JP5968707B2 - Oral skin color improver - Google Patents
Oral skin color improver Download PDFInfo
- Publication number
- JP5968707B2 JP5968707B2 JP2012163360A JP2012163360A JP5968707B2 JP 5968707 B2 JP5968707 B2 JP 5968707B2 JP 2012163360 A JP2012163360 A JP 2012163360A JP 2012163360 A JP2012163360 A JP 2012163360A JP 5968707 B2 JP5968707 B2 JP 5968707B2
- Authority
- JP
- Japan
- Prior art keywords
- crocetin
- skin
- skin color
- oral
- water
- Prior art date
- 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
本発明は、クロセチンまたはその薬理学的に許容し得る塩を有効成分とし、肌のくすみを改善できる経口肌色改善剤に関する。 The present invention relates to an oral skin color improving agent that can improve skin dullness using crocetin or a pharmacologically acceptable salt thereof as an active ingredient.
「くすみ」は、加齢とともに肌に出現してくる現象であり、具体的には、肌の赤みが減少して黄みが増し、肌の透明感が喪失され、老廃物によるにごり感があり、肌が色ムラになった状態を総合的に表す用語である。くすみは、肌の明度が落ちて容易に暗く見えることから、女性にとって美容上の大きな問題であり、その対策が望まれてきている。 “Dullness” is a phenomenon that appears on the skin with aging. Specifically, the redness of the skin decreases, yellowing increases, the transparency of the skin is lost, and there is a feeling of cloudiness due to waste products. It is a term that comprehensively represents the state in which the skin is uneven in color. Dullness is a major cosmetic problem for women because the lightness of the skin falls and it looks dark easily, and countermeasures have been desired.
また、くすみは、加齢に伴う角質層の肥厚による濁りや陰影、皮膚の赤みの低下、色素の沈着、皮膚の弾力の低下、皮膚の黄色化、汗や皮脂等の汚れ等の多数の要因が相互に関与することによって発生すると考えられている。このため、肌のシミなどの改善に有用とされる物質であっても、より多くの要因が関与するくすみについては効果的に改善できない場合が多い。 Dullness is caused by a number of factors such as turbidity and shadows due to thickening of the stratum corneum with age, decreased skin redness, pigmentation, decreased skin elasticity, yellowing of the skin, dirt such as sweat and sebum, etc. Is thought to be caused by mutual involvement. For this reason, even if it is a substance useful for improvement of skin spots, dullness involving more factors cannot often be effectively improved.
一方、カロテノイドの一種であり、クチナシの果実、サフランの雌しべなどの可食経験の有る植物から抽出されるクロセチンについては、グルタチオンの産生を促進することが報告されている(特許文献1)。グルタチオンの産生促進は、肝斑や炎症後の色素沈着などに有用であるとされているものの、より多くの要因が関与して発生するくすみについて十分な改善効果を有することは確認されていない。 On the other hand, crocetin, which is a kind of carotenoid and extracted from plants with edible experience such as gardenia fruit and saffron pistil, has been reported to promote the production of glutathione (Patent Document 1). Although the promotion of glutathione production is said to be useful for melasma and pigmentation after inflammation, it has not been confirmed that it has a sufficient improvement effect on dullness caused by more factors involved.
本発明は、可食経験の有る植物由来の抽出物を用いて、経口摂取により肌のくすみを改善する経口肌色改善剤を提供することを課題とする。 This invention makes it a subject to provide the oral skin color improving agent which improves the dullness of skin by oral ingestion using the extract derived from the plant with an edible experience.
本発明者は、上記課題を解決するため、鋭意検討した結果、クロセチンの経口摂取により肌のくすみが改善されることを見出し、この知見に基づいて本発明をなすに至った。 As a result of intensive studies in order to solve the above-mentioned problems, the present inventor has found that dullness of the skin is improved by oral intake of crocetin, and has reached the present invention based on this finding.
即ち、本発明は、
[1].下記式
That is, the present invention
[1]. Following formula
[2].クロセチンが水溶液中に分散し、且つ該クロセチンの粒子径がメジアン径で0.5μm未満であることを特徴とする前記[1]に記載の経口肌色改善剤、
からなっている。
[2]. The oral skin color improving agent according to [1], wherein crocetin is dispersed in an aqueous solution, and the particle size of the crocetin is less than 0.5 μm in median size,
It is made up of.
本発明の経口肌色改善剤は、経口摂取することにより、肌のくすみを改善し、肌の明度を上昇させる効果を発揮する。 The oral skin color improving agent of the present invention exhibits the effect of improving the dullness of the skin and increasing the brightness of the skin when taken orally.
本発明で用いられるクロセチンは、式 Crocetin used in the present invention has the formula
本発明において、上記植物基原からクロシンを抽出する方法に制限はなく、例えば、粉砕されたクチナシの乾燥果実から水またはアルコール(例えば、メタノール、エタノールなど)、或いはそれらの混合液を用いて抽出するなどの公知の方法が用いられる。抽出条件は、例えば水・アルコール混合液を用いた場合、室温(約0〜30℃)〜50℃で約1〜18時間が好ましく、約30〜40℃で約2〜4時間がより好ましい。抽出操作は通常複数回繰り返される。 In the present invention, there is no limitation on the method for extracting crocin from the above plant base, for example, extraction from pulverized dry fruit of gardenia using water, alcohol (eg, methanol, ethanol, etc.), or a mixture thereof. A known method, such as, is used. For example, in the case of using a water / alcohol mixed solution, the extraction condition is preferably room temperature (about 0 to 30 ° C.) to 50 ° C. for about 1 to 18 hours, more preferably about 30 to 40 ° C. for about 2 to 4 hours. The extraction operation is usually repeated several times.
クロシンを含む抽出液は自体公知の方法により濃縮され、通常、濃縮液として冷蔵保存される。また、該抽出液は、更に吸着樹脂処理或いは膜分離処理し、ゲニポサイドなどのイリドイド配糖体を除去しクロシンの濃度を高めることが、好ましく行われる。 The extract containing crocin is concentrated by a method known per se, and is usually stored refrigerated as a concentrated solution. Further, the extract is preferably subjected to an adsorption resin treatment or membrane separation treatment to remove iridoid glycosides such as geniposide and increase the concentration of crocin.
クロシンの加水分解は常法に従って行われてよく、通常、酸、アルカリ或いは適当な加水分解酵素の作用で行われる。ここで酸としては、例えば塩酸、硫酸およびリン酸などが挙げられ、アルカリとしては例えば、水酸化ナトリウム、水酸化カリウム、炭酸ナトリウムおよび炭酸カリウムなどが挙げられる。また加水分解酵素としては、β−グルコシダーゼなどが挙げられる。 The hydrolysis of crocin may be carried out according to a conventional method, and is usually carried out by the action of acid, alkali or an appropriate hydrolase. Here, examples of the acid include hydrochloric acid, sulfuric acid, and phosphoric acid, and examples of the alkali include sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate. Examples of hydrolases include β-glucosidase.
工業的には、クロシンの加水分解がアルカリによる加水分解であるのが好ましい。該加水分解は、攪拌および/または加熱下で行われることが好ましく、例えば、攪拌下、約20〜70℃、好ましくは約40〜60℃に加熱し、約1〜24時間、好ましくは約3〜5時間行われ得る。 Industrially, the hydrolysis of crocin is preferably hydrolysis with alkali. The hydrolysis is preferably performed with stirring and / or heating, for example, heating to about 20 to 70 ° C., preferably about 40 to 60 ° C. with stirring, for about 1 to 24 hours, preferably about 3 Can be done for ~ 5 hours.
また、クロシンの加水分解がアルカリによるものである場合、通常、加水分解終了後、反応液に塩酸、硫酸またはリン酸などの無機酸、もしくはクエン酸などの有機酸の水溶液を適量加え、液性をpH約4.0以下、好ましくはpH約1.0〜3.0にするか、または反応液を塩酸、硫酸またはリン酸などの無機酸、もしくはクエン酸などの有機酸の水溶液に加え、液性をpH約4.0以下、好ましくはpH約1.0〜3.0にすることで、クロセチンを析出させる。その後、クロセチンを析出させた混合液を、遠心分離するか或いはろ紙もしくはろ布に通してろ過することにより、クロセチンをペースト状の固形物として回収できる。 In addition, when hydrolysis of crocin is due to alkali, usually after completion of hydrolysis, an appropriate amount of an aqueous solution of an inorganic acid such as hydrochloric acid, sulfuric acid or phosphoric acid, or an organic acid such as citric acid is added to the reaction solution to Is added to an aqueous solution of an inorganic acid such as hydrochloric acid, sulfuric acid or phosphoric acid, or an organic acid such as citric acid. Crocetin is precipitated by adjusting the liquidity to about pH 4.0 or less, preferably about pH 1.0 to 3.0. Thereafter, the crocetin can be recovered as a paste-like solid by centrifuging the mixed liquid in which crocetin is precipitated or filtering through a filter paper or a filter cloth.
また、クロシンの加水分解が酸による加水分解である場合、通常、加水分解と同時にクロセチンが析出するため、反応液は懸濁液として得られる。反応終了後、得られた懸濁液を、遠心分離するか或いはろ紙もしくはろ布に通してろ過することにより、クロセチンをペースト状の固形物として回収できる。 When crocin is hydrolyzed with acid, crocetin is usually precipitated simultaneously with the hydrolysis, so that the reaction solution is obtained as a suspension. After completion of the reaction, crocetin can be recovered as a pasty solid by centrifuging the obtained suspension or filtering through a filter paper or filter cloth.
このようにして得られたクロセチン(ペースト状の固形物)には、通常、酸、中和塩および原料由来の不純物が固形物表面に付着しているため、該不純物を除去する目的で、洗浄処理が行われる。該処理は、例えば、上記ペースト状の固形物を十分量の水を用いて水洗するなど、公知の方法を用いて行ってよい。次に、例えば棚式の通風乾燥機または真空乾燥機などを用いて、好ましくは窒素ガスの雰囲気下約50℃を越えない温度で乾燥し、固形物に残留する水を除去してもよい。 The crocetin obtained in this way (paste-like solid) usually has acid, neutralized salt, and impurities derived from the raw material attached to the surface of the solid, so that it is washed for the purpose of removing the impurities. Processing is performed. The treatment may be performed using a known method, for example, washing the pasty solid with a sufficient amount of water. Next, the water remaining in the solid material may be removed by drying using a shelf-type ventilation dryer or a vacuum dryer, preferably at a temperature not exceeding about 50 ° C. in an atmosphere of nitrogen gas.
本発明に用いられるクロセチンとしては、上記ペースト状の固形物を水洗したもの、または水洗したものを乾燥したものが好ましく用いられるが、更に、これらクロセチン(クロセチン組成物)を精製した精製クロセチンを用いてもよい。ここで、クロセチンを精製する方法に制限は無く、例えばカラムクロマトグラフィー、再結晶など自体公知の方法が用いられる。 As the crocetin used in the present invention, those obtained by washing the pasty solid with water or those obtained by drying the water are preferably used, and further, purified crocetin obtained by purifying these crocetin (crocetin composition) is used. May be. Here, there is no restriction | limiting in the method of refine | purifying crocetin, For example, methods known per se, such as column chromatography and recrystallization, are used.
本発明において、クロセチンの薬理学的に許容しうる塩としては、例えば、ナトリウム、カリウムなどの第1族元素の塩、マグネシウム、カルシウムなどの第2族元素の塩、ピリジン、ジメチルアミン、ジエチルアミン、エタノールアミンなどの医薬的に許容される有機アミノ化合物の塩などが挙げられる。 In the present invention, pharmacologically acceptable salts of crocetin include, for example, salts of group 1 elements such as sodium and potassium, salts of group 2 elements such as magnesium and calcium, pyridine, dimethylamine, diethylamine, Examples thereof include pharmaceutically acceptable salts of organic amino compounds such as ethanolamine.
本発明の経口肌色改善剤は、上記クロセチンもしくはその薬理学的に許容しうる塩をそのまま、あるいは医薬品添加物、食品添加物および食品素材などを適宜配合し、常法に従い、例えば液剤(ドリンク剤など)、散剤、顆粒剤、錠剤、マイクロカプセル、ソフトカプセル、ハードカプセル、油脂組成物、O/W型乳化液、W/O型乳化液または可溶化液などの形態の製剤として製造され得る。 The oral skin color-improving agent of the present invention comprises the above crocetin or a pharmacologically acceptable salt thereof as it is, or a pharmaceutical additive, a food additive, a food material and the like are appropriately blended, and according to a conventional method, for example, a liquid (drink agent) Etc.), powders, granules, tablets, microcapsules, soft capsules, hard capsules, oil / fat compositions, O / W emulsions, W / O emulsions or solubilized liquids.
上記製剤100質量%中、クロセチンの含有量は、純度100質量%のクロセチンに換算して、通常約0.0001〜50質量%、好ましくは約0.001〜20質量%、より好ましくは約0.01〜5質量%である。 In 100% by mass of the preparation, the content of crocetin is usually about 0.0001 to 50% by mass, preferably about 0.001 to 20% by mass, more preferably about 0, in terms of crocetin having a purity of 100% by mass. 0.01 to 5% by mass.
ここで、上記した製剤の形態の中でも、腸等の体内でのクロセチンの吸収率および吸収速度を高める観点から、クロセチンが水溶液中に分散し、且つ該クロセチンの粒子径がメジアン径で0.5μm未満の液剤が好ましい。 Here, among the above-mentioned preparation forms, crocetin is dispersed in an aqueous solution from the viewpoint of increasing the absorption rate and absorption rate of crocetin in the body such as the intestine, and the particle diameter of the crocetin is 0.5 μm in median size. Less than the liquid is preferred.
このような液剤の製造には、クロセチンの水分散性を高めたクロセチン製剤を用いることができる。該クロセチン製剤の製造方法としては、糖類を含有する水溶液中にクロセチンを分散して分散液を調製する際に、該分散液のクロセチンの粒子径(メジアン径)を約0.5μm未満とする方法が挙げられる。より具体的には、例えば下記の方法1および2を例示できる。 For the production of such a liquid preparation, a crocetin preparation with improved water dispersibility of crocetin can be used. As a method for producing the crocetin preparation, when preparing a dispersion by dispersing crocetin in an aqueous solution containing a saccharide, the particle diameter (median diameter) of the crocetin of the dispersion is less than about 0.5 μm. Is mentioned. More specifically, for example, the following methods 1 and 2 can be exemplified.
[方法1]
水洗したクロセチン(ペースト状の固形物)を水に懸濁して得た懸濁液を、室温(約0〜30℃)〜100℃、好ましくは約40〜65℃に加温した糖類を含有する水溶液に加え、これを高圧式均質化処理機を用いて処理することにより、クロセチン製剤を得る。
[Method 1]
A suspension obtained by suspending water-washed crocetin (a paste-like solid) in water contains a saccharide heated to room temperature (about 0 to 30 ° C.) to 100 ° C., preferably about 40 to 65 ° C. A crocetin formulation is obtained by adding to an aqueous solution and processing this using a high-pressure homogenizer.
[方法2]
水洗したクロセチン(ペースト状の固形物)を水に懸濁して得た懸濁液を高圧式均質化処理機を用いて処理する。得られた処理液を、室温(約0〜30℃)〜100℃、好ましくは約40〜65℃に加温した糖類を含有する水溶液に加え、攪拌機、加熱用のジャケットおよび邪魔板等を備えた通常の攪拌・混合槽を用いて攪拌し、クロセチン製剤を得る。
[Method 2]
A suspension obtained by suspending water-washed crocetin (a pasty solid) in water is processed using a high-pressure homogenizer. The obtained treatment liquid is added to an aqueous solution containing sugars heated to room temperature (about 0 to 30 ° C.) to 100 ° C., preferably about 40 to 65 ° C., and equipped with a stirrer, a heating jacket, a baffle plate, and the like. The mixture is stirred using a normal stirring / mixing tank to obtain a crocetin preparation.
上記糖類としては特に制限はなく、例えばブドウ糖、果糖、ガラクトースなどの単糖、麦芽糖、乳糖、蔗糖などの二糖、澱粉、加工澱粉、アミロース、アミロペクチン、デキストリン、シクロデキストリンなどの多糖、フラクトオリゴ糖、ガラクトオリゴ糖、マルトトリオース、マルトテトラオース、マルトペンタオースおよびマルトヘキサオースなどのマルトオリゴ糖などの少糖、アラビアガム、カラギナン、カラヤガム、寒天、キサンタンガム、グアーガム、タマリンドシードガム、トラガントガム、ペクチンおよびローカストビーンガムなどの多糖類、ソルビトール、マンニトール、マルチトールまたは還元水飴などの糖アルコールなどが挙げられ、好ましくはアラビアガムなどの多糖類などである。 The saccharide is not particularly limited, and examples thereof include monosaccharides such as glucose, fructose and galactose, disaccharides such as maltose, lactose and sucrose, starch, modified starch, polysaccharides such as amylose, amylopectin, dextrin and cyclodextrin, fructooligosaccharides, Oligosaccharides such as malto-oligosaccharides such as galactooligosaccharide, maltotriose, maltotetraose, maltopentaose and maltohexaose, gum arabic, carrageenan, caraya gum, agar, xanthan gum, guar gum, tamarind seed gum, tragacanth gum, pectin and locust bean Examples thereof include polysaccharides such as gum, sugar alcohols such as sorbitol, mannitol, maltitol or reduced starch syrup, preferably polysaccharides such as gum arabic.
上記高圧式均質化処理機としては、例えばクレアミックスWモーション(エムテクニック社製)、APVゴーリンホモジナイザー(APV社製)、マイクロフルイダイザー(みづほ工業社製)、アルティマイザー(スギノマシン社製)またはナノマイザー(大和製罐社製)などが挙げられる。該均質化処理機による操作条件としては、装置の仕様により異なり一様ではないが、例えば約5〜80MPaで1パス(単回数処理)又は多パス(複数回数処理)とするのが好ましい。 Examples of the high-pressure homogenizer include Claremix W Motion (M Technique), APV Gorin homogenizer (APV), Microfluidizer (Mizuho Kogyo), Ultimateizer (Sugino Machine) or Nanomizer (manufactured by Yamato Steel Co., Ltd.) The operating conditions by the homogenizer vary depending on the specifications of the apparatus and are not uniform. However, for example, it is preferable to set one pass (single-time treatment) or multiple passes (multiple-time treatment) at about 5 to 80 MPa.
上記攪拌機としては、例えばTKホモミクサー(特殊機化工業社製)またはクレアミックス(エムテクニック社製)などの高速回転式分散・乳化機が好ましく用いられる。該分散・乳化機の操作条件としては、例えば実験室用の小型機では、回転数約2000〜20000rpm、攪拌時間約5〜60分間を例示できる。 As the agitator, for example, a high-speed rotating dispersion / emulsifier such as TK homomixer (made by Tokushu Kika Kogyo Co., Ltd.) or Claremix (made by M Technique Co., Ltd.) is preferably used. As the operating conditions of the dispersing / emulsifying machine, for example, in a small laboratory machine, a rotation speed of about 2000 to 20000 rpm and a stirring time of about 5 to 60 minutes can be exemplified.
上記処理により得られる分散液中のクロセチンの粒子径(メジアン径)は約0.5μm未満であることが好ましく、約0.4μm未満であることがより好ましい。該粒子径が0.5μmを超えると、得られたクロセチン製剤を配合して製造した経口肌色改善剤のクロセチンの沈殿抑制が十分でなく、また、体内でのクロセチンの吸収率および吸収速度の観点から好ましくない。一方、該粒子径が小さすぎると、粒子が凝集し分散状態が保たれなくなり好ましくないため、その下限は、通常0.06μm程度である。 The particle diameter (median diameter) of crocetin in the dispersion obtained by the above treatment is preferably less than about 0.5 μm, and more preferably less than about 0.4 μm. When the particle diameter exceeds 0.5 μm, the oral skin color improving agent produced by blending the obtained crocetin preparation does not have sufficient inhibition of crocetin precipitation, and the crocetin absorption rate and absorption rate in the body Is not preferable. On the other hand, if the particle diameter is too small, the particles are aggregated and the dispersed state cannot be maintained, which is not preferable. Therefore, the lower limit is usually about 0.06 μm.
本発明に従うクロセチン製剤100質量%中には、クロセチン約0.05〜6質量%、好ましくは約0.5〜5質量%、糖類を約0.05〜60質量%、好ましくは約1〜30質量%、残余が水となるように調整するのが好ましい。また、クロセチンと糖類の比率は、約1:1〜1:10、好ましくは約1:2〜1:6となるように調整するのが好ましい。 In 100% by mass of the crocetin preparation according to the present invention, about 0.05 to 6% by mass of crocetin, preferably about 0.5 to 5% by mass, and about 0.05 to 60% by mass of saccharide, preferably about 1 to 30%. It is preferable to adjust the mass% so that the balance is water. The ratio of crocetin and saccharide is preferably adjusted to be about 1: 1 to 1:10, preferably about 1: 2 to 1: 6.
なお、上記方法1および2により製造されるクロセチン製剤は、クロセチンが水溶液中に分散した水分散性のものであるが、これら水分散性のクロセチン製剤を自体公知の方法により乾燥し、粉末状のクロセチン製剤としても良い。 The crocetin preparations produced by the above methods 1 and 2 are water-dispersible in which crocetin is dispersed in an aqueous solution. These water-dispersible crocetin preparations are dried by a method known per se to obtain powdery It may be a crocetin preparation.
乾燥方法としては、例えば、噴霧乾燥、ドラム乾燥、ベルト乾燥、真空乾燥あるいは真空凍結乾燥などが挙げられ、好ましくは真空凍結乾燥または噴霧乾燥である。 Examples of the drying method include spray drying, drum drying, belt drying, vacuum drying, vacuum freeze drying, and the like, preferably vacuum freeze drying or spray drying.
真空凍結乾燥に使用される装置としては特に制限は無く、自体公知の装置を使用することができる。真空凍結乾燥の方法は自体公知の方法に従って良く、例えば、水分散性のクロセチン製剤(好ましくは該製剤と適量の水およびデキストリンなどの賦形剤とを混合したもの)を−20℃以下、約−30〜−40℃にて凍結させ、得られた凍結物を約10〜100Pa程度の真空下、約30〜60℃で加熱しながら、約10〜72時間乾燥するのが好ましい。得られた凍結乾燥物を自体公知の方法により粉砕し、好ましくは篩い分けすることにより粉末状のクロセチン製剤を得ることができる。得られる粉末状のクロセチン製剤の乾燥減量は通常約5質量%以下、好ましくは約1〜3質量%である。 There is no restriction | limiting in particular as an apparatus used for vacuum freeze-drying, A itself well-known apparatus can be used. The method of vacuum lyophilization may be in accordance with a method known per se. For example, a water-dispersible crocetin preparation (preferably a mixture of the preparation and an appropriate amount of water and an excipient such as dextrin) at −20 ° C. or less, about It is preferable to freeze at −30 to −40 ° C. and dry the obtained frozen product for about 10 to 72 hours while heating at about 30 to 60 ° C. under a vacuum of about 10 to 100 Pa. The obtained freeze-dried product is pulverized by a method known per se and preferably sieved to obtain a powdery crocetin preparation. The loss on drying of the resulting powdery crocetin preparation is usually about 5% by mass or less, preferably about 1 to 3% by mass.
噴霧乾燥に使用される装置としては特に制限は無く、噴射式噴霧乾燥装置または回転円盤式噴霧乾燥装置など、公知の装置を使用することができる。また、噴霧乾燥の操作条件としては、例えば分散液を加圧ノズル式噴霧乾燥装置に供給し、熱風入口温度約120〜170℃、好ましくは約140〜150℃、排気温度約70〜140℃、好ましくは約85〜90℃の条件下で噴霧乾燥し、乾燥物をサイクロンで捕集することにより、粉末状のクロセチン製剤を得ることができる。得られる粉末状のクロセチン製剤の平均粒子径は約20〜200μm、好ましくは約60〜100μmである。また、その乾燥減量は約10質量%以下が好ましく、約7質量%以下であることがより好ましい。 There is no restriction | limiting in particular as an apparatus used for spray-drying, Well-known apparatuses, such as a spray-type spray-drying apparatus or a rotary disk-type spray-drying apparatus, can be used. In addition, as operation conditions for spray drying, for example, the dispersion is supplied to a pressure nozzle type spray drying apparatus, hot air inlet temperature is about 120 to 170 ° C, preferably about 140 to 150 ° C, exhaust temperature is about 70 to 140 ° C, Preferably, the powdered crocetin preparation can be obtained by spray-drying under conditions of about 85 to 90 ° C. and collecting the dried product with a cyclone. The powdery crocetin preparation obtained has an average particle size of about 20 to 200 μm, preferably about 60 to 100 μm. Further, the loss on drying is preferably about 10% by mass or less, and more preferably about 7% by mass or less.
上記粉末状のクロセチン製剤の好ましい実施態様の一例は、該製剤100質量%中、クロセチンを約0.1〜10質量%、好ましくは約0.2〜4質量%、糖類を約90〜99.9質量%、好ましくは約96〜99.8質量%を含む粉末である。その色価は約50〜1000が好ましく、約100〜400であることがより好ましい。 An example of a preferred embodiment of the powdery crocetin preparation is as follows. In 100% by weight of the preparation, crocetin is about 0.1 to 10% by weight, preferably about 0.2 to 4% by weight, and saccharides are about 90 to 99.99. A powder containing 9% by weight, preferably about 96-99.8% by weight. The color value is preferably about 50 to 1000, and more preferably about 100 to 400.
上記クロセチン製剤(粉末状のクロセチン製剤を含む)を用いて「クロセチンが水溶液中に分散し、且つ該クロセチンの粒子径がメジアン径で0.5μm未満の液剤」を調製する方法に特に制限はないが、例えば、クロセチン製剤、甘味料、酸味料などの各原材料を水に加えて充分混合して溶解・分散した後に、除菌フィルターでろ過して容器に無菌充填するなどの方法により容易に調製することができる。 There is no particular limitation on the method for preparing “a liquid agent in which crocetin is dispersed in an aqueous solution and the particle diameter of the crocetin is less than 0.5 μm in median size” using the crocetin preparation (including powdered crocetin preparation). However, for example, each raw material such as crocetin preparation, sweetener, acidulant, etc. is added to water, mixed well, dissolved and dispersed, then filtered through a sterilization filter and aseptically filled into a container. can do.
更に、本発明の経口肌色改善剤は、飲食品の形態をとることが可能である。該飲食品としては、例えば清涼飲料、ドロップ、キャンディ、チューインガム、チョコレート、グミ、ヨーグルト、アイスクリーム、プリン、ゼリー菓子、クッキーなどが挙げられる。 Furthermore, the oral skin color improving agent of this invention can take the form of food-drinks. Examples of the food and drink include soft drinks, drops, candy, chewing gum, chocolate, gummy, yogurt, ice cream, pudding, jelly confectionery, and cookies.
上記飲食品100質量%中、クロセチンもしくはその薬理学的に許容しうる塩の含有量は、純度100質量%のクロセチンに換算して、通常約0.00003〜10質量%、好ましくは約0.01〜5質量%である。 In 100% by mass of the food and drink, the content of crocetin or a pharmacologically acceptable salt thereof is usually about 0.00003 to 10% by mass, preferably about 0.000, in terms of crocetin having a purity of 100% by mass. 01 to 5% by mass.
また、本発明の経口肌色改善剤は、クロセチンもしくはその薬理学的に許容しうる塩を有効成分として単独で用いることができるほか、皮膚の健康維持に良いとされる他の成分、例えば、ビタミンB1、ビタミンB2、ビタミンB6、ビタミンB12、ナイアシン、ビオチン、パントテン酸、ビタミンC、ビタミンEなどのビタミン類、亜鉛、セレン、硫黄、カルシウム、鉄などのミネラル類、β−カロテン、α−カロテン、リコピン、フィトエン、フィトフルエン、アスタキサンチン、ルテイン、ゼアキサンチン、カプサンチン、カプソルビン、β−クリプトキサンチン、フコキサンチン、ビキシン、ノルビキシンなどのカロテノイド類、アントシアニン、アントシアニジン、プロアントシアニジン、カテキン、ヒドロキシチロソール、オレウロペイン、イソフラボン配糖体又はそのアグリコンなどのポリフェノール類、さらにはアルギニン、グリシン、メチオニン、システイン、オルニチンなどのアミノ酸、シスチン、グルタチオン、コラーゲン又はその分解物などのたんぱく質又はその分解物(ペプチド)、ヒアルロン酸、グルクロン酸、コンドロイチン硫酸などのグリコサミノグルカン、シトルリン、タウリン、グルコサミン、コウジ酸、α−リポ酸、CoQ10、スクワレン、エラスチン、セラミドなどと組み合わせて用いることが可能である。 In addition, the oral skin color improving agent of the present invention can be used alone as an active ingredient crocetin or a pharmacologically acceptable salt thereof, and other ingredients that are considered good for maintaining skin health, such as vitamins Vitamins such as B1, vitamin B2, vitamin B6, vitamin B12, niacin, biotin, pantothenic acid, vitamin C, vitamin E, minerals such as zinc, selenium, sulfur, calcium, iron, β-carotene, α-carotene, Carotenoids such as lycopene, phytoene, phytofluene, astaxanthin, lutein, zeaxanthin, capsanthin, capsorbin, β-cryptoxanthin, fucoxanthin, bixin, norbixin, anthocyanins, anthocyanidins, proanthocyanidins, catechins, hydroxytyrosol, ole Polyphenols such as ropain, isoflavone glycosides or aglycones thereof, amino acids such as arginine, glycine, methionine, cysteine, ornithine, proteins such as cystine, glutathione, collagen or degradation products thereof (peptides), hyaluron It can be used in combination with glycosaminoglucan such as acid, glucuronic acid, chondroitin sulfate, citrulline, taurine, glucosamine, kojic acid, α-lipoic acid, CoQ10, squalene, elastin, ceramide and the like.
本発明の経口肌色改善剤を経口摂取する際のクロセチンもしくはその薬理学的に許容しうる塩の成人1日当たりの用量は、純度100質量%のクロセチンに換算して、約0.1〜500mgの範囲である。 The daily dose of crocetin or a pharmacologically acceptable salt thereof when orally ingesting the oral skin color improving agent of the present invention is about 0.1 to 500 mg in terms of crocetin having a purity of 100% by mass. It is a range.
以下に本発明を実施例に基づいてより具体的に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described more specifically based on examples, but the present invention is not limited thereto.
[クロセチン組成物の製造]
粉砕したクチナシの乾燥果実30kgにエタノール・水混合液(50:50)60Lを加え、室温で3時間攪拌した後吸引ろ過した。ろ過後、抽出残にエタノール・水混合液(50:50)60Lを加え、室温で30分間攪拌した後吸引ろ過する操作を2回繰り返し、ろ液として計約175Lの抽出液を得た。この抽出液を、ロータリーエバポレーターを用いて約60℃、約4kPaの条件で濃縮し、濃縮物1(色価=約570)約10.5kgを得た。
[Production of crocetin composition]
60 L of an ethanol / water mixture (50:50) was added to 30 kg of the pulverized dried fruit of gardenia and stirred at room temperature for 3 hours, followed by suction filtration. After filtration, 60 L of an ethanol / water mixture (50:50) was added to the extraction residue, and the mixture was stirred at room temperature for 30 minutes and then suction filtered twice to obtain about 175 L of extract as a filtrate. The extract was concentrated using a rotary evaporator under the conditions of about 60 ° C. and about 4 kPa to obtain about 10.5 kg of a concentrate 1 (color value = about 570).
得られた濃縮物1に精製水を加えて100Lとし、得られた溶液を吸引ろ過し、ろ液をアンバーライトXAD−7(オルガノ社製)50Lを充填したカラムに流速SV=0.5で通液した。続いて、精製水400Lをカラムに流速SV=0.5で通液し、排出液を廃棄した。次にエタノール・水混合液(70:30)50Lを流速SV=0.5で通液し、色素を脱着・溶出した。得られた溶出液を、エバポレータを用いて約60℃、約4kPaの条件で濃縮し、クロシンを含む濃縮物2(色価=約1600)約3.5kgを得た。 Purified water is added to the obtained concentrate 1 to make 100 L, the resulting solution is suction filtered, and the filtrate is packed in a column packed with 50 L of Amberlite XAD-7 (manufactured by Organo) at a flow rate of SV = 0.5. The liquid was passed. Subsequently, 400 L of purified water was passed through the column at a flow rate SV = 0.5, and the discharged liquid was discarded. Next, 50 L of an ethanol / water mixture (70:30) was passed at a flow rate SV = 0.5 to desorb and elute the dye. The obtained eluate was concentrated using an evaporator under the conditions of about 60 ° C. and about 4 kPa to obtain about 3.5 kg of concentrate 2 (color value = about 1600) containing crocin.
得られた濃縮物2と40質量%水酸化ナトリウム水溶液600gとを混合し、撹拌下60℃で約3.5時間加水分解反応を行った。反応終了後、反応液を4質量%リン酸水溶液15Lに加えて酸性とした後、そのまま約3時間室温で放置した。次に、析出した沈殿を遠心分離(10,000×g、10分間)により回収し、更に水5Lで洗浄し、遠心分離する操作を2回繰り返し、ペースト状の固形物であるクロセチン組成物(色価=約2000)約2750gを得た。該クロセチン組成物中のクロセチン含有量は約5.5質量%であった。 The obtained concentrate 2 and 600 g of 40% by mass aqueous sodium hydroxide solution were mixed and subjected to a hydrolysis reaction at 60 ° C. for about 3.5 hours with stirring. After completion of the reaction, the reaction solution was acidified by adding it to 15 L of 4% by mass phosphoric acid aqueous solution, and then allowed to stand at room temperature for about 3 hours. Next, the precipitated precipitate was collected by centrifugation (10,000 × g, 10 minutes), further washed with 5 L of water, and centrifuged twice to repeat the operation of crocetin composition (a pasty solid) ( (Color value = about 2000) About 2750 g was obtained. The crocetin content in the crocetin composition was about 5.5% by mass.
なお、上記色価は、下記の[色価測定方法]により測定した。 The color value was measured by the following [Color value measuring method].
[色価測定方法]
1)測定する吸光度が0.3〜0.7の範囲になるように、試料を精密に量り、ジメチルスルホキシドに溶かして正確に100mlとする。
2)その5mlを正確に量り、Kolthoff氏緩衝液(50mM Na2CO3−50mM Na2B4O7,pH10.0)を加えて50mlとする。
3)その5mlを正確に量り、Kolthoff氏緩衝液(pH10.0)を加えて50mlとする。
4)その5mlを正確に量り、Kolthoff氏緩衝液(pH10.0)を加えて50mlとし、試験溶液とする。
5)Kolthoff氏緩衝液(pH10.0)を対照とし、液層の長さ1cmで420nm付近の極大吸収部における吸光度Aを測定し、次式により色価を求める。
[Color value measurement method]
1) A sample is accurately weighed so that the absorbance to be measured is in the range of 0.3 to 0.7, and dissolved in dimethyl sulfoxide to make exactly 100 ml.
2) Weigh exactly 5 ml, and add Kolthoff buffer (50 mM Na 2 CO 3 -50 mM Na 2 B 4 O 7 , pH 10.0) to make 50 ml.
3) Weigh exactly 5 ml of the solution, and add Kolthoff buffer (pH 10.0) to make 50 ml.
4) Weigh exactly 5 ml, add Kolthoff buffer (pH 10.0) to make 50 ml, and use this solution as the test solution.
5) Using a Kolthoff buffer solution (pH 10.0) as a control, measure the absorbance A at the maximum absorption portion near 420 nm with a liquid layer length of 1 cm, and obtain the color value by the following formula.
[クロセチン製剤の製造]
(1)試作品1の製造
先に調製したクロセチン組成物(色価=約2000)685.0gを精製水436.0gで懸濁し、クロセチン懸濁液1121.0gを得た。次に3000mL容ビーカーにアラビアガム(商品名:サンアラビック;三栄薬品貿易社製)149.4g、精製水779.0gを加え、40℃に加温して溶解した後、該クロセチン懸濁液を加え均一に混合した。得られた混合液を83メッシュ篩に通した後、マイクロフルイダイザー(みづほ工業社製;L−210Zチャンバー装着)を用いて50MPaで2パス処理し、処理液を得た。この処理液中のクロセチンの粒子径は約0.34μmであった。
次いで、該処理液2049.4gに対して、デキストリン(商品名:サンデック#300;三和澱粉株式会社製)1293.8gを加えて、混合した。得られた混合液を、縦298mm、横435mm、高さ25mmの金属製トレイに充填し、凍結乾燥機(型式:DC500;ヤマト科学社製)を用いて、−35℃で24時間予備凍結した後、真空度13Paの条件下、棚温50℃で約27〜28時間かけて凍結乾燥した。得られた凍結乾燥物を0.5mmのスクリーンを有するピンミルを用いて粉砕し、粉末状のクロセチン製剤(試作品1;クロセチン含有量2.5%)1493gを得た。
[Manufacture of crocetin preparation]
(1) Production of Prototype 1 685.0 g of the crocetin composition (color value = approximately 2000) prepared earlier was suspended in 436.0 g of purified water to obtain 1121.0 g of crocetin suspension. Next, 149.4 g of gum arabic (trade name: San-Arabic; manufactured by Sanei Pharmaceutical Co., Ltd.) and 779.0 g of purified water were added to a 3000 mL beaker and dissolved by heating to 40 ° C. Then, the crocetin suspension was added. Added and mixed uniformly. The obtained mixed solution was passed through an 83 mesh sieve and then subjected to two passes at 50 MPa using a microfluidizer (manufactured by Mizuho Kogyo Co., Ltd .; L-210Z chamber mounted) to obtain a treatment solution. The particle diameter of crocetin in this treatment liquid was about 0.34 μm.
Subsequently, 1293.8 g of dextrin (trade name: Sandeck # 300; manufactured by Sanwa Starch Co., Ltd.) was added to and mixed with 2049.4 g of the treatment liquid. The obtained mixed liquid was filled in a metal tray having a length of 298 mm, a width of 435 mm, and a height of 25 mm, and pre-frozen at -35 ° C. for 24 hours using a freeze dryer (model: DC500; manufactured by Yamato Scientific Co., Ltd.). Thereafter, it was freeze-dried at a shelf temperature of 50 ° C. for about 27 to 28 hours under a condition of a vacuum degree of 13 Pa. The obtained freeze-dried product was pulverized using a pin mill having a 0.5 mm screen to obtain 1493 g of a powdery crocetin preparation (prototype 1; crocetin content 2.5%).
(2)試作品2の製造
先に調製したクロセチン組成物(色価=約2000)342.5gを精製水217.0gで懸濁し、クロセチン懸濁液559.5gを得た。次に1000mL容液量計にアラビアガム(商品名:サンアラビック;三栄薬品貿易社製)74.7g、精製水389.5gを加え、40℃に加温して溶解した後、該クロセチン懸濁液559.5gを加え均一に混合した。得られた混合液を83メッシュ篩に通した後、40℃に保温しながらクレアミックス(エムテクニック社製)を用いて回転数17000rpm、12分間攪拌し、処理液を得た。得られた処理液中のクロセチンの粒子径は約0.77μmであった。
次いで、該処理液1023.7gに対して、デキストリン(商品名:サンデック#300;三和澱粉株式会社製)646.4gを加えて、混合した。得られた混合液を、縦298mm、横435mm、高さ25mmの金属製トレイに充填し、凍結乾燥機(型式:DC500;ヤマト科学社製)を用いて、−35℃で24時間予備凍結した後、真空度13Paの条件下、棚温50℃で約27〜28時間かけて凍結乾燥した。得られた凍結乾燥物を0.5mmのスクリーンを有するピンミルを用いて粉砕し、粉末状のクロセチン製剤(試作品2;クロセチン含有量2.5%)746gを得た。
(2) Production of Prototype 2 342.5 g of the previously prepared crocetin composition (color value = approximately 2000) was suspended in 217.0 g of purified water to obtain 559.5 g of crocetin suspension. Next, 74.7 g of gum arabic (trade name: San Arabic, manufactured by Sanei Pharmaceutical Co., Ltd.) and 389.5 g of purified water were added to a 1000 mL volume meter, dissolved by heating to 40 ° C., and the crocetin suspension The liquid 559.5g was added and mixed uniformly. The obtained mixed solution was passed through an 83 mesh sieve and then stirred at 12 000 rpm for 12 minutes using Claremix (manufactured by M Technique Co., Ltd.) while being kept at 40 ° C. to obtain a treatment solution. The particle diameter of crocetin in the obtained treatment liquid was about 0.77 μm.
Next, 646.4 g of dextrin (trade name: Sandeck # 300; manufactured by Sanwa Starch Co., Ltd.) was added to and mixed with 1023.7 g of the treatment liquid. The obtained mixed liquid was filled in a metal tray having a length of 298 mm, a width of 435 mm, and a height of 25 mm, and pre-frozen at -35 ° C. for 24 hours using a freeze dryer (model: DC500; manufactured by Yamato Scientific Co., Ltd.). Thereafter, it was freeze-dried at a shelf temperature of 50 ° C. for about 27 to 28 hours under a condition of a vacuum degree of 13 Pa. The obtained freeze-dried product was pulverized using a pin mill having a 0.5 mm screen to obtain 746 g of a powdery crocetin preparation (prototype 2; crocetin content 2.5%).
(3)試作品3の製造
1000mL容液量計にアラビアガム(商品名:サンアラビック;三栄薬品貿易社製)149.4g、精製水1850.2gを加え、40℃に加温して溶解した後、市販のクロセチン(商品名:クロビットP;理研ビタミン株式会社製)49.8gを加え、均一に混合した。得られた混合液を40℃に保温しながらクレアミックス(エムテクニック社製)を用いて回転数1700rpm、12分間撹拌し、処理液を得た。得られた処理液中のクロセチンの粒子径は約2.83μmであった。
次いで、該処理液2049.4gに対して、デキストリン(商品名:サンデック#300;三和澱粉株式会社製)1293.8gを加えて、混合した。得られた混合液を、縦298mm、横435mm、高さ25mmの金属製トレイに充填し、凍結乾燥機(型式:DC500;ヤマト科学社製)を用いて、−35℃で24時間予備凍結した後、真空度13Paの条件下、棚温50℃で約27〜28時間かけて凍結乾燥した。得られた凍結乾燥物を0.5mmのスクリーンを有するピンミルを用いて粉砕し、粉末状のクロセチン製剤(試作品3;クロセチン含有量2.5%)1493gを得た。
(3) Manufacture of prototype 3 149.4 g of gum arabic (trade name: San Arabic, manufactured by Sanei Pharmaceutical Trading Co., Ltd.) and 1850.2 g of purified water were added to a 1000 mL volumetric meter, and heated to 40 ° C. to dissolve. Thereafter, 49.8 g of commercially available crocetin (trade name: Clobit P; manufactured by Riken Vitamin Co., Ltd.) was added and mixed uniformly. The obtained mixed solution was stirred for 12 minutes at 1700 rpm using Claremix (manufactured by M Technique Co., Ltd.) while keeping the temperature at 40 ° C. to obtain a treatment solution. The particle diameter of crocetin in the obtained treatment liquid was about 2.83 μm.
Subsequently, 1293.8 g of dextrin (trade name: Sandeck # 300; manufactured by Sanwa Starch Co., Ltd.) was added to and mixed with 2049.4 g of the treatment liquid. The obtained mixed liquid was filled in a metal tray having a length of 298 mm, a width of 435 mm, and a height of 25 mm, and pre-frozen at -35 ° C. for 24 hours using a freeze dryer (model: DC500; manufactured by Yamato Scientific Co., Ltd.). Thereafter, it was freeze-dried at a shelf temperature of 50 ° C. for about 27 to 28 hours under a condition of a vacuum degree of 13 Pa. The obtained freeze-dried product was pulverized using a pin mill having a 0.5 mm screen to obtain 1493 g of a powdery crocetin preparation (prototype 3; crocetin content 2.5%).
[粒子径の測定方法]
上記クロセチン製剤(試作品1〜3)の製造における粒子径の測定では、レーザー回折/分散粒度分布測定機(型式:LA−920;堀場製作所社製)を使用し、粒子径の大きさを体積頻度からメジアン径として算出した。なお、クロセチンの粒子径は水を媒体として測定した。
[Measurement method of particle size]
In the measurement of the particle diameter in the production of the above crocetin preparations (prototypes 1 to 3), a laser diffraction / dispersion particle size distribution measuring machine (model: LA-920; manufactured by HORIBA, Ltd.) is used. The median diameter was calculated from the frequency. The particle size of crocetin was measured using water as a medium.
[経口肌色改善剤の製造]
表1の配合組成に従い、全ての原材料をタンクに仕込み混合した。十分混合した後、液は200メッシュストレーナーによるろ過を行い、全量424kgの分散液を得た。
分散液はプレート式殺菌機(98±2℃、3秒間保持)による殺菌を行った後、50mLずつ褐色瓶へ充填、キャッピングした(充填時の温度は65℃以上)。キャッピング後、パストライザー(シャワー殺菌機)を用いて殺菌し、エアーにより水滴除去して経口肌色改善剤1〜3(50mL/1本のドリンク剤;クロセチン含有量0.015質量%)を得た。また、経口肌色改善剤1〜3に分散するクロセチンの粒子径(メジアン径)を上述の方法に従い測定した。結果を表2に示す。
なお、水分散性を付与するための製剤化がなされていない市販のクロセチン(商品名:クロビットP;クロセチン含有量75%;理研ビタミン製)は、イオン交換水に加えて混合しても分散せずにタンク内で浮上するため、経口肌色改善剤4を製造することはできなかった。
[Manufacture of oral skin color improvers]
According to the composition shown in Table 1, all raw materials were charged into a tank and mixed. After mixing sufficiently, the liquid was filtered with a 200 mesh strainer to obtain a total amount of 424 kg dispersion.
The dispersion was sterilized using a plate sterilizer (98 ± 2 ° C., held for 3 seconds), then filled and capped in 50 mL brown bottles (filling temperature was 65 ° C. or higher). After capping, pasteurizer (shower sterilizer) was used to sterilize, and water droplets were removed with air to obtain oral skin color improvers 1 to 3 (50 mL / one drink; crocetin content 0.015% by mass). . Moreover, the particle diameter (median diameter) of crocetin dispersed in the oral skin color improving agents 1 to 3 was measured according to the above-described method. The results are shown in Table 2.
Commercially available crocetin (trade name: clobit P; crocetin content 75%; manufactured by Riken Vitamin), which has not been formulated to impart water dispersibility, can be dispersed by mixing in addition to ion-exchanged water. Therefore, the oral skin color improving agent 4 could not be produced.
[試験例]
[経口摂取による肌のくすみ改善評価試験]
くすみによる肌の明度低下に対するクロセチンの改善効果を検証するため、経口肌色改善剤1を被験薬としたオープン試験を実施した。
[Test example]
[Skin dullness improvement evaluation test by oral intake]
In order to verify the improvement effect of crocetin on the decrease in lightness of the skin due to dullness, an open test was conducted using the oral skin color improver 1 as a test drug.
(1)肌の明度測定
顔面のくすみ、色むらが気になる30歳から50歳までの日本人女性ボランティア44名を対象に、被験薬として経口肌色改善剤1を8週間連続摂取(1本/日)させ、摂取前後の肌の明度を測定して比較した。
測定は、先ず被験者が洗顔後、恒温恒湿室(湿度50%±10%、室温22℃±2℃に設定)にて安静な状態で肌を30分馴化させた後、スキントーン・カラースケール(インフォワード社製)を用いて、被験者の左耳朶下の付け根と唇の左端とを結ぶ直線上の中心付近の肌について行った。より具体的には、1YR、3YR、5YR、7YR、9YRの5色相からなるスケールのうち、被験者の肌色にもっとも近いスケールを選択し、そのスケール上で被験者の肌の色と最もコントラストが小さい色の明度を被験者の肌の明度値とした。また、被験薬の摂取後の明度測定では、摂取前の測定で用いたスケールと同一色相のものを使用した。
試験結果として、被験薬摂取前後の肌の明度値の平均値および標準偏差を表3に示す。
(1) Skin lightness measurement For 44 Japanese female volunteers aged 30 to 50 who are worried about dullness and color unevenness, take oral skin color improver 1 as a test drug for 8 consecutive weeks (1 bottle) / Day), and the brightness of the skin before and after ingestion was measured and compared.
First, after the face was washed by the subject, the skin was acclimated for 30 minutes in a constant temperature and humidity room (humidity: 50% ± 10%, room temperature: 22 ° C ± 2 ° C), and then the skin tone and color scale. (In-Forward Co., Ltd.) was used for the skin near the center on the straight line connecting the base of the subject's left ear arm and the left end of the lips. More specifically, a scale closest to the subject's skin color is selected from the scales of five hues of 1YR, 3YR, 5YR, 7YR, and 9YR, and the color having the smallest contrast with the skin color of the subject on the scale. Was used as the brightness value of the subject's skin. Moreover, in the brightness measurement after ingestion of a test drug, the same hue as the scale used in the measurement before ingestion was used.
Table 3 shows the average value and standard deviation of the lightness values of the skin before and after taking the test drug as test results.
表3の結果は、集計されたデータに基づき対応のあるt検定を行ったところ、摂取前と摂取後において有意な差(危険率1%未満)が認められ、被験薬の摂取により肌の明度が有意に上昇することを示している。 The results in Table 3 show that a significant difference (risk rate of less than 1%) was observed before and after ingestion when a corresponding t-test was performed based on the aggregated data. Indicates a significant increase.
(2)アンケート調査
被験薬の摂取後にアンケート調査を実施し、くすみの改善効果に関する被験者の体感を調べた。
アンケート調査における質問は、被験薬の摂取前と比べた摂取後の肌の状態に関して、質問1「肌の感じが明るくなった」、質問2「顔のくすみが減少した」とした。質問への回答では、1.「そう思う」、2.「ややそう思う」、3.「どちらともいえない」、4.「あまりそう思わない」5.「そう思わない」の中から被験者自身が最も近いと思うものを選択させた。
その結果、質問1「肌の感じが明るくなった」に対し、1.「そう思う」または2.「ややそう思う」を選択した被験者の割合は68.2%(30/44)であった。また、質問2「顔のくすみが減少した」に対し、同様の選択をした被験者の割合は61.4%(27/44)であった。
(2) Questionnaire survey A questionnaire survey was conducted after taking the test drug to examine the subject's experience regarding the dullness improvement effect.
The questions in the questionnaire survey were as follows: Question 1 “feeling of skin became brighter” and Question 2 “Dullness of face decreased” regarding the condition of the skin after ingestion compared to before taking the test drug. In answering the questions: "I think so", 2. “Somewhat I think.” 3. “I can't say either.” "I don't think so" 5. From “I don't think so”, I selected the subject that I thought was the closest.
As a result, for question 1 “feeling of skin became brighter”, "I think so" or 2. The percentage of subjects who selected “somewhat agree” was 68.2% (30/44). In addition, the percentage of subjects who made the same selection for question 2 “facial dullness decreased” was 61.4% (27/44).
以上の結果から、本発明の経口肌色改善剤は、肌のくすみを改善し、肌の明度を上昇させる効果を奏することが明らかである。 From the above results, it is clear that the oral skin color improving agent of the present invention has the effect of improving the dullness of the skin and increasing the lightness of the skin.
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