JP2007008927A - Plaster - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a plaster capable of enhancing releasability of an anti-inflammatory agent and suppressing impregnation of ointment to a support by using a styrene-isoprene-styrene block copolymer as an adhesive component. <P>SOLUTION: The plaster comprises the support and an ointment layer laminated on the support. The ointment layer comprises the styrene-isoprene-styrene block copolymer, a tackifier, a plasticizer, the anti-inflammatory agent and a hardening oil. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a patch, and more particularly, to an anti-inflammatory agent-containing patch containing an anti-inflammatory agent in a plaster layer.

  Conventionally, an anti-inflammatory agent-containing patch comprising a support and a paste layer laminated on the support and containing an anti-inflammatory agent in the paste layer is widely known. In such an anti-inflammatory agent-containing patch, among the adhesive components contained in the plaster layer, a styrene-isoprene-styrene block copolymer (hereinafter referred to as “SIS”) that can be produced by hot melting without using a solvent. Attention is also focused on “block copolymers”.

  For example, a patch containing indomethacin, SIS block copolymer, liquid paraffin, and polyethylene glycol in the plaster layer (see Patent Document 1), a patch containing SIS block copolymer, crotamiton, and anti-inflammatory analgesic An agent (see Patent Document 2) and the like are disclosed. In addition, in order to improve the release of an active ingredient (diclofenac sodium) from a base containing a SIS block copolymer, a patch containing pyrrolidone or the like (see Patent Document 3) has been studied.

According to these patches, since the SIS block copolymer is blended in the plaster layer, it can be manufactured by hot melting without using a solvent, so that it can be manufactured easily and inexpensively, and the environmental load can be reduced. .
JP 2001-302502 A JP-A-4-321624 JP 2002-338462 A

  However, the above-mentioned patch is not sufficiently satisfactory with respect to the release of the anti-inflammatory agent (active ingredient). For this reason, the further improvement of the release | release property of an anti-inflammatory agent was desired.

  Further, in the above-mentioned patch, penetration of the plaster into the support has been a problem. For example, when the patch was applied to the skin for several hours, the plaster soaked into the support layer, and the patch often peeled off the skin or was difficult to be reattached. .

  As a countermeasure against this penetration problem, it is conceivable to cure the plaster layer. However, when the paste layer is hardened, the penetration of the paste into the support is suppressed, but the release of the anti-inflammatory agent from the paste is deteriorated. Further, when an additive for improving the release of the anti-inflammatory agent is added, the penetration of the plaster into the support is induced.

  The present invention has been made in view of the above problems, and is a patch using a SIS block copolymer as a pressure-sensitive adhesive component, which can further improve the release of an anti-inflammatory agent and provide a support. An object of the present invention is to provide a patch capable of suppressing the penetration of the paste.

  The inventors of the present invention conducted intensive research to achieve the above object, and formulated a hardened oil into a plaster layer containing a SIS block copolymer, a tackifier, a plasticizer, and an anti-inflammatory agent. As a result, it was found that the release property of the anti-inflammatory agent can be further improved and the penetration of the plaster into the support can be suppressed, and the present invention has been completed. Specifically, the present invention provides the following.

  (1) A patch comprising a support and a paste layer laminated on the support, wherein the paste layer comprises a styrene-isoprene-styrene block copolymer, a tackifier, a plasticizer A patch comprising an agent, an anti-inflammatory agent, and a hardened oil.

  (2) The anti-inflammatory agent is at least one selected from the group consisting of indomethacin, ketoprofen, diclofenac, felbinac, loxoprofen, flurbiprofen, piroxicam, meloxicam, ketorolac, and pharmacologically acceptable salts thereof. The patch according to (1).

  (3) The patch according to (2), wherein the anti-inflammatory agent is diclofenac and / or a pharmacologically acceptable salt thereof.

  (4) The patch according to any one of (1) to (3), wherein the paste layer further contains an organic acid.

  (5) The patch according to (4), wherein the organic acid is isostearic acid and / or citric acid.

  (6) The patch according to any one of (1) to (5), wherein the plaster layer further contains N-methyl-2-pyrrolidone.

  (7) The patch according to any one of (1) to (6), wherein the plasticizer is liquid paraffin.

  (8) The styrene-isoprene-styrene block copolymer has a mass ratio of styrene and isoprene (styrene / isoprene) of 20/80 to 25/75, according to any one of (1) to (7) Patch.

  According to the present invention, since the hardened oil is blended in the plaster layer containing the SIS block copolymer, the release property of the anti-inflammatory agent can be further improved and the penetration of the plaster into the support can be suppressed.

  Hereinafter, although an example of an embodiment of the present invention is explained, the present invention is not limited to the following embodiment. The patch of the present invention comprises a support and a plaster layer laminated on the support.

<Plaster layer>
The plaster layer constituting the patch of the present invention contains a SIS block copolymer, a tackifier, a plasticizer, an anti-inflammatory agent, and a hardened oil.

[SIS block copolymer]
The SIS block copolymer used in the present invention is a kind of rubber-based pressure-sensitive adhesive. Specifically, it is a styrene-based thermoplastic elastomer belonging to an ABA type polymer and having a molecular structure model in which the terminal block A is polystyrene and the rubber intermediate block B is polyisoprene. The SIS block copolymer used in the present invention is not particularly limited, and those conventionally used can be used. Generally, the ratio (mass ratio) of styrene to rubber is 10/90 to 30 /. 70 and those having a solution viscosity (MPa · s [cps], 25 ° C.) of about 100 to 3000 can be used. As the SIS block copolymer, those having a mass ratio of styrene to isoprene (styrene / isoprene) of 20/80 to 25/75 are preferable. In the patch using the SIS block copolymer having a mass ratio in this range, the effect of improving the release of the anti-inflammatory agent and the effect of suppressing the penetration of the plaster due to the addition of the hardened oil or the like are more likely to appear.

  A commercially available SIS resin can be used as the SIS block copolymer. Examples of commercially available SIS resins include those having a styrene / rubber ratio (mass%) of 15/85 and a solution viscosity (MPa · s [cps], 25 ° C.) of 1,500 (trade name: Kraton D -1107), a styrene / rubber ratio (mass%) of 15/85, and a solution viscosity (MPa · s [cps], 25 ° C.) of 900 (trade name: Kraton D-1112), styrene / rubber ratio ( (Mass%) is 17/83, solution viscosity (MPa · s [cps], 25 ° C.) is 500 (trade name: Kraton D-1117P), styrene / rubber ratio (mass%) is 22/78 (Trade name: Kraton D-KX401), styrene / rubber ratio (mass%) of 16/84 (trade name: Kraton D-KX406), styrene / rubber ratio (mass%) of 30/70, solution viscosity (MPa · s [c s], 25 ° C.) is 300 (trade name: Kraton D-1125x), the styrene / rubber ratio (mass%) is 10/90, and the solution viscosity (MPa · s [cps], 25 ° C.) is 2, 500 (trade name: Clayton D-1320x), etc. (all are manufactured by Clayton Polymer Japan Co., Ltd.), and these can be used alone or in combination of two or more.

  The SIS block copolymer used in the present invention preferably has a high styrene mass ratio, specifically, a styrene / rubber ratio (mass%) of 22/78 (trade name: Kraton D-KX401). Is mentioned. It is preferable that content of the SIS block copolymer used for this invention is 10-40 mass% with respect to the whole plaster.

[Tackifier]
Although it does not specifically limit as a tackifier used by this invention, An alicyclic saturated hydrocarbon resin (synthetic petroleum resin), a rosin ester derivative, a terpene resin, a phenol resin, etc. are preferable. Examples of the alicyclic saturated hydrocarbon resin include Alcon P-100 (trade name: manufactured by Arakawa Chemical Industries). Examples of the rosin ester derivative include ester gum H (trade name: manufactured by Arakawa Chemical Industries), KE-311 (trade name: manufactured by Arakawa Chemical Industries), and KE-100 (trade name: manufactured by Arakawa Chemical Industries). Examples of the terpene resin include YS resin (trade name: manufactured by Yasuhara Chemical Co., Ltd.). As a tackifier used for this invention, these 1 type (s) or 2 or more types can be selected and used, for example. Although content of a tackifier is not specifically limited, It is preferable that it is 10-35 mass% with respect to the whole plaster.

[Plasticizer]
In the present invention, a plasticizer is blended in the plaster layer. The plasticizer is not particularly limited, and those commonly used can be used. For example, liquid alcohol, higher alcohol such as octyldodecanol, squalane, squalene, castor oil, liquid rubber (polybutene), isopropyl myristate, etc. Examples include fatty acid esters. Preferably, it is a liquid paraffin. Although content of a plasticizer is not specifically limited, Generally it is 20-60 mass% with respect to the whole plaster.

[Anti-inflammatory agent]
As the anti-inflammatory agent used in the present invention, commercially available drugs can be used, and examples thereof include indomethacin, ketoprofen, flurbiprofen, loxoprofen, loxoprofen sodium, piroxicam, meloxicam, ketorolac, felbinac, diclofenac and diclofenac sodium. Preferably, it is at least one selected from the group consisting of indomethacin, ketoprofen, diclofenac, felbinac, loxoprofen and pharmacologically acceptable salts thereof, more preferably diclofenac and / or pharmacologically acceptable salts thereof. is there. Although content of an anti-inflammatory agent is not specifically limited, Generally, it is 0.1-20 mass% with respect to the whole plaster.

[Hardened oil]
The patch according to the present invention contains a hardened oil in the plaster layer. Conventionally, when trying to improve the release of the anti-inflammatory agent from the plaster layer, the plaster layer becomes excessively soft and the penetration of the plaster into the support is induced, while the cohesive force is suppressed to suppress the penetration. When strengthening or the like, the plaster layer became excessively hard and the release of the anti-inflammatory agent was deteriorated. However, when hardened oil is added to the paste, the anti-inflammatory agent release from the paste layer is improved due to the improvement of the diffusibility of the anti-inflammatory agent in the paste layer. Infiltration into the support is suppressed. Thereby, the patch which is excellent in resticking property is obtained.

  The hydrogenated oil used in the present invention is not particularly limited, and those hydrogenated using raw materials such as cottonseed oil, soybean oil, castor oil, rapeseed oil, palm oil, fish oil, and the like can be used. Hardened oil is more preferable than partially hardened oil, specifically, hardened castor oil. Moreover, melting | fusing point may be about 80-90 degreeC, and content may be 0.1 mass% or more with respect to the whole plaster. The content is preferably 0.5% by mass or more, more preferably 1% by mass from the viewpoint that the release of the anti-inflammatory agent can be sufficiently improved and the penetration of the plaster into the support can be sufficiently suppressed. That's it. Although the upper limit of content is not specifically limited, It may be 20 mass% or less, and it is preferable that it is 5 mass% or less. The range of the content of the hardened oil is most preferably 0.5% by mass or more and 5% by mass or less.

[Optional ingredients]
The patch of the present invention may contain, as optional components, excipients, antioxidants, drug solubilizers, percutaneous absorption enhancers, fragrances, coloring agents, and the like.

(Excipient)
Excipients used in the present invention 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, and polyvinyl alcohol. Examples thereof include water-soluble polymers, dry aluminum hydroxide gel, aluminum compounds such as hydrous aluminum silicate, kaolin, and titanium oxide.

(Antioxidant)
Examples of the antioxidant used in the present invention include dibutylhydroxytoluene, ascorbic acid, tocopherol, tocopherol ester derivatives, butylhydroxyanisole, and 2-mercaptobenzimidazole.

(Drug dissolution agent, transdermal absorption enhancer)
Examples of the drug solubilizer and transdermal absorption enhancer used in the present invention include organic acids, polyethylene glycol (average molecular weight: 200 to 30000), polyhydric alcohols such as glycerin, ethylene glycol, and diethylene glycol, isopropyl myristate, and palmitic acid. Fatty acid esters such as isopropyl acid and diisopropyl adipate, fatty acid polyhydric alcohol esters such as caprylic acid monoglyceride, caprylic acid triglyceride, sorbitan fatty acid ester, menthol, menthol derivatives, terpenes such as peppermint oil, limonene, N-methyl-2- Examples include pyrrolidone, crotamiton, and polyvinyl alcohol. Of these, organic acids, l-menthol, and N-methyl-2-pyrrolidone are preferable because they can further improve the release and transdermal absorbability of the anti-inflammatory agent.

  Organic acids used in the present invention include aliphatic (mono, di, or tri) carboxylic acids (acetic acid, propionic acid, oleic acid, linoleic acid, linolenic acid, isostearic acid, myristic acid, lauric acid, citric acid ( (Including citric anhydride), isobutyric acid, caproic acid, caprylic acid, lactic acid, maleic acid, pyruvic acid, oxalic acid, succinic acid, tartaric acid, etc., aromatic carboxylic acid (phthalic acid, salicylic acid, benzoic acid, acetylsalicylic acid, etc.) ), Alkyl sulfonic acid, (methane sulfonic acid, ethane sulfonic acid, propyl sulfonic acid, butane sulfonic acid, polyoxyethylene alkyl ether sulfonic acid, etc.), alkyl sulfonic acid derivative (N-2-hydroxyethylpiperidine-N′-2) -Ethanesulfonic acid), cholic acid derivatives (such as dehydrocholic acid), or salts thereof For example, alkali metal salts) such as sodium salts. Among these, carboxylic acids and salts thereof are preferable, and isostearic acid and citric acid are more preferable in terms of further improving the release and transdermal absorbability of the anti-inflammatory agent. These organic acids may be used alone or in combination of two or more.

<Support>
The support used in the present invention is not particularly limited, and stretchable or non-stretchable woven fabrics such as polyethylene and polypropylene, non-woven fabrics, polyethylene, polypropylene, ethylene vinyl acetate copolymers, films such as vinyl chloride, or Examples thereof include foamable supports such as urethane and polyurethane. These may be used alone, or may be used as a laminate of a plurality of types.

<Liner>
The patch of the present invention is a patch comprising a support and a paste layer in which the paste is laminated on the support, and usually a peelable liner is disposed on the paste layer. Provided in form.

  As the releasable liner, polyethylene, polypropylene, ethylene vinyl acetate copolymer, vinyl chloride film, aluminum-deposited metallic film, or the like can be used. Further, a liner surface that has been subjected to a peeling treatment such as a silicon treatment may be used. Moreover, it is preferable that the liner is provided with a linear or curved notch from the viewpoint of facilitating peeling, and as the installation method of the notch, two or more liners may be arranged in layers so as to partially overlap. A folding portion may be provided.

  EXAMPLES Next, although an Example and a comparative example are given and this invention is demonstrated concretely, this invention is not restrict | limited by these Examples.

<Example 1>
Add liquid paraffin, ester gum H (rosin ester resin; manufactured by Arakawa Chemical Industry Co., Ltd.), dibutylhydroxytoluene, hydrogenated oil (K-3 wax 200; manufactured by Kawaken Fine Chemical Co., Ltd.) to Henschel Mixer (registered trademark) and mix. Stir. By adding SIS block copolymer (D-KX401CS; manufactured by Kraton Polymer Japan Co., Ltd.) to this mixture, and further adding l-menthol, N-methyl-2-pyrrolidone, diclofenac sodium, and mixing and stirring, plaster It was created. The plaster was created, was spread on a support (100 g / m ² basis weight of knitted (a polyester)), by laminating the release liner film on the plaster to prepare a patch. The amount of each component was as shown in Table 1.

<Example 2>
Furthermore, a patch was prepared in the same procedure as in Example 1 except that isostearic acid and citric acid were added. The amount of each component was as shown in Table 1.

<Example 3>
A patch was prepared in the same manner as in Example 1 except that ketoprofen was added instead of diclofenac sodium. The amount of each component was as shown in Table 1.

<Example 4>
A patch was prepared in the same manner as in Example 1 except that Alcon P-100 (manufactured by Arakawa Chemical Industries) was added instead of Ester Gum H and indomethacin was added instead of diclofenac sodium. The amount of each component was as shown in Table 1.

<Example 5>
Further, a patch was prepared in the same procedure as in Example 1 except that felbinac was added. The amount of each component was as shown in Table 1.

<Example 6>
Furthermore, a patch was prepared in the same procedure as in Example 1 except that loxoprofen sodium was added. The amount of each component was as shown in Table 1.

(Comparative Example 1)
A patch was prepared in the same procedure as in Example 1 except that no hardened oil was added. The amount of each component was as shown in Table 1.

ＳＩＳ ：ＳＩＳブロック共重合体
ＥＧＨ ：エステルガムＨ（ロジンエステル誘導体）
アルコン ：アルコンＰ−１００（脂環式飽和炭化水素樹脂）
ＬＰ ：流動パラフィン
ＮＭＰ ：Ｎ−メチル−２−ピロリドン
Ｌ−ＭＥＮ ：ｌ−メントール
ＢＨＴ ：ジブチルヒドロキシトルエン
ＤＦＮａ ：ジクロフェナクナトリウム
ＫＰ ：ケトプロフェン
ＩＤ ：インドメタシン
ＦＢ ：フェルビナク
ＬＸＮａ ：ロキソプロフェンナトリウム

SIS: SIS block copolymer EGH: Ester gum H (rosin ester derivative)
Archon: Archon P-100 (alicyclic saturated hydrocarbon resin)
LP: liquid paraffin NMP: N-methyl-2-pyrrolidone L-MEN: 1-menthol BHT: dibutylhydroxytoluene DFNa: diclofenac sodium KP: ketoprofen ID: indomethacin FB: felbinac LXNa: loxoprofen sodium

<Evaluation>
The patches prepared in Examples 1 to 6 and Comparative Example 1 were evaluated for drug release properties, penetration properties, and resticking properties.

[Test Example 1 (Drug Release)]
The test patches (Example 1, Example 2, and Comparative Example 1) were affixed on the back of the minipig, and each patch was peeled off after 2 hours. Next, diclofenac sodium in the peeled test patch was extracted, and the amount of diclofenac sodium remaining was quantified. Based on this residual amount, the drug release from the patch was evaluated by calculating the amount of drug transferred / released from the patch to the skin. The results are shown in Table 2.

  The numerical values in Table 2 indicate the drug release rate (% by mass) relative to the mass of diclofenac sodium contained in the initial patch. As shown in Table 2, it was confirmed that the patch of the present invention showed superior drug release properties than the patch of Comparative Example 1.

[Test Example 2 (Penetration)]
The patches (10 cm × 7 cm) prepared in Examples 1 to 6 and Comparative Example 1 were immediately sealed in a packaging bag and then stored at 60 ° C. for 11 days. Thereafter, the penetration of the plaster into the support was visually observed and evaluated based on the following criteria. The results are shown in Table 3.
“Evaluation criteria for penetration”
○: No penetration was observed.
Δ: Slight penetration is observed.
X: Large penetration is observed.

[Test Example 3 (a. Re-sticking property, b. Stain after skin application)]
The patches (10 cm × 7 cm) prepared in Examples 1 to 6 and Comparative Example 1 were applied to the upper right arm of five monitors. After 12 hours had elapsed, each patch was once peeled and then re-applied to the upper right arm to evaluate re-stickability. Evaluation of restickability was performed based on the following evaluation criteria.
"Evaluation criteria for re-stickability"
○: Adhesiveness is good and can be applied without problems.
(Triangle | delta): Sticking property is a little bad and cannot stick for a long time.
X: Adhesiveness is poor and desorbs in a short time.

  Moreover, when it peeled after progress for 12 hours, the penetration | infiltration situation to the support body of a paste was observed visually and the penetration was evaluated. The evaluation of soaking was performed according to the same criteria as in Test Example 2. The results are shown in Table 3.

  As shown in Table 3, all of the patches prepared in Examples 1 to 6 were not observed to seep into the plaster during storage, and re-sticked to the skin even after 12 hours. It was good and no penetration of the plaster was observed.

  From the above results, it is possible to improve the release of the anti-inflammatory agent by further containing a hardened oil in the paste layer containing the SIS block copolymer, the tackifier, the plasticizer, and the anti-inflammatory agent. It was found that it was possible to suppress the penetration of the resin into the support and to improve the re-sticking property.

Claims (8)

A patch comprising a support and a plaster layer laminated on the support,
The plaster layer contains a styrene-isoprene-styrene block copolymer, a tackifier, a plasticizer, an anti-inflammatory agent, and a hardened oil.   2. The anti-inflammatory agent is at least one selected from the group consisting of indomethacin, ketoprofen, diclofenac, felbinac, loxoprofen, flurbiprofen, piroxicam, meloxicam, ketorolac, and pharmacologically acceptable salts thereof. The patch described in 1.   The patch according to claim 2, wherein the anti-inflammatory agent is diclofenac and / or a pharmacologically acceptable salt thereof.   The patch according to any one of claims 1 to 3, wherein the paste layer further contains an organic acid.   The patch according to claim 4, wherein the organic acid is isostearic acid and / or citric acid.   The patch according to any one of claims 1 to 5, wherein the paste layer further contains N-methyl-2-pyrrolidone.   The patch according to any one of claims 1 to 6, wherein the plasticizer is liquid paraffin.   The patch according to any one of claims 1 to 7, wherein the styrene-isoprene-styrene block copolymer has a styrene / isoprene mass ratio (styrene / isoprene) of 20/80 or more and 25/75 or less.