JP2008143866A - Adhesive and patch - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an adhesive and a patch each having sufficiently high transdermal absorption of a COX-2 inhibitor. <P>SOLUTION: The adhesive comprises (A) at least one kind of compound selected from the group consisting of meloxicam, lornoxicam, celecoxib and pharmaceutically permissible salts thereof, (B) a hydrophobic adhesive base, (C) N-methylpyrrolidone and (D) a hydrophilic polymer. The patch comprises a support and a medicine layer composed of the above adhesive and laminated on at least either one surface of the support. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an adhesive and a patch, and more particularly, to an adhesive and a patch containing a COX-2 inhibitor selected from meloxicam, lornoxicam and celecoxib.

  Conventionally, oral administration methods using tablets, capsules, syrups and the like are known as drug administration methods, but in recent years, attempts have been made to administer these drugs from the skin using a patch. In addition to eliminating the problems associated with oral administration, the patch administration method has advantages such as reduction in the number of administrations, improvement in compliance, ease of administration and discontinuation, etc., especially for elderly and pediatric patients. It is expected to be a useful drug administration method in treatment.

  However, the stratum corneum of normal skin has a barrier function that prevents foreign substances from entering the body, and the base used in normal patches can provide sufficient transdermal absorption of the formulated medicinal ingredients. Often not. In addition, since the stratum corneum has high fat solubility, generally the drug permeability is extremely low. Therefore, when a drug is administered from the skin using a patch, it is necessary to increase the transdermal absorbability of the drug through the stratum corneum of the skin.

  On the other hand, among non-steroidal anti-inflammatory drugs used for the treatment of rheumatic diseases, arthritis, arthritic and degenerative joint diseases, pain, etc., cyclooxygenase-2 (COX-2) is selectively inhibited, In recent years, COX-2 inhibitors have been developed as a medicinal group that reduces the risk of side effects in the digestive system. According to such a COX-2 inhibitor, side effects in the digestive system that have been a problem with conventional nonsteroidal anti-inflammatory drugs (NSAIDs) such as ketorolac, diclofenac, naproxen, etc. can be minimized, or side effects There is an advantage that does not cause.

  That is, conventional non-steroidal anti-inflammatory drugs produce not only the COX-2 isoform of cyclooxygenase that accompanies or induces inflammation, but also prostaglandins required for normal cellular function at doses used for treatment. Since it also inhibits cyclooxygenase-1 (COX-1), it exerts anti-inflammatory, antipyretic, and analgesic effects and has side effects in the digestive system. In contrast, a COX-2 inhibitor does not substantially inhibit COX-1, but selectively inhibits COX-2, and thus exhibits anti-inflammatory, antipyretic, analgesic and other useful therapeutic effects. However, side effects are minimized or do not cause side effects.

  Known COX-2 inhibitors include meloxicam, lornoxicam, celecoxib, etoroxixib, valdecoxib, valecoxib and the like. Such COX-2 inhibitors are mainly administered by the oral administration method, but recently administration by a patch having the advantages as described above has been reported.

For example, Patent Document 1 discloses a patch containing a COX-2 inhibitor, particularly valdecoxib, and further containing N-methylpyrrolidone as a solvent (dissolving agent). Two types of patches are disclosed: a “tape” in which an active substance is dispersed in a lipophilic matrix and a “pap” in which an active substance is dispersed in a hydrophilic matrix.
Patent Document 2 discloses a patch containing a COX-2 inhibitor, particularly meloxicam, and further containing an aliphatic amine or amide compound as an absorption accelerator (“plaster agent (tape agent)” and “pap agent”). It is disclosed.
Patent Document 3 discloses a patch containing a COX-2 inhibitor, particularly rofecoxib.
JP-T-2006-509762 JP 2004-131495 A JP-T-2004-501971

  However, the conventional COX-2 inhibitor-containing patches described in Patent Documents 1 to 3 have a problem that the transdermal absorbability is not sufficient.

  The present invention has been made in view of the above circumstances, and an object thereof is to provide a pressure-sensitive adhesive and a patch having a sufficiently high transdermal absorbability of a COX-2 inhibitor.

  As a result of extensive research, the present inventors have found that (A) at least one compound selected from the group consisting of meloxicam, lornoxicam, celecoxib, and pharmaceutically acceptable salts thereof (hereinafter referred to as component (A) ), (B) a lipophilic adhesive base (hereinafter also referred to as component (B)), (C) N-methylpyrrolidone (hereinafter also referred to as component (C)), and (D). It has been found that the above object can be achieved by a pressure-sensitive adhesive containing a hydrophilic polymer (hereinafter also referred to as component (D)).

  Such a patch has a sufficiently high transdermal absorbability of a COX-2 inhibitor (hereinafter also referred to as “drug”) and exhibits an excellent anti-inflammatory effect. The reason why such an effect occurs is not necessarily clear, but the following may be considered, for example.

  First, for example, the presence of a hydrophilic polymer having a polar functional group such as a hydroxyl group or a carboxyl group in the pressure-sensitive adhesive causes the polar functional group to interact with the drug. As a result, it is considered that the affinity of the drug for the lipophilic adhesive base is lowered and the transdermal absorbability is improved. Further, the presence of N-methylpyrrolidone as a solubilizer in the adhesive causes the drug in the adhesive to be dissolved. Thereby, at the time of percutaneous absorption, it is also considered that the total amount of the drug present in the pressure-sensitive adhesive can be effectively involved in distribution to the skin. In addition to these, the presence of a lipophilic adhesive base in the adhesive is considered to improve the physical properties of the adhesive and improve the skin permeability of the drug. Since these compounds are used in combination, the patch of the present invention is considered to have a sufficiently high transdermal absorbability of the drug.

  The component (D) preferably contains at least one group selected from the group consisting of a hydroxyl group and a carboxyl group, and is selected from the group consisting of sodium carboxymethylcellulose, hydroxypropylmethylcellulose, or sodium polyacrylate. It is preferable that there is at least one. This further improves the transdermal absorbability of the drug.

  Moreover, it is preferable that the said (B) component contains a styrene-isoprene-styrene block copolymer. This improves both the transdermal absorbability of the drug and the physical properties of the patch.

  The patch of the present invention comprises a support and a drug layer that is laminated on at least one surface of the support and is made of the above-mentioned adhesive. Since the patch of the present invention includes a drug layer made of an adhesive that exhibits the above-described excellent effects, the transdermal absorbability of the drug is sufficiently high.

  ADVANTAGE OF THE INVENTION According to this invention, the adhesive and patch which show the transdermal absorbability of a COX-2 inhibitor sufficiently high, and show | played the outstanding anti-inflammatory action are provided. Further, the patch of the present invention has good adhesiveness to the skin, sufficiently small skin irritation, and excellent long-term storage stability.

  Hereinafter, preferred embodiments of the present invention will be described in detail, but the present invention is not limited thereto. In the present specification, unless otherwise specified, “%” means “% by mass”.

  The pressure-sensitive adhesive of the present invention comprises (A) at least one compound selected from the group consisting of meloxicam, lornoxicam, celecoxib, and pharmaceutically acceptable salts thereof, (B) a lipophilic pressure-sensitive adhesive base, C) contains N-methylpyrrolidone and (D) a hydrophilic polymer.

  Although the adhesive of this invention contains (A) component as a COX-2 inhibitor, this does not prevent containing another COX-2 inhibitor. For example, it may further contain COX-2 inhibitors such as etoroxixib, valdecoxib, valecoxib and the like.

  The “pharmaceutically acceptable salt” in component (A) is not particularly limited, and examples thereof include sodium salts, potassium salts, and ammonium salts.

  In addition, it is preferable that the compounding quantity of (A) component in an adhesive is 0.1 to 10% on the basis of the total amount of the compound contained in an adhesive, and it is especially preferable that it is 0.5 to 6%. . When the blending amount is 0.1% or more, the anti-inflammatory action is improved as compared with the case of less than 0.1%. Further, by setting the blending amount to 10% or less, there is no risk of drug crystals being precipitated, and the effect of increasing the blending amount of the drug can be sufficiently obtained.

  The (B) component lipophilic adhesive base is not particularly limited as long as it is an adhesive base that does not dissolve and / or swell in water, but is mainly composed of a hydrophobic component and does not substantially contain water. It means an adhesive base that is difficult to mix with water. For example, a rubber-based polymer elastomer can be used. The rubber-based polymer elastomer means a polymer elastomer having elasticity at room temperature, and examples thereof include natural rubber, synthetic rubber, and thermoplastic elastomer. Examples of the synthetic rubber include polyisobutylene, isoprene rubber, and silicone rubber. Examples of the thermoplastic elastomer include styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, and styrene-butadiene. Examples thereof include rubber, and a styrene-isoprene-styrene block copolymer is preferable from the viewpoint of improving both the skin permeability of the drug and the physical properties of the preparation.

  These rubber-based polymers may be used alone or in combination of two or more. For example, it is preferable to use a styrene-isoprene-styrene block copolymer in combination with polyisobutylene because both the skin absorbability of the drug and the physical properties of the drug tend to be further improved. Examples of the styrene-isoprene-styrene block copolymer include styrene-isoprene-styrene block copolymers (trade names: Clayton D-1107 and Clayton D-1111) manufactured by Kraton Polymer Co., Ltd., and styrene- manufactured by Nippon Synthetic Rubber Co., Ltd. Examples include isoprene-styrene block copolymers (trade names: JSR5002, JSR5200), styrene-isoprene-styrene block copolymers (trade name: QUINT 3421) manufactured by Nippon Zeon Co., Ltd., and the like. Examples of polyisobutylene include polyisobutylene (trade name: Vistanex) manufactured by ExxonMobil.

  In addition, it is preferable that the compounding quantity of (B) component in an adhesive is 10 to 90% on the basis of the total amount of the compound contained in an adhesive. When the blending amount is 10% or more, the shape retention of the preparation is improved as compared with the case where the blending amount is less than 10%. Moreover, by making a compounding quantity 90% or less, compared with the case where it exceeds 90%, a softness | flexibility becomes favorable and the adhesiveness to skin improves. Further, when the styrene-isoprene-styrene block copolymer and other rubber adhesive are used in combination as the component (B), the styrene-isoprene-styrene block is based on the total amount of the compounds contained in the adhesive. The blending amount of the copolymer is preferably 7 to 63%, and the blending amount of the other rubber-based pressure-sensitive adhesive is preferably 3 to 27%. Thereby, both the skin permeability of the drug and the physical properties of the preparation can be further improved.

  The amount of component (C) in the pressure-sensitive adhesive is preferably 1 to 20%, more preferably 2 to 8%, based on the total amount of compounds contained in the pressure-sensitive adhesive. By setting the blending amount to 1% or more, transdermal absorbability is improved as compared with the case of less than 1%. Moreover, adhesiveness improves by making a compounding quantity into 20% or less compared with the case where it exceeds 20%.

  The hydrophilic polymer of component (D) means a polymer that is easily miscible with water, and has a polar functional group such as a carboxyl group, a sulfonic acid group, a hydroxyl group, an amino group in the molecule, Alternatively, it has a polarized partial structure. As the polar functional group, a carboxyl group and a hydroxyl group are preferable. Such hydrophilic polymers include, for example, gelatin, collagen, pectin, starch, chitin, albumin, casein, polyacrylic acid and / or polyacrylate derivatives, carboxyvinyl polymer, vinylpyrrolidone-acrylic acid copolymer, vinyl Pyrrolidone-styrene copolymer, vinylpyrrolidone-vinyl acetate copolymer, vinyl acetate- (meth) acrylic acid copolymer, polyvinyl acetate-crotonic acid copolymer, N-vinylacetamide copolymer, polyvinyl sulfonic acid, Polyitaconic acid, polyhydroxyethyl acrylate, styrene-maleic anhydride copolymer, acrylamide-acrylic acid copolymer, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, etc. Is, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, sodium polyacrylate is preferable.

  In addition, it is preferable that the compounding quantity of (D) component in an adhesive is 1-20% on the basis of the total amount of the compound contained in an adhesive, and it is especially preferable that it is 2-10%. When the blending amount is 1% or more, the transdermal absorbability is improved as compared with the case of less than 1%. Moreover, adhesiveness improves by making a compounding quantity into 20% or more compared with the case where it exceeds 20%.

  The pressure-sensitive adhesive of the present invention may contain a plasticizer, a tackifying resin, and an absorption accelerator as necessary in addition to the above-described components (A), (B), (C) and (D). Good.

  The plasticizer is not particularly limited. For example, petroleum oil (liquid paraffin, paraffin process oil, naphthenic process oil, aromatic process oil, etc.), squalane, squalene, vegetable oil (olive oil, camellia oil, castor oil) , Tall oil, peanut oil, etc.), silicon oil, dibasic acid esters (dibutyl phthalate, dioctyl phthalate, etc.), liquid rubber (liquid polybutene, liquid isoprene rubber, etc.), liquid fatty acid esters (isopropyl myristate, hexyl laurate, Diethyl sebacate, diisopropyl sebacate, etc.), polyhydric alcohols (diethylene glycol, polyethylene glycol, glycol salicylate, propylene glycol, dipropylene glycol, etc.), triacetin, triethyl citrate And the like. Among these plasticizers, polyhydric alcohol, liquid paraffin, liquid polybutene, diethyl sebacate, and hexyl laurate are more preferable, and liquid paraffin is particularly preferable. These plasticizers may be used alone or in combination of two or more.

  The blending amount when the plasticizer is blended with the pressure-sensitive adhesive is preferably 5 to 70%, particularly preferably 10 to 60%, based on the total amount of compounds contained in the pressure-sensitive adhesive. By setting the blending amount to be 5% or more, a higher softening effect is exhibited and the adhesive force is improved as compared with the case where it is less than 5%. Moreover, by making a compounding quantity 70% or less, compared with the case where it exceeds 70%, a formulation physical property improves.

  The tackifying resin is not particularly limited, and examples thereof include rosin derivatives (rosin, rosin glycerin ester, hydrogenated rosin, hydrogenated rosin glycerin ester, rosin pentaerythrester, etc.), alicyclic saturated hydrocarbon resins. (Alcon P100 (made by Arakawa Chemical Co., Ltd.)), aliphatic hydrocarbon resin (Quinton B-170 (made by Nippon Zeon Co., Ltd.)), terpene resin (Clearon P-125 (made by Yasuhara Chemical Co., Ltd.)), maleic acid Among them, hydrogenated rosin glycerin ester, alicyclic saturated hydrocarbon resin, aliphatic hydrocarbon resin, and terpene resin are preferable.

  When the tackifying resin is blended with the pressure-sensitive adhesive, the blending amount is preferably 5 to 70%, particularly preferably 5 to 60%, based on the total amount of the compounds contained in the pressure-sensitive adhesive. When the blending amount is 5% or more, the effect of improving the adhesive strength by blending the tackifying resin is improved as compared with the case where the blending amount is less than 5%. Moreover, by making a compounding quantity 70% or less, the skin irritation at the time of peeling an adhesive falls compared with the case where it exceeds 70%.

  The absorption enhancer is not particularly limited as long as it is a compound that has been conventionally recognized to absorb absorption in the skin. For example, fatty acids having 6 to 20 carbon atoms, aliphatic alcohols, fatty acid esters, aliphatic amides, aliphatic Examples thereof include ethers, aromatic organic acids, aromatic alcohols, aromatic organic acid esters, and aromatic ethers. These compounds may be saturated or unsaturated, and may be linear, branched, or cyclic. Furthermore, lactic acid esters, acetate esters, monoterpene compounds, sesquiterpene compounds, Azone, Azone derivatives, glycerin fatty acid esters, propylene glycol fatty acid esters, sorbitan fatty acid esters (Span system) , Polysorbate compounds (Tween), polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oil compounds (HCO), polyoxyethylene alkyl ethers, sucrose fatty acid esters, vegetable oils and the like as absorption promoters Can do. Among these absorption enhancers, caprylic acid, capric acid, caproic acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, lauryl alcohol, myristyl alcohol, oleyl alcohol, Isostearyl alcohol, cetyl alcohol, methyl laurate, hexyl laurate, diethanolamide laurate, isopropyl myristate, myristyl myristate, octyldodecyl myristate, cetyl palmitate, salicylic acid, methyl salicylate, ethylene glycol salicylate, cinnamic acid, Methyl cinnamate, cresol, cetyl lactate, lauryl lactate, ethyl acetate, propyl acetate, geraniol, thymol, eugenol, terpineol, l-menthol, Luneolol, d-limonene, isoeugenol, isoborneol, nerol, dl-camphor, glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate, glycerol monooleate, sorbitan monolaurate, sucrose monolaurate, polysorbate 20 , Propylene glycol, propylene glycol monolaurate, polyethylene glycol monolaurate, polyethylene glycol monostearate, polyoxyethylene lauryl ether, HCO-60, pyrothiodecane, olive oil is preferred, pyrothiodecane, isopropyl myristate, lauryl alcohol, myristyl alcohol, Isostearyl alcohol, lauric acid diethanolamide, glycerin monocaprylate, glycerin Monocaprate, glycerin monooleate, sorbitan monolaurate, more preferably propylene glycol monolaurate and polyoxyethylene lauryl ether, pirotiodecane and isopropyl myristate are particularly preferred. One of these absorption promoters may be used alone, or two or more thereof may be used in combination.

  When the absorption promoter is blended with the pressure-sensitive adhesive, the blending amount is preferably 0.1 to 20%, particularly preferably 1 to 10%, based on the total amount of compounds contained in the pressure-sensitive adhesive. . By setting the blending amount to be 0.1% or more, the effect of improving the skin permeability of the drug by blending the absorption enhancer is improved as compared with the case of less than 0.1%. Moreover, the irritation | stimulation to a skin falls by setting a compounding quantity as 20% or less compared with the case where it exceeds 20%.

  Furthermore, the pressure-sensitive adhesive of the present invention may contain additives such as an antioxidant, a filler, a crosslinking agent, a preservative, and an ultraviolet absorber as necessary.

As the antioxidant, tocopherol and their ester derivatives, ascorbic acid, ascorbic acid stearic acid ester, nordihuman logayaretinic acid, dibutylhydroxytoluene (BHT), butylhydroxyanisole are preferred;
As the filler, calcium carbonate, magnesium carbonate, silicate (eg, aluminum silicate, magnesium silicate, etc.), silicic acid, barium sulfate, calcium sulfate, calcium zincate, zinc oxide, titanium oxide are preferable;
Examples of the crosslinking agent include thermosetting resins such as amino resins, phenol resins, epoxy resins, alkyd resins, and unsaturated polyesters, isocyanate compounds, blocked isocyanate compounds, organic crosslinking agents, and inorganic crosslinking agents such as metals or metal compounds. Preferably;
As preservatives, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate are preferred;
As the ultraviolet absorber, p-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, coumarin derivatives, amino acid compounds, imidazoline derivatives, pyrimidine derivatives, and dioxane derivatives are preferable.

  Each compounding amount when these additives are blended with the pressure-sensitive adhesive is not particularly limited, but the total amount of these additives is 0.01 to 10% based on the total amount of the compounds contained in the pressure-sensitive adhesive. Is preferable, and 0.01 to 5% is particularly preferable.

  The above-mentioned pressure-sensitive adhesive may be used alone, but it is preferably used as a patch comprising a support and a drug layer which are laminated as a drug layer on a support. The drug layer may be laminated on at least one surface of the support, but the drug layer may be laminated on both surfaces of the support.

  The support is not particularly limited as long as it can support the drug layer, and a stretchable or non-stretchable support can be used. Examples of such a support include cloth, nonwoven fabric, polyurethane, polyester, polyvinyl acetate, polyvinylidene chloride, polyethylene, polyethylene terephthalate, an aluminum sheet, or a composite material thereof.

  In addition, although the thickness of a support body is not specifically limited, It is preferable that it is 5-1000 micrometers. By making the thickness of the support 5 μm or more, the workability at the time of application is improved as compared with the case of being less than 5 μm. Moreover, the influence on the adhesiveness by the hardness etc. of a support body can be prevented by the thickness of a support body being 1000 micrometers or less.

  In the patch of the present invention, the drug layer can be protected with a release liner during storage, that is, before use. The release liner is not particularly limited as long as it has sufficient release properties from the drug layer, but a polyethylene terephthalate (PET) film, a polyethylene film, a polypropylene film, a polytetrafluoroethylene film, or the like is preferably used. it can.

  The patch of the present invention can be produced by a conventional method such as a solvent method or a hot melt method. For example, in the case of producing by the solvent method, the adhesive base component and the solvent are previously stirred and mixed, then mixed with the drug and other components, and spread on a support or release liner. After drying, the patch of the present invention can be obtained by cutting into an appropriate size. In the case of producing by the hot melt method, the adhesive base component is previously stirred, mixed and dissolved at a high temperature, then mixed with the drug and other components, and spread on a support or a release liner. Thereafter, the patch of the present invention can be obtained by cutting into an appropriate size.

  Examples of the solvent used in the production by the solvent method include production solvents such as lower alcohol, toluene, ethyl acetate, hexane and cyclohexane. Among these, methanol, ethanol, isopropanol, toluene, ethyl acetate and cyclohexane are preferable, and toluene and ethyl acetate are particularly preferable.

  In addition, after forming a drug layer using a release liner instead of the support, the patch of the present invention can be obtained by pasting the support.

  In the patch of the present invention, the other layers and the components constituting them are not particularly limited as long as the drug layer has the above composition and has a support for supporting it. For example, the patch of the present invention can contain a release liner provided on the drug layer in addition to the support and the drug layer.

  The thickness of the drug layer is not particularly limited, but is preferably 20 to 200 μm. By setting the thickness of the drug layer to 20 μm or more, the skin permeability of the drug is improved as compared with the case of being less than 20 μm. In addition, by setting the thickness of the drug layer to 200 μm or less, it is possible to prevent a phenomenon in which the adhesive remains on the skin after application (adhesive residue).

In addition, according to the patch of the present invention, the active drug application amount can be easily adjusted according to the patient's symptoms, age, weight, sex, etc. by cutting the patch, etc. . But are not limited to the area of the drug layer to contact with the skin patch of the present invention is preferably 1～300Cm ^2, and more preferably 10 to 200 cm ^2. By making the area of the drug layer to be in contact with the skin of the patch 1 cm ² or more, it becomes easy to maintain sufficient skin permeability of the drug, and by making it 300 cm ² or less, handling at the time of application is suitable become.

  Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

(Example 1)
Styrene-isoprene-styrene block copolymer (trade name: QUINTAC 3570C) 17.90 parts by mass, polyisobutylene (trade name: Vistanex LM-MH-LC) 9.64 parts by mass, hydrogenated rosin glycerin ester derivative ( Product name: KE-311) 6.92 parts by mass and liquid paraffin (product name: Christol 352) 34.41 parts by mass were stirred and mixed at about 120 ° C. Thereafter, 8.0 parts by mass of N-methylpyrrolidone, 3.0 parts by mass of sodium carboxymethylcellulose, 3.0 parts by mass of pyrothiodecane and 2.0 parts by mass of meloxicam were mixed and applied to a release liner made of polyethylene terephthalate for support. The body (polyethylene terephthalate film) was laminated to obtain the patch of Example 1.

(Examples 2 to 5)
Patches of Examples 2 to 5 were obtained in the same manner as in Example 1 except that the components (A), (B), (C), and (D) and additives were as shown in Table 1. In addition, the numerical value in Table 1 shows a mass part.

(Comparative Examples 1-4)
Patches of Comparative Examples 1 to 4 were obtained in the same manner as in Example 1 except that the components (A), (B), (C), and (D) and additives were as shown in Table 2. In addition, the numerical value in Table 2 shows a mass part.

(Skin permeability test)
The dorsal skin of the hairless mouse was peeled off, and attached to a flow-through cell in which warm water at 32 ° C. was circulated around the outer periphery with the dermis side as the receptor side layer. Next, the patches of Examples 1 to 5 and Comparative Examples 1 to 4 (formulation application area 5 cm ² ) were applied to the stratum corneum side of the skin, and phosphate buffer was used as the receptor layer at 5 ml / hr for 3 hours. The receptor solution was sampled every 48 hours, the flow rate was measured, and the drug concentration was measured using high performance liquid chromatography. The drug permeation rate per hour was calculated from the obtained measured values, and the drug permeation rate per unit area of the skin in a steady state was obtained. The results are shown in Tables 1 and 2.

  As is clear from these results, the patches of Examples 1 to 4 in which the drug is meloxicam showed a marked improvement in the skin permeability of the drugs compared to the patches of Comparative Examples 1 to 3. . Furthermore, in the patches of Examples 1 to 3 to which pyrothiodecane was added, the skin permeability of the drug was further improved.

  In addition, in Example 5 and Comparative Example 4 where the drug was lornoxicam, the patch of Example 5 showed a marked improvement in the skin permeability of the drug compared to the patch of Comparative Example 4.

Claims (5)

(A) at least one compound selected from the group consisting of meloxicam, lornoxicam, celecoxib, and pharmaceutically acceptable salts thereof;
(B) a lipophilic adhesive base;
(C) N-methylpyrrolidone;
(D) a hydrophilic polymer;
Containing pressure-sensitive adhesive.   The pressure-sensitive adhesive according to claim 1, wherein the component (D) includes at least one group selected from the group consisting of a hydroxyl group and a carboxyl group.   The pressure-sensitive adhesive according to claim 1 or 2, wherein the component (D) is at least one selected from the group consisting of sodium carboxymethylcellulose, hydroxypropylmethylcellulose, or sodium polyacrylate.   The said (B) component is an adhesive as described in any one of Claims 1-3 containing a styrene-isoprene-styrene block copolymer.   A patch comprising: a support; and a drug layer laminated on at least one surface of the support and made of the adhesive according to any one of claims 1 to 4.