TW202220681A - Skin flora improving agent and skin topical agent for improving skin flora in which skin bacterial flora improving agent includes fermented milk whey obtained by fermenting milk with Lactobacillus helveticus, and a skin topical agent - Google Patents

Skin flora improving agent and skin topical agent for improving skin flora in which skin bacterial flora improving agent includes fermented milk whey obtained by fermenting milk with Lactobacillus helveticus, and a skin topical agent Download PDF

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TW202220681A
TW202220681A TW110125978A TW110125978A TW202220681A TW 202220681 A TW202220681 A TW 202220681A TW 110125978 A TW110125978 A TW 110125978A TW 110125978 A TW110125978 A TW 110125978A TW 202220681 A TW202220681 A TW 202220681A
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skin
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bacterial flora
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畑中美咲
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日商朝日集團食品股份有限公司
日商朝日集團控股股份有限公司
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Abstract

A skin flora improving agent includes fermented milk whey obtained by fermenting milk with Lactobacillus helveticus; and a skin topical agent for improving skin bacterial flora which comprises the skin bacterial flora improving agent. The present invention provides a skin bacterial flora improving agent which is highly safe and capable improving the skin bacterial flora, and further provides a skin topical agent for improving skin bacterial flora.

Description

皮膚細菌叢改善劑及皮膚細菌叢改善用皮膚外用劑Skin bacterial flora improving agent and skin external preparation for skin bacterial flora improving

本發明係關於皮膚細菌叢改善劑及皮膚細菌叢改善用皮膚外用劑。The present invention relates to an agent for improving skin bacterial flora and an external preparation for skin for improving skin bacterial flora.

人體中有數百種、數百兆個細菌棲息,遍及口腔、胃、腸、皮膚等全身各處,並形成具有各自不同的菌種及組成的固有細菌叢。近年來,研究最具進展之腸道細菌叢(亦稱為「腸道菌群」)已知具有各種生理作用。例如,作為有益的作用,可列舉:抑制病原菌定植、活化免疫系統、產生維生素等,作為有害的作用,可列舉:產生腐敗產物或致癌物、參與各種腸道疾病等。因此,可以說腸道細菌叢與健康息息相關。There are hundreds of species and hundreds of trillions of bacteria inhabiting the human body, covering the mouth, stomach, intestines, skin and other parts of the body, and forming inherent bacterial clusters with different bacterial species and compositions. In recent years, the most advanced intestinal flora (also known as "gut flora") is known to have various physiological roles. For example, beneficial effects include inhibition of colonization of pathogenic bacteria, activation of the immune system, and production of vitamins, and harmful effects include production of spoilage products or carcinogens, participation in various intestinal diseases, and the like. Therefore, it can be said that the intestinal flora is closely related to health.

此外,皮膚細菌叢(亦稱為「皮膚菌群」、「肌膚細菌叢」、「肌膚菌群」)近年來也非常受到矚目,據說若皮膚細菌叢的均衡良好且為穩定狀態,就易於保持肌膚的健康。作為皮膚細菌叢的主要菌屬,可列舉:棒狀桿菌(Corynebactrium)屬、丙酸桿菌(Propionibacterium)屬、葡萄球菌(Stapylococcus)屬、β-變形菌(β-Proteobacteria)綱、γ-變形菌(γ-Proteobacteria)綱,據報導,根據肌膚的狀態使得皮膚細菌叢有所差異(例如參照非專利文獻1)。已知在屬於γ-變形菌綱的腸道細菌科的菌種中,於肌膚中豐度比相對較高的拉氏西地西菌(Cedecea lapagei)、阿氏腸桿菌(Enterobacter asburiae)、解鳥氨酸勞特氏菌(Raoultella ornithinolytica)之菌種,以及銅綠假單胞菌(Pseudomonas aeruginosa)、化膿鏈球菌(Streptococcus pyogenes)、腸球菌(Enterococcus)屬之菌種,係存在具有致癌可能性的有害菌(例如參照非專利文獻1~5)。In addition, the skin flora (also known as "skin flora", "skin flora", and "skin flora") has been attracting attention in recent years, and it is said that if the skin flora is well balanced and stable, it is easier to maintain skin health. The main bacterial genera of the skin bacterial flora include: Corynebactrium, Propionibacterium, Stapylococcus, β-Proteobacteria, γ-Proteobacteria (γ-Proteobacteria) class, it is reported that the bacterial flora of the skin varies according to the state of the skin (for example, see Non-Patent Document 1). It is known that Cedecea lapagei, Enterobacter asburiae, Enterobacter asburiae, Cedecea lapagei, Enterobacter The strains of Raoultella ornithinolytica, as well as the strains of Pseudomonas aeruginosa, Streptococcus pyogenes, and Enterococcus, have carcinogenic potential of harmful bacteria (for example, refer to Non-Patent Documents 1 to 5).

另外,據報導,特定的疾病與皮膚細菌叢之間存在關聯性,而許多報導稱痤瘡桿菌(Propionibacterium acnes)對痤瘡有加重作用,金黃色葡萄球菌(Staphlococcus aureus)與異位性皮膚炎的加重有關(例如參照非專利文獻1,5)。另一方面,據報導,屬於與金黃色葡萄球菌(Staphlococcus aureus)相同菌屬的表皮葡萄球菌(Staphylococcus epidermidis)具有產生針對金黃色葡萄球菌的抗菌肽、藉由增強肌膚屏障來提高保濕力、提高肌膚免疫力之作用,於皮膚細菌叢中係作為有益菌而作用(例如參照非專利文獻1,5)。In addition, it has been reported that certain diseases are associated with the bacterial flora of the skin, while many reports of Propionibacterium acnes aggravating acne, Staphlococcus aureus and atopic dermatitis related (for example, refer to Non-Patent Documents 1 and 5). On the other hand, it has been reported that Staphylococcus epidermidis, which belongs to the same genus as Staphlococcus aureus, produces antimicrobial peptides against Staphylococcus aureus, enhances moisturizing power by strengthening the skin barrier, improves the The role of skin immunity is to act as beneficial bacteria in the skin bacterial flora (for example, refer to Non-Patent Documents 1 and 5).

至今為止,作為評價皮膚狀態的方法,已有提案一種以皮膚細菌叢中的黃單胞菌(Xanthomonadaceae)科細菌的比例作為指標的方法(例如參照專利文獻1)。As a method for evaluating skin condition, a method using the ratio of Xanthomonadaceae bacteria in skin bacterial flora as an index has been proposed (for example, refer to Patent Document 1).

然而,目前仍然沒有提供出能夠充分滿足安全性高、可使皮膚細菌叢呈良好狀態的材料,迫切需要迅速地開發。However, there is still no material that can sufficiently satisfy the high safety requirements and can keep the skin bacterial flora in a good state, and there is an urgent need for rapid development.

另外,據報導,藉由瑞士乳酸桿菌(lactobacillus helveticus)來使乳發酵而獲得的發酵乳乳清,係可用作保濕劑(例如參照專利文獻2)、表皮細胞分化及角質化促進劑(例如參照專利文獻3)、皮膚中的紫外線感受性抑制劑(例如參照專利文獻4)等有效成分。In addition, it is reported that fermented whey obtained by fermenting milk with Lactobacillus helveticus can be used as a moisturizing agent (for example, refer to Patent Document 2), an epidermal cell differentiation and keratinization promoter (for example, See Patent Document 3), and active ingredients such as UV-sensitivity inhibitors in the skin (for example, see Patent Document 4).

[先前技術文獻] [專利文獻] [專利文獻1] 日本特開2017-209055號公報 [專利文獻2] 日本特開2005-206578號公報 [專利文獻3] 國際專利公開第2006/137513公報 [專利文獻4] 國際專利公開第2006/095764公報 [Prior Art Literature] [Patent Literature] [Patent Document 1] Japanese Patent Application Laid-Open No. 2017-209055 [Patent Document 2] Japanese Patent Laid-Open No. 2005-206578 [Patent Document 3] International Patent Publication No. 2006/137513 [Patent Document 4] International Patent Publication No. 2006/095764

[非專利文獻] [非專利文獻1] Uwe Wollina. Microbiome in atopic Dermatitis, Clinical Cometic and Investigational Dermatology, (2017), 10:51-56. [非專利文獻2] Chavez Herrera et al., Death related to Cedecea lapagei in a soft tissue bullae infection: a case report, Journal of Medical Case Reports, (2018) 12:328. [非專利文獻3] Jalal Mardaneh et al., Isolation and Identification Enterobacter asburiae from Consumed Powdered Infant Formula Milk (PIF) in the Neonatal Intensive Care Unit (NICU), Acta Medica Iranica, Vol.54, No.1(2016), 39-43. [非專利文獻4] Piseth Seng et al., Emerging role of Raoultella ornithinolytica in human infections: a series of cases and review of the literature, International Journal of Infectious Diseases, 45(2016), 65-71. [非專利文獻5] Elizabeth A. Grice et al., The skin microbiome, Nat Rev Microbiol, 9(2011), 244-253. [Non-patent literature] [Non-Patent Literature 1] Uwe Wollina. Microbiome in atopic Dermatitis, Clinical Cometic and Investigational Dermatology, (2017), 10:51-56. [Non-Patent Document 2] Chavez Herrera et al., Death related to Cedecea lapagei in a soft tissue bullae infection: a case report, Journal of Medical Case Reports, (2018) 12:328. [Non-Patent Document 3] Jalal Mardaneh et al., Isolation and Identification Enterobacter asburiae from Consumed Powdered Infant Formula Milk (PIF) in the Neonatal Intensive Care Unit (NICU), Acta Medica Iranica, Vol.54, No.1(2016) , 39-43. [Non-Patent Literature 4] Piseth Seng et al., Emerging role of Raoultella ornithinolytica in human infections: a series of cases and review of the literature, International Journal of Infectious Diseases, 45(2016), 65-71. [Non-Patent Document 5] Elizabeth A. Grice et al., The skin microbiome, Nat Rev Microbiol, 9(2011), 244-253.

[發明所欲解決問題] 本發明所欲解決問題為解決上述以往的諸問題,並且達成以下目的。即,本發明的目的為提供安全性高,且能夠使皮膚細菌叢呈良好狀態的皮膚細菌叢改善劑及皮膚細菌叢改善用皮膚外用劑。 [Problems to be Solved by Invention] The problem to be solved by the present invention is to solve the above-mentioned conventional problems and achieve the following objects. That is, an object of the present invention is to provide a skin bacterial flora improving agent and a skin external preparation for skin bacterial flora improving, which are highly safe and can keep the skin bacterial flora in a good state.

[解決問題之手段] 為了解決所述問題,本發明人反覆致力研究,結果發現藉由瑞士乳酸桿菌來使乳發酵而獲得的發酵乳乳清具有使皮膚細菌叢呈良好狀態的作用。 [means to solve the problem] In order to solve the above-mentioned problems, the present inventors have repeatedly studied and found that fermented whey obtained by fermenting milk with Lactobacillus helveticus has an effect of keeping the skin bacterial flora in a good state.

本發明係本發明人基於上述發現而成,作為用於解決所述問題之手段,其係如下所述。即: <1>一種皮膚細菌叢改善劑,其特徵在於含有藉由瑞士乳酸桿菌(Lactobacillus helveticus)來使乳發酵而獲得的發酵乳乳清。 <2>如<1>所述之皮膚細菌叢改善劑,其中,皮膚細菌叢的改善係為選自:皮膚細菌叢中有益菌的比例之維持、有益菌的比例之增加、有害菌的比例之降低中的至少其中之一。 <3> 如<2>所述之皮膚細菌叢改善劑,其中,有害菌係具有引起炎症的可能性的細菌。 <4> 如<1>至<3>中任一項所述之皮膚細菌叢改善劑,其中,瑞士乳酸桿菌係瑞士乳酸桿菌CM4菌株(寄存編號:FERM BP-6060)。 <5>一種皮膚細菌叢改善用皮膚外用劑,其特徵在於含有如<1>至<4>中任一項所述之皮膚細菌叢改善劑。 The present invention is made by the present inventors based on the above-mentioned findings, and as means for solving the above-mentioned problems, it is as follows. which is: <1> A skin flora improving agent characterized by containing fermented whey obtained by fermenting milk with Lactobacillus helveticus. <2> The skin bacterial flora improving agent according to <1>, wherein the improving skin bacterial flora is selected from the group consisting of maintaining the ratio of beneficial bacteria in the skin bacterial flora, increasing the ratio of beneficial bacteria, and the ratio of harmful bacteria at least one of the reductions. <3> The skin flora improving agent according to <2>, wherein the harmful bacteria are bacteria that may cause inflammation. <4> The skin flora improving agent according to any one of <1> to <3>, wherein the Lactobacillus helveticus is a Lactobacillus helveticus CM4 strain (accession number: FERM BP-6060). <5> A skin external preparation for improving skin bacterial flora, comprising the skin bacterial flora improving agent according to any one of <1> to <4>.

[發明功效] 根據本發明,可提供能夠解決以往的上述諸問題,能夠達成上述目的,且安全性高,能夠使皮膚細菌叢呈良好狀態的皮膚細菌叢改善劑及皮膚細菌叢改善用皮膚外用劑。 [Inventive effect] According to the present invention, it is possible to provide a skin bacterial flora improving agent and a skin bacterial flora improving skin external preparation which can solve the above-mentioned problems and achieve the above object, are highly safe, and can keep the skin bacterial flora in a good state.

(皮膚細菌叢改善劑) 本發明之皮膚細菌叢改善劑至少含有藉由瑞士乳酸桿菌來使乳發酵而獲得的發酵乳乳清(以下或稱「LH發酵乳乳清」),且根據所需進一步包含其他成分。 (Skin bacterial flora improver) The skin flora improving agent of the present invention contains at least fermented whey obtained by fermenting milk with Lactobacillus helveticus (hereinafter referred to as "LH fermented whey"), and further contains other components as needed.

所述皮膚細菌叢改善劑具有改善皮膚細菌叢之狀態的作用。 於本說明書中,改善皮膚細菌叢之狀態係指使皮膚細菌叢之狀態呈良好狀態(或稱「健康狀態」),其中也包括將良好狀態予以維持。 較佳地,所述皮膚細菌叢改善劑係具有選自:皮膚細菌叢中有益菌的比例之維持、有益菌的比例之增加、有害菌的比例之降低中的至少其中一個作用。 The skin bacterial flora improving agent has the effect of improving the state of the skin bacterial flora. In this specification, improving the state of the skin bacterial flora refers to keeping the skin bacterial flora in a good state (or "healthy state"), which also includes maintaining the good state. Preferably, the skin bacterial flora improving agent has at least one effect selected from the group consisting of maintaining the ratio of beneficial bacteria in the bacterial flora of the skin, increasing the ratio of beneficial bacteria, and reducing the ratio of harmful bacteria.

作為所述有益菌,只要可使肌膚呈良好狀態就沒有特別限制,可根據目的適當選擇,可列舉例如表皮葡萄球菌(Staphylococcus epidermidis)等。The beneficial bacteria are not particularly limited as long as they can keep the skin in a good state, and can be appropriately selected according to the purpose, and examples thereof include Staphylococcus epidermidis and the like.

作為所述有害菌,只要對肌膚狀態有不良影響就沒有特別限制,可根據目的適當選擇,可列舉例如:具有引發炎症的可能性之屬於γ-變形菌綱的腸道細菌科的腸道細菌科之菌種、金黃色葡萄球菌(Staphylococcus aureus)、痤瘡丙酸桿菌(Propionibacterium acnes)、化膿性鏈球菌(Streptococcus pyogenes)等。The harmful bacteria are not particularly limited as long as they have an adverse effect on the skin condition, and can be appropriately selected according to the purpose. Branches of bacteria, Staphylococcus aureus, Propionibacterium acnes, Streptococcus pyogenes, etc.

作為所述具有引發炎症的可能性之有害菌,並無特別限制,可根據目的適當選擇,可列舉例如選自金黃色葡萄球菌(Staphylococcus aureus)、拉氏西地西菌(Cedecea lapagei)、阿氏腸桿菌(Enterobacter asburiae)、解鳥氨酸勞特氏菌(Raoultella ornithinolytica)所組成群組中的至少其中一種。The harmful bacteria having the possibility of causing inflammation is not particularly limited, and can be appropriately selected according to the purpose, and examples thereof include Staphylococcus aureus, Cedecea lapagei, At least one of the group consisting of Enterobacter asburiae and Raoultella ornithinolytica.

雖然LH發酵乳乳清所具有的發揮改善皮膚細菌叢狀態之作用的物質的細節並不清楚,但所述LH發酵乳乳清具有如此優異作用,作為皮膚細菌叢改善劑的有用之處以往完全不為人知,乃本發明人的嶄新發現。Although the details of the substances that LH-fermented whey possesses to improve the state of skin bacterial flora are not clear, the LH-fermented whey has such an excellent effect that its usefulness as a skin flora improving agent has not been known until now. It is unknown, but a new discovery by the inventors of the present invention.

<LH發酵乳乳清> -瑞士乳酸桿菌- 作為所述瑞士乳酸桿菌的菌株,並無特別限制,可根據目的適當選擇,較佳為胞外蛋白酶活性高的菌株。例如,較佳為依照以Twining等人的方法(Twining, S. Anal. Biochem. 143 3410(1984))為基礎的Yamamoto等人的方法(Yamamoto, N. etc J. Biochem. (1993) 114, 740)所測量出的U/OD590的值為400以上的菌株。此外,可使用具有以下菌學性質的瑞士乳酸桿菌之菌株。 <LH Fermented Whey> - Lactobacillus helveticus - The strain of Lactobacillus helveticus is not particularly limited, and can be appropriately selected according to the purpose, but a strain with high extracellular protease activity is preferred. For example, it is preferable to follow the method of Yamamoto et al. (Yamamoto, N. etc J. Biochem. (1993) 114) based on the method of Twining et al. (Twining, S. Anal. Biochem. 143 3410 (1984)), 740) strains with a measured U/OD590 value of 400 or more. In addition, strains of Lactobacillus helveticus having the following mycological properties can be used.

[菌學性質] 1. 形態學性質: 1)細胞形狀:桿菌 2)運動性:無 3)有無孢子:無 4)革蘭氏染色:陽性 2. 生理學性質: 1)過氧化氫酶:陰性 2)吲哚生成:陰性 3)硝酸鹽還原:陰性 4)對氧的表現:兼性厭氧菌 5)由葡萄糖進行同型乳酸發酵而產生DL(-)乳酸,不產生氣體。 [Bacteriological properties] 1. Morphological properties: 1) Cell shape: Bacillus 2) Mobility: none 3) With or without spores: none 4) Gram stain: positive 2. Physiological properties: 1) Catalase: negative 2) Indole production: negative 3) Nitrate reduction: negative 4) Performance on oxygen: facultative anaerobic bacteria 5) DL(-) lactic acid is produced by homolactic fermentation of glucose, and no gas is produced.

於所述瑞士乳酸桿菌中,較佳為瑞士乳酸桿菌CM4菌株。所述瑞士乳酸桿菌CM4菌株係於1997年8月15日以寄存編號FERM BP-6060,寄存於獨立行政法人產業技術綜合研究所專利微生物寄存中心(日本茨城縣筑波市東中 6 號 1-1-1)。此瑞士乳酸桿菌CM4菌株係以上述寄存編號註冊於-專利程序上的微生物寄存的國際承認的布達佩斯條約,此菌株係已獲得專利。Among the Lactobacillus helveticus, the Lactobacillus helveticus CM4 strain is preferred. The described Lactobacillus helveticus CM4 strain was deposited in the Patent Microorganism Deposit Center of the National Institute of Industrial Technology and Research on August 15, 1997 with the deposit number FERM BP-6060 (1-1-1-1-1-1-1-1-1-1- 1). This Lactobacillus helveticus CM4 strain is registered under the above-mentioned deposit number in - Budapest Treaty of International Recognition of Microorganism Deposits on Patent Procedures, and this strain is patented.

作為所述LH發酵乳乳清的製造方法,並無特別限制,可根據目的適當選擇,例如直接將所述瑞士乳酸桿菌添加至乳中,或是將含有所述瑞士乳酸桿菌的發酵乳發酵劑添加至乳中,透過適當選擇發酵溫度等發酵條件並使其發酵而獲得。The method for producing the LH fermented whey is not particularly limited, and can be appropriately selected according to the purpose. For example, the Lactobacillus helveticus is directly added to milk, or the fermented milk starter containing the Lactobacillus helveticus is added. It is obtained by adding it to milk, selecting fermentation conditions such as fermentation temperature appropriately, and fermenting it.

作為有效成分的所述LH發酵乳乳清係可藉由如遠心分離、過濾等常規的分離操作,從所獲得的發酵乳中分離出乳清而獲得,惟在使用時,在未分離的發酵乳狀態下或是對已分離出的乳清適當地進行分餾、濃縮、純化等而使用,除此之外亦可透過將所述乳清或其濃縮物藉由冷凍乾燥、噴霧乾燥等作為粉末而使用。The LH fermented whey system as an active ingredient can be obtained by separating whey from the obtained fermented milk by conventional separation operations such as telecentric separation and filtration. It can be used in a milk state or by appropriately fractionating, concentrating, and purifying the separated whey, and in addition, the whey or its concentrate can also be used as a powder by freeze-drying, spray-drying, etc. and use.

所述瑞士乳酸桿菌中,較佳地,使用預先進行預培養好的具有充分高活性的起子菌。初始菌數量較佳為約10 5~10 9個/mL。 Among the Lactobacillus helveticus, preferably, starter bacteria with sufficient high activity that have been pre-cultured in advance are used. The initial bacterial count is preferably about 10 5 to 10 9 cells/mL.

在不損害本發明的效果前提下,所述發酵中也可包括瑞士乳酸桿菌之外的乳酸菌或酵母等其他菌。On the premise that the effect of the present invention is not impaired, other bacteria such as lactic acid bacteria and yeast other than Lactobacillus helveticus may also be included in the fermentation.

作為原料乳並無特別限制,可根據目的適當選擇,可列舉例如:如牛乳、馬乳、羊乳、山羊乳等動物乳;如豆乳等植物乳;此等的加工乳之脫脂乳、還原乳、奶粉、煉乳等,其中較佳為牛乳、豆乳、此等之加工乳,更佳為牛乳或是其加工乳。 作為乳的固體成分濃度,並無特別限制,可根據目的適當選擇,惟較佳為例如當使用脫脂乳時的無脂乳固體成分濃度通常為約3~15質量%,以生產性來看較佳為6~15質量%。 The raw material milk is not particularly limited and can be appropriately selected according to the purpose. Examples include animal milk such as cow's milk, horse's milk, goat's milk, and goat's milk; vegetable milk such as soy milk; skimmed milk and reduced milk such as processed milk , milk powder, condensed milk, etc., among which cow's milk, soy milk, and processed milk thereof are preferred, and cow's milk or its processed milk is more preferred. The solid content concentration of milk is not particularly limited and can be appropriately selected according to the purpose, but is preferably, for example, when skim milk is used. Preferably it is 6-15 mass %.

所述發酵通常透過靜置或是攪拌培養,並透過例如下述方法進行:在發酵溫度25~45℃、較佳為30~45℃,且發酵時間為3~72小時,較佳為12~36小時下,並在乳酸酸度達1.5以上時停止發酵。The fermentation is usually carried out by standing or stirring culture, for example, by the following method: the fermentation temperature is 25-45°C, preferably 30-45°C, and the fermentation time is 3-72 hours, preferably 12- 36 hours, and stop fermentation when the acidity of lactic acid reaches 1.5 or more.

作為所述LH發酵乳乳清的皮膚細菌叢改善劑中的含量,並無特別限制,可根據所述LH發酵乳乳清的生理活性等適當調整。所述皮膚細菌叢改善劑可為僅由所述LH發酵乳乳清所組成。The content in the skin flora improving agent of the LH-fermented whey is not particularly limited, and can be appropriately adjusted according to the physiological activity of the LH-fermented whey and the like. The skin flora improving agent may consist only of the LH fermented whey.

<其他成分> 作為所述其他成分,只要在不損害本發明功效的前提下就沒有特別限制,可根據目的適當選擇,可列舉例如與後述的皮膚細菌叢改善用皮膚外用劑中的其他成分的相同物等。 作為所述其他成分於皮膚細菌叢改善劑中的含量,並無特別限制,可根據目的適當選擇。 <Other ingredients> The other components are not particularly limited unless they impair the efficacy of the present invention, and can be appropriately selected according to the purpose. The content of the other components in the skin bacterial flora improving agent is not particularly limited, and can be appropriately selected according to the purpose.

<用途> 作為本發明之皮膚細菌叢改善劑之用途,並無特別限制,可根據目的適當選擇,惟例如可良好地用作後述的皮膚細菌叢改善用皮膚外用劑的有效成分。 <Use> The use of the skin flora improving agent of the present invention is not particularly limited, and can be appropriately selected according to the purpose, but for example, it can be favorably used as an active ingredient of the skin external preparation for skin flora improving described later.

所述皮膚細菌叢改善劑可每天使用,透過作為有效成分的LH發酵乳乳清的作用,能夠極為有效地發揮皮膚細菌叢的改善效果。The skin bacterial flora improving agent can be used every day, and through the action of LH fermented whey as an active ingredient, the skin bacterial flora improving effect can be exerted extremely effectively.

所述皮膚細菌叢改善劑的每日使用量係取決於使用對象、使用型態等種類、使用間隔等因素而有變動,並無特別限制,惟例如作為一個成人每日塗抹至臉上的皮膚塗抹量,較佳為將摻有0.01~20質量%的所述LH發酵乳乳清之皮膚細菌叢改善劑予以均勻地塗抹0.01~5g,更佳為予以均勻地塗抹0.1~0.5g。此日劑量可一次使用,亦可分成多次來使用。The daily usage amount of the skin bacterial flora improving agent varies depending on the object of use, the type of use, the use interval and other factors, and there are no special restrictions, but for example, as an adult, apply it to the skin of the face every day. The amount to be applied is preferably 0.01 to 5 g, more preferably 0.1 to 0.5 g, of the skin bacterial flora improving agent containing 0.01 to 20 mass % of the LH fermented whey. This daily dose can be used once or divided into multiple doses.

所述皮膚細菌叢改善劑的使用時機並無特別限制,可根據目的適當選擇,例如,可在接觸需要改善皮膚細菌叢的環境等之前持續或間歇地使用,亦可在接觸如此環境之後,持續或間歇地使用。The use timing of the skin bacterial flora improving agent is not particularly limited, and can be appropriately selected according to the purpose. or intermittently.

本發明之皮膚細菌叢改善劑可良好地適用於人,在其作用功效作用的前提下,亦可適用於人以外的動物。The skin bacterial flora improving agent of the present invention can be well applied to humans, and can also be applied to animals other than humans under the premise of its action and efficacy.

此外,本發明之皮膚細菌叢改善劑係可用作為研究皮膚細菌叢改善作用或皮膚細菌叢的試劑。In addition, the skin bacterial flora improving agent of the present invention can be used as a reagent for studying skin bacterial flora improving effect or skin bacterial flora.

(皮膚細菌叢改善用皮膚外用劑) 本發明之皮膚細菌叢改善用皮膚外用劑係至少含有本發明的皮膚細菌叢改善劑,且根據所需進一步含有其他成分。 (external preparation for skin bacterial flora improvement) The skin external preparation for improving skin flora of the present invention contains at least the skin flora improving agent of the present invention, and further contains other components as needed.

<皮膚細菌叢改善劑> 所述皮膚細菌叢改善劑係為上述的本發明之皮膚細菌叢改善劑。 <Skin bacterial flora improver> The skin bacterial flora improving agent is the above-mentioned skin bacterial flora improving agent of the present invention.

作為所述皮膚細菌叢改善劑於皮膚細菌叢改善用皮膚外用劑中的含量,並無特別限制,可根據所述皮膚細菌改善劑中所含的LH發酵乳乳清的生理活性等而適當調整,例如,作為所述LH發酵乳乳清的量,較佳為0.01~20質量%,更佳為0.05~10質量%。另外,所述LH發酵乳乳清的量係指經乾燥而成為固體時的質量。 所述皮膚細菌叢改善用皮膚外用劑係可僅由所述皮膚細菌叢改善劑組成。 The content of the skin bacterial flora improving agent in the external preparation for skin bacterial flora improving is not particularly limited, and can be appropriately adjusted according to the physiological activity of LH fermented whey contained in the skin bacteria improving agent, etc. For example, the amount of the LH fermented whey is preferably 0.01 to 20% by mass, more preferably 0.05 to 10% by mass. In addition, the quantity of the said LH fermented whey means the mass when it becomes solid by drying. The skin external preparation system for improving skin bacterial flora may consist only of the skin bacterial flora improving agent.

<其他成分> 作為所述皮膚細菌叢改善用皮膚外用劑中的其他成分,在不損害本發明功效的前提下,並無特別限制,可根據所述皮膚細菌叢改善用皮膚外用劑的使用型態而適當選擇,可列舉例如:油脂類、蠟類、烴類、脂肪酸類、醇類、酯類、表面活性劑、金屬皂、pH調整劑、防腐劑、香精、保濕劑、粉末、紫外線吸收劑、增稠劑、色素、抗氧化劑等。此外,也可含有具有用於使已知的皮膚細菌叢呈良好狀態之作用的物質。此等可單獨使用一種,亦可併用兩種以上。 作為所述其他成分於皮膚細菌叢改善用皮膚外用劑中的含量,並無特別限制,可根據目的適當選擇。 <Other ingredients> The other components in the external preparation for improving skin bacterial flora are not particularly limited as long as the efficacy of the present invention is not impaired, and can be appropriately selected according to the usage pattern of the external preparation for improving skin bacterial flora. , for example: oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, ultraviolet absorbers, thickeners agents, pigments, antioxidants, etc. In addition, substances having the effect of keeping the known skin bacterial flora in good condition may also be contained. These may be used individually by 1 type, and may use 2 or more types together. The content of the other components in the external preparation for skin bacterial flora improvement is not particularly limited, and can be appropriately selected according to the purpose.

作為所述皮膚外用劑,並無特別限制,可根據目的適當選擇,可列舉例如:化妝品、類藥品、藥品等。於此等中,如後述的試驗例所示,當塗抹所述皮膚外用劑時,由於皮膚水分量及肌膚的紋理得到改善,因此可良好地用作為化妝品。The external preparation for skin is not particularly limited, and can be appropriately selected according to the purpose, and examples thereof include cosmetics, quasi-drugs, and pharmaceuticals. Among these, as shown in the test examples described later, when the external preparation for skin is applied, the moisture content of the skin and the texture of the skin are improved, so that it can be favorably used as a cosmetic.

作為所述皮膚細菌叢改善用皮膚外用劑的劑型,並無特別限制,可根據目的適當選擇,可列舉例如:化妝水、乳霜、乳液、美容液、化妝液、凝膠、噴霧劑、軟膏、泥敷劑、精華液、面膜、清洗劑、沐浴乳、粉底等。The dosage form of the external preparation for skin flora improvement is not particularly limited, and can be appropriately selected according to the purpose. , poultice, essence, mask, cleanser, shower gel, foundation, etc.

作為所述皮膚細菌叢改善用皮膚外用劑的製造方法,並無特別限制,可根據劑型等適當選擇,例如,可使用習知方法將各種成分進行混合或是乳化,以進行製造。The method for producing the external preparation for skin flora improvement is not particularly limited, and can be appropriately selected according to the dosage form. For example, various components can be mixed or emulsified using a conventional method to produce.

所述皮膚細菌叢改善用皮膚外用劑可每天使用,透過作為有效成分之LH發酵乳乳清的作用,能夠極有效地發揮改善皮膚細菌叢的作用。The skin external preparation for improving skin bacterial flora can be used every day, and through the action of LH fermented whey as an active ingredient, the skin bacterial flora can be improved very effectively.

作為所述皮膚細菌叢改善用皮膚外用劑的每日使用量,其係取決於使用對象、使用型態等種類、使用間隔等因素而有所變動,其並無特別限制,例如,作為成人每日塗抹至臉上的皮膚塗抹量,將摻入0.01~20質量%的所述LH發酵乳乳清之皮膚細菌叢改善用皮膚外用劑予以均勻地塗抹0.01~5g為較佳,予以均勻地塗抹0.1~0.5g為更佳。此日劑量可一次使用,也可分為多次使用。The daily usage amount of the skin external preparation for improving skin bacterial flora varies depending on factors such as the object of use, the type of usage, and the usage interval, and is not particularly limited. The daily amount applied to the skin on the face is to apply 0.01 to 5 g of the external preparation for skin bacterial flora improvement mixed with 0.01 to 20 mass% of the LH fermented whey, and evenly apply 0.01 to 5 g, and apply evenly. 0.1~0.5g is more preferable. This daily dose can be used once or divided into multiple doses.

作為所述皮膚細菌叢改善用皮膚外用劑的使用時機,並無特別限制,可根據目的適當選擇,例如,可在接觸需要改善皮膚細菌叢的環境之前,持續或是間歇地使用,也可在與此類環境接觸之後持續或是間歇地使用。The timing of use of the external preparation for improving skin bacterial flora is not particularly limited, and can be appropriately selected according to the purpose. Use continuously or intermittently after exposure to such environments.

所述皮膚細菌叢改善用外用劑可良好地適用於人,在發揮其作用效果的前提下,也可適用於人以外的動物。The external preparation for improving skin bacterial flora can be well applied to humans, and can also be applied to animals other than humans on the premise of exerting its effects.

[實施例] 以下說明本發明之試驗例、處方例,惟本發明並不限於此等試驗劑、處理例。 [Example] Test examples and formulation examples of the present invention will be described below, but the present invention is not limited to these test agents and treatment examples.

(試驗例1) 作為化妝水,準備含有5質量%發酵乳乳清之化妝水(Lactina Moist Lotion,朝日卡爾必斯健康股份有限公司製),該發酵乳乳清係藉由瑞士乳酸桿菌CM4菌株(寄存編號:FERM BP-6060)將乳發酵而得。 (Test Example 1) As a lotion, a lotion (Lactina Moist Lotion, manufactured by Asahi Calpis Health Co., Ltd.) containing 5% by mass of fermented whey obtained from Lactobacillus helveticus CM4 strain (accession number: FERM) was prepared. BP-6060) is obtained by fermenting milk.

<試驗方法> 請45歲至59歲且平均年齡為54.0±3.3歲的15位日本人女性,於早晚洗臉後塗抹上述化妝水一個禮拜。 <Test method> 15 Japanese women aged 45 to 59 with an average age of 54.0±3.3 were asked to apply the above lotion for one week after washing their faces in the morning and evening.

-皮膚細菌叢分析- 於開始塗抹試驗前的早上及塗抹一個禮拜之後的早上時,於洗臉前使用浸泡過生理食鹽水中的棉棒擦拭前額及臉頰5~6次,以採集樣品。 從所採集的樣品中提取DNA,將使用ION 16S宏基因組試驗盒(ION 16S metagenomics kit)(賽默飛世爾科技公司製造)而擴增的16S核醣體蛋白的V2~V4及V6~V9區域的序列,使用次世代測序儀(Ion Personal Genome Machine TM(PGM TM)sequencer,賽默飛世爾科技公司製造)進行分析。 針對所獲得的序列進行基本局部比對搜尋工具(Basic Local Alignment Search Tool, BLAST)搜尋,將具有95%以上相似度的菌株中最高的相同菌株分配給各菌株。另外,排除了低品質的鹼基、120bp以下的短的片段,以及相似度小於95%的序列。 將結果表示於表1。 - Analysis of skin bacterial flora - In the morning before the start of the application test and in the morning after application for a week, use a cotton swab soaked in physiological saline to wipe the forehead and cheeks 5 to 6 times before washing the face to collect samples. DNA was extracted from the collected samples, and the V2 to V4 and V6 to V9 regions of the 16S ribosomal protein amplified using the ION 16S metagenomics kit (manufactured by Thermo Fisher Scientific) were analyzed. Sequences were analyzed using a next-generation sequencer (Ion Personal Genome Machine (PGM ) sequencer, manufactured by Thermo Fisher Scientific). A Basic Local Alignment Search Tool (BLAST) search was performed on the obtained sequences, and the highest identical strain among strains with a similarity of more than 95% was assigned to each strain. In addition, low-quality bases, short fragments below 120 bp, and sequences with a similarity less than 95% were excluded. The results are shown in Table 1.

[表1] 佔比(%) 有對應的t檢定 菌種 塗抹前 塗抹後 拉氏西地西菌 (Cedecea lapagei) 2.861 0.054 <0.001 阿氏腸桿菌 (Enterobacter asburiae) 2.099 0.009 <0.001 解鳥氨酸勞特氏菌 (Raoultella ornithinolytica) 1.086 0.007 0.001 金黃色葡萄球菌 (Staphylococcus aureus) 0.079 0.060 0.703 表皮葡萄球菌(Staphylococcus epidermidis) 4.812 9.196 0.138 [Table 1] Proportion (%) There is a corresponding t-test strain Before applying after application Cedecea lapagei 2.861 0.054 <0.001 Enterobacter asburiae 2.099 0.009 <0.001 Raoultella ornithinolytica 1.086 0.007 0.001 Staphylococcus aureus 0.079 0.060 0.703 Staphylococcus epidermidis 4.812 9.196 0.138

如表1所示,表明了當塗抹了其中含有藉由瑞士乳酸桿菌來使乳發酵而獲得的發酵乳乳清之化妝水時,具有引起炎症的可能性之有害菌之拉氏西地西菌(Cedecea lapagei)、阿氏腸桿菌(Enterobacter asburiae)、解鳥氨酸勞特氏菌(Raoultella ornithinolytica)的比例下降(全員15位)。 此外,雖然沒有統計學上的顯著差異,但是確認到了被認為是有益菌,與肌膚的保溼作用有關並且具有抑制有害菌增殖作用的表皮葡萄球菌(Staphylococcus epidermidis)的比例在15名中增加了9名,被認為是有害菌的金黃色葡萄球菌(Staphylococcus aureus)的比例在15名中減少了8名。 因此,顯示出藉由瑞士乳酸桿菌來使乳發酵而獲得的發酵乳乳清係將皮膚細菌叢轉變為健康狀態並維持此狀態的可能性。 As shown in Table 1, when a lotion containing fermented whey obtained by fermenting milk with Lactobacillus helveticus was applied, it was shown that Sildena larvae, a harmful bacteria that may cause inflammation (Cedecea lapagei), Enterobacter asburiae, and Raoultella ornithinolytica decreased (15th in all members). In addition, although there was no statistically significant difference, it was confirmed that the ratio of Staphylococcus epidermidis, which is considered to be beneficial bacteria, is related to the moisturizing effect of the skin and has the effect of inhibiting the proliferation of harmful bacteria, increased in 15 students. Nine out of 15, the ratio of Staphylococcus aureus, which is considered a harmful bacteria, decreased by 8. Therefore, the fermented whey system obtained by fermenting milk with Lactobacillus helveticus has been shown to convert the skin bacterial flora into a healthy state and maintain this state.

─皮膚含水量、皮膚紋理 (紋理體積率、紋理數量) ─ 於塗抹試驗開始前及塗抹一個禮拜之後,測量右臉頰的皮膚含水量、皮膚紋理(紋理體積率、紋理數量)。 皮膚含水量的測量係使用Corneometer CM825(英格雷股份有限公司製)進行。其結果如圖1所示。 皮膚紋理的測量係在製作皮膚的複製品,並使用分析系統(反射用複製品分析系統,朝日生物醫學公司)之下進行。紋理體積率的測量結果係如圖2所示,紋理數量的測量結果係如圖3所示。 ─Skin moisture content, skin texture (texture volume ratio, texture number) ─ Before the start of the application test and one week after application, the skin moisture content and skin texture (texture volume ratio, texture number) of the right cheek were measured. The measurement of the skin moisture content was performed using Corneometer CM825 (manufactured by Ingray Co., Ltd.). The results are shown in Figure 1 . The measurement of skin texture was carried out by making a replica of the skin and using an analysis system (Replica Analysis System for Reflection, Asahi Biomedical Co., Ltd.). The measurement results of the texture volume ratio are shown in FIG. 2 , and the measurement results of the texture quantity are shown in FIG. 3 .

如圖1~圖3所示,在塗抹其中含有藉由瑞士乳酸桿菌來使乳發酵而獲得的發酵乳乳清之化妝水之後,皮膚含水量、紋理體積率、紋理數量顯著地增加,並確認到作為皮膚外用劑為有用。As shown in FIGS. 1 to 3 , after applying a lotion containing fermented whey obtained by fermenting milk with Lactobacillus helveticus, the skin moisture content, texture volume ratio, and texture number increased significantly, and it was confirmed that To be useful as an external preparation for the skin.

(試驗例2:基於培養實驗來實驗發酵乳乳清之有害菌抑制作用) 以下述方式,以體外(in vitro)試驗來確認於試驗例1中所認定的有害菌抑制作用是否為藉由瑞士乳酸桿菌來使乳發酵而獲得的發酵乳乳清的直接作用。 (Test Example 2: The harmful bacteria inhibitory effect of fermented whey was tested based on a culture experiment) Whether or not the harmful bacteria inhibitory action identified in Test Example 1 was a direct action of fermented whey obtained by fermenting milk with Lactobacillus helveticus was performed in the following manner by in vitro tests.

<發酵乳乳清之製備> 在由固體含量9質量%的脫脂奶粉所形成的乳培養基中,接種下述任一種的乳酸菌(最終接種量:菌數1~2 × 10 6個/mL),於35℃下靜置培養24小時,獲得發酵乳。將所獲得的發酵乳進行超濾(MW<5kDa),獲得各種發酵乳乳清。 [乳酸菌] 使用下述乳酸菌。另外,瑞士乳酸桿菌CM4菌株以外的乳酸菌係使用其各自的標準菌株。 ・瑞士乳酸桿菌 CM4菌株 ・瑞士乳酸桿菌 ・保加利亞德氏乳桿菌(Lactobacillus delbrueckii bulgaricus) ・嗜熱鏈球菌(Streptococcus thermophilus) ・嗜酸乳桿菌(Lactobacillus acidophilus) ・加氏乳桿菌(Lactobacillus gasseri) ・乾酪乳桿菌(Lactobacillus casei) <Preparation of fermented milk whey> In a milk medium formed of skimmed milk powder with a solid content of 9% by mass, any one of the following lactic acid bacteria was inoculated (final inoculation amount: 1 to 2 × 10 6 bacteria/mL), The fermented milk was obtained by stationary culture at 35°C for 24 hours. The obtained fermented milk was subjected to ultrafiltration (MW<5kDa) to obtain various fermented whey. [Lactic acid bacteria] The following lactic acid bacteria were used. In addition, the lactic acid bacteria strains other than the Lactobacillus helveticus CM4 strain used the respective standard strains.・Lactobacillus helveticus CM4 strain ・Lactobacillus helveticus ・Lactobacillus delbrueckii bulgaricus ・Streptococcus thermophilus ・Lactobacillus acidophilus ・Lactobacillus gasseri ・Cheese Lactobacillus casei

<試驗方法> (1) 於營養培養液(Nutrient Broth,日本BD公司製)中,接種拉氏西地西菌(Cedecea lapagei)、阿氏腸桿菌(Enterobacter asburiae)或解鳥氨酸勞特氏菌(Raoultella ornithinolytica),進行預培養。 (2)將上述製備的各種發酵乳乳清以5質量%添加至營養培養液中,並接種3%上述(1)中所培養的三種菌種的任一種,於37℃下培養16~24小時。將未添加發酵乳乳清的組作為對照組(control)。 (3)測量培養後的光學密度(Optical Density, OD)(600nm),並計算對照組OD值為100時的相對值。 (4)進行三次試驗,計算平均值,以司徒頓t檢定(Student's t-test)進行統計分析。將結果示於圖4。 <Test method> (1) Inoculate a nutrient medium (Nutrient Broth, manufactured by BD, Japan) with Cedecea lapagei, Enterobacter asburiae, or Raoultella ornithinolytica ) for pre-incubation. (2) The various fermented whey prepared above were added to the nutrient culture liquid at 5% by mass, inoculated with 3% of any one of the three strains cultivated in the above (1), and cultured at 37°C for 16 to 24 Hour. The group to which fermented whey was not added was set as a control. (3) Measure the optical density (Optical Density, OD) (600 nm) after culture, and calculate the relative value when the OD value of the control group is 100. (4) Carry out three experiments, calculate the average value, and perform statistical analysis by Student's t-test. The results are shown in FIG. 4 .

如圖4所示,表明了即使是在乳酸菌中,也只有藉由瑞士乳酸桿菌來使乳發酵而獲得的發酵乳乳清,具有抑制常駐肌膚菌中的有害菌之作用。As shown in FIG. 4 , even among lactic acid bacteria, only the fermented whey obtained by fermenting milk with Lactobacillus helveticus has the effect of suppressing harmful bacteria resident in skin bacteria.

(處方例1:軟膏) 根據常規方法製造具有以下組成之軟膏。另外,作為發酵乳乳清,於試驗例2中使用了用瑞士乳酸桿菌CM4菌株所製備的發酵乳乳清。 ・發酵乳乳清                                                                  ・・・ 0.05質量% ・苯扎氯銨                                                                      ・・・ 0.1質量% ・尿素                                                                             ・・・  20.0質量% ・白色凡士林                                                                  ・・・  15.0質量% ・輕質液體石蠟                                                              ・・・ 6.0質量% ・鯨蠟醇                                                                         ・・・ 3.0質量% ・硬脂醇                                                                         ・・・ 3.0質量% ・單硬脂酸甘油酯                                                          ・・・ 5.0質量% ・香精                                                                             ・・・  適量 ・防腐劑                                                                         ・・・  適量 ・緩衝劑                                                                         ・・・ 1.0質量% ・純淨水                                                                         ・・・  其餘 總量    100.0質量% (Prescription Example 1: Ointment) An ointment having the following composition was produced according to a conventional method. In addition, as fermented whey, in Test Example 2, fermented whey prepared with Lactobacillus helveticus CM4 strain was used. ・Fermented whey ・・・ 0.05% by mass ・Benzalkonium chloride             ・Urea・・・ 20.0% by mass ・White Vaseline   ・Light liquid paraffin・・・6.0% by mass ・Cetyl alcohol 3.0% by mass ・Stearyl alcohol 3.0% by mass ・Glyceryl monostearate ・・・ 5.0% by mass ・Fragrance            ・Preservatives ・・・ Appropriate amount ・Buffering agent ・Purified water・・・The rest Total 100.0% by mass

(處方例2:化妝液) 根據常規方法製造具有以下組成之化妝液。另外,作為發酵乳乳清,於試驗例2中使用了用瑞士乳酸桿菌CM4菌株所製備的發酵乳乳清。 ・發酵乳乳清                                                                  ・・・ 5.0質量% ・乳酸                                                                             ・・・ 0.1質量% ・果酸                                                                             ・・・ 0.1質量% ・甘油                                                                             ・・・ 4.0質量% ・高嶺土                                                                         ・・・ 1.0質量% ・爐甘石                                                                         ・・・ 0.7質量% ・樟腦                                                                             ・・・ 0.2質量% ・乙醇                                                                             ・・・  14.0質量% ・香精                                                                             ・・・  適量 ・純淨水                                                                         ・・・  其餘 總量    100.0質量% (Prescription Example 2: Cosmetic Liquid) Cosmetic liquids having the following compositions were produced according to conventional methods. In addition, as fermented whey, in Test Example 2, fermented whey prepared with Lactobacillus helveticus CM4 strain was used. ・Fermented whey ・・・ 5.0% by mass ・Lactic acid ・・・ 0.1% by mass ・Fruit acid              ・Glycerin   ・Kaolin Clay 1.0% by mass ・Calamine ・Camphor・・・ 0.2% by mass ・Ethanol・・・ 14.0% by mass ・Fragrance            ・Purified water・・・The rest Total 100.0% by mass

(處方例3:乳霜) 根據常規方法製造具有以下組成之乳霜。另外,作為發酵乳乳清,於試驗例2中使用了用瑞士乳酸桿菌CM4菌株所製備的發酵乳乳清。 ・發酵乳乳清                                                                  ・・・ 8.0質量% ・天然維生素E                                                               ・・・ 0.1質量% ・甘草黃酮                                                                      ・・・    0.005質量% ・固體石蠟                                                                      ・・・ 5.0質量% ・蜂蠟                                                                             ・・・  10.0質量% ・凡士林                                                                         ・・・  15.0質量% ・液體石蠟                                                                      ・・・  41.0質量% ・1,3-丁二醇                                                                   ・・・ 4.0質量% ・甘油單硬脂酸酯                                                          ・・・ 2.0質量% ・聚氧乙烯山梨醇酐單月桂酸酯(20)                            ・・・ 2.0質量% ・各種氨基酸                                                                  ・・・ 1.0質量% ・硼砂                                                                             ・・・ 0.2質量% ・防腐劑                                                                         ・・・  適量 ・香精                                                                             ・・・  適量 ・抗氧化劑                                                                      ・・・  適量 ・純淨水                                                                         ・・・  其餘 總量    100.0質量% (Prescription Example 3: Cream) A cream having the following composition was produced according to a conventional method. In addition, as fermented whey, in Test Example 2, fermented whey prepared with Lactobacillus helveticus CM4 strain was used. ・Fermented whey ・・・ 8.0% by mass ・Natural vitamin E  ・Glycyrrhiza flavonoids 0.005% by mass ・Solid paraffin wax 5.0% by mass ・Beeswax 10.0% by mass ・Vaseline 15.0% by mass ・Liquid paraffin 41.0% by mass ・1,3-Butanediol ・・・4.0% by mass ・Glyceryl monostearate ・・・ 2.0% by mass ・Polyoxyethylene sorbitan monolaurate (20) ・・・ 2.0% by mass ・Various amino acids ・・・ 1.0% by mass ・Borax・・・ 0.2% by mass ・Preservatives ・・・ Appropriate amount ・Fragrance            ・Antioxidants          ・Purified water・・・The rest Total 100.0% by mass

(處方例4:乳液) 根據常規方法製造具有以下組成之乳液。另外,作為發酵乳乳清,於試驗例2中使用了用瑞士乳酸桿菌CM4菌株所製備的發酵乳乳清。 ・發酵乳乳清                                                                  ・・・ 1.0質量% ・乳酸                                                                             ・・・ 2.0質量% ・硬脂醇                                                                         ・・・ 0.5質量% ・硬化棕櫚油                                                                  ・・・ 3.0質量% ・液體石蠟                                                                      ・・・  35.0質量% ・二丙二醇                                                                      ・・・ 6.0質量% ・聚乙二醇 (400)                                                            ・・・ 4.0質量% ・山梨糖醇倍半油酸酯                                                  ・・・ 1.6質量% ・聚氧乙烯 (20) 油基醚                                                 ・・・ 2.4質量% ・羧乙烯基聚合物                                                          ・・・ 1.5質量% ・氫氧化鉀                                                                      ・・・ 0.1質量% ・螯合劑                                                                         ・・・  適量 ・防腐劑                                                                         ・・・  適量 ・香精                                                                             ・・・  適量 ・純淨水                                                                         ・・・  其餘 總量    100.0質量% (Formulation Example 4: Emulsion) An emulsion having the following composition was produced according to a conventional method. In addition, as fermented whey, in Test Example 2, fermented whey prepared with Lactobacillus helveticus CM4 strain was used. ・Fermented whey ・・・ 1.0% by mass ・Lactic acid ・・・ 2.0% by mass ・Stearyl alcohol   ・Hardened palm oil  ・Liquid paraffin 35.0% by mass ・Dipropylene glycol              ・Polyethylene glycol (400)         ・Sorbit sesquioleate ・・・ 1.6% by mass ・Polyoxyethylene (20) oleyl ether       ・Carboxyvinyl polymer ・・・ 1.5% by mass ・Potassium Hydroxide   ・Chelating agent ・Preservatives ・・・ Appropriate amount ・Fragrance            ・Purified water・・・The rest Total 100.0% by mass

(處方例5:美容液) 根據常規方法製造具有以下組成之美容液。另外,作為發酵乳乳清,於試驗例2中使用了用瑞士乳酸桿菌CM4菌株所製備的發酵乳乳清。 ・發酵乳乳清                                                                  ・・・ 3.0質量% ・果酸                                                                             ・・・ 0.5質量% ・二丙二醇                                                                      ・・・ 5.0質量% ・聚乙二醇 (400)                                                            ・・・ 5.0質量% ・乙醇                                                                             ・・・  10.0質量% ・羧基乙烯基聚合物                                                      ・・・ 0.5質量% ・海藻酸鈉                                                                      ・・・ 0.5質量% ・氫氧化鉀                                                                      ・・・ 0.2質量% ・聚氧乙烯單硬脂酸酯 (20) 山梨糖醇酐                       ・・・ 1.0質量% ・單油酸山梨糖醇                                                          ・・・ 0.5質量% ・油醇                                                                             ・・・ 0.5質量% ・胎盤萃取物                                                                  ・・・ 0.2質量% ・乙酸dl-α-生育醇酯                                                      ・・・ 0.2質量% ・香精                                                                             ・・・  適量 ・防腐劑                                                                         ・・・  適量 ・防退色劑                                                                      ・・・  適量 ・純淨水                                                                         ・・・  其餘 總量    100.0質量% (Prescription example 5: Cosmetic liquid) A cosmetic liquid having the following composition was produced according to a conventional method. In addition, as fermented whey, in Test Example 2, fermented whey prepared with Lactobacillus helveticus CM4 strain was used. ・Fermented whey ・・・ 3.0% by mass ・Fruit acid              ・Dipropylene glycol              ・Polyethylene glycol (400)     ・Ethanol    ・Carboxy vinyl polymer ・・・ 0.5% by mass ・Sodium alginate           ・Potassium Hydroxide             ・Polyoxyethylene monostearate (20) Sorbitan ・・・ 1.0% by mass ・Sorbitol monooleate・・・ 0.5% by mass ・Oleyl alcohol            ・Placenta Extract                                                            ・dl-α-tocopherol acetate ・・・ 0.2% by mass ・Fragrance            ・Preservatives ・・・ Appropriate amount ・Anti-fading agent・・・Appropriate amount ・Purified water・・・The rest Total 100.0% by mass

[寄存編號] FERM BP-6060 [deposit number] FERM BP-6060

無。none.

[圖1]係表示於試驗例1中皮膚含水量的測量結果的圖。 [圖2]係表示於試驗例1中紋理體積率的測量結果的圖。 [圖3]係表示於試驗例1中紋理數量的測量結果的圖。 [圖4]係表示於試驗例2中使用各種乳酸菌的發酵乳乳清對有害菌的增殖抑制作用的測量結果的圖。 FIG. 1 is a graph showing the measurement results of skin moisture content in Test Example 1. FIG. FIG. 2 is a diagram showing the measurement results of the texture volume ratio in Test Example 1. FIG. FIG. 3 is a diagram showing the measurement results of the number of textures in Test Example 1. FIG. [ Fig. 4] Fig. 4 is a graph showing the results of measurement of the growth inhibitory effect of fermented whey using various lactic acid bacteria on harmful bacteria in Test Example 2. [Fig.

無。none.

Claims (5)

一種皮膚細菌叢改善劑,其特徵在於含有藉由瑞士乳酸桿菌(Lactobacillus helveticus)來使乳發酵而獲得的發酵乳乳清。A skin bacterial flora improving agent characterized by containing fermented whey obtained by fermenting milk with Lactobacillus helveticus. 如請求項1所述之皮膚細菌叢改善劑,其中,皮膚細菌叢的改善係為選自:皮膚細菌叢中有益菌的比例之維持、有益菌的比例之增加、有害菌的比例之降低中的至少其中之一。The skin bacterial flora improving agent according to claim 1, wherein the improvement of the skin bacterial flora is selected from the group consisting of maintaining the ratio of beneficial bacteria, increasing the ratio of beneficial bacteria, and reducing the ratio of harmful bacteria in the bacterial flora of the skin at least one of them. 如請求項2所述之皮膚細菌叢改善劑,其中,有害菌係具有引起炎症的可能性的細菌。The skin flora improving agent according to claim 2, wherein the harmful bacteria are bacteria that may cause inflammation. 如請求項1至3中任一項所述之皮膚細菌叢改善劑,其中,瑞士乳酸桿菌係瑞士乳酸桿菌CM4菌株(寄存編號:FERM BP-6060)。The skin bacterial flora improving agent according to any one of claims 1 to 3, wherein the Lactobacillus helveticus is a strain of Lactobacillus helveticus CM4 (accession number: FERM BP-6060). 一種皮膚細菌叢改善用皮膚外用劑,其特徵在於含有如請求項1至4中任一項所述之皮膚細菌叢改善劑。A skin external preparation for improving skin bacterial flora, characterized by containing the skin bacterial flora improving agent according to any one of claims 1 to 4.
TW110125978A 2020-09-29 2021-07-15 Skin flora improving agent and skin topical agent for improving skin flora in which skin bacterial flora improving agent includes fermented milk whey obtained by fermenting milk with Lactobacillus helveticus, and a skin topical agent TW202220681A (en)

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