JP2013241388A - Foamable skin external preparation - Google Patents

Foamable skin external preparation Download PDF

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Publication number
JP2013241388A
JP2013241388A JP2012198582A JP2012198582A JP2013241388A JP 2013241388 A JP2013241388 A JP 2013241388A JP 2012198582 A JP2012198582 A JP 2012198582A JP 2012198582 A JP2012198582 A JP 2012198582A JP 2013241388 A JP2013241388 A JP 2013241388A
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external preparation
skin external
viscous composition
skin
acidic
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Nobutada Kusaba
宣廷 草場
Saeko Isaka
小枝子 井阪
Takayuki Shikano
隆行 鹿野
Hiroya Takahashi
宏哉 高橋
Kinya Takagaki
欣也 高垣
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Toyo Shinyaku Co Ltd
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Toyo Shinyaku Co Ltd
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Abstract

PROBLEM TO BE SOLVED: To provide a foamable skin external preparation capable of achieving both two effects, increase in amount of cutaneous blood flow and rise in water amount of a horny cell layer, in higher level.SOLUTION: A foamable skin external preparation is a two component type foamable skin external preparation consisting of a viscous composition and acid granules, and the viscous composition and the acid granules are mixed together on use. The viscous composition includes carbonate, pine bark extract and caffeine at least. The acid granules include at least an acidic substance reacting with the carbonate to foam.

Description

本発明は、炭酸塩と酸とを使用時に混合する2剤型の発泡性皮膚外用剤に関する。   The present invention relates to a two-part foaming skin external preparation in which carbonate and acid are mixed at the time of use.

従来、美容を目的として、炭酸塩と酸とを水の存在下において混合し、炭酸ガスを発生させて使用するジェルタイプの発泡性皮膚外用剤(炭酸ジェルパック)が提案されている(例えば、特許文献1参照)。しかし、既存の炭酸ジェルパックでは、皮膚血流量の増加効果が必ずしも十分であるとはいえないという問題がある。   Conventionally, for the purpose of beauty, a gel type foaming skin external preparation (carbonic acid gel pack) that is used by mixing carbonate and acid in the presence of water and generating carbon dioxide gas has been proposed (for example, Patent Document 1). However, the existing carbonic acid gel pack has a problem that the effect of increasing the skin blood flow is not always sufficient.

一方、松樹皮抽出物に含まれるプロアントシアニジンは、皮膚血流量の改善効果を有することが知られている(例えば、特許文献2参照)。この松樹皮抽出物を炭酸ジェルパックに配合させても、所望の効果が発現されるかどうか、更には炭酸ジェルパックとして望まれる性能が得られるのかどうかは明らかでない。   On the other hand, it is known that proanthocyanidins contained in the pine bark extract have an effect of improving skin blood flow (see, for example, Patent Document 2). It is not clear whether the pine bark extract can be blended with the carbonic acid gel pack to achieve the desired effect, and further whether the desired performance as the carbonic acid gel pack can be obtained.

更に、発泡性皮膚外用剤において、肌のみずみずしさに起因する“角層水分量”を効果的に上昇させたいというニーズがある。しかし、既存の炭酸ジェルパックでは、角層水分量の上昇効果が必ずしも十分とはいえないという問題がある。   Furthermore, there is a need to effectively increase the “amount of stratum corneum moisture” resulting from freshness of the skin in the foamable external preparation for skin. However, the existing carbonic acid gel pack has a problem that the effect of increasing the stratum corneum moisture content is not always sufficient.

したがって、皮膚血流量の増加及び角層水分量の上昇という2つの効果を高次で両立できる発泡性皮膚外用剤の速やかな提供が強く求められているのが現状である。   Therefore, at present, there is a strong demand for prompt provision of an external preparation for foaming skin that can achieve both the high effects of the two effects of increasing skin blood flow and increasing stratum corneum moisture.

特許第4659980号公報Japanese Patent No. 4659980 特開2004−123622号公報JP 2004-123622 A

本発明は、前記従来における諸問題を解決し、以下の目的を達成することを課題とする。即ち、本発明は、皮膚血流量の増加及び角層水分量の上昇という2つの効果を高次で両立できる発泡性皮膚外用剤を提供することを目的とする。   An object of the present invention is to solve the conventional problems and achieve the following objects. That is, an object of the present invention is to provide an effervescent skin external preparation capable of achieving both the high effects of the two effects of increasing the skin blood flow rate and increasing the stratum corneum moisture content.

前記課題を解決するため、本発明者らは鋭意検討した結果、以下のような知見を得た。即ち、粘性組成物と酸性顆粒とからなり、該粘性組成物と該酸性顆粒とを使用時に混合する2剤型の発泡性皮膚外用剤であって、前記粘性組成物が、炭酸塩、松樹皮抽出物、及びカフェインを少なくとも含有し、前記酸性顆粒が、前記炭酸塩と反応して発泡を生じさせる酸性物質を少なくとも含有する発泡性皮膚外用剤を用いると、皮膚血流量の増加及び角層水分量の上昇という2つの効果を高次で両立できることを見出した。   In order to solve the above-mentioned problems, the present inventors have made extensive studies and as a result, obtained the following findings. That is, a two-part foaming skin external preparation comprising a viscous composition and acidic granules and mixing the viscous composition and acidic granules at the time of use, wherein the viscous composition comprises carbonate, pine bark When using an effervescent skin external preparation containing at least an extract and caffeine, and the acidic granule contains at least an acidic substance that reacts with the carbonate to cause foaming, an increase in skin blood flow and a stratum corneum It has been found that the two effects of increasing the water content can be achieved at a high order.

本発明は、前記知見に基づくものであり、前記課題を解決するための手段としては、以下の通りである。即ち、
<1> 粘性組成物と酸性顆粒とからなり、該粘性組成物と該酸性顆粒とを使用時に混合する2剤型の発泡性皮膚外用剤であって、前記粘性組成物が、炭酸塩、松樹皮抽出物、及びカフェインを少なくとも含有し、前記酸性顆粒が、前記炭酸塩と反応して発泡を生じさせる酸性物質を少なくとも含有することを特徴とする発泡性皮膚外用剤である。
<2> 使用時における粘性組成物と酸性顆粒との混合質量比(粘性組成物:酸性顆粒)が、10:1〜20:1である前記<1>に記載の発泡性皮膚外用剤である。
<3> 粘性組成物における、炭酸塩の含有量が1質量%以上5質量%以下であり、松樹皮抽出物の含有量が0超0.15質量%以下であり、カフェインの含有量が0超0.5質量%以下である前記<1>から<2>のいずれかに記載の発泡性皮膚外用剤である。
The present invention is based on the above knowledge, and means for solving the above problems are as follows. That is,
<1> A two-part foaming skin external preparation comprising a viscous composition and acidic granules, wherein the viscous composition and acidic granules are mixed at the time of use, wherein the viscous composition comprises carbonate, pine A foamable skin external preparation containing at least a bark extract and caffeine, wherein the acidic granule contains at least an acidic substance that reacts with the carbonate to cause foaming.
<2> The foamable skin external preparation according to <1>, wherein a mixing mass ratio of the viscous composition and acidic granules (viscous composition: acidic granules) in use is 10: 1 to 20: 1. .
<3> The content of carbonate in the viscous composition is 1% by mass or more and 5% by mass or less, the content of the pine bark extract is more than 0 and 0.15% by mass or less, and the content of caffeine is The foamable external preparation for skin according to any one of <1> to <2>, which is more than 0 and 0.5% by mass or less.

本発明によると、前記従来における諸問題を解決することができ、皮膚血流量の増加及び角層水分量の上昇という2つの効果を高次で両立できる発泡性皮膚外用剤を提供することができる。   ADVANTAGE OF THE INVENTION According to this invention, the said various problems in the past can be solved, and the foamable skin external preparation which can make compatible the two effects of the increase in skin blood flow rate and a raise of a stratum corneum water content in higher order can be provided. .

(発泡性皮膚外用剤)
本発明の発泡性皮膚外用剤は、粘性組成物と酸性顆粒とを使用時に混合する2剤型の発泡性皮膚外用剤であり、更に必要に応じてその他の成分を含有させてもよい。
(Foamable external preparation for skin)
The foamable skin external preparation of the present invention is a two-part foamable skin external preparation in which a viscous composition and acidic granules are mixed at the time of use, and may further contain other components as necessary.

<粘性組成物>
前記粘性組成物は、炭酸塩、松樹皮抽出物、及びカフェインを少なくとも含有し、増粘剤及び水を更に含有することが好ましい。
<Viscous composition>
The viscous composition preferably contains at least carbonate, pine bark extract, and caffeine, and further contains a thickener and water.

−炭酸塩−
前記炭酸塩としては、前記酸性顆粒中に含有される酸性物質と反応して二酸化炭素を発生させる炭酸塩であれば、特に制限はなく、目的に応じて適宜選択することができ、例えば、炭酸アンモニウム、炭酸水素アンモニウム、炭酸カリウム、炭酸水素カリウム、セスキ炭酸カリウム、炭酸ナトリウム、重炭酸ナトリウム、炭酸水素ナトリウム、セスキ炭酸ナトリウム、炭酸リチウム、炭酸水素リチウム、セスキ炭酸リチウム、炭酸セシウム、炭酸水素セシウム、セスキ炭酸セシウム、炭酸マグネシウム、炭酸水素マグネシウム、炭酸水素カルシウム、炭酸水酸化マグネシウム、炭酸バリウムなどが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。これらの中でも、炭酸水素ナトリウムが好ましい。
-Carbonate-
The carbonate is not particularly limited as long as it is a carbonate that reacts with an acidic substance contained in the acidic granule to generate carbon dioxide, and can be appropriately selected according to the purpose. Ammonium, ammonium bicarbonate, potassium carbonate, potassium bicarbonate, potassium sesquicarbonate, sodium carbonate, sodium bicarbonate, sodium bicarbonate, sodium sesquicarbonate, lithium carbonate, lithium bicarbonate, lithium sesquicarbonate, cesium carbonate, cesium bicarbonate, Examples include cesium carbonate, magnesium carbonate, magnesium hydrogen carbonate, calcium hydrogen carbonate, magnesium carbonate hydroxide, and barium carbonate. These may be used alone or in combination of two or more. Among these, sodium hydrogen carbonate is preferable.

前記炭酸塩の前記粘性組成物における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、1質量%以上5質量%以下が好ましい。前記含有量が、1質量%未満であると、炭酸発生量が少なくなり、炭酸により得られる効果が十分に発揮されない可能性があり、5質量%を超えると、経時で析出して製品外観が悪くなるだけでなく、調合時の作業が難しくなることがある。   There is no restriction | limiting in particular as content in the said viscous composition of the said carbonate, Although it can select suitably according to the objective, 1 mass% or more and 5 mass% or less are preferable. When the content is less than 1% by mass, the amount of carbonic acid generated is reduced, and the effect obtained by carbonation may not be sufficiently exhibited. When the content exceeds 5% by mass, the product appearance is precipitated over time. Not only will it get worse, it may make it difficult to work at the time of preparation.

−松樹皮抽出物−
前記松樹皮抽出物は、有効成分として、プロアントシアニジンを含有する。前記プロアントシアニジンは、フラバン−3−オール及び/又はフラバン−3,4−ジオールを構成単位とする重合度が2以上の縮重合体からなる化合物群であり、植物が作り出す強力な抗酸化物質として知られている。
-Pine bark extract-
The pine bark extract contains proanthocyanidins as an active ingredient. The proanthocyanidins are a group of compounds composed of a condensation polymer having a degree of polymerization of 2 or more having flavan-3-ol and / or flavan-3,4-diol as a structural unit, and as a powerful antioxidant produced by plants. Are known.

前記松樹皮抽出物としては、松の樹皮から抽出された抽出物であれば、特に制限はなく、目的に応じて適宜選択することができ、例えば、フランス海岸松(Pinus Martima)、クロマツ(Pinus thunbergii)、アカマツ(Pinus densiflora)、ヒメコマツ(Pinus parviflora)、ゴヨウマツ(Pinus parviflora)、チョウセンマツ(Pinus koraiensis)、ハイマツ(Pinus pumila)、リュウキュウマツ(Pinus luchuensis)、ウツクシマツ(Pinus densiflora umbraculifera)、ダイオウマツ(Pinus palustris)、シロマツ(Pinus bungeana)、カラマツ(Larix kaempferi)等の松の樹皮から抽出された抽出物などが挙げられる。これらの中でも、フランス海岸松の樹皮から抽出された抽出物が好ましい。 As the pine bark extract, if extracts from pine bark is not particularly limited and may be appropriately selected depending on the purpose, for example, French maritime pine (Pinus martima), black pine (Pinus thunbergii), Japanese red pine (Pinus densiflora), Himekomatsu (Pinus parviflora), pine (Pinus parviflora), Korean pine (Pinus koraiensis), stone pine (Pinus pumila), Ryukyu pine (Pinus luchuensis), Utsukushimatsu (Pinus densiflora f. umbraculifera) , Pinus palustris (Pinus palustris), white pine (Pinus bungea a), and the like larch (Larix kaempferi) extracts from the bark of pine, and the like. Among these, an extract extracted from the bark of French coastal pine is preferable.

前記松樹皮抽出物の抽出方法としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、加温抽出法、超臨界流体抽出法などが挙げられ、抽出溶媒としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、温水、熱水等の水;メタノール、エタノール、1−プロパノール、2−プロパノール、1−ブタノール、2−ブタノール、ブタン、アセトン、ヘキサン、シクロヘキサン、プロピレングリコール、含水エタノール、含水プロピレングリコール等の食品又は薬剤の製造に許容される有機溶媒;などが挙げられるが、水、エタノール、含水エタノールが好ましい。   The extraction method of the pine bark extract is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a warm extraction method and a supercritical fluid extraction method. There is no restriction | limiting, According to the objective, it can select suitably, For example, water, such as warm water and hot water; Methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane , Cyclohexane, propylene glycol, water-containing ethanol, water-containing propylene glycol, and other organic solvents that are acceptable for the production of foods or drugs; water, ethanol, and water-containing ethanol are preferred.

前記松樹皮抽出物としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、上記抽出方法により得られた抽出物を公知の方法により、濃縮、溶出、乾燥等して、液状、ペースト状、粉末等に調製した抽出物を使用してもよいが、市販品である株式会社東洋新薬製の松樹皮抽出物を用いることが好ましい。   The pine bark extract is not particularly limited and can be appropriately selected according to the purpose.For example, the extract obtained by the above extraction method is concentrated, eluted, dried, etc. by a known method, Although an extract prepared in a liquid form, a paste form, a powder, or the like may be used, it is preferable to use a commercially available pine bark extract manufactured by Toyo Shinyaku Co., Ltd.

前記松樹皮抽出物の前記粘性組成物における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、0.2質量%以下が好ましく、0超0.15質量%以下がより好ましく、0.01質量%以上0.15質量%以下が特に好ましい。前記含有量が、0.15質量%を超えると、炭酸ジェルパックの色調が濃赤茶色となり、見た目が悪く、商品価値が下がることがあるだけでなく、調合時の作業が難しくなることがある。   There is no restriction | limiting in particular as content in the said viscous composition of the said pine bark extract, Although it can select suitably according to the objective, 0.2 mass% or less is preferable, and more than 0 is 0.15 mass% or less. Is more preferable, and 0.01% by mass or more and 0.15% by mass or less is particularly preferable. When the content exceeds 0.15% by mass, the color tone of the carbonic acid gel pack becomes dark reddish brown, it looks bad, and the commercial value may be lowered, and the work at the time of preparation may be difficult. .

−カフェイン−
前記カフェインは、プリン環を持つプリンアルカロイドの一種である。
前記カフェインとしては、例えば、下記構造式(1−1)で表される無水カフェイン(C10;分子量:194.19)、下記構造式(1−2)で表されるカフェイン水和物(C10・HO;分子量:212.21)などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。これらの中でも、カフェイン水和物が好ましい。
-Caffeine-
The caffeine is a kind of purine alkaloid having a purine ring.
Examples of the caffeine include anhydrous caffeine represented by the following structural formula (1-1) (C 8 H 10 N 4 O 2 ; molecular weight: 194.19), and represented by the following structural formula (1-2). And caffeine hydrate (C 8 H 10 N 4 O 2 .H 2 O; molecular weight: 212.21). These may be used alone or in combination of two or more. Among these, caffeine hydrate is preferable.

前記カフェインとしては、特に制限はなく、適宜合成したものを使用してもよいし、市販品を使用してもよい。   There is no restriction | limiting in particular as said caffeine, What was synthesize | combined suitably may be used and a commercial item may be used.

前記カフェインの前記粘性組成物における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、0.5質量%以下が好ましく、0超0.5質量%以下がより好ましく、0.25質量%以上0.35質量%以下が特に好ましい。   There is no restriction | limiting in particular as content in the said viscous composition of the said caffeine, Although it can select suitably according to the objective, 0.5 mass% or less is preferable, and more than 0 and 0.5 mass% or less are more. Preferably, 0.25 mass% or more and 0.35 mass% or less are especially preferable.

−増粘剤−
前記増粘剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、カルボキシメチルセルロースNa、スルホン化セルロース誘導体、ヒドロキシエチルセルロース系増粘剤などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
-Thickener-
There is no restriction | limiting in particular as said thickener, According to the objective, it can select suitably, For example, carboxymethylcellulose Na, a sulfonated cellulose derivative, a hydroxyethylcellulose type | system | group thickener etc. are mentioned. These may be used alone or in combination of two or more.

前記増粘剤の前記粘性組成物における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、0.5質量%以上5質量%以下が好ましい。前記増粘剤の含有量が、0.5質量%未満であると、前記粘性組成物の粘度が低くなり、皮膚への塗布時に炭酸ジェルパックが垂れ落ち、製品価値が下がる可能性があり、5質量%を超えると、前記粘性組成物の粘度が高くなり、前記粘性組成物の調製が難しくなるだけでなく、後述する酸性顆粒との混合が難しくなり、商品使用が困難となることがある。   There is no restriction | limiting in particular as content in the said viscous composition of the said thickener, Although it can select suitably according to the objective, 0.5 mass% or more and 5 mass% or less are preferable. When the content of the thickener is less than 0.5% by mass, the viscosity of the viscous composition becomes low, and the gel pack of carbonic acid drips when applied to the skin, which may reduce the product value. When it exceeds 5% by mass, the viscosity of the viscous composition becomes high, and it becomes difficult not only to prepare the viscous composition but also to mix with acidic granules described later, which may make it difficult to use the product. .

−水−
前記水としては、通常、化粧品、医薬品等に用いられる水であれば、特に制限はなく、目的に応じて適宜選択することができ、例えば、蒸留水、膜濾過水、イオン交換水などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
-Water-
The water is not particularly limited as long as it is usually used for cosmetics, pharmaceuticals, and the like, and can be appropriately selected according to the purpose. Examples thereof include distilled water, membrane filtered water, and ion-exchanged water. It is done. These may be used alone or in combination of two or more.

前記水の前記粘性組成物における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、30質量%以上が好ましく、50質量%以上98質量%以下がより好ましく、60質量%以上95質量%以下が特に好ましい。前記水の含有量が30質量%未満であると、粘性組成物の粘性が高すぎて流動性、柔軟性等に欠けることがあり、98質量%を超えると、増粘剤の配合量が相対的に減るため粘度が低くなり、皮膚への塗布時に炭酸ジェルパックが垂れ落ち、製品価値が下がる可能性がある。   There is no restriction | limiting in particular as content in the said viscous composition of the said water, Although it can select suitably according to the objective, 30 mass% or more is preferable, 50 mass% or more and 98 mass% or less are more preferable, 60 A mass% or more and 95 mass% or less is particularly preferable. If the water content is less than 30% by mass, the viscosity of the viscous composition may be too high, resulting in lack of fluidity, flexibility, and the like. Therefore, the viscosity is lowered and the gel pack is dripped when applied to the skin, which may reduce the product value.

−粘性組成物の調製方法−
前記粘性組成物の調製方法としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、前記増粘剤を温水に溶解させた後、この溶解液に対して、前記炭酸塩と前記松樹皮抽出物と前記カフェインとを水に溶解させた溶液を入れて、混合することにより調製する方法などが挙げられる。
-Method for preparing viscous composition-
The method for preparing the viscous composition is not particularly limited and may be appropriately selected depending on the purpose. For example, after the thickener is dissolved in warm water, the carbonate is added to the solution. And a method in which a solution prepared by dissolving pine bark extract and caffeine in water is added and mixed.

前記粘性組成物の形状としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、ジェル状、スラリー状などが挙げられる。これらの中でも、皮膚外用剤として用いた場合の柔軟性を担保することができる(使用感に優れる)点で、ジェル状が好ましい。   There is no restriction | limiting in particular as a shape of the said viscous composition, According to the objective, it can select suitably, For example, a gel form, a slurry form, etc. are mentioned. Among these, a gel shape is preferable in that it can ensure flexibility when used as an external preparation for skin (excellent feeling in use).

前記粘性組成物の粘度としては、特に制限はなく、目的に応じて適宜選択することができるが、ずり速度5rpmで測定した時の粘度は、150,000mPa・s〜490,000mPa・sが好ましく、200,000mPa・s〜440,000mPa・sがより好ましい。なお、前記粘度は、25℃においてブルックフィールド型粘度計で測定することができる。   The viscosity of the viscous composition is not particularly limited and may be appropriately selected depending on the intended purpose, but the viscosity when measured at a shear rate of 5 rpm is preferably 150,000 mPa · s to 490,000 mPa · s. 200,000 mPa · s to 440,000 mPa · s is more preferable. The viscosity can be measured with a Brookfield viscometer at 25 ° C.

<酸性顆粒>
本発明の酸性顆粒は、前記発泡性皮膚外用剤の使用時に前記粘性組成物と混合される酸性顆粒であり、少なくとも酸性物質を含み、顆粒化剤を含んでもよい。
<Acid granules>
The acidic granule of the present invention is an acidic granule that is mixed with the viscous composition when the foamable skin external preparation is used, and includes at least an acidic substance and may include a granulating agent.

−酸性物質−
前記酸性物質としては、前記炭酸塩と反応して発泡(二酸化炭素)を生じさせる酸性物質であれば、特に制限はなく、目的に応じて適宜選択することができ、例えば、アスコルビン酸、クエン酸、リンゴ酸、コハク酸などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。これらの中でも、コハク酸が好ましい。
-Acidic substances-
The acidic substance is not particularly limited as long as it is an acidic substance that reacts with the carbonate to generate foam (carbon dioxide), and can be appropriately selected according to the purpose. For example, ascorbic acid, citric acid , Malic acid, succinic acid and the like. These may be used alone or in combination of two or more. Among these, succinic acid is preferable.

前記酸性物質の前記酸性顆粒における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、発泡量の点で、10質量%以上が好ましく、15質量%以上25質量%以下がより好ましい。   There is no restriction | limiting in particular as content in the said acidic granule of the said acidic substance, Although it can select suitably according to the objective, 10 mass% or more is preferable at the point of foaming amount, 15 mass% or more and 25 mass%. The following is more preferable.

−顆粒化剤−
前記顆粒化剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、乳糖、粉糖、デンプン等の粉体などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。これらの中でも、乳糖が好ましい。
-Granulating agent-
There is no restriction | limiting in particular as said granulating agent, According to the objective, it can select suitably, For example, powders, such as lactose, powdered sugar, starch, etc. are mentioned. These may be used alone or in combination of two or more. Among these, lactose is preferable.

前記顆粒化剤の前記酸性顆粒における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、発泡量の点で、90質量%以下が好ましく、70質量%以上85質量%以下がより好ましい。   There is no restriction | limiting in particular as content in the said acidic granule of the said granulating agent, Although it can select suitably according to the objective, 90 mass% or less is preferable at the point of foaming amount, 70 mass% or more and 85 mass% % Or less is more preferable.

−酸性顆粒の製造方法−
前記酸性顆粒の製造方法としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、前記酸性物質と前記顆粒化剤とを混合し、押出造粒により製造する方法、混合造粒により製造する方法などが挙げられる。
-Method for producing acidic granules-
There is no restriction | limiting in particular as a manufacturing method of the said acidic granule, According to the objective, it can select suitably, For example, the said acidic substance and the said granulating agent are mixed, the method of manufacturing by extrusion granulation, mixed production For example, a method of manufacturing with grains.

前記酸性顆粒の形状としては、特に制限はなく、嵩密度、流動性、成形性等に応じて適宜選択することができ、例えば、顆粒状だけでなく、粉末状、微粒子状、不規則な形状、平面的な形状、多面的な形状、球状、しずく状、繊維状、円柱状などが挙げられる。   The shape of the acidic granule is not particularly limited and can be appropriately selected according to the bulk density, fluidity, moldability, and the like. For example, it is not only granular, but also powder, fine particles, and irregular shapes. , Planar shape, multi-faceted shape, spherical shape, drop shape, fibrous shape, cylindrical shape, and the like.

<その他の成分>
前記その他の成分としては、化粧品等に用いられる成分であれば、特に制限はなく、目的に応じて適宜選択することができ、例えば、界面活性剤、pH調整剤、防腐剤、香料、保湿剤、紫外線吸収剤、色素、酸化防止剤、滑沢剤(ステアリン酸マグネシウム等)などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
<Other ingredients>
The other components are not particularly limited as long as they are components used in cosmetics and the like, and can be appropriately selected according to the purpose. For example, surfactants, pH adjusters, preservatives, fragrances, moisturizers UV absorbers, dyes, antioxidants, lubricants (magnesium stearate, etc.), and the like. These may be used alone or in combination of two or more.

<発泡性皮膚外用剤の使用形態>
前記発泡性皮膚外用剤の使用形態としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、使用時に、前記粘性組成物と前記酸性顆粒とを混合して発泡させ、皮膚に適用させることにより使用する形態などが挙げられる。
<Usage form of effervescent skin external preparation>
There is no restriction | limiting in particular as a usage form of the said foamable skin external preparation, According to the objective, it can select suitably, For example, the said viscous composition and the said acidic granule are mixed and foamed at the time of use, and skin The form etc. which are used by making it apply to are mentioned.

前記発泡性皮膚外用剤の使用時における前記粘性組成物と前記酸性顆粒との混合質量比(粘性組成物:酸性顆粒)としては、特に制限はなく、目的に応じて適宜選択することができるが、混合性(分散性)の点で、10:1〜20:1が好ましい。   The mixing mass ratio between the viscous composition and the acidic granules (viscous composition: acidic granules) at the time of using the foamable skin external preparation is not particularly limited and can be appropriately selected according to the purpose. From the viewpoint of mixing (dispersibility), 10: 1 to 20: 1 is preferable.

前記発泡性皮膚外用剤における前記粘性組成物と前記酸性顆粒との混合方法としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、スパチュラ、ヘラ、手のひら等を用いて、ガラス、プラスチック等の容器内で混合する方法、手のひら等の皮膚上で混合する方法などが挙げられ、前記酸性顆粒(粉状物)が目視で消えない程度に混合する方法が好ましい。   The method for mixing the viscous composition and the acidic granule in the foamable external preparation for skin is not particularly limited and can be appropriately selected according to the purpose.For example, using a spatula, a spatula, a palm, Examples thereof include a method of mixing in a container such as glass and plastic, a method of mixing on the skin such as the palm, and the like, and a method of mixing to such an extent that the acidic granules (powder) do not disappear visually is preferable.

前記発泡性皮膚外用剤の使用方法としては、特に制限はなく、目的に応じて適宜選択することができるが、皮膚等に塗布後、1分間〜30分間放置して使用する方法などが好ましい。前記発泡性皮膚外用剤は、垂れ落ちず皮膚等に留まり続けるため、サロン等でなく家庭で用いる場合、前記発泡性皮膚外用剤を皮膚等に塗布している間、立ち歩きや、掃除等の簡単な日常動作を行うことができる。   There is no restriction | limiting in particular as the usage method of the said foamable skin external preparation, Although it can select suitably according to the objective, The method etc. which leave it for 1 to 30 minutes after applying to skin etc. are preferable. Since the foamable skin external preparation continues to stay on the skin without dripping down, when used at home instead of a salon, etc., while applying the foamable skin external preparation to the skin, etc. Simple daily operations can be performed.

前記発泡性皮膚外用剤における前記粘性組成物及び前記酸性顆粒の保存形態としては、前記粘性組成物と前記酸性顆粒とが接触しない状態で保存されていれば、特に制限はなく、目的に応じて適宜選択することができるが、前記粘性組成物及び前記酸性顆粒をそれぞれ各保存容器内に密封状態で保存する形態が好ましい。   The storage form of the viscous composition and the acidic granules in the foamable external preparation for skin is not particularly limited as long as the viscous composition and the acidic granules are stored in a non-contact state, depending on the purpose. Although it can select suitably, the form which preserve | saves the said viscous composition and the said acidic granule in each storage container in the sealed state is preferable.

前記発泡性皮膚外用剤における前記粘性組成物及び前記酸性顆粒の保存容器の形状としては、特に制限はなく、目的に応じて適宜選択することができ、カップ状、チューブ状、バッグ状、瓶状、スティック状、ポンプ状などが挙げられる。
前記発泡性皮膚外用剤における前記粘性組成物及び前記酸性顆粒の保存容器の大きさとしては、特に制限はなく、目的に応じて適宜選択することができる。
前記発泡性皮膚外用剤における前記粘性組成物及び前記酸性顆粒の保存容器の材質としては、例えば、プラスチック、ガラス、アルミニウム、紙、各種ポリマーなどが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
There is no restriction | limiting in particular as a shape of the storage container of the said viscous composition and the said acidic granule in the said foamable skin external preparation, According to the objective, it can select suitably, Cup shape, tube shape, bag shape, bottle shape , Stick shape, pump shape and the like.
There is no restriction | limiting in particular as a magnitude | size of the storage container of the said viscous composition in the said effervescent skin external preparation, and the said acidic granule, According to the objective, it can select suitably.
Examples of the material for the storage container for the viscous composition and the acidic granules in the foamable external preparation for skin include plastics, glass, aluminum, paper, and various polymers. These may be used alone or in combination of two or more.

前記発泡性皮膚外用剤における前記粘性組成物及び前記酸性顆粒の保存容器の具体例としては、特に制限はなく、目的に応じて適宜選択することができるが、密閉性、内容物の保存安定性、製造コスト等の点で、内面をポリエチレンテレフタレートでラミネートしたアルミスティック、アルミバック等のポリエチレンテレフタレート製の保存容器;内面をポリエチレンテレフタレートでラミネートしたアルミフィルム等で蓋をヒートシールしたポリエチレンテレフタレート製の保存容器などが好ましい。   Specific examples of the storage container for the viscous composition and the acidic granules in the foamable external preparation for skin are not particularly limited and may be appropriately selected depending on the intended purpose. However, hermeticity, storage stability of contents Storage container made of polyethylene terephthalate such as aluminum stick laminated on inner surface with polyethylene terephthalate, aluminum back, etc. in terms of production cost, etc .; Storage made of polyethylene terephthalate with lid sealed with aluminum film laminated on inner surface with polyethylene terephthalate Containers are preferred.

<発泡性皮膚外用剤の用途>
本発明の発泡性皮膚外用剤は、皮膚血流量の増加及び角層水分量の上昇という2つの効果を高次で両立できるものであり、化粧水、乳液、クリーム、パック剤、ピーリング剤等の化粧品だけでなく、毛髪用剤、洗浄剤、浴用剤等の医薬部外品、医薬品のいずれにも好適に使用することができる。
<Use of foaming skin external preparation>
The effervescent skin external preparation of the present invention can achieve the two effects of increasing skin blood flow and increasing stratum corneum water content at a higher order, such as lotions, emulsions, creams, packs, peeling agents, etc. It can be suitably used not only for cosmetics but also for quasi-drugs such as hair agents, cleaning agents, bathing agents, and pharmaceuticals.

以下に本発明の実施例を説明するが、本発明は、これらの実施例に何ら限定されるものではない。   Examples of the present invention will be described below, but the present invention is not limited to these examples.

(実施例1:発泡性皮膚外用剤1の調製)
表1に示した組成に従い、発泡性皮膚外用剤1を製造した。
粘性組成物は、表1に記載の組成の増粘剤(カルボキシメチルセルロースNa、スルホン化セルロース誘導体)を温水に溶解して室温まで冷却した後、この溶解液に、表1に記載の組成の炭酸塩、松樹皮抽出物及びカフェインを水で溶解した溶液を加えて、調製した。
酸性顆粒は、表1に記載の組成の酸性物質(コハク酸)、顆粒化剤(乳糖)、及び滑沢剤(ステアリン酸マグネシウム)を、高速混合造粒機(バーチカルグラニュレーター)により混合して、顆粒状の粒を得た。
なお、発泡性皮膚外用剤における粘性組成物及び酸性顆粒は、使用直前に粘性組成物と酸性顆粒とが目視で均一に混ざるまでヘラで混合した。
(Example 1: Preparation of foamable skin external preparation 1)
According to the composition shown in Table 1, a foamable skin external preparation 1 was produced.
The viscous composition was prepared by dissolving a thickener (carboxymethylcellulose Na, sulfonated cellulose derivative) having the composition described in Table 1 in warm water and cooling to room temperature, and then adding carbonic acid having the composition described in Table 1 to this solution. A solution prepared by dissolving salt, pine bark extract and caffeine in water was added to prepare.
The acidic granules are prepared by mixing an acidic substance (succinic acid) having the composition shown in Table 1, a granulating agent (lactose), and a lubricant (magnesium stearate) with a high speed mixing granulator (vertical granulator). A granular particle was obtained.
In addition, the viscous composition and acidic granule in an effervescent skin external preparation were mixed with a spatula until the viscous composition and acidic granule were visually mixed evenly just before use.

(比較例1:比較発泡性皮膚外用剤1の調製)
実施例1において、カフェインを用いなかったこと以外は、実施例1と同様にして比較発泡性皮膚外用剤1を製造した。なお、発泡性皮膚外用剤における粘性組成物及び酸性顆粒は、使用直前に粘性組成物と酸性顆粒とが目視で均一に混ざるまでヘラで混合した。比較発泡性皮膚外用剤1の組成を表1に示す。
(Comparative Example 1: Preparation of comparative foaming skin external preparation 1)
In Example 1, comparative foamable skin external preparation 1 was produced in the same manner as in Example 1 except that caffeine was not used. In addition, the viscous composition and acidic granule in an effervescent skin external preparation were mixed with a spatula until the viscous composition and acidic granule were visually mixed evenly just before use. The composition of the comparative foamable skin external preparation 1 is shown in Table 1.

(比較例2:比較発泡性皮膚外用剤2の調製)
実施例1において、松樹皮抽出物を用いなかったこと以外は、実施例1と同様にして比較発泡性皮膚外用剤2を製造した。なお、発泡性皮膚外用剤における粘性組成物及び酸性顆粒は、使用直前に粘性組成物と酸性顆粒とが目視で均一に混ざるまでヘラで混合した。比較発泡性皮膚外用剤2の組成を表1に示す。
(Comparative Example 2: Preparation of comparative foaming skin external preparation 2)
In Example 1, comparative foamable skin external preparation 2 was produced in the same manner as Example 1 except that the pine bark extract was not used. In addition, the viscous composition and acidic granule in an effervescent skin external preparation were mixed with a spatula until the viscous composition and acidic granule were visually mixed evenly just before use. The composition of the comparative foamable skin external preparation 2 is shown in Table 1.

(比較例3:比較発泡性皮膚外用剤3の調製)
実施例1において、松樹皮抽出物及びカフェインを用いなかったこと以外は、実施例1と同様にして比較発泡性皮膚外用剤3を製造した。なお、発泡性皮膚外用剤における粘性組成物及び酸性顆粒は、使用直前に粘性組成物と酸性顆粒とが目視で均一に混ざるまでヘラで混合した。比較発泡性皮膚外用剤3の組成を表1に示す。
(Comparative Example 3: Preparation of comparative foaming skin external preparation 3)
In Example 1, comparative foamable skin external preparation 3 was produced in the same manner as Example 1 except that the pine bark extract and caffeine were not used. In addition, the viscous composition and acidic granule in an effervescent skin external preparation were mixed with a spatula until the viscous composition and acidic granule were visually mixed evenly just before use. The composition of the comparative foamable skin external preparation 3 is shown in Table 1.

(試験例1:皮膚血流量の測定)
試験例1では、実施例及び比較例で製造した発泡性皮膚外用剤を用いて皮膚血流量の増加を比較する試験を実施した。皮膚血流量の測定方法及び測定結果を以下に示す。
(Test Example 1: Measurement of skin blood flow)
In Test Example 1, a test was performed to compare the increase in skin blood flow using the foamable external preparation for skin prepared in Examples and Comparative Examples. The measurement method and measurement result of skin blood flow are shown below.

−測定方法−
測定項目:皮膚血流量
測定機器:レーザードップラー血流画像化装置
(PeriScan PIM3、PERIMED社製)
被験者 :女性5名(平均年齢27.0±4.3歳)
測定部位:左手中指
塗布量 :適量(左手の掌全体を覆う量)
試験品 :発泡性皮膚外用剤1(実施例1)
:比較発泡性皮膚外用剤1(比較例1)
:比較発泡性皮膚外用剤2(比較例2)
:比較発泡性皮膚外用剤3(比較例3)
測定手順:
(1)前腕部分を洗顔料で洗った。
(2)密閉した部屋で、安静にして15分間馴化を行った。
(3)塗布前の左手中指の血流量を測定した。
(4)試験品を左手の掌全体にヘラで塗布し、塗布した状態で15分間安静に過ごした。
(5)塗布時間終了後に試験品を指になるべく刺激を与えないようにヘラで除去し、塗布後の左手中指の血流量を測定した。
-Measurement method-
Measurement item: Skin blood flow measurement device: Laser Doppler blood flow imaging device
(PeriScan PIM3, manufactured by PERIMED)
Subjects: 5 women (average age: 27.0 ± 4.3 years)
Measurement site: Middle finger application amount on the left hand: Appropriate amount (amount covering the entire palm of the left hand)
Test article: Foamable skin external preparation 1 (Example 1)
: Comparative foaming skin external preparation 1 (Comparative Example 1)
: Comparative foaming skin external preparation 2 (Comparative Example 2)
: Comparative foaming skin external preparation 3 (Comparative Example 3)
Measurement procedure:
(1) The forearm was washed with a face wash.
(2) In a sealed room, rest and acclimatize for 15 minutes.
(3) The blood flow rate of the middle finger of the left hand before application was measured.
(4) The test product was applied to the entire palm of the left hand with a spatula and rested for 15 minutes in the applied state.
(5) After the application time, the test product was removed with a spatula so as not to irritate the finger as much as possible, and the blood flow volume of the middle finger on the left hand after application was measured.

−測定結果−
試験例1の測定結果を表2に示した。
-Measurement results-
The measurement results of Test Example 1 are shown in Table 2.

なお、塗布した試薬品の温度が低いため、各測定では塗布前に比べて塗布後の血流量が低下していた。そこで、コントロールである比較発泡性皮膚外用剤3の塗布前後の変化値を基準として、発泡性皮膚外用剤1及び比較発泡性皮膚外用剤1の変化値を検討した。その結果、炭酸塩及び松樹皮抽出物を含有する発泡性皮膚外用剤1は、コントロールである比較発泡性皮膚外用剤3よりも、皮膚血流量が38.7増加することがわかった。更に、発泡性皮膚外用剤1は、比較発泡性皮膚外用剤1よりも皮膚血流量が16.2増加し、比較発泡性皮膚外用剤2よりも皮膚血流量が26.8増加し、皮膚血流量に優れることが示された。以上より、本発明の発泡性皮膚外用剤を用いると、皮膚血流量が顕著に増加されることがわかった。   In addition, since the temperature of the applied reagent product was low, the blood flow after application was lower in each measurement than before application. Then, the change value of the foamable skin external preparation 1 and the comparative foamable skin external preparation 1 was examined on the basis of the change value before and after the application of the comparative foamable skin external preparation 3 as a control. As a result, it was found that effervescent skin external preparation 1 containing carbonate and pine bark extract increased the skin blood flow by 38.7 compared to comparative effervescent skin external preparation 3 as a control. Furthermore, the foamable skin external preparation 1 has an increase in skin blood flow of 16.2 compared with the comparative foamable skin external preparation 1, and the skin blood flow increased by 26.8 compared with the comparative foamable skin external preparation 2, so that the dermal blood It was shown that the flow rate was excellent. From the above, it was found that when the foamable skin external preparation of the present invention is used, the skin blood flow rate is remarkably increased.

(試験例2:角層水分量の測定)
試験例2では、実施例及び比較例で製造した発泡性皮膚外用剤を用いて角層水分量の上昇を比較する試験を実施した。角層水分量の測定方法及び測定結果を以下に示す。
(Test Example 2: Measurement of stratum corneum moisture content)
In Test Example 2, a test for comparing the increase in the amount of moisture in the stratum corneum was performed using the foamable skin external preparations produced in Examples and Comparative Examples. The measurement method and measurement result of the stratum corneum moisture content are shown below.

−測定方法−
測定項目:角層水分量
測定機器:SKICON−200EX
被験者 :女性5名(平均年齢27.0±4.3歳)
測定部位:左前腕内側の4cm×4cmの範囲
塗布量 :適量(4cm×4cmの範囲を覆う量)
試験品 :発泡性皮膚外用剤1(実施例1)
:比較発泡性皮膚外用剤1(比較例1)
:比較発泡性皮膚外用剤2(比較例2)
:比較発泡性皮膚外用剤3(比較例3)
測定手順:
(1)前腕部分を洗顔料で洗った。
(2)密閉した部屋で、安静にして15分間馴化を行った。
(3)塗布前の左前腕内側(4cm×4cm)の水分量を測定した。
(4)試験品を左前腕内側(4cm×4cm)にヘラで塗布し、塗布した状態で15分間安静に過ごした。
(5)塗布時間終了後に、肌になるべく刺激をあたえないように試験品をヘラで除去し、左前腕内側(4cm×4cm)を水で洗った。
(6)洗った後に15分間馴化し、塗布後の水分量(左前腕内側)を測定した。
※ 水分量:測定の際に数値が安定しない場合には、7回以上(奇数回)測定した。また、得られた測定値の上限値及び下限値の値を除いた、中央値(7回測定した場合には、上限値及び下限値を除いた5地点での値)の平均値を測定値とした。
-Measurement method-
Measurement item: stratum corneum moisture measuring device: SKICON-200EX
Subjects: 5 women (average age: 27.0 ± 4.3 years)
Measurement site: 4 cm × 4 cm range inside the left forearm Application amount: appropriate amount (amount covering 4 cm × 4 cm range)
Test article: Foamable skin external preparation 1 (Example 1)
: Comparative foaming skin external preparation 1 (Comparative Example 1)
: Comparative foaming skin external preparation 2 (Comparative Example 2)
: Comparative foaming skin external preparation 3 (Comparative Example 3)
Measurement procedure:
(1) The forearm was washed with a face wash.
(2) In a sealed room, rest and acclimatize for 15 minutes.
(3) The moisture content inside the left forearm (4 cm × 4 cm) before application was measured.
(4) The test product was applied to the inside of the left forearm (4 cm × 4 cm) with a spatula, and rested for 15 minutes while being applied.
(5) After completion of the application time, the test product was removed with a spatula so that the skin was not stimulated as much as possible, and the inner left forearm (4 cm × 4 cm) was washed with water.
(6) After washing, the sample was acclimated for 15 minutes, and the water content after application (inner left forearm) was measured.
* Moisture content: If the value was not stable during the measurement, it was measured at least 7 times (odd times). In addition, the average value of the median values (values at five points excluding the upper limit value and the lower limit value when measured 7 times) excluding the upper limit value and the lower limit value of the obtained measurement values is the measured value. It was.

−測定結果−
試験例2の測定結果を表3に示した。
-Measurement results-
The measurement results of Test Example 2 are shown in Table 3.

試験例2より、本発明の発泡性皮膚外用剤を用いることにより、角層水分量が顕著に上昇されることがわかった。   From Test Example 2, it was found that the moisture content of the stratum corneum was significantly increased by using the foamable skin external preparation of the present invention.

炭酸塩及び松樹皮抽出物を含有する比較発泡性皮膚外用剤1、及び炭酸塩及びカフェインを含有する比較発泡性皮膚外用剤2に比し、炭酸塩、松樹皮抽出物、及びカフェインを含有する本発明の発泡性皮膚外用剤1の方が、角層水分量の上昇効果が顕著に優れていた。そればかりか、本発明の発泡性皮膚外用剤1では、比較発泡性皮膚外用剤1及び2よりも皮膚血流量の増加効果が顕著であるという予想し得ない結果も得られた。本発明の発泡性皮膚外用剤1は、皮膚血流量の増加及び角層水分量の上昇という2つの効果を高次で両立できるという、比較発泡性皮膚外用剤1及び2では奏することのできない顕著な優れた効果を有していた。   Compared to comparative foaming skin external preparation 1 containing carbonate and pine bark extract and comparative foaming skin external preparation 2 containing carbonate and caffeine, carbonate, pine bark extract and caffeine The foaming skin external preparation 1 of the present invention contained was significantly superior in the effect of increasing the stratum corneum moisture content. In addition, in the foamable external preparation for skin 1 of the present invention, an unexpected result that the effect of increasing the skin blood flow was more remarkable than in the comparative foamable external preparation for skin 1 and 2 was obtained. The effervescent skin external preparation 1 of the present invention is not able to be achieved by the comparative effervescent skin external preparations 1 and 2, which can achieve the two effects of increasing the skin blood flow and increasing the stratum corneum water content at a higher order. It had an excellent effect.

本発明の発泡性皮膚外用剤は、皮膚血流量の増加及び角層水分量の上昇という2つの効果を高次で両立できるため、化粧水、乳液、クリーム、パック剤、ピーリング剤等の化粧品だけでなく、毛髪用剤、洗浄剤、浴用剤等の医薬部外品、医薬品のいずれにも好適に使用することができる。   Since the foamable external preparation for skin of the present invention can achieve the two effects of increasing the skin blood flow and increasing the stratum corneum water content at a high order, only cosmetics such as lotions, emulsions, creams, packs, peeling agents, etc. In addition, it can be suitably used for any of quasi-drugs such as hair preparations, cleaning agents, bath preparations, and pharmaceuticals.

Claims (2)

粘性組成物と酸性顆粒とからなり、該粘性組成物と該酸性顆粒とを使用時に混合する2剤型の発泡性皮膚外用剤であって、
前記粘性組成物が、炭酸塩、松樹皮抽出物、及びカフェインを少なくとも含有し、
前記酸性顆粒が、前記炭酸塩と反応して発泡を生じさせる酸性物質を少なくとも含有することを特徴とする発泡性皮膚外用剤。
A two-part foaming skin external preparation comprising a viscous composition and acidic granules, wherein the viscous composition and acidic granules are mixed at the time of use,
The viscous composition contains at least carbonate, pine bark extract, and caffeine;
The foamable external preparation for skin, wherein the acidic granule contains at least an acidic substance that reacts with the carbonate to cause foaming.
使用時における粘性組成物と酸性顆粒との混合質量比(粘性組成物:酸性顆粒)が、10:1〜20:1である請求項1に記載の発泡性皮膚外用剤。   The foamable skin external preparation according to claim 1, wherein a mixing mass ratio of the viscous composition and acidic granules (viscous composition: acidic granules) in use is 10: 1 to 20: 1.
JP2012198582A 2012-04-23 2012-09-10 Foamable skin external preparation Pending JP2013241388A (en)

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JP2018052906A (en) * 2016-09-30 2018-04-05 株式会社東洋新薬 Foamable skin external preparation kit
JP2023029502A (en) * 2020-09-16 2023-03-03 株式会社東洋新薬 Blood flow improver

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