JP2008273941A - Adapalene-containing external agent composition - Google Patents
Adapalene-containing external agent composition Download PDFInfo
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- JP2008273941A JP2008273941A JP2008073712A JP2008073712A JP2008273941A JP 2008273941 A JP2008273941 A JP 2008273941A JP 2008073712 A JP2008073712 A JP 2008073712A JP 2008073712 A JP2008073712 A JP 2008073712A JP 2008273941 A JP2008273941 A JP 2008273941A
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- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 title claims abstract description 78
- 229960002916 adapalene Drugs 0.000 title claims abstract description 78
- 239000000203 mixture Substances 0.000 title claims abstract description 27
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 53
- 229960003080 taurine Drugs 0.000 claims abstract description 26
- 238000002360 preparation method Methods 0.000 claims description 25
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- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
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Images
Abstract
Description
本発明は、角質及び皮膚への浸透性に優れたアダパレン含有外用剤組成物に関する。 The present invention relates to an adapalene-containing external preparation composition excellent in permeability to keratin and skin.
アダパレンは、第三世代の合成レチノイド類の１つで、脂腺、毛包に浸透して効果を発揮し、ニキビの初発疹である面皰のサイズを縮小することが知られており、また、アダパレン含有製剤については、従来の外用レチノイド剤の高い治療効果を維持しつつ、落屑、灼熱感などの副作用が少ないという報告がある（非特許文献１参照）。 Adapalene is one of the third-generation synthetic retinoids that are known to penetrate the sebaceous glands and hair follicles and reduce the size of comedones, the first acne rash. Regarding adapalene-containing preparations, there are reports that side effects such as desquamation and burning sensation are few while maintaining the high therapeutic effects of conventional external retinoid agents (see Non-Patent Document 1).
しかしながら、本来、皮膚は、外界からの異物の侵入を防ぐバリアー機能（角質層）を有しているため、単に外用剤中に薬効成分を配合しただけでは、充分な皮膚浸透性が得られず、充分な薬効を発現できないことが多い。 However, since the skin inherently has a barrier function (stratum corneum) that prevents foreign substances from entering from the outside, sufficient skin permeability cannot be obtained simply by blending a medicinal component into an external preparation. In many cases, sufficient medicinal effects cannot be expressed.
そして、０．１％アダパレン含有ゲル剤について、拡散セルを用いたin vitro経皮吸収性試験を実施したところ、毛包への素早い浸透が確認されたものの、投与１５時間後においてもアダパレンは対投与量で僅か０．０１％しかレシーバ液に移行しないことが報告されており（非特許文献２参照）、角質を介した皮膚への浸透性が低いことが推察される。 Then, when an in vitro transdermal absorbability test using a diffusion cell was performed on a gel containing 0.1% adapalene, quick penetration into the hair follicle was confirmed, but adapalene was not treated even 15 hours after administration. It has been reported that only 0.01% of the dose is transferred to the receiver solution (see Non-Patent Document 2), and it is presumed that the permeability to the skin through the stratum corneum is low.
アダパレンはレチノイド類であるため、ビタミンＡ類と同様にニキビ、角化症、乾癬、シワ及びシミ等の皮膚疾患に有効であることが期待される。しかしながら、上述したようにアダパレンは角質や皮膚への浸透性が低く、表皮や真皮で起こる疾患に対して充分な治療効果を発揮できていないと考えられる。 Since adapalene is a retinoid, it is expected to be effective for skin diseases such as acne, keratosis, psoriasis, wrinkles, and spots as well as vitamin A. However, as described above, adapalene has low permeability to the keratin and skin, and it is considered that it does not exhibit a sufficient therapeutic effect for diseases that occur in the epidermis and dermis.
そこで、本発明は、角質や皮膚への浸透性に優れたアダパレン含有外用剤組成物を提供することを課題とする。 Then, this invention makes it a subject to provide the adapalene containing external preparation composition excellent in the permeability | transmittance to a keratin and skin.
本発明者らは、前記課題を解決すべく鋭意検討を重ねた結果、アダパレンと共にタウリンを配合することによって、アダパレンの角質や皮膚への浸透性が向上することを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that by blending taurine with adapalene, the permeability of adapalene to keratin and skin is improved, and the present invention is completed. It came.
すなわち、本発明の態様は、アダパレン及びタウリンを含有することを特徴とする外用剤組成物である。 That is, the aspect of this invention is an external preparation composition characterized by containing adapalene and taurine.
本発明により、角質や皮膚への浸透性に優れたアダパレン含有外用剤組成物を提供することが可能となった。 According to the present invention, it is possible to provide an adapalene-containing external preparation composition excellent in permeability to keratin and skin.
「アダパレン」は、アダマンチル骨格を持った分子量４１２．５２の化合物で、テトロヒドロフランに溶解するが、エタノールにやや溶け難く、水に不溶といった特徴を有する（THE MERCK INDEX参照）。アダパレンの含有（配合）量は、本外用剤組成物中０．０１〜１．０質量％であり、アダパレンの有効性と安全性のバランスから０．０５〜０．５質量％が好ましい。 “Adapalene” is a compound having an adamantyl skeleton and a molecular weight of 412.52, which is soluble in tetrohydrofuran but slightly soluble in ethanol and insoluble in water (see THE MERCK INDEX). The content (formulation) of adapalene is 0.01 to 1.0% by mass in the external preparation composition, and 0.05 to 0.5% by mass is preferable from the balance between the effectiveness and safety of adapalene.
「タウリン」の含有（配合）量は、アダパレンの１質量部に対して０．５〜２５質量部である。 The content (formulation) of “taurine” is 0.5 to 25 parts by mass with respect to 1 part by mass of adapalene.
タウリンの含有量が０．５質量部未満であるとアダパレンの皮膚への浸透性が充分でないと考えられ、好ましくないからである。一方、本外用剤組成物を用いて外用剤を調製するときにアダパレンが外用剤中に１．０質量％を超えて含有されていると、アダパレンの１質量部に対して２５質量部を超えるタウリンを配合した際に、アダパレンの皮膚への浸透性は充分にあると思われるが、タウリンの配合量が多くなりすぎて、溶解し難くなり製剤化が困難になるなど好ましくないからである。 This is because if the content of taurine is less than 0.5 parts by mass, the permeability of adapalene to the skin is considered insufficient, which is not preferable. On the other hand, when preparing external preparation using this external preparation composition, if adapalene is contained in the external preparation in an amount exceeding 1.0% by mass, it exceeds 25 parts by mass with respect to 1 part by mass of adapalene. When taurine is blended, adapalene seems to have sufficient permeability to the skin, but it is not preferable because the amount of taurine is too large to be dissolved and difficult to formulate.
なお、タウリンはアミノエチルスルホン酸とも呼ばれる含硫アミノ酸の一種で、一般的には疲労回復作用等を期待してドリンク剤等に配合されるが、脂質合成促進や浸透圧調整による保湿効果、抗炎症効果、活性酸素除去によるアクネ菌抑制効果及び損傷皮膚回復促進効果をも有していることが知られているため（非特許文献３〜６参照）、本発明の外用剤組成物は単にアダパレンの角質や皮膚への浸透性を増強するだけでなく、乾燥肌、炎症、損傷皮膚を併有するニキビ、角化症、乾癬、シワ及びシミ等の皮膚疾患において優れた治療効果を発揮するものと予想される。 Taurine is a kind of sulfur-containing amino acid, also called aminoethyl sulfonic acid, and is generally formulated in drinks with the expectation of fatigue recovery action, etc. Since it is known to have an inflammatory effect, an effect of suppressing acne bacteria by removing active oxygen, and an effect of promoting the recovery of damaged skin (see Non-Patent Documents 3 to 6), the external preparation composition of the present invention is simply adapalene. In addition to enhancing the skin's keratin and skin permeability, it also has an excellent therapeutic effect on skin diseases such as acne, keratosis, psoriasis, wrinkles and blemishes with dry skin, inflammation, and damaged skin is expected.
本発明のアダパレン含有外用剤組成物は、液剤、ローション剤、ゲル剤、エアゾール剤、クリーム剤、水性軟膏剤等の各種外用剤として提供される。 The adapalene-containing external preparation composition of the present invention is provided as various external preparations such as liquids, lotions, gels, aerosols, creams and aqueous ointments.
液剤は、アダパレン及びタウリンを、水、低級アルコール、多価アルコール又はこれらの混液に溶解・分散させて調製することができる。なお、タウリンや油成分を完全に溶解できない場合には可溶化するのに必要な溶剤または界面活性剤を配合すればよい。また、このような液剤と適当な液化ガス（液化石油ガス、ジメチルエーテルなど）をアルミ製耐圧容器に入れてエアゾール剤を調製することもできる。さらに、このような液剤に適当なゲル化剤を配合してゲル剤を調製することも可能である。 The liquid preparation can be prepared by dissolving and dispersing adapalene and taurine in water, lower alcohol, polyhydric alcohol or a mixture thereof. In the case where taurine and oil components cannot be completely dissolved, a solvent or a surfactant necessary for solubilization may be added. Further, an aerosol agent can be prepared by putting such a liquid agent and an appropriate liquefied gas (liquefied petroleum gas, dimethyl ether, etc.) into an aluminum pressure vessel. Furthermore, it is also possible to prepare a gel agent by blending such a liquid agent with an appropriate gelling agent.
クリーム剤も常法により調製が可能である。例えば、水と多価アルコール相にアダパレン及び界面活性剤を添加して、ホモミキサー用容器に入れて脱気・加温する。ホッパーからタウリンの溶解相や加温した油分及び／又は界面活性剤を溶解させた油相を添加し、高速攪拌（ホモジナイズ）した後、室温まで冷却することによってクリーム剤を調製することができる。ここで、ＨＬＢの高い界面活性剤を用いればＯ／Ｗクリーム剤が調製できるし、ＨＬＢの低い界面活性剤を用いればＷ／Ｏクリーム剤が調製できる。 Creams can also be prepared by conventional methods. For example, adapalene and a surfactant are added to water and a polyhydric alcohol phase, and the mixture is put into a homomixer container and deaerated and heated. A cream agent can be prepared by adding a dissolved phase of taurine or a heated oil component and / or an oil phase in which a surfactant is dissolved from a hopper, stirring at high speed (homogenizing), and then cooling to room temperature. Here, an O / W cream can be prepared by using a surfactant having a high HLB, and a W / O cream can be prepared by using a surfactant having a low HLB.
水性軟膏剤は、室温で固体のポリエチレングリコールと室温で液状の多価アルコールをそれぞれ任意の量とり、加温融解後、アダパレン、タウリンを加え、分散させた後、室温まで冷却することによって調製できる。 The aqueous ointment can be prepared by taking any amount of polyethylene glycol that is solid at room temperature and polyhydric alcohol that is liquid at room temperature, adding and dispersing adapalene and taurine after heating and melting, and then cooling to room temperature. .
本発明の外用剤組成物には、局所麻酔剤、抗菌剤、殺菌剤、抗炎症剤、鎮痛剤、抗ヒスタミン剤、組織修復剤、鎮痒剤、保湿剤、血管収縮剤、抗アレルギー剤、清涼化剤、酸素除去剤、ビタミン、紫外線吸収剤、紫外線散乱剤などを本発明の効果を損なわない範囲で適宜に配合することができる。 The external preparation composition of the present invention includes a local anesthetic agent, antibacterial agent, bactericidal agent, anti-inflammatory agent, analgesic agent, antihistamine, tissue repair agent, antipruritic agent, moisturizer, vasoconstrictor, antiallergic agent, and cooling agent. An oxygen scavenger, a vitamin, an ultraviolet absorber, an ultraviolet scattering agent, and the like can be appropriately blended within a range not impairing the effects of the present invention.
本発明の外用剤組成物には、医薬品や医薬部外品に配合可能な種々の基剤成分を本発明の効果を損なわない範囲で適宜に含有することができる。このような基剤成分としては、精製水、低級アルコールや多価アルコール等の溶解補助剤、炭化水素、グリセリン脂肪酸エステル、ワックス成分、界面活性剤、抗酸化剤、乳化安定剤、ゲル化剤、粘着剤等、各種動植物からの抽出物、ｐＨ調整剤、防腐剤、キレート剤、香料、色素、液化ガスなどが挙げられる。 In the external preparation composition of the present invention, various base components that can be blended in pharmaceuticals and quasi drugs can be appropriately contained within a range not impairing the effects of the present invention. Examples of such base components include purified water, solubilizing agents such as lower alcohols and polyhydric alcohols, hydrocarbons, glycerin fatty acid esters, wax components, surfactants, antioxidants, emulsion stabilizers, gelling agents, Examples include extracts from various animals and plants such as pressure-sensitive adhesives, pH adjusters, preservatives, chelating agents, fragrances, pigments, and liquefied gases.
以下に、実施例、比較例及び試験例を挙げ、本発明をさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.
下表1に示した比較例1〜４及び実施例１〜４の各液剤は、アダパレンを配合して２４時間攪拌したアダパレンの分散液である。すなわち、比較例１はアダパレン、エタノール及び精製水を混合した液剤であり、比較例２〜４及び実施例１〜４は、アダパレン以外の配合成分をその濃度を変えてエタノール、ｐＨ調整剤及び精製水の混液に溶解させた後、さらにアダパレンを分散させて調製した液剤である。比較例２〜４は比較例１の組成に外用剤の有効成分として汎用されているパントテニルエチルエーテルを種々の濃度で配合した液剤であり、実施例１〜４はタウリンを種々の濃度で配合した液剤である。なお、ｐＨ調整剤としては、水酸化ナトリウム、リン酸ニ水素カリウム及び希塩酸を用い、各液剤のｐＨを約８に調整した。 Each liquid agent of Comparative Examples 1 to 4 and Examples 1 to 4 shown in Table 1 below is a dispersion of adapalene in which adapalene is blended and stirred for 24 hours. That is, Comparative Example 1 is a liquid agent in which adapalene, ethanol and purified water are mixed, and Comparative Examples 2 to 4 and Examples 1 to 4 have different concentrations of compounding ingredients other than adapalene, ethanol, pH adjuster and purification. A solution prepared by dissolving adapalene after being dissolved in a mixture of water. Comparative Examples 2 to 4 are solutions in which pantothenyl ethyl ether, which is widely used as an active ingredient for external preparations, is blended in various concentrations in the composition of Comparative Example 1, and Examples 1 to 4 blend taurine in various concentrations. Liquid. In addition, as a pH adjuster, sodium hydroxide, potassium dihydrogen phosphate, and dilute hydrochloric acid were used, and pH of each liquid agent was adjusted to about 8.
試験例１ アダパレンのシリコン膜移行性試験
前提：Tanakaらによれば、開放系でのシリコン膜を用いた移行性試験は局所投与製剤の経皮吸収性の評価に適しているとされている（S.Tanaka, et al., International Journal of Pharmaceutics, 27:29-38(1985)）ことから、角質への浸透性をシリコン膜移行性試験により評価した。また、シリコン膜にすることで、アダパレンが浸透しやすい毛穴の影響を排除することができるので、単純にアダパレンの角質への移行性を評価できると考えられる。
Test Example 1 Silicon film transferability test of adapalene Premise: According to Tanaka et al., Transferability test using silicon film in open system is said to be suitable for evaluation of transdermal absorbability of topically administered preparations ( S. Tanaka, et al., International Journal of Pharmaceutics, 27: 29-38 (1985)), the permeability to the stratum corneum was evaluated by a silicon membrane transfer test. Further, by using a silicon film, it is possible to eliminate the influence of pores through which adapalene easily permeates, so that it is considered that adapalene's ability to move to the keratin can be simply evaluated.
方法：シリコンゴム膜（２．５ｃｍ×２．５ｃｍ×０．５ｍｍ）上に比較例１〜４及び実施例１〜４の液剤を均一に塗布するためのガーゼを置き、各液剤を全体に広がるように１５０μＬずつ塗布し、直ちに恒温器（約３５℃、湿度成行）に投入した。１時間後、恒温器からシリコンゴム膜を取り出し、表面上の液剤残渣を水で良く洗い流し、水気を良く拭き取った。これをメタノール中に１晩放置し、さらに超音波発生器にて完全にアダパレンをシリコン膜から抽出し、抽出液中のアダパレンの含有量を液体クロマトグラフィーにて測定した。各液剤のアダパレンのシリコン膜移行性を比較例1のシリコン膜移行率を1とした場合の移行率値として求めた。 Method: A gauze for uniformly applying the liquid agents of Comparative Examples 1 to 4 and Examples 1 to 4 is placed on a silicon rubber film (2.5 cm × 2.5 cm × 0.5 mm), and each liquid agent is spread throughout. 150 μL each was applied and immediately put into a thermostat (about 35 ° C., humidity control). After 1 hour, the silicon rubber film was taken out from the thermostatic chamber, the liquid residue on the surface was thoroughly washed with water, and the moisture was wiped off well. This was left in methanol overnight, and adapalene was completely extracted from the silicon film with an ultrasonic generator, and the content of adapalene in the extract was measured by liquid chromatography. The migration of adapalene in each liquid agent to the silicon film was determined as a migration rate value when the silicon membrane migration rate of Comparative Example 1 was 1.
結果：実施例１〜４（アダパレンの１質量部に対して０．５〜２５質量部のタウリン）及び比較例１〜４におけるシリコン膜移行性試験結果を図１に示す。なお、相対的移行率が１．４倍以上で効果ありと判断した。 Results: The silicon film migration test results in Examples 1 to 4 (0.5 to 25 parts by mass of taurine with respect to 1 part by mass of adapalene) and Comparative Examples 1 to 4 are shown in FIG. In addition, it was judged that the relative transition rate was 1.4 times or more and there was an effect.
比較例１に対する移行率は、実施例１（アダパレンの１質量部に対して０．５質量部のタウリン）で約３．３倍、実施例２（アダパレンの１質量部に対して２．５質量部のタウリンン）で約６．４倍、実施例４（アダパレンの１質量部に対して２５質量部のタウリン）で約７．６倍と濃度依存的に増大した。 The migration rate relative to Comparative Example 1 is about 3.3 times in Example 1 (0.5 parts by mass of taurine with respect to 1 part by mass of adapalene), and Example 2 (2.5 parts per 1 part by mass of adapalene). The concentration increased in a concentration-dependent manner by about 6.4 times in the case of taurine (part by mass) and about 7.6 times in Example 4 (25 parts by mass of taurine with respect to 1 part by mass of adapalene).
一方、比較例２〜４（アダパレンの１質量部に対して２．５〜２５質量部のパントテニルエチルエーテル）においては、薬物によってアダパレンのシリコン膜移行性は殆ど増大しなかった。 On the other hand, in Comparative Examples 2 to 4 (2.5 to 25 parts by mass of pantothenyl ethyl ether relative to 1 part by mass of adapalene), the migration of adapalene to the silicon film was hardly increased by the drug.
以上の結果より、タウリンは、アダパレンのシリコン膜移行性を増大させる効果を有していることが明らかとなった。シリコン膜移行性と皮膚浸透性には相関関係があると考えられるため、タウリンはアダパレンの皮膚浸透性を増大させると考えられる。 From the above results, it has been clarified that taurine has an effect of increasing adapalene's ability to migrate to a silicon film. Taurine is thought to increase the skin permeability of adapalene because it is thought that there is a correlation between the transferability of the silicon film and the skin permeability.
試験例２ アダパレン溶解度のシリコン膜移行性に対する影響
表１記載の各液剤中に溶解しているアダパレン量に依存してアダパレンのシリコン膜移行性が増大しているとも考えられることから、各液剤のアダパレンの溶解度とシリコン膜移行性との関係を調べるため、各液剤中のアダパレンの飽和溶解度を測定した。
Test Example 2 Influence of adapalene solubility on silicon film transferability It is considered that the silicon film transferability of adapalene is increased depending on the amount of adapalene dissolved in each solution listed in Table 1. In order to investigate the relationship between the solubility of adapalene and the transferability to the silicon film, the saturation solubility of adapalene in each solution was measured.
方法：表１に記載の比較例１〜４及び実施例１〜４の液剤を濾過し、濾液中のアダパレン量を、液体クロマトグラフィーを用いて定量した。各液剤の飽和溶解度を比較例１の溶解度を１としたときの溶解度比率として求めた。 Method: The liquid agents of Comparative Examples 1 to 4 and Examples 1 to 4 described in Table 1 were filtered, and the amount of adapalene in the filtrate was quantified using liquid chromatography. The saturation solubility of each solution was determined as the solubility ratio when the solubility of Comparative Example 1 was 1.
結果：結果を図２に示す。
比較例２（アダパレンの１質量部に対して２．５質量部のパントテニルエチルエーテル）では１．５倍、比較例４（アダパレンの１質量部に対して２５質量部のパントテニルエチルエーテル）では約３倍と、パントテニルエチルエーテルは濃度依存的にアダパレンの溶解度比率を増大させた。実施例１(アダパレンの１質量部に対して０．５質量部のタウリン)では１．０倍、実施例２（アダパレンの１質量部に対して２．５質量部のタウリン）では約1．０倍、実施例４（アダパレンの１質量部に対して２５質量部のタウリン）では約０．８倍と、タウリンの濃度が増大してもアダパレンの溶解度比率を増大させる効果はなかった。
Results: The results are shown in FIG.
Comparative Example 2 (2.5 parts by mass of pantothenyl ethyl ether with respect to 1 part by mass of adapalene) 1.5 times, Comparative Example 4 (25 parts by mass of pantothenyl ethyl ether with respect to 1 part by mass of adapalene) Then, about 3 times, pantothenyl ethyl ether increased the solubility ratio of adapalene in a concentration-dependent manner. In Example 1 (0.5 parts by mass of taurine with respect to 1 part by mass of adapalene), 1.0 times, and in Example 2 (2.5 parts by mass of taurine with respect to 1 part by mass of adapalene), about 1. 0 times, Example 4 (25 parts by weight of taurine with respect to 1 part by weight of adapalene) was about 0.8 times, and even if the concentration of taurine was increased, there was no effect of increasing the solubility ratio of adapalene.
濃度依存的にアダパレンの溶解度比率を増大させたパントテニルエチルエーテルを配合した比較例２〜４の液剤では、アダパレンのシリコン膜移行性の増大は見られなかったが、タウリンを配合した実施例１〜４では、アダパレンの溶解度比率は変わらないが、濃度依存的にシリコン膜移行性は増大した（以上、図１及び２参照）。 In the liquid preparations of Comparative Examples 2 to 4 containing pantothenyl ethyl ether in which the solubility ratio of adapalene was increased in a concentration-dependent manner, no increase in the migration of adapalene to the silicon film was observed, but Example 1 containing taurine In -4, the solubility ratio of adapalene did not change, but the silicon film migration increased in a concentration-dependent manner (see FIGS. 1 and 2 above).
以上のことを勘案すると、アダパレンのシリコン膜移行性は液剤中に溶解しているアダパレンの濃度に無関係で、アダパレンが液剤中に分散状態で存在していても変わらず、また、タウリンの配合により、その濃度依存的にアダパレンのシリコン膜移行性が増大していると考えられる。 Considering the above, the migration of adapalene to the silicon film is independent of the concentration of adapalene dissolved in the solution, and does not change even if adapalene is present in a dispersed state in the solution. The adapalene migration into the silicon film is thought to increase depending on the concentration.
すなわち、アダパレンの角質や皮膚への浸透性は液剤中に溶解しているアダパレンの濃度に無関係で、アダパレンが液剤中に分散状態で存在していても変わらず、また、タウリンの配合により、その濃度依存的にアダパレンの角質や皮膚への浸透性が増大すると考えられる。 That is, the permeability of adapalene to the stratum corneum and skin is independent of the concentration of adapalene dissolved in the solution, and does not change even if adapalene is present in a dispersed state in the solution. It is thought that the permeability of adapalene to keratin and skin increases depending on the concentration.
本発明により、アダパレンを含有し、ニキビ、角化症、乾癬、シワ及びシミ等に有効な液剤、ローション剤、ゲル剤、エアゾール剤、クリーム剤、水性軟膏剤等の各種外用剤を提供することが期待される。 According to the present invention, there are provided various external preparations containing adapalene and effective for acne, keratosis, psoriasis, wrinkles and stains, lotions, gels, aerosols, creams, aqueous ointments and the like. There is expected.
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