JP4159217B2 - Topical skin preparation - Google Patents
Topical skin preparation Download PDFInfo
- Publication number
- JP4159217B2 JP4159217B2 JP35560799A JP35560799A JP4159217B2 JP 4159217 B2 JP4159217 B2 JP 4159217B2 JP 35560799 A JP35560799 A JP 35560799A JP 35560799 A JP35560799 A JP 35560799A JP 4159217 B2 JP4159217 B2 JP 4159217B2
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- Prior art keywords
- skin
- present
- carboxyl group
- effect
- containing compound
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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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する。更に詳しくは、水溶性生理活性成分であるカルボキシル基含有化合物の経皮吸収を促進させ、荒れ肌改善効果、角質改善効果、ターンオーバー速度を早くする効果、美肌効果等の優れた皮膚外用剤に関する。
【0002】
【従来の技術および発明が解決しようとする課題】
水溶性生理活性成分は油溶性生理活性成分と比べて経皮吸収速度が小さい事が知られている。本出願人は、先に、γ−アミノ酪酸及びその誘導体(特公昭58−26726号公報)や、ジイソプロピルアミンジクロロアセテート(特開昭53−136528号公報)など、水溶性生理活性成分であるカルボキシル基含有化合物の皮膚機能改善による老化防止効果や美肌効果を有することを提案した。そして、これら水溶性生理活性成分の経皮吸収を促進させることにより、その効果を製剤中の濃度を増加させる事なく皮膚への効果をさらに向上させることが期待される。
【0003】
これまでにも皮膚外用剤としてDMSOのような非プロトン溶媒やAZONE、テルペン類、メントール類などが報告されている。しかしながら、これらを配合した製剤は表皮にダメージを与えたり、刺激を感じるなど皮膚外用剤として好ましくない点がある。本発明は、このような実情に鑑みなされたものであって、皮膚への刺激が少なく水溶性生理活性成分の経皮吸収性にすぐれる皮膚外用剤を提供することを目的とするものである。
【0004】
【課題を解決するための手段】
すなわち、本願の請求項1の発明は、γ−アミノ酪酸、γ−アミノヒドロキシ酪酸及びジイソプロピルアミンジクロロアセテートから選ばれるカルボキシル基含有化合物又はその塩の一種または二種以上、水及びアルカリゲネス・レータス(Alcaligenes latus)B−16株(FERM BP-2015号)の産生多糖類を含有することを特徴とする、該カルボキシル基含有化合物又はその塩の経皮吸収促進剤である。
【0005】
【発明の実施の形態】
以下、発明の実施の形態を述べる。
本発明のカルボキシル基含有化合物又はその塩は、通常本発明の皮膚外用剤に0.005〜2.0質量%含有させることが好ましい。0.005質量%未満では、効果が十分ではなく、2.0質量%を超えるとき、それに見合った効果がないことが多い。本発明のカルボキシル基含有化合物又はその塩としては、例えばγ−アミノ酪酸及びその誘導体やジイソプロピルアミンジクロロアセテートなど構造の一部にカルボキシル基を有する有機化合物やその塩が挙げられる。これらの中でγ−アミノ酪酸(以下、GABAと略記する)、γ−アミノヒドロキシ酪酸及びジイソプロピルアミンジクロロアセテート(以下、DADAと略記する)が特に効果の点で好ましい。
【0006】
本発明の微生物産生多糖増粘剤は、通常本発明の皮膚外用剤に0.0001〜0.5質量%含有させることが好ましい。0.0001質量%未満では、効果が十分ではなく、0.5質量%を超えるとき、それに見合った効果がないことが多い。本発明の微生物産生多糖増粘剤は、アルカリゲネス・レータス(Alcaligenes latus)B−16株(FERM BP-2015号)の産生多糖類(以下、B-16ポリマーと略称する)である。
【0007】
本発明の水は、通常本発明の皮膚外用剤に40〜99質量%含有させることが好ましい。本発明の皮膚外用剤は、前述の如く、カルボキシル基含有化合物又はその塩から選ばれる一種または二種以上、水、B-16ポリマーを含有するものであって、これらが相乗的に皮膚に作用して、カルボキシル基含有化合物の経皮吸収を促進し、皮膚機能を亢進して、優れた皮膚改善効果(荒れ肌改善効果、角質改善効果、ターンオーバー速度を早くする効果など)を短時間に発現し、持続する等、顕著な効果を表す。
【0008】
本発明の皮膚外用剤は、例えば、化粧料や医薬品として適用することができ、剤型としてはローション類,乳液類,クリーム類,パック類等に適用することができる。本発明の皮膚外用剤には上記の他に、ワックス類、色素、香料、
防腐剤、界面活性剤、顔料、ビタミン類、キレート剤、清涼剤、湿潤剤、乳化助剤、ホルモン類、抗酸化剤等を本発明の目的を達成する範囲内で適宜配合することができる。
【0009】
【実施例】
以下、実施例及び比較例に基づいて本発明を詳細に説明する。尚、実施例に記載の配合量は質量%である。経皮吸収試験は次の通りである。
【0010】
フランツ型垂直拡散セルのアクセプター部にリン酸緩衝液(150mM塩化ナトリウム含有、pH7.2)を満たし、剥離したヘアレスラットの腹部皮膚を装着する。試料を皮膚上に供し、皮膚を透過してアクセプター部のリン酸緩衝液中に蓄積したカルボキシル基含有化合物を高速液体クロマトグラフィーにより定量した。DADAの場合、固定相としてL−カラムODS、移動相として0.1質量%リン酸/メタノール、検出器として紫外部分光光度計(210nm)を用いた。GABAの場合、固定相としてSodex Asahikak OPD50−4D、移動相として25mMほう酸緩衝液/アセトニトリル(85/15,体積%)、検出器として分光蛍光光度計(Ex330nm,Em450nm)を用いた。実験は3群で行い、平均値を算出した。
【0011】
実施例1、比較例1〜3
DADAを表1に記載の通りに配合し、皮膚外用剤を調製し、これを試料として上記の試験方法に従って行い、試料を皮膚上に供してから8時間後のDADAを定量した。
【0012】
【表1】
【0013】
(1)調製方法
(A)、(B)各々を室温にて均一に溶解し、撹拌下(A)に(B)を加え、乳化分散を行い調製する。これを試料とする。
【0014】
(2)特性
経皮吸収試験の結果を表1に記載した。表1に示すごとく、実施例1の皮膚外用剤は比較例1〜3のそれよりもDADAの経皮吸収に於いて顕著な促進効果が見られた。
【0015】
実施例2,比較例4〜5
カルボキシル基含有化合物を表2に記載の通りに配合し、皮膚外用剤を調製し、これを試料として、上記の試験方法に従って行い、試料を皮膚上に供してから5時間後のカルボキシル基含有化合物を定量した。
【0016】
【表2】
【0017】
(1)調製方法
(A)、(B)各々を室温にて均一に溶解し、撹拌下(A)に(B)を加え、乳化分散を行って調製する。これを試料とする。
【0018】
(2)特性
経皮吸収試験の結果を表2に記載した。表2に示すごとく、実施例2の皮膚外用剤は比較例4〜5のそれよりも本発明のカルボキシル基含有化合物の経皮吸収に於いて顕著な促進効果が見られた。
【0019】
【発明の効果】
以上記載のごとく、本発明が、水溶性生理活性成分であるカルボキシル基含有化合物の経皮吸収性の高い皮膚外用剤を提供することは明らかである。[0001]
[Industrial application fields]
The present invention relates to an external preparation for skin. More specifically, the present invention relates to an external preparation for skin that promotes percutaneous absorption of a carboxyl group-containing compound, which is a water-soluble physiologically active ingredient, and has excellent rough skin improving effect, keratin improving effect, quick turnover speed, skin beautifying effect and the like.
[0002]
[Background Art and Problems to be Solved by the Invention]
It is known that water-soluble physiologically active ingredients have a lower percutaneous absorption rate than oil-soluble physiologically active ingredients. The present applicant has previously described carboxyls which are water-soluble physiologically active components such as γ-aminobutyric acid and its derivatives (Japanese Patent Publication No. 58-26726) and diisopropylamine dichloroacetate (Japanese Patent Laid-Open No. 53-136528). It was proposed that the group-containing compound has an anti-aging effect and a beautiful skin effect by improving the skin function. Then, by promoting percutaneous absorption of these water-soluble physiologically active ingredients, it is expected that the effect on the skin is further improved without increasing the concentration in the preparation.
[0003]
So far, aprotic solvents such as DMSO, AZONE, terpenes, and menthols have been reported as external preparations for skin. However, preparations containing these are not preferable as external preparations for skin, such as damaging the epidermis or feeling irritation. The present invention has been made in view of such circumstances, and an object of the present invention is to provide an external preparation for skin that is less irritating to the skin and excellent in transdermal absorbability of water-soluble physiologically active ingredients. .
[0004]
[Means for Solving the Problems]
Ie, the invention following claims 1, .gamma.-aminobutyric acid, .gamma.-amino-hydroxybutyric acid and carboxyl group-containing compound selected from diisopropylamine dichloroacetate or one or two or more of its salts, water and Alcaligenes Retasu (Alcaligenes latus) A percutaneous absorption enhancer of a carboxyl group-containing compound or a salt thereof, characterized by containing a polysaccharide produced by B-16 strain (FERM BP-2015).
[0005]
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of the invention will be described below.
It is preferable that the carboxyl group-containing compound or salt thereof of the present invention is usually contained in an amount of 0.005 to 2.0% by mass in the skin external preparation of the present invention. If it is less than 0.005% by mass, the effect is not sufficient, and if it exceeds 2.0% by mass, there is often no corresponding effect. Examples of the carboxyl group-containing compound or a salt thereof according to the present invention include organic compounds having a carboxyl group in a part of the structure, such as γ-aminobutyric acid and derivatives thereof and diisopropylamine dichloroacetate, and salts thereof. Among these, γ-aminobutyric acid (hereinafter abbreviated as GABA), γ-aminohydroxybutyric acid and diisopropylamine dichloroacetate (hereinafter abbreviated as DADA) are particularly preferable in terms of effect.
[0006]
It is preferable that the microorganism-produced polysaccharide thickener of the present invention is usually contained in the skin external preparation of the present invention in an amount of 0.0001 to 0.5% by mass. If it is less than 0.0001% by mass, the effect is not sufficient, and if it exceeds 0.5% by mass, there is often no corresponding effect. The microorganism-produced polysaccharide thickener of the present invention is a polysaccharide produced from Alcaligenes latus B-16 strain (FERM BP-2015) (hereinafter abbreviated as B-16 polymer).
[0007]
It is preferable that the water of the present invention is usually contained in the skin external preparation of the present invention in an amount of 40 to 99% by mass. As described above, the external preparation for skin of the present invention contains one or more selected from a carboxyl group-containing compound or a salt thereof, water, and a B-16 polymer, and these act synergistically on the skin. And promotes percutaneous absorption of carboxyl group-containing compounds, enhances skin function, and exhibits excellent skin improvement effects (rough skin improvement effect, keratin improvement effect, effect of increasing turnover speed, etc.) in a short time It shows a remarkable effect such as sustaining.
[0008]
The external preparation for skin of the present invention can be applied as, for example, cosmetics and pharmaceuticals, and can be applied to lotions, emulsions, creams, packs and the like as dosage forms. In addition to the above, the skin external preparation of the present invention includes waxes, pigments, fragrances,
Preservatives, surfactants, pigments, vitamins, chelating agents, refreshing agents, wetting agents, emulsifying aids, hormones, antioxidants and the like can be appropriately blended within the scope of achieving the object of the present invention.
[0009]
【Example】
Hereinafter, the present invention will be described in detail based on examples and comparative examples. In addition, the compounding quantity as described in an Example is the mass%. The transdermal absorption test is as follows.
[0010]
The acceptor part of the Franz-type vertical diffusion cell is filled with phosphate buffer (containing 150 mM sodium chloride, pH 7.2), and the abdomen skin of the peeled hairless rat is attached. The sample was provided on the skin, and the carboxyl group-containing compound that permeated the skin and accumulated in the phosphate buffer in the acceptor part was quantified by high performance liquid chromatography. In the case of DADA, an L-column ODS as a stationary phase, 0.1% by mass phosphoric acid / methanol as a mobile phase, and an ultraviolet partial photometer (210 nm) as a detector were used. In the case of GABA, Sodex Asahikak OPD50-4D was used as a stationary phase, 25 mM borate buffer / acetonitrile (85/15, volume%) was used as a mobile phase, and a spectrofluorometer (Ex 330 nm, Em 450 nm) was used as a detector. The experiment was performed in three groups, and the average value was calculated.
[0011]
Example 1, Comparative Examples 1-3
DADA was blended as shown in Table 1 to prepare an external preparation for skin, and this was used as a sample according to the test method described above, and DADA was quantified 8 hours after the sample was placed on the skin.
[0012]
[Table 1]
[0013]
(1) Preparation methods (A) and (B) are each uniformly dissolved at room temperature, and (B) is added to (A) under stirring, followed by emulsification and dispersion. This is used as a sample.
[0014]
(2) Table 1 shows the results of the characteristic transdermal absorption test. As shown in Table 1, the external preparation for skin of Example 1 showed a remarkable acceleration effect in percutaneous absorption of DADA than that of Comparative Examples 1 to 3.
[0015]
Example 2, Comparative Examples 4-5
Carboxyl group-containing compound was prepared as shown in Table 2, and a skin external preparation was prepared. This was used as a sample in accordance with the above test method, and the carboxyl group-containing compound 5 hours after the sample was placed on the skin. Was quantified.
[0016]
[Table 2]
[0017]
(1) Preparation methods (A) and (B) are each uniformly dissolved at room temperature, and (B) is added to (A) under stirring, followed by emulsification and dispersion. This is used as a sample.
[0018]
(2) Table 2 shows the results of the characteristic transdermal absorption test. As shown in Table 2, the skin external preparation of Example 2 showed a remarkable acceleration effect in the percutaneous absorption of the carboxyl group-containing compound of the present invention than that of Comparative Examples 4-5.
[0019]
【The invention's effect】
As described above, it is apparent that the present invention provides a skin external preparation having a high transdermal absorbability of a carboxyl group-containing compound which is a water-soluble physiologically active ingredient.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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JP35560799A JP4159217B2 (en) | 1999-12-15 | 1999-12-15 | Topical skin preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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JP35560799A JP4159217B2 (en) | 1999-12-15 | 1999-12-15 | Topical skin preparation |
Publications (2)
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JP2001172156A JP2001172156A (en) | 2001-06-26 |
JP4159217B2 true JP4159217B2 (en) | 2008-10-01 |
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JP35560799A Expired - Fee Related JP4159217B2 (en) | 1999-12-15 | 1999-12-15 | Topical skin preparation |
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1999
- 1999-12-15 JP JP35560799A patent/JP4159217B2/en not_active Expired - Fee Related
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US8029823B2 (en) | 1999-06-14 | 2011-10-04 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US8293273B2 (en) | 1999-06-14 | 2012-10-23 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
USRE43799E1 (en) | 1999-06-14 | 2012-11-13 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US9192581B2 (en) | 1999-06-14 | 2015-11-24 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US9320716B2 (en) | 1999-06-14 | 2016-04-26 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical compositions |
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US10064878B2 (en) | 1999-06-14 | 2018-09-04 | Cosmo Technologies Ltd. | Controlled release and taste masking oral pharmaceutical compositions |
US10143698B2 (en) | 1999-06-14 | 2018-12-04 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical compositions |
US10154964B2 (en) | 2011-09-07 | 2018-12-18 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10172799B1 (en) | 2011-09-07 | 2019-01-08 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10307375B2 (en) | 2011-09-07 | 2019-06-04 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10660858B2 (en) | 2011-09-07 | 2020-05-26 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
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