TWI445542B - Birch sap as to the efficacy of their use for the active ingredient - Google Patents

Birch sap as to the efficacy of their use for the active ingredient Download PDF

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TWI445542B
TWI445542B TW096105565A TW96105565A TWI445542B TW I445542 B TWI445542 B TW I445542B TW 096105565 A TW096105565 A TW 096105565A TW 96105565 A TW96105565 A TW 96105565A TW I445542 B TWI445542 B TW I445542B
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skin
extract
added
components
mixing
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TW200808332A (en
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Masahiro Moriyama
Eiji Naru
Minako Konno
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Kose Corp
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Priority claimed from JP2006047594A external-priority patent/JP4938319B2/en
Priority claimed from JP2006055906A external-priority patent/JP4758252B2/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/49Fagaceae (Beech family), e.g. oak or chestnut
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/007Preparations for dry skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin

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  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
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  • Chemical & Material Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Birds (AREA)
  • Cosmetics (AREA)

Description

以白樺樹液作為有效成分之藥效劑及其使用A potent agent with birch sap as an active ingredient and its use

本發明係關於白樺(Betula platyphylla Sukatchev var.japonica Hara)樹液(以下僅以白樺樹液表示)作為有效成分之種種藥效劑,又,亦關於白樺樹液之種種藥效劑的使用。該利用領域例如為化妝料、醫藥部外品、外用醫藥品等皮膚外用劑的領域。The present invention relates to various medicinal agents of Betula platyphylla Sukatchev var. japonica Hara sap (hereinafter, only expressed by birch sap) as an active ingredient, and also relates to various medicinal agents of birch sap. The field of use is, for example, in the field of skin external preparations such as cosmetics, pharmaceutical products, and external medicines.

過去如乳液、乳霜、化妝水、美容液、面膜、洗淨劑、分散液、軟膏、氣溶膠、貼劑、擦劑等等皮膚外用劑中,以賦予彼等所定藥效為目的而加入種種藥效劑。In the past, skin external preparations such as lotions, creams, lotions, beauty lotions, masks, detergents, dispersions, ointments, aerosols, patches, liniments, etc., were added for the purpose of giving them the prescribed effects. Various pharmacodynamic agents.

例如作為改善皮膚粗糙、皺紋等之保濕成分,已提出甘油或丙二醇、糖類、胺基酸類等(flagrance journal臨時增刊vol.9(1988)、第116-117頁;flagrance journal臨時增刊vol.9(1988)、第127-128頁;flagrance journal vol.23、No.1(1995)第71-79頁)。For example, glycerin, propylene glycol, saccharides, amino acids, etc. have been proposed as moisturizing ingredients for improving skin roughness, wrinkles, etc. (flagrance journal provisional supplement vol. 9 (1988), pp. 116-117; flagrance journal temporary supplement vol. 9 ( 1988), pp. 127-128; flagrance journal vol. 23, No. 1 (1995) pp. 71-79).

對於藉由塗佈含有保濕成分之皮膚外用劑,雖已嘗試維持肌膚的濕潤,但至今作為保濕成分之效果僅為暫時性之保濕效果,無法於長時間下維持肌膚的保濕。欲維持長期間之肌膚保濕,必須先瞭解該保濕機制,提供一種直接對該機制作直接性或間接性作用之用劑。Although it has been tried to maintain the moisturization of the skin by applying a skin external preparation containing a moisturizing ingredient, the effect as a moisturizing ingredient has only been a temporary moisturizing effect, and it is impossible to maintain the moisturizing effect of the skin for a long period of time. To maintain long-term skin moisturization, you must first understand the moisturizing mechanism and provide a direct or indirect effect on the machine.

作為經長時間可維持肌膚保濕之其中一要因,可舉出促進肌膚本身之天然保濕因子的原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)之產生。然而,對於促進該原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)之產生的用劑至今為未知。As one of the main reasons for maintaining skin moisturization over a long period of time, the production of profilaggrin and/or filaggrin which promotes the natural moisturizing factor of the skin itself can be mentioned. However, agents for promoting the production of profilaggrin and/or filaggrin have not been known until now.

又,作為對於改善肌膚表皮之阻礙功能降低所引起的肌膚粗糙等肌膚問題之用劑已被提出Ceramide(賽絡美)(flagrance journal臨時增刊vol.15(1996)第117-127頁)、保濕促進或阻礙功能之補助為目的之用劑、膽固醇衍生物(flagrance journal臨時增刊vol.17(2000)第123-128頁)、作為皮膚保護為目的之用劑的膨潤石(Smectite)(flagrance journal臨時增刊vol.17(2000)第175-184頁)等。In addition, it has been proposed as a medicinal agent for skin problems such as skin roughness caused by a decrease in the barrier function of the skin epidermis (Ceramide) (flagrance journal vol. 15 (1996) pp. 117-127), moisturizing For the purpose of promoting or hindering the function of the subsidy, the cholesterol derivative (flagrance journal, Temporary Supplement vol. 17 (2000), pp. 123-128), and Smectite (the flagrance journal) for the purpose of skin protection. Temporary Supplement vol. 17 (2000) pp. 175-184).

上述賽絡美已知為作為構成細胞脂質之成分,作為抑制由皮膚之水分損失的角層阻礙功能上為極重要角色。另一方面,該角層阻礙功能中,包殼蛋白(involucrin)亦擔任重要角色。如上述賽絡美,對於過去使用於角層阻礙功能降低防止之用劑,補充細胞間脂質或肌膚表皮上形成皮膜而達到阻礙功能之改善效果者為多,藉由促進包殼蛋白(involucrin)之產生而達成阻礙功能的改善效果者則尚未知。The above-mentioned celecoxi is known as a component constituting cellular lipids, and is a very important function as a function of preventing the cornea from being lost by moisture of the skin. On the other hand, in the nucleus barrier function, involucrin also plays an important role. For example, in the case of the above-mentioned celoxi, it is used in the past for the prevention of the prevention of the prevention of the protective layer of the cornea, and the effect of the formation of the membrane on the intercellular lipid or the epidermis of the skin to improve the barrier function, by promoting the involucrin. The improvement effect of the obstacle function is not known.

又,膽固醇亦為角層細胞間脂質的一構成成分(佔角層細胞間脂質之約25%的成分),已知可防止由表皮之水分蒸散。因此,欲要維持肌膚的濕潤,必須提高膽固醇之產生(flagrance journal臨時增刊No.17(2000)第20-26頁)。然而,對於促進該膽固醇之產生的用劑尚未知。Further, cholesterol is also a constituent component of the intercellular lipids of the cornea (a component which accounts for about 25% of the intercellular lipids), and it is known to prevent evaporation of water from the epidermis. Therefore, in order to maintain the moisturization of the skin, it is necessary to increase the production of cholesterol (flagrance journal provisional supplement No. 17 (2000), pp. 20-26). However, agents for promoting the production of this cholesterol are not known.

又,過去隨著年齡增加會使得細胞代謝功能降低,成為皮膚的新陳代謝速度之降低或皮膚粗糙的原因,又造成膠原蛋白或彈力蛋白等真皮矩陣的減少或變性,與皺紋或皮膚彈性降低等現象有關。且,因老化廢棄物無法順利排出亦為色素沈澱或皮膚黯淡的原因。以防止或改善這些現象的進行,正探討達到細胞活化且促進增殖之用劑,即探討細胞賦活劑。例如已提出作為細胞賦活劑之海蘊萃取物(特開2003-267852號公報參照)、或由番紅花的雄蕊得到之萃取物(特開2005-041812號公報參照)等。In addition, in the past, as the age increased, the metabolic function of the cells decreased, which caused the skin's metabolic rate to decrease or the skin to be rough, and the dermis matrix such as collagen or elastin was reduced or denatured, and wrinkles or skin elasticity decreased. related. Moreover, the aging waste cannot be discharged smoothly, which is also the cause of pigmentation or dull skin. In order to prevent or improve the progress of these phenomena, an agent for achieving cell activation and promoting proliferation, that is, a cell activating agent, is being explored. For example, it has been proposed as an extract of a marine activator (refer to Japanese Laid-Open Patent Publication No. 2003-267852), or an extract obtained from the stamen of saffron (refer to Japanese Laid-Open Patent Publication No. 2005-041812).

如上所示之細胞賦活劑,作為最近皮膚外用劑的添加成分,由安全性等面來看,與化學物質相比來自天然物質的成分有較佳的傾向。例如,嘗試將來自天然物之材料的白樺類之萃取液或樹液使用於皮膚外用劑的成分上。例如白樺萃取液具有保濕作用,組合該白樺萃取液與西印度櫻桃(acerola)萃取物之皮膚老化防止用或肌膚粗糙改善用之皮膚外用劑(特開2000-212027號參照)、或添加白樺樹液之保濕作用優良的肌膚粗糙改善用化妝料(特開09-291013號參照)。The cell activator as described above has a tendency to be a component derived from a natural substance as compared with a chemical substance, as an additive component of a recent skin external preparation. For example, an attempt is made to use an extract or sap of white birch from a material of a natural material for the composition of the external preparation for skin. For example, the white birch extract has a moisturizing effect, and the skin external preparation for skin aging prevention or skin roughness improvement of the white birch extract and the acerola extract (refer to Japanese Patent Laid-Open No. 2000-212027), or the addition of white birch sap A cosmetic material that is excellent in moisturizing effect and improved in roughness (refer to JP-A 09-291013).

然而,白樺萃取液或白樺樹液具有上述原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生促進作用、包殼蛋白(involucrin)產生促進作用、膽固醇產生促進作用或細胞賦活作用則完全為未知。However, the white birch extract or the birch sap has the above-mentioned profilaggrin or filaggrin production promoting action, involucrin production promoting effect, cholesterol production promoting action or cell activating effect. It is completely unknown.

本發明有鑑於上述課題所成者本發明的第1課題為提供一種促進來自天然物質的原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生的新穎用劑;第2課題為提供一種促進來自天然物質的包殼蛋白(involucrin)產生的新穎用劑;第3課題為提供一種促進來自天然物質的膽固醇產生之新穎用劑;及第4課題為提供一種具有來自天然物之細胞賦活作用的新穎用劑。The present invention has been made in view of the above problems, and a first object of the present invention is to provide a novel agent for promoting the production of profilaggrin or filaggrin from a natural substance; To provide a novel agent for promoting the production of involucrin from a natural substance; a third object is to provide a novel agent for promoting the production of cholesterol from a natural substance; and a fourth object is to provide a product having a natural product. A novel agent for cell activation.

有鑑於上述本發明者欲解決上述課題,著重於來自天然物之成分中的來自植物的成分,進行詳細研究結果,作為具有上述作用的用劑,發現白樺樹液具有其效果。In view of the above-mentioned problems, the inventors of the present invention have focused on the plant-derived components from the components of natural materials, and have conducted detailed studies. As a drug having the above-described effects, it has been found that the birch sap has an effect.

即,本發明係關於白樺(Betula platyphylla Sukatchev var.japonica Hara)樹液作為有效成分之原聚角微絲蛋白(profilaggrin)、或聚角微絲蛋白(filaggrin)產生促進劑;包殼蛋白(involucrin)產生促進劑;膽固醇產生促進劑;及細胞賦活劑。That is, the present invention relates to a profilaggrin or a filaggrin production promoter of Betula platyphylla Sukatchev var. japonica Hara sap as an active ingredient; involucrin Producing a promoter; a cholesterol production promoter; and a cell activating agent.

又,本發明由另一觀點來看,提供可作為白樺(Betula platyphylla Sukatchev var.japonica Hara)樹液的原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生促進劑使用;可作為包殼蛋白(involucrin)產生促進劑使用;可作為膽固醇產生促進劑使用;及可作為細胞賦活劑使用。Further, the present invention provides, from another point of view, a pro-aggregin or a filaggrin-producing promoter which can be used as a sap of Betula platyphylla Sukatchev var. japonica Hara; It is used as an involucrin production promoter; it can be used as a cholesterol production promoter; and can be used as a cell activating agent.

又,由本發明的另一觀點來看,本發提供一種藉由使用白樺(Betula platyphylla Sukatchev var.japonica Hara)樹液而促進原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生之方法;促進包殼蛋白(involucrin)產生之方法;促進膽固醇產生方法;及細胞賦活方法(但,任皆除去對於人類的治療方法)。Further, from another point of view of the present invention, the present invention provides a method for promoting the production of profilaggrin or filaggrin by using a sap of Betula platyphylla Sukatchev var. japonica Hara. Methods; methods for promoting the production of involucrin; methods for promoting cholesterol production; and methods for cell activation (however, all treatment methods for humans are removed).

本發明為提供一種來自天然物,且安全性良好之新穎原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生促進劑、包殼蛋白(involucrin)產生促進提供、膽固醇產生促進劑、及細胞賦活劑。The present invention provides a novel profilaggrin or filaggrin production promoter, engulucrin production promotion, cholesterol production promotion, which is safe from natural products. Agents, and cell activators.

又,本發明的含有原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進劑之皮膚外用劑可對肌膚本身促進天然保濕因子之產生,可持續維持肌膚的濕潤。Further, the skin external preparation containing the profilaggrin and/or the filaggrin production promoter of the present invention can promote the production of natural moisturizing factors on the skin itself, and maintain the moisturization of the skin. .

又,本發明的含有包殼蛋白(involucrin)產生促進劑之皮膚外用劑,可期待使肌膚表皮的阻礙功能正常化,使肌膚表皮的水分保持得到改善效果,且可達到肌膚粗糙防止效果等。Moreover, the skin external preparation containing the involucrin production promoter of the present invention can be expected to normalize the barrier function of the skin epidermis, improve the moisture retention of the skin epidermis, and achieve a skin roughness prevention effect.

又,本發明的含有膽固醇產生促進劑之皮膚外用劑,可對於肌膚本身促進膽固醇的產生,其結果可防止水分蒸散,持續維持肌膚的濕潤。Moreover, the skin external preparation containing a cholesterol production promoter of the present invention can promote the production of cholesterol to the skin itself, and as a result, it can prevent moisture from escaping and maintain the moisturization of the skin.

又,本發明的含有細胞賦活劑之皮膚外用劑,可達到抑制或改善肌膚粗糙、皮膚黯淡等優良美膚效果。Moreover, the skin external preparation containing a cell activator of the present invention can achieve an excellent skin-beautifying effect of suppressing or improving rough skin and dull skin.

以下對本發明作詳細説明。且,本說明書中所謂「~」為前後所記載之數值表示含有下限值及上限值的意義。The invention is described in detail below. In addition, the "~" in this specification is a numerical value which shows the meaning of the lower limit and upper limit.

本發明所使用的白樺(Betula platyphylla Sukatchev var.japonica Hara)為樺木科植物,其別名亦稱為白樺、雁皮,分佈於岐阜縣以東的本州、北海道、千島列島、薩哈林、朝鮮、中國、西伯利亞之落葉高木,本發明所使用的白樺樹液為,僅於早春至開花及開葉的1個月間,於樹幹上穿孔所溢出之樹液。作為該樹液的成分含有礦物質、糖類、有機酸、胺基酸等。且,本發明中並無特別限定該栽培方法或產地。The white birch (Betula platyphylla Sukatchev var. japonica Hara) used in the present invention is a birch family, and its alias is also known as white birch and geese, distributed in Honshu, Hokkaido, Thousand Islands, Sakhalin, North Korea, and China east of Pixian County. The sapwood sap used in the present invention is a sap that is perforated on the trunk only during the first spring of flowering and opening of the leaves in the early spring. The component of the sap contains minerals, sugars, organic acids, amino acids, and the like. Further, the cultivation method or the production place is not particularly limited in the present invention.

本發明所使用的白樺樹液之調製法並無特別限定,但作為本發明所使用的調製法一例可舉出由樹幹採取之樹液經95℃下10分鐘加熱滅菌後冷卻、過濾者再放置於5℃中3天,過濾沈澱物後所得者等。又,可利用白樺樹液之販賣品,作為販賣品可舉出森之雫(莎布有限公司製)等。The preparation method of the birch sap used in the present invention is not particularly limited. However, as an example of the preparation method used in the present invention, the sap taken from the trunk is heated and sterilized at 95 ° C for 10 minutes, and then cooled and filtered. After 3 days in °C, the precipitate was filtered and the like. In addition, the sale of the birch sap can be used, and as a sales item, Mori 雫 (made by Sabu Co., Ltd.) and the like can be cited.

對於聚角微絲蛋白(filaggrin)及原聚角微絲蛋白(profilaggrin)作說明。聚角微絲蛋白(filaggrin)為分子量30萬以上之前驅蛋白,原聚角微絲蛋白(profilaggrin)為分解至胺基酸等天然保濕因子的過程中之中間代謝物。該原聚角微絲蛋白(profilaggrin)為,表皮顆粒細胞隨著角層細胞的移動而受到蛋白分解酵素之分解,最後成為可維持皮膚表皮濕潤的天然保濕因子(皮膚科Mook、No.15(1989)、第49-55頁)。因此,欲維持肌膚的濕潤必須含有原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)。本發明為使用白樺樹液而促進原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)的產生。For the description of filaggrin and profilaggrin. The filaggrin is a precursor protein with a molecular weight of 300,000 or more, and the profilaggrin is an intermediate metabolite in the process of decomposing to a natural moisturizing factor such as an amino acid. The profilaggrin is that the epidermal granule cells are decomposed by proteolytic enzymes as the cells of the horn cells move, and finally become a natural moisturizing factor that maintains the skin epidermis (Medical Mook, No. 15 ( 1989), pp. 49-55). Therefore, in order to maintain the moisturization of the skin, it is necessary to contain profilaggrin and/or filaggrin. The present invention promotes the production of profilaggrin and/or filaggrin using birch sap.

包殼蛋白(involucrin)為隨著表皮角化細胞之分化藉由麩醯基轉移(Transglutaminase)交聯,於細胞周圍形成不溶之膜Cornified Envelope(CE),其為CE前驅蛋白。該包殼蛋白(involucrin)之細胞膜藉由與細胞間脂質之賽絡美的一部份結合,形成角層阻礙功能。即,角層阻礙功能的形成中,不僅細胞間脂質之賽絡美,與其結合之膜蛋白的包殼蛋白(involucrin)之存在亦非常重要。本發明為使用白樺樹液而可促進包殼蛋白(involucrin)之產生。The involucrin is a cross-linked membrane of transglutaminase which differentiates with epidermal keratinocytes to form an insoluble membrane around the cells, which is a CE precursor protein. The cell membrane of the involucrin combines with a part of the cell-synthesis of the intercellular lipid to form a layer barrier function. That is, in the formation of the corneal barrier function, not only the cytochrome of the intercellular lipid, but also the presence of the involucrin of the membrane protein bound thereto is very important. The present invention promotes the production of involucrin by using birch sap.

膽固醇為角層細胞間脂質的一構成成分(佔據角層細胞間脂質的約25%之成分),其顯示防止由表皮蒸發水分之功能。又,已知經老化之皮膚為產生膽固醇之功能已劣化。欲保持濕潤的皮膚,必須促進含於細胞間脂質之膽固醇的產生。本發明因使用白樺樹液可促進含於細胞間脂質之膽固醇的產生。Cholesterol is a constituent of corneal intercellular lipids (a component that occupies about 25% of intercellular lipids), which exhibits a function of preventing evaporation of moisture from the epidermis. Further, it is known that the function of aging skin to produce cholesterol has deteriorated. To maintain moist skin, it is necessary to promote the production of cholesterol containing intercellular lipids. The present invention promotes the production of cholesterol contained in intercellular lipids by using birch sap.

又,因年齡的增加等所引起的細胞代謝功能之下降,已知其成為皮膚新陳代謝速度降低或肌膚粗糙的原因,或引起膠原蛋白或彈力蛋白等真皮矩陣之減少或產生改性,與皺紋或皮膚彈性低下等現象有關。且,因廢棄物無法順利排出而成為色素沈澱或皮膚黯淡之原因,欲防止或改善這些現象的進行,故必須求得細胞之活化。本發明為因使用白樺樹液可活化細胞。In addition, the decrease in cellular metabolic function caused by an increase in age is known to be a cause of a decrease in skin metabolism rate or a rough skin, or a reduction or modification of a dermal matrix such as collagen or elastin, and wrinkles or It is related to the phenomenon of low skin elasticity. Further, since the waste cannot be discharged smoothly, it is a cause of pigmentation or dull skin. To prevent or improve the progress of these phenomena, activation of cells must be obtained. The present invention is to activate cells by using birch sap.

本發明的原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生促進劑、包殼蛋白(involucrin)產生促進劑、膽固醇產生促進劑、或細胞賦活劑之用途並無特別限定,將來自天然物之白樺樹液作為有效成分使用時,其安全性良好,由相關觀點得知可作為皮膚外用劑的藥效成分使用時為佳。皮膚外用劑之本發明的藥效劑之含有量並無特別限定,但其有效成分的白樺樹液含有量為0.0001~50質量%(以下僅以「%」表示)為佳,較佳為0.001~30%。僅為該範圍內,可安定地含有該樹液,且具有較高原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生促進作用、包殼蛋白(involucrin)產生促進作用、膽固醇產生促進作用、或細胞賦活作用,藉此結果可發揮保濕效果及其持續效果。The use of the profilaggrin or filaggrin production promoter, the involucrin production promoter, the cholesterol production promoter, or the cell activating agent of the present invention is not particularly limited. When the birch sap from natural products is used as an active ingredient, it is excellent in safety, and it is preferable from the related viewpoint that it can be used as a medicinal ingredient of a skin external preparation. The content of the medicinal agent of the present invention is not particularly limited, but the content of the birch sap of the active ingredient is preferably 0.0001 to 50% by mass (hereinafter referred to as "%"), preferably 0.001%. 30%. Only in this range, the sap can be contained stably, and has a higher pro-aggregating effect or filaggrin production promoting effect, involucrin production promoting effect, and cholesterol production. Promoting action, or cell activating effect, thereby achieving a moisturizing effect and a sustained effect.

又,將本發明中作為種種藥效劑所使用的白樺樹液添加於皮膚外用劑中時,可並用於皮膚外用劑常用的各種其他藥效劑,例如一種或二種以上選自抗氧化劑、消炎劑、細胞賦活劑、紫外線防止劑、保濕劑、血循環促進劑等藥效劑,可更提更本發明之效果。In addition, when the birch sap used as a medicinal agent in the present invention is added to an external preparation for skin, it can be used in combination with various other medicinal agents commonly used for external preparations for the skin, for example, one or more selected from the group consisting of antioxidants and anti-inflammatory agents. A pharmacophore such as a agent, a cell activating agent, an ultraviolet ray preventing agent, a moisturizing agent, and a blood circulation promoting agent can further improve the effects of the present invention.

作為這些藥效劑之具體例子,各可舉出下述者。其中「衍生物」為含有可能形成之酯或鹽。又,有時一種物質中具有複數種藥效,故複數種的藥效劑以一名稱記載。(且,植物的情況為,別名的漢藥名等記載於括弧內)。Specific examples of these medicinal agents include the following. The "derivative" is a salt or salt which may be formed. Moreover, sometimes a substance has a plurality of pharmacological effects, and therefore, a plurality of pharmacodynamic agents are described by one name. (And, in the case of plants, the names of the Chinese medicines of the aliases are described in parentheses).

作為抗氧化劑可舉出維他命E及其衍生物、維他命C及其衍生物、類胡蘿蔔素、二丁基羥基甲苯、丁羥基苯甲醚、芸香素及其衍生物、麩胱甘肽及其衍生物、超氧化物歧化酵素、甘露糖醇、雞血藤萃取物、尼泊爾老觀草萃取物、山楂子萃取物、芍藥萃取物、銀杏萃取物、黃金花萃取物、玫瑰花(山楂花、濱梨)萃取物、P.tormentilla萃取物、葡萄萃取物、矢車實(矢車)萃取物、草莓虎耳草萃取物、迷迭香(R.officinalis)萃取物、茶萃取物(烏龍茶、紅茶、綠等)等。Examples of the antioxidant include vitamin E and its derivatives, vitamin C and its derivatives, carotenoids, dibutylhydroxytoluene, butylated hydroxyanisole, ruthenium and its derivatives, glutathione and its derivatives. , superoxide dismutase, mannitol, spatholobus extract, Nepal old grass extract, hawthorn extract, peony extract, ginkgo extract, gold flower extract, rose flower (Hawthorn flower, shore Pear) extract, P. tormentilla extract, grape extract, cornflower extract, strawberry saxifrage extract, rosemary (R. officinalis extract), tea extract (oolong tea, black tea, green and many more.

作為可舉出消炎劑、甘草酸及其衍生物、甘草次酸及其衍生物、硫及其衍生物、蘆薈萃取物、明日葉萃取物、蕁麻萃取物、茵蔯蒿(Artemisia capillaris)萃取物、鬱金萃取物、黃菠蘿(黃柏)萃取物、小連翹萃取物、洋甘菊萃取物、康復力(鰭玻璃草)萃取物、忍冬(金銀花)萃取物、和蘭芥子萃取物、鼠尾草(sage)萃取物、吾亦紅(榆)萃取物、紫蘇萃取物、白樺萃取物、接骨木萃取物、香蒲(蒲黃)萃取物、無患子萃取物、尤加利萃取物、宿根草萃取物、蓮華草萃取物、赤竹萃取物、氧化鋅等。Examples thereof include an anti-inflammatory agent, glycyrrhizic acid and derivatives thereof, glycyrrhetinic acid and derivatives thereof, sulfur and derivatives thereof, aloe extract, tomorrow leaf extract, castor extract, and Artemisia capillaris extract. , turmeric extract, yellow pineapple (cork) extract, small forsythia extract, chamomile extract, healing power (fin glass grass) extract, honeysuckle (honeysuckle) extract, and blue mustard extract, sage ( Sage) extract, wuhong (榆) extract, perilla extract, birch extract, elderberry extract, cattail extract, sapindus extract, eucalyptus extract, bergamot extract, lotus leaf extract , red bamboo extract, zinc oxide, etc.

作為細胞賦活劑可舉出維他命A及其衍生物、蘆筍萃取物、大豆萃取物、棗(大棗)萃取物、蒜頭萃取物、人參萃取物、殼斗萃取物、蜂王漿、酵母萃取物、微生物發酵代謝產物、靈芝萃取物等。Examples of the cell activator include vitamin A and its derivatives, asparagus extract, soybean extract, jujube (jujube) extract, garlic extract, ginseng extract, shell extract, royal jelly, yeast extract, microorganism Fermentation metabolites, Ganoderma lucidum extracts, and the like.

作為紫外線防止劑可舉出對甲氧基桂皮酸-2-乙基己酯、4-第三丁基-4’-甲氧基二苯甲醯基甲烷、羥苯甲酮及其衍生物、氧化鈦、微粒子氧化鈦、氧化鋅及微粒子氧化鋅等。氧化鈦、氧化鋅等無機粉體使用微粒子者時可發揮更高效果。Examples of the ultraviolet ray preventing agent include p-methoxycinnamic acid-2-ethylhexyl ester, 4-tert-butyl-4'-methoxydibenzopyridylmethane, oxybenzone and derivatives thereof. Titanium oxide, fine particle titanium oxide, zinc oxide, and fine particle zinc oxide. When inorganic powders such as titanium oxide and zinc oxide are used, fine particles can be used.

作為保濕劑可舉出甘油、1,3-丁二醇、蛋白質或此等之衍生物或水解物以及這些鹽(膠原蛋白、彈力蛋白等)、透明質酸及其鹽、胺基酸及此等之衍生物、糖類、D-泛酸醇及其衍生物、糖脂質、磷脂質、賽絡美、尿素、黏蛋白、杏仁萃取物、酪梨萃取物、屬葵萃取物、溫泉水、蘆薈萃取物、大花葵萃取物、刺芒柄花萃取物、野燕麥萃取物、光甘草定、光果甘草素、liquilitin、isoliquilitin及含有此等之甘草萃取物、溫桲種子萃取物、苦參萃取物、梔子花萃取物、葡萄柚萃取物、和蘭芥子萃取物、龍膽萃取物、龍膽老觀草萃取物、牛蒡萃取物、小麥萃取物、辣椒素萃取物、仙人掌萃取物、石鹼草萃取物、山楂子萃取物、地黃萃取物、下野草萃取物、生薑萃取物、大花葵花(薄紅立葵)萃取物、桑(桑白皮)萃取物、銀斑百里香(百里香)萃取物、冬蟲夏草萃取物、魚腥草萃取物、薄荷萃取物、薏仁萃取物、金縷梅萃取物、薔薇萃取物、檜萃取物、款冬花萃取物、葡萄萃取物、蜜棗萃取物、絲瓜萃取物、菩提樹萃取物、蛇麻草萃取物、松萃取物、桲萃取物、七葉樹萃取物、香蜂草萃取物、矢車草萃取物、百合萃取物、萊姆萃取物、薰衣草萃取物、蘋果萃取物、米及米糠萃取物、黑醋栗萃取物、拳參萃取物、野薔薇萃取物、刺五加萃取物、海藻萃取物等。Examples of the humectant include glycerin, 1,3-butylene glycol, protein or derivatives or hydrolyzates thereof, and these salts (collagen, elastin, etc.), hyaluronic acid and salts thereof, amino acids and the like. Derivatives, sugars, D-pantothenic acid and its derivatives, glycolipids, phospholipids, celecoxime, urea, mucin, almond extract, avocado extract, genus sunflower extract, hot spring water, aloe extract , geranium extract, thorn flower extract, wild oat extract, licorice, licorice, liquilitin, isoliquilitin and licorice extract containing the same, sorghum seed extract, Sophora flavescens extract , Gardenia Extract, Grapefruit Extract, and Mustard Seed Extract, Gentian Extract, Gentian Extract, Burdock Extract, Wheat Extract, Capsaicin Extract, Cactus Extract, Stone Alkali extract, hawthorn extract, rehmannia extract, lower grass extract, ginger extract, malva flower (thin red sunflower) extract, mulberry (mulberry white) extract, silver thyme (thyme) ) extract, Cordyceps extract, Valerian extract, peppermint extract, coix seed extract, witch hazel extract, rose extract, alfalfa extract, coltsfoot flower extract, grape extract, candied fruit extract, loofah extract, linden extract, hop Extract, pine extract, alfalfa extract, horse chestnut extract, lemon balm extract, cornflower extract, lily extract, lime extract, lavender extract, apple extract, rice and rice bran extract, Blackcurrant extract, box finger extract, wild rose extract, acanthopanax extract, seaweed extract, etc.

且,作為藉由皮膚表面封閉之保濕劑可舉出荷荷芭油、澳洲堅果油、橄欖油、杏仁油、杏仁油、葵花油、向日葵油、酪梨油、白芒花籽油(Meadowfoam)、椿油、杏仁油、荏胡麻油、芝麻油、琉璃苣油、可可脂、乳油木果脂等。Moreover, as a moisturizing agent which is closed by the skin surface, jojoba oil, macadamia nut oil, olive oil, almond oil, almond oil, sunflower oil, sunflower oil, avocado oil, white flower oil (Meadowfoam), Emu oil, almond oil, eucalyptus oil, sesame oil, borage oil, cocoa butter, shea butter, etc.

作為血液循環促進劑可舉出柚子萃取物、山金車萃取物、辣椒酊、菖蒲萃取物、γ-谷維素等。Examples of the blood circulation promoting agent include grapefruit extract, arnica extract, capsicum annuum, calamus extract, and γ-oryzanol.

這些抗氧化劑、消炎劑、細胞賦活劑、紫外線防止劑、保濕劑、血液循環促進劑的各成分可組合一種或二種以上使用。Each of the components of the antioxidant, the anti-inflammatory agent, the cell activating agent, the ultraviolet ray preventing agent, the humectant, and the blood circulation promoting agent may be used alone or in combination of two or more.

又,含有本發明藥效劑之皮膚外用劑中除上述成分以外亦可添加一般使用於化妝料或醫藥部外品、外用醫藥品等之各種成分,即水、醇類、多元醇、油劑、界面活性劑、增黏劑、粉體、螯合劑、殺菌劑、酵素、pH調整劑、來自動植物.微生物之萃取物、香料等,以不損害本發明的效果之範圍內可適宜添加。Further, in addition to the above-mentioned components, the skin external preparation containing the medicinal agent of the present invention may be added to various components such as a cosmetic, a pharmaceutical external product, or an external pharmaceutical product, that is, water, an alcohol, a polyhydric alcohol, or an oil. , surfactants, tackifiers, powders, chelating agents, fungicides, enzymes, pH adjusters, to automatic plants. The extract, the fragrance, and the like of the microorganism can be appropriately added within a range that does not impair the effects of the present invention.

作為含有本發明的藥效劑之皮膚外用劑的添加形態例子,並無特別限定,例如可使用選自乳液、乳霜、化妝水、美容液、面膜、洗淨劑、彩妝化妝料、分散液、軟膏、液劑、氣溶膠、貼付劑等之任意形態的化妝料、或外用醫藥品等。The example of the form of addition of the external preparation for skin containing the medicinal agent of the present invention is not particularly limited, and for example, it can be selected from the group consisting of an emulsion, a cream, a lotion, a cosmetic liquid, a mask, a detergent, a make-up cosmetic, and a dispersion. Any type of cosmetic material such as an ointment, a liquid preparation, an aerosol, or a patch, or a pharmaceutical for external use.

〔實施例〕[Examples]

其次舉出製造例、試驗例、實施例對本發明作更具體説明,但本發明未受到這些之任何限定。Hereinafter, the present invention will be more specifically described by way of Production Examples, Test Examples, and Examples, but the present invention is not limited by these.

試驗例1:原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生量測定Test Example 1: Determination of profilaggrin and/or filaggrin production

作為白樺樹液(商品名「森之雫」、莎布有限公司製)的對照組,使用已知具有對於人類表皮細胞可提高分化促進作用之鈣溶液(氯化鈣溶液;以下僅稱為「鈣溶液」)),又,將僅以培養基生長者作為對照組,對於賦予原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生量之作用作調查。正常人類新生而表皮細胞經前培養後,欲防止培養基的浸透壓降低,對於培養基量將白樺樹液30v/v%、20v/v%、10v/v%、1v/v%等量藉由冷凍乾燥濃縮至1/10倍後添加。又,對於對照組添加至鈣溶液含於原先培養基中的鈣離子濃度至0.03mM/mL而使總量為1.5mM/mL,各培養基條件下進行一星期培養後,取出培養基,以PBS(-)洗淨一次後,回收表皮細胞。其此於回收的細胞中添加pH7.5的10mMTris-NaCl緩衝液(含有8M尿素、1v/v%Triton X-100、蛋白酶抑製劑雞尾酒(protease inhibitor cocktail)(調整EDTA、PMSF、NMF至最終濃度為1mM))後,以超音波於4℃下進行10分鐘處理使細胞破碎,經由離心分離取出細胞殘渣後進行蛋白質定量,欲使各樣品之蛋白質量為一定,於4~12%的聚丙烯醯胺凝膠中處理樣品,進行SDS-PAGE。電泳終了後於凝膠上將蛋白質轉錄於硝纖維素膜,藉由進行西方墨點法檢測出原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)。1次抗體為使用抗人類聚角微絲蛋白(filaggrin)來自老鼠之單株抗體(Biomedical Technologies公司製),2次抗體為使用抗老鼠過氧化酶標識IgG(Amersham公司製)藉由化學發光法進行檢測。經檢測之一段以螢光測定儀讀取,測定面積作為生成量,對於對照組的生成量比如表1所示。As a control group of the birch sap (trade name "Mori's", manufactured by Saab Co., Ltd.), a calcium solution (calcium chloride solution) which is known to have a differentiation promoting effect on human epidermal cells is used; The solution ")), in addition, only the growth of the medium was used as a control group, and the effect of imparting the amount of profilaggrin and/or filaggrin produced was investigated. After normal human newborn and epidermal cells are pre-cultured, it is necessary to prevent the permeation pressure of the medium from decreasing. For the amount of the medium, 30v/v%, 20v/v%, 10v/v%, 1v/v% of the birch sap is freeze-dried. Add to 1/10 times after concentration. Further, the control group was added to the calcium solution to have a calcium ion concentration of 0.03 mM/mL in the original medium to a total amount of 1.5 mM/mL, and after one week of culture under each medium condition, the medium was taken out, and PBS (- After washing once, the epidermal cells are recovered. This added 10 mM Tris-NaCl buffer (containing 8 M urea, 1 v/v% Triton X-100, protease inhibitor cocktail) (adjusted EDTA, PMSF, NMF to final concentration) at pH 7.5. After 1 mM)), the cells were disrupted by ultrasonic treatment at 4 ° C for 10 minutes, and the cell residue was taken out by centrifugation to quantify the protein. The amount of protein in each sample was determined to be 4 to 12% of polypropylene. Samples were processed in a gellanine gel and subjected to SDS-PAGE. After the end of the electrophoresis, the protein was transcribed on the nitrocellulose membrane, and the profilaggrin and/or filaggrin were detected by Western blotting. The primary antibody was a monoclonal antibody (manufactured by Biomedical Technologies) using mouse anti-human filaggrin (filaggrin), and the secondary antibody was labeled with IgG (Amersham) using anti-mouse peroxidase by chemiluminescence method. Test. One of the detected sections was read by a fluorometer, and the area was measured as the amount of production, and the amount of production for the control group is shown in Table 1.

由表1得知白樺樹液及鈣中具有同時促進原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)之作用。對於鈣白樺樹液為1v/v%濃度時顯示較為差,此以上之試驗濃度中則顯示較高之原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進作用。因此,白樺樹液與已知可促進原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生之鈣具有同等或較高原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進作用。It is known from Table 1 that the birch sap and calcium have the effect of simultaneously promoting profilaggrin and/or filaggrin. The calcium birch sap solution showed a poor concentration at 1 v/v%, and the above test concentrations showed higher profilaggrin and/or filaggrin production promoting effects. Therefore, the birch sap has the same or higher profilaggrin and/or poly angle as the calcium which is known to promote the production of profilaggrin and/or filaggrin. Filaggrin produces a promoting effect.

試驗例2:包殼蛋白(involucrin)產生量測定Test Example 2: Determination of the production amount of involucrin

作為白樺樹液之對照組,使用已知對人類表皮細胞具有較高分化促進作用之鈣溶液(氯化鈣溶液;以下僅記為「鈣溶液」),又將僅於培養基生長者作為對照組,對於賦予包殼蛋白(involucrin)產生量之作用做調查。正常人類新生兒表皮細胞經前培養後,欲防止培養基的浸透壓降低,添加對培養基量為30v/v%、20v/v%、10v/v%、1v/v%等量之經冷凍乾燥後濃縮至1/10倍的白樺樹液。又’對照組中添加鈣溶液至加上原先培養基中所含之鈣離子濃度0.03mM/mL使總量為1.5mM/mL,各培養基條件下進行一星期培養後,取出培養基以PBS(-)進行1次洗淨後回收表皮細胞。其次於回收細胞中添加pH7.5的10mMTris-NaCl緩衝液(含有8M尿素、1v/v%Triton X-100、蛋白酶抑製劑雞尾酒(protease inhibitor cocktail)(調整各EDTA、PMSF、NMF最終濃度為1mM))後,以超音波於4℃下進行10分鐘處理使細胞破碎,經離心分離取出細胞殘渣後進行蛋白質定量,欲使各樣品的蛋白質量為一定,於4~12%的聚丙烯醯胺凝膠進行樣品處理,進行SDS-PAGE。電泳終了後,將凝膠上的蛋白質轉錄於硝纖維素膜上,藉由進行西方墨點法檢測包殼蛋白(involucrin)。1次抗體為使用抗人類包殼蛋白(involucrin)來自老鼠的單株抗體(abcam公司製),2次抗體為使用抗老鼠過氧化酶標識IgG(Amersham公司製)藉由化學發光法進行檢測。經檢測的一段由螢光測定儀讀取,測定面積作為生成量,對於對照組的生成量比如表2所示。As a control group of the birch sap, a calcium solution (calcium chloride solution; hereinafter, simply referred to as "calcium solution") which is known to have a high differentiation promoting effect on human epidermal cells, and a growth medium only as a control group are used. The effect of imparting the amount of involucrin produced was investigated. After pre-culture of normal human neonatal epidermal cells, in order to prevent the hypotonic pressure of the culture medium from decreasing, the amount of the culture medium is 30v/v%, 20v/v%, 10v/v%, 1v/v%, etc. after lyophilization. Concentrated to 1/10 times the birch sap. In addition, the calcium solution was added to the control group to a concentration of 0.03 mM/mL of calcium ions contained in the original medium, and the total amount was 1.5 mM/mL. After one week of culture under each medium condition, the medium was taken out with PBS(-). The epidermal cells were recovered after one wash. Next, add 10 mM Tris-NaCl buffer (containing 8 M urea, 1 v/v% Triton X-100, protease inhibitor cocktail) (reducing the final concentration of each EDTA, PMSF, NMF to 1 mM) to the recovered cells. After), the cells were disrupted by ultrasonic treatment at 4 ° C for 10 minutes, and the cell residue was taken out by centrifugation to quantify the protein. To make the protein amount of each sample constant, 4 to 12% of polyacrylamide was used. The gel was subjected to sample treatment and subjected to SDS-PAGE. After the end of the electrophoresis, the protein on the gel was transcribed on the nitrocellulose membrane, and the involucrin was detected by Western blotting. The primary antibody was a monoclonal antibody (manufactured by Abcam) from mouse using anti-human crust protein (involucrin), and the secondary antibody was detected by chemiluminescence using an anti-mouse peroxidase-labeled IgG (manufactured by Amersham). The detected section was read by a fluorometer, and the area was measured as the amount of production. The amount of production for the control group is shown in Table 2.

由表2得知白樺樹液及鈣皆具有促進包殼蛋白(involucrin)產生之作用,對於鈣而言,白樺樹液具有較高包殼蛋白(involucrin)產生促進作用。因此,可確認白樺樹液必過去公知可促進包殼蛋白(involucrin)產生之鈣具有更優良的包殼蛋白(involucrin)產生促進作用。It is known from Table 2 that both birch sap and calcium have the effect of promoting the production of involucrin. For calcium, birch sap has a higher promoting effect on involucrin. Therefore, it has been confirmed that the birch sap must be known to promote the production of involucrin to have a more excellent involucrin-producing action.

試驗例3:膽固醇產生率的測定Test Example 3: Determination of cholesterol production rate

作為白樺樹液的對照組,使用已知對於人類表皮細胞可提高分化促進作用的鈣溶液(氯化鈣;以下僅記為「鈣溶液」),又僅以培養基下生長者作為對照組,對於賦予膽固醇產生之作用進行調查。將正常人類新生兒表皮細胞進行前培養後,欲防止培養基的浸透壓降低,添加對於培養基量為30v/v%、20v/v%、10v/v%、1v/v%各等量經冷凍乾燥濃縮為1/10倍之白樺液。又,於對照組中添加鈣溶液至加上原先培養基中所含之鈣離子濃度0.03mM/mL使其總量為1.5mM/mL,各培養基條件下進行一星期培養後,取出培養基再以PBS(-)進行1次洗淨後回收表皮細胞。於該人類表皮細胞中添加水、氯仿及甲醇各2.5mL並混合後,分離氯仿層並乾燥固體化。經萃取的脂質以HPTLC盤〔矽膠G60(20×10cm)Art.5641;Merck公司製〕,經混合溶媒(氯仿:甲醇:乙酸=190:9:1)進行2次展開。噴霧40%硫酸後以180度進行15分鐘加熱後使其發色,將TLC上的膽固醇以螢光測定儀進行比色定量。僅於培養基下生長的控制組作為1.0,算出膽固醇產生促進率,其結果如表3所示。As a control group of the birch sap, a calcium solution (calcium chloride; hereinafter, simply referred to as "calcium solution") which is known to enhance the differentiation promoting effect on human epidermal cells is used, and only the growth in the medium is used as a control group. The role of cholesterol production was investigated. After pre-culture of normal human neonatal epidermal cells, to prevent the hypotonic pressure of the medium from decreasing, the amount of the medium is 30v/v%, 20v/v%, 10v/v%, 1v/v%, and the same amount is freeze-dried. Concentrated to 1/10 times the white birch solution. Further, a calcium solution was added to the control group to add a calcium ion concentration of 0.03 mM/mL contained in the original medium to a total amount of 1.5 mM/mL, and after one week of culture under each medium condition, the medium was taken out and then PBS was taken. (-) The epidermal cells were recovered after one wash. To the human epidermal cells, 2.5 mL of water, chloroform and methanol were added and mixed, and then the chloroform layer was separated and solidified by drying. The extracted lipid was developed twice by a HPTLC disk [Glue G60 (20 × 10 cm) Art.5641; manufactured by Merck) through a mixed solvent (chloroform:methanol:acetic acid = 190:9:1). After spraying 40% sulfuric acid, it was heated at 180 degrees for 15 minutes, and then colored, and the cholesterol on TLC was colorimetrically quantified by a fluorescence meter. The control group grown only in the medium was counted as 1.0, and the cholesterol production promotion rate was calculated. The results are shown in Table 3.

由表3得知白樺樹液及鈣具有可促進膽固醇產生之作用,但對於鈣而言白樺樹液,於所有試驗濃度中顯示較高膽固醇產生促進作用。因此,白樺樹液比過去已知可促進膽固醇產生之鈣具有更高膽固醇產生促進作用。It is known from Table 3 that birch sap and calcium have an effect of promoting cholesterol production, but for calcium, birch sap liquid exhibits a higher cholesterol-promoting effect in all test concentrations. Therefore, the birch sap has a higher cholesterol-promoting effect than calcium which has been known to promote cholesterol production.

試驗例4:對於表皮角化細胞之角化促進作用Test Example 4: Keratinization promoting effect on epidermal keratinocytes

將正常人類新生兒皮膚表皮角化細胞(KURABO公司製)使用表皮角化細胞增殖用培養基(KURABO公司製),於直徑24多重格子盤上以6000個/格播種,於5%vol二氧化碳環境下,於37℃下進行24小時培養。培養後添加白樺樹液至最終濃度10%的例子(實施例1)、作為比較例為無添加的例子(比較例1)及作為陽性對象之添加氯化鈣至最終濃度為1.5mM的例子(比較例2)經3天培養。培養後,對各試料的細胞進行攝影,調查其形態。攝影的照片如圖1~3所示。又,攝影後以MTT(3-(4,5-Dimethyl-2-thiazolyl)-2,5-dipheny1-2H-tetrazoriumbromide)assay算出活細胞數。其結果如圖4所示。Normal human neonatal skin epidermal keratinocytes (manufactured by KURABO Co., Ltd.) were seeded at 6000 cells per cell on a diameter 24 multi-grid plate using a culture medium for epidermal keratinocyte proliferation (manufactured by KURABO Co., Ltd.) in a 5% vol carbon dioxide atmosphere. The culture was carried out at 37 ° C for 24 hours. An example in which a birch sap solution was added after culture to a final concentration of 10% (Example 1), a non-addition example (Comparative Example 1) as a comparative example, and an example of adding calcium chloride as a positive target to a final concentration of 1.5 mM (Comparative) Example 2) Cultured over 3 days. After the cultivation, the cells of each sample were photographed, and the morphology thereof was examined. Photographs of the photos are shown in Figures 1-3. Further, after photography, the number of viable cells was calculated by MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-dipheny1-2H-tetrazoriumbromide)assay. The result is shown in Figure 4.

如圖1~3所示,由各細胞形態,添加白樺樹液之例子(實施例1:圖1)及添加氯化鈣的例子(比較例2:圖3)與無添加這些成分之無添加比較例(比較例1:圖2)比較,發現細胞的肥大化與重層化,表示角質化被促進。細胞的角化為,皮膚新陳代謝速度越快,即代謝功能越高越被促進,故角化越被促進,更顯示越高細胞賦活作用。As shown in Figs. 1 to 3, an example in which a birch sap liquid was added in each cell form (Example 1: Fig. 1) and an example in which calcium chloride was added (Comparative Example 2: Fig. 3) were compared with no addition without adding these components. In the comparison of Comparative Example 1: FIG. 2, it was found that hypertrophy and re-stratification of cells indicated that keratinization was promoted. The keratinization of the cells is that the faster the skin's metabolism is faster, that is, the higher the metabolic function is promoted, the more the keratinization is promoted, and the higher the cell activation is.

圖4表示各試料的活細胞數的圖。會呼吸的一般細胞會因角化而停止呼吸,角質細胞若不剝離,培養細胞之氧消耗量變少。因此,藉由定量氧消耗量可算出活細胞數。活細胞數越少的試料表示角化更被促進。即,顯示較高細胞賦活作用。Fig. 4 is a graph showing the number of viable cells of each sample. The general cells that will breathe will stop breathing due to keratinization. If the keratinocytes are not peeled off, the oxygen consumption of the cultured cells will decrease. Therefore, the number of viable cells can be calculated by quantifying the amount of oxygen consumed. The sample with fewer viable cells indicates that keratinization is promoted. That is, it shows a higher cell activating effect.

由圖4的結果得知,添加各白樺樹液及公知角化劑之氯化鈣的試料(實施例1及比較例2)與無添加的試料(比較例1)相比,皆顯示活細胞數的更減少,具有同程度的角化促進作用。From the results of FIG. 4, it was found that the samples in which each of the birch sap and the calcium chloride of the known keratinizing agent were added (Example 1 and Comparative Example 2) showed the number of viable cells as compared with the sample without the addition (Comparative Example 1). It is more reduced and has the same degree of keratinization.

試驗例5:細胞增殖促進作用Test Example 5: Cell proliferation promoting effect

使用MTT assay法測定來自人類新生兒的線維芽細胞(NB1RGB)之細胞賦活率。MTT為進入活細胞中,與存在於粒線體內之酵素(NADH)反應而進行還原性開裂,生成於570nm具有吸收波的不溶性甲臘。已知這些生成的甲臘量與NADH量具有相關性,故可溶化藉由本法所生成的甲臘,經測定吸光度可測定間接性細胞能量代謝活性或細胞數。The cell viability of line-dimensional bud cells (NB1RGB) from human neonates was determined using the MTT assay. MTT is a reactive cell that undergoes reductive cleavage by reacting with an enzyme (NADH) present in the mitochondria to form an insoluble wax having an absorption wave at 570 nm. It is known that the amount of the produced wax is related to the amount of NADH, so that the indirect cellular energy metabolism activity or the number of cells can be measured by measuring the absorbance by the wax produced by the method.

由24格微盤取出適量培養基,種入來自人類新生兒之線維芽細胞,於37℃下二氧化碳濃度5%中靜置。另一方面,取代一般使用的純水以白樺樹液製造出依格MEM(日水公司製),以一般MEM培養基做成稀釋系列。第二天添加稀釋成白樺樹液含量為75%(實施例2)、100%(實施例3)之培養基。使用於一般培養基進行培養者作為對照組(比較例3)。培養第4天交換培養基,再次添加試料。第二天欲使MTT(SIGMA公司製)成為5mg/mL將所製作的溶液100 μL添加於各格。經4小時培養後,除去培養基,溶解使用異丙醇所生成的甲臘。使用微盤分析儀,以630nm作為參考值,測定570nm下的吸光度,算出對於對照之比率。其結果如圖5。An appropriate amount of the medium was taken out from a 24-cell microplate, and the bud cells from human neonatal neonates were seeded and allowed to stand at 5% CO2 concentration at 37 °C. On the other hand, Ig MEM (manufactured by Nishui Co., Ltd.) was produced from the birch sap liquid instead of the pure water used in general, and a dilution series was prepared in a general MEM medium. On the next day, the medium diluted to a bovine sap liquid content of 75% (Example 2) and 100% (Example 3) was added. The culture was carried out in a general culture medium as a control group (Comparative Example 3). The medium was exchanged on the fourth day of culture, and the sample was added again. On the next day, MTT (manufactured by SIGMA) was added to 5 mg/mL, and 100 μL of the prepared solution was added to each cell. After incubation for 4 hours, the medium was removed, and the wax formed by using isopropyl alcohol was dissolved. The absorbance at 570 nm was measured using a microdisk analyzer with 630 nm as a reference value, and the ratio to the control was calculated. The result is shown in Fig. 5.

由圖5所示結果得知,添加白樺樹液的試料以濃度依賴性下促進細胞增殖。由上述可確認白樺樹液中具有促進細胞增殖之細胞賦活效果。From the results shown in Fig. 5, it was found that the sample to which the birch sap was added promoted cell proliferation in a concentration-dependent manner. From the above, it was confirmed that the birch sap liquid has a cell activating effect which promotes cell proliferation.

以下舉例出含有本發明的種種藥效劑之各種形態的皮膚外用劑。且,實施例1-1~1-9為含有原聚角微絲蛋白(profilaggrin)或聚角微絲蛋白(filaggrin)產生促進劑之皮膚外用劑的例子,實施例2-1~2-9為含有本發明的包殼蛋白(involucrin)產生促進劑之皮膚外用劑的例子,實施例3-1~3-9為含有本發明的膽固醇產生促進劑之皮膚外用劑的例子,實施例4-1~4-9為含有本發明的細胞賦活劑之皮膚外用劑的例子。The skin external preparation containing various forms of the various pharmacodynamic agents of the present invention is exemplified below. Further, Examples 1-1 to 1-9 are examples of skin external preparations containing a profilaggrin or a filaggrin production promoter, and Examples 2-1 to 2-9 Examples of the external preparation for skin containing the promoter of the involucrin of the present invention, Examples 3-1 to 3-9 are examples of the external preparation for skin containing the cholesterol production promoter of the present invention, and Example 4 1 to 4-9 are examples of skin external preparations containing the cell activating agent of the present invention.

(實施例1-1:化妝水)(Example 1-1: lotion)

(製法)A.成分(1)~(10)經混合溶解。(Preparation method) A. Components (1) to (10) are dissolved by mixing.

B.成分(11)~(17)經混合溶解。B. Ingredients (11) to (17) are dissolved by mixing.

C. A中加入B後均勻混合得到化妝水。C. A is added to B and uniformly mixed to obtain a lotion.

(實施例1-2:乳霜)(Example 1-2: Cream)

*1 Eisai公司製*2丸善製藥公司製*3丸善製藥公司製*4常磐植物化學研究所公司製*5丸善製藥公司製*6丸善製藥公司製*7 TECHNO-BULL公司製*8丸善製藥公司製*9日本粉末藥品公司製*10莎布公司製(森之雫) *1 made by Eisai Co., Ltd. *2 Maruzen Pharmaceutical Co., Ltd. *3 Maruzen Pharmaceutical Co., Ltd. *4 Changji Institute of Plant Chemistry, Ltd. *5 Maruzen Pharmaceutical Co., Ltd. *6 Maruzen Pharmaceutical Co., Ltd. *7 TECHNO-BULL Co., Ltd. *8 Maruzen Pharmaceutical Co., Ltd. *9 Japan Powder Pharmaceutical Co., Ltd. *10 Saab company system (Sen Zhi)

(製法)A.成分(1)~(10)加熱混合後保持70℃。(Preparation method) A. The components (1) to (10) were kept at 70 ° C after heating and mixing.

B.成分(11)~(20)加熱混合後保持70℃。B. The components (11) to (20) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.冷卻後,C中加入成分(21)而得到乳霜。D. After cooling, component (21) is added to C to obtain a cream.

實施例1-1及實施例1-2皆使用於皮膚時,藉由原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進作用可對於肌膚本身產生天然保濕因子,故其為可持續性地維持肌膚的濕潤性的化妝水與乳霜。When both of Example 1-1 and Example 1-2 are used on the skin, the pro-aggregating effect of profilaggrin and/or filaggrin can produce a natural moisturizing factor for the skin itself. Therefore, it is a lotion and cream that can maintain the moisturization of the skin sustainably.

(實施例1-3:潔面乳霜)(Example 1-3: Cleansing cream)

(製法)A.成分(1)~(9)加熱混合後保持70℃。(Preparation method) A. The components (1) to (9) were kept at 70 ° C after heating and mixing.

B.成分(10)~(14)加熱混合後保持70℃。B. Ingredients (10) to (14) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.冷卻後,C中加入成分(15)後得到潔面乳霜。D. After cooling, add component (15) to C to get a cleansing cream.

實施例1-3使用於皮膚時,可藉由原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進作用,而使肌膚本身產生天然保濕因子,故其為可持續維持肌膚滑潤的潔面乳霜。When the 1-3 is used on the skin, it can be promoted by profilaggrin and/or filaggrin, so that the skin itself produces a natural moisturizing factor, so it is A cleansing cream that maintains a smooth skin.

(實施例1-4:乳液)(Example 1-4: Emulsion)

(製法)A.成分(14)~(23)加熱混合後保持70℃。(Preparation method) A. The components (14) to (23) were heated and mixed, and kept at 70 °C.

B.成分(1)~(13)加熱混合後保持70℃。B. The components (1) to (13) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.冷卻後,C中加入成分(24)、(25)、(26)後得到乳液。D. After cooling, ingredients (24), (25), and (26) are added to C to obtain an emulsion.

(實施例1-5:乳液)(Example 1-5: Emulsion)

(製法)A.成分(13)~(23)加熱混合後保持70℃。(Preparation method) A. The components (13) to (23) were heated and mixed, and kept at 70 °C.

B.成分(1)~(12)加熱混合後保持70℃。B. Ingredients (1) to (12) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.冷卻後,C中加入成分(24)、(25)得到乳液。D. After cooling, ingredients (24) and (25) are added to C to obtain an emulsion.

實施例1-4及實施例1-5皆使用於皮膚時,可藉由原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進作用使肌膚本身產生天然保濕因子,故其為可持續維持肌膚滑潤的乳液。When both of Examples 1-4 and Examples 1-5 are used on the skin, the skin itself can produce a natural moisturizing factor by promoting the profilaggrin and/or filaggrin. Therefore, it is an emulsion that can maintain smooth skin.

(實施例1-6:面膜)(Example 1-6: mask)

(製法)A.成分(1)~(7)混合後於70℃中加熱並溶解。(Preparation method) A. The components (1) to (7) were mixed and heated and dissolved at 70 °C.

B.成分(8)~(13)經混合溶解。B. Ingredients (8) to (13) are dissolved by mixing.

C.成分(14)~(16)經混合溶解。C. Ingredients (14) to (16) are dissolved by mixing.

D. A中加入B混合後,冷卻下加入C混合得到面膜。D. A was added to B and mixed, and C was added under cooling to obtain a mask.

實施例1-6使用於皮膚時,可藉由原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進作用使得肌膚本身產生天然保濕因子,故其為可持續維持肌膚滑潤的面膜。When used in the skin of Example 1-6, it can be promoted by the profilaggrin and/or filaggrin to cause the skin itself to produce a natural moisturizing factor, so it is sustainable. A smoothing mask for the skin.

(實施例1-7:乳霜粉底)(Examples 1-7: Cream Foundation)

(製法)A.成分(1)~(11)加熱混合後保持70℃。(Preparation method) A. The components (1) to (11) were kept at 70 ° C after heating and mixing.

B.成分(12)~(17)加熱混合後保持70℃。B. Ingredients (12) to (17) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.冷卻後,C中加入成分(18)得到乳霜粉底。D. After cooling, component (18) is added to C to obtain a cream foundation.

(實施例1-8:液態粉底)(Example 1-8: liquid foundation)

*1日本羅修公司製*2丸善製藥公司製*3 Sigma公司製*4莎布公司製(森之雫)*5丸善製藥公司製*6丸善製藥公司製 *1 Made by Japan Rosho Corporation *2 Maruzen Pharmaceutical Co., Ltd. *3 Sigma Co., Ltd. *4 Saab Co., Ltd. (Mori no Kyo) *5 Maruzen Pharmaceutical Co., Ltd. *6 Maruzen Pharmaceutical Co., Ltd.

(製法)A.成分(1)~(9)經混合溶解。(Preparation method) A. Components (1) to (9) are dissolved by mixing.

B. A中加入成分(17)~(22)後均勻混合,保持70℃。B. A is added to the ingredients (17) to (22) and uniformly mixed to maintain 70 °C.

C.成分(10)~(16)均勻地溶解,保持70℃。C. Components (10) to (16) were uniformly dissolved and kept at 70 °C.

D. C中添加B後,均勻地進行乳化。After adding B to D. C, the emulsion was uniformly performed.

E.使D冷卻後,添加成分(23)~(26)得到液態粉底。E. After cooling D, ingredients (23) to (26) are added to obtain a liquid foundation.

(實施例1-9:防曬乳液)(Examples 1-9: sunscreen lotion)

(製法)A.混合成分(1)~(10),保持70℃。(Preparation method) A. Mix the components (1) to (10) and keep at 70 °C.

B.混合成分(11)~(15),保持70℃。B. Mix the ingredients (11) to (15) and keep at 70 °C.

C. A中添加B後均勻地進行乳化。After adding B to C. A, it is uniformly emulsified.

D.冷卻後,C中加入成分(16)~(19)得到防曬乳液。D. After cooling, ingredients (16) to (19) are added to C to obtain a sunscreen lotion.

實施例1-7~9皆使用於皮膚時,可藉由原聚角微絲蛋白(profilaggrin)及/或聚角微絲蛋白(filaggrin)產生促進作用,使得肌膚本身產生天然保濕因子,故其為可持續維持肌膚滑潤的乳霜粉底、液態粉底及防曬乳液。When all of the examples 1-7 to 9 are used on the skin, the pro-aggregin and/or the filaggrin can promote the skin, so that the skin itself produces a natural moisturizing factor, so A cream foundation, liquid foundation and sunscreen lotion that maintains smooth skin.

(實施例2-1:化妝水)(Example 2-1: lotion)

*1 Eisai公司製*2丸善製藥公司製*3丸善製藥公司製*4味之素公司製*5丸善製藥公司製*6莎布公司製(森之雫) *1 made by Eisai Co., Ltd. *2 Maruzen Pharmaceutical Co., Ltd. *3 Maruzen Pharmaceutical Co., Ltd. *4 Ajinomoto Co., Ltd. *5 Maruzen Pharmaceutical Co., Ltd. *6 Saab Co., Ltd.

(製法)A.成分(1)~(10)經混合溶解。(Preparation method) A. Components (1) to (10) are dissolved by mixing.

B.成分(11)~(17)經混合溶解。B. Ingredients (11) to (17) are dissolved by mixing.

C. A中加入B後均勻混合得到化妝水。C. A is added to B and uniformly mixed to obtain a lotion.

(實施例2-2:乳霜)(Example 2-2: Cream)

(製法)A.成分(1)~(10)加熱混合後保持70℃。(Preparation method) A. The components (1) to (10) were kept at 70 ° C after heating and mixing.

B.成分(11)~(20)加熱混合後保持70℃。B. The components (11) to (20) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(21)後混合,得到乳霜。D. After cooling C, the component (21) is added and mixed to obtain a cream.

實施例2-1及實施例2-2皆使用於皮膚時,可藉由包殼蛋白(involucrin)產生促進作用使得肌膚表皮的阻礙功能正常化,其為肌膚表皮的水分保持改善效果、肌膚粗糙防止效果優良的化妝水與乳霜。When both of Example 2-1 and Example 2-2 are used on the skin, the inhibition function of the skin epidermis can be normalized by the promotion of involucrin, which improves the moisture retention of the skin epidermis and the skin is rough. Prevents excellent lotions and creams.

(實施例2-3:潔面乳霜)(Example 2-3: Cleansing cream)

*1日本界面活性劑公司製*2香榮興業公司製*3丸善製藥公司製*4丸善製藥公司製*5莎布公司製(森之雫) *1 Japanese interface active agent company system *2 Fragrant Industrial Co., Ltd. *3 Maruzen Pharmaceutical Co., Ltd. *4 Maruzen Pharmaceutical Co., Ltd. *5 Saab Co., Ltd.

(製法)A.成分(1)~(9)加熱混合後保持70℃。(Preparation method) A. The components (1) to (9) were kept at 70 ° C after heating and mixing.

B.成分(10)~(14)加熱混合後保持70℃。B. Ingredients (10) to (14) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.將C冷卻後,加入成分(15)後混合得到潔面乳霜。D. After cooling C, add component (15) and mix to obtain a cleansing cream.

實施例2-3使用皮膚時,可藉由包殼蛋白(involucrin)產生促進作用使得肌膚表皮的阻礙功能正常化,其為肌膚表皮的水分保持改善效果、肌膚粗糙防止效果等優良之潔面乳霜。In the case of the skin of Example 2-3, it is possible to normalize the barrier function of the epidermis by promoting the action of the involucrin, and it is an excellent cleansing cream for improving the moisture retention of the skin epidermis and preventing the skin from being rough. .

(實施例2-4:乳液)(Example 2-4: Emulsion)

*1日光化學公司製*2 Eisai公司製*3莎布公司製(森之雫)*4丸善製藥公司製*5丸善製藥公司製*6日光化學公司製*7協和發酵公司製 *1 manufactured by Nikko Chemical Co., Ltd. *2 manufactured by Eisai Co., Ltd. *3 Saab Co., Ltd. (Mori no Yu) *4 Maruzen Pharmaceutical Co., Ltd. *5 Maruzen Pharmaceutical Co., Ltd. *6 Nikko Chemical Co., Ltd. *7 Concord Fermentation Co., Ltd.

(製法)A.成分(14)~(24)加熱混合後保持70℃。(Preparation method) A. The components (14) to (24) were heated and mixed, and kept at 70 °C.

B.成分(1)~(13)加熱混合後保持70℃。B. The components (1) to (13) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.將C冷卻後,加入成分(25)、(26)混合得到乳液。D. After cooling C, the components (25) and (26) are added to obtain an emulsion.

(實施例2-5:乳液)(Example 2-5: Emulsion)

(製法)A.成分(13)~(23)加熱混合後保持70℃。(Preparation method) A. The components (13) to (23) were heated and mixed, and kept at 70 °C.

B.成分(1)~(12)加熱混合後保持70℃。B. Ingredients (1) to (12) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.將C冷卻後,加入成分(24)、(25)混合得到乳液。D. After cooling C, the components (24) and (25) are added to obtain an emulsion.

實施例2-4及實施例2-5皆使用於皮膚時,可藉由包殼蛋白(involucrin)產生促進作用而使肌膚表皮的阻礙功能正常化,其為肌膚表皮的水分保持改善效果、肌膚粗糙防止效果優良的乳液。When both of the examples 2-4 and the examples 2-5 are used on the skin, the effect of the involucrin can be promoted to normalize the barrier function of the epidermis of the skin, which is an improvement effect on the skin of the skin. An emulsion that is excellent in roughening prevention.

(實施例2-6:面膜)(Example 2-6: mask)

*1日本界面活性劑公司製*2丸善製藥公司製*3丸善製藥公司製*4純正藥品工業公司製*5莎布公司製(森之雫)*6日光化學公司製 *1 Japan surfactant company*2 Maruzen Pharmaceutical Co., Ltd.*3 Maruzen Pharmaceutical Co., Ltd.*4 Pure Pharmaceutical Industry Co., Ltd.*5 Saab Co., Ltd. (Senzhi) *6 Sunlight Chemical Co., Ltd.

(製法)A.成分(1)~(7)混合後於70℃中加熱並溶解。(Preparation method) A. The components (1) to (7) were mixed and heated and dissolved at 70 °C.

B.成分(8)~(12)經混合溶解。B. Ingredients (8) to (12) are dissolved by mixing.

C.成分(13)~(15)經混合溶解。C. Ingredients (13) to (15) are dissolved by mixing.

D. A中加入B混合並冷卻後,加入C混合得到面膜。D. A was added to B and mixed, and then cooled, and C was added to obtain a mask.

實施例2-6使用皮膚時,可藉由包殼蛋白(involucrin)產生促進作用使得肌膚表皮的阻礙功能正常化,其為肌表皮的水分保持改善效果、肌膚粗糙防止效果等優良的面膜。In the case of using the skin of Example 2-6, the barrier function of the skin epidermis can be normalized by the promotion of involucrin, and it is an excellent mask for improving the moisture retention of the muscle epidermis and the skin roughness preventing effect.

(實施例2-7:乳霜粉底)(Example 2-7: Cream Foundation)

(製法)A.成分(1)~(11)加熱混合後保持70℃。(Preparation method) A. The components (1) to (11) were kept at 70 ° C after heating and mixing.

B.成分(12)~(17)加熱混合後保持70℃。B. Ingredients (12) to (17) were kept at 70 ° C after heating and mixing.

C. A中加入B後混合,均勻地進行乳化。C. A was added to B and mixed, and emulsified uniformly.

D.將C冷卻後,加入成分(18)並混合得到乳霜粉底。D. After cooling C, the component (18) is added and mixed to obtain a cream foundation.

(實施例2-8:液態粉底)(Example 2-8: Liquid Foundation)

(製法)A.成分(1)~(9)經混合溶解。(Preparation method) A. Components (1) to (9) are dissolved by mixing.

B. A中加入成分(17)~(22)後均勻混合,保持70℃。B. A is added to the ingredients (17) to (22) and uniformly mixed to maintain 70 °C.

C.成分(10)~(16)均勻地溶解,保持70℃。C. Components (10) to (16) were uniformly dissolved and kept at 70 °C.

D. C中加入B後均勻地乳化。D. C was uniformly emulsified after adding B.

E.將D冷卻後,加入成分(23)~(26)混合,得到液態粉底。E. After cooling D, the components (23) to (26) are added to obtain a liquid foundation.

(實施例2-9:防曬乳液)(Examples 2-9: sunscreen lotion)

(製法)A.混合成分(1)~(10),保持70℃。(Preparation method) A. Mix the components (1) to (10) and keep at 70 °C.

B.混合成分(11)~(15),保持70℃。B. Mix the ingredients (11) to (15) and keep at 70 °C.

C. A中添加B,均勻地進行乳化。B is added to C. A, and emulsification is performed uniformly.

D.將C冷卻後,加入成分(16)~(19)混合得到防曬乳液。D. After cooling C, add ingredients (16) to (19) to obtain a sunscreen lotion.

實施例2-7~9皆使用於皮膚時,可藉由包殼蛋白(involucrin)產生促進作用使得肌膚表皮的阻礙功能正常化,其為肌膚表皮的水分保持改善效果、肌膚粗糙防止效果優良的乳霜粉底、液態粉底及防曬乳液。When all of the examples 2-7 to 9 are used on the skin, the effect of the involucrin can be promoted to normalize the barrier function of the epidermis of the skin, which is an effect of improving the moisture retention of the skin epidermis and preventing the skin from being rough. Cream foundation, liquid foundation and sunscreen lotion.

(實施例3-1:化妝水)(Example 3-1: lotion)

(製法)A.成分(1)~(11)經混合溶解。(Preparation method) A. Components (1) to (11) are dissolved by mixing.

B.成分(12)~(18)經混合溶解。B. Ingredients (12) to (18) are dissolved by mixing.

C. A中加入B後均勻混合得到化妝水。C. A is added to B and uniformly mixed to obtain a lotion.

實施例3-1具有水樣清爽的使用感,賦予肌膚濕潤感,其為可持續維持肌膚滑潤之化妝水。Example 3-1 has a refreshing feeling of use in water, and gives a moist feeling to the skin, and is a lotion which can maintain the smoothness of the skin.

(實施例3-2:乳霜)(Example 3-2: Cream)

*1 Eisai公司製*2丸善製藥公司製*3丸善製藥公司製*4常磐植物化學研究所公司製*5丸善製藥公司製*6丸善製藥公司製*7 TECHNO-BULL公司製*8丸善製藥公司製*9日本粉末藥品公司製*10莎布公司製(森之雫) *1 made by Eisai Co., Ltd. *2 Maruzen Pharmaceutical Co., Ltd. *3 Maruzen Pharmaceutical Co., Ltd. *4 Changji Institute of Plant Chemistry, Ltd. *5 Maruzen Pharmaceutical Co., Ltd. *6 Maruzen Pharmaceutical Co., Ltd. *7 TECHNO-BULL Co., Ltd. *8 Maruzen Pharmaceutical Co., Ltd. *9 Japan Powder Pharmaceutical Co., Ltd. *10 Saab company system (Sen Zhi)

(製法)A.成分(1)~(10)加熱混合後保持70℃。(Preparation method) A. The components (1) to (10) were kept at 70 ° C after heating and mixing.

B.成分(11)~(20)加熱混合後保持70℃。B. The components (11) to (20) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(21)並混合得到乳霜。D. After cooling C, the component (21) is added and mixed to obtain a cream.

實施例3-2具有滑潤且濃厚之使用感,賦予肌膚滑潤與保濕感,其為可持續維持肌膚滑潤的乳霜。Example 3-2 has a smooth and strong feeling of use, and gives the skin a smooth and moisturizing feeling, and is a cream which can maintain a smooth skin.

(實施例3-3:潔面乳霜)(Example 3-3: Cleansing Cream)

(製法)A.成分(1)~(9)加熱混合後保持70℃。(Preparation method) A. The components (1) to (9) were kept at 70 ° C after heating and mixing.

B.成分(10)~(14)加熱混合後保持70℃。B. Ingredients (10) to (14) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(15)並混合得到潔面乳霜。D. After cooling C, add component (15) and mix to obtain a cleansing cream.

實施例3-3具有輕薄滑潤的使用感,與彩妝的融合性良好,潔面後之可持續維持肌膚滑潤的潔面乳霜。Example 3-3 has a light and smooth feeling of use, and has good fusion with makeup, and a cleansing cream which can maintain a smooth skin after cleansing.

(實施例3-4:乳液)(Example 3-4: Emulsion)

(製法)A.成分(14)~(23)加熱混合後保持70℃。(Preparation method) A. The components (14) to (23) were heated and mixed, and kept at 70 °C.

B.成分(1)~(13)加熱混合後保持70℃。B. The components (1) to (13) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(24)、(25)、(26)並混合得到乳液。D. After cooling C, components (24), (25), and (26) are added and mixed to obtain an emulsion.

(實施例3-5:乳液)(Example 3-5: Emulsion)

*1 Sigma公司製*2莎布公司製(森之雫)*3 BIO-DELL公司製*4丸善製藥公司製*5丸善製藥公司製*6丸善製藥公司製 *1 Sigma company*2 Saab company system (Mori no 雫)*3 BIO-DELL company system*4 Maruzen Pharmaceutical Co., Ltd.*5 Maruzen Pharmaceutical Co., Ltd.*6 Maruzen Pharmaceutical Co., Ltd.

(製法)A.成分(13)~(22)加熱混合後保持70℃。(Preparation method) A. The components (13) to (22) were heated and mixed, and kept at 70 °C.

B.成分(1)~(12)加熱混合後保持70℃。B. Ingredients (1) to (12) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(23)、(24)、(25)並混合得到乳液。D. After cooling C, components (23), (24), and (25) are added and mixed to obtain an emulsion.

實施例3-4及實施例3-5具有滑潤且柔和的使用感,可賦予肌膚滑潤與適度保濕感,其為可持續維持肌膚滑潤的乳液。Examples 3-4 and Examples 3-5 have a smooth and soft feeling of use, which can impart a smooth and moderate moisturizing feeling to the skin, and are an emulsion which can maintain the smoothness of the skin.

(實施例3-6:面膜)(Example 3-6: mask)

(製法)A.成分(1)~(7)混合後於70℃中加熱並溶解。(Preparation method) A. The components (1) to (7) were mixed and heated and dissolved at 70 °C.

B.成分(8)~(12)經混合溶解。B. Ingredients (8) to (12) are dissolved by mixing.

C.成分(13)~(15)經混合溶解。C. Ingredients (13) to (15) are dissolved by mixing.

D.將B添加於A中,混合後冷卻,再混合C得到面膜。D. Add B to A, mix and cool, then mix C to obtain a mask.

實施例3-6為具有適度清涼感與緊張感,經面膜後的肌膚具有滑潤感與彈性感,其為可持續維持肌膚滑潤的面膜。Example 3-6 is a mask having a moderately cool feeling and a feeling of tension, and the skin after the mask has a smooth feeling and a feeling of elasticity, and is a mask which can maintain the smoothness of the skin.

(實施例3-7:乳霜粉底)(Example 3-7: Cream Foundation)

(製法)A.成分(1)~(11)加熱混合後保持70℃。(Preparation method) A. The components (1) to (11) were kept at 70 ° C after heating and mixing.

B.成分(12)~(17)加熱混合後保持70℃。B. Ingredients (12) to (17) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(18)後混合得到乳霜粉底。D. After cooling C, the component (18) is added and mixed to obtain a cream foundation.

(實施例3-8:液態粉底)(Example 3-8: Liquid Foundation)

(製法)A.成分(1)~(9)經加熱溶解。(Preparation method) A. Components (1) to (9) are dissolved by heating.

B. A中加入成分(16)~(21)並均勻混合,保持70℃。Add ingredients (16) to (21) to B. A and mix them evenly and keep at 70 °C.

C.成分(10)~(15)經加熱溶解,保持70℃。C. Ingredients (10) to (15) were dissolved by heating and kept at 70 °C.

D. C中添加B後均勻地進行乳化。After adding B to D. C, the emulsion was uniformly performed.

E.將D冷卻後,加入成分(22)~(26)並混合得到液態粉底。E. After cooling D, ingredients (22) to (26) are added and mixed to obtain a liquid foundation.

實施例3-7及實施例3-8具有濃厚且滑潤的使用感,可得到均勻美感的上妝效果,且為可持續維持肌膚滑潤的乳霜粉底及液態粉底。Each of Examples 3-7 and Examples 3-8 has a strong and smooth feeling of use, and can provide a uniform and aesthetically pleasing makeup effect, and is a cream foundation and a liquid foundation which can maintain the smoothness of the skin.

(實施例3-9:防曬乳液)(Examples 3-9: sunscreen lotion)

(製法)A.成分(1)~(10)加熱混合後保持70℃。(Preparation method) A. The components (1) to (10) were kept at 70 ° C after heating and mixing.

B.成分(11)~(15)加熱混合後保持70℃。B. Ingredients (11) to (15) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(16)~(19)並混合得到防曬乳液。D. After cooling C, ingredients (16) to (19) are added and mixed to obtain a sunscreen lotion.

實施例3-9具有無黏沾感且滑潤的使用感,可由紫外線保護肌膚的同時亦可持續維持肌膚滑潤的防曬乳液。Examples 3-9 have a non-sticky and smooth feeling of use, and can protect the skin from ultraviolet rays while maintaining a smooth sunscreen lotion.

(實施例4-1:化妝水)(Example 4-1: lotion)

(製法)A.成分(1)~(11)經混合溶解。(Preparation method) A. Components (1) to (11) are dissolved by mixing.

B.成分(12)~(18)經混合溶解。B. Ingredients (12) to (18) are dissolved by mixing.

C. A中加入B並均勻混合後得到化妝水。Add B to C. A and mix well to obtain a lotion.

實施例4-1具有水樣清爽的使用感,可得到無肌膚粗糙或肌膚黯淡等美麗肌膚之化妝水。Example 4-1 has a refreshing feeling of use in water, and it is possible to obtain a lotion that is free from rough skin or dull skin.

(實施例4-2:乳霜)(Example 4-2: Cream)

(製法)A.成分(1)~(10)加熱混合後保持70℃。(Preparation method) A. The components (1) to (10) were kept at 70 ° C after heating and mixing.

B.成分(11)~(20)加熱混合後保持70℃。B. The components (11) to (20) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(21)並混合得到乳霜。D. After cooling C, the component (21) is added and mixed to obtain a cream.

實施4-2為具有滑潤且濃厚的使用感,可得到無肌膚粗糙或肌膚黯淡之美麗肌膚的乳霜。The 4-2 is a cream that has a smooth and strong feeling of use and can be used for beautiful skin without rough skin or dull skin.

(實施例4-3:潔面乳霜)(Example 4-3: Cleansing Cream)

(製法)A.成分(1)~(9)加熱混合後保持70℃。(Preparation method) A. The components (1) to (9) were kept at 70 ° C after heating and mixing.

B.成分(10)~(14)加熱混合後保持70℃。B. Ingredients (10) to (14) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(15)並混合得到潔面乳霜。D. After cooling C, add component (15) and mix to obtain a cleansing cream.

實施例4-3具有輕薄且滑潤的使用感,與彩妝的融合性良好,具有優良的卸妝去污性,可得到無肌膚粗糙或肌膚黯淡的美麗肌膚之潔面乳霜。Example 4-3 has a light and smooth feeling of use, has good fusion with makeup, and has excellent cleansing and decontaminating properties, and can provide a cleansing cream for beautiful skin without rough skin or dull skin.

(實施例4-4:乳液)(Example 4-4: Emulsion)

(製法)A.成分(14)~(23)加熱混合後保持70℃。(Preparation method) A. The components (14) to (23) were heated and mixed, and kept at 70 °C.

B.成分(1)~(13)加熱混合後保持70℃。B. The components (1) to (13) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(24)、(25)、(26)並混合得到乳液。D. After cooling C, components (24), (25), and (26) are added and mixed to obtain an emulsion.

(實施例4-5:乳液)(Example 4-5: Emulsion)

(製法)A.成分(13)~(22)加熱混合後保持70℃。(Preparation method) A. The components (13) to (22) were heated and mixed, and kept at 70 °C.

B.成分(1)~(12)加熱混合後保持70℃。B. Ingredients (1) to (12) were kept at 70 ° C after heating and mixing.

C. A中加入B後均勻地進行乳化。C. A was added to B and emulsified uniformly.

D.將C冷卻後,加入成分(23)、(24)、(25)並混合得到乳液。D. After cooling C, components (23), (24), and (25) are added and mixed to obtain an emulsion.

實施例4-4及實施例4-5具有滑潤且柔和的使用感,可得到無肌膚粗糙或肌膚黯淡的美麗肌膚之乳液。In Example 4-4 and Example 4-5, a smooth and soft feeling of use was obtained, and an emulsion of beautiful skin without rough skin or dull skin was obtained.

(實施例4-6:面膜)(Example 4-6: Mask)

(製法)A.成分(1)~(7)混合後於70℃中加熱並溶解。(Preparation method) A. The components (1) to (7) were mixed and heated and dissolved at 70 °C.

B.成分(8)~(13)經混合溶解。B. Ingredients (8) to (13) are dissolved by mixing.

C.成分(14)~(16)經混合溶解。C. Ingredients (14) to (16) are dissolved by mixing.

D.將B添加於A,混合後冷卻,再加入C並混合得到面膜。D. Add B to A, mix and cool, then add C and mix to obtain a mask.

實施例4-6具有適度清涼感與緊張感,經面膜後之肌膚具有彈性,其為可得到無肌膚粗糙或肌膚黯淡的美麗肌膚之面膜。Example 4-6 has a moderate cooling feeling and a feeling of tension, and the skin after the mask has elasticity, and it is a mask for obtaining beautiful skin without rough skin or dull skin.

(實施例4-7:乳霜粉底)(Examples 4-7: Cream Foundation)

(製法)A.成分(1)~(11)加熱混合後保持70℃。(Preparation method) A. The components (1) to (11) were kept at 70 ° C after heating and mixing.

B.成分(12)~(17)加熱混合後保持70℃。B. Ingredients (12) to (17) were kept at 70 ° C after heating and mixing.

C. A中加入B後進行乳化。C. A was added to B and then emulsified.

D.將C冷卻後,加入成分(18)並混合得到乳霜粉底。D. After cooling C, the component (18) is added and mixed to obtain a cream foundation.

(實施例4-8:液態粉底)(Example 4-8: Liquid Foundation)

*1日本羅修公司製*2丸善製藥公司製*3 Sigma公司製*4莎布公司製(森之雫)*5丸善製藥公司製*6丸善製藥公司製 *1 Made by Japan Rosho Corporation *2 Maruzen Pharmaceutical Co., Ltd. *3 Sigma Co., Ltd. *4 Saab Co., Ltd. (Mori no Kyo) *5 Maruzen Pharmaceutical Co., Ltd. *6 Maruzen Pharmaceutical Co., Ltd.

(製法)A.成分(1)~(9)經混合溶解。(Preparation method) A. Components (1) to (9) are dissolved by mixing.

B. A中加入成分(20)~(25)並均勻混合,保持70℃。Add ingredients (20) to (25) to B. A and mix them evenly and keep at 70 °C.

C.成分(10)~(19)均勻地溶解,保持70℃。C. Components (10) to (19) were uniformly dissolved and kept at 70 °C.

D. C中加入B後進行乳化。D. C was added to B and then emulsified.

E.將D冷卻後,加入成分(26)並混合得到液態粉底。E. After cooling D, the component (26) is added and mixed to obtain a liquid foundation.

實施例4-7及4-8具有濃厚且滑潤的使用感,可得到均勻且美麗的上妝效果,其為可得到無肌膚粗糙或肌膚黯淡的美麗肌膚之乳霜粉底、液態粉底。Each of Examples 4-7 and 4-8 has a strong and smooth feeling of use, and a uniform and beautiful makeup effect can be obtained, and it is a cream foundation and a liquid foundation which can obtain beautiful skin without rough skin or dull skin.

(實施例4-9:防曬乳液)(Examples 4-9: sunscreen lotion)

(製法)A.混合成分(1)~(10),保持70℃。(Preparation method) A. Mix the components (1) to (10) and keep at 70 °C.

B.混合成分(11)~(15),保持70℃。B. Mix the ingredients (11) to (15) and keep at 70 °C.

C. A中添加B後均勻地進行乳化。After adding B to C. A, it is uniformly emulsified.

D.將C冷卻後,加入成分(16)~(19)並混合得到防曬乳液。D. After cooling C, ingredients (16) to (19) are added and mixed to obtain a sunscreen lotion.

實施例4-9具有無黏沾感且滑潤的使用感,可由紫外線保護肌膚的同時,可得到無肌膚粗糙或肌膚黯淡的美麗肌膚之防曬乳液。Examples 4-9 have a non-sticky feeling and a smooth feeling of use, and can protect the skin by ultraviolet rays, and can obtain a sunscreen lotion of a beautiful skin without rough skin or dull skin.

〔圖1〕表皮細胞角化促進作用試驗結果;添加白樺樹液10%時的細胞形態(實施例1)〔圖2〕表皮細胞角化促進作用試驗結果;無添加時的細胞形態(比較例1)〔圖3〕表皮細胞角化促進作用試驗結果;添加1.5mM氯化鈣時的細胞形態(比較例2)〔圖4〕表皮細胞角化促進作用試驗;藉由MTTassay之活細胞數比較〔圖5〕細胞增殖促進試驗結果[Fig. 1] Test results of epidermal cell keratinization promoting effect; cell morphology when 10% of birch sap solution was added (Example 1) [Fig. 2] Test results of epidermal keratinization promoting effect; cell morphology without addition (Comparative Example 1) [Fig. 3] Test results of epidermal cell keratinization promoting effect; cell morphology when 1.5 mM calcium chloride was added (Comparative Example 2) [Fig. 4] Epidermal keratinization promoting test; comparison of living cells by MTTassay [ Figure 5] Results of cell proliferation promotion test

Claims (2)

一種使用白樺樹液製造包殼蛋白(involucrin)產生促進劑之用途,其中白樺(Betula platyphylla Sukatchev var.japonica Hara)樹液為僅於早春至開花及開葉的1個月間,於樹幹上穿孔所溢出之樹液。 The use of a birch sap to produce an involucrin-producing agent, wherein the sap of Betula platyphylla Sukatchev var.japonica Hara is perforated on the trunk only during the first spring of flowering and opening of the leaves in early spring. sap. 一種使用白樺樹液製造人類表皮細胞之膽固醇產生促進劑之用途,其中白樺(Betula platyphylla Sukatchev var.iaponica Hara)樹液為僅於早春至開花及開葉的1個月間,於樹幹上穿孔所溢出之樹液。 The use of a birch sap to produce a cholesterol production promoter for human epidermal cells, wherein the sap of Betula platyphylla Sukatchev var.iaponica Hara is a sap overflowing through the trunk only during the first spring of flowering and opening of the leaves. .
TW096105565A 2006-02-16 2007-02-14 Birch sap as to the efficacy of their use for the active ingredient TWI445542B (en)

Applications Claiming Priority (4)

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JP2006038695A JP2007217325A (en) 2006-02-16 2006-02-16 Promoter for production of profillagrin and/or fillagrin
JP2006038696A JP5068952B2 (en) 2006-02-16 2006-02-16 Involucrin production promoter
JP2006047594A JP4938319B2 (en) 2006-02-24 2006-02-24 Cholesterol production promoter and skin external preparation containing the same
JP2006055906A JP4758252B2 (en) 2006-03-02 2006-03-02 Cell activator and skin external preparation containing the same

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