JP4050635B2 - Skin preparation - Google Patents

Description

【００２０】
【表１】
細胞増殖率（%）

【００２１】
表1に示した結果のように、抽出溶媒の種類に関わらず、ヒソップ抽出物においても高い線維芽細胞増殖効果が認められた。相対的にコラーゲン産生能が高まることによりシワ改善効果が期待できることがわかる。
【００２２】
【実施例２】
美白効果の評価 メラニン産生抑制による評価
皮膚のシミには皮膚内色素であるメラニンが深く関係している。すなわちメラニンが紫外線などの外的ストレスにより産生され、その結果、皮膚の黒化が進み、シミ・ソバカス・色黒などの症状が引き起こされると報告されている。よって、皮膚の美白作用をマウスメラノーマを用いたメラニン産生量測定試験にて評価した。細胞はマウスメラノーマＢ−１６ Ｆ−１０を培地はDMEMにFBSを１0％になるように添加した培地を用いた。メラノーマを８cmシャーレに培養した。培養２４時間後、各試料を最終濃度０．００１から０．０５％となるように添加を行い、添加後3日後に試験を終了した。シャーレに増殖した細胞をセルスクリーパーで集め、透明な遠心チューブに入れ、３０００rpm，１０分遠心し細胞を集めた。集まった細胞ペレットの色を肉眼判定し、５段階評価した。本試験ではコントロールとして試料の溶媒、陽性対象としてアルブチンを使用した。
【００２３】
（判定基準）
５：コントロールと比較して黒い
４：コントロールと同じ
３：コントロールと比較して僅かに白い
２：コントロールと比較して白い
１：コントロールと比較し非常に白い
【００２４】
【表２】

【００２５】
表２に示した結果のように、抽出溶媒の種類に関わらずヒソップ抽出物においてメラニン量の減少が見られ、メラニン産生抑制効果が認められた。美白効果が知られているアルブチンと同程度の美白効果が期待できることがわかる。
【００２６】
【実施例３】
スキコンによる保湿効果の測定
本発明にかかる抽出物の保湿性をSKICON-２００（IBS）を用いて測定した。被験者に室温１９℃，湿度６０％の部屋にて２０分間安静にしてもらい、その後前腕部内側に試料を塗布（２×２ｃｍ）し１分後コットンで軽くふき取り、経時的に３０分後まで皮膚の伝導度（コンダクタンス）を測定した。精製水をコントロールとし陽性対照として１，3ブチレングリコール５％水溶液を用いた。
【００２７】
【表３】
皮膚の伝導度（Ω）

【００２８】
表３に示した結果のように、抽出溶媒の種類に関わらずヒソップ抽出物において、高い保湿効果が認められ、またその効果に持続性があることがわかる。
【００２９】
【実施例４】
皮膚外用剤の使用によるシワ,乾燥改善効果の測定
さらに、本発明にかかる化粧料を用いて、実際に使用した場合の効果について検討を行った。顔のシワが気になる乾燥肌の40〜60代女性10名に３ヶ月間連続で一日２回（朝・夕）塗布してもらい連用試験を行った。被験者の左顔に実施例として処方例1の軟膏を塗布、右顔には処方例1からヒソップ抽出物を除きワセリンに置き換えたものを比較例として塗布してもらい、皮膚の改善度を評価した。評価方法は開始時と塗布3ヶ月後に皮膚のレプリカを採取し、最も大きなシワの長さからシワ改善度を評価した。さらに使用後の乾燥状態,シワを被験者に４段階評価してもらった。結果を表４,表５，表６に示す。また、使用期間中に肌の異常を訴えた被験者はいなかった。
【００３０】
（レプリカのシワ判定基準）
５：開始時と比較してシワの長さ50％減少
４：開始時と比較してシワの長さ30％減少
３：開始時と比較してシワの長さ10％減少
２：開始時と比較してシワの長さ同じ
１：開始時と比較してシワの長さ増加
（被験者のシワ度判定基準）
顕著に有効：シワがなくなった
有効：開始時と比較してシワが短くなり浅くなった
やや有効：開始時と比較してやや短くなり、浅くなった
無効：開始時と比較して同じ
（被験者の乾燥度判定基準）
顕著に有効：全く乾燥しなくなった。
有効：開始時と比較して乾燥しなくなった
やや有効：開始時と比較してやや乾燥しなくなった
無効：開始時と比較して同じ
【００３１】
【表４】
レプリカ評価

【００３２】
【表５】
被験者のシワ改善効果への評価

【００３３】
【表６】
被験者の乾燥改善効果への評価

【００３４】
表４,５,６の結果から、比較例を塗布した右顔に比べ、実施例を塗布した左顔のシワおよび乾燥の改善は顕著であり、被験者の実感効果も高く、ヒソップ抽出物により、皮膚のシワ,乾燥が改善されたことがわかる。
【００３５】
【実施例５】
ヒソップ抽出物による皮膚の肌荒れ緩和効果の測定
2.5%ラウリル硫酸ナトリウム水溶液により引き起こされる刺激に対して緩和効果について検討を行った。被験者20名の前腕に試料として2.5%ラウリル硫酸ナトリウム水溶液，0.01％ヒソップ抽出物混合液を1日閉塞パッチテスト行った。2.5%ラウリル硫酸ナトリウムを対照としてパッチ除去後48hr後の紅斑度合いを目視判定した。結果を表7に示す。
【００３６】
判定基準
（目視判定基準）
５：開始時と比較して紅斑度50％減少
４：開始時と比較して紅斑度30％減少
３：開始時と比較して紅斑度10％減少
２：開始時と比較して紅斑度同じ
１：開始時と比較して紅斑度増加
【００３７】
【表７】
紅斑度評価

【００３８】
【実施例６】
皮膚外用剤の使用による皮膚のニキビ改善効果の測定
さらに、本発明にかかる化粧料を用いて、実際に使用した場合の効果について検討を行った。顔のニキビを訴える20〜30代女性15名に1ヶ月間連続で一日２回（朝・夕）塗布してもらい連用試験を行った。被験者の左顔に実施例として処方例1の軟膏を塗布、右顔には処方例1からヒソップ抽出物を除きワセリンに置き換えたものを比較例として塗布してもらい、皮膚の改善度を評価した。評価方法は開始時と塗布1ヶ月後の皮膚の状態をデジタルカメラにて撮影し、ニキビを観察し、ニキビの数を数え、半顔ずつの改善効果を比較し評価した。さらに使用後の実感度を被験者に４段階評価してもらった。結果を表８,表９に示す。また、使用期間中に肌の異常を訴えた被験者はいなかった。また、使用期間中に肌の異常を訴えた被験者はいなかった。
【００３９】
（判定基準）
５：開始時と比較してニキビの数が50％減少
４：開始時と比較してニキビの数が30％減少
３：開始時と比較してニキビの数が10％減少
２：開始時と比較してニキビの数が同じ
１：開始時と比較してニキビの数が増加
（被験者のニキビ判定基準）
顕著に有効：ニキビがなくなった
有効：開始時と比較してニキビが顕著に減った
やや有効：開始時と比較してニキビが減った
無効：開始時と比較して同じ
【００４０】
【表８】

【００４１】
【表９】
被験者のニキビ改善効果への評価

【００４２】
表８,９の結果から、比較例を塗布した右顔に比べ、実施例を塗布した左顔のニキビ改善度は顕著であり、被験者の実感効果も高く、ヒソップ抽出物により、ニキビが改善されたことがわかる。
【００４３】
【実施例７】
皮膚外用剤の使用による皮膚のくま,くすみ改善効果の測定
さらに、本発明にかかる化粧料を用いて、実際に使用した場合の効果について検討を行った。顔のくまおよびくすみを訴える女性10名に1ヶ月間連続で一日２回（朝・夕）塗布してもらい連用試験を行った。被験者の左顔に実施例として処方例1の軟膏を塗布、右顔には処方例1からヒソップ抽出物を除きワセリンに置き換えたものを比較例として塗布してもらい、皮膚の改善度を評価した。
評価方法は開始時と塗布1ヶ月後の皮膚の状態を分光測色計（横河）にて各波長の分光反射率の測定を行った。くすみがない肌では400〜700nm波長域、特に酸化型ヘモグロビンの吸収波長域（415,542,576nm）での反射率が高いことが報告されている。（滝脇弘嗣,西日本皮膚科 55,415,1993）そこで、分光測色計で得られた560nm反射率の差にて、くまおよびくすみの改善効果を評価した。さらに使用後の実感度を被験者に４段階評価してもらった。結果を表１０，表１１,表１２に示す。また、使用期間中に肌の異常を訴えた被験者はいなかった。
【００４４】
【数２】

【００４５】
（くま,くすみ判定基準）
５：開始時と比較して反射率が20％増加
４：開始時と比較して反射率が10％増加
３：開始時と比較して反射率が5％増加
２：開始時と比較して反射率が同じ
１：開始時と比較して反射率が減少
（被験者のくま,くすみ判定基準）
顕著に有効：くま,くすみがなくなった、肌がとても明るくなった
有効：開始時と比較してくま,くすみが薄くなった、肌が明るくなった
やや有効：開始時と比較してくま,くすみがやや薄くなった、肌がやや明るくなった
無効：開始時と比較して同じ
【００４６】
【表１０】
分光反射率による評価評価

【００４７】
【表１１】
被験者のくま改善効果への評価

【００４８】
【表１２】
被験者のくすみ改善効果への評価

【００４９】
表１０，１１,１２の結果から、比較例を塗布した右顔に比べ、実施例を塗布した左顔のくまおよびくすみ改善度は顕著であり、被験者の実感効果も高く、ヒソップ抽出物により、くま,くすみが改善されたことがわかる。
【００５０】
【実施例８】
化粧料の使用によるハリ・たるみ改善効果の測定
さらに、本発明にかかる化粧料を用いて、実際に使用した場合の効果について検討を行った。顔のたるみを訴える40〜50代の女性10名に1ヶ月間連続で一日２回（朝・夕）塗布してもらい連用試験を行った。被験者の左顔に実施例として処方例1の軟膏を塗布、右顔には処方例1からヒソップ抽出物を除きワセリンに置き換えたものを比較例として塗布してもらい、皮膚の改善度を評価した。評価方法は開始時と塗布1ヶ月後に半顔ずつの改善効果を比較し評価した。評価方法は開始時と塗布1ヶ月後に皮膚のハリ,弾力改善度をCutomater
SEM474（Curage and Khazaka）を用い評価した。Cutomaterにて皮膚の弾力回復率を測定し、塗布後の弾力回復率から開始時の弾力回復率を差し引き評価した。さらに、使用後の実感度を被験者に頬,目元部位のたるみ改善度,および頬のハリ改善度に関して４段階評価してもらった。結果を表６,７に示す。また、使用期間中に肌の異常を訴えた被験者はいなかった。
【００５１】
皮膚弾力性
Cutomaterの陰圧吸引により伸びた皮膚の高さを伸展長（mm）とし、陰圧開放後に吸引前の状態に戻らず盛り上がったままの皮膚の高さを非退縮長（mm）とする。
【００５２】
【数３】

【００５３】
（弾力回復率判定基準）
５：弾力回復率30％以上
４：弾力回復率20〜30％以上
３：弾力回復率10〜20％
２：弾力回復率0〜10％
１：弾力回復率0％以下
（被験者のたるみ度判定基準）
顕著に有効：たるみがなくなった
有効：開始時と比較してたるみが減った
やや有効：開始時と比較してややたるみが減った
無効：開始時と比較して同じ
（被験者のハリ度判定基準）
顕著に有効：ハリがかなりでてきた
有効：開始時と比較してがハリがでてきた
やや有効：開始時と比較してややハリがでてきた
無効：開始時と比較して同じ
【００５４】
【表１３】
弾力回復度

【００５５】
【表１４】
被験者のたるみ改善効果への評価

【００５６】
【表１５】
被験者のハリ改善効果への評価

【００５７】
表１４，１５の結果から、比較例を塗布した右顔に比べ実施例を塗布した左顔がハリ・たるみとも改善は顕著であり、被験者の実感効果も高く、ヒソップ抽出物により、ハリ・たるみが改善されたことがわかる
【００５８】
【実施例９】
皮膚外用剤の使用による皮膚のシミ改善効果の測定
さらに、本発明にかかる化粧料を用いて、実際に使用した場合の効果について検討を行った。顔のシミを訴える50代女性10名に3ヶ月間連続で一日２回（朝・夕）塗布してもらい連用試験を行った。被験者の左顔に実施例として処方例1の軟膏を塗布、右顔には処方例1からヒソップ抽出物を除きワセリンに置き換えたものを比較例として塗布してもらい、シミの改善度を評価した。評価方法は開始時と塗布3ヶ月後にシミ改善度を被験者に４段階評価してもらった。結果を表１６に示す。また、使用期間中に肌の異常を訴えた被験者はいなかった。
【００５９】
（被験者のシミ改善度判定基準）
顕著に有効：シミがなくなった、顕著に薄くなった
有効：開始時と比較してシミが減った、薄くなった
やや有効：開始時と比較してややシミが減った、薄くなった
無効：開始時と比較して同じ
【００６０】
【表１６】
被験者のシミ改善効果への評価

【００６１】
表１６の結果から被験者の実感効果は高く、ヒソップ抽出物によりシミが改善されたことがわかる。
【００６２】
本発明に基づき、外用剤の処方例を示すが、本発明はかかる処方例のみに限定されるものではない。
【００６３】
処方例１
（１）軟膏（重量％）
a)ヒソップ抽出物…0.01
b)酸化防止剤…適量
c）ワセリン…残部
製法a)〜c)までを加え、４０℃に加温し、十分に混合する。
【００６４】
処方例２
（２）クリーム状外用剤
a)ミツロウ …2.0
b)ステアリルアルコール…5.0
c)ステアリン酸…8.0
d)スクワラン…10.0
e)自己乳化型グリセリルモノステアレート…3.0
f)ポリオキシエチレンセチルエーテル(20E.O.)…1.0
g) ヒソップ抽出物…1.0
ｈ) 1,3-ブチレングリコール…5.0
i)水酸化カリウム…0.3
j)防腐剤・酸化防止剤…適量
k）精製水…残部
製法a)〜f)、ｊ）を加熱溶解し、80℃に保ち油相とする。ｈ）、i）、ｋ）を混合し80℃に保ち水相とする。油相に水相を加え乳化する。乳化後、攪拌しながら冷却し60℃になったらｇ）を加え40℃になったら取りだしクリーム状外用剤を得る。
【００６５】
処方例３
（３）乳液状外用剤（重量％）
a)ミツロウ…0.5
b)ワセリン…2.0
c)スクワラン…8.0
d)ソルビタンセスキオレエート…0.8
e)ポリオキシエチレンオレイルエーテル(20E.O.)…1.2
f) ヒソップ抽出物…0.05
g)1,3-ブチレングリコール…7.0
h)カルボキシビニルポリマー…0.2
i)水酸化カリウム…0.1
j)精製水…残部
k)防腐剤・酸化防止剤…適量
l)エタノール…7.0
製法a)〜e)までを加熱溶解し、80℃に保つ。ｇ)〜ｋ)までを加熱溶解し、
80℃に保ち、a)〜e)に加えて乳化し60℃でｆ）を加え、50℃まで撹拌しながら冷却する。50℃でｌ)を添加し、40℃まで冷却し、乳液状外用剤を得る。
【００６６】
処方例４
（４）化粧水(重量%)
a) ヒソップ抽出物…0.0005
b)グリセリン…5.0
c)ポリオキシエチレンソルビタンモノラウレート(20E.O.)…1.0
d)エタノール…6.0
e)香料…適量
f)防腐剤・酸化防止剤…適量
g)精製水…残部
製法a)〜g)までを随時加え混合し、均一に溶解する。
【００６７】
【発明の効果】
本発明のヒソップ抽出物を皮膚外用剤に配合することによって、抗老化作用，保湿作用，抗炎症作用，美白作用,ニキビ改善作用，くま改善作用，くすみ改善作用,たるみ改善作用を有し、皮膚のシワ，乾燥，肌荒れ，シミ，ニキビ，くま，くすみ,たるみ改善効果の期待できる皮膚外用剤の提供が可能となった。[0001]
[Industrial application fields]
The present invention relates to an external preparation for skin containing a hyssop extract, and more specifically has an anti-aging effect, a moisturizing effect, an anti-inflammatory effect, a whitening effect, an acne improving effect, a bear improving effect, a dullness improving effect, and a sagging improving effect. Furthermore, the present invention relates to an external preparation for skin which can be expected to have an effect of improving wrinkles, dryness, rough skin, spots, acne, bears, dullness and sagging.
[0002]
[Prior art and problems to be solved by the invention]
Hyssop is a semi-evergreen shrub or sub-shrub plant belonging to the genus Pelargaceae. Hyssop leaves are aromatic and used in the West as spices and essential oils for cooking. Therefore, in skin external preparation, paying attention to the fragrance of the oil component, only utilization as a fragrance (for example, see Patent Document 1 to Patent Document 6) is known. However, these are simply blended to hide the raw material odor blended in the external preparation or enjoy the scent, and do not exert any action / effect on the skin due to the nature of the fragrance itself. In addition, the hyssop extract has not been used so far and its effect is not known at all.
[0003]
The skin is subjected to external stresses such as ultraviolet rays and chemical substances, but these have various effects such as degeneration of skin components such as collagen of the skin, and all skin such as dryness, rough skin, acne, bears, dullness, etc. It has been shown to cause trouble. And it is clarified that these skin troubles become chronic when stress exposure lasts for a long time, worsening the skin condition, and eventually aging phenomena such as wrinkles, spots and sagging of the skin progress. .
[0004]
Therefore, an effective material for preventing the above-mentioned skin troubles from drying, rough skin, acne, bears, dullness, wrinkles, spots and sagging is desired, and the search has been conducted. For example, collagen, hyaluronic acid, retinol, ascorbic acid, glycyrrhizic acid, glutylretinoic acid, allantoin, arbutin, kojic acid, and derivatives thereof have been used. However, many of the above-described components that have been conventionally used are unstable with respect to light and heat, and their actions are not sufficient. Furthermore, there are no components effective for all effects, and in order to have these effects, it is necessary to use all the components in combination.
[0005]
[Patent Document 1]
Patent 3317886 [Patent Document 2]
JP 2002-128658 [Patent Document 3]
JP2002-20257 [Patent Document 4]
Special Table 2000-504344 [Patent Document 5]
Special Table 2000-53528 [Patent Document 6]
JP-A-11-116458 [0006]
[Means for solving problems]
Therefore, as a result of diligent studies to solve the above problems, the present inventor has found that an extract of Hyssopus officinalis belonging to the genus Willow genus is dry skin and rough skin, acne, bears, dullness, wrinkles, spots, tension -It has been found that when it is added to a skin external preparation, it has excellent storage stability when it is excellent in sagging improving action, and the present invention has been completed.
That is, this invention provides the skin external preparation containing a hyssop extract.
[0007]
The extraction site of hyssop used in the present invention is not particularly limited. It can also be extracted using petals, leaves, stems, roots, seeds, fruits, etc., or whole plants that have been processed raw, dried or crushed.
[0008]
The extract used in the present invention can be extracted with various solvents. Besides using water alone, a polar solvent miscible with water can be used alone. Ethanol, propylene glycol, ethylene glycol, 1,3-butylene glycol, and the like can be used as the polar solvent, but the polar solvent is not limited thereto. Further, one or more mixed solvents of ethanol, propylene glycol, ethylene glycol, and 1,3-butylene glycol can be used.
[0009]
Extraction time and extraction temperature are not particularly limited. In the case of extraction with water, extraction is usually performed at 60 ° C. for 3 to 4 hours, and when a low-boiling solvent such as ethanol is used, an extraction device with a reflux is used. An extracted solution can be obtained by filtering the extracted solution after cooling. Further, deodorization and decolorization can be performed using activated carbon, other resins, etc. If necessary, the solvent can be removed by a method such as heating, and it can be used as an extract (dry product).
[0010]
The compounding quantity concerning this invention is not specifically limited. In principle, an effective amount should be present, but generally a dry weight of 0.0000 to 100% by weight in the composition can be used, preferably 0.0001 to 0.5% by weight, and more preferably 0.001 to 0.05% by weight. Is the best. In particular, only the hyssop extract according to the present invention can be used as a skin external preparation prepared at the time of use.
[0011]
Moreover, the application range of the external preparation for skin concerning this invention is not specifically limited. That is, the present invention can be applied to all external preparations for skin that can use each function and effect according to the function and effect of the active ingredient of the present invention.
[0012]
For example, the active ingredient according to the present invention can be used in various external preparations (including preparations used for animals) in general, specifically, ampoules, powders, granules, solids, liquids, gels or bubbles 1) Pharmaceuticals, 2) Quasi-drugs, 3) Topical or systemic skin cosmetics (for example, various basic cosmetics such as creams, emulsions, lotions, packs, face wash, etc.), 4) Satellite products, etc. Is mentioned.
[0013]
Hereinafter, although the test example by this invention is shown and the usage example in the prescription example of the cosmetics using the raw material of this invention is shown, it is not limited to the Example described here.
[0014]
Preparation of sample solution Preparation Example 1 (water extract)
100 g of dried hyssop was taken, 1000 mL of purified water was added, and extraction was performed at 60 ° C. for 3 hours. After cooling, filtration was performed to obtain a filtrate. The filtrate was concentrated under reduced pressure and sufficiently dried to obtain 10 g of a water extract.
[0015]
Preparation Example 2 (Ethyl alcohol extract)
10 g of dried hyssop was taken and extracted with ethyl alcohol for 5 hours using a Soxhlet extractor. After cooling, filtration was performed to obtain a filtrate. The filtrate was concentrated under reduced pressure and sufficiently dried to obtain 0.9 g of an ethyl alcohol extract.
[0016]
Preparation Example 3 (Ethyl alcohol water mixed extract)
In the extraction method for the water extract, a 50% ethyl alcohol 50% water mixture was used instead of water. The extract was concentrated after removing the solvent as much as possible, and then sufficiently dried to obtain 9.8 g of 50% ethyl alcohol extract.
[0017]
The plant extract was dissolved in 50% ethyl alcohol to a concentration of 1.0%, and then sterilized by filtration through a 0.2 μm membrane filter to obtain each plant extract.
[0018]
[Example 1]
Evaluation of cell proliferation The cell proliferation of various plant extracts was evaluated using Cell Counting Kit (Dojin). The cells used were normal human diploid fibroblasts HFSKF-II (RIKEN), and the medium was Ham-F12 supplemented with 15% FBS. Fibroblasts were cultured in 24 well plates, and after 24 hours, the medium was changed to Ham-F12 with 5% FBS, and each sample was added to a final concentration of 0.001 to 0.05%. A sample solvent was used as a control, and a magnesium ascorbate phosphate solution was used as a positive target. After further incubation for 48 hours, 50 μl of Cell Counting Kit reagent was added and mixed, and the color reaction was carried out for 2 hours. After the reaction, 100 μl of the culture solution was transferred to a 96 well plate and measured at 412 nm using a microplate radar. In this test, PBS (-) was used as a blank. The results are shown in Table 1, with the cell growth rate (%) calculated by subtracting the blank from the absorbance value and taking the control as 100%.
[0019]
[Expression 1]

[0020]
[Table 1]
Cell growth rate (%)

[0021]
As shown in Table 1, a high fibroblast proliferation effect was observed in the hyssop extract regardless of the type of extraction solvent. It turns out that a wrinkle improvement effect can be anticipated by collagen production ability increasing relatively.
[0022]
[Example 2]
Evaluation of whitening effect Evaluation by suppression of melanin production The skin stain is closely related to melanin, an intradermal pigment. In other words, it has been reported that melanin is produced by external stress such as ultraviolet rays, and as a result, the skin becomes darkened, causing symptoms such as spots, freckles, and dark black. Therefore, the skin whitening effect was evaluated in a melanin production measurement test using mouse melanoma. As the cells, mouse melanoma B-16 F-10 was used, and as the medium, a medium obtained by adding FBS to DMEM to 10% was used. Melanoma was cultured in 8 cm dishes. After 24 hours of culture, each sample was added to a final concentration of 0.001 to 0.05%, and the test was terminated 3 days after the addition. Cells grown in a petri dish were collected with a cell scraper, placed in a transparent centrifuge tube, and centrifuged at 3000 rpm for 10 minutes to collect the cells. The color of the collected cell pellet was visually judged and evaluated on a five-point scale. In this test, the sample solvent was used as a control, and arbutin was used as a positive target.
[0023]
(Criteria)
5: Black compared to control 4: Same as control 3: Slightly white compared to control 2: White compared to control 1: Very white compared to control
[Table 2]

[0025]
As in the results shown in Table 2, a decrease in the amount of melanin was observed in the hyssop extract regardless of the type of extraction solvent, and the melanin production inhibitory effect was observed. It can be seen that a whitening effect comparable to that of arbutin, which has a known whitening effect, can be expected.
[0026]
[Example 3]
Measurement of moisturizing effect by skicon The moisturizing property of the extract according to the present invention was measured using SKICON-200 (IBS). The subject was allowed to rest for 20 minutes in a room at room temperature of 19 ° C and humidity of 60%, after which a sample was applied to the inner side of the forearm (2 x 2 cm), and after 1 minute, gently wiped off with cotton, until 30 minutes later. The conductance was measured. Purified water was used as a control, and 1,3-butylene glycol 5% aqueous solution was used as a positive control.
[0027]
[Table 3]
Skin conductivity (Ω)

[0028]
As shown in Table 3, it can be seen that the hyssop extract has a high moisturizing effect regardless of the type of extraction solvent, and the effect is persistent.
[0029]
[Example 4]
Measurement of wrinkle and dryness improvement effect by use of external preparation for skin Furthermore, the effect when actually used was examined using the cosmetic according to the present invention. A continuous test was conducted with 10 women in their 40s and 60s who were worried about facial wrinkles applied twice a day (morning and evening) for 3 consecutive months. The ointment of Formulation Example 1 was applied to the subject's left face as an example, and the right face was applied as a comparative example except for removing Hyssop extract from Formulation Example 1, and the degree of improvement in skin was evaluated. . In the evaluation method, skin replicas were collected at the beginning and 3 months after application, and the degree of wrinkle improvement was evaluated from the length of the largest wrinkle. The subjects were also asked to evaluate the dry state and wrinkles after use in four stages. The results are shown in Table 4, Table 5, and Table 6. In addition, no subject complained of skin abnormalities during the period of use.
[0030]
(Wrinkle criteria for replicas)
5: 50% reduction in wrinkle length compared to the start 4: 30% reduction in wrinkle length compared to the start 3: 10% reduction in wrinkle length compared to the start 2: Compared to the same wrinkle length 1: Increase in wrinkle length compared to the start time (subject's wrinkle degree criterion)
Remarkably effective: Wrinkle disappeared Effective: Wrinkles became shorter and shallower than at the start slightly effective: Slightly shorter than the start and shallower disabled: Same as the start (subject's Dryness criteria)
Remarkably effective: no drying at all.
Valid: Slightly no longer dry compared to the start: Invalid: Slightly dry compared to the start Invalid: Same as the start [0031]
[Table 4]
Replica evaluation

[0032]
[Table 5]
Evaluation of wrinkle improvement effect of subjects

[0033]
[Table 6]
Evaluation of dryness improvement effect of subjects

[0034]
From the results of Tables 4, 5, and 6, the improvement of wrinkles and dryness of the left face applied with the example is remarkable compared with the right face applied with the comparative example, and the actual feeling effect of the subject is high. It can be seen that skin wrinkles and dryness were improved.
[0035]
[Example 5]
Measurement of the effect of hyssop extract on reducing skin roughness
The effect of mitigating the stimulus caused by 2.5% sodium lauryl sulfate aqueous solution was investigated. A 20-day occlusion patch test was performed with a 2.5% sodium lauryl sulfate aqueous solution and a 0.01% hyssop extract as samples on the forearms of 20 subjects. Using 2.5% sodium lauryl sulfate as a control, the degree of erythema 48 hours after patch removal was visually determined. The results are shown in Table 7.
[0036]
Judgment criteria (visual judgment criteria)
5: 50% decrease in erythema compared to the start 4: 30% decrease in erythema compared to the start 3: 10% decrease in erythema compared to the start 2: Same erythema compared to the start 1: Increased erythema level compared to the beginning [0037]
[Table 7]
Erythema evaluation

[0038]
[Example 6]
Measurement of skin acne improvement effect by use of external preparation for skin Furthermore, the effect when actually used was examined using the cosmetics according to the present invention. A continuous test was conducted by fifteen women in their 20s and 30s who complained of acne on their face, and applied twice a day (morning and evening) for one consecutive month. The ointment of Formulation Example 1 was applied to the subject's left face as an example, and the right face was applied as a comparative example except for removing Hyssop extract from Formulation Example 1, and the degree of improvement in skin was evaluated. . In the evaluation method, the state of the skin at the start and one month after application was photographed with a digital camera, acne was observed, the number of acne was counted, and the improvement effect of each half face was compared and evaluated. Further, the actual sensitivity after use was evaluated by the test subject in four levels. The results are shown in Tables 8 and 9. In addition, no subject complained of skin abnormalities during the period of use. In addition, no subject complained of skin abnormalities during the period of use.
[0039]
(Criteria)
5: The number of acne is reduced by 50% compared to the start 4: The number of acne is reduced by 30% compared to the start 3: The number of acne is reduced by 10% compared to the start 2: The start Compared with the same number of acne 1: Increased number of acne compared to the beginning (subject's acne criteria)
Remarkably effective: Acne disappeared Effective: Acne significantly decreased compared to the start slightly effective: Acne decreased compared to the start Invalid: Same as compared to the start [0040]
[Table 8]

[0041]
[Table 9]
Evaluation of acne improvement effect of test subjects

[0042]
From the results of Tables 8 and 9, the acne improvement degree of the left face applied with the example is remarkable compared with the right face applied with the comparative example, the actual feeling effect of the subject is high, and the acne is improved by the hyssop extract. I understand that.
[0043]
[Example 7]
Measurement of the effect of improving skin darkness and dullness due to the use of the external preparation for skin. Further, the effect of actual use of the cosmetic according to the present invention was examined. Ten women who complained of facial bears and dullness were applied twice a day (morning and evening) for 1 month in a row for a continuous test. The ointment of Formulation Example 1 was applied to the subject's left face as an example, and the right face was applied as a comparative example except for removing Hyssop extract from Formulation Example 1, and the degree of improvement in skin was evaluated. .
The evaluation method was to measure the spectral reflectance of each wavelength with a spectrocolorimeter (Yokogawa) at the start and after 1 month of application. It has been reported that the skin having no dullness has a high reflectance in the wavelength range of 400 to 700 nm, particularly in the absorption wavelength range of oxidized hemoglobin (415, 542, 576 nm). (Hiroaki Takiwaki, West Japanese Dermatology 55,415, 1993) Therefore, the effect of improving darkness and dullness was evaluated based on the difference in reflectance at 560 nm obtained with a spectrocolorimeter. Further, the actual sensitivity after use was evaluated by the test subject in four levels. The results are shown in Table 10, Table 11, and Table 12. In addition, no subject complained of skin abnormalities during the period of use.
[0044]
[Expression 2]

[0045]
(Kuma, dullness criteria)
5: Reflectance increased by 20% compared to the start 4: Reflectance increased by 10% compared to the start 3: Reflectance increased by 5% compared to the start 2: Compared to the start Same reflectance 1: Reduced reflectance compared to the start (subject's darkness, dullness criteria)
Remarkably effective: Bear, dullness disappeared, skin became very bright Effective: Compared to the start, thinned, dull skin, slightly effective: Compared to the start, dull Slightly thinned, skin slightly lightened Invalid: Same compared to the start [0046]
[Table 10]
Evaluation by spectral reflectance

[0047]
[Table 11]
Evaluation of the bear improvement effect of subjects

[0048]
[Table 12]
Evaluation of dullness improvement effect of subjects

[0049]
From the results of Tables 10, 11, and 12, compared to the right face to which the comparative example was applied, the improvement in the darkness and dullness of the left face to which the example was applied was significant, and the actual feeling effect of the subject was high. It can be seen that bear and dullness have been improved.
[0050]
[Example 8]
Measurement of elasticity / sag improvement effect by use of cosmetics Further, the effects of actual use of the cosmetics according to the present invention were examined. Ten women in their 40s and 50s who complain of sagging of the face were applied twice a day (morning and evening) for 1 month in a row for a continuous test. The ointment of Formulation Example 1 was applied to the subject's left face as an example, and the right face was applied as a comparative example except for removing Hyssop extract from Formulation Example 1, and the degree of improvement in skin was evaluated. . The evaluation method compared and evaluated the improvement effect of each half face at the start and one month after application. The evaluation method is Cutomater for skin firmness and elasticity improvement at the start and one month after application.
Evaluation was performed using SEM474 (Curage and Khazaka). The skin elasticity recovery rate was measured with Cutomater, and the elasticity recovery rate at the start was subtracted from the elasticity recovery rate after application. Furthermore, the actual sensitivity after use was evaluated by the test subject in four grades regarding the degree of improvement in sagging of the cheek, eye area, and the degree of improvement in cheek tension. The results are shown in Tables 6 and 7. In addition, no subject complained of skin abnormalities during the period of use.
[0051]
Skin elasticity
The height of the skin stretched by the negative pressure suction of Cutomater is defined as the extension length (mm), and the height of the skin that remains raised after the negative pressure release without returning to the state before suction is defined as the non-retraction length (mm).
[0052]
[Equation 3]

[0053]
(Elastic recovery rate criteria)
5: Elastic recovery rate 30% or more 4: Elastic recovery rate 20-30% or more 3: Elastic recovery rate 10-20%
2: Elasticity recovery rate 0 to 10%
1: Elasticity recovery rate 0% or less (subject's sagging degree criterion)
Remarkably effective: Elimination of sagging Effectiveness: Slightly reduced sagging compared to the beginning: Invalid: Slightly less sagging compared to the starting time Invalid: Same as starting time (subject's firmness criteria)
Remarkably effective: Effectiveness that has been considerably increased Effectiveness: Slightly effective compared to the start time Slightly effective: Slightly increased compared to the start time Invalid: Same as compared to the start time [0054]
[Table 13]
Elasticity recovery

[0055]
[Table 14]
Evaluation of the subject's sagging improvement effect

[0056]
[Table 15]
Evaluation of the subject's elasticity improvement effect

[0057]
From the results of Tables 14 and 15, the improvement in both the elasticity and sagging of the left face to which the example was applied compared to the right face to which the comparative example was applied was significant, and the actual feeling effect of the subject was high. It can be seen that has been improved [0058]
[Example 9]
Measurement of skin spot improvement effect by use of external preparation for skin Furthermore, the effect when actually used was examined using the cosmetics according to the present invention. A 10-year-old woman complaining of facial spots was applied twice a day (morning and evening) for 3 consecutive months, and a continuous test was conducted. The ointment of Formulation Example 1 was applied to the subject's left face as an example, and the right face was applied as a comparative example except for removing Hyssop extract from Formulation Example 1, and the degree of improvement in spots was evaluated. . As for the evaluation method, the subjects were asked to evaluate the stain improvement degree on a four-point scale at the start and 3 months after application. The results are shown in Table 16. In addition, no subject complained of skin abnormalities during the period of use.
[0059]
(Subject's stain improvement criteria)
Significantly effective: no spots, noticeably thinner Effective: less spots compared to the start, slightly less effective: slightly less spots than the start, thinner disabled: start Same as time [0060]
[Table 16]
Evaluation of the subject's stain improvement effect

[0061]
From the results shown in Table 16, it can be seen that the actual feeling effect of the subject is high, and the stain is improved by the hyssop extract.
[0062]
Although the formulation example of an external preparation is shown based on this invention, this invention is not limited only to this formulation example.
[0063]
Formulation Example 1
(1) Ointment (wt%)
a) Hyssop extract ... 0.01
b) Antioxidant: appropriate amount
c) Petrolatum: Add the remaining preparations a) to c), warm to 40 ° C., and mix thoroughly.
[0064]
Formulation Example 2
(2) Creamy external preparation
a) Beeswax 2.0
b) Stearyl alcohol… 5.0
c) Stearic acid… 8.0
d) Squalane… 10.0
e) Self-emulsifying glyceryl monostearate ... 3.0
f) Polyoxyethylene cetyl ether (20E.O.) ... 1.0
g) Hyssop extract ... 1.0
h) 1,3-Butylene glycol… 5.0
i) Potassium hydroxide ... 0.3
j) Preservatives / Antioxidants: appropriate amount
k) Purified water: The remaining production methods a) to f) and j) are dissolved by heating and kept at 80 ° C. to obtain an oil phase. h), i) and k) are mixed and kept at 80 ° C. to obtain an aqueous phase. Add water phase to oil phase and emulsify. After emulsification, the mixture is cooled with stirring and g) is added when the temperature reaches 60 ° C. When the temperature reaches 40 ° C, the creamy external preparation is obtained.
[0065]
Formulation Example 3
(3) Milky topical preparation (wt%)
a) Beeswax ... 0.5
b) Petrolatum ... 2.0
c) Squalane… 8.0
d) Sorbitan sesquioleate ... 0.8
e) Polyoxyethylene oleyl ether (20E.O.) ... 1.2
f) Hyssop extract ... 0.05
g) 1,3-Butylene glycol… 7.0
h) Carboxyvinyl polymer ... 0.2
i) Potassium hydroxide ... 0.1
j) Purified water ... balance
k) Preservatives / Antioxidants: appropriate amount
l) Ethanol… 7.0
The production methods a) to e) are dissolved by heating and maintained at 80 ° C. g) to k) are dissolved by heating,
Maintain at 80 ° C., emulsify in addition to a) to e), add f) at 60 ° C., and cool to 50 ° C. with stirring. Add l) at 50 ° C. and cool to 40 ° C. to obtain an emulsion external preparation.
[0066]
Formulation Example 4
(4) Lotion (wt%)
a) Hyssop extract… 0.0005
b) Glycerin ... 5.0
c) Polyoxyethylene sorbitan monolaurate (20E.O.) ... 1.0
d) Ethanol ... 6.0
e) Fragrance: appropriate amount
f) Preservatives / Antioxidants ... appropriate amount
g) Purified water: The remaining preparations a) to g) are added as needed and mixed to dissolve evenly.
[0067]
【The invention's effect】
By blending the hyssop extract of the present invention into the external preparation for skin, it has anti-aging action, moisturizing action, anti-inflammatory action, whitening action, acne improving action, bear improving action, dullness improving action, sagging improving action, and skin It has become possible to provide an external preparation for skin that can be expected to improve wrinkles, dryness, rough skin, spots, acne, bears, dullness, and sagging.

Claims (1)

The melanin production inhibitor characterized by using Hyssopus officinalis extract as an active ingredient.