JP2005281284A - Skin care preparation for external use for promoting collagen synthesis - Google Patents

Skin care preparation for external use for promoting collagen synthesis Download PDF

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JP2005281284A
JP2005281284A JP2004126113A JP2004126113A JP2005281284A JP 2005281284 A JP2005281284 A JP 2005281284A JP 2004126113 A JP2004126113 A JP 2004126113A JP 2004126113 A JP2004126113 A JP 2004126113A JP 2005281284 A JP2005281284 A JP 2005281284A
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collagen synthesis
extract
skin care
external use
skin
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Ai Nishizawa
愛 西澤
Takamasa Atsumi
隆正 渥美
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IVY COSMETICS CORP
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IVY COSMETICS CORP
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use, having collagen synthesis promoting effect, and effectively preventing age-related skin aging. <P>SOLUTION: The biogenic collagen synthesis promotor of the skin care preparation for external use contains a powder, extracts or extracted components containing Coptis japonica and/or at least one selected from berberine, palmatine, coptisine, worenine, jateorrhizine, magnoflorine, ferulic acid and chlorogenic acid as an active component. The biogenic collagen synthesis promotor of the skin care preparation for external use promotor collagen synthesis in vivo, and improves tissue fatigue and hypofunction due to age-related change. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、生体内でのコラーゲン合成促進能を高めることにより、皮膚の加齢に伴う変化を防止する皮膚外用剤に関するものである。  The present invention relates to an external preparation for skin that prevents changes associated with aging of the skin by enhancing the ability to promote collagen synthesis in a living body.

コラーゲンは真皮内の約70%を占める皮膚の主たる構成成分であり、ほとんどの組織に存在して細胞を保護し、細胞間因子として細胞の結合などの重要な生理的役割を果たしている。生体において重要な役割を持つコラーゲンも加齢による新陳代謝の低下に伴い減少し、老化の進行などの要因となり、改善する対応策が望まれている。皮膚の老化は進行しやすく、老化の兆候も観察されやすい。皮膚老化のシワやタルミは皮膚の弾力性、柔軟性の低下が原因とされ、コラーゲンの減少より引き起こされている。  Collagen is a major component of the skin that occupies about 70% of the dermis, and is present in most tissues to protect cells and play an important physiological role such as cell binding as an intercellular factor. Collagen that plays an important role in the living body also decreases with a decrease in metabolism due to aging, which causes factors such as aging, and a countermeasure to improve it is desired. Skin aging is likely to progress and signs of aging are likely to be observed. Skin aging wrinkles and tarmi are caused by a decrease in skin elasticity and flexibility, and are caused by a decrease in collagen.

現在までのところ、特許文献1に示すように、経口摂取によるコラーゲン合成促進剤などは多少開発されている。しかしながら、皮膚外用剤においては、特許文献2に示すように、コラゲナーゼを阻害して間接的にコラーゲンの減少を防止する技術等が開示されているものの、顕著にコラーゲン合成を促進し得るものは未だごくわずかである。また、コラーゲンそのものを配合することも可能であるが、高分子であるため、経皮吸収され難いことや安定性などの面から問題がある。
特開2003−277286号公報 特開2001−316221号公報
Until now, as shown in Patent Document 1, a collagen synthesis promoter by oral intake has been developed to some extent. However, as disclosed in Patent Document 2, a technique for inhibiting collagenase to indirectly prevent a decrease in collagen has been disclosed as an external preparation for skin, but there is still no one that can significantly promote collagen synthesis. Very few. Collagen itself can also be blended, but since it is a polymer, there are problems in terms of being difficult to absorb percutaneously and stability.
JP 2003-277286 A JP 2001-316221 A

本発明の目的は、コラーゲン合成能を高めることの出来るコラーゲン合成促進皮膚外用剤を提供することにある。  An object of the present invention is to provide a collagen synthesis-promoting skin external preparation capable of enhancing the ability to synthesize collagen.

本発明においては、オウレンの粉末もしくは抽出物等及び/又はベルベリン(berberine),パルマチン(palmatine),コプチジン(coptisine),ウォレニン(worenine),ジャテオリジン(jateorrhizine),マグノフロリン(magnoflorine),フェルラ酸(ferulic acid),クロロゲン酸(chlorogenic acid)より選択した1種以上を含む粉末もしくは抽出物等を皮膚外用剤基剤に含有させることにより、上記課題を解決した。以下に、本発明に関して詳細に説明する。  In the present invention, powders or extracts of oren and / or berberine, palmatin, coptidine, worenine, jateorrhizine, magnoflorine, magnoflorine (magnofluorine) The above-mentioned problems have been solved by incorporating a powder or extract containing at least one selected from acid and chlorogenic acid into a skin external preparation base. The present invention will be described in detail below.

本発明のコラーゲン合成促進皮膚外用剤は、上記したようにオウレンの粉末、抽出物もしくは抽出成分及び/又はベルベリン(berberine),パルマチン(palmatine),コプチジン(coptisine),ウォレニン(worenine),ジャテオリジン(jateorrhizine),マグノフロリン(magnoflorine),フェルラ酸(ferulic acid),クロロゲン酸(chlorogenic acid)から選択した1種以上を含む粉末、抽出物又は抽出成分を含有して成る。オウレンに関しては、特に根茎の使用が好ましい。また、ベルベリン等は、これらを含有する植物から抽出したものであることが好ましい。ベルベリン等を含有する植物としては、オウレン,ミカン科(Rutaeceae)オウバク(Phellodendri Cortex),ケシ科(Papaveraceae)エンゴサク(Corydalis Tuber),キンポウゲ科(Ranunculaceae)ショウマ(Cimicifugae Rhizoma)等が挙げられる。抽出物より濃縮、精製したものを用いることもできる。  As described above, the collagen synthesis-promoting skin external preparation of the present invention comprises a powder of aurene, an extract or an extract component and / or berberine, palmatin, coptidine, worenine, jateorridine. ), Magnoflorine, ferulic acid, chlorogenic acid, or a powder, extract or extract component containing at least one selected from chlorogenic acid. With regard to aurene, the use of rhizomes is particularly preferred. Moreover, it is preferable that berberine etc. are extracted from the plant containing these. Examples of plants containing berberine and the like include Auren, Rutaeceae, Phellodendri Cortex, Papaveraceae, Corydalisa, and Ranunculacem. What was concentrated and refine | purified from the extract can also be used.

上記植物の粉末化や抽出は常法によって行えばよい。抽出は、例えば上記植物を乾燥して刻み、または粉末状にして抽出溶媒を加え、冷浸または加熱することによって行うことが出来る。抽出溶媒としては、水、エタノール、1,3−ブタンジオール、イソプロパノール等の1種又は2種以上の混合溶媒を使用することが出来る。  What is necessary is just to perform powdering and extraction of the said plant by a conventional method. Extraction can be performed, for example, by drying and chopping the plant, or powdering it, adding an extraction solvent, and cooling or heating. As an extraction solvent, 1 type, or 2 or more types of mixed solvents, such as water, ethanol, 1, 3- butanediol, and isopropanol, can be used.

なお、本発明における抽出物とは、抽出液、該抽出液の希釈液もしくは濃縮液、該抽出物を乾燥して得られる乾燥物、または抽出エキスのいずれをも意味するものとする。上記抽出物の粗精製および精製は常法によって行えばよく、例えばMCIゲル(Sigma−Aldrich社製)等の吸着剤による吸着および溶出、クロマトグラフィー等を適当に組み合わせて実施することが出来る。  The extract in the present invention means any of an extract, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or an extract. Rough purification and purification of the extract may be performed by a conventional method, and for example, adsorption and elution with an adsorbent such as MCI gel (manufactured by Sigma-Aldrich), chromatography, and the like can be performed in an appropriate combination.

以上のようにして得られる上記植物の1種又は2種以上の粉末、抽出物、該抽出物の粗精製物、精製物及び成分は、後述する実施例から明らかなように、コラーゲン合成促進作用を有するため、コラーゲン合成促進皮膚外用剤の有効成分として使用することが出来る。本発明のコラーゲン合成促進皮膚外用剤は、生薬由来のものを有効成分としているため、安全性が高いと考えられる。  One or more kinds of powders, extracts, and crude purified products, purified products, and components of the plant obtained as described above are collagen synthesis promoting effects, as will be apparent from Examples described later. Therefore, it can be used as an active ingredient of a skin preparation for promoting collagen synthesis. The collagen synthesis-promoting skin external preparation of the present invention is considered to be highly safe because it is derived from a crude drug as an active ingredient.

本発明のコラーゲン合成促進皮膚外用剤は、医薬部外品や化粧品として提供して問題ない。配合量は外用剤中の有効濃度や外用剤の安定性等を考慮して10重量%程度以下が適当である。外用剤の形態としては、ローション、乳剤、クリーム、軟膏等、種々の形態をとる事が出来る。また、化粧水、美容液、乳液等のコラーゲン合成促進皮膚化粧料としても提供することができる。  The collagen synthesis-promoting skin external preparation of the present invention can be provided as a quasi-drug or a cosmetic without any problem. The blending amount is suitably about 10% by weight or less in consideration of the effective concentration in the external preparation and the stability of the external preparation. The form of the external preparation can take various forms such as lotion, emulsion, cream, ointment and the like. It can also be provided as a collagen synthesis-promoting skin cosmetic such as skin lotion, cosmetic liquid, and milky lotion.

以下、実施例により本発明を更に具体的に説明するが、本発明の範囲はこれらの実施例に限定されるものではない。なお「%」は特に断らない限り重量%を意味する。  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited to these examples. “%” Means% by weight unless otherwise specified.

本発明の実施例として、コラーゲン合成促進皮膚クリームの処方を表1に示す。表1中、(1)〜(5)を混合後加熱溶解して75℃とし、これに混合、加熱溶解し75℃とした(6)〜(9)及び(12)を添加して乳化し、攪拌冷却後50℃にて(10)及び(11)を添加、混合する。表1中(10)のオウレン抽出分画液は、オウレン500gを5Lの50%エタノールにて室温で1週間抽出し、MCIゲルにて分画して調製した。また、表1中(10)の替わりにエタノールを配合したものを比較例とした。

Figure 2005281284
As an example of the present invention, the formulation of a collagen synthesis promoting skin cream is shown in Table 1. In Table 1, (1) to (5) were mixed and dissolved by heating to 75 ° C., and mixed, heated and dissolved to 75 ° C., and (6) to (9) and (12) were added and emulsified. (10) and (11) are added and mixed at 50 ° C. after stirring and cooling. In Table 1, (10) Ourene extraction fraction solution was prepared by extracting 500 g of Ourene with 5 L of 50% ethanol for 1 week at room temperature and fractionating with MCI gel. Moreover, what mixed ethanol instead of (10) in Table 1 was made into the comparative example.
Figure 2005281284

本発明の実施例について、コラーゲン合成能上昇試験をヒト正常新生児皮膚繊維芽細胞を用いた評価により検討した。まず、次の(1)0.5容量%牛胎仔血清(FBS)含有ダルベッコ修正基礎培地(DMEM)、(2)コーティング緩衝液、(3)洗浄緩衝液、(4)発色液を調製する。
(1)0.5容量%FBS含有DMEM:DMEM(Sigma社製)に、終濃度0.5容量%FBSを添加して調製する。
(2)コーティング緩衝液:炭酸ナトリウム 0.8g、炭酸水素ナトリウム 1.5g、アジ化ナトリウム 0.1g/精製水500mlを調製する。
(3)洗浄緩衝液:0.05容量%Tween20/リン酸緩衝生理食塩水(PBS(−))溶液。
(4)発色液:0.1Mリン酸水素一ナトリウム(pH4.0)水溶液。
With respect to the examples of the present invention, the collagen synthesis ability increase test was examined by evaluation using human normal neonatal skin fibroblasts. First, the following (1) 0.5% by volume fetal bovine serum (FBS) -containing Dulbecco's modified basal medium (DMEM), (2) coating buffer, (3) washing buffer, and (4) coloring solution are prepared.
(1) 0.5 volume% FBS-containing DMEM : Prepared by adding a final concentration of 0.5 volume% FBS to DMEM (manufactured by Sigma).
(2) Coating buffer solution : 0.8 g of sodium carbonate, 1.5 g of sodium bicarbonate, 0.1 g of sodium azide / 500 ml of purified water are prepared.
(3) Wash buffer : 0.05 vol% Tween 20 / phosphate buffered saline (PBS (-)) solution.
(4) Coloring solution : 0.1 M aqueous solution of sodium hydrogen phosphate (pH 4.0).

正常ヒト新生児皮膚繊維芽細胞株(NHDF)を0.5容量%FBS含有DMEMにて2×10個/mlに調製し、96穴プレートに100μlずつ播種して、5%炭酸ガス、飽和水蒸気下、37℃で培養した。Normal human neonatal dermal fibroblast cell line (NHDF) was prepared at 2 × 10 4 cells / ml in DMEM containing 0.5% by volume FBS, seeded in 100 μl each in a 96-well plate, 5% carbon dioxide gas, saturated water vapor Then, the cells were cultured at 37 ° C.

24時間後、培養液を吸引除去し、植物抽出物50%エタノール水溶液を最高濃度2mg/ml(終濃度)で0.5容量%FBS含有DMEMに添加して培養をし、5%炭酸ガス、飽和水蒸気下、37℃で培養した。  After 24 hours, the culture solution was removed by suction, and the plant extract 50% aqueous ethanol solution was added to DMEM containing 0.5% by volume FBS at a maximum concentration of 2 mg / ml (final concentration). Culturing was performed at 37 ° C. under saturated steam.

48時間後、0.5容量%FBS含有DMEM:コーティング緩衝液=1:3になるよう調製し、そこに、培養上清を添加し、混和後、酵素免疫測定(ELISA)用96穴プレートに100μlずつ添加する。また、同様に検量線用にコラーゲン溶液を調製し、プレートに100μlずつ添加する。37℃で2時間反応させ、洗浄緩衝液で3回洗浄を行い、アルブミンでブロッキングする。その後、37℃で1時間反応させ、洗浄緩衝液で3回洗浄し、1次抗体を100μl添加し、37℃で1時間反応させ、また、洗浄緩衝液で3回洗浄する。その後、2次抗体を同様に反応させ、洗浄後、発色試薬で発色させ、マイクロプレートリーダー405nmで測定した。  48 hours later, 0.5 volume% FBS-containing DMEM: coating buffer = 1: 3 was prepared, culture supernatant was added thereto, mixed, and then added to a 96-well plate for enzyme immunoassay (ELISA) Add 100 μl each. Similarly, a collagen solution is prepared for the calibration curve, and 100 μl is added to the plate. React at 37 ° C. for 2 hours, wash 3 times with wash buffer and block with albumin. Thereafter, the mixture is reacted at 37 ° C. for 1 hour, washed 3 times with a washing buffer, added with 100 μl of primary antibody, reacted at 37 ° C. for 1 hour, and washed with a washing buffer 3 times. Thereafter, the secondary antibody was reacted in the same manner, washed, developed with a coloring reagent, and measured with a microplate reader at 405 nm.

コラーゲンの検量線より培養上清中のコラーゲン量を算出し、蛋白量で除して、コラーゲン生成量として求めた。結果を表2に示す。以下に示すようにオウレン抽出分画液濃度依存的にコラーゲン生成量が顕著に増えた。

Figure 2005281284
The amount of collagen in the culture supernatant was calculated from the collagen calibration curve, and divided by the amount of protein to obtain the amount of collagen produced. The results are shown in Table 2. As shown below, the amount of collagen produced increased significantly depending on the concentration of the fraction extracted from the aurene.
Figure 2005281284

続いて本発明の実施例及び比較例について使用試験を行った。コラーゲン合成が促進されると、肌に弾力が戻り、シワが出来にくくなることが推察されるため、以下の試験を行った。日常戸外で作業するパネラー15名を1群とし、各群にそれぞれ実施例及び比較例をブラインドにて顔面及び手に使用させ、シワ及び皮膚弾性の変化を観察し、評価した。使用期間は1月から12月の1年間とした。シワについては「減少」、「変化なし」、「微小なシワが増加」、「明確なシワが増加」の4段階、皮膚弾性については「上昇」、「変化なし」、「やや低下」、「低下」の4段階で評価し、各評価を得たパネラー数を表3に示した。以下に示すようにエタノール配合の比較例と比べ、オウレン抽出分画液を含有する実施例の使用により、シワが減少し、皮膚弾性が顕著に上昇した。

Figure 2005281284
Subsequently, a use test was performed on the examples and comparative examples of the present invention. When collagen synthesis is promoted, it is assumed that elasticity returns to the skin and it becomes difficult to wrinkle, so the following test was performed. A panel of 15 panelists working outdoors was used as a group, and each group was used for the examples and comparative examples blindly on the face and hands, and changes in wrinkles and skin elasticity were observed and evaluated. The period of use was one year from January to December. For wrinkles, there are four stages: “decrease”, “no change”, “increase in fine wrinkles”, “increase in clear wrinkles”, and skin elasticity “increase”, “no change”, “slightly decrease”, “ Table 3 shows the number of panelists that have obtained the respective evaluations. As shown below, wrinkles were reduced and skin elasticity was remarkably increased by the use of the examples containing the Ouren extract fraction, as compared with the comparative examples containing ethanol.
Figure 2005281284

発明の効果The invention's effect

以上詳述したように、本発明に係るコラーゲン合成促進皮膚外用剤は、皮膚内でのコラーゲン生合成を促進し、加齢変化に伴うシワ、タルミなどの老化防止に効果を発揮させることが出来る。また、生薬由来のものを有効成分としているため、副作用が比較的少なく、安全性にも優れた皮膚外用剤である。  As described above in detail, the collagen synthesis-promoting skin external preparation according to the present invention can promote the biosynthesis of collagen in the skin and can be effective in preventing aging such as wrinkles and tarmi accompanying aging changes. . In addition, since it is an active ingredient derived from herbal medicine, it is a skin external preparation with relatively few side effects and excellent safety.

Claims (3)

キンポウゲ科(Ranunculaceae)オウレン(Coptis japonica)の粉末、抽出物又は抽出成分を含有することを特徴とする、生体のコラーゲン生成を促進する皮膚外用剤。  A skin external preparation for promoting collagen production in a living body, comprising a powder, extract or extract component of Ranunculaceae auren (Coptis japonica). ベルベリン(berberine),パルマチン(palmatine),コプチジン(coptisine),ウォレニン(worenine),ジャテオリジン(jateorrhizine),マグノフロリン(magnoflorine),フェルラ酸(ferulic acid),クロロゲン酸(chlorogenic acid)より選ばれる1種又は2種以上を含む粉末、抽出物又は抽出成分を含有することを特徴とする、生体のコラーゲン生成を促進する皮膚外用剤。  Berberine, palmatin, coptidine, worenine, jateorrhizine, magnoflorine, ferulic acid (1), chlorogenic acid, 1 A skin external preparation for promoting collagen production in a living body, comprising a powder, an extract or an extract component containing two or more kinds. オウレンの粉末、抽出物又は抽出成分と、ベルベリン(berberine),パルマチン(palmatine),コプチジン(coptisine),ウォレニン(worenine),ジャテオリジン(jateorrhizine),マグノフロリン(magnoflorine),フェルラ酸(ferulic acid),クロロゲン酸(chlorogenic acid)より選ばれる1種又は2種以上を含む粉末、抽出物又は抽出成分を含有することを特徴とする、生体のコラーゲン生成を促進する皮膚外用剤。  Powder, extract or extract of auren and berberine, palmatin, coptidine, worenine, jateorrizine, magnoflorine, ferulic acid, ullucic acid A skin external preparation for promoting collagen production in a living body, comprising a powder, an extract or an extract component containing one or more selected from acids (chlorogenic acid).
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EP2071975A2 (en) 2007-12-20 2009-06-24 Unilever PLC Antiperspirant or deodorant products comprising labile agent and pigments
WO2009080625A1 (en) * 2007-12-20 2009-07-02 UNILEVER PLC, a company registered in England and Wales under company no. 41424 of Cosmetic sticks comprising labile active
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EP2071975A3 (en) * 2007-12-20 2009-07-15 Unilever PLC Antiperspirant or deodorant products comprising labile agent and pigments
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US9084744B1 (en) * 2008-12-30 2015-07-21 Avon Products, Inc. Use of Tiliacora triandra in cosmetics and compositions thereof
JP2011088845A (en) * 2009-10-21 2011-05-06 Kao Corp Involucrin expression inhibitor
KR101855094B1 (en) * 2012-01-13 2018-05-08 주식회사 엘지생활건강 Composition for improving skin wrinkle and enhancing elasticity
JP2016056116A (en) * 2014-09-08 2016-04-21 株式会社ディーエイチシー Composition for promoting collagen production
KR101800498B1 (en) * 2014-10-15 2017-11-27 동의대학교 산학협력단 Composition for improving skin wrinkle comprising extract or compounds derived from unripe apple
JP2017537091A (en) * 2014-12-09 2017-12-14 ラボラトワール クラランス Cosmetic use of Eschorsia californica extract
JP2022023187A (en) * 2015-10-21 2022-02-07 大正製薬株式会社 Scalp agents
JP7264200B2 (en) 2015-10-21 2023-04-25 大正製薬株式会社 scalp agent
CN110787162A (en) * 2019-12-09 2020-02-14 朱峰 Use of methylprednisolone coptisine as JNK2 kinase inhibitor and for treating psoriasis
WO2022196614A1 (en) * 2021-03-17 2022-09-22 国立大学法人 長崎大学 Agent for treating or preventing chagas disease

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