JP3573803B2 - External preparation for skin - Google Patents
External preparation for skin Download PDFInfo
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- JP3573803B2 JP3573803B2 JP24745294A JP24745294A JP3573803B2 JP 3573803 B2 JP3573803 B2 JP 3573803B2 JP 24745294 A JP24745294 A JP 24745294A JP 24745294 A JP24745294 A JP 24745294A JP 3573803 B2 JP3573803 B2 JP 3573803B2
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- skin
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- external preparation
- film
- plasticizer
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Description
【０００１】
【産業上の利用分野】
本発明は皮膚外用剤に関し、更に詳しくは皮膚真菌症治療用の皮膚外用剤に関する。
【０００２】
【従来の技術】
水虫に代表される皮膚真菌症は、罹患者数が多く、しかも治癒しにくいので隠れた大きな社会問題であるといわれている。この疾病が治癒しにくい理由は、病原菌の存在場所が角質層内であるため、薬物が浸透しにくく、また浸透してもすぐに角質層を通過して血中へ移行してしまうため、角質層内に薬物が貯留せず、薬物の治療効果が発揮しにくいことにあるといわれている。
かかる状況のもとに、角質層内の薬物濃度を上昇させる試みが、多くの人によって為されてきている。例えば、薬物と相溶性の良い溶解媒体に薬物を溶解させることにより、薬物の皮膚内への浸透を促進したり、プラスター等の閉塞機材を用いて皮膚を閉塞することによって薬物が皮膚に浸透する効果を高めたり、薬物に被膜形成剤を配合し、薬物を含んだ被膜を皮膚上に形成させることにより、薬物の皮膚内への浸透を高めたりする試みが為されてきた。
【０００３】
しかしながら、薬物と相溶性の良い溶解媒体は往々にして揮発性が高く、従ってこれを含有する製剤を皮膚に塗布すると間もなく薬物の結晶が析出するため、かえって薬物の吸収性が妨げられたり、閉塞機材による閉塞がなされた場合は使用感が著しく損なわれてしまう上、粘着剤による皮膚のかぶれなどの好ましくない皮膚反応を引き起こし易く実用的でない。
また、被膜形成剤を配合した製剤においては、被膜形成剤が水溶性の場合は汗などによって被膜が散逸し易く、また、被膜形成剤が非水溶性の場合は、非水溶性被膜形成剤が往々にして剛性が高く脆いため、被膜が割れて薬物が皮膚から剥離脱落し易い傾向にあり、薬物の角質層内に於ける貯留の改善に関しては大きな問題があった。
【０００４】
【発明が解決しようとする課題】
従って本発明の目的は、抗真菌剤を効率よく角質層内に貯留させ得る皮膚真菌治療用の皮膚外用剤を提供することにある。
【０００５】
【課題を解決するための手段】
かかる実状に鑑み、本発明者らは角質層内に抗真菌剤を貯留させ得る製剤について鋭意検討を重ねた結果、２種類以上の被膜形成剤を配合し、且つ可塑剤の被膜形成剤に対する割合が重量比で２．２〜５となるように可塑剤を配合することにより、柔軟性に優れ、且つ閉塞性と角質層内に薬物を浸透させる作用に優れた製剤が得られることを見出し、発明を完成させた。
【０００６】
即ち、本発明はエチルセルロース１〜４重量％及びメタアクリル酸メタアクリル酸メチルコポリマー０．１〜１重量％からなる被膜形成剤、水１〜１０重量％、可塑剤２．２〜２５重量％、抗真菌剤０．１〜５重量％、並びにアルコール５０〜９５重量％を含有し、且つ可塑剤の被膜形成剤に対する割合が重量比で２．２〜５であることを特徴とする皮膚外用剤を提供するものである。
【０００７】
ここで、本発明で用いる被膜形成剤は、エチルセルロースとメタアクリル酸メタアクリル酸メチルコポリマーを組み合わせて使用する。その理由は、１種のみの被膜形成剤を使用した場合には形成される被膜が硬く且つ割れ易いため、割れて皮膚から脱落するが、２種組み合わせて用いると被膜の剛性が抑制され、脱落が防止できるためである。
【０００８】
これら被膜形成剤の配合量は皮膚外用剤全量の１〜５重量％（以下、単に％で示す）、特に３．５〜４．５％とすることが好ましい。配合量が１％未満では被膜形成性が十分ではなく、また、５％を超えても閉塞性が変わらないばかりか皮膜が厚くなりすぎるため、塗布した製剤が皮膚から脱落し易くなる。
【０００９】
更に、エチルセルロースとメタアクリル酸メタアクリル酸メチルコポリマーの組み合わせに於いて、この二つの被膜形成剤の重量比を５：１〜８：１とすることが好ましい。この重量比で被膜形成剤を配合することにより、皮膚に塗布した場合に適度な剛性と柔軟性を持つ剥離しにくい被膜を形成する皮膚外用剤を得ることができる。
【００１０】
本発明の皮膚外用剤に配合する水は２種の被膜形成剤を相溶させる作用を持っており、本発明に於いて不可欠の要素である。水が適切な相溶作用を発揮するためには、皮膚外用剤全量に対して１〜１０％、特に３〜６％とすることが好ましい。水の量が１％未満では相溶作用が期待できず、また、１０％を超えると分離などを引き起こし、皮膚外用剤の系の不安定化の原因となる。
【００１１】
本発明の皮膚外用剤に配合する可塑剤としては、被膜に柔軟性を与える得るものであれば特に限定されないが、多塩基酸のエステル、多価アルコール又は多価アルコールのエステルが好適である。かかる可塑剤としては、アジピン酸ジイソプロピル、セバシン酸ジエチル、フタル酸ジエチル、クエン酸トリエチル、グリセリン、プロピレングリコール、１，３−ブタンジオール、グリセリルモノオレート等が例示できる。このうち特にアジピン酸ジイソプロピル、セバシン酸ジエチル、フタル酸ジエチル、クエン酸トリエチルを用いることが好ましい。
【００１２】
かかる可塑剤の配合量は、被膜形成剤に対して重量比で２．２〜５、特に２．３〜３、従って、皮膚外用剤全量に対して２．２〜２５％、特に８〜１３．５％であることが好適である。可塑剤が皮膚形成剤の２．２倍量未満であると剛性のある被膜となるため皮膚から剥離し易くなり、また、５倍量を超えると被膜形成を阻害するばかりか、分離などを引き起こし、皮膚外用剤の系の不安定化の原因となる。
【００１３】
本発明の皮膚外用剤に於ける抗真菌剤としては、クロトリマゾール、硝酸ミコナゾール、硝酸エコナゾール、硝酸イソコナゾール、ピロールニトリン、トルナフテート、ビフマシン、トリコマイシン、シクロピロクスオクラミン、エキサラミド、ハロプロジンなどが好適に使用される。これらは１種を単独で用いても２種以上を組み合わせて用いてもよい。
この抗真菌剤の配合量は抗真菌剤の種類により、安全性と抗真菌作用を勘案して決められるものであるが、皮膚外用剤全量の０．１〜５％、特に０．８〜１．５％とすることが好ましい。
【００１４】
本発明の皮膚外用剤に配合するアルコールとは、低鎖長のアルキル基を有するアルコールであり、具体的にはメタノール、エタノール、ノルマルプロパノール、イソプロパノール、ノルマルブタノール、ｔ−ブチルアルコール等の炭素数１〜４のアルコールが例示できる。これらは１種を単独でも２種以上を混合して用いることもできるが、安全性及び皮膚浸透性の観点から、特にエタノール及び／又はイソプロパノールを用いることが好ましく、最も好適なのはエタノールを単独で用いることである。
アルコールの配合量は皮膚外用剤全量の５０〜９５％、特に６０〜８０％とすることが好ましい。配合量が５０％未満では被膜形成剤が十分に溶解しないため、薬物の角質層への浸透性が悪くなるなどの不都合があり、また配合量が９０％を超えると他の成分の自由度が制限され過ぎることとなる。
【００１５】
本発明の皮膚外用剤として特に好ましい成分及びその含有割合は、被膜形成剤としてエチルセルロース１〜４％、特に２．９〜４％及びメタアクリル酸メタアクリル酸メチルコポリマー０．１〜１％、特に０．４〜０．８％、水１〜１０％、特に３〜６％、可塑剤２．５〜２５％、特に８〜１３．５％、抗真菌剤としてクロトリマゾール０．１〜２％、特に０．８〜１．５％、アルコールとしてエタノール５０〜９５％、特に６０〜８０％である。
【００１６】
本発明の皮膚外用剤には、これらの必須成分以外に通常の皮膚外用剤で用いられる任意成分を本発明の効果を損なわない範囲に於いて配合することができる。任意成分としては、例えばｐＨ調整剤、界面活性剤、増粘剤、メチルパラベン、ブチルパラベン等の防腐剤、ベンゾフェノン誘導体、アミノ安息香酸誘導体等の紫外線吸収剤、γ−トコフェロール、ＢＨＴ等の抗酸化剤、香料などが挙げられる。更に、ジフェンヒドラミン等の抗ヒスタミン剤、クロタミトン等の鎮痒剤、グリチルレチン酸等の抗炎症剤、局所麻酔剤などのような皮膚真菌症に伴う炎症などの付随症状を緩和或いは治療する成分を配合することもできる。
これらの必須成分及び任意成分より本発明の皮膚外用剤を製造するには、通常の方法を用いて行えばよく、例えば、これら成分を秤量し、加熱撹拌して溶解させた後、冷却するなどの方法を採用することができる。
【００１７】
【実施例】
以下、実施例を挙げて更に詳しく本発明について説明するが、本発明がこれら実施例に限定されないことはいうまでもない。
【００１８】
実施例１〜３及び比較例１〜３
表１に示す成分を秤量し、８０℃に加熱撹拌して溶解させ、冷却することにより実施例１〜３及び比較例１〜３の皮膚外用剤を得た。これらを下腕部に塗布した後、水で湿らせたガーゼでこすり、下記基準に従って皮膚からの剥離性を評価した。結果を表１に示す。
− ：剥離しにくい。
＋ ：剥離し易い。
＋＋：極めて剥離し易い。
表１から、２種以上の被膜形成剤を配合した本発明の皮膚外用剤は優れた剥離抵抗性を有していることが分かる。
【００１９】
【表１】
実施例４〜７及び比較例４〜５
表２に示す成分を秤量し、実施例１〜３と同様にして実施例４〜７及び比較例４〜５の皮膚外用剤を得た。これらの溶状を目視で観察したところ、水を含んでいない比較例４〜５の皮膚外用剤は何れもやや白濁しており均一性に問題があったが、実施例４〜７の皮膚外用剤は何れも無色透明で均一性に優れたものであった。結果を表２に示す。
【００２１】
【表２】
実施例８〜１２
表３に示す成分を秤量し、実施例１〜３と同様にして実施例８〜１２の皮膚外用剤を得た。併せて実施例１〜３と同様にして剥離性の評価を行った。結果を表３に示す。表３から、表３に示すいずれの可塑剤を用いても本発明の効果を阻害しないことが分かる。
【００２３】
【表３】
実施例１３
比較例１及び実施例８で得られた皮膚外用剤について、モルモットを用いた角質層内薬物貯留性試験を行った。即ち、検体０．１ｍｌをクローズドパッチしたハートレイ系白色種モルモット（雄性、３００〜３５０ｇ）を一定時間ごとに屠殺して背部皮膚を剥離し、直径３０ｍｍの円形にパンチで打ち抜き、３０ｍｌのメタノール中に浸漬して超音波を３分間かけ、その後２４時間浸漬し、再び超音波に３分間かけて抽出した後、メスフラスコへ洗い込み５０ｍｌにメスアップしてＨＰＬＣにより貯留しているクロトリマゾールの量を定量した。結果を表４に示す。表４から、実施例８の皮膚外用剤は、抗真菌剤を角質層内に高濃度に且つ長時間貯留させていることが分かる。
【００２５】
【表４】
【発明の効果】
本発明の皮膚外用剤は、抗真菌剤を高濃度に且つ長時間、即ち極めて効率的に、角質層内に貯留させることができるので、真菌症の治療に大変有益なものである。[0001]
[Industrial applications]
The present invention relates to a skin external preparation, and more particularly, to a skin external preparation for treating dermatomycosis.
[0002]
[Prior art]
It is said that dermatomycosis typified by athlete's foot is a big social problem that is hidden because it has a large number of affected individuals and is difficult to cure. The reason that this disease is hard to cure is that the pathogen is located in the stratum corneum, so it is difficult for the drug to penetrate, and even if it penetrates, the drug passes through the stratum corneum and enters the blood. It is said that the drug does not accumulate in the layer and the therapeutic effect of the drug is hardly exhibited.
Under such circumstances, many people have attempted to increase the drug concentration in the stratum corneum. For example, by dissolving a drug in a dissolution medium having good compatibility with the drug, the penetration of the drug into the skin is promoted, or the drug penetrates the skin by closing the skin using an occluding device such as a plaster. Attempts have been made to enhance the effect or increase the penetration of the drug into the skin by blending the drug with a film-forming agent and forming a film containing the drug on the skin.
[0003]
However, dissolution media having good compatibility with drugs often have high volatility, so that when a preparation containing the same is applied to the skin, the crystals of the drug precipitate out soon after the application, so that the absorption of the drug is hindered or blocked. If the device is blocked, the feeling of use is significantly impaired, and an undesired skin reaction such as skin irritation due to the adhesive is easily caused, which is not practical.
In a formulation containing a film-forming agent, when the film-forming agent is water-soluble, the film is easily dissipated by sweat or the like, and when the film-forming agent is water-insoluble, the water-insoluble film-forming agent is used. Often, because of high rigidity and brittleness, the coating tends to crack and the drug tends to peel off from the skin, and there has been a major problem in improving the retention of the drug in the stratum corneum.
[0004]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide a skin external preparation for treating skin fungi that can efficiently store an antifungal agent in the stratum corneum.
[0005]
[Means for Solving the Problems]
In view of such circumstances, the present inventors have conducted intensive studies on a preparation capable of storing an antifungal agent in the stratum corneum. As a result, the ratio of the plasticizer to the film forming agent in which two or more kinds of film forming agents are blended and By blending a plasticizer so that the weight ratio becomes 2.2 to 5, it is found that a formulation excellent in flexibility, and excellent in occlusive properties and action of penetrating the drug into the stratum corneum can be obtained. Completed the invention.
[0006]
That is, the present invention provides a film-forming agent comprising 1 to 4% by weight of ethyl cellulose and 0.1 to 1% by weight of a methyl methacrylate / methyl methacrylate copolymer, 1 to 10% by weight of water, 2.2 to 25% by weight of a plasticizer, An external skin preparation comprising 0.1 to 5% by weight of an antifungal agent and 50 to 95% by weight of an alcohol, and a weight ratio of a plasticizer to a film-forming agent of 2.2 to 5. Is provided.
[0007]
Here, as the film forming agent used in the present invention , ethyl cellulose and methacrylic acid methyl methacrylate copolymer are used in combination . The reason is that when only one kind of film forming agent is used, the formed film is hard and easily broken, so that the film breaks and falls off the skin. There Ru der order can be prevented.
[0008]
The amount of these film-forming agents is preferably 1 to 5% by weight (hereinafter simply referred to as%), particularly 3.5 to 4.5% of the total amount of the external preparation for skin. If the amount is less than 1%, the film-forming property is not sufficient, and if it exceeds 5%, not only does the occlusive property remain unchanged, but the film becomes too thick, so that the applied preparation easily falls off the skin.
[0009]
Furthermore, in the combination of ethyl cellulose and methacrylic acid methyl methacrylate copolymer, the weight ratio of the two film-forming agents is preferably 5: 1 to 8: 1. By blending a film-forming agent at this weight ratio, a skin external preparation that forms a film that has a suitable rigidity and flexibility and is difficult to peel off when applied to the skin can be obtained.
[0010]
Water incorporated in the external preparation for skin of the present invention has an action of making two kinds of film forming agents compatible with each other, and is an essential element in the present invention. In order for water to exert an appropriate compatibility action, it is preferably from 1 to 10%, particularly preferably from 3 to 6%, based on the total amount of the external preparation for skin. If the amount of water is less than 1%, no compatible action can be expected, and if it exceeds 10%, separation or the like is caused, which causes the system of the external preparation for skin to become unstable.
[0011]
The plasticizer to be added to the external preparation for skin of the present invention is not particularly limited as long as it can impart flexibility to the film, but is preferably a polybasic acid ester, a polyhydric alcohol, or a polyhydric alcohol ester. Examples of such a plasticizer include diisopropyl adipate, diethyl sebacate, diethyl phthalate, triethyl citrate, glycerin, propylene glycol, 1,3-butanediol, and glyceryl monooleate. Among them, it is particularly preferable to use diisopropyl adipate, diethyl sebacate, diethyl phthalate, and triethyl citrate.
[0012]
The compounding amount of such a plasticizer is 2.2 to 5, particularly 2.3 to 3, in weight ratio to the film-forming agent, and therefore 2.2 to 25%, especially 8 to 13%, based on the total amount of the external preparation for skin. It is preferably 0.5%. If the plasticizer is less than 2.2 times the amount of the skin-forming agent, it becomes a stiff film, which makes it easy to peel off from the skin. If the plasticizer exceeds 5 times the amount, it not only inhibits film formation but also causes separation. This may cause instability of the skin external preparation system.
[0013]
Examples of the antifungal agent in the external preparation for skin of the present invention include clotrimazole, miconazole nitrate, econazole nitrate, isoconazole nitrate, pyrrolnitrin, tolnaphthate, bifumacin, tricomycin, ciclopirox oclamin, exalamide, haloprosin and the like. It is preferably used. These may be used alone or in combination of two or more.
The amount of the antifungal agent is determined according to the type of the antifungal agent in consideration of the safety and the antifungal effect, but it is 0.1 to 5%, particularly 0.8 to 1% of the total amount of the external preparation for skin. It is preferably set to 0.5%.
[0014]
The alcohol to be incorporated in the external preparation for skin of the present invention is an alcohol having an alkyl group having a low chain length, and specifically has 1 carbon atom such as methanol, ethanol, normal propanol, isopropanol, normal butanol, and t-butyl alcohol. To 4 alcohols. These can be used alone or in combination of two or more, but from the viewpoint of safety and skin permeability, it is particularly preferable to use ethanol and / or isopropanol, and most preferable to use ethanol alone. That is.
The amount of the alcohol is preferably 50 to 95%, more preferably 60 to 80% of the total amount of the external preparation for skin. If the blending amount is less than 50%, the film-forming agent is not sufficiently dissolved, so that there are disadvantages such as poor penetration of the drug into the stratum corneum. If the blending amount exceeds 90%, the degree of freedom of other components is reduced. It would be too restrictive.
[0015]
Particularly preferred components and the content ratio of the external preparation for skin of the present invention are, as a film-forming agent, 1 to 4%, particularly 2.9 to 4%, of ethylcellulose and 0.1 to 1% of methyl methacrylate-methyl methacrylate copolymer, particularly 0.4-0.8%, water 1-10%, especially 3-6%, plasticizer 2.5-25%, especially 8-13.5%, clotrimazole 0.1-2 as antifungal agent %, Especially 0.8-1.5%, ethanol as alcohol 50-95%, especially 60-80%.
[0016]
The skin external preparation of the present invention may contain, in addition to these essential components, optional components used in ordinary skin external preparations as long as the effects of the present invention are not impaired. Optional components include, for example, pH adjusters, surfactants, thickeners, preservatives such as methylparaben and butylparaben, ultraviolet absorbers such as benzophenone derivatives and aminobenzoic acid derivatives, and antioxidants such as γ-tocopherol and BHT. And fragrances. Further, an antihistamine such as diphenhydramine, an antipruritic such as crotamiton, an anti-inflammatory agent such as glycyrrhetinic acid, and a component for reducing or treating accompanying symptoms such as inflammation associated with dermatomycosis, such as a local anesthetic, can be added. .
In order to produce the skin external preparation of the present invention from these essential components and optional components, it may be carried out using a usual method.For example, these components are weighed, heated and stirred, dissolved, and then cooled. Can be adopted.
[0017]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples, but it goes without saying that the present invention is not limited to these Examples.
[0018]
Examples 1-3 and Comparative Examples 1-3
The components shown in Table 1 were weighed, dissolved by heating and stirring at 80 ° C., and cooled to obtain skin external preparations of Examples 1 to 3 and Comparative Examples 1 to 3. After these were applied to the lower arm, they were rubbed with gauze moistened with water, and the peelability from the skin was evaluated according to the following criteria. Table 1 shows the results.
-: Difficult to peel.
+: Easy to peel.
++: Extremely easy to peel.
Table 1 shows that the external preparation for skin of the present invention containing two or more film-forming agents has excellent peel resistance.
[0019]
[Table 1]
Examples 4 to 7 and Comparative Examples 4 to 5
The components shown in Table 2 were weighed, and skin external preparations of Examples 4 to 7 and Comparative Examples 4 and 5 were obtained in the same manner as in Examples 1 to 3. When these dissolution states were visually observed, the skin external preparations of Comparative Examples 4 to 5 containing no water were slightly cloudy and had a problem in uniformity, but the skin external preparations of Examples 4 to 7 Were colorless and transparent and excellent in uniformity. Table 2 shows the results.
[0021]
[Table 2]
Examples 8 to 12
The components shown in Table 3 were weighed, and skin external preparations of Examples 8 to 12 were obtained in the same manner as in Examples 1 to 3. At the same time, the peelability was evaluated in the same manner as in Examples 1 to 3. Table 3 shows the results. Table 3 shows that the effects of the present invention are not impaired by using any of the plasticizers shown in Table 3.
[0023]
[Table 3]
Example 13
The skin external preparations obtained in Comparative Example 1 and Example 8 were subjected to a drug retention test in the stratum corneum using a guinea pig. That is, a Hartley white guinea pig (male, 300 to 350 g) in which 0.1 ml of a sample is closed and patched is slaughtered at regular intervals, the back skin is peeled off, a 30 mm diameter circle is punched out with a punch, and 30 ml of methanol is injected. Immerse and sonicate for 3 minutes, immerse for 24 hours, extract again for 3 minutes with ultrasonic wave, rinse into a volumetric flask, make up to 50 ml, and store the amount of clotrimazole stored by HPLC Was quantified. Table 4 shows the results. From Table 4, it can be seen that the skin external preparation of Example 8 stores the antifungal agent in the stratum corneum at a high concentration for a long time.
[0025]
[Table 4]
【The invention's effect】
INDUSTRIAL APPLICABILITY The topical skin preparation of the present invention is very useful for the treatment of mycosis because the antifungal agent can be stored in the stratum corneum at a high concentration and for a long time, that is, very efficiently.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24745294A JP3573803B2 (en) | 1994-02-16 | 1994-10-13 | External preparation for skin |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6-18780 | 1994-02-16 | ||
| JP1878094 | 1994-02-16 | ||
| JP24745294A JP3573803B2 (en) | 1994-02-16 | 1994-10-13 | External preparation for skin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH07277975A JPH07277975A (en) | 1995-10-24 |
| JP3573803B2 true JP3573803B2 (en) | 2004-10-06 |
Family
ID=26355510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24745294A Expired - Lifetime JP3573803B2 (en) | 1994-02-16 | 1994-10-13 | External preparation for skin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3573803B2 (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19653606A1 (en) * | 1996-12-20 | 1998-06-25 | Roehm Gmbh | Adhesive and binder made from (meth) acrylate polymer, organic acid and plasticizer |
| US6899897B2 (en) * | 2001-06-18 | 2005-05-31 | Jaleva, Inc. | Gum resin as a carrier for topical application of pharmacologically active agents |
| US8039452B2 (en) | 2002-06-18 | 2011-10-18 | Pola Pharma Inc. | Antifungal medicinal compositions |
| WO2004002452A1 (en) * | 2002-06-27 | 2004-01-08 | Pola Chemical Industries Inc. | Drug composition |
| EP1901709A2 (en) * | 2005-06-10 | 2008-03-26 | Galderma S.A. | Controlled release of a drug through skin on the basis of a topical composition comprising a drug, a film-forming silicone and at least one volatile solvent |
| JP2010279384A (en) * | 2005-08-31 | 2010-12-16 | Pola Pharma Inc | Method for evaluating antifungal agent |
| JP5319950B2 (en) | 2008-04-08 | 2013-10-16 | 帝國製薬株式会社 | Aqueous patch containing butenafine hydrochloride |
| WO2010093992A1 (en) | 2009-02-13 | 2010-08-19 | Topica Pharmaceuticals, Inc | Anti-fungal formulation |
| JP6077081B2 (en) * | 2015-10-06 | 2017-02-08 | 株式会社ポーラファルマ | Pharmaceutical composition |
| WO2020161771A1 (en) * | 2019-02-04 | 2020-08-13 | マルホ株式会社 | Skin composition |
| WO2022029938A1 (en) * | 2020-08-05 | 2022-02-10 | マルホ株式会社 | Skin composition |
-
1994
- 1994-10-13 JP JP24745294A patent/JP3573803B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07277975A (en) | 1995-10-24 |
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