JP5878715B2 - Patch - Google Patents

Description

  The present invention relates to a patch.

  Various methods such as oral administration, rectal administration, intradermal administration, intravenous administration and the like have been conventionally known as drug administration methods, and are less susceptible to primary metabolism in the liver after absorption, and have fewer side effects and are safe and safe. As a method that can be expected to absorb the drug continuously, a method of transdermal administration using a patch or the like has attracted attention. However, skin that has a barrier function to prevent foreign substances from entering the body exerts a strong barrier function against the drug. Therefore, in the case of transdermal administration, drug permeability is low and sufficient medicinal effects cannot be expected. Had the problem. Therefore, various studies for enhancing the skin permeability of drugs in transdermal administration have been made. For example, International Publication No. 01/005381 (Patent Document 1) describes acidic drugs having a salt form and ammonium chloride. A transdermally absorbable preparation containing an addition salt compound of such a basic substance is described.

  Beraprost is a drug having a strong platelet aggregation inhibitory action and vasodilatory action, and is expected as a therapeutic drug for vascular disorders. However, since beraprost is chemically extremely unstable, conventionally, there have been only limited methods such as intravenous administration and oral administration. At present, development related to transdermal administration of beraprost has been carried out. For example, International Publication No. 1996/015793 (Patent Document 2) is applied as a transdermal absorption preparation containing beraprost and saturated fatty acid or unsaturated fatty acid. Agents are described. However, in the patch described in Patent Document 2, the skin permeability of beraprost has not been sufficient yet.

International Publication No. 01/005381 International Publication No. 1996/015793

  This invention is made | formed in view of the subject which the said prior art has, and aims at providing the patch excellent in the skin permeability of beraprost.

  As a result of intensive studies to achieve the above object, the present inventors have found that in a patch comprising a support and an adhesive layer, belaprost or its pharmacologically acceptable as an active ingredient in the adhesive layer. It was found that the permeation of beraprost was improved by containing a combination of a salt to be added and an aliphatic alcohol having 14 to 20 carbon atoms as a transdermal absorption enhancer, and the present invention was completed. In Patent Documents 1 and 2, there is no mention of combining beraprost and an aliphatic alcohol having 14 to 20 carbon atoms in the patch.

That is, the patch of the present invention is
Bellaprost or a pharmacologically acceptable salt thereof as an active ingredient, and a linear aliphatic alcohol having 14 to 20 carbon atoms as a transdermal absorption enhancer, comprising an adhesive layer and a support layer And ammonium chloride and a styrene-isoprene-styrene block copolymer are contained in the pressure-sensitive adhesive layer.

  In the patch of the present invention, the aliphatic alcohol is preferably myristyl alcohol or oleyl alcohol. Further, when the aliphatic alcohol is myristyl alcohol, the content thereof is preferably 5 to 10% by mass in the pressure-sensitive adhesive layer, and when the aliphatic alcohol is oleyl alcohol, The content is more preferably 2.5 to 10% by mass in the pressure-sensitive adhesive layer.

Further, as the adhesive patch of the present invention preferably further contains a tackifier and a plasticizer before SL adhesive layer.

  ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to provide the patch excellent in the skin permeability of beraprost.

  Hereinafter, the present invention will be described in detail with reference to preferred embodiments thereof.

  The patch of the present invention includes an adhesive layer and a support layer. The pressure-sensitive adhesive layer is a layer formed on the surface of the support layer (usually on one surface), and is a layer containing an active ingredient, a percutaneous absorption promoter, and a pressure-sensitive adhesive base. The pressure-sensitive adhesive layer according to the present invention contains beraprost or a pharmacologically acceptable salt thereof as the active ingredient, and contains an aliphatic alcohol having 14 to 20 carbon atoms as the transdermal absorption promoter. Yes. Further, the thickness of the pressure-sensitive adhesive layer is not particularly limited, but is usually preferably about 10 to 300 μm.

The beraprost is 2,3,3a, 8b-tetrahydro-2-hydroxy-1- (3-hydroxy-4-methyl-1-octene-6-in-1-- represented by the molecular formula C ₂₄ H ₃₀ O ₅ Yl) -1H-cyclopenta (b) benzofuran-5-butanoic acid [2,3,3a, 8b-tetrahydro-2-hydroxy-1- (3-hydroxy-4-methyl-1-octen-6-yn-1 -Yl) -1H-cyclopenta (b) benzofuran-5-butanoic acid]. The beraprost is one of prostaglandin I ₂ derivatives and is a drug having a platelet aggregation inhibitory action and a vasodilator action.

  The form of beraprost contained as an active ingredient in the present invention may be a free form or a pharmacologically acceptable salt thereof, and the salt of beraprost during production and / or in the produced preparation. May be desalted to form a free form, and one of these may be used, or two or more may be mixed. Among these, the form of beraprost according to the present invention includes beraprost pharmacology from the viewpoint that the stability of the drug is improved and the skin irritation caused by acid and the decrease in physical properties of the preparation tend to be suppressed. Preferably, the salt is acceptable.

  Examples of the pharmacologically acceptable salt of beraprost include metal salts such as alkali metals, alkaline earth metals, and aluminum; amine salts such as tromethamine, among which sodium salts are preferable.

  In the patch of the present invention, the total content of such beraprost and a pharmacologically acceptable salt thereof is preferably 0.2 to 10% by mass in the pressure-sensitive adhesive layer. More preferably, it is -5 mass%. When the content is less than the lower limit, the skin permeability of beraprost tends to be insufficient. On the other hand, when the content exceeds the upper limit, the beraprost crystals precipitate and the adhesive strength of the adhesive layer is increased. Tend to decrease.

  The aliphatic alcohol having 14 to 20 carbon atoms according to the present invention may be linear or branched, and may be saturated or unsaturated. Examples of the aliphatic alcohol having 14 to 20 carbon atoms include myristyl alcohol, oleyl alcohol, octyldodecanol, isostearyl alcohol, stearyl alcohol, cetyl alcohol, and linoleyl alcohol. Among these, beraprost penetrates the skin. From the viewpoint that the property tends to be further improved, it is preferably a linear aliphatic alcohol having 14 to 20 carbon atoms, more preferably myristyl alcohol or oleyl alcohol. Moreover, as a C14-C20 aliphatic alcohol based on this invention, you may use individually by 1 type, or may be used in combination of 2 or more type.

  In the patch of the present invention, the content of the aliphatic alcohol having 14 to 20 carbon atoms is preferably 1 to 20% by mass in the pressure-sensitive adhesive layer, and preferably 2.5 to 10% by mass. More preferably. When the content is less than the lower limit, the skin permeability of beraprost tends to be insufficient. On the other hand, when the content exceeds the upper limit, the adhesive strength and cohesive strength of the pressure-sensitive adhesive layer tend to decrease. It is in. In particular, when the aliphatic alcohol having 14 to 20 carbon atoms according to the present invention is myristyl alcohol, the content is preferably 1 to 20% by mass in the pressure-sensitive adhesive layer, and 5 to 10% by mass. It is more preferable that Moreover, when C14-20 aliphatic alcohol which concerns on this invention is oleyl alcohol, it is preferable that the content is 1-20 mass% in the said adhesive layer, and is 2.5-10. More preferably, it is mass%. When the content of the myristyl alcohol or oleyl alcohol is less than the lower limit, the skin permeability of beraprost tends to be insufficient, whereas when the content exceeds the upper limit, The cohesive force tends to decrease.

  The patch of the present invention preferably further contains ammonium chloride in the pressure-sensitive adhesive layer. By further containing ammonium chloride, the skin permeability of beraprost tends to be further improved. In particular, when the drug is in the form of a salt, the barrier function for preventing the entry of foreign substances in the skin into the body is exerted more strongly, so the drug permeability is low and sufficient drug efficacy cannot be expected. There is a tendency, but by further containing the ammonium chloride, the skin permeability tends to be further improved even if beraprost is in the form of a salt.

  When the ammonium chloride is contained in the patch of the present invention, the content thereof is preferably 0.13 to 2.5% by mass in the pressure-sensitive adhesive layer, and 0.13 to 1.3% by mass. It is more preferable that When the content of the ammonium chloride is less than the lower limit, the skin permeability of beraprost tends to decrease. On the other hand, when the content exceeds the upper limit, the solubility of ammonium chloride decreases and the physical properties of the preparation are reduced. It tends to decrease.

  Moreover, as content of the said ammonium chloride in the said adhesive layer, it is 0.5-10 times mole with respect to the total content of the said beraprost and its pharmacologically acceptable salt, More preferably, it is 0.5. The content is preferably ˜7 times mol. When the content is less than the lower limit, the skin permeability of beraprost is insufficient and sufficient medicinal effects tend not to be obtained. On the other hand, when the upper limit is exceeded, although the skin permeability of beraprost is improved, the solubility of ammonium chloride is lowered and the physical properties of the preparation tend to be lowered.

  Further, as the adhesive base in the adhesive layer according to the present invention, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, styrene-isoprene rubber, styrene-butadiene rubber, polyisoprene, poly Examples include isobutylene, polybutadiene rubber, silicone rubber, acrylic polymer, natural rubber, polyurethane rubber, and the like. One of these may be used alone, or two or more may be used in combination.

  In the present invention, the adhesive base is preferably a styrene-isoprene-styrene block copolymer from the viewpoint that the skin permeability of beraprost tends to be further improved. Specific examples of the styrene-isoprene-styrene block copolymer include Califlex TR-1107, TR-1111, TR-1112, or TR-1117 (trade name, manufactured by Shell Chemical Co., Ltd.), QUINTAC 3530. 3570C or 3421 (trade name, manufactured by Nippon Zeon Co., Ltd.), JSR SIS-5000 or 5002 (trade name, manufactured by Nippon Synthetic Rubber Co., Ltd.), Sorprene 428 (trade name, manufactured by Philippe Petroleum Co., Ltd.), etc. One of these may be used alone, or two or more may be used in combination.

  When the styrene-isoprene-styrene block copolymer is contained in the patch, the content thereof is preferably 5 to 50% by mass in the pressure-sensitive adhesive layer, and 10 to 40% by mass. Is more preferable. By making the content within such a range, the adhesiveness, adhesion to the skin for a long time, transdermal absorbability / dispersibility of the drug, pain at the time of peeling, skin irritation, etc. are greatly improved. There is a tendency. Moreover, when the content is less than the lower limit, the cohesive force and shape retention of the pressure-sensitive adhesive layer tend to be reduced. On the other hand, when the content exceeds the upper limit, the cohesive force of the pressure-sensitive adhesive layer is low. It tends to increase and cause a decrease in adhesive strength and non-uniformity of the adhesive layer.

  Specific examples of the polyisobutylene include Opanol B-3, B-10, B-15, B-50, B-100, B-200 (trade name, manufactured by BASF), Vistanex LM-MS, LM. -MH, MML-80, LLM-100, LLM-120, LLM-140 (trade name, manufactured by Exxon Chemical Co., Ltd.), Tetrax 3T, 4T, 5T, 6T (trade name, manufactured by Nippon Petrochemical Co., Ltd.) ) And the like, and one of these may be used alone, or two or more may be used in combination. When the polyisobutylene is contained in the patch, the content thereof is preferably 2 to 30% by mass in the pressure-sensitive adhesive layer, and more preferably 4 to 20% by mass. By making the content within such a range, the adhesiveness, adhesion to the skin for a long time, transdermal absorbability / dispersibility of the drug, pain at the time of peeling, skin irritation, etc. are greatly improved. There is a tendency. Moreover, when the said content is less than the said minimum, adhesive force and the adhesiveness to the skin for a long time will fall, and there exists a tendency for the pain at the time of peeling, skin irritation, etc. to increase. On the other hand, when it exceeds the upper limit, the shape retention of the pressure-sensitive adhesive layer and the like tend to decrease and the stickiness tends to increase.

  Examples of the acrylic polymer include a copolymer of at least two compounds selected from the group consisting of butyl acrylate, 2-ethylhexyl acrylate, vinyl acetate, methacrylate, hydroxyethyl acrylate, glycidyl methacrylate, methoxyethyl acrylate, and acrylic acid. Specifically, DURO-TAK 87-2097, 87-2194, 87-2196, 87-2287, 87-2516, 87-2852, 87-235A (trade name, manufactured by Henkel Japan), Nissetsu KP -77, AS-370 (trade name, manufactured by Nippon Carbide Industry Co., Ltd.), etc., may be used alone or in combination of two or more. In the case where the acrylic polymer is contained in the patch, the content is 93% by mass or less in the pressure-sensitive adhesive layer from the viewpoint that the skin permeability of beraprost tends to be further improved. It is preferable.

  Moreover, as said patch, it is preferable to further contain a tackifier and a plasticizer in the said adhesive layer. Examples of the tackifier include rosin ester, hydrogenated rosin ester, maleated rosin, alicyclic saturated hydrocarbon resin, terpene phenol, and the like. Specifically, ester gum A, AA-G, H Or HP (trade name, manufactured by Arakawa Chemical Industries, Ltd.), Harrier Star L, S or P (trade name, manufactured by Arakawa Chemical Industries, Ltd.), Pine Crystal KE-100 (trade name, Arakawa Chemical Industries, Ltd.) ), KE-311 (trade name, manufactured by Arakawa Chemical Co., Ltd.), Hercolin D (trade name, manufactured by Rika Hercules Co., Ltd.), Foral 85 or 105 (trade name, manufactured by Rika Hercules Co., Ltd.), Steve Light ester 7 or 10 (trade name, manufactured by Rika Hercules Co., Ltd.), pentalin 4820 or 4740 (trade name, manufactured by Rika Hercules Co., Ltd.), Alcon P-85 or P-10 (Trade name, manufactured by Arakawa Chemical Industries, Ltd.) and the like, may be used in combination of two or more be used one of these singly.

  When the adhesive agent is included in the patch, the content thereof is preferably 5 to 60% by mass and more preferably 10 to 50% by mass in the adhesive layer. By making the content within such a range, the adhesiveness, adhesion to the skin for a long time, transdermal absorbability / dispersibility of the drug, pain at the time of peeling, skin irritation, etc. are greatly improved. There is a tendency. Further, when the content is less than the lower limit, the adhesive force and long-term skin adhesion tend to decrease, while when the content exceeds the upper limit, the drug transdermal absorbability, The shape retention of the pressure-sensitive adhesive layer is lowered, and there is a tendency that pain at the time of peeling, skin irritation, stickiness and the like increase.

  Examples of the plasticizer include petroleum oils (for example, paraffinic process oils such as liquid paraffin, naphthenic process oils, aromatic process oils, etc.), squalane, squalene, vegetable oils (for example, olive oil, camellia oil, castor oil). , Tall oil, peanut oil), dibasic acid esters (for example, dibutyl phthalate, dioctyl phthalate, etc.), liquid rubbers (for example, liquid polybutene, liquid isoprene rubber, etc.), etc. You may use it, or may use it in combination of 2 or more types. As such a plasticizer, liquid paraffin and liquid polybutene are preferable from the viewpoint that the adhesiveness of the pressure-sensitive adhesive layer to the skin is further improved and irritation to the skin tends to be reduced.

  When the plasticizer is contained in the patch, the content thereof is preferably 7 to 70% by mass and more preferably 10 to 60% by mass in the pressure-sensitive adhesive layer. By making the content within such a range, the adhesiveness, adhesion to the skin for a long time, transdermal absorbability / dispersibility of the drug, pain at the time of peeling, skin irritation, etc. are greatly improved. There is a tendency. In addition, when the content is less than the lower limit, the adhesive strength and the transdermal absorbability / dispersibility of the drug tend to be reduced. On the other hand, when the content exceeds the upper limit, the cohesive strength of the adhesive layer In addition, the shape retention tends to decrease, and the pain and stickiness at the time of peeling tend to increase.

  Further, as the patch, an antioxidant (for example, ascorbic acid, propyl gallate, butylhydroxyanisole, dibutylhydroxytoluene (BHT), nordihydroguaiaretic acid, tocopherol, Tocopherol acetate, etc.), UV absorbers (e.g. paraaminobenzoic acid, paraaminobenzoic acid ester, amyl paradimethylaminobenzoic acid, salicylic acid ester, methyl anthranilate, umbelliferone, esculin, benzyl cinnamate, cinoxalate, guaiazulene, urocanic acid, 2- (2-hydroxy-5-methylphenyl) benzotriazole, 4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone, octapentone, dioxybenzone, dihydroxy Dimethoxybenzophenone, slumpenzone, benzolercinol, octyldimethylparaaminobenzoate, ethylhexylparamethoxycynamate, etc.), antibacterial agents (eg paraoxybenzoate, benzoic acid, benzoate, sorbic acid, sorbate, dehydroacetate, 4 -Isopropyl-3-methylphenol, 2-isopropyl-5-methylphenol, hinokitiol, cresol, 2,4,4-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanide, chlorobutanol, etc.) , Fillers (eg aluminum hydroxide, hydrous aluminum silicate, kaolin, titanium oxide, talc, zinc oxide, hydrous silica, magnesium carbonate, calcium hydrogen phosphate, magnesium silicate, diatomaceous earth, anhydrous Iic acid, bentonite, sodium stearate, calcium stearate, potassium stearate, magnesium stearate, zinc stearate, etc.), antihistamines (eg isopentyl chloride, diphenhydramine hydrochloride, iproheptin hydrochloride, diphenylpyralin hydrochloride, cyproheptadine hydrochloride, triprolidine hydrochloride, hydrochloric acid Promethazine, homochlorcyclidine hydrochloride, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline teocrate, clemastine fumarate, chlorpheniramine maleate, dimethindene maleate, mequitazine, etc.), cooling agents, perfumes, etc. in the adhesive layer You may contain.

  The support layer according to the present invention is not particularly limited as long as it can support the pressure-sensitive adhesive layer, but has moderate flexibility from the viewpoint of increasing the adhesiveness of the patch to the skin. It is preferable. Further, the thickness of the support layer is not particularly limited, but is usually preferably about 2 to 3000 μm.

  Examples of such a support layer include a film, a woven fabric, and a non-woven fabric. The material for the film, woven fabric, and nonwoven fabric is not particularly limited, and any material that can be used as a material for the support layer of a patch can be used as appropriate. Examples of such materials include polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, polyurethane, polyethylene terephthalate, polybutylene terephthalate, and other polyesters; polyamides such as nylon; rayon, pulp, cotton And the like; polyacrylonitrile and the like, and one of these may be used alone, or two or more thereof may be used in combination.

  The patch of the present invention may further include a release liner layer for covering and protecting the surface of the pressure-sensitive adhesive layer until the patch is used. The material of the release liner layer is not particularly limited, and a material that can be used as a material of a release liner layer of a normal patch can be appropriately used. Examples of such materials include polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ethylene-vinyl alcohol copolymer, polyvinyl chloride, polyurethane, polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate. Polyesters; polyamides such as nylon; polyacrylonitrile; cellulose or derivatives thereof; metal foils such as aluminum, and the like. One of these may be used alone, or two or more may be used in combination. Examples of the release liner layer include films and sheets made of the above-described materials. In order to increase the releasability of such films and sheets, the surface in contact with the pressure-sensitive adhesive layer is preliminarily treated with silicone or fluororesin. It may be processed.

  The patch according to the present invention is not particularly limited and can be produced by appropriately adopting a known method for producing a patch. For example, it can be produced by the following method. First, a uniform pressure-sensitive adhesive layer composition obtained by kneading the beraprost or a pharmacologically acceptable salt thereof, the aliphatic alcohol, and if necessary, the ammonium chloride and the pressure-sensitive adhesive base according to a conventional method. Get things. Next, this pressure-sensitive adhesive layer composition is applied on the surface of the support layer (usually on one surface) with a predetermined thickness to form a pressure-sensitive adhesive layer. Next, the adhesive liner of the present invention can be obtained by laminating the release liner layer on the surface of the pressure-sensitive adhesive layer opposite to the support layer and cutting it into a predetermined shape. Alternatively, the pressure-sensitive adhesive layer composition is first applied on one surface of the release liner layer with a predetermined thickness to form a pressure-sensitive adhesive layer, and then the pressure-sensitive adhesive layer is formed on the surface opposite to the release liner layer. You may obtain the patch of this invention by bonding the said support body layer and cut | judging to a predetermined shape.

  EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example and a comparative example, this invention is not limited to a following example. In the patches obtained in each of the examples and comparative examples, the skin permeation test was performed by the method shown below.

(Skin penetration test)
First, the dorsal skin of a hairless mouse was peeled off, and the dermis side was placed on the receptor tank side, and attached to a Franz-type flow-through cell in which hot water of 32 ° C. was circulated around the outer periphery. Then, a patch obtained by cutting the release liner layer by cutting to a size of 5 cm ² was applied to the skin stratum corneum side. A phosphate buffer solution (pH 7.4) is flowed into the receptor tank of the flow-through cell at a flow rate of 5 mL / hr, and a sample solution is collected from the receptor tank every 24 hours for up to 24 hours. The concentration of the drug (beraprost) was measured for the liquid by high performance liquid chromatography, and the maximum value of the skin permeation rate of the drug per hour (Jmax: μg / cm ² / hr) was determined from the obtained measured value as follows: formula:
Jmax (μg / cm ² / hr) = [drug concentration (μg / ml) × flow rate (ml)] / patch area (cm ² ) / hour (hr)
Calculated by Furthermore, from the start of the measurement until after 24 hours, the cumulative skin permeation amount of 24 hours of drug ^{(μg / cm 2 / 24hr)} , the drug permeation amount obtained by the above was determined by integrating 24 hours. In addition, the drug utilization rate (%) is calculated using the following formula:
Utilization rate (%) = {(cumulative skin permeation amount of drug for 24 hours) / (content of drug per 1 cm ^{2 of} patch)} × 100
Calculated by A preparation having a maximum value of skin permeation rate and / or a large cumulative skin permeation value is recognized as having excellent drug skin permeability.

Example 1
First, 2.00% by mass of beraprost sodium, 5.00% by mass of myristyl alcohol, 0.25% by mass of ammonium chloride, 24.41% by mass of styrene-isoprene-styrene block copolymer (SIS), tackifying The adhesive (“Arcon P-100”, manufactured by Arakawa Chemical Industries, Ltd.) was weighed and mixed so that the amount was 43.93% by mass and the liquid paraffin was 24.41% by mass. Obtained. Next, after the obtained pressure-sensitive adhesive layer composition was spread on one surface of the polyester film so as to be 100 g / m ² , the coated surface of the pressure-sensitive adhesive layer composition was covered with a release liner layer made of polypropylene. Then, it was cut into a predetermined size (10 cm × 14 cm) to obtain a patch (adhesive). Table 1 shows the results of skin permeation tests on the obtained patches together with the composition of the pressure-sensitive adhesive layer composition.

(Example 2 , Comparative Examples 14 and 15 )
A patch was obtained in the same manner as in Example 1 except that oleyl alcohol, octyldodecanol and isostearyl alcohol were used in place of myristyl alcohol. The results of skin permeation tests on the obtained patches are shown in Table 1 together with the composition of each adhesive layer composition.

(Comparative Examples 1 to 13)
A patch was obtained in the same manner as in Example 1 except that the percutaneous absorption enhancer shown in Table 1 was used instead of myristyl alcohol. The results of skin permeation tests on the obtained patches are shown in Table 1 together with the composition of each adhesive layer composition. In Table 1, “Eudragit (* 1)” refers to “Eudragid L-100” manufactured by Rohm Pharma.

(Examples 5-6)
A patch was obtained in the same manner as in Example 1 except that the contents of ammonium chloride, SIS, tackifier and liquid paraffin were changed to the contents shown in Table 2, respectively. Table 2 shows the results of skin permeation tests on the obtained patches together with the composition of each pressure-sensitive adhesive layer composition. In addition, the patch obtained in Example 1 is also shown.

(Examples 7 to 9)
A patch was obtained in the same manner as in Example 1 except that the contents of myristyl alcohol, SIS, tackifier, and liquid paraffin were changed to the contents shown in Table 3, respectively. Table 3 shows the results of skin permeation tests performed on the obtained patches together with the composition of each pressure-sensitive adhesive layer composition. In addition, the patch obtained in Example 1 is also shown.

(Examples 10 to 12)
A patch was obtained in the same manner as in Example 2 except that the contents of oleyl alcohol, SIS, tackifier and liquid paraffin were changed to the contents shown in Table 4, respectively. Table 4 shows the results of skin permeation tests on the obtained patches together with the composition of each pressure-sensitive adhesive layer composition. In addition, the patch obtained in Example 2 is also shown.

  As is clear from the results shown in Tables 1 to 4, it was confirmed that the patch of the present invention was excellent in the skin permeability of beraprost. On the other hand, it was confirmed that a patch containing no aliphatic alcohol having 14 to 20 carbon atoms is inferior in skin permeability of beraprost even when a conventional transdermal absorption enhancer is contained.

  As described above, according to the present invention, it is possible to provide a patch excellent in skin permeability of beraprost.

Claims (5)

Bellaprost or a pharmacologically acceptable salt thereof as an active ingredient, and a linear aliphatic alcohol having 14 to 20 carbon atoms as a transdermal absorption enhancer, comprising an adhesive layer and a support layer And an ammonium chloride and a styrene-isoprene-styrene block copolymer in the pressure-sensitive adhesive layer.   The patch according to claim 1, wherein the aliphatic alcohol is myristyl alcohol or oleyl alcohol.   The patch according to claim 1 or 2, wherein the aliphatic alcohol is myristyl alcohol, and the content thereof is 5 to 10% by mass in the pressure-sensitive adhesive layer.   The patch according to claim 1 or 2, wherein the aliphatic alcohol is oleyl alcohol, and the content thereof is 2.5 to 10% by mass in the pressure-sensitive adhesive layer.   The adhesive patch according to any one of claims 1 to 4, further comprising a tackifier and a plasticizer in the adhesive layer.