮膚貼付用粘着シート。
- 粘着剤層中の粘着付与剤の含有量が10重量%以下である、請求項9記載の皮膚貼付用粘着シート。
- 粘着剤層中に粘着付与剤を含まない、請求項1~8のいずれか1項に記載の皮膚貼付用粘着シート。
- 請求項1~11のいずれか1項に記載の粘着シートの粘着剤層に、薬物またはその薬学的に許容し得る塩を含有せしめてなる経皮吸収製剤。
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PL14810664T PL3040068T3 (pl) | 2013-06-12 | 2014-06-12 | Arkusz samoprzylepny do zastosowania na skórę i kompozycja o absorpcji przezskórnej zastosowana w nim |
SI201431910T SI3040068T1 (sl) | 2013-06-12 | 2014-06-12 | Adhezivna folija za uporabo na koži in perkutani absorpcijski preparat, ki jo uporablja |
US14/897,641 US20160206568A1 (en) | 2013-06-12 | 2014-06-12 | Adhesive sheet for application to the skin, and percutaneous absorption preparation using same |
EP14810664.4A EP3040068B1 (en) | 2013-06-12 | 2014-06-12 | Adhesive sheet for application to the skin, and percutaneous absorption preparation using same |
JP2015522865A JP6427733B2 (ja) | 2013-06-12 | 2014-06-12 | 皮膚貼付用粘着シートおよびそれを用いた経皮吸収製剤 |
ES14810664T ES2897696T3 (es) | 2013-06-12 | 2014-06-12 | Hoja adhesiva para aplicación sobre la piel y preparación de absorción percutánea que utiliza la misma |
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US16/819,408 Division US20200214991A1 (en) | 2013-06-12 | 2020-03-16 | Adhesive sheet for application to the skin, and percutaneous absorption preparation using same |
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JP2019014694A (ja) * | 2017-07-10 | 2019-01-31 | 株式会社セニースタジオ | カプサイシンを含む熱可塑性エラストマーゲル組成物を使用したダイエット用パッチ |
JP2021130693A (ja) * | 2015-12-10 | 2021-09-09 | 株式会社 ケイ・エム トランスダーム | 経皮吸収製剤 |
WO2023022097A1 (ja) * | 2021-08-17 | 2023-02-23 | 株式会社カネカ | 貼付剤、及びその製造方法 |
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KR20200138229A (ko) * | 2018-04-03 | 2020-12-09 | 니폰 제온 가부시키가이샤 | 비수계 이차 전지 기능층용 조성물, 비수계 이차 전지 부재, 및 비수계 이차 전지 |
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US20200214991A1 (en) | 2020-07-09 |
JPWO2014200072A1 (ja) | 2017-02-23 |
US20160206568A1 (en) | 2016-07-21 |
EP3040068A4 (en) | 2017-03-22 |
JP6427733B2 (ja) | 2018-11-28 |
SI3040068T1 (sl) | 2021-12-31 |
PL3040068T3 (pl) | 2022-01-10 |
JP2018172420A (ja) | 2018-11-08 |
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