JP5527917B2 - Arginase activity promoter and skin external preparation containing the same - Google Patents
Arginase activity promoter and skin external preparation containing the same Download PDFInfo
- Publication number
- JP5527917B2 JP5527917B2 JP2004332467A JP2004332467A JP5527917B2 JP 5527917 B2 JP5527917 B2 JP 5527917B2 JP 2004332467 A JP2004332467 A JP 2004332467A JP 2004332467 A JP2004332467 A JP 2004332467A JP 5527917 B2 JP5527917 B2 JP 5527917B2
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- Prior art keywords
- skin
- external preparation
- arginase activity
- effect
- moisturizing
- Prior art date
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- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- RXMQCXCANMAVIO-CEOVSRFSSA-L magnesium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound [H+].[H+].[Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O RXMQCXCANMAVIO-CEOVSRFSSA-L 0.000 description 1
- MYUGVHJLXONYNC-QHTZZOMLSA-L magnesium;(2s)-2-amino-5-hydroxy-5-oxopentanoate Chemical compound [Mg+2].[O-]C(=O)[C@@H](N)CCC(O)=O.[O-]C(=O)[C@@H](N)CCC(O)=O MYUGVHJLXONYNC-QHTZZOMLSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012860 organic pigment Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000010292 orthophenyl phenol Nutrition 0.000 description 1
- 239000004306 orthophenyl phenol Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 229940071139 pyrrolidone carboxylate Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229940045920 sodium pyrrolidone carboxylate Drugs 0.000 description 1
- HYRLWUFWDYFEES-UHFFFAOYSA-M sodium;2-oxopyrrolidine-1-carboxylate Chemical compound [Na+].[O-]C(=O)N1CCCC1=O HYRLWUFWDYFEES-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical class NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000005068 transpiration Effects 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Landscapes
- Cosmetics (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Description
本発明はアルギナーゼ活性促進剤及びそれを含有する皮膚外用剤に関する。 The present invention relates to an arginase activity promoter and an external preparation for skin containing the same.
通常、人の皮膚の最外層は角層に覆われていて、そこで水分の蒸散が制御されている。皮膚の水分を適切な範囲に保つことは皮膚の健康の面から見て大変重要なことであり、水分が不足すると肌荒れ等を生じやすくなる。そこで、化粧料や皮膚外用剤においては、肌荒れの防止、改善等の為に、グリセリン、１，３−ブチレングリコール、ソルビトール等の多価アルコール類、ピロリドンカルボン酸塩、ヒアルロン酸等の酸性ムコ多糖類、キチン、キトサン及びそれらの誘導体、蛋白加水分解物、植物抽出物及び尿素等の保湿成分が配合されてきた。しかしながら、これらの保湿成分は皮膚表面においてその物質の物理化学的な保湿の性質を利用しているだけであり、その物質の皮膚細胞におよぼす生理的な機能に基づくものではない。また、化粧料、皮膚外用剤中の配合量が多い場合は、不快なべたつき感を有し、感触が好まれない場合がある。さらに、これらの保湿成分は皮膚より除去されると効果は消失するため、その効果は一過性であると言わざるを得ない。なお、これらのうち、尿素は高い保湿能だけでなく、角質溶解剥離作用や角質柔軟化作用を有する点で好ましいものであるが、その反面、水と反応して分解し易く、分解するとアンモニアと炭酸ガスを生じることから、臭気や安全性の点で問題を生じ易く、また、尿素を配合した皮膚外用剤は特有の刺激感を有する為、使用部位が限定されるという欠点がある。 Usually, the outermost layer of human skin is covered with a stratum corneum, where moisture transpiration is controlled. Keeping the skin moisture within an appropriate range is very important from the viewpoint of skin health. If the moisture is insufficient, rough skin and the like are likely to occur. Therefore, in cosmetics and external preparations for skin, in order to prevent or improve rough skin, polyhydric alcohols such as glycerin, 1,3-butylene glycol and sorbitol, acidic mucos such as pyrrolidone carboxylate and hyaluronic acid are used. Moisturizing ingredients such as sugars, chitin, chitosan and their derivatives, protein hydrolysates, plant extracts and urea have been blended. However, these moisturizing components only use the physicochemical moisturizing properties of the substance on the skin surface and are not based on the physiological function of the substance on the skin cells. Moreover, when there are many compounding quantities in cosmetics and a skin external preparation, it has an unpleasant sticky feeling and a touch may not be liked. Furthermore, since these moisturizing components lose their effects when removed from the skin, it must be said that the effects are temporary. Of these, urea is preferable in that it has not only a high moisturizing ability but also a keratolytic exfoliating action and a keratin softening action. On the other hand, it is easily decomposed by reacting with water, and when decomposed, ammonia and Since carbon dioxide is generated, problems are likely to occur in terms of odor and safety, and the external preparation for skin containing urea has a unique irritation sensation.
一方、アルギナーゼはアルギニンをオルニチンと尿素に加水分解する酵素で、通常、肝臓においてアンモニアから尿素を生成する尿素回路を構成する酵素の一つであり、表皮においてもアルギナーゼの存在が認められている。すなわち、表皮中のアルギナーゼは表皮細胞の増殖に関連したポリアミン生合成やコラーゲン新生に必要なプロリン生合成のためのオルニチン供給酵素として知られている。したがって、アルギナーゼ活性促進剤によって尿素を皮膚内で生合成させることは、上記の“尿素”を配合した皮膚外用剤が有する欠点を解消しながら、“尿素”が有する保湿成分としての優れた効果を引き出すこと、さらに該効果の持続性も期待できるので、非常に有用な手段といえる（すなわち、アルギナーゼ活性促進剤は、皮膚細胞に働きかけ、保湿成分の産出を促す薬剤として使用できる。）。このような尿素の皮膚内で生合成を意図したアルギナーゼ活性促進剤としては、例えば、木通抽出物によるもの（特許文献１）、桔梗抽出物によるもの（特許文献２）、呉茱萸抽出物によるもの（特許文献３）及び麦門冬抽出物によるもの（特許文献４）等が知られているが、これらの抽出物によるアルギナーゼの活性促進効果は充分に高いとは言い難く、より高いアルギナーゼの活性促進効果が得られるアルギナーゼ活性促進剤が望まれている。
上記事情に鑑み、本発明の目的は、従来よりもアルギナーゼの活性促進効果が高いアルギナーゼ活性促進剤を提供することである。また、優れた保湿持続効果及び肌荒れ改善効果が得られる皮膚外用剤を提供することである。 In view of the above circumstances, an object of the present invention is to provide an arginase activity promoter having a higher arginase activity promoting effect than before. Moreover, it is providing the skin external preparation from which the outstanding moisturizing sustaining effect and the rough skin improvement effect are acquired.
本発明者等は、上記の目的を達成すべく鋭意研究した結果、アンズ果汁が極めて高いアルギナーゼ活性促進効果を有すること、さらに、かかるアンズ果汁（アルギナーゼ活性促進剤）と、Ｌ−アスパラギン酸、Ｌ−グルタミン酸またはそれらの塩との組合せによって、皮膚外用剤の保湿持続効果及び肌荒れ改善効果が大きく向上することを知見し、該知見に基づき本発明を完成するに至った。 As a result of intensive studies to achieve the above object, the present inventors have found that apricot juice has an extremely high arginase activity promoting effect, and further, apricot juice (arginase activity promoter), L-aspartic acid, L -It was found that the combination of glutamic acid or a salt thereof with the skin external preparation greatly improves the moisturizing and skin roughening effect, and the present invention has been completed based on this finding.
すなわち、本発明は以下の通りである。
（１）アンズ果汁を有効成分として含有するアルギナーゼ活性促進剤。
（２）（ａ）上記（１）記載のアルギナーゼ活性促進剤をアンズ果汁の乾燥残留物として０．０００１〜５重量％及び（ｂ）Ｌ−アスパラギン酸、Ｌ−グルタミン酸またはそれらの塩から選ばれる１種以上を０．００１〜１０重量％含有する皮膚外用剤。
That is, the present invention is as follows.
(1) Arginase activity promoter containing apricot juice as an active ingredient.
(2) (a) The arginase activity promoter described in (1) above is selected from 0.0001 to 5% by weight as a dry residue of apricot juice and (b) L-aspartic acid, L-glutamic acid or a salt thereof. A skin external preparation containing one or more of 0.001 to 10% by weight.
特許文献５〜９に記載の化粧料のように、アンズ果汁を含有する皮膚外用剤は公知である。しかし、これら従来のアンズ果汁を含有する化粧料（皮膚外用剤）は、いずれも、保湿持続効果や肌荒れ改善効果は必ずしも充分ではなかった（すなわち、保湿持続効果と肌荒れ改善効果の両方を充分に満足できるものはなかった）。本発明は、アンズ果汁を有効成分として含有するアルギナーゼ活性促進剤と、Ｌ−アスパラギン酸、Ｌ−グルタミン酸またはそれらの塩から選ばれる１種または２種以上を配合して皮膚外用剤を調製することで、従来では達成できなかった高いレベルの保湿持続効果と肌荒れ改善効果を有する皮膚外用剤を提供するものである。 The skin external preparation containing apricot juice like the cosmetics of patent documents 5-9 is well-known. However, any of these conventional apricot juice-containing cosmetics (skin preparations for external use) has not always had sufficient moisturizing effect and rough skin improvement effect (that is, both moisturizing long-lasting effect and rough skin improving effect are sufficient). Nothing was satisfactory). The present invention is to prepare an external preparation for skin by blending an arginase activity promoter containing apricot juice as an active ingredient and one or more selected from L-aspartic acid, L-glutamic acid or salts thereof. Thus, the present invention provides a skin external preparation having a high level of moisturizing sustaining effect and a rough skin improving effect that could not be achieved conventionally.
本発明によれば、従来のアルギナーゼ活性促進剤よりも高いアルギナーゼ活性促進効果を示すアルギナーゼ活性促進剤を得ることができ、該アルギナーゼ活性促進剤を使用することで、尿素産生の効率を高めることができる。
また、本発明によれば、優れた保湿持続効果及び肌荒れ改善効果を有し、製剤的経時安定性も良好な皮膚外用剤を実現できる。
ADVANTAGE OF THE INVENTION According to this invention, the arginase activity promoter which shows a higher arginase activity promotion effect than the conventional arginase activity promoter can be obtained, and the efficiency of urea production can be improved by using this arginase activity promoter. it can.
Moreover, according to the present invention, it is possible to realize an external preparation for skin having excellent moisturizing sustaining effect and skin roughness improving effect, and having good formulation stability over time.
以下、本発明を詳細に説明する。
本発明におけるアンズ果汁とは、植物学上バラ科サクラ属のホンアンズ（学名：Prunus armenica L.）、ホンアンズの栽培品種であるアンズ（学名：Prunus armeniaca L. var. ansu Maxim.）、マンシュウアンズ（学名：Prunus mandshurica Koehne）およびモウコアンズ（学名：Prunus sibirica L.）等の果実から得られる果汁のことであり、ホンアンズ又は／及びアンズの果実から得られる果汁が特に好ましい。
Hereinafter, the present invention will be described in detail.
The apricot juice in the present invention is honzu (scientific name: Prunus armenica L.) belonging to the genus Rosaceae in botanical terms, apricot (cultural name: Prunus armeniaca L. var. Ansu Maxim.), Manshu apricot ( It is a fruit juice obtained from fruits such as scientific name: Prunus mandshurica Koehne) and Moukoans (scientific name: Prunus sibirica L.), and fruit juice obtained from honanzu or / and apricot fruit is particularly preferred.
本発明におけるアンズ果汁は、果実を圧搾して得られた果汁をそのまま使用しても、これをさらに濃縮した濃縮果汁を使用してもよい。また、果実を圧搾して得られた果汁に、ろ過、希釈、有機溶媒等による抽出などの処理を施した処理物を使用することも可能である。すなわち、本発明における「アンズ果汁」とは、果実を圧搾して得た果汁そのもの、濃縮果汁若しくはこれらの処理物をいう。
なお、本発明における「アンズ果汁」は、アンズの種子（生薬名をキョウニンという）から各種溶媒にて抽出して得られるエキスである「キョウニンエキス」とは異なる。「キョウニンエキス」では本発明の課題を解決することはできない。
As apricot juice in the present invention, fruit juice obtained by pressing a fruit may be used as it is, or concentrated fruit juice obtained by further concentrating it may be used. Moreover, it is also possible to use the processed material which performed processing, such as filtration, dilution, extraction with an organic solvent, etc. to the fruit juice obtained by pressing a fruit. That is, the “apricot juice” in the present invention refers to a fruit juice itself obtained by pressing a fruit, a concentrated fruit juice, or a processed product thereof.
In addition, the “apricot juice” in the present invention is different from the “apricot extract” which is an extract obtained by extracting from apricot seeds (the name of herbal medicine is kyonin) with various solvents. “Kyonin extract” cannot solve the problems of the present invention.
本発明のアルギナーゼ活性促進剤は、アンズ果汁を有効成分とするものであり、アンズ果汁単体であっても、アンズ果汁のアルギナーゼ活性促進作用を阻害しない範囲で、その他の添加剤を適宜配合した組成物であってもよい。該組成物としては、例えば、アンズ果汁の腐敗、菌の繁殖などを防止するために、エタノール、パラオキシ安息香酸エステルまたはその塩類、安息香酸またはその塩類、サルチル酸またはその塩類、ソルビン酸またはその塩類、イソプロピルメチルフェノール、オルトフェニルフェノール、クレゾール、フェノキシエタノールなどの防腐剤や腐敗を抑えるための、１，３−ブチレングリコール、プロピレングリコールなどの多価アルコールを適宜添加した組成物が挙げられる。 The arginase activity promoter of the present invention contains apricot juice as an active ingredient, and even if it is apricot juice alone, it is a composition in which other additives are appropriately blended within a range not inhibiting the arginase activity promoting action of apricot juice. It may be a thing. Examples of the composition include ethanol, paraoxybenzoic acid ester or a salt thereof, benzoic acid or a salt thereof, salicylic acid or a salt thereof, sorbic acid or a salt thereof, for example, in order to prevent spoilage of apricot juice and bacterial growth. , Isopropylmethylphenol, orthophenylphenol, cresol, phenoxyethanol and the like, and a composition to which polyhydric alcohols such as 1,3-butylene glycol and propylene glycol are appropriately added to prevent decay.
本発明のアルギナーゼ活性促進剤は、従来のアルギナーゼ活性促進剤に比べてより高いアルギナーゼ活性促進効果を示す。従って、本発明のアルギナーゼ活性促進剤を使用することで、尿素の産生効率を向上させることができる。 The arginase activity promoter of the present invention exhibits a higher arginase activity promoting effect than conventional arginase activity promoters. Therefore, the production efficiency of urea can be improved by using the arginase activity promoter of the present invention.
本発明の皮膚外用剤は、次のａ及びｂを有効成分として含有する組成物である。
ａ．上記のアンズ果汁を有効成分とするアルギナーゼ活性促進剤
ｂ．Ｌ−アスパラギン酸及びＬ−グルタミン酸またはそれらの塩から選ばれる１種または２種以上
The external preparation for skin of the present invention is a composition containing the following a and b as active ingredients.
a. Arginase activity promoter comprising the apricot juice as an active ingredient b. One or more selected from L-aspartic acid and L-glutamic acid or salts thereof
本発明の皮膚外用剤において、ａ成分のアルギナーゼ活性促進剤の含有量は、皮膚外用剤（組成物全量）中の当該アルギナーゼ活性促進剤の有効成分であるアンズ果汁の含有量が乾燥残留物として０．０００１〜５重量％となる量にすることが重要であり、好ましくは当該アンズ果汁（乾燥残留物）の含有量が０．０００５〜３重量％となる量である。アンズ果汁（乾燥残留物）の含有量が０．０００１重量％未満である場合、優れた保湿持続効果や肌荒れ改善効果が得られにくくなる。一方、アンズ果汁（乾燥残留物）の含有量が５重量％を超える場合は、皮膚外用剤（組成物）の経時安定性が低下し、またコスト的に不利になる。 In the external preparation for skin of the present invention, the content of the a component arginase activity promoter is such that the content of apricot juice, which is the active ingredient of the arginase activity promoter in the external skin preparation (total composition), is a dry residue. It is important that the amount is 0.0001 to 5% by weight, and the amount of the apricot juice (dried residue) is preferably 0.0005 to 3% by weight. When the content of apricot juice (dried residue) is less than 0.0001% by weight, it becomes difficult to obtain an excellent moisturizing effect and a rough skin improving effect. On the other hand, when the content of apricot juice (dry residue) exceeds 5% by weight, the temporal stability of the external preparation for skin (composition) is lowered, and the cost becomes disadvantageous.
なお、「アンズ果汁の乾燥残留物」は、アンズ果汁を１０５℃で乾燥するかまたは減圧乾固して溶媒を除去した時の残留物である溶質を指し、乾燥または減圧乾固する前後の重量を測定することによって定量される。なお、抽出溶媒が不揮発性の場合にはガスクロマトグラフィー、高速液体クロマトグラフィー等により溶媒量を定量した値から溶質量を計算値として求め、乾燥残留物量とみなす。 The “dried residue of apricot juice” refers to a solute that is a residue when apricot juice is dried at 105 ° C. or dried under reduced pressure to remove the solvent, and the weight before and after drying or drying under reduced pressure. Is quantified by measuring When the extraction solvent is non-volatile, the dissolved mass is obtained as a calculated value from the value obtained by quantifying the amount of solvent by gas chromatography, high performance liquid chromatography or the like, and is regarded as the dry residue amount.
本発明の皮膚外用剤において、ｂ成分のＬ−アスパラギン酸、Ｌ−グルタミン酸またはそれらの塩は、製剤学的に組成物中に配合できるのであれば特に制限されない。すなわち、Ｌ−アスパラギン酸及びＬ−グルタミン酸はそれらの塩の形でも用いることができ、Ｌ−アスパラギン酸の塩としては、例えばＬ−アスパラギン酸カリウム、Ｌ−アスパラギン酸ナトリウム、Ｌ−アスパラギン酸マグネシウム等が挙げられ、Ｌ−グルタミン酸の塩としては、例えばＬ−グルタミン酸カリウム、Ｌ−グルタミン酸ナトリウム、Ｌ−グルタミン酸マグネシウム等が挙げられる。これら以外の塩であっても製剤学的に配合可能であればいずれの塩であっても使用することができる。該ｂ成分のＬ−アスパラギン酸、Ｌ−グルタミン酸またはそれらの塩は、いずれか１種または２種以上を使用でき、その配合量は、皮膚外用剤全体（組成物全量）当たり０．００１〜１０重量％が好ましく、より好ましくは０．００５〜５重量％である。配合量が０．００１重量％未満の場合、そのような皮膚外用剤は優れた保湿持続効果や肌荒れ改善効果を発揮し難いものとなり、１０重量％を超える場合は皮膚外用剤の経時安定性が低下し、またコスト的に不利になる。 In the external preparation for skin of the present invention, the L component as L-aspartic acid, L-glutamic acid or a salt thereof is not particularly limited as long as it can be formulated pharmaceutically. That is, L-aspartic acid and L-glutamic acid can also be used in the form of their salts. Examples of L-aspartic acid salts include potassium L-aspartate, sodium L-aspartate, and magnesium L-aspartate. Examples of the salt of L-glutamic acid include potassium L-glutamate, sodium L-glutamate, magnesium L-glutamate and the like. Any salt other than these can be used as long as it can be formulated pharmaceutically. Any one or more of L-aspartic acid, L-glutamic acid or salts thereof as component b can be used, and the blending amount is 0.001 to 10 per whole external preparation for skin (composition total amount). % By weight is preferred, more preferably 0.005 to 5% by weight. When the blending amount is less than 0.001% by weight, such an external preparation for skin is difficult to exert an excellent moisturizing sustaining effect and an effect of improving rough skin, and when it exceeds 10% by weight, the stability of the external preparation for skin over time is improved. It is lowered and it becomes disadvantageous in cost.
すなわち、本発明の皮膚外用剤は、ａ成分のアルギナーゼ活性促進剤を、当該アルギナーゼ活性促進剤の有効成分であるアンズ果汁の含有量が乾燥残留物として０．０００１〜５重量％となる量含有し、かつ、ｂ成分のＬ−アスパラギン酸、Ｌ−グルタミン酸またはそれらの塩から選ばれる１種または２種以上を０．００１〜１０重量％含有する組成に調製することで、優れた保湿持続効果及び肌荒れ改善効果を有し、製剤的経時安定性も良好なものとなる。 That is, the external preparation for skin of the present invention contains an arginase activity promoter of component a in an amount such that the content of apricot juice as an active ingredient of the arginase activity promoter is 0.0001 to 5% by weight as a dry residue. In addition, by preparing a composition containing 0.001 to 10% by weight of one or more selected from L-aspartic acid, L-glutamic acid or salts thereof as component b, an excellent moisturizing sustained effect In addition, it has an effect of improving rough skin and has good formulation stability over time.
上記の通り、本発明のアルギナーゼ活性促進剤は、特に皮膚外用剤に配合して好適に使用でき、優れた保湿性の化粧料、医薬品等の皮膚外用剤を構成し得る。なお、本発明の皮膚外用剤においては、化粧料や医薬品等の皮膚外用剤に常用されている添加剤を本発明の性能を損なわない範囲で配合することも可能である。例えば、流動パラフィン、流動イソパラフィン、スクワラン、ワセリン、固形パラフィン等の炭化水素系油、牛脂、豚脂、魚油等の天然油脂、エステル油、ロウ、直鎖および環状のジメチルポリシロキサン、ポリエーテル変性ジメチルポリシロキサン、アミノ変性ジメチルポリシロキサン等のシリコーン誘導体、セラミド、コレステロール、蛋白誘導体、ラノリン、ラノリン誘導体、レシチン等の油性基剤；ポリオキシエチレンアルキルエーテル、ポリエチレングリコール脂肪酸エステル、ポリオキシプロピレンアルキルエーテル、ポリプロピレングリコール脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレン硬化ひまし油、ポリグリセリン脂肪酸エステル、ポリオキシエチレングリセリン脂肪酸エステル、グリセリンモノ脂肪酸エステル、アルキルポリグルコシド、ポリオキシエチレンポリオキシプロピレンブロックポリマー、アルカノールアミド等の非イオン性界面活性剤；せっけん、アルキル硫酸エステル塩、アルキルエーテル硫酸エステル塩、α−オレフィンスルホン酸塩、アシルメチルタウリン塩、アシルグルタミン酸塩、アシルグリシン塩、アシルザルコシン塩、アシルイセチオン酸塩、アルキルエーテルカルボン酸塩、アミドエーテル硫酸エステル塩、アルキル燐酸エステル塩等の陰イオン性界面活性剤；アルキルジメチルアミノ酢酸ベタイン、アミドプロピルジメチルアミノ酢酸ベタイン、アミドアミノ酸塩、アルキルイミノジ酢酸塩等の両性界面活性剤；アルキルアミンオキシド、ポリオキシエチレンアルキルアミンオキシド等の半極性界面活性剤、塩化アルキルトリメチルアンモニウム、塩化ジアルキルジメチルアンモニウム等の陽イオン性界面活性剤；アルキルアミン、アミドアミン等の塩酸塩または酢酸塩；無機顔料、パール顔料、金属粉末顔料、有機顔料、ジルコニウム等の顔料；クロロフィル、β−カロチン等の天然色素、アルギン酸、カルボキシビニルポリマー、カルボキシメチルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、キサンタンガム、ヒアルロン酸等の水溶性高分子；硫酸マグネシウム、塩化ナトリウム、クエン酸ナトリウム、ピロリドンカルボン酸ナトリウム等の無機塩または有機塩；ｐＨ調製剤である酸およびアルカリ；殺菌剤、キレート剤、抗酸化剤、抗炎症剤、紫外線吸収剤、動植物由来の天然エキス、香料等を配合できる。 As described above, the arginase activity promoter of the present invention can be suitably used particularly by blending with an external preparation for skin, and can constitute an external preparation for skin such as an excellent moisturizing cosmetic or pharmaceutical. In addition, in the skin external preparation of this invention, it is also possible to mix | blend the additive normally used for skin external preparations, such as cosmetics and a pharmaceutical, in the range which does not impair the performance of this invention. For example, hydrocarbon oils such as liquid paraffin, liquid isoparaffin, squalane, petrolatum, solid paraffin, natural fats such as beef tallow, lard, fish oil, ester oil, wax, linear and cyclic dimethylpolysiloxane, polyether modified dimethyl Oily bases such as polysiloxane, amino-modified dimethylpolysiloxane, silicone derivatives, ceramide, cholesterol, protein derivatives, lanolin, lanolin derivatives, lecithin; polyoxyethylene alkyl ether, polyethylene glycol fatty acid ester, polyoxypropylene alkyl ether, polypropylene Glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, polyoxyethylene Nonionic surfactants such as glycerin fatty acid ester, glycerin monofatty acid ester, alkyl polyglucoside, polyoxyethylene polyoxypropylene block polymer, alkanolamide; soap, alkyl sulfate ester salt, alkyl ether sulfate ester salt, α-olefin sulfone Anionic surfactants such as acid salts, acylmethyl taurate salts, acyl glutamate salts, acyl glycine salts, acyl sarcosine salts, acyl isethionate salts, alkyl ether carboxylate salts, amide ether sulfate ester salts, alkyl phosphate ester salts; Amphoteric surfactants such as aminoacetic acid betaine, amidopropyldimethylaminoacetic acid betaine, amide amino acid salts, alkyliminodiacetic acid salts; alkylamine oxides, polyoxyethylenes Semi-polar surfactants such as alkylamine oxides, cationic surfactants such as alkyltrimethylammonium chloride and dialkyldimethylammonium chloride; hydrochlorides or acetates such as alkylamines and amidoamines; inorganic pigments, pearl pigments, metal powders Pigments, organic pigments, pigments such as zirconium; natural pigments such as chlorophyll, β-carotene, water-soluble polymers such as alginic acid, carboxyvinyl polymer, carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, xanthan gum, hyaluronic acid; magnesium sulfate, Inorganic or organic salts such as sodium chloride, sodium citrate, sodium pyrrolidone carboxylate; acids and alkalis that are pH adjusting agents; bactericides, chelating agents, antioxidants, anti-inflammatory agents, ultraviolet rays Adsorbents, natural extracts derived from animals and plants, the flavor and the like can be blended.
本発明の皮膚外用剤の剤型は特に限定されず、例えば、溶液、乳化液、分散液、ジェル、クリーム、軟膏などの任意の剤型を採ることができる。また、その製法は各剤型での定法に従えばよい。 The dosage form of the external preparation for skin of the present invention is not particularly limited, and for example, any dosage form such as a solution, an emulsion, a dispersion, a gel, a cream, and an ointment can be taken. Moreover, the manufacturing method should just follow the usual method in each dosage form.
以下、実施例と比較例を示して本発明をより具体的に説明する。
１．アンズ果汁の調製
アンズの果実を圧搾した果汁を１週間冷蔵保存した後、おりをろ過し、アンズ果汁を得た。このアンズ果汁の乾燥残留分は１０．１重量％であった。
Hereinafter, the present invention will be described more specifically with reference to examples and comparative examples.
1. Preparation of apricot juice The fruit juice obtained by pressing apricot fruit was refrigerated for 1 week, and then the cage was filtered to obtain apricot juice. The dried residue of this apricot juice was 10.1% by weight.
２．木通エキスの調製
乾燥後粉砕した３０ｇの木通に３００ｍＬの水を加え７０℃で３時間加熱し、その後濾過により抽出液から不溶物を除去し、得られた瀘液を減圧乾固して木通エキスを得た。この木通エキスの乾燥残留分は１．５重量％であった。
2. Preparation of the tree extract 300 mL of water was added to 30 g of the tree after drying and heated at 70 ° C. for 3 hours, after which insoluble matter was removed from the extract by filtration, and the resulting filtrate was dried under reduced pressure. A tree extract was obtained. The dry residue of this tree extract was 1.5% by weight.
３．桔梗エキスの調製
乾燥後粉砕した３０ｇの桔梗に３００ｍＬの水を加え７０℃で３時間加熱し、その後濾過により抽出液から不溶物を除去し、得られた瀘液を減圧乾固して桔梗エキスを得た。この桔梗エキスの乾燥残留分は４．０重量％であった。
3. Preparation of bellflower extract Add 30 mL of water to 30 g of bellflower that has been crushed after drying, heat at 70 ° C. for 3 hours, remove the insoluble matter from the extract by filtration. Got. The dry residue of this bellflower extract was 4.0% by weight.
４．麦門冬エキスの調製
乾燥後粉砕した３０ｇの麦門冬に３００ｍＬの水を加え７０℃で３時間加熱し、その後濾過により抽出液から不溶物を除去し、得られた瀘液を減圧乾固して麦門冬エキスを得た。この麦門冬エキスの乾燥残留分は７．４重量％であった。
4). Preparation of Bakumon Winter Extract 300 g of water was added to 30 g of Bakumon Winter that was crushed after drying, heated at 70 ° C. for 3 hours, and then insolubles were removed from the extract by filtration. As a result, barley winter extract was obtained. The dry residue of this barley winter extract was 7.4% by weight.
なお、上記アンズ果汁、木通エキス、桔梗エキス及び麦門冬エキスの乾燥残留分は、乾燥または減圧乾固する前後の重量を測定することで定量した。 In addition, the dry residue of the apricot juice, woody extract, bellflower extract and barley winter extract was quantified by measuring the weight before and after drying or drying under reduced pressure.
実験例１（培養細胞によるアルギナーゼ活性促進効果の確認実験）
マウス表皮細胞（ＰＡＭ２１２株）を直径１０ｃｍの培養皿に蒔き、ダルベッコ改変イーグル培地に牛胎児血清を１０％配合した培地で、培養皿が細胞で完全に覆われるまで培養を継続した。その後、被験物としてアンズ果汁および各種エキスをその培地中濃度が乾燥残留物として０〜０．０５重量％となるように添加し、３日間培養した。培養後、細胞を回収し、細胞内のアルギナーゼ活性量を被験物の各濃度につき５回ずつ測定し、その平均値を算出した。細胞内のアルギナーゼ活性量は細胞を１ｍＬの２５ｍＭトリス−塩酸緩衝液（ｐＨ＝７．５）中でホモジナイズしたホモジネートを用いて測定した。ホモジネート０．０５ｍｌを１．５ｍＬの栓付きのマイクロチューブに移し取り、アルギナーゼの活性化のため５０℃で１０分間加熱処理を行った。０．０４ｍＬの０．１ＭＬ−アルギニン溶液を添加し３７℃にて３０分間インキュベートした。
インキュベート終了後０．０１ｍＬの６０％過塩素酸を添加、混和し酵素反応を停止させ、１００００Ｇで遠心分離を行い、得られた上清中の尿素量を測定した。細胞内のアルギナーゼ活性量は、無添加の場合の生成尿素量を１００％とすることで相対的に表した。結果を表１に示す。なお、尿素量は和光純薬工業株式会社製の尿素窒素−テストワコーを用い、取扱説明書通りに使用した。つまり、上清０．０２ｍＬと発色試液（発色原液Ａと発色原液Ｂを５：１で混合したもの）５ｍＬを混和し、沸騰水浴中で２５分間加熱後、流水中で冷却し、分光光度計を用いて５３０ｎｍの吸光度を測定し、別に求めた尿素の検量線より上清中の尿素量を算出した。
Experimental Example 1 (Confirmation experiment of arginase activity promoting effect by cultured cells)
Mouse epidermal cells (PAM212 strain) were spread on a culture dish having a diameter of 10 cm, and the culture was continued in a medium containing 10% fetal bovine serum in Dulbecco's modified Eagle medium until the culture dish was completely covered with cells. Then, apricot juice and various extracts were added as test substances so that the concentration in the medium was 0 to 0.05% by weight as a dry residue, and cultured for 3 days. After culturing, the cells were collected, the amount of arginase activity in the cells was measured 5 times for each concentration of the test substance, and the average value was calculated. The amount of arginase activity in the cells was measured using a homogenate obtained by homogenizing the cells in 1 mL of 25 mM Tris-HCl buffer (pH = 7.5). 0.05 ml of the homogenate was transferred to a 1.5 mL stoppered microtube and heat-treated at 50 ° C. for 10 minutes to activate arginase. 0.04 mL of 0.1 ML-arginine solution was added and incubated at 37 ° C. for 30 minutes.
After completion of the incubation, 0.01 mL of 60% perchloric acid was added and mixed to stop the enzyme reaction, centrifuged at 10,000 G, and the amount of urea in the resulting supernatant was measured. The amount of intracellular arginase activity was relatively expressed by setting the amount of produced urea when not added to 100%. The results are shown in Table 1. In addition, the urea amount was used according to the instruction manual using urea nitrogen-test Wako manufactured by Wako Pure Chemical Industries, Ltd. That is, 0.02 mL of the supernatant and 5 mL of the color developing solution (mixed color developing solution A and color developing solution B mixed at 5: 1) are mixed, heated in a boiling water bath for 25 minutes, cooled in running water, and spectrophotometer Was used to measure the absorbance at 530 nm, and the urea amount in the supernatant was calculated from the separately obtained urea calibration curve.
表１より、アンズ果汁（実施例１）は低濃度から優れた細胞内アルギナーゼ活性促進効果を示し、特に０.０５％濃度において、従来技術の木通エキス（比較例１）、桔梗エキス（比較例２）及び麦門冬エキス（比較例３）よりも著しくその促進効果が高く、アンズ果汁が強力なアルギナーゼ活性促進剤と成り得ることが分かった。 From Table 1, apricot juice (Example 1) shows an excellent effect of promoting intracellular arginase activity from a low concentration, and in particular at a concentration of 0.05%, the traditional tree extract (Comparative Example 1) and bellflower extract (Comparison) It was found that the promotion effect was significantly higher than in Example 2) and Bakumon winter extract (Comparative Example 3), and apricot juice could be a strong arginase activity promoter.
実験例２
定法に従って、表２に示す配合組成のクリームである皮膚外用剤を調製し、乾燥による肌荒れを生じている１０名の女性（２５才〜３５才）を被験者として、塗布部位を左腕上腕内側部、無塗布部位を右腕上腕内側部と定め、クリームを朝の洗顔後と夜の入浴後の一日２回ずつ（１回の使用量：０．１ｇ）連続２週間使用してもらい、（１）保湿持続効果及び（２）肌荒れ改善効果について下記のように評価した。また、調製したクリームの（３）経時安定性についても下記のように評価した。結果を表２に示す。
Experimental example 2
According to a conventional method, a skin external preparation that is a cream having the composition shown in Table 2 was prepared, and 10 females (25 to 35 years old) who had rough skin due to drying were used as subjects. The non-application site is defined as the inner part of the upper arm of the right arm, and the cream is used twice a day after washing in the morning and after taking a bath in the evening (amount of use: 0.1 g) for two consecutive weeks, (1) The moisturizing sustaining effect and (2) rough skin improving effect were evaluated as follows. In addition, (3) stability over time of the prepared cream was also evaluated as follows. The results are shown in Table 2.
（１）保湿持続効果
塗布終了の翌日と１週間後にＳＫＩＣＯＮ−２００（ＩＢＳ社製）を用いて、各皮膚外用剤の塗布部位と無塗布部位の角層水分含量を測定した。塗布終了の翌日において塗布部位の角層水分含量値から無塗布部位の角層水分含量値を差し引いた値をＷ(０)とし、塗布終了の１週間後において塗布部位の角層水分含量値から無塗布部位の角層水分含量値を差し引いた値をＷ(１)とした場合、次式により保湿持続効果を求めた。
保湿持続効果（％）＝Ｗ(１)／Ｗ(０)ｘ100
該式から求めた保湿持続効果の値について、１０名の平均値を求め、その平均値が８０％以上を示したときを保湿持続効果の良好な皮膚外用剤であると判定した。
(1) Moisturizing sustaining effect The horny layer moisture content of the application site and the non-application site of each external preparation for skin was measured using SKICON-200 (manufactured by IBS) on the next day and one week after the application was completed. The value obtained by subtracting the stratum corneum water content value of the non-application site from the stratum corneum water content value of the application site on the next day after the application is finished is defined as W (0). When the value obtained by subtracting the moisture content value of the stratum corneum at the uncoated part is defined as W (1), the moisturizing effect is obtained by the following formula.
Moisturizing effect (%) = W (1) / W (0) x100
With respect to the value of the moisturizing effect obtained from the formula, an average value of 10 people was obtained, and when the average value showed 80% or more, it was determined that the skin external preparation had a good moisturizing effect.
（２）肌荒れ改善効果
連続２週間使用した時の肌荒れの状態変化について下記のように評価点を付け、１０名の評価点の平均値を求めて、平均値１．５点以上を肌荒れ改善効果に優れた皮膚外用剤であると判定した。
２点：肌荒れが明らかに治ってきたと感じた場合。
１点：肌荒れがやや治ってきたと感じた場合。
０点：肌荒れ改善効果が全くないと感じた場合。
(2) Skin roughening effect The following points are assigned to the changes in the state of rough skin when used for 2 consecutive weeks, and the average value of 10 evaluation points is obtained. It was determined to be an excellent skin external preparation.
2 points: When it is felt that rough skin has been cured.
1 point: When it feels that the rough skin has been cured somewhat.
0 point: When it feels that there is no skin roughening effect at all.
（３）経時安定性
クリームを透明ガラス容器に密封して−５℃、２５℃および４０℃で３ヶ月間保存したときの状態を調査し、下記に示す３段階で評価した。
○：安定性良好（いずれの温度においても外観の変化がなくブツ等も生じない。）
△：安定性やや不良（いずれかの温度において僅かに沈殿を生じるか僅かに分離が見られる。または僅かにブツやダマを生じる。）
×：安定性不良（いずれの温度においても明らかに沈殿を生じるか分離する。またはブツやダマを生じる。）
(3) Stability over time The state when the cream was sealed in a transparent glass container and stored at −5 ° C., 25 ° C. and 40 ° C. for 3 months was evaluated and evaluated in the following three stages.
○: Stability is good (no change in appearance at any temperature and no flickering etc.)
Δ: Slightly inferior (slight precipitation or slight separation at any temperature, or slight bumps and lumps)
X: Poor stability (precipitates or separates at any temperature, or causes lumps and lumps)
表２から、アンズ果汁と、Ｌ−アスパラギン酸ナトリウムまたはＬ−グルタミン酸ナトリウムとを配合した実施例２、３の剤は優れた肌の保湿持続効果及び肌荒れ改善効果を有し、保存時の経時安定性も良好であることが分かる。一方、アンズ果汁に替えて麦門冬エキスを配合した比較例４の剤は肌の保湿持続効果及び肌荒れ改善効果がともに低く、アンズ果汁及びＬ−アスパラギン酸ナトリウムを最適配合量を超えて配合した比較例５の剤は経時安定性が悪かった。 From Table 2, the agents of Examples 2 and 3 blended with apricot juice and sodium L-aspartate or sodium L-glutamate have excellent skin moisturizing and skin roughening effects, and are stable over time during storage. It turns out that property is also favorable. On the other hand, the agent of Comparative Example 4 in which Bakumon winter extract was blended in place of apricot juice had both low skin moisturizing effect and rough skin improvement effect, and blended apricot juice and sodium L-aspartate in excess of the optimum blending amount. The agent of Comparative Example 5 was poor in stability over time.
実験例３
定法に従って、表３に示す組成の化粧水である皮膚外用剤を調製し、クリームのときの評価と同様に、乾燥による肌荒れを感じている１０名の女性（２５才〜３５才）を被験者として、化粧水を朝の洗顔後と夜の入浴後の一日２回ずつ連続２週間使用してもらい、（１）保湿持続効果及び（２）肌荒れ改善効果についてはクリームのときと同様にして評価した。また、調製した化粧水の（４）経時安定性についても下記のように評価した。結果を表３に示す。
Experimental example 3
According to a conventional method, a skin external preparation having the composition shown in Table 3 was prepared, and 10 women (25 to 35 years old) who feel rough skin due to dryness were tested as subjects as in the case of cream. Use skin lotion twice a day after face washing in the morning and after bathing at night for two consecutive weeks, and evaluate (1) moisturizing effect and (2) skin roughness improving effect in the same way as for cream. did. In addition, (4) stability over time of the prepared lotion was also evaluated as follows. The results are shown in Table 3.
（４）経時安定性
化粧水を透明ガラス容器に密封して０℃、２５℃および４０℃で３ヶ月間保存し、その外観を観察して、下記に示す３段階で評価した。
○：安定性良好（いずれの温度でも外観の変化がない。）
△：安定性やや不良（いずれかの温度において若干おり、沈殿を生じるか若しくは若干着色を生じる。）
×：安定性不良（いずれの温度においてもおり、沈殿を生じるか若しくは分離するか、または着色が著しい。）
(4) Stability over time The skin lotion was sealed in a transparent glass container and stored at 0 ° C., 25 ° C. and 40 ° C. for 3 months. The appearance was observed and evaluated in the following three stages.
○: Good stability (no change in appearance at any temperature)
Δ: Slightly poor (slightly at any temperature, causing precipitation or slight coloration)
X: Stability failure (at any temperature, precipitation occurs or separates, or coloring is significant)
表３から、アンズ果汁と、Ｌ−アスパラギン酸ナトリウムまたはＬ−グルタミン酸ナトリウムとを配合した実施例４、５の剤は、優れた肌の保湿持続効果及び肌荒れ改善効果を有し、しかも保存時の経時安定性も良好であることが分かる。一方、アンズ果汁に替えて麦門冬エキスを配合した比較例６の剤は肌の保湿持続効果及び肌荒れ改善効果がともに低く、アンズ果汁及びＬ−アスパラギン酸ナトリウムを最適配合量を超えて配合した比較例７の剤は経時安定性が悪かった。 From Table 3, the agents of Examples 4 and 5 blended with apricot juice and sodium L-aspartate or sodium L-glutamate have an excellent skin moisturizing and skin roughening effect, and at the time of storage. It can be seen that the stability over time is also good. On the other hand, the agent of Comparative Example 6 in which Bakumon winter extract was blended instead of apricot juice had both low skin moisturizing effect and rough skin improvement effect, and blended apricot juice and sodium L-aspartate in excess of the optimum blending amount. The agent of Comparative Example 7 had poor stability over time.
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