TWI743747B - External agent for hair growth and growth - Google Patents
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Abstract
本發明之課題在於提供一種安全性高,且具有優異生毛髮、育毛髮效果的育毛髮、生毛髮用外用劑以及脫毛症之治療劑。 解決手段在於,本發明之育毛髮、生毛髮外用劑或脫毛症治療劑含有經麴菌發酵之麴菌發酵物或該麴菌發酵物之萃取物。The subject of the present invention is to provide an external agent for hair growth and hair growth, and a therapeutic agent for hair loss, which is highly safe and has excellent hair growth and hair growth effects. The solution is that the external preparation for hair growth, hair growth, or hair loss treatment agent of the present invention contains a fermented koji mold or an extract of the fermentation product of koji mold.
Description
本發明關於一種含有麴菌發酵物或麴菌發酵物之萃取物的育毛髮、生毛髮用之皮膚外用劑及脫毛症之治療劑。The present invention relates to an external skin agent for hair growth and hair growth, and a therapeutic agent for hair loss that contains fermented koji fungus or extracts of fermented koji fungus.
最近,遭受所謂頭部掉毛髮、毛髮稀疏之脫毛症狀的男女是正在增加當中。為了改善這樣的症狀,已在進行關於生毛髮、毛髮循環之機制的研究,且正在進行促進生毛髮、抑制脫毛髮之有效成分的開發。現在,代表性者可舉米諾地爾(minoxidil,參考專利文獻1),且已開發出多數並且製品化出摻合有其之育毛髮、生毛髮用之皮膚外用劑等、毛髪用化妝品。Recently, the number of men and women suffering from so-called head hair loss and thinning hair loss symptoms is increasing. In order to improve such symptoms, research has been conducted on the mechanism of hair growth and hair circulation, and the development of effective ingredients that promote hair growth and inhibit hair loss is underway. At present, a representative one can include minoxidil (minoxidil, refer to Patent Document 1), and a large number of them have been developed and formulated into cosmetics for hair, such as external skin preparations for hair growth and hair growth, and the like incorporated therein.
另一方面,近年來,日本酒、燒酒、甘酒、味噌、醬油等利用麴的日本傳統麴發酵食品的價值再度受到認知而使麴的人氣高漲。所謂的麴,是將米、米糠、麥或豆等進行蒸煮並使麴菌繁殖者,例如,使麴菌在米上繁殖者稱為米麴。已知麴菌具有生產可製造發酵食品之多種酵素的機能,然不拘於此一領域,麴菌所具新機能之研究及奠基於此之用途開發因本案發明人而有所進展。專利文獻2報告指出,使穀物等以麴菌發酵所得之飼料會促進動物的成長;專利文獻3報告指出,在茶葉上接種麴菌並培養所得之麴發酵組成物具有抗氧化活性。On the other hand, in recent years, the value of traditional Japanese koji fermented foods using koji, such as Japanese sake, shochu, sweet sake, miso, and soy sauce, has been recognized again, and the popularity of koji has increased. The so-called koji is a person who steams rice, rice bran, wheat, or beans, and causes the koji bacteria to multiply. For example, the koji bacteria that multiply on the rice are called rice koji. It is known that Koji has the function of producing a variety of enzymes that can produce fermented food. However, it is not limited to this field. The research on new functions of Koji and the development of applications based on it have progressed due to the inventors of this case.
先行技術文獻 專利文獻 專利文獻1:日本特許第2733980號 專利文獻2:日本特許第6111416號 專利文獻3:國際公開第2015/119036號Advanced technical literature Patent literature Patent Document 1: Japanese Patent No. 2733980 Patent Document 2: Japanese Patent No. 6111416 Patent Document 3: International Publication No. 2015/119036
發明欲解決之課題
然而,專利文獻1所記載之生毛髮成分之米諾地爾原本是用來作為高血壓治療藥的成分,因此據報導會有產生血壓降低等副作用的可能性。因此,期待提供一種具有更高安全性、優異生毛髮、育毛髮效果的新材料。The problem to be solved by the invention
However, Minoxidil, which is a hair growth ingredient described in
又,專利文獻2及專利文獻3分別記載到以麴菌使穀物、茶葉發酵獲得的麴發酵物,然並未探討將該麴發酵物用於治療脫毛症、促進育毛髮、生毛髮,且其有效性不明。In addition,
因此,本發明是有鑑於上述要點而成者,且其目的在於提供一種具有高度安全性、優異生毛髮、育毛髮效果的育毛髮、生毛髮用外用劑及脫毛症之治療劑。Therefore, the present invention was made in view of the above-mentioned points, and its object is to provide an external agent for hair growth and hair growth, and a therapeutic agent for hair loss that has high safety, excellent hair growth and hair growth effects.
用以解決課題之手段 為了解決上述問題,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑含有經麴菌發酵之麴菌發酵物或該麴菌發物之萃取物。Means to solve the problem In order to solve the above-mentioned problems, the external agent for hair growth or hair growth or the treatment agent for hair loss of the present invention contains a fermented aspergillus fermented by aspergillus or an extract of the aspergillus hair.
該麴菌發酵物及該麴菌發酵物之萃取物具有優異的生毛髮促進作用,進一步,對所謂雄性型脫髮症(male pattern hair loss、androgenetic alopecia)、老年脫髮症之脫毛症的治療、預防或改善亦有用。The fermented koji fungus and the extract of the fermented koji fungus have an excellent hair growth promoting effect, and further, the treatment and prevention of the so-called male pattern hair loss (androgenetic alopecia) and the alopecia of senile alopecia Or improvement is also useful.
又,上述麴菌發酵物亦宜以源自茶葉、穀物或豆類之原料作為發酵原料。藉此,可選擇出較適合的作為麴菌發酵物的原料。In addition, the above-mentioned fermented koji fungus is also suitable to use raw materials derived from tea, grains or beans as fermentation raw materials. In this way, a more suitable raw material for the fermented koji fungus can be selected.
又,上述之麴菌亦宜為黑麴菌或白麴菌。藉此,可選擇出合適的麴菌,且能夠由該麴菌獲得本發明之育毛髮、生毛髮用外用劑或脫毛症之治療劑之活性成分的麴菌發酵物。In addition, the above-mentioned aspergillus is also preferably aspergillus nigricans or aspergillus spp. Thereby, a suitable koji mold can be selected, and the koji mold fermentation product of the active ingredient of the external agent for hair growth and hair growth or the therapeutic agent for hair loss of the present invention can be obtained from the koji mold.
又,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑進一步宜含有乳酸菌。藉此,當生產麴菌發酵物時,可促進麴菌之增殖而可穩定的進行利用麴菌之發酵,而可獲得具有高活性的麴菌發酵物。In addition, the external preparation for hair growth or hair growth or the therapeutic agent for hair loss of the present invention further preferably contains lactic acid bacteria. As a result, when the koji fungus fermented product is produced, the proliferation of koji fungus can be promoted, and the fermentation using the koji fungus can be stably performed, and a koji fungus fermentation product with high activity can be obtained.
又,本發明中之麴菌發酵物之萃取物亦宜為麴菌發酵物之水或含水醇萃取物。藉此,可容易且低成本的獲得具有優異生毛髮促進效果之育毛髮、生毛髮用外用劑或脫毛症治療劑。In addition, the extract of the fermented koji fungus in the present invention is preferably a water or water-containing alcohol extract of the fermented koji fungus. Thereby, an external agent for hair growth, hair growth, or hair loss treatment agent with excellent hair growth promoting effect can be easily obtained at low cost.
又,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑的製造方法具有以下步驟:對源自茶葉、穀物或豆類之發酵原料接種麴菌之步驟,及以該麴菌使發酵原料發酵而獲得麴菌發酵物之步驟。藉此,可獲得具有優異生毛髮促進作用,且對所謂雄性型脫髮症、老年脫髮症之脫毛症的治療、預防或改善亦有用的育毛髮、生毛髮用外用劑或脫毛症治療劑。In addition, the method for producing an external agent for hair growth and hair growth or a hair loss treatment agent of the present invention has the following steps: a step of inoculating fermented raw materials derived from tea, grains or beans with koji bacteria, and using the koji bacteria to ferment the raw materials The step of obtaining fermented koji bacteria by fermentation. Thereby, it is possible to obtain an external agent for hair growth or hair growth or a therapeutic agent for hair loss, which has an excellent hair growth promoting effect and is useful for the treatment, prevention, or improvement of so-called androgenetic alopecia and senile alopecia.
又,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑的製造方法具有以下步驟:對源自茶葉、穀物或豆類之發酵原料接種麴菌與乳酸菌之步驟,及以該麴菌與該乳酸菌使前述發酵原料發酵而獲得麴菌發酵物之步驟。藉此,可獲得具有優異生毛髮促進作用之育毛髮、生毛髮用外用劑或脫毛症治療劑。進一步,藉由將乳酸菌與麴菌共培養,可促進麴菌之增殖而可穩定的進行利用麴菌之發酵,故可獲得穩定且具有高活性的麴菌發酵物,且亦可縮短發酵時間。In addition, the method for producing an external agent for hair growth and hair growth or a depilatory treatment agent of the present invention has the following steps: a step of inoculating fermented raw materials derived from tea, grains or beans with koji bacteria and lactic acid bacteria, and using the koji bacteria with The step of fermenting the aforementioned fermentation raw material by the lactic acid bacteria to obtain a fermented koji mold. Thereby, it is possible to obtain an external agent for hair growth or hair growth or a therapeutic agent for hair loss which has an excellent hair growth promoting effect. Furthermore, by co-cultivating lactic acid bacteria and koji bacteria, the proliferation of koji bacteria can be promoted and the fermentation using the koji bacteria can be stably performed, so a stable and highly active fermentation product of koji bacteria can be obtained, and the fermentation time can also be shortened.
又,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑的製造方法中,上述麴菌亦宜為曲黑麴菌或白麴菌。藉此,可選擇出合適的麴菌,且能夠由該麴菌獲得本發明之育毛髮、生毛髮用外用劑或脫毛症之治療劑之活性成分的麴菌發酵物。In addition, in the method for producing the external preparation for hair growth or hair growth or the therapeutic agent for hair loss of the present invention, the above-mentioned aspergillus is also preferably aspergillus or white aspergillus. Thereby, a suitable koji mold can be selected, and the koji mold fermentation product of the active ingredient of the external agent for hair growth and hair growth or the therapeutic agent for hair loss of the present invention can be obtained from the koji mold.
又,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑的製造方法,亦宜具有以下步驟:將獲得之麴菌發酵物以水或含水醇進行萃取以獲得麴菌發酵物之萃取物之步驟。藉此,可容易且低成本的獲得具有優異生毛髮促進效果之育毛髮、生毛髮用外用劑或脫毛症治療劑。In addition, the method for manufacturing the external preparation for hair growth and hair growth or the treatment agent for depilation of the present invention preferably has the following steps: extracting the obtained fermented koji fungus with water or water-containing alcohol to obtain the extraction of the fermented koji fungus The steps of things. Thereby, an external agent for hair growth, hair growth, or hair loss treatment agent with excellent hair growth promoting effect can be easily obtained at low cost.
發明效果 根據本發明,可提供一種具有如下優異效果之育毛髮、生毛髮用外用劑或脫毛症治療劑。 (1)在促進育毛髮及生毛髮上是優異的。 (2)可以治療、預防或改善脫毛症。 (3)由於是以利用在食品製造上亦可使用之麴菌的發酵物作為有效成分,因此安全性高。 (4)僅將麴菌發酵物利用水或含水醇來萃取,便可獲得洗劑型的育毛髮、生毛髮用外用劑或脫毛症治療劑,因此容易製造。Invention effect According to the present invention, it is possible to provide an external agent for hair growth or hair growth or a therapeutic agent for hair loss which has the following excellent effects. (1) It is excellent in promoting hair growth and hair growth. (2) It can treat, prevent or improve alopecia. (3) Since it uses the fermented product of koji fungus that can also be used in food manufacturing as an active ingredient, it is highly safe. (4) Only by extracting the fermented koji fungus with water or water-containing alcohol, a lotion-type external agent for hair growth and hair growth or a hair loss treatment agent can be obtained, so it is easy to manufacture.
用以實施發明之形態The form used to implement the invention
首先,參照圖1,說明本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑所含有的經麴菌發酵之麴菌發酵物P1的製造方法。First, referring to FIG. 1, the method for producing the fermented koji fungus P1 contained in the external preparation for hair growth and hair growth or the treatment agent for hair loss according to the present invention will be described.
如圖1所示,有關本發明實施形態之麴菌發酵物P1的製造方法是由以下步驟概略構成:準備發酵原料的步驟S0、對發酵原料添加水並使其吸水的步驟S1、蒸煮發酵原料的步驟S2、對經蒸煮之發酵原料接種麴菌的步驟S3、進行發酵的步驟S4。As shown in Fig. 1, the method for producing the fermented koji fungus P1 according to the embodiment of the present invention is roughly composed of the following steps: step S0 of preparing fermentation raw materials, step S0 of adding water to the fermentation raw materials and making them absorb water, and cooking the fermentation raw materials Step S2, step S3 of inoculating the fermented raw materials with koji, and step S4 of fermenting.
(準備發酵原料) 首先,針對圖1所示之準備發酵原料的步驟S0進行說明。本發明中之發酵原料可選擇源自植物的原料,且可使用植物的葉、莖、根、花及果實作為發酵原料。其中,較佳可使用茶葉、穀物或豆類,且以使用茶葉作為發酵原料特別為佳。穀物廣泛包含米、玉米、小麥、大麥、黑麥、燕麥、高粱、蕎麥及其他雜穀類。又,茶葉不只包含茶的葉子,亦包含從茶樹採取之莖、枝等。作為本發明麴菌發酵物之原料所使用的茶葉可適宜使用直接採取後狀態之生的茶葉,然亦可為採取後立刻經加熱處理之茶葉、採取後以茶葉所含之氧化酵素使茶葉氧化發酵的烏龍茶或紅茶、還有後發酵茶。又,亦可使用將該等綠茶、烏龍茶或紅茶等泡過後的茶渣。又,為了提高之後的蒸煮處理、麴菌之培養效率,茶葉、茶莖亦宜可破碎至某程度使其不會過大。(Prepare fermentation ingredients) First, the step S0 of preparing fermentation raw materials shown in FIG. 1 will be described. The fermentation raw materials in the present invention can be selected from plant-derived raw materials, and plant leaves, stems, roots, flowers and fruits can be used as fermentation raw materials. Among them, it is preferable to use tea leaves, grains or beans, and it is particularly preferable to use tea leaves as a fermentation raw material. Cereals include rice, corn, wheat, barley, rye, oats, sorghum, buckwheat and other miscellaneous cereals. In addition, tea leaves include not only tea leaves, but also stems and branches taken from tea plants. The tea used as the raw material of the fermented koji fungus of the present invention can be suitably used as raw tea in the state after being taken directly, but it can also be tea that is heated immediately after being taken, and oxidized by the oxidizing enzyme contained in the tea after being taken. Fermented oolong tea or black tea, and post-fermented tea. Moreover, the tea dregs after brewing these green tea, oolong tea, black tea, etc. can also be used. In addition, in order to improve the efficiency of subsequent steaming and koji culturing, the tea leaves and tea stems should also be broken to a certain extent so that they are not too large.
(吸水處理) 接著,針對吸水處理步驟S1進行說明。本步驟可對發酵原料添加水,或進行使發酵原料浸漬在水中使其吸水的處理。吸水量,例如,在使用茶葉作為發酵原料時,可調整使茶葉的水分成為20~60%、且宜成為30~50%。(Water absorption treatment) Next, the water absorption treatment step S1 will be described. In this step, water can be added to the fermentation raw material, or the fermentation raw material can be immersed in water to make it absorb water. The amount of water absorption, for example, when using tea leaves as a fermentation raw material, can be adjusted so that the moisture content of the tea leaves becomes 20-60%, and preferably 30-50%.
(蒸煮處理) 接著,針對蒸煮處理步驟S2進行說明。將已在上述步驟中吸水的發酵原料置入蒸煮器並蓋上蓋子,透過加熱蒸煮器使水蒸氣直接對發酵原料進行加熱。蒸煮處理的時間宜為30分~120分左右,且以45分~90分左右為佳,以60分左右更佳。透過進行本步驟,可將原料中的雜菌進行殺菌,且在之後的發酵步驟中,麴菌可作為優勢種進行發酵。又,在發酵原料方面使用生的茶葉時,透過進行本步驟,在將茶葉中之雜菌進行殺菌之同時,可去活化茶葉所含之氧化酵素,因此在之後的步驟中,可使麴菌在茶葉上有效率的繁殖。結束蒸煮的原料從蒸煮器取出,在台上均等展開,使之冷卻到30~40℃左右。藉此,將可把麴菌接種到發酵原料上。(Steaming treatment) Next, the retort treatment step S2 will be described. Put the fermented raw materials that have absorbed water in the above steps into the digester and cover the lid, and heat the fermented raw materials directly by steam through the heating digester. The cooking time is preferably about 30 minutes to 120 minutes, preferably about 45 minutes to 90 minutes, and more preferably about 60 minutes. By performing this step, the miscellaneous bacteria in the raw materials can be sterilized, and in the subsequent fermentation step, the koji bacteria can be used as the dominant species for fermentation. In addition, when raw tea leaves are used as raw materials for fermentation, this step can sterilize the miscellaneous bacteria in the tea and at the same time deactivate the oxidase contained in the tea. Therefore, in the subsequent steps, the koji bacteria can be used. Efficient reproduction on tea leaves. The raw materials that have finished cooking are taken out from the digester, spread out evenly on the table, and cooled to about 30-40°C. In this way, the fermented raw materials can be inoculated with koji bacteria.
(接種麴菌) 接著,針對將麴菌接種(播種)到發酵原料的步驟S3進行說明。本步驟是對經上述蒸煮步驟且已冷卻的發酵原料接種麴菌。本發明中的麴菌主要是在製造麴發酵食品時所使用的微生物,具體而言,可舉黑麴菌、白麴菌或黃麴菌。其中,所謂黑麴菌是說在製造沖繩之泡盛、鹿兒島之芋燒酒等蒸餾酒所使用,且會形成黑色或黑褐色分生胞子(無性胞子的一種)之麴菌屬之黴菌的一群組。具體上並無特別限定,可舉河內黑麴菌(Aspergillus awamori var. kawachii)、琉球麴菌、泡盛麴菌、Aspergillus saitoi、Aspergillus inuii、宇佐美麴菌(Aspergillus Usami)、Aspergillus Auresu等。又,所謂白麴菌是說會形成白黃土色分生胞子之麴菌屬之黴菌的一群組,具體可舉例如河內白麴菌(Aspergillus kawachii)。進一步,所謂黃麴菌是說會形成黃色或黃綠色分生胞子之麴菌屬之黴菌的一群組,且主要是可使用在製造清酒、味噌、醬油等的微生物。具體上並無特別限定,可舉米麴菌(Aspergillus oryzae)、醬油麴菌(Aspergillus sojae)等。本發明中,從優異之生毛髮促進效果的觀點,及因麴菌本身會產生檸檬酸故具有pH調整作用的觀點來看,宜使用黑麴菌或白麴菌。其中,較適合使用黑麴菌之河內黑麴菌(Aspergillus awamori var. kawachii)、琉球麴菌(Aspergillus luchuensis)或Aspergillus inuii,白麴菌之河內白麴菌(Aspergillus kawachii),及其等之組合,且特別宜為河內黑麴菌(Aspergillus awamori var. kawachii)。該等麴菌之接種可藉由,例如,於置入經滅菌之袋中的發酵原料中混合、攪拌麴菌來進行。麴菌是以接種其胞子為宜,且對發酵原料1g(乾燥重量),麴菌之胞子是宜添加成50萬個以上、且較佳是成為100萬個以上來進行接種。例如,在種麴1g所含之胞子數為20億個的情況,對發酵原料1kg添加種麴0.5g(0.05重量%)左右即可。麴菌接種到發酵原料後,宜充分攪拌使麴菌分散到原料整體。(Inoculation of Koji bacteria) Next, the step S3 of inoculating (seeding) the koji bacteria to the fermentation raw material will be described. This step is to inoculate the fermented raw materials that have undergone the above-mentioned cooking step and have been cooled with koji bacteria. The koji bacteria in the present invention are mainly microorganisms used in the production of koji fermented foods, and specifically, black koji fungi, white koji fungi, or yellow koji fungi can be mentioned. Among them, the so-called black koji mold refers to a type of mold of the koji mold that is used in the production of distilled liquors such as Awamori in Okinawa and taro shochu from Kagoshima, and forms black or dark brown conidia (a type of asexual spores). Group. It is not particularly limited, and examples include Aspergillus awamori var. kawachii, Aspergillus awamori var. In addition, the so-called white koji mold refers to a group of molds of the genus Koji that form white yellow soil-colored conidia, specifically, for example, Aspergillus kawachii (Aspergillus kawachii). Furthermore, the so-called yellow koji mold refers to a group of molds of the genus Koji that form yellow or yellow-green conidia, and are mainly microorganisms that can be used in the production of sake, miso, and soy sauce. It is not specifically limited in particular, Aspergillus oryzae, Aspergillus sojae, etc. are mentioned. In the present invention, from the viewpoint of the excellent hair growth promoting effect, and the viewpoint that the koji mold itself produces citric acid and therefore has a pH adjustment effect, it is preferable to use the black koji mold or the white koji mold. Among them, it is more suitable to use Aspergillus awamori var. kawachii, Aspergillus luchuensis or Aspergillus inuii, Aspergillus kawachii, and combinations thereof , And particularly suitable for Aspergillus awamori var. kawachii. The inoculation of these koji bacteria can be carried out, for example, by mixing and stirring the koji bacteria in the fermentation raw materials placed in the sterilized bag. Koji bacteria is preferably inoculated with its spores, and 1 g (dry weight) of the fermentation raw material, the spores of Koji bacteria are preferably added to 500,000 or more, and preferably 1 million or more for inoculation. For example, when the number of spores contained in 1 g of seed koji is 2 billion, about 0.5 g (0.05% by weight) of seed koji may be added to 1 kg of fermentation raw material. After the koji bacteria are inoculated into the fermentation raw materials, it is advisable to stir thoroughly to disperse the koji bacteria to the whole raw material.
又,在麴菌之接種步驟S3中,亦宜進一步接種乳酸菌,使麴菌與乳酸菌共培養。透過共培養麴菌與乳酸菌,可促進麴菌之增殖並進行穩定的發酵處理,且可縮短發酵時間,同時,該等接種的菌會成為優勢種,因此可抑制其他雜菌等的繁殖。乳酸菌可使用在乳酸菌發酵食品所使用的乳酸菌,可舉例如乾酪乳桿菌(Lactobacillus casei)、發酵乳桿菌(Lactobacillus fermentum)或保加利亞乳桿菌(Lactobacillus bulgaricus)等乳桿菌屬,比菲德氏菌(Bifidobacterium bifidum)等雙歧桿菌,乳酸乳球菌(Lactococcus lactis)等乳球菌屬,糞腸球菌(Enterococcus faecium)等腸球菌屬。接種之乳酸菌是使用先進行預培養者,且對發酵原料1kg,菌體是添加0.1重量%左右即可。以麴菌與乳酸菌發酵所得之麴菌發酵物中,除了含有麴菌及乳酸菌生產之多種酵素之外,亦含有麴菌、其胞子及乳酸菌。In addition, in the inoculation step S3 of koji bacteria, it is also suitable to further inoculate lactic acid bacteria to co-culture the koji bacteria and lactic acid bacteria. By co-cultivating koji bacteria and lactic acid bacteria, the proliferation of koji bacteria can be promoted and stable fermentation treatment can be carried out, and the fermentation time can be shortened. At the same time, the inoculated bacteria will become the dominant species, so the growth of other miscellaneous bacteria can be inhibited. Lactic acid bacteria can be used in lactic acid bacteria fermented foods. Examples include Lactobacillus casei, Lactobacillus fermentum, or Lactobacillus bulgaricus. bifidum) and other Bifidobacterium, Lactococcus lactis and other Lactococcus genera, Enterococcus faecium and other Enterococcus genera. The lactic acid bacteria to be inoculated are those that have been pre-cultured first, and about 0.1% by weight of the bacteria is added to 1kg of the fermentation raw material. The fermented koji bacteria obtained by fermenting with koji bacteria and lactic acid bacteria contains not only the various enzymes produced by koji bacteria and lactic acid bacteria, but also koji bacteria, its spores and lactic acid bacteria.
(發酵) 接著,針對將已接種到發酵原料之麴菌進行培養並發酵的步驟S4進行說明。本步驟是在已接種麴菌的原料中使麴菌繁殖。首先,將已添加麴菌之發酵原料放入已保持在30℃上下之培養室。隨著時間的經過而進行發酵,茶葉等發酵原料的溫度會上昇,然而,麴菌一般而言若超過40℃會變得難以增殖,因此進行通風降低原料的溫度,並調整通風量使發酵原料的溫度維持在30℃~42℃、且宜為30℃~40℃。此外,發酵溫度可因應發酵所使用之麴菌種類來適宜調整。具體而言,麴菌方面選擇黑麴菌或白麴菌時,作為一例,從培養開始起12~30小時,藉由通風將茶葉等發酵原料之溫度調整成35℃~40℃。之後,同樣的進行通風量之調整等,將溫度調整成稍低的30℃~35℃,並將從培養開始起合計培養1~4日、且宜為36~72小時、以40~60小時左右為佳的時間點,設定為麴菌發酵物P1的完成。(Fermentation) Next, step S4 of cultivating and fermenting the koji bacteria inoculated into the fermentation raw material will be described. This step is to make the koji bacteria multiply in the raw material that has been inoculated with the koji bacteria. First, put the fermented raw materials of koji bacteria into the culture room that has been kept at around 30°C. As time elapses, the temperature of fermentation raw materials such as tea leaves will rise. However, it is generally difficult for koji bacteria to proliferate if it exceeds 40°C. Therefore, ventilation is performed to lower the temperature of the raw materials, and the amount of ventilation is adjusted to make the raw materials fermented. The temperature is maintained at 30℃~42℃, and preferably 30℃~40℃. In addition, the fermentation temperature can be appropriately adjusted according to the type of koji bacteria used in the fermentation. Specifically, when selecting black koji or white koji for koji bacteria, as an example, 12 to 30 hours from the start of culture, the temperature of fermentation raw materials such as tea leaves is adjusted to 35°C to 40°C by ventilation. After that, adjust the ventilation rate in the same way, adjust the temperature to a slightly lower 30°C to 35°C, and incubate for a total of 1 to 4 days, preferably 36 to 72 hours, and 40 to 60 hours from the start of the culture. The right time is the best time point, and it is set as the completion of the koji fungus fermentation product P1.
再者,在上述麴菌發酵物P1之製造步驟S1~S4時,原料之清洗、吸水、蒸煮、麴菌之接種及發酵(製麴)亦可藉由能在同一裝置內進行之機械(例如,滾筒式自動製麴裝置等)來進行。Furthermore, in the manufacturing steps S1 to S4 of the above-mentioned koji fermentation product P1, the washing of raw materials, water absorption, steaming, inoculation and fermentation (koji production) of koji bacteria can also be carried out by a machine that can be carried out in the same device (for example, , Drum-type automatic koji making device, etc.).
(麴菌發酵物) 獲得之麴菌發酵物P1,是麴菌已經在發酵原料繁殖之所謂的「麴」。該麴菌發酵物P1在育毛髮及生毛髮促進方面優異,而可治療、預防或改善脫毛症。利用上述步驟獲得之麴菌發酵物P1是呈含有一定水分之狀態,然透過使其自然乾燥、或使其低溫除濕乾燥,可去除水分。又,亦可將已去除水分之麴菌發酵物P1進行粉碎做成粉末狀、或做成顆粒狀。透過降低麴菌發酵物P1之水分含量,可抑制麴菌發酵物P1中之麴菌、乳酸菌之活動、生育,進一步可藉由冷藏保存以長期保存麴菌發酵物P1。即便在暫時去除水分者上,亦可有效保持作為麴菌發酵物P1之育毛髮及生毛髮促進機能。(Koji fungus fermentation product) The obtained koji fermentation product P1 is the so-called "Koji" in which the koji bacteria have grown in the fermentation raw material. The fermented koji fungus P1 is excellent in hair growth and hair growth promotion, and can treat, prevent or ameliorate alopecia. The fermented product P1 of koji bacteria obtained by the above steps is in a state of containing a certain amount of moisture, and the moisture can be removed by drying it naturally or dehumidifying and drying it at a low temperature. In addition, the fermented koji fungus P1 from which moisture has been removed may be crushed into a powder form or into a granular form. By reducing the moisture content of the koji fermentation product P1, the activity and growth of the koji bacteria and lactic acid bacteria in the koji fermentation product P1 can be inhibited, and furthermore, the koji bacteria fermentation product P1 can be stored for a long time by refrigerating storage. Even when moisture is temporarily removed, it can effectively maintain the hair growth and hair growth promotion function as the fermented koji fungus P1.
接著,將針對本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑中所含有之麴菌發酵物之萃取物P2的製造方法進行說明。如圖1所示,有關本發明實施型態之麴菌發酵物之萃取物P2的製造方法,是由下述步驟概略構成:對以上述步驟S1~S4所獲得之麴菌發酵物P1添加萃取溶劑,並進行萃取步驟S5。Next, the method for producing the extract P2 of the fermented koji fungus contained in the external preparation for hair growth and hair growth or the hair loss treatment agent of the present invention will be described. As shown in Figure 1, the method for producing the extract P2 of the fermented koji fungus related to the embodiment of the present invention is roughly composed of the following steps: adding an extraction to the fermented koji fungus P1 obtained in the above steps S1 to S4 Solvent, and proceed to extraction step S5.
(萃取) 以下,將詳述萃取步驟S5。在該萃取步驟S5中,對麴菌發酵物P1添加萃取溶劑並實施萃取處理,獲得麴菌發酵物之萃取物P2。作為萃取溶劑,只要是可從麴菌發酵物P1萃取出具有生毛髮促進作用者即可,而無特別限定,然從萃取效率及操作容易性的觀點來看,宜為水或含水醇。其中,用於含水醇之醇可舉例如乙醇、異丙醇、1,3-丁二醇、丙二醇、甘油等,且亦可使用該等之一種或組合兩種以上使用。進一步,作為上述乙醇,亦可使用藉由發酵醇所獲得之發酵液。具體而言,可使用釀造酒、蒸餾其所獲得之蒸餾酒,其中,較佳可使用蒸餾酒。蒸餾酒可舉源自米、麥、玉米等穀物原料者,源自塊根或塊莖類者,源自甘蔗者,源自椰棗的果實(date)者等。其中,源自椰棗果實之蒸餾酒含有皮膚刺激性特別少且對肌膚溫和之成分的棕櫚酸乙酯,因此可選擇作為製造外用劑的較佳萃取溶劑。含水醇之醇濃度宜為1~50v/v%,且以3~30v/v%為佳、以5~15v/v%特別為佳。又,當萃取溶劑使用水時,宜使用經高壓蒸氣滅菌、過濾滅菌處理等滅菌處理的水。藉由使用經滅菌處理的水,可防止雜菌之混入,而且可穩定的萃取出麴菌發酵物P1中所含有之以各種蛋白質、酵素為首之有用成分。此外,萃取溶劑中,在不妨礙從麴菌發酵物P1中萃取有用成分的範圍內,除了上述水或含水醇,還可含有pH調整劑、防腐劑、萃取助劑等其他成分。(extraction) Hereinafter, the extraction step S5 will be described in detail. In the extraction step S5, an extraction solvent is added to the koji fungus fermentation product P1 and an extraction process is performed to obtain an extract P2 of the koji fungus fermentation product. The extraction solvent is not particularly limited as long as it can extract the hair growth promoting effect from the koji fermentation product P1. However, from the viewpoint of extraction efficiency and ease of operation, water or a hydrous alcohol is preferable. Among them, the alcohol used for the water-containing alcohol includes, for example, ethanol, isopropanol, 1,3-butanediol, propylene glycol, glycerin, etc., and one of these or a combination of two or more of them can also be used. Furthermore, as the above-mentioned ethanol, a fermentation broth obtained by fermenting alcohol can also be used. Specifically, distilled alcohol obtained by brewing and distilling the alcohol can be used, and among them, distilled alcohol can be preferably used. Examples of distilled spirits include those derived from grain raw materials such as rice, wheat, and corn, those derived from roots or tubers, those derived from sugar cane, and those derived from the fruit (date) of the date palm. Among them, the distilled wine derived from the date palm fruit contains ethyl palmitate, which is a component that is particularly less irritating to the skin and gentle on the skin, so it can be selected as a preferable extraction solvent for the manufacture of external preparations. The alcohol concentration of the water-containing alcohol is preferably 1-50v/v%, preferably 3-30v/v%, and particularly preferably 5-15v/v%. In addition, when water is used as the extraction solvent, it is preferable to use water that has been sterilized by high-pressure steam sterilization, filter sterilization, or the like. By using sterilized water, the mixing of miscellaneous bacteria can be prevented, and useful components including various proteins and enzymes contained in the fermented koji fungus P1 can be stably extracted. In addition, the extraction solvent may contain other components such as pH adjusters, preservatives, extraction aids, etc., in addition to the above-mentioned water or water-containing alcohol, within a range that does not hinder the extraction of useful components from the koji fermentation product P1.
作為麴菌發酵物P1之萃取方法,宜將麴菌發酵物P1添加到萃取溶劑中使之浸漬,並進行萃取,且相對於萃取溶劑1L、將麴菌發酵物P1做成含水率小於10%之乾燥物的情況下,宜添加其1g~300g,且以添加5g~150g為佳、以10g~100g特別為佳。又,作為萃取條件,為了維持麴菌發酵物P1中所含有的各種蛋白質、酵素之活性,萃取溫度宜設在0~30℃左右,且以設在2~20℃為佳、以設在4~10℃特別為佳。又,萃取時間宜設在2小時~5日左右,且以設在6小時~3日左右為佳、以設在12小時~1.5日左右特別為佳。As the extraction method of the koji fungus fermentation product P1, it is advisable to add the koji fungus fermentation product P1 to the extraction solvent to immerse it, and then perform extraction, and the water content of the koji fungus fermentation product P1 is less than 10% relative to 1L of the extraction solvent. In the case of dry matter, it is advisable to add 1g~300g, and 5g~150g is preferred, and 10g~100g is especially preferred. In addition, as extraction conditions, in order to maintain the activity of various proteins and enzymes contained in the koji fermentation product P1, the extraction temperature is preferably set at about 0-30°C, preferably at 2-20°C, and at 4 ~10°C is particularly preferred. Moreover, the extraction time is preferably set at about 2 hours to 5 days, and is preferably set at about 6 hours to 3 days, and particularly preferably set at about 12 hours to 1.5 days.
在上述萃取處理之後,透過傾析、離心分離或過濾等將殘渣除去,可獲得麴菌發酵物之萃取物P2。作為本發明之麴菌發酵物之萃取物P2,除了以萃取步驟S5所獲得之麴菌發酵物之萃取物P2本身之外,還包含將萃取物P2利用減壓濃縮等濃縮處理做成濃縮液者;對麴菌發酵物之萃取物P2實施冷凍乾燥處理等乾燥處理,做成固替狀、粉末狀者等。After the above-mentioned extraction treatment, the residue is removed by decantation, centrifugal separation or filtration, etc., and the extract P2 of the fermented koji fungus can be obtained. As the extract P2 of the fermented koji fungus of the present invention, in addition to the extract P2 of the fermented koji fungus obtained in the extraction step S5, the extract P2 is made into a concentrated liquid by a concentration treatment such as reduced pressure concentration. Those: The extract P2 of the fermented koji bacteria is subjected to drying treatments such as freeze-drying treatment to make it into a solid replacement form or a powder form.
本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑,是含有上述經麴菌發酵之麴菌發酵物P1或麴菌發酵物之萃取物P2作為有效成分者;且具有育毛髮作用、生毛髮促進作用,治療、預防或改善雄性型脫髮症、老年脫髮症等各種脱毛症之作用。故,含有本發明麴菌發酵物或麴菌發酵物之萃取物的外用劑可使用作為用以預防、治療或改善所謂毛髮稀疏、掉毛髮之症狀、脫毛症的醫藥品、醫藥部外品及毛髪用化妝品。本發明的之外用劑是以利用在食品製造上亦可使用之麴菌的發酵物作為有效成分,因此安全性高,可不問年齡、性別、慢性病等而安心且簡便的使用。The external agent for hair growth or hair growth or the therapeutic agent for hair loss of the present invention contains the above-mentioned aspergillus fermented aspergillus fermented product P1 or the aspergillus fermented extract P2 as an effective ingredient; and has a hair-growing effect, Hair growth promotion, treatment, prevention or amelioration of various types of hair loss such as male alopecia and senile alopecia. Therefore, the external preparation containing the fermented koji fungus of the present invention or the extract of the fermented koji fungus of the present invention can be used as medicines, quasi-drugs, and quasi-medicinal products for preventing, treating, or ameliorating the symptoms of so-called thinning of hair, hair loss, and alopecia. Hair hair with cosmetics. The external preparation of the present invention uses the fermented product of koji bacterium that can also be used in food manufacturing as an active ingredient, so it is highly safe and can be used safely and easily regardless of age, sex, chronic disease, etc.
本發明育毛髮、生毛髮用外用劑或脫毛症治療劑中之麴菌發酵物P1的含量,宜為0.1重量%~20重量%左右,且以0.3重量%~10重量%左右為佳、以1重量%~5重量%左右特別為佳。又,針對麴菌發酵物之萃取物P2,可將經萃取步驟S5獲得之麴菌發酵物之萃取物(萃取液)P2本身應用為育毛髮、生毛髮用外用劑或脫毛症治療劑;從萃取效率及生毛髮效果的觀點來看,宜為相對於萃取溶劑100mL,添加0.1g~30g被萃取物之麴菌發酵物P1(乾燥物)所獲得之萃取液,且以添加0.5g~15g麴菌發酵物P1(乾燥物)所獲得之萃取液為佳、以添加1g~10g麴菌發酵物P1(乾燥物)所獲得之萃取液特別為佳。此外,麴菌發酵物之萃取物(萃取液)P2本身未應用為育毛髮、生毛髮用外用劑等時,每100mL外用劑,宜摻合0.1g~30g之將麴菌發酵物P1(乾燥物)萃取所得之萃取物P2,且以摻合0.5g~15g之將麴菌發酵物P1(乾燥物)萃取所得之萃取物P2為佳,以摻合1g~10g之將麴菌發酵物P1(乾燥物)萃取所得之萃取物P2特別為佳。The content of the fermented koji fungus P1 in the external preparation for hair growth and hair growth of the present invention or the therapeutic agent for hair loss is preferably about 0.1% to 20% by weight, and preferably about 0.3% to 10% by weight. About 1% by weight to 5% by weight is particularly preferred. In addition, for the extract P2 of the fermented koji fungus, the extract P2 of the fermented koji fungus obtained in the extraction step S5 (extract solution) itself can be used as an external agent for hair growth, hair growth, or a hair loss treatment agent; From the viewpoint of extraction efficiency and hair growth effect, it is preferable to add 0.1g~30g of the fermented aspergillus fermented product P1 (dried) to the extraction solvent 100mL, and add 0.5g~15g The extract obtained from the fermented koji fungus P1 (dried substance) is preferable, and the extract obtained by adding 1 g~10g of the fermented koji fungus P1 (dried substance) is particularly preferable. In addition, when the extract (extract solution) P2 of the fermented koji fungus itself is not used as an external agent for hair growth and hair growth, etc., it is advisable to mix 0.1g~30g of the fermented koji fungus P1 (dry物) The extract P2 obtained by extraction, and preferably the extract P2 obtained by blending 0.5g~15g of the fermented koji fungus P1 (dried), and preferably the extract P2 obtained by blending 1g~10g of the fermented koji fungus P1 (Dry) The extract P2 obtained by extraction is particularly preferred.
由於本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑的使用量會根據改善之目標或治療效果、症狀、患處之大小、投予方法、年齡或外用製劑之劑型等而變化,故無法一概規定,然通常1日之使用量宜為0.1~20mL(g),且以0.3~10mL(g)為佳、以0.5~5mL(g)特別為佳。Since the amount of the external agent for hair growth and hair growth or the therapeutic agent for alopecia of the present invention varies according to the improvement goal or therapeutic effect, symptoms, size of the affected area, administration method, age, or dosage form of the external preparation, etc., It cannot be stipulated in general, but the daily dosage is usually 0.1~20mL(g), and 0.3~10mL(g) is preferred, and 0.5~5mL(g) is particularly preferred.
考慮到對皮膚的安全性,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑之pH宜調整至4.0~6.5。在不損害本發明效果之範圍內,可使用通常摻合在外用劑中之適當的酸或鹼來調整外用劑之pH。如此pH調節劑的例子可舉鹽酸、乳酸、磷酸、酒石酸、蘋果酸或葡萄糖酸等酸,二異丙醇胺、三異丙醇胺、氫氧化鈉、檸檬酸鈉或精胺酸等鹼,且可使用1種,亦可組合2種以上使用。此外,在獲得麴菌發酵物時,在使用了產生檸檬酸的黑麴菌、白麴菌作為麴菌的情況,由於麴菌發酵物中含有檸檬酸,因此可容易做成弱酸性的製劑。In consideration of the safety to the skin, the pH of the external preparation for hair growth and growth or the treatment agent for hair loss of the present invention should be adjusted to 4.0-6.5. In the range that does not impair the effects of the present invention, an appropriate acid or base usually blended in an external agent can be used to adjust the pH of the external agent. Examples of such pH adjusting agents include acids such as hydrochloric acid, lactic acid, phosphoric acid, tartaric acid, malic acid or gluconic acid, alkalis such as diisopropanolamine, triisopropanolamine, sodium hydroxide, sodium citrate or arginine, Furthermore, one type can be used, or two or more types can be used in combination. In addition, when the koji fungus fermented product is obtained, when the koji fungus or white koji fungus that produces citric acid is used as the koji fungus, since the koji fungus fermentation product contains citric acid, it can be easily made into a weakly acidic preparation.
又,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑,可在不損害本發明效果之範圍內,摻合通常在外用劑中可使用的各種成分。可舉例如血管擴張劑、血液循環促進劑、界面活性劑、抗組織胺劑、抗炎症劑、增稠劑、維生素類、胺基酸類、保濕劑、防腐劑、抗菌劑、香料及色素等。又,本發明之外用劑中亦可摻合除麴菌發酵物P1及麴菌發酵物之萃取物P2之外的育毛髮、生毛髮成分。其他育毛髮、生毛髮成分可舉例如米諾地爾、腺苷或當藥(swertia herb)精華等。In addition, the external agent for hair growth and growth or the therapeutic agent for hair loss of the present invention can be blended with various components that are generally used in external agents within a range that does not impair the effects of the present invention. Examples include vasodilators, blood circulation promoters, surfactants, antihistamines, anti-inflammatory agents, thickeners, vitamins, amino acids, moisturizers, preservatives, antibacterial agents, fragrances, and pigments. In addition, the external agent of the present invention may also incorporate hair-growing and hair-growth ingredients other than the fermented koji mold P1 and the extract P2 of the fermented koji mold. Other hair-growing and hair-growing ingredients include minoxidil, adenosine, or swertia herb essence.
進一步,本發明之育毛髮、生毛髮用外用劑或脫毛症治療劑可做成通常能應用在頭皮、皮膚的劑形,且可透過以往慣用之方法應用於各種外用劑之劑型,可舉例如化妝水(tonic)、洗劑(lotion)等液劑,氣霧劑、凝膠劑、軟膏、乳霜(cream)劑或乳液劑。又,亦可應用在洗髮劑、肥皂或潤髮劑等。Furthermore, the external preparation for hair growth and growth or the treatment agent for hair loss of the present invention can be made into a dosage form that can be applied to the scalp and skin, and can be applied to various external preparations by conventional methods, such as Liquid agents such as tonic and lotion, aerosol, gel, ointment, cream or lotion. In addition, it can also be applied to shampoos, soaps, or conditioners.
接著,將本發明以實施例進行更詳細的說明,然本發明並不會因該等實施例而受到限定。Next, the present invention will be described in more detail with examples, but the present invention is not limited by these examples.
[實施例] [實施例1] 1.調製麴菌發酵物 在本實施例,是使用生茶葉作為發酵原料。使茶葉的水分成為約50%來添加水並實施吸水處理,之後,置入加壓式蒸氣釜並進行蒸煮處理。蒸煮處理之條件是設為115℃且60分鐘,並且隔著1次冷卻進行2次蒸煮處理。之後,在將茶葉冷卻至30℃後,於茶葉中添加河內黑麴菌(Aspergillus awamori var. kawachii)之種麴(胞子數20億個/種麴1g)使其相對於發酵原料之茶葉重量為0.1重量%、添加乳酸菌(Lactobacillus casei)使其為0.1重量%,進行混合,並製麴3日。此外,製麴溫度在添加種麴起24小時是透過通風來調整使茶葉溫度成為35℃~40℃,之後的48小時,同樣的進行通風量之調整等,使茶葉的溫度調整成稍低的30℃~35℃。之後,對製麴3天而得之麴菌發酵物實施乾燥處理,成為含水率8%,將其粉碎以獲得粉末狀麴菌發酵物。[Example] [Example 1] 1. Preparation of fermented koji bacteria In this embodiment, raw tea leaves are used as the fermentation raw material. The water content of the tea leaves is about 50%, water is added, and water absorption is performed. After that, the tea leaves are placed in a pressurized steam kettle and steamed. The conditions of the retort treatment were set at 115°C for 60 minutes, and the retort treatment was performed twice with one cooling. Then, after cooling the tea leaves to 30°C, the seed koji of Aspergillus awamori var. kawachii (Aspergillus awamori var. kawachii) (the number of spores is 2 billion/the seed koji 1g) is added to the tea so that the weight of the tea leaves relative to the fermentation raw material is 0.1% by weight, Lactobacillus casei was added to 0.1% by weight, mixed, and koji was prepared for 3 days. In addition, the temperature of koji making is adjusted by ventilation for 24 hours after adding seed koji so that the temperature of the tea leaves becomes 35°C to 40°C. For the next 48 hours, the same ventilation rate is adjusted to adjust the temperature of the tea leaves to a slightly lower temperature. 30℃~35℃. After that, the koji mold fermented product obtained from koji preparation for 3 days was dried to have a moisture content of 8%, and it was pulverized to obtain a powdery koji mold fermentation product.
[實施例2] 2.調製麴菌發酵物萃取液(1) 在本實施例是使用水作為萃取溶劑。對100mL的滅菌水,以2g的比例添加以實施例1獲得之麴菌發酵物(乾燥後之粉末狀者)。將其靜置在4℃條件下的冷藏庫中,並進行20小時萃取處理。收集上清液,獲得在以下實施例中使用的麴菌發酵物萃取液(1)。[Example 2] 2. Preparing the extract of the fermented koji fungus (1) In this embodiment, water is used as the extraction solvent. To 100 mL of sterilized water, the fermented koji mold obtained in Example 1 (powder after drying) was added at a ratio of 2 g. It was placed in a refrigerator at 4°C and subjected to extraction treatment for 20 hours. The supernatant was collected to obtain the koji fungus fermentation product extract (1) used in the following examples.
[實施例3] 3.調製麴菌發酵物萃取液(2) 在本實施例是使用含醇之萃取溶劑以獲得麴菌發酵物萃取液(2)。首先,對以椰棗果實為原料之蒸餾酒(商品名:隼人之涙,錦灘酒造株式會社製品,酒精度數30)添加經135℃高壓蒸氣滅菌之水,調製乙醇濃度為10v/v%的萃取溶劑。對該萃取溶劑100m中,以2g的比例添加在實施例1獲得之麴菌發酵物。將其靜置在4℃條件下的冷藏庫中,並進行20小時萃取處理。收集上清液,獲得在以下實施例中使用的麴菌發酵物萃取液(2)。[Example 3] 3. Preparing the extract of the fermented koji fungus (2) In this example, an alcohol-containing extraction solvent was used to obtain the koji fungus fermentation product extract (2). First, add water sterilized by autoclaving at 135°C to a distilled liquor made from date palm fruits (trade name: Hayato no Ryu, product of Kintan Shuzo Co., Ltd., alcohol content 30) to prepare a water with an ethanol concentration of 10v/v% Extraction solvent. The koji fungus fermented product obtained in Example 1 was added to 100 m of the extraction solvent at a ratio of 2 g. It was placed in a refrigerator at 4°C and subjected to extraction treatment for 20 hours. The supernatant was collected to obtain the koji fungus fermentation product extract (2) used in the following examples.
[實施例4] 4.麴菌發酵物萃取液(1)所致小鼠的生毛促進 將出生後8周齡之C3H/HeN雌小鼠,各分配4隻於以下表1所示2組中。以理髮器(hair clipper)將小鼠的背部毛剃毛,並且1日1次、持續30日對剃毛部塗布試料溶液。塗布量設為0.15mL/日。如以下表1所示,對照組的試料液中是使用在實施例2製造麴菌發酵物萃取液(1)時用作為萃取溶劑的滅菌水,試驗組的試料液中則是使用以實施例2獲得之麴菌發酵物萃取液(1)。[Example 4] 4. Promotion of hair growth in mice caused by the fermented extract of koji fungus (1) Four C3H/HeN female mice at the age of 8 weeks after birth were assigned to the two groups shown in Table 1 below. The back hair of the mouse was shaved with a hair clipper, and the sample solution was applied to the shaved part once a day for 30 days. The coating amount was set to 0.15 mL/day. As shown in Table 1 below, the sample solution of the control group used the sterilized water used as the extraction solvent in the preparation of the koji fungus fermentation extract (1) in Example 2, and the sample solution of the test group used the example 2 The obtained extract of the fermented koji fungus (1).
[表1]
在進行第30次塗布的隔日、從試驗開始第31日,以肉眼觀察每隻小鼠之剃毛部之體毛濃色度及體毛伸長度,並依據下述表2所示基準求出生毛分數。此外,生毛分數之評價,是讓無法區別對照組小鼠與試驗組小鼠的人來進行,以排除實驗者造成的偏誤。關於對照組及試驗組之生毛分數,是利用顯著水準5%、曼-惠特尼之U檢定來評價顯著差異。結果顯示在圖2及以下表3中。On the next day after the 30th coating, and on the 31st day from the start of the test, the body hair density and body hair elongation of the shaved part of each mouse were observed with the naked eye, and the birth was determined according to the standards shown in Table 2 below. Gross score. In addition, the evaluation of the hair growth score is performed by people who cannot distinguish between the control group and the test group, so as to eliminate the bias caused by the experimenter. Regarding the hair growth scores of the control group and the test group, the significant difference was evaluated using the significance level of 5% and the Mann-Whitney U test. The results are shown in Figure 2 and Table 3 below.
[表2]
[表3]
根據該等結果表明,塗布有麴菌發酵物萃取液(1)之試驗組小鼠,相較於對照組小鼠,在生毛狀態及毛的伸長方面明顯優異。又,比較兩者之p值為p<0.05,顯示出有顯著性。Based on these results, it was shown that the mice of the test group coated with the fermented koji fungus extract (1) were significantly better than the mice of the control group in terms of hair growth and hair elongation. In addition, the p value of the comparison between the two is p<0.05, which shows that it is significant.
[實施例5] 5.麴菌發酵物萃取液(2)所致小鼠的生毛促進 將出生後8周齡之C3H/HeN雌小鼠,各分配5隻於以下表4所示2組中。以理髮器將小鼠的背部毛剃毛,並且1日1次、持續30日對剃毛部塗布試料溶液。塗布量設為0.15mL/日。如以下表4所示,對照組的試料液中是使用在實施例3中調製麴菌發酵物萃取液(2)時使用的萃取溶劑(對以椰棗為原料之蒸餾酒(商品名:隼人之涙,錦灘酒造株式會社製品,酒精度數30)添加滅菌水並將乙醇濃度做成10v/v%的溶液);試驗組的試料液中則是使用以實施例3獲得之麴菌發酵物萃取液(2)。[Example 5] 5. Promotion of hair growth in mice caused by the fermented koji fungus extract (2) Five C3H/HeN female mice aged 8 weeks after birth were assigned to the two groups shown in Table 4 below. The mouse's back hair was shaved with a hair clipper, and the sample solution was applied to the shaved part once a day for 30 days. The coating amount was set to 0.15 mL/day. As shown in Table 4 below, in the sample solution of the control group, the extraction solvent used when preparing the koji fungus fermented product extract (2) in Example 3 (for distilled spirits using date palms as raw materials (trade name: Hayato) Zhizhu, a product of Kintan Distillery Co., Ltd., with an alcohol content of 30) add sterilized water and make the ethanol concentration into a solution of 10v/v%); the sample solution of the test group uses the fermented koji bacteria obtained in Example 3 Extract (2).
[表4]
在進行第30次塗布的隔日、從試驗開始第31日,以肉眼觀察每隻小鼠之剃毛部之體毛濃色度及體毛伸長度,並依據上述表2所示基準求出生毛分數。此外,生毛分數之評價,是讓無法區別對照組小鼠與試驗組小鼠的人來進行,以排除實驗者造成的偏誤。關於對照組及試驗組之生毛分數,是利用顯著水準5%、曼-惠特尼之U檢定來評價顯著差異。結果顯示在圖3及以下表5中。On the next day after the 30th coating, and on the 31st day from the start of the test, the body hair density and body hair elongation of the shaved part of each mouse were observed with the naked eye, and the birth hair was obtained according to the standards shown in Table 2 above. Fraction. In addition, the evaluation of the hair growth score is performed by people who cannot distinguish between the control group and the test group, so as to eliminate the bias caused by the experimenter. Regarding the hair growth scores of the control group and the test group, the significant difference was evaluated using the significance level of 5% and the Mann-Whitney U test. The results are shown in Figure 3 and Table 5 below.
[表5]
根據該等結果表明,塗布有麴菌發酵物萃取液(2)之試驗組小鼠,相較於對照組小鼠,在生毛狀態及毛的伸長方面明顯優異。又,比較兩者之p值為p<0.01,顯示出有極高的顯著性。According to these results, the mice in the test group coated with the fermented koji fungus extract (2) were significantly better in hair growth and hair elongation than the control mice. In addition, the p value of the comparison between the two is p<0.01, which shows extremely high significance.
[實施例6] 6.麴菌發酵物萃取液(1)所致人類的生毛髮促進 將以實施例2獲得之麴菌發酵物萃取液(1)裝在噴霧瓶中,對以下表6所示的3名受試者A~C早上與晚上1日2次在頭部噴麴菌發酵物萃取液(1)數次並以手搓揉,藉此來投予。投予期間為1~3個月。將各受試者投予前後自頭部上方攝影之照片顯示在圖4。圖4(A)顯示受試者A,圖4(B)顯示受試者B,圖4(C)顯示受試者C。每張照片之下側表示正面,上側則是朝向背側。[Example 6] 6. Promotion of human hair growth caused by the fermented koji fungus extract (1) The koji fungus fermentation product extract (1) obtained in Example 2 was placed in a spray bottle, and three subjects A~C shown in Table 6 below were sprayed with koji bacteria on their heads twice a day in the morning and in the evening. The fermented product extract (1) is administered several times and rubbed with hands. The period of administration is 1 to 3 months. The photos taken from the top of the head of each subject before and after the administration are shown in Fig. 4. Figure 4(A) shows subject A, Figure 4(B) shows subject B, and Figure 4(C) shows subject C. The lower side of each photo represents the front side, and the upper side faces the back side.
[表6]
受試者A在投予前可觀察到主要在頭頂部有脫髮的雄性型脫髮症,然透過使用麴菌發酵物萃取液(1)約3個月,可觀察到頭頂部之脫髮範圍的縮小以及脫髮範圍內的生髮。又,在3個月之使用期間內,未觀察到皮膚異常。受試者B在投予前可觀察到特別是在額頭髮際之退後為顯著的雄性型脫髮症。該受試者B透過使用麴菌發酵物萃取液(1),在額頭的髮際部分可觀察到明顯的生毛髮。又,使用期間未觀察到皮膚異常,且頭皮狀態良好。受試者C在投予前可觀察到頭部整體有毛髮稀疏傾向的老年脫髮症,然透過使用麴菌發酵物萃取液(1),可觀察到整體性的生毛髮且頭髮產生韌性、體積增加。又,使用期間未觀察到皮膚異常。如此,藉由使用本發明之麴菌發酵物萃取液,會發生生髮,且可見脫髮症之改善。又,亦可得知會減少掉髮,且頭髮出現韌性、體積增加。任何受試者之頭皮皆無異常,且為與投予同樣或比投予前更佳之狀態。根據該等結果,顯示出本發明之麴菌發酵物及麴菌發酵物之萃取液在育毛髮及生毛髮促進方面優異,而可治療、預防或改善脫毛症。Subject A was able to observe male-type alopecia with alopecia mainly on the top of the head before the administration, but after using the koji fermentation extract (1) for about 3 months, the reduction in the range of hair loss on the top of the head could be observed And hair growth within the range of hair loss. In addition, no skin abnormalities were observed during the 3-month period of use. Subject B was able to observe significant androgenetic alopecia, especially in the receding area between the forehead, before the administration. The subject B used the fermented koji bacteria extract (1), and obvious hair growth was observed on the hairline part of the forehead. In addition, no skin abnormalities were observed during use, and the scalp was in good condition. Subject C was able to observe senile alopecia that tends to thin hair on the entire head before the administration. However, through the use of the fermented koji bacteria extract (1), the overall growth of hair can be observed and the hair develops toughness and volume. Increase. In addition, no skin abnormalities were observed during use. In this way, by using the fermented koji fungus extract of the present invention, hair growth occurs, and alopecia can be improved. In addition, it is also known that hair loss will be reduced, and the hair will appear tenacity and volume increase. The scalp of any subject has no abnormalities and is in the same condition as or better than before the administration. Based on these results, it is shown that the fermented koji mold and the extract of the fermented koji mold of the present invention are excellent in hair growth and hair growth promotion, and can treat, prevent, or improve alopecia.
[實施例7] 7.麴菌發酵物萃取液所致小鼠之生毛促進與麴菌發酵物之濃度的探討 將出生後8周齡之C3H/HeN雌小鼠,各分配5~6隻於以下表7所示4組中。以理髮器將小鼠的背部毛剃毛,並且1日1次、持續28日對剃毛部塗布各試料液。塗布量設為0.15mL/日。如以下表7所示,對照組(對照區)之試料液是使用滅菌水。又,試驗組2%區之試料液是使用如下上清液:對100mL滅菌水,以2g之比例添加以實施例1獲得之麴菌發酵物(乾燥後之粉末狀者),在4℃條件下之冷藏庫靜置並進行20小時萃取處理後,所回收之上清液(萃取液)。同樣的,在試驗組4%區之試料液是使用對100mL滅菌水,以4g之比例添加麴菌發酵物並萃取出的上清液(萃取液);試驗組8%區之試料液是使用對100mL無菌水,以8g之比例添加麴菌發酵物所獲得之上清液(萃取液)。[Example 7] 7. Discussion on the promotion of hair growth in mice induced by the fermented extract of Koji bacteria and the concentration of the fermentation product of Koji bacteria The C3H/HeN female mice at the age of 8 weeks after birth were assigned 5 to 6 mice in each of the 4 groups shown in Table 7 below. The back hair of the mouse was shaved with a hair clipper, and each sample solution was applied to the shaved part once a day for 28 days. The coating amount was set to 0.15 mL/day. As shown in Table 7 below, the sample solution of the control group (control area) was sterilized water. In addition, the sample solution in the 2% area of the test group uses the following supernatant: to 100 mL of sterilized water, add the koji fungus fermented product (in powder form after drying) obtained in Example 1 at a ratio of 2 g to 100 mL of sterilized water at 4°C. After the lower refrigerator is allowed to stand still and subjected to extraction treatment for 20 hours, the supernatant liquid (extract liquid) is recovered. Similarly, the sample solution in the 4% area of the test group is the supernatant (extract) obtained by adding 4 g of sterile water to 100 mL of sterilized water; the sample solution in the 8% area of the test group is used To 100 mL of sterile water, the supernatant (extract) obtained by adding the fermented koji fungus at a ratio of 8 g.
[表7] [Table 7]
在進行第28次塗布的隔日、從試驗開始第29日,以肉眼觀察每隻小鼠之剃毛部之體毛濃色度及體毛伸長度,並依據下述表8所示基準求出生毛分數。此外,生毛分數之評價,是讓無法區別對照組小鼠與試驗組小鼠的人來進行,以排除實驗者造成的偏誤。結果顯示在圖5及以下表9中。On the next day after the 28th coating, and on the 29th day from the start of the test, observe the body hair density and body hair elongation of the shaved part of each mouse with the naked eye, and determine the birth according to the standards shown in Table 8 below. Gross score. In addition, the evaluation of the hair growth score is performed by people who cannot distinguish between the control group and the test group, so as to eliminate the bias caused by the experimenter. The results are shown in Figure 5 and Table 9 below.
[表8] [Table 8]
[表9] [Table 9]
根據該等結果表明,塗布有麴菌發酵物萃取液之試驗組小鼠,相較於對照組小鼠,在生毛狀態及毛的伸長方面明顯優異。又,在調製麴菌發酵物萃取液時,即便在使用對每100ml溶劑添加2g(2%區)~4g(4%區)被萃取物之麴菌發酵物來調整的試料液時,仍有充分的生毛髮效果,然而,進一步在使用對每100ml溶劑添加8g(8%區)被萃取物之麴菌發酵物來調整的試料液時,生毛髮分數是進一步提高,可知生毛髮效果會以麴菌發酵物之濃度依賴性的的方式上升。According to these results, the mice in the test group coated with the fermented koji bacteria extract were significantly better than the mice in the control group in terms of hair growth and hair elongation. In addition, when preparing the koji fungus fermentation product extract, even when using a sample solution prepared by adding 2 g (2% area) to 4 g (4% area) of the koji fungus fermentation product of the extract per 100 ml of solvent, there is still Sufficient hair growth effect, however, when using a sample solution adjusted by adding 8 g (8% area) of the fermented koji bacteria of the extract per 100 ml of solvent, the hair growth score is further improved, and it can be seen that the hair growth effect will be improved The concentration-dependent manner of the fermented koji bacteria rises.
產業上之可利用性 本發明提供一種在育毛髮及生毛髮促進方面優異,且可治療、預防或改善脫毛症的育毛髮、生毛髮用外用劑或脫毛症治療劑,因此在毛髮保養化妝品領域、醫藥品、醫藥部外品等領域之產業上具有廣泛用處。Industrial availability The present invention provides an external agent for hair growth and hair growth or a hair loss treatment agent that is excellent in hair growth and hair growth promotion, and can treat, prevent, or ameliorate hair loss. It has a wide range of uses in industries such as foreign products.
本發明並未受限於上述之實施形態或實施例,還包含在不脫離申請專利範圍所記載之發明要旨範圍內,且進行了各種設計變更形態的技術性範圍。The present invention is not limited to the above-mentioned embodiments or examples, and is also included in the technical scope of various design changes without departing from the scope of the invention described in the scope of the patent application.
圖1是一流程圖,其概略顯示有關本發明實施形態之麴菌發酵物及麴菌發酵物之萃取物的製造方法。 圖2是顯示實施例4中對照組及試驗組之生毛分數的圖表。 圖3是顯示實施例5中對照組及試驗組之生毛分數的圖表。 圖4是顯示實施例6中受測者之生毛髮狀態的照片。 圖5是顯示實施例7中對照組(對照區)及試驗組(2%區、4%區及8%區)之生毛分數的圖表。Fig. 1 is a flow chart schematically showing the method of manufacturing the fermented koji fungus and the extract of the fermented koji fungus related to the embodiment of the present invention. Figure 2 is a graph showing the hair growth scores of the control group and the test group in Example 4. Fig. 3 is a graph showing the hair growth scores of the control group and the test group in Example 5. FIG. 4 is a photograph showing the hair growth state of the test subject in Example 6. FIG. Fig. 5 is a graph showing the hair growth scores of the control group (control area) and the test group (2% area, 4% area, and 8% area) in Example 7.
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TW109112857A TWI743747B (en) | 2019-05-07 | 2020-04-16 | External agent for hair growth and growth |
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TW (1) | TWI743747B (en) |
WO (1) | WO2020226022A1 (en) |
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JP2022151047A (en) * | 2021-03-26 | 2022-10-07 | 鹿児島県 | Post-fermented tea and drink and food using the same |
Citations (2)
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KR101704645B1 (en) * | 2014-12-10 | 2017-02-08 | (주)하이모 | Fermented Food for Preventing Hair Loss or Promoting Hair Growth |
JP2018039766A (en) * | 2016-09-09 | 2018-03-15 | キ・ホ・バン | Composition having hair loss prevention function or hair growth function using natural materials |
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JP2952627B2 (en) * | 1991-11-29 | 1999-09-27 | 株式会社タニサケ | Hair restoration liquid and method for producing the same |
JPH083021A (en) * | 1994-06-16 | 1996-01-09 | Yoshito Hasegawa | Hair growth stimulant |
EP1097700A4 (en) * | 1999-05-14 | 2003-01-15 | Japan Applied Microbiology Res | Hair growth stimulants |
JP2005278519A (en) * | 2004-03-30 | 2005-10-13 | Japan Tobacco Inc | Post-heating fermented tea beverage and method for producing the same |
JP2005341876A (en) * | 2004-06-03 | 2005-12-15 | Hideo Hasegawa | Maltase inhibiting tea |
JP2008044925A (en) * | 2006-08-21 | 2008-02-28 | Masao Aoike | Method for activating scalp and scalp-activating composition |
JP4583417B2 (en) * | 2007-07-30 | 2010-11-17 | 日本サプリメント株式会社 | Method for producing fermented tea |
JP2009234947A (en) * | 2008-03-26 | 2009-10-15 | Bionex 21:Kk | Hydrolyzate, hair growth promoter containing the same and the like |
JP5783648B2 (en) * | 2013-11-18 | 2015-09-24 | 国立研究開発法人農業・食品産業技術総合研究機構 | Skin external preparation for suppressing melanin production or for hair growth / hair growth using lactic acid bacteria |
EP3109316A4 (en) * | 2014-02-10 | 2017-10-25 | Kirishima Highland Beer Co., Ltd. | Koji fermented composition, seasoning using same, antioxidant, and food or beverage |
KR102394638B1 (en) * | 2015-09-30 | 2022-05-09 | (주)아모레퍼시픽 | Composition comprising lactic acid bacteria derived extracellular vesicles for preventing hair loss or promoting hair growth |
JP6788966B2 (en) * | 2015-12-24 | 2020-11-25 | 丸善製薬株式会社 | Cosmetics |
JP7300695B2 (en) * | 2017-06-23 | 2023-06-30 | 丸善製薬株式会社 | Hair restorer and cosmetics |
JP7300694B2 (en) * | 2017-06-23 | 2023-06-30 | 丸善製薬株式会社 | Anti-aging agents and cosmetics in the epidermis |
TWI709409B (en) * | 2018-07-02 | 2020-11-11 | 一般社團法人 夢源 | Composition for treatment, prevention or improvement of male infertility |
-
2020
- 2020-04-09 WO PCT/JP2020/015912 patent/WO2020226022A1/en active Application Filing
- 2020-04-09 JP JP2021518323A patent/JP7170357B2/en active Active
- 2020-04-16 TW TW109112857A patent/TWI743747B/en active
Patent Citations (2)
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KR101704645B1 (en) * | 2014-12-10 | 2017-02-08 | (주)하이모 | Fermented Food for Preventing Hair Loss or Promoting Hair Growth |
JP2018039766A (en) * | 2016-09-09 | 2018-03-15 | キ・ホ・バン | Composition having hair loss prevention function or hair growth function using natural materials |
Non-Patent Citations (2)
Title |
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Hiroyuki Fujita et al,"Extract of Black Tea (Pu-Ehr) Inhibits Postprandial Rise in Serum Cholesterol in Mice, and With Long Term Use Reduces Serum Cholesterol and Low Density Lipoprotein Levels and Renal Fat Weight in Rats", PHYTOTHERAPY RESEARCH, 2008, 22:1275-1281. |
I-Ching Hou et al,"A Hair Growth-Promoting Effect of Chinese Black Tea Extract in Mice", Biosci. Biotechnol. Biochem., 2013, 77(7):1606-1607. |
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JPWO2020226022A1 (en) | 2020-11-12 |
TW202108122A (en) | 2021-03-01 |
JP7170357B2 (en) | 2022-11-14 |
WO2020226022A1 (en) | 2020-11-12 |
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