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WO2011145737A1 - Composition pour améliorer l'état de la peau - Google Patents

Composition pour améliorer l'état de la peau Download PDF

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Publication number
WO2011145737A1
WO2011145737A1 PCT/JP2011/061695 JP2011061695W WO2011145737A1 WO 2011145737 A1 WO2011145737 A1 WO 2011145737A1 JP 2011061695 W JP2011061695 W JP 2011061695W WO 2011145737 A1 WO2011145737 A1 WO 2011145737A1
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WIPO (PCT)
Prior art keywords
composition
skin
acid bacteria
propionic acid
culture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2011/061695
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English (en)
Japanese (ja)
Inventor
秀二 池上
孝之 利光
義男 大原
英恵 土橋
伊藤　裕之
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Meiji Co Ltd
Original Assignee
Meiji Co Ltd
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Filing date
Publication date
Application filed by Meiji Co Ltd filed Critical Meiji Co Ltd
Priority to CN201180035694.7A priority Critical patent/CN103025338B/zh
Priority to JP2012515953A priority patent/JP5954828B2/ja
Priority to SG2012081121A priority patent/SG185410A1/en
Priority to HK13106302.5A priority patent/HK1178465B/xx
Publication of WO2011145737A1 publication Critical patent/WO2011145737A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K2035/11—Medicinal preparations comprising living procariotic cells

Definitions

  • the present invention relates to a composition for improving skin condition comprising a culture of propionic acid bacteria.
  • the present invention also relates to DHNA (1,4-dihydroxy-2-naphthoic acid; 1,4-dihydroxy-2-naphthoic acid), ACNQ (2-amino-3-carboxy-1,4-naphthoquinone; 2-amino -3-carboxy-1,4-naphthoquinone), or an analogue thereof, relates to a composition for improving skin condition.
  • Profec (Profec; manufactured by Meiji, trade name; "Profec” is a registered trademark of Meiji Co., Ltd.) is a fermented whey product of Propionibacterium freudenreichii ET-3 strain isolated from Emmental cheese, It has been developed as a material containing a component having an action of promoting the growth of bifidobacteria among internal bacteria (Non-patent Document 1). In subsequent studies, DHNA (1,4-dihydroxy-2-naphthoic acid) was identified as the main component involved in the growth promotion of bifidobacteria contained in Profec.
  • Non-patent Document 2 When humans ingest Profec, it becomes clear that the bifidobacteria possessed in the intestines of individuals increases and the effect of intestinal regulation is demonstrated (Non-patent Document 2). ; “Mother's vitality” is a registered trademark of Meiji Co., Ltd.), “Mother's vitality milk” (Meiji, “Mother's vitality” is a registered trademark of Meiji Co., Ltd.), etc. have been commercialized and approved as food for specified health use. Yes. It has also been clarified that DHNA is administered to a colitis model animal to exhibit the effect of improving / preventing enteritis (Non-patent Document 3).
  • Non-patent Document 4 the skin beautifying effect by ingesting yogurt has been studied mainly in human tests, and it has been confirmed that the intestinal regulation effect and the skin condition improving effect correlate well. Moreover, in the investigation test which compares a constipation person and a non-constipation person, possibility that the intestinal environment and a skin state are related is confirmed (nonpatent literature 5).
  • An object of the present invention is to provide a composition for improving skin condition including a culture of propionic acid bacteria. And the subject of this invention is providing the composition containing the culture of propionic acid bacteria which has the improvement effect of skin condition especially.
  • the present inventors have repeatedly investigated the effect of skin beautification by ingesting yogurt, mainly in human tests. Among them, the present inventors confirmed that the intestinal regulating effect and the skin condition improving effect are well correlated. Furthermore, in the investigation study comparing constipation and non constipated person, to confirm the possibility of intestinal environment and skin condition is concerned. Accordingly, the present inventors have intake Profec the intestinal action is authorized attempts whether consideration to improve skin condition. From the results, the present inventors found that the stratum corneum water content and texture score were significantly improved in the Profec intake group compared to the placebo group. In addition, it was confirmed that DHNA, which is an active ingredient of Profec, has an action of suppressing the production of melanin that causes stains.
  • DHNA which is an active ingredient of Profec
  • a composition for improving skin condition comprising at least one component selected from the group consisting of the following (a) to (c): (A) a culture of propionic acid bacteria, (B) DHNA or an analog thereof, and (c) ACNQ or an analog thereof.
  • a composition according to [1] wherein the propionic acid bacterium is Propionibacterium freudenreichii.
  • composition according to [3] wherein the milk fermentation component is milk fermented with lactic acid bacteria belonging to the genus Lactobacillus and / or lactic acid bacteria belonging to the genus Streptococcus, or a mixture thereof.
  • Analogs of DHNA or ACNQ are 1,4-naphthoquinone, 2-methyl-1,4-naphthoquinone, 4-amino-2-methyl-1-naphthol, and 2-amino-3-chloro-1,
  • a pigmentation inhibitor in skin comprising at least one component selected from the group consisting of the following (a) to (c): (A) a culture of propionic acid bacteria, (B) DHNA or an analog thereof, and (c) ACNQ or an analog thereof.
  • the composition of the present invention has an action of improving the skin condition, particularly an action of inhibiting the production of melanin in the skin. Moreover, it has the effect
  • the composition of the present invention can be produced by blending ingredients that have already been administered to humans as food or the like. Therefore, the composition of the present invention is already guaranteed a high level of safety and can be taken continuously. That is, with the composition of the present invention, continuous improvement of the skin condition can be expected.
  • the composition of the present invention is provided by a combination of components that are already widely consumed as general foods, liquid foods, and the like. Therefore, by continuously ingesting the composition of the present invention as a food such as yogurt, a state in which the production of melanin in the skin is inhibited can be continued.
  • the vertical axis represents the amount of keratin water (arbitrary unit; AU).
  • the horizontal axis represents the test meal A (placebo) intake group, test meal B (Profec-containing acidic drink) intake group, and test meal C (Profecfe-containing yogurt drink) intake group, respectively.
  • the vertical axis represents the amount of horny water calculated from the capacitance measured with a corneometer, and the horizontal axis represents the intake period (weeks) of the test meals A to C.
  • * indicates a significant difference in risk rate p ⁇ 0.05.
  • the vertical axis shows the texture score.
  • the horizontal axis represents the test meal A (placebo) intake group, the test meal B (Profec-containing acidic drink) intake group, and the test meal C (Profec-containing yogurt drink) intake group, respectively.
  • the vertical axis represents the texture score measured with “Robo Skin Analyzer” (trade name), and the horizontal axis represents the intake period (weeks) of the test meals A to C.
  • * indicates a significant difference in risk rate p ⁇ 0.05.
  • the vertical axis shows the average number of defecations per week.
  • the horizontal axis represents the test meal A (placebo) intake group, the test meal B (Profec-containing acidic drink) intake group, and the test meal C (Profec-containing yogurt drink) intake group, respectively.
  • * indicates a significant difference in risk rate p ⁇ 0.05.
  • the vertical axis represents the IL-1ra / IL-1 ⁇ ratio of each group. It is a graph which shows IL-8 in a stratum corneum. In the figure, the vertical axis represents the content (pg) of IL-8 per 1 ⁇ g of protein in the stratum corneum. IL-8 in the stratum corneum was significantly increased before and after intake in the test meal A (placebo) intake group. In groups other than the test food A (placebo) intake group, there was no change in the IL-8 concentration before and after the intake. It is a graph which shows the melanin production inhibitory effect of DHNA and ACNQ.
  • the vertical axis represents the amount of melanin produced in the cell culture (absorbance at 405 nm), and the horizontal axis represents each test compound. Both DHNA and ACNQ were suggested to have a strong melanin production inhibitory effect.
  • the present invention provides a composition for improving skin condition, or a pigmentation inhibitor in skin, comprising at least one component selected from the group consisting of (a) to (c) below.
  • A) culture of propionic acid bacteria (b) DHNA or analog thereof (c) ACNQ or analog thereof
  • the composition for improving skin condition of the present invention, or a pigmentation inhibitor in skin is a culture of propionic acid bacteria.
  • Propionic acid bacteria are gram-positive anaerobic bacteria belonging to the genus Propionibacterium, and are microorganisms that produce propionic acid oxygen-freely from sugars. Specifically, the following microorganism cultures can be added to the composition of the present invention.
  • Propionibacterium freudenreichii Propionibacterium toeni (P. thoenii), Propionibacterium acidipropionici (P. acidipropionici), Propionibacterium genseny (P. jensenii) and the like.
  • These propionic acid bacteria are microorganisms used for cheese production.
  • the following microorganisms can also be shown as propionic acid bacteria. Ie, Propionibacterium avidum (P. avidum), Propionibacterium acnes (P. acnes), Propionibacterium lymphophilum (P. lymphophilum), Propionibacterium granulosam (P. granulosam) is there.
  • Propionic acid bacteria can also utilize microorganisms that are used in Swiss cheese production and the like.
  • the culture of propionic acid bacteria in the present invention refers to those obtained by culturing the above propionic acid bacteria under appropriate culture conditions. Methods for culturing propionic acid bacteria are known. In the culture of propionic acid bacteria, the conditions described in WO03 / 016544A1 and the like can be applied.
  • a medium for culturing propionic acid bacteria a composition in which beer yeast extract or the like is added to skim milk powder or a proteolytic processed product of skim milk powder is known.
  • a culture of propionic acid bacteria can be obtained by inoculating a suitable medium with Propionibacterium re freudenreichii and culturing under conditions that allow propionic acid bacteria to grow.
  • whey protein concentrate Whey Protein Concentrate:, hereinafter also referred to as WPC
  • WPC Whey Protein Concentrate
  • its enzyme degradation product as a processed product of whey, minerals and monosaccharides
  • a method of culturing propionic acid bacteria using an added medium Japanese Patent Publication No. 10-304871.
  • a culture obtained by culturing Propionibacterium oni freudenreichii in a medium containing WPC is preferable as the culture of propionic acid bacteria in the present invention.
  • a processed product of whey as a whey protein source as a main component of the medium
  • propionic acid bacteria can be cultured at high density.
  • a mixture of minerals and monosaccharides can be used as a medium component.
  • the following components can be exemplified as processed products of whey. That is, it is a whey powder, a protease-treated product of whey or whey powder.
  • WPC and / or whey protein isolate Whey Protein Isolate: hereinafter referred to as WPI
  • WPI whey Protein Isolate
  • whey is a water-soluble component remaining when, for example, fat, casein, fat-soluble vitamins and the like are removed from milk.
  • Whey generally produces acid casein and quark from cheese whey, rennet whey (or sweet whey) and skim milk that are obtained as by-products when natural cheese and rennet casein are produced.
  • Casein whey and quark whey or acid (acid) whey are obtained as by-products.
  • the main components of whey include protein ( ⁇ -lactoglobulin, ⁇ -lactalbumin, etc.), lactose, water-soluble vitamins, and salts (minerals). It is clarified from research as an ingredient.
  • whey concentrated whey, whey powder dried whey (whey powder), and major proteins in whey are subjected to ultrafiltration (UF) method
  • WPC Ultrafiltration
  • WPC Degreased whey protein concentrate
  • MF microfiltration
  • MF microfiltration
  • NF nanofiltration
  • desalted by electrodialysis etc.
  • dried desalted whey, minerals derived from whey-derived mineral components and concentrated by centrifugation etc.
  • concentrated whey concentrated whey.
  • WPC containing 15% to 80% dry protein (solid content) as dry weight is a protein-concentrated whey powder on 30 March 1998 due to a partial amendment to the Ordinance of the Ministry of Milk, etc. Defined in the product (concentrated whey, whey powder, WPC, whey protein concentrated powder, regardless of the presence or absence of a desalting step, as long as they have undergone the manufacturing process specified by the Ministerial Ordinance)
  • WPC is obtained by concentrating main whey proteins and the like by ultrafiltration and then drying.
  • it is a generic name for whey proteins in which about 25% or more of the solid content is whey protein. It can be obtained by reducing lactose, salts, etc. from whey, relatively strengthening whey protein, and adjusting the solid content to about 25% to about 80%.
  • the WPC in particular containing 15 to 80% milk protein as dry weight, the milk or the like ordinance, it is defined as a protein concentrate whey powder.
  • the standard method for producing whey protein concentrate (WPC) is as follows. (1) A step of concentrating whey after membrane separation. Or (2) A step of concentrating and drying the whey after membrane separation.
  • a general apparatus and method can be used for the concentration treatment, for example, a vacuum evaporator (evaporator), a vacuum kettle, a thin film vertical ascending tubular concentrator, a thin film vertical descending tubular concentrator, a plate type concentrator.
  • concentration treatment for example, a vacuum evaporator (evaporator), a vacuum kettle, a thin film vertical ascending tubular concentrator, a thin film vertical descending tubular concentrator, a plate type concentrator.
  • a method of heating under reduced pressure using a machine or the like can be used.
  • a general apparatus or method can be used for the drying process, for example, spray drying (spray dryer) method, drum drying method, freeze vacuum drying (freeze dryer) method, vacuum (reduced pressure) drying method, etc. Can be used.
  • WPI is obtained by concentrating main whey proteins and the like by an ion exchange resin method, an electrodialysis method, and the like, and then drying them.
  • ion exchange resin method an electrodialysis method, and the like
  • WPI is a generic term for those in which about 85% to about 95% of the solid content is whey protein. It can be obtained by reducing lactose, salts, etc. from whey, relatively strengthening whey protein, and adjusting it to about 90% (85% to 95%) of the solid content.
  • a standard method for producing whey protein isolate (WPI) is as follows. (1) A step of concentrating whey after membrane separation, ion exchange resin treatment or electrodialysis treatment.
  • a step of concentrating and drying the whey after membrane separation, ion exchange resin treatment or electrodialysis treatment a general apparatus and method can be used for the concentration treatment, for example, a vacuum evaporator (evaporator), a vacuum kettle, a thin film vertical ascending tubular concentrator, a thin film vertical descending tubular concentrator, a plate type concentrator.
  • concentration treatment for example, a vacuum evaporator (evaporator), a vacuum kettle, a thin film vertical ascending tubular concentrator, a thin film vertical descending tubular concentrator, a plate type concentrator.
  • a method of heating under reduced pressure using a machine or the like can be used.
  • a general apparatus or method can be used for the drying process, for example, spray drying (spray dryer) method, drum drying method, freeze vacuum drying (freeze dryer) method, vacuum (reduced pressure) drying method, etc. Can be used.
  • the following composition can be exemplified as a medium suitable for cultivation of propionic acid bacteria. That is, the protein content is 1% to 5%, preferably 1.5% to 4%.
  • the carbohydrate content is 1% to 4%, preferably 1.5% to 3%.
  • the addition amount (blending amount) of whey, a processed product of whey or the like, or a processed protease product thereof is adjusted.
  • the sugar is preferably not a lactose but a monosaccharide obtained by treating glucose or lactose with lactase.
  • all the numerical values shown in this specification are weight ratios (W / W%). When the composition is expressed in% (percentage), it is the weight ratio (W / W%) unless otherwise specified.
  • a lactase treatment solution of whey mineral can be used as a source of carbohydrates and minerals.
  • WPC or WPI can be used as a protein source
  • whey minerals can be used as a saccharide source and a mineral source.
  • propionic acid bacteria can be cultured at a higher concentration than when whey powder is used as the raw material for the medium.
  • a detailed method for preparing a medium for culturing propionic acid bacteria is shown below. That is, after reducing WPC or WPI (bovine), the protein is degraded with a protease.
  • Protease is an endo-exo type derived from Aspergillus oryzae, and the amount of protease used is 3% of the protein to be degraded.
  • the protease reaction proceeds at a temperature of 50 ° C. and a pH of 7, and is continuously stirred for 3 to 5 hours until the pH does not drop.
  • lactase is used to break down lactose.
  • the amount of lactase used should be 2% to 8% of the carbohydrates that are degraded.
  • the lactase reaction proceeds at a temperature of 50 ° C. to 60 ° C. (preferably 55 ° C.), a pH of 5 to 6, and is continuously stirred until lactose is completely decomposed.
  • the final medium composition is a protein concentration of 1% to 5% (preferably 1.5% to 4%), and a carbohydrate concentration of 1% to 4% (preferably 1.5% to 3%). %)), These two WPC or WPI protease-treated products and whey mineral lactase-treated products are mixed. Finally, after adding ingredients commonly used for the culture of propionic acid bacteria such as yeast extract, sodium sulfate and asparagine as the composition of the medium, the pH is adjusted to 5-8 (preferably 5.5-7.5), The medium preparation is finished.
  • the culture process of propionic acid bacteria is as follows. Specifically, the temperature of the medium is adjusted to 20 ° C. to 40 ° C., and the starter is inoculated so that the viable cell count immediately after the start of culture is 10 7 to 10 8 cfu / ml, and cultured for 3 to 4 days. . The pH is maintained at 5.5 to 7.5 with an aqueous potassium carbonate solution. Glucose can be additionally added during the culture. The concentration of propionic acid bacteria contained in the thus obtained culture reaches about 5 times the conventional concentration.
  • the above culture conditions are particularly suitable for culturing propionic acid bacteria for cheese.
  • Propionibacterium freudenreichii Propionibacterium acidipropionici, Propionibacterium jensenii, Propionibacterium thoenii and the like can be used as propionic acid bacteria for cheese.
  • a culture from which the following strains can be obtained as propionic acid bacteria can be used in the present invention. That is, Propionibacterium freudenreichii ATCC 6207, P. freudenreichii ATCC 8262, P. freudenreichii IFO 12424, P. freudenreichii IFO 12426, P. freudenreichii IFO 12391, P.
  • freudenreichii ET-8 These propionic acid bacteria can be cultivated alone, or a plurality of strains can be mixed and cultured. Alternatively, after culturing a plurality of microorganisms alone, the obtained cultures can be mixed. The culture thus obtained can be directly used for eating and drinking. Alternatively, it can be pulverized or liquefied, and processed into a form that is easy to handle as a functional raw material. That is, the culture obtained by culturing the propionic acid bacterium can be blended with the composition of the present invention directly or after being processed.
  • those skilled in the art can appropriately adjust the composition of the medium and the culture conditions in order to optimize these known methods.
  • the medium composition in addition to casein, WPC, WPI, etc. as a nitrogen source, various amino acids and their salts are additionally added to optimize and enhance the propionic acid bacteria growth ability and skin condition improvement effect.
  • the culture conditions can be adjusted to increase the concentration, temperature, pressure, etc. of the oxygen in the culture atmosphere to optimize and enhance the propionic acid bacteria proliferative ability and skin condition improving effect.
  • the culture of propionic acid bacteria of the present invention includes, for example, the culture itself of propionic acid bacteria, the culture supernatant, the cells themselves, their extracts, their dried products, or their dilutions.
  • the action of promoting the improvement of the skin condition of the fraction component of the culture of propionic acid bacteria is, for example, 30% or more compared to the culture of propionic acid bacteria of the same origin (before fractionation), When it is preferably 50% or more, more preferably 70% or more, it can be said that the effect of improving the skin condition of the propionic acid bacteria culture itself was maintained.
  • the culture of the propionic acid bacterium of the present invention can be sterilized after the cultivation is completed and can be blended in the composition of the present invention.
  • the composition (mixture) can be sterilized after blending with milk fermentation components and the like.
  • a sterilization method or the like is defined in an ordinance such as milk, and the following heat sterilization treatment is generally performed. That is, low temperature long time sterilization, high temperature short time sterilization, ultra high temperature (instant) sterilization.
  • the sterilization method or heat sterilization treatment equivalent to that of milk can be applied to the culture of propionic acid bacteria of the present invention or a composition containing the same.
  • These heat sterilization treatments can be performed batchwise (in batch units) or continuously.
  • the treatment temperature and treatment time vary depending on the respective heat sterilization treatment, but preferably 60 ° C. to 150 ° C., in the range of 0.1 second to 1 hour, more preferably 70 ° C. to 150 ° C., 0.5 second to 45 minutes.
  • the range is more preferably 80 ° C. to 150 ° C., and the range of 1 second to 30 minutes is selected according to the sterilization method described above.
  • the inert gas atmosphere is continuously maintained as necessary.
  • the inert gas include nitrogen gas, argon gas, carbon dioxide gas, etc.
  • nitrogen gas is present in a large amount in the air, the cost is relatively low, and safety has been confirmed. It is desirable as an inert gas because it does not affect the flavor and quality of food and drink.
  • the present inventors have confirmed that the skin condition improving effect is maintained in the sterilized product of the propionic acid bacteria culture. That is, in the present invention, the effect of improving the skin condition of the culture of propionic acid bacteria is maintained even after the culture is sterilized. Normally, the effect of lactic acid bacteria on the host depends on the action of live bacteria. Therefore, it was an unexpected finding that a beneficial effect (a useful function) was found not only before and after sterilization of the culture of propionic acid bacteria.
  • Probiotics and prebiotics have been reported to improve the intestinal environment and stimulate immunity. In general, probiotics refer to microorganisms that have a beneficial effect on the host when introduced into the intestine of the host in a living state.
  • prebiotics refer to substances that have a beneficial effect on the host by acting on microorganisms that originally lived in the intestines.
  • lactic acid bacteria have been reported as probiotics having skin beautifying effects, particularly in human tests.
  • probiotics are probiotics that act as live bacteria, their production and quality control have not been easy.
  • a microbial preparation has a limit in storage stability. For example, after a microbial preparation is produced, it is often unbearable for a long time even if it is stored at a low temperature.
  • the culture of propionic acid bacteria of the present invention also functions as prebiotics.
  • the sterilized product (prebiotic) of the culture of the propionic acid bacterium of the present invention the activity of the microorganism (propionic acid bacterium) is stopped, and the quality does not change. Therefore, the prebiotics such as the culture of propionic acid bacteria of the present invention can stably maintain the skin condition improving effect. That is, since the culture of propionic acid bacteria of the present invention or a composition containing the same is a prebiotic that also acts as a dead bacteria, its production and quality control are easy.
  • the preparations and the like based on the present invention can be stored at room temperature for a long period of time.
  • the effect of lactic acid bacteria is expected by oral administration, it often depends on the action of live bacteria, and the influence of gastric acid must be considered. This is because the number of viable bacteria of lactic acid bacteria decreases due to the influence of gastric acid, and a sufficient amount of live bacteria cannot be delivered into the intestine.
  • the improvement effect of the skin state by the culture of propionic acid bacteria does not depend on the effect
  • the intestinal regulation effect by improving the intestinal flora and the skin beautifying effect always correlate. That is, in the case of lactic acid bacteria, the effect of improving the skin condition is exhibited depending on the effect of regulating the intestines. Similarly, in the case of propionic acid bacteria, it has been clarified that the effect of improving the skin condition is exhibited depending on the intestinal regulating effect. However, in the case of the culture of propionic acid bacteria of the present invention, it has also been clarified that the skin beautifying effect is exhibited independently of the intestinal regulating effect.
  • composition or the pigment formation inhibitor of the present invention is expected to have a skin beautifying effect independent of the intestinal regulating effect in addition to the skin beautifying effect based on the intestinal regulating effect by using a culture of propionic acid bacteria. can do.
  • the culture or sterilized product of the propionic acid bacterium of the present invention can be processed into powder or liquid.
  • an appropriate excipient may be added to the culture or sterilized product of the present invention to adjust the solid content concentration to 30% to 40%, and then dried to be powdered.
  • known excipients can be used, such as skim milk powder, whey powder, raw starch, dextrin, etc., as well as WPC, WPI, modified starch, etc. as necessary. Can be used.
  • a known method can also be used for drying. For example, a method of spray-drying the culture or sterilized product of the present invention as it is, or the culture or sterilized product of the present invention can be used.
  • a method of spray drying after mixing the reducing solution of the excipient and concentrating until the solid content concentration becomes 30% to 40% can also be used.
  • the dried product (powder, etc.) of the culture or sterilized product of the present invention can be stably treated for a long period of time by deoxidation treatment (such as nitrogen encapsulation or addition of oxygen scavenger) when filling the packaging material or container. Can be saved. In addition, it can be processed into a triturated preparation (0.2% powdered powder) for easy use in foods.
  • deoxidation treatment such as nitrogen encapsulation or addition of oxygen scavenger
  • it can be processed into a triturated preparation (0.2% powdered powder) for easy use in foods.
  • the modified starch specifically, soluble starch, British gum, oxidized starch, starch ester, starch ether and the like can be used in addition to dextrin.
  • BGS Bacillus subtilis
  • a whey fermented product by the propionic acid bacterium is preferable.
  • a propionic acid bacterium culture obtained by fermenting Propionibacterium oni freudenreichii -3 ET-3 strain producing BGS with whey powder reducing solution (10%) can be contained as an active ingredient in the composition of the present invention.
  • the culture of propionic acid bacteria containing BGS is called “Profec”, and it is approved as a component involved in food for specified health use.
  • B.G.S.powder made by Meiji, trade name
  • tummy vitality tablet made by Meiji, trade name; “Takaka vitality” is a registered trademark of Meiji Co., Ltd.
  • “B.G.S.powder” or “tummy vitality tablet” can also be used as the composition of the present invention. It is known that an excellent intestinal effect can be expected from fermented whey of propionic acid bacteria. However, it has not been known that the culture of propionic acid bacteria shows an effect of improving the skin condition.
  • BGS contained in Profec includes 1,4-dihydroxy-2-naphthoic acid; 1,4-dihydroxy-2-naphthoic acid (DHNA) and 2-amino-3-carboxy-1,4-naphthoquinone ; 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ).
  • DHNA is a biosynthetic intermediate of vitamin K2 (menaquinone) in microorganisms. These DHNA and ACNQ promote the growth of bifidobacteria by efficiently reoxidizing NADH produced during the energy metabolism process of bifidobacteria.
  • either or both of the following components (i) and (ii) can be used as a culture of propionic acid bacteria. That is, the present invention (I) 1,4-dihydroxy-2-naphthoic acid (DHNA) or an analogue thereof, and (ii) 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ) or an analogue thereof, or Provided is a composition for improving skin condition comprising both.
  • DHNA 1,4-dihydroxy-2-naphthoic acid
  • ACNQ 2-amino-3-carboxy-1,4-naphthoquinone
  • DHNA and ACNQ production methods have already been established, and those skilled in the art can easily synthesize and obtain them based on known literatures.
  • DHNA can be synthesized according to the method described in JP-A-2007-284449, but is not limited thereto.
  • ACNQ can be synthesized according to the methods described in JP-A-7-289273, JP-A-3265193, JP-A-2003-89683, JP-A-4072430, JP-A-35332226 and the like, but is not limited thereto.
  • the present invention relates to a composition for improving skin condition, comprising either an analog of DHNA, an analog of ACNQ, or both.
  • analogs of DHNA and ACNQ include, but are not limited to, the following compounds: That is, 1, 4-naphthoquinone, 2-methyl-1, 4-naphthoquinone, 4-amino-2-methyl-1-naphthol, 2-amino-3-chloro-1, 4-naphthoquinone.
  • These analogs are also known to be produced in cultures of microorganisms used in the production of fermented milk (Japanese Patent Laid-Open No. 7-289273). Therefore, these analogs can be used as they are in the composition of the present invention by blending the culture or the fraction components thereof. Alternatively, these analogs can be purified together with DHNA or ACNQ and used in the composition of the present invention.
  • the dose of the composition for improving skin condition containing the above components (i) and / or (ii) is usually determined for adults using the amount of DHNA contained in the culture of propionic acid bacteria as an index.
  • the amount of DHNA contained in the culture of propionic acid bacteria is generally in the range of 0.01 ⁇ g / kg to 100 mg / kg.
  • lower doses may be sufficient, and conversely higher doses may be required.
  • it can be divided into 2 to 4 times a day for administration.
  • the specific dose can be set in consideration of the patient's condition such as age and weight, the administration route, the degree of improvement effect actually expected, and the like.
  • the preferred administration route in the present invention is oral administration.
  • Profec is specifically approved as an ingredient in foods for specified health use because it specifically increases Bifidobacterium in the human intestine (Nobuo Yoda: ILSI, No. 80, 5-13) (2004)).
  • BGSpowder and “Tummy Vitality Tablet” are commercially available as compositions containing Profec. Therefore, it can be said that there is no difficulty in obtaining the composition of the present invention.
  • feeding animals with Profec inhibits pigment formation in the skin.
  • the present invention (I) 1,4-dihydroxy-2-naphthoic acid (DHNA) or an analog thereof, and (ii) 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ) or an analog thereof, or A pigmentation inhibitor in the skin comprising both is provided.
  • the present invention any of the components (i) and (ii), or includes both relates to a pharmaceutical composition for inhibiting the formation of the dye in the animal skin.
  • the preferred animal in the present invention is a human.
  • DHNA 1,4-dihydroxy-2-naphthoic acid
  • a method for reducing the amount of dissolved oxygen in a composition containing DHNA is known (WO2004 / 85364). Specifically, when the composition of the present invention is in a liquid state, dissolved oxygen can be replaced with a gas other than oxygen by bubbling the liquid composition with a gas not containing oxygen. At this time, nitrogen gas is preferable as the gas not containing oxygen.
  • dissolved oxygen can be removed by subjecting the liquid composition to a vacuum degassing treatment or the like.
  • the amount of dissolved oxygen can be kept low by blending a compound having antioxidant ability together with DHNA.
  • a known antioxidant can be used for the compound having antioxidant ability. Specific examples include hyposulfite, ascorbic acid (vitamin C), erythorbic acid, carotene, tocopherol, and polyphenols having an antioxidant action.
  • polyphenols derived from natural products can also be used as polyphenols.
  • polyphenols derived from teas, grapes, lemons, coffee, Murasakimochi, soybeans and the like are known.
  • Juices such as fruits, vegetables, seeds, plant leaves, etc., containing these polyphenols, or extracts thereof can be blended as polyphenols in the composition of the present invention.
  • a polyphenol extract can be obtained by extraction with water or an organic solvent. Concentrates, purified products, and dried products of products containing these natural polyphenols can also be blended in the composition of the present invention as polyphenols.
  • the amount of dissolved oxygen can be reduced by setting the additive amount of the antioxidant to be equal to or more than the additive amount normally used for antioxidant purposes, depending on the type of antioxidant. For example, when ascorbic acid is added alone to the composition of the present invention without bubbling with an inert gas and the stability of DHNA is expected reliably, 1g or more will be added.
  • the amount of antioxidant generally added can be set, for example, to 1 ⁇ g to 2 g, preferably 150 ⁇ g to 1.5 g, more preferably about 1 mg to 1 g. At this time, the antioxidant can be added before, after or simultaneously with the addition of DHNA to the composition of the present invention.
  • the culture of the propionic acid bacterium of the present invention is blended in a ratio of, for example, 0.001% to 20%, preferably 0.01% to 15%, more preferably 0.05% to 10% with respect to the entire composition of the present invention. be able to.
  • the composition of the present invention can be made into an arbitrary dosage form such as powder, solid, etc. by liquid, paste, or drying.
  • the composition of the present invention can be prepared by blending propionic acid bacteria cultures with ingredients suitable for oral administration, pharmaceutically acceptable carriers, and the like. More specifically, it can be formulated into tablets, capsules, granules, powders, syrups and the like. Or it can also supply in the state which disperse
  • compositions are mainly used in the pharmaceutical formulation technology field such as excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspending agents, coating agents, solvents, and isotonic agents. It can be formulated according to conventional methods while applying known adjuvants that can be used normally. Moreover, minerals, such as calcium, can be mix
  • a milk fermentation component can be additionally blended.
  • the milk fermentation component refers to a processed milk product obtained by fermenting animal milk by the action of microorganisms or enzymes.
  • animal milk refers to milk, buffalo milk, goat milk, sheep milk, horse milk, and the like.
  • milk (cow milk) is economically advantageous because it can be easily obtained in large quantities.
  • the milk fermentation component of the present invention can be prepared not only from the milk itself collected from the animal's living body, but also from its fractionated components and processed products.
  • skim milk as a milk fraction component or processed product, skim milk, partially skim milk, reduced full fat milk, reduced skim milk, reduced partial skim milk, full fat concentrated milk, skim concentrated milk, partial skim concentrated milk, full fat powder
  • milk skim milk powder, partially skim milk powder, casein, whey, reduced whey, concentrated whey, whey powder, WPC, WPI, cream, butter, buttermilk, buttermilk powder and the like.
  • These fractionated components or processed products derived from milk are sometimes called raw milk.
  • the raw milk can be used as a raw material for the milk fermentation component alone or mixed with different raw milk.
  • the milk fermentation component can be obtained as a culture fermented by adding microorganisms to milk.
  • the fraction component can be used as the milk fermentation component of the present invention.
  • Microorganisms used for the purpose of milk fermentation are generally called starters, and lactic acid bacteria or bifidobacteria are preferred as the microorganisms.
  • milk fermentation components can be obtained using lactic acid bacteria or bifidobacteria belonging to the following genera as a starter.
  • the genus Lactobacillus, Streptococcus, Enterococcus, Lactococcus, Leuconostoc, Pediococcus, Bifidobacterium and the like More specifically, it is preferable to obtain a milk fermentation component by the following microorganisms.
  • the lactic acid bacteria Streptococcus lactis, Streptococcus cremoris, Streptococcus diacetylactis, Enterococcus faecium, Enterococcus faecalis, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus delbrueckii subsp. Bulgaricus, Lactobacillus delbrueckii subsp.
  • Bifidobacterium include Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium breve and the like.
  • the Bulgarian bacterium (Lactobacillus delbrueckii subspecies bulgaricus) of the present invention is used in a starter in combination with Thermophilus OLS3059 (Streptococcus thermophilus OLS3059), and has the ability to form a card of fermented milk (milk fermentation component)
  • Thermophilus OLS3059 Streptococcus thermophilus OLS3059
  • fermented milk milk fermentation component
  • Examples include, but are not limited to, lactic acid bacteria obtained by separating (isolating) from plain yogurt, hard yogurt, and soft yogurt manufactured by Meiji Co., Ltd.
  • Thermophilus OLS3059 (Streptococcus ophilthermophilus OLS3059) is registered with the independent administrative corporation National Institute of Advanced Industrial Science and Technology Patent Organism Depository Center: Ferm BP-10740 (Indication for identification: Streptococcus thermophilus OLS3059, Deposit date (date of deposit): Heisei November 29, 18).
  • Bulgaria bacteria for example, in the administrative agency National Institute of Advanced Industrial Science and Technology Patent Biological Deposit Center: FERM BP-10741 (Indication for identification: Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1, deposit date (date of deposit): November 29, 2006), which is the Bulgarian fungus OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1).
  • a method for separating these microorganisms from the natural world and fermented milk is known.
  • microorganisms that have already been separated (isolated) can be obtained by distribution of cell banks or the like.
  • some starters for obtaining milk fermentation components are commercially available.
  • loop fermentation component prepared with these commercially available starters can also be utilized by mix
  • several products are marketed by the difference in pH, physical property, etc. of fermented milk (milk fermentation component) actually prepared.
  • the physical properties of fermented milk refer to tension, smoothness, and the like.
  • a commercially available starter should be used as a starter for obtaining the fermented milk component of the present invention as long as it improves the skin condition when administered with a culture of propionic acid bacteria, and particularly inhibits pigment formation in the skin. Can do.
  • raw milk can be inoculated using the following microorganism as a starter. That is, Lactobacillus bulgaricus (L. bulgaricus), Streptococcus thermophilus (S. thermophilus), Lactobacillus lactis (L. lactis) and the like.
  • Lactobacillus bulgaricus L. bulgaricus
  • Streptococcus thermophilus S. thermophilus
  • Lactobacillus lactis L. lactis
  • raw material milk may be added with one or more selected from lactic acid bacteria and yeast other than these lactic acid bacteria.
  • thermophilus standardized as a yogurt starter in the Codex standard. preferable.
  • the microorganisms can be additionally mixed in these mixed starters in consideration of the final fermentation temperature and fermentation time of the fermented milk. Examples of microorganisms additionally used in these mixed starters include Lactobacillus gasseri (L. gasseri) and / or Bifidobacterium.
  • microorganisms to be inoculated into raw milk can be selected from microorganisms deposited in cell banks and the like.
  • examples of desirable strains that can be used in the mixed starter of the present invention are as follows.
  • Bulgarian bacteria include Lactobacillus delbrueckii subspecies bulgaricus JCM 1002T, Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 (FERM BP-10741), Lactobacillus delbrueckgaricum Streptococcus thermophilus ATCC 19258, Streptococcus thermophilus OLS3059 (FERM BP-10740), Streptococcus thermophilus OLS3294 (NITE P-77).
  • milk fermentation component of the present invention examples include cheese, yogurt, fermented milk, whey (whey) fermented product, etc. that can be obtained by fermentation of microorganisms as described above. Further, for example, fermented milk (yogurt) to water (whey) ) (For example, Japanese Patent No. 3,179,555).
  • fermented milk (yogurt) to water (whey) ) (For example, Japanese Patent No. 3,179,555).
  • the protein derived from fermented milk (yogurt) has an amino acid score of 100, and the digestibility of the protein is enhanced by fermentation, and the nutritional value is said to be high. Therefore, in the present invention, among these milk fermentation components, yogurt (fermented milk) is particularly desirable.
  • fermented milk means “fermented milk or milk containing non-fat milk solids equal to or higher than this with lactic acid bacteria or yeast. , A paste or liquid, or a frozen product thereof ”. Furthermore, it is defined as containing 10% or more of live lactic acid bacteria or yeast and not detecting Escherichia coli, containing 8% or more of non-fat milk solids as its components.
  • Yogurt is a product made from lactic acid fermentation of both Lactobacillus bulgaricus and Streptococcus salivarius subsp. Thermophilus.
  • yogurt includes those specified by both of these definitions.
  • yogurt includes any of yogurt to eat (solid, pasty), drink yogurt (liquid), frozen yogurt (frozen), powder yogurt (powder), and the like. Methods for producing these yogurts are known to those skilled in the art.
  • An example of a method for producing yogurt is as follows: a step of preparing a mixed starter using the aforementioned Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 and Streptococcus thermophilus OLS3059; a step of inoculating the mixed starter into raw milk; The process of performing, the process of flavoring, the process of filling a packaging material and a container, etc. will be passed.
  • the present inventors have found that in humans who have taken at least one component selected from the group consisting of (a) to (c) below, the skin condition is improved, in particular, pigment formation is inhibited. It was. That is, the present invention provides a composition comprising at least one component selected from the group consisting of the following (a) to (c), which is used for oral administration to an animal. Alternatively, the present invention provides a pigment formation inhibitor comprising at least one component selected from the group consisting of the following (a) to (c). (A) culture of propionic acid bacteria (b) DHNA or analog thereof (c) ACNQ or analog thereof).
  • the composition of the present invention, or the pigment formation inhibitor in a preferred embodiment, additionally contains a milk fermentation component Can (including).
  • the present invention also relates to a method for improving skin condition, comprising the step of orally administering at least one component selected from the group consisting of (a) to (c) below to an animal.
  • A) Propionic acid bacteria culture (b) DHNA or analog thereof
  • the subject to which the composition of the present invention is administered is a mammal.
  • a mammal is preferably a human.
  • the present invention relates to the use of at least one component selected from the group consisting of (a) to (c) below in the production of a pigmentation inhibitor in the skin.
  • the present invention relates to the following (a) ⁇ of at least one component selected from the group consisting of (c), their use in dye-forming inhibition in the skin.
  • the present invention provides a method for producing a pigmentation inhibitor in skin, comprising the step of blending at least one component selected from the group consisting of the following (a) to (c) with a pharmaceutically acceptable carrier: About.
  • the present invention comprises at least one component selected from the group consisting of the following (a) ⁇ (c), relates to the use in the manufacture of a composition for improving skin conditions.
  • the present invention relates to the use of at least one component selected from the group consisting of (a) to (c) below in improving skin conditions.
  • (A) culture of propionic acid bacteria (b) DHNA or analog thereof
  • the present invention includes at least one component selected from the group consisting of the following (a) ⁇ (c), provides a pharmaceutical composition for improving skin conditions. Furthermore, the present invention relates to the use of at least one component selected from the group consisting of (a) to (c) below in the manufacture of a pharmaceutical composition for improving skin conditions.
  • the pharmaceutical composition of the present invention contains a pharmaceutically effective amount of at least one component selected from the group consisting of the following (a) to (c).
  • the pharmaceutical composition of the present invention can contain a carrier suitable for oral administration.
  • the pharmaceutical composition of the present invention can be administered as a food for the purpose of improving the skin condition.
  • the present invention provides the following (a) method for improving skin conditions comprising the step of at least one component is administered to the animal is selected from the group consisting of ⁇ (c).
  • (A) culture of propionic acid bacteria (b) DHNA or analog thereof
  • “improvement of the skin condition” means skin and skin gloss, beam, dullness, pigmentation (stain), sagging, pore conspicuousness, texture, wrinkle, dryness (horny layer moisture content), stickiness, transparent It means that at least one condition selected from the group consisting of feeling, redness, paste on foundation, swelling, bear noticeability, skin rash, moisturizing, and pigmentation is improved.
  • “improvement of skin condition” includes improvement of skin symptoms and suppression of onset due to various allergic dermatitis including atopic dermatitis.
  • Preferred examples of the “improving skin condition” of the present invention include, but are not limited to, improvement of texture density (texture score), increase of stratum corneum water content, and decrease of pigmentation.
  • a texture as an index representing the surface form of the skin.
  • fine grooves run like a mesh, and the portion surrounded by the grooves is a triangle, a diamond, or a rectangle.
  • This groove is called a skin groove, and the part surrounded by the skin groove is called a hide hill.
  • the crevice is narrow and shallow, and the skin is regularly shaped.
  • the wider and deeper the crevice is the more conspicuous the skin is, and when the skin becomes uneven, the texture of the skin surface is rough and rough (the texture density is low).
  • the texture density can be measured by the following method.
  • ⁇ A method to accurately measure unevenness on the replica surface in three dimensions using laser light (replica three-dimensional measurement method).
  • a method of taking a skin surface image using a video microscope or direct skin analyzer and analyzing the image skin surface shape image analysis method using a video microscope).
  • a method of projecting a grid pattern on the skin and obtaining three-dimensional information of the skin from the distortion of the image (three-dimensional direct measurement method without using a replica).
  • the texture density when the texture density is higher than when the composition of the present invention is not used, it can be evaluated (determined) that the texture density is improved.
  • the texture density is compared before and after the administration of the composition of the present invention, and it can be evaluated that the texture density is improved even if the texture density is increased.
  • the texture score is a numerical value for relatively evaluating texture measured by the Robo Skin Analyzer (In-Forward Co., Ltd.) of the whole face image capturing / image analysis system.
  • the texture score is set to 100, and it is expressed by a numerical value from 0 to 100. More specifically, in a monochrome image of a skin photographed with a microscope, the dark part is a skin groove and the bright part is a skin hill, and the dark part and the bright part are enhanced and binarized, respectively. : 0.4mm)
  • the area that can be judged as a texture model is a numerical value that is relatively expressed by the area ratio with respect to 100 of the constant area of the skin photographed with a microscope.
  • Image processing and image analysis are controlled under certain conditions by the Robo Skin Analyzer device and software. Done.
  • the texture score when the texture score is higher than when the composition of the present invention is not used, it can be evaluated (determined) that the texture score (texture) has been improved.
  • the texture score is compared before and after the administration of the composition of the present invention, and it can be evaluated that the texture score (texture) is improved even if the texture score increases.
  • the improvement in texture score can be said to be an improvement in texture density, that is, an improvement in texture.
  • the stratum corneum is located on the outermost layer of the skin, and is a layer in which flat keratinocytes are superposed, with keratinized epidermal keratinocytes.
  • the smoothness of the skin is closely related to the moisture content of the stratum corneum, and it is said that the moisture content of the stratum corneum is 15% to 20% in the case of normal skin with a smooth state.
  • the stratum corneum moisture content can be measured by methods well known to those skilled in the art, such as using an image analysis system such as a Corneometer (Anti-Aging Series No. 2 Frontier of Anti-Aging of Skin, NTS Corporation). (2006)).
  • the stratum corneum moisture content can be measured by the following method.
  • Melanin production is known as a cause of pigmentation (stains).
  • stains stains
  • Melanin is usually present in the skin and is an important medical and cosmetic factor that plays an important role in protecting the body from the effects of ultraviolet radiation.
  • Melanin is considered to be synthesized via 5, 6-dihydroxyindole, etc. in the pigment cells in the skin tissue, by the action of tyrosinase, where tyrosine changes to dopa and then to dopaquinone. Therefore, the production of melanin can be suppressed by inhibiting the tyrosinase activity.
  • Substances that inhibit tyrosinase activity are useful as the skin condition improving composition of the present invention or as a pigmentation inhibitor in the skin.
  • the inhibitory activity of tyrosinase activity can be measured using, for example, the degree of production of dopaquinone or dopachrome, which is an intermediate of the production of melanin as a black substance, as an index.
  • the degree of production of dopachrome can be measured, for example, from the change in absorbance (475 nm). In such a measurement method, when the absorbance is low, it can be evaluated that the tyrosinase activity is inhibited.
  • melanin is synthesized excessively, it will appear black.
  • uneven distribution of melanin on the skin forms spots, freckles and the like.
  • Such pigmentation such as spots and freckles is exacerbated by ultraviolet irradiation.
  • Examples of the promotion of the production of melanin in pigment cells induced by irradiation with ultraviolet rays include information transmitters such as cytokines, chemokines, cell growth factors, and hormones. More specifically, for example, prostaglandins, melanocyte stimulating hormone ( ⁇ -MSH), endothelin, stem cell factor (SCF), ACTH, IL-1, IL-8, TNF- ⁇ and the like are involved.
  • Melanin production can be detected using, for example, mouse B16 melanoma cells.
  • mouse B16 melanoma cells for example, RIKEN, RCB1283
  • a substance that promotes or inhibits the production of melanin for example, the composition of the present invention
  • it can be evaluated that the production of melanin is promoted when the absorbance is increased as compared to before adding the target substance.
  • the absorbance decreases, it can be evaluated that the production of melanin is inhibited.
  • the reduction in pigmentation can be confirmed by measuring tyrosinase inhibitory activity and melanin production inhibitory activity by the method as described above.
  • the presence / absence and quantity (evaluation of the number, area, and shade) of pigmentation can be measured more directly.
  • a method using an image analysis system such as a Robo skin analyzer is well known to those skilled in the art (skin measurement / evaluation on site level-trouble cases / measures-Science & Technology Co., Ltd. (2007 ) Anti-aging series No.2 The forefront of anti-aging of skin, NTS Corporation (2006)).
  • BLUE blue
  • shape features number, area
  • “Small pigmentation” is a continuous area with an area of 0.6mm 2 to 1.2mm 2 among the parts that can be detected as “slightly dark parts” and “dark parts” in a monochrome image. can do.
  • “large pigmentation” is a continuous region with an area of 1.2 mm 2 or more in a monochrome image that can be detected as a “slightly dark part” and a “dark part” compared to the surrounding part. be able to. Further, by using “redness” as an index, for example, acne and erythema can be detected.
  • the composition of the present invention can be used in the form of pharmaceuticals, foods and drinks, skin cosmetics and the like.
  • the skin condition can be improved by direct administration as a pharmaceutical.
  • the culture of propionic acid bacteria can be included in various states.
  • it can be contained in the form of a suspension of propionic acid bacteria, a culture of propionic acid bacteria (cells, culture supernatant (including medium components)), a fermented product of propionic acid bacteria, and the like.
  • the composition of the present invention or the pigmentation inhibitor in skin can contain a culture of propionic acid bacteria as it is. Or it can also contain as a processed product of propionic acid bacteria which processed the culture of propionic acid bacteria with something.
  • the processed product of propionic acid bacteria used in the composition of the present invention or the pigmentation inhibitor in the skin include, for example, propionic acid bacteria itself, propionic acid bacteria content, concentrated fermented milk, pasted product, and dried product. (At least one selected from spray-dried products, freeze-dried products, vacuum-dried products, and drum-dried products), liquid products, diluted products, and crushed products.
  • the propionic acid bacteria live cells, wet bacteria, dry bacteria and the like can be used as appropriate.
  • the pigment formation inhibitor in the composition of the present invention or skin can also be added to pharmaceuticals and / or foods and drinks having biological standards such as infant formula (so-called powdered milk). Moreover, it can apply to various pharmaceuticals and / or food / beverage products by forms other than the form normally used as a pharmaceutical and / or food / beverage products.
  • composition of the present invention or the skin pigmentation inhibitor can be orally administered alone or mixed with other components commonly used in pharmaceuticals and foods. At this time, particularly when used in combination with other compounds or microorganisms having an effect of improving the skin condition, it is effective for improving the skin condition in humans and animals.
  • the daily intake of the pharmaceutical composition or food or drink containing the pigment formation inhibitor in the composition of the present invention or skin is not particularly limited because it varies depending on age, symptoms, body weight, use, etc. 10000 mg / kg body weight can be ingested, preferably 0.1 to 1000 mg / kg body weight can be ingested.
  • special purpose foods such as foods for specified health use, nutritional functional foods, infant formulas, infant formulas, infant formulas, health functional foods, sick people It can also be ingested as edible foods, dairy products, fermented milk and the like. Furthermore, it can also be ingested as food / beverage products by mix
  • the pH can be set to 2.0 to 6.0, preferably 3.0 to 5.0.
  • composition of the present invention or the pigmentation inhibitor in the skin When the composition of the present invention or the pigmentation inhibitor in the skin is continuously administered to animals, it can be orally administered as a nutrient, food / drink, food or the like.
  • the composition of the present invention or the pigmentation inhibitor in the skin is administered as a nutrient, food or drink, food, etc., in addition to the milk fermentation component and the culture of propionic acid bacteria, the nutrients are additionally blended. Its nutritional composition can be adjusted.
  • additional nutrient of the present invention water, protein, carbohydrate, lipid, vitamins, minerals, organic acid, short chain fatty acid, organic base, fruit juice, flavors, and the like can be used. For these nutrients, for example, the following components can be used.
  • Protein (animal protein or vegetable protein or their degradation products), whole milk powder, skim milk powder, partially skimmed milk powder, casein, whey, whey powder, whey protein, whey protein concentrate (WPC), whey protein separation (WPI), ⁇ -casein, ⁇ -casein, ⁇ -casein, ⁇ -lactoglobulin, ⁇ -lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein, etc.
  • Milk-derived lipids and saccharides, etc . butter, whey Minerals, creams, non-protein nitrogen, various milk-derived components such as sialic acid, phospholipids, and lactose Peptides and amino acids: various peptides such as casein phosphopeptide and collagen peptide, various amino acids such as lysine and arginine
  • Sugars modified starch (dextrin (maltodextrin, resistant dextrin, etc.), soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, fermented glucosamine, reduced maltose, pullulan, etc.
  • Vitamins Vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline, folic acid, elsorbine Minerals such as acids: Calcium, phosphorus, potassium, chlorine, magnesium, sodium, copper, iron, manganese, zinc, selenium, chromium, molybdenum and other organic acids: Malic acid, citric acid, lactic acid, tartaric acid and other short chain fatty acids: acetic acid , Propionic acid, Butyric acid, Valeric acid, Caproic acid, etc.
  • acids Calcium, phosphorus, potassium, chlorine, magnesium, sodium, copper, iron, manganese, zinc, selenium, chromium, molybdenum and other organic acids: Malic acid, citric acid, lactic acid, tartaric acid and other short chain fatty acids: acetic acid ,
  • Fatty acid ester Glycerin fatty acid ester, Polyglycerin fatty acid ester, Sucrose fatty acid ester, etc.
  • These additional nutrients are derived from chemically synthesized ingredients and natural products Any of the components to be used can be used. And the foodstuff which finally contains the target component can also be mix
  • These components are finally matched to the composition of the nutrient of interest, it can be formulated in combination with at least at least one or two or.
  • the form of the composition may be solid or liquid, and can be prepared in a gel or semi-solid form. Therefore, these nutrients can also be administered orally as a functional food.
  • the composition of the present invention improved the skin condition by ingestion as a composition containing a culture of propionic acid bacteria. Therefore, a functional food containing at least one component selected from the group consisting of (a) to (c) below, or a composition having a composition as a pharmaceutical is one of the preferred embodiments of the present invention. That is, the present invention improves the skin condition including the step of blending at least one component selected from the group consisting of (a) to (c) below into a functional food or a pharmaceutically acceptable carrier.
  • the present invention relates to a method for producing a functional food or a pharmaceutical composition.
  • the present invention provides a method for imparting an ability to improve skin condition to a functional food, comprising the step of blending the functional food with at least one component selected from the group consisting of the following (a) to (c): To do.
  • (A) Propionic acid bacteria culture (b) DHNA or analog thereof
  • the present invention provides a composition for improving skin condition comprising the following nutrients. That is, Propionic acid cultures Milk fermentation components Sugars, etc.
  • the culture of propionic acid bacteria is, for example, (i) 1,4-dihydroxy-2-naphthoic acid (DHNA) or an analog thereof, and (ii) 2-amino-3-carboxy-1,4- It can be either naphthoquinone (ACNQ) or an analog thereof, or both.
  • DHNA 1,4-dihydroxy-2-naphthoic acid
  • ACNQ 2-amino-3-carboxy-1,4- It can be either naphthoquinone
  • ACNQ naphthoquinone
  • the milk fermentation component in the said composition contains a protein, the protein from which it originates differently as a protein can also be further mix
  • a milk component can be blended in addition to the milk fermentation component.
  • Each component which comprises the composition of this invention can be suitably adjusted according to various conditions, such as a physique, age, sex, etc. of the object administered as a functional food. More specifically, the following composition (per 100 mL
  • 1 mg to 22 g usually 10 mg to 17 g, preferably 10 mg to 11 g, or 0.01 ⁇ g to 15 mg, usually 0.5 ⁇ g to 10 mg, preferably 0.5 ⁇ g to 0.1 mg in terms of the amount of DHNA may be added as a culture of propionic acid bacteria. it can.
  • the fermented milk ingredient 0.01 g ⁇ 100 g, usually 10 g ⁇ 90 g, preferably 30 g ⁇ 80 g, more preferably, to 50 g ⁇ 70 g formulation.
  • a milk fermentation component it is possible to improve the palatability of the composition such as flavor and texture.
  • the composition in the present invention When improving palatability, it is desirable to make most of the composition in the present invention a milk fermentation component. Therefore, for example, in addition to the culture addition amount of propionic acid bacteria illustrated above, it can be set as the composition in this invention by mix
  • 1 mg to 22 g of culture of propionic acid bacteria usually 10 mg to 17 g, preferably 10 mg to 11 g, or 0.01 ⁇ g to 15 mg, usually 0.5 ⁇ g to 10 mg, preferably 0.5 ⁇ g to 0.1 mg in terms of DHNA 1 g to 100 g, usually 30 g to 100 g, preferably 50 g to 100 g, more preferably 60 g to 100 g of a milk fermentation component can be blended.
  • saccharides can be added in an amount of 0.1 to 20 g, usually 0.3 to 15 g, preferably 0.6 to 10 g.
  • the amount of the culture can be blended so as to have the above composition in terms of DHNA.
  • the composition of the present invention may additionally contain at least one nutrient selected from the group consisting of vitamins, peptides, minerals, organic acids or short-chain fatty acids, fatty acid esters and organic bases.
  • a fragrance, sweetener, acidulant, colorant, or the like can be blended.
  • known ingredients that are known to have an effect of improving the skin condition can be additionally blended.
  • coenzyme Q10 and its derivatives are said to improve the skin condition by oral administration.
  • the composition in the case of blending these components can be appropriately adjusted according to various conditions such as the physique, age, and sex of the subject to be administered as a functional food or pharmaceutical composition.
  • composition per 100 mL or 100 g
  • Vitamins 0-20g, usually 0-10g, preferably 0-1200mg
  • Minerals 0-5g, usually 0-3g, preferably 0-2g
  • Organic acid or short chain fatty acid 0-5g, usually 0-3g, preferably 0-2g
  • Fatty acid ester 0 to 10 g, usually 0 to 5 g, preferably 0 to 3 g. That is, this invention provides the manufacturing method of the functional foodstuff or pharmaceutical composition for improving a skin state including the process of mix
  • the functional food or pharmaceutical composition produced according to the present invention can indicate that the intake of the functional food or pharmaceutical composition promotes improvement of the skin condition in the subject.
  • vitamins can be shown as vitamins for blending into the functional food or pharmaceutical composition of the present invention.
  • vitamins can also contain a pharmaceutically acceptable salt. That is, Vitamin A, B vitamins such as vitamin B1, Vitamin C (ascorbic acid) and its sodium salt (sodium ascorbate) Etc.
  • blending with the functional food of this invention or a pharmaceutical composition can be selected from a polysaccharide or a monosaccharide.
  • insoluble saccharides can also be blended. More specifically, at least one saccharide selected from the group consisting of the following saccharides or a derivative thereof can be blended.
  • Examples of monosaccharides include glucose (glucose), mannose, and xylose.
  • Examples of disaccharides include sucrose (sucrose, sugar), lactose (lactose), maltose, trehalose, and palatinose (isomaltulose).
  • the oligosaccharide, fructo-oligosaccharide has a galacto-oligosaccharide, etc.
  • Examples of the polysaccharides starch, dextrin, and the like.
  • the pharmaceutical composition of the present invention can be prepared by blending at least one component selected from the group consisting of (a) to (c) below, for example, with a pharmaceutically acceptable carrier.
  • a pharmaceutically acceptable carrier for example, a pharmaceutically acceptable carrier.
  • DHNA or analog thereof a pharmaceutically acceptable carrier
  • ACNQ or analog thereof when additional ingredients are blended, the above-mentioned saccharides and the like are used as a carrier and mixed homogeneously.
  • the composition is preferably so that the milk-fermented component and the protein derived from the culture of propionic acid bacteria have a ratio of about 1% or more of the saccharide in the composition, for example, a ratio of about 30% or more.
  • composition of the present invention can be prepared so as to have a ratio of 70% or more of the saccharides therein, more preferably about 100%.
  • the composition of the present invention is prepared as a pharmaceutical composition, it is desirable to adjust it to be 0.1 to 3 kcal, preferably 0.7 to 2 kcal per mL.
  • at the time of mixing at least 1 or more of the additional component which consists of vitamins and minerals and also dietary fiber can also be added. Dietary fiber is divided into water-soluble dietary fiber and insoluble dietary fiber, and both can be used.
  • examples of the water-soluble dietary fiber include the following components.
  • pectin protopectin, pectinic acid, pectinic acid
  • gum arabic guar gum hydrolyzate
  • glucomannan galactomannan
  • psyllium corn fiber
  • alginic acid alginic acid degradation product
  • carrageenan and the like.
  • the functional food or pharmaceutical composition of the present invention can be supplied in a liquid, semi-solid or dry state.
  • Semi-solid forms include pastes such as yogurt and gels.
  • a paste-like composition can be obtained by blending a thickener such as pectin.
  • a gel-like composition can be obtained.
  • the composition can be dried and processed into a powder form or a tablet.
  • the composition in a dry state can be taken as it is or after being dispersed or dissolved in water or milk.
  • Powdered or tablet-like compositions can be taken as they are.
  • it can also be ingested by making it contain in confectionery, such as a gummy candy and a tablet confectionery.
  • composition of this invention can also be utilized with the form of cosmetics.
  • the cosmetic according to the present invention contains 0.01 to 10%, preferably 0.05 to 5% (as dry weight) of the propionic acid bacteria culture and / or processed product of the present invention as an active ingredient, and is commonly used for this.
  • a cosmetic base By adding a cosmetic base, it can be formulated into a solid, semi-solid or liquid form according to a conventional method to obtain a general cosmetic or a skin cosmetic.
  • the cosmetics according to the present invention include various optional ingredients (oil agents, moisturizers, thickeners, preservatives, emulsifiers, pigments, pH adjusters) used in normal cosmetics, external preparations for skin, quasi drugs, pharmaceuticals, etc. Agents, medicinal ingredients, ultraviolet absorbers, fragrances, etc.) can be appropriately blended.
  • the cosmetics which concern on this invention can be manufactured according to a conventional method.
  • the cosmetic of the present invention generally cosmetics, is not limited to skin cosmetics, quasi drugs, may be an externally applied drugs and the like.
  • the dosage form can also be arbitrarily selected according to the purpose, such as cream, emulsion, foundation, pack, lotion, gel, solution, and stick.
  • the necessary amount may be applied several times as appropriate.
  • the skin cosmetics according to the present invention can be skin lotions, creams, emulsions, packs and other skin cosmetics.
  • an appropriate amount for example, 0.001% to 15%, preferably 0.001% to 15% of an active ingredient (existing whey mineral) as a base, auxiliary agent or the like commonly used in skin cosmetics according to a conventional method, 0.01% to 10% can be blended. Since the active ingredient is derived from food, there is essentially no problem with toxicity. Since the skin cosmetic according to the present invention is externally applied to the skin, safety is particularly important.
  • the skin lotion can be prepared as follows.
  • humectants such as glycerin, propylene glycol, and citric acid, pH adjusters, and the like are dissolved in purified water.
  • surfactants, preservatives, fragrances and the like are dissolved in alcohol.
  • a general lotion can be produced by mixing and solubilizing both.
  • Toner lotion can contain 0.01% to 10% of the active ingredient of the present invention (such as a culture of propionic acid bacteria) in the aqueous phase.
  • the cream can be prepared as follows.
  • the aqueous phase and oil phase were prepared, by heating the respective resulting aqueous phase and oil phase mixture is stirred, may be prepared by emulsifying.
  • the aqueous phase part can be prepared by adding a hydrophilic component to purified water.
  • the hydrophilic component include humectants such as glycerin and sorbit, but are not limited thereto.
  • the oil phase part can be prepared by mixing a solid oil component, a liquid oil component, and an oil component.
  • the solid oil include, but are not limited to, the following. That is, beeswax, paraffin, microcrystalline wax, ceresin, higher fatty acids and the like.
  • Examples of the liquid oil include, but are not limited to, the following. That is, squalane, liquid paraffin, various ester oil components and the like.
  • an active ingredient such as a culture of propionic acid bacteria
  • the emulsion can be prepared as follows. For example, it can be prepared by preparing a water phase part and an oil phase part, emulsifying, and adding a thickener thereto.
  • the aqueous phase part can be prepared by adding a humectant such as glycerin or 1,3-butylene glycol to purified water and mixing with heating.
  • the oil phase part can be prepared by adding oily components such as preservatives and surfactants to the solid oil, semi-solid oil and liquid oil. Examples of the solid oil include, but are not limited to, beeswax and paraffin.
  • the semi-solid oil content is not limited to those including petrolatum, lanolin and the like.
  • liquid oil examples include, but are not limited to, squalane, liquid paraffin, various ester oils, and the like.
  • the thickener examples include, but are not limited to, carboxyvinyl polymer and carboxymethyl cellulose.
  • the pack can be prepared as follows. For example, moisturizing agents in purified water, allowed to swell by adding a coating agent, etc. are added kaolin, talc, powders of titanium oxide if necessary to this. Furthermore, the ethanol which melt
  • the humectant include, but are not limited to, glycerin and sorbit.
  • the film agent include, but are not limited to, polyvinyl alcohol and polyvinyl pyrrolidone.
  • the active ingredient of the present invention is added so as to be 0.01% to 10% to make a pack.
  • a preservative generally used as a preservative for cosmetics can be blended in the cosmetic of the present invention.
  • the preservative include the following. That is, paraoxybenzoic acid ester, phenonip (paraben phenoxyethanol solution), phenoxyethanol, phenol, resorcin, hinokitiol, benzoic acid or its salt, salicylic acid or its salt, sorbic acid or its salt, hexachlorophene, benzalkonium chloride, phenols , acids, halogenated bisphenols, amides, quaternary ammonium compounds, various fungicides such as are commonly used in detergent such cosmetics industry.
  • Paraoxybenzoates are also referred to as parabens.
  • Parabens include, but are not limited to: That is, methyl paraben, ethyl paraben, propyl paraben, butyl paraben and the like.
  • the lotion obtained as described above can be used as it is.
  • the processed material can also be used.
  • processed products include (reduced pressure) concentrates, pasted products, dried products (spray dry, freeze dry, etc.), diluted products, and the like.
  • the said lotion and its processed material can also be addition-blended with various cosmetics as a raw material compounding component of cosmetics.
  • the composition or pigment formation inhibitor of the present invention can be in the form of a tablet. That is, the present invention relates to a skin condition improving composition molded into a tablet. Or this invention relates to the pigmentation inhibitor in the skin shape
  • a tablet generally refers to a solidified product obtained by adding an active ingredient or an active ingredient to an excipient to a certain shape by a method such as compression molding. Tablet molding methods are well known to those skilled in the art, and can be molded using, for example, a known tableting device.
  • the tablet of the present invention can be chewable or non-chewable, but non-chewable is preferred.
  • the size and weight of the tablet can be designed as appropriate according to its intake form.
  • the diameter when swallowing without chewing with water or beverage, the diameter can be, for example, 10 mm or less, but is not limited thereto.
  • the diameter in the case of a tablet confection that enjoys flavor by chewing, the diameter can be 25 mm or less, but is not limited thereto.
  • the size of the tablet is, for example, 1 mm or more and 25 mm or less, and preferably 5 mm to 15 mm in diameter.
  • the weight is, for example, 10 to 5000 mg, preferably 100 to 1000 mg.
  • the hardness of the tablet can be appropriately designed according to the intake form, and is preferably 2 kgf or more and 5 kgf or less. If it is less than 2 kgf, the binding force is small and the tablet shape cannot be maintained. On the other hand, if it exceeds 5 kgf, disintegration in the stomach will be worse when eating.
  • the tablet of the present invention contains excipients, fluidizers, proteins, lipids, sugars, peptides and amino acids, vitamins, esters, fruit juices, pigments, flavors, and the like. Can be included. Examples of the compounding amount of these substances include, but are not limited to, the following values with respect to 200 parts by weight of the propionic acid bacteria culture.
  • Peptides and amino acids For example, 500 to 200,000 parts by weight, preferably 500 to 1000 parts by weight Sugars: for example, 0.1 to 100 parts by weight, preferably 1 to 50 parts by weight Esters: for example, 0.1 to 100 parts by weight, preferably 1.0 to 50 parts by weight, more preferably 10 to 30 parts by weight Fruit juice: for example 0.01 to 500 parts by weight, preferably 0.1 to 100 parts by weight, more preferably 1 to 50 parts by weight Dye: for example 0.01 to 500 parts by weight , Preferably 0.1-50 parts by weight, more preferably 1-10 parts by weight perfume: for example 0.01-500 parts by weight, preferably 0.1-100 parts by weight, more preferably 1-50 parts by weight
  • Flavor can be imparted to the tablet by adding fruit juice to the tablet.
  • fruit juices well known to those skilled in the art such as fruit juice and mint juice can be used.
  • fruit juices include orange juice, orange juice, lemon juice, grapefruit juice, grape juice, apple juice, banana juice, pear juice, pineapple juice, fruit mix juice, etc., but are not limited thereto.
  • mint juice include peppermint juice, spearmint juice, peach mint juice, grapemint juice, orange citrus mint juice, apple mint juice, hascup mint juice, cherry mint juice, pineapple mint juice, and the like. It is not limited to these.
  • the fruit juice of the present invention either natural fruit juice or artificially synthesized fruit juice can be used.
  • Anato pigment As a pigment, Anato pigment (Anato, carotenoid, carotenoid pigment, carotenoid, carotenoid pigment), Turmeric pigment (curcumin, turmeric pigment), Caramel I, Caramel II, Caramel III, Caramel IV (Caramel, Caramel Color), Imamo carotene, Dinariella carotene, carrot carotene, etc.
  • flavor can use a thing well-known to those skilled in the art.
  • citrus flavor range, lemon, grapefruit juice
  • fruit flavor pineapple, strawberry, melon, banana, etc.
  • milk flavor milk, butter, yogurt, etc.
  • coffee, cocoa, chocolate flavor, tea Fragrance Black tea, Matcha, Green tea, etc.
  • Vanilla flavor Mint flavor (Peppermint, Spearmint, etc.)
  • Spice flavor Shiso, Ginger, Cinnamon, Wasabi, etc.
  • Nut flavor Piero, Almonds, Marron, etc.
  • Meat ⁇ Seafood flavors beef, pork, chicken, crab, shrimp, bonito, etc.
  • vegetable flavors tomato, corn, onion, etc.
  • Western flavors whiskey, brandy, wine, rum, etc.
  • seasoning flavors etc.
  • flavor it can be set as a form well-known to those skilled in the art, such as a water-soluble fragrance
  • light anhydrous silicic acid (silicon dioxide) is mentioned as a fluidizing agent.
  • the blending amount of the fluidizing agent per tablet is 0.5% to 3%, preferably 0.5% to 2.0%.
  • shellac or the like may be sprayed to coat the tablet after tableting.
  • composition or pigment formation inhibitor molded into the tablet of the present invention can stably contain DHNA.
  • the composition or the pigment formation inhibitor of the present invention can obtain the following effects by adopting a tablet form. In other words, it is easy to carry, easy to ingest, can be ingested in a certain amount (ease of optimizing and standardizing the amount used), easy to identify by appearance compared to powders, etc. Adjustments are possible, and effects such as masking of taste can be expected by coating the surface.
  • all prior art documents cited in the present specification are incorporated herein by reference.
  • Example 1 Evaluation test of effects of Profec (propionic acid bacteria culture) on skin function improvement and intestinal regulation 1.
  • Subject selection criteria
  • Women aged 20 to 39 years with chronic constipation defecation days average 4 days or less per week) and dry skin.
  • inclusion criteria (1) Pregnant women and those who are breastfeeding (2)
  • Those who regularly use constipation medicine taken every time constipation)
  • People with atopic dermatitis (4) Those who have severe heart / renal / liver disorder, respiratory disease, cardiovascular disease, etc.
  • Test meal / acid drink (placebo) (Test meal A) ⁇ Profec-containing acidic beverage (test meal B) ⁇ Profec-containing yogurt drink (test meal C) (Test meal A) "Acid drink” (placebo) It is an acidic beverage with pectin, lactic acid, yogurt flavor, vitamin C and aspartame added to water, and does not contain milk components or lactic acid bacteria.
  • Test meal B "Profec-containing acidic beverage” An acidic beverage obtained by adding Profec (propionic acid bacteria culture) at 1% to the above-mentioned “acidic beverage” and does not contain milk components other than Profec and lactic acid bacteria.
  • test meal was stored refrigerated at 10 ° C or lower.
  • Test food intake Profec culture of propionic acid bacteria
  • test drink 120 mL
  • Ingestion frequency The test meal was ingested once a day (120 mL) for 4 weeks.
  • Test meal intake (morning, noon, evening, before meals, and after meals) was voluntary by subjects.
  • Test method (1) Study design : Double-blind placebo control study Group composition: Placebo diet group, 2 groups of test diet groups, 3 groups, 32 patients in each group, 96 patients in total (2) Subject assignment test The controller assigned subjects to three groups. At that time, the test treating physician noted that does not occur bias as possible to the result of determination based on the criterion of facial skin findings. (3) Test schedule Skin test, blood collection, and stool collection were performed before taking the test meal. The test meal was ingested for 4 weeks, and then skin examination, blood collection, and stool collection were performed again.
  • Evaluation method The multiple comparison test (Tukey-Kramer method) between three groups in the amount of change (rate) before and after intake and the intra-group comparison test before and after intake. Specifically, for discrete data (score, number of times, data expressed in number), perform “Wilcoxon signed rank sum test”, and for continuous data (measured value), the result of normality test of each data Based on the above, a “corresponding t-test” or “Wilcoxon signed rank sum test” was performed.
  • test food B intake group one person who became pregnant during the study period (test food B intake group) was regarded as a discontinuation case and excluded from the analysis.
  • Drugs that may affect the intestinal flora in 3 cases (test food B intake group: 1 person, test food C intake group: 2 persons) that had matters that were thought to affect the test results was excluded from the assessment (2 cases of intestinal use: 1 case, antibiotic use: 1 case).
  • the capacitance measurement method was used for the measurement of the stratum corneum moisture content.
  • Courage + Khazaka electronic GmbH's Corneometer (registered trademark) makes use of the fact that the dielectric constant of water is significantly different from that of other substances. )
  • the unit is expressed in terms of horny moisture (arbitrary unit; AU) (skin measurement / evaluation at site level-trouble cases / measures-Chapter 8 of Science & Technology Co., Ltd. (2007)).
  • Comparison between groups of image analysis results Comparison between groups was performed on the image analysis results ⁇ (starting measurement value ⁇ measurement value after 4 weeks) of each group.
  • the texture was significantly improved in the test meal B (Profec-containing acidic beverage) intake group and the test meal C (Profec-containing yogurt drink) intake group compared to the test meal A (placebo) intake group.
  • about pigmentation large II (number), large III (number), large II (area), compared with test food A (placebo) intake group, test food C (Profec-containing yogurt drink) intake group significantly Improved.
  • Example 2 Measurement of stratum corneum cytokine It is known that an exposed part such as a measurement target face is in a weakly inflammatory state as compared to a non-exposed part hidden in clothes. Therefore, a stratum corneum sample was collected by tape stripping, and inflammatory cytokines (IL-1 ⁇ , IL-1ra, IL-8, TNF- ⁇ ) in the stratum corneum were measured. In particular, it has been reported that IL-1ra / IL-1 ⁇ is increased in exposed areas, UV irradiation sites, and atopic dermatitis lesions. Therefore, these cytokines were evaluated as indicators of the inflammatory state of the skin. IL-8 and TNF- ⁇ are known to be associated with acne and spots.
  • Measurement method Collected tape (PPS tape 2.5 x 4 cm, 3 sheets) is cut into small pieces, placed in an Eppendorf tube (2 mL) containing 0.1 mL of PBS containing 0.1% Tween 20, and sonicated (on ice). It was. Soluble protein is eluted from the tape into PBS by sonication (15 minutes). After extraction, the tape was taken out and centrifuged (15000 ⁇ g, 1 minute, 4 ° C.) to obtain 1 mL of supernatant. The protein concentration in the supernatant was measured by Micro BCA protein assay, and cytokines (IL-1 ⁇ , IL-1ra, IL-8, TNF- ⁇ ) were measured. IL-1 ⁇ and IL-1ra were proportioned, and IL-8 and TNF- ⁇ were corrected by protein amount.
  • Example 3 Microflora analysis The purpose of this study was to analyze the changes in the number of Bifidobacterium and Bacteroides spp. In fecal samples submitted to the subjects before and after the test period. More specifically, it was examined whether an increase in the number of Bifidobacterium spp. Or a relative decrease in the number of Bacteroides spp.
  • Profec may have the effect of suppressing the decrease in people with a large number of initial bifidobacteria and increasing it in people with a relatively small number of initial bifidobacteria It was done.
  • the ratio of the number of Bifidobacterium to the number of Bacteroides was analyzed for each layer. However, there was no significant difference between each layer in any group.
  • TEWL transepidermal water transpiration
  • the TEWL measurement value of the placebo intake group is from 20.5 ⁇ 6.6 g / m 2 ⁇ h before intake, to 18.7 ⁇ 5.9 g / m 2 after intake. It changed to 2 ⁇ h, and a statistically significant difference was observed.
  • stratum corneum water content did not improve significantly before and after ingestion, and texture showed a tendency to deteriorate (p ⁇ 0.1). If this result is comprehensively judged, it is estimated that the placebo intake group may have been affected by the seasonal change, that is, the turnover delay may have occurred with the seasonal change.
  • the delay of turnover in the placebo intake group may have caused a delay in melanin discharge (suppression).
  • melanin produced by melanocytes is recognized as a stain because it accumulates in keratinocytes. Because the turnover was delayed in the placebo group, it is possible that melanin proliferated and blemishes grew before keratinocytes detached.
  • the index indicating the turnover is not measured, but in addition to the improvement of the stratum corneum moisture content and the texture score, the questionnaire index (conspicuous pores, closely related to those measured values) The improvement effect is also observed in the texture, wrinkles, and transparency, suggesting that Profec may have a normalizing effect of turnover.
  • the relationship between each questionnaire item and stratum corneum water content, texture score, and turnover is described below.
  • Conspicuous pores means that the periphery of the pore outlet is recessed in a mortar shape and is recognized as a pore in the shadow. It is known that the stratum corneum in the part where the pores are depressed is in an abnormal turnover state (failed keratinization state) (Fragrance J. 35 (1): p19, 2007). Such parakeratosis is induced by unsaturated fatty acids in the sebum. In this example, there was no result of measuring the turnover of the stratum corneum, and there was no change in the amount of sebum. However, in the Profec ingestion group, the skin pH changed from pH 6.0 before ingestion to pH 5.5 after ingestion, suggesting that the composition of sebum has changed. Profec intake may improve the sebum composition and improve the turnover of the stratum corneum in the pores, which may result in the pores becoming inconspicuous.
  • Texture Texture is an index that represents the surface morphology of the skin. Observing the skin, which runs fine grooves reticulated, portions surrounded by the groove has a triangular, rhombic or square. This groove is called a skin groove, and the part surrounded by the skin groove is called a hide hill. In general, when it is said that the skin is fine, the crevice is narrow and shallow, and the cuticle has a regular shape. Conversely, the wider and deeper the crevice is, the more conspicuous the hill is. Furthermore, if the skin is uneven, the skin surface feels rough and the skin becomes rough.
  • the shape of the keratinocytes becomes uniform and a healthy stratum corneum with high water retention is formed. This is said to be in order.
  • the stratum corneum moisture content is significantly increased in addition to the improvement of the index indicating texture. It can be said that the improvement result of the texture score (image analysis) in the Profec intake group observed in this study is an improvement effect accompanied by actual feeling.
  • IL-8 was significantly increased in the placebo-ingested group, but IL-8 production was not changed in the Profec-ingested group.
  • Profec is thought to suppress the growth (increase / expansion) of spots by suppressing IL-8 production.
  • Such inflammation-suppressing effects of Profec have been confirmed in animal experiments.
  • the inhibitory effect of tyrosinase activity has been confirmed in vitro by the action of DHNA contained in Profec. It is also possible that DHNA contained in Profec taken orally moved into the blood and directly acted on melanocytes.
  • keratinocytes exfoliated before melanin proliferated was also considered to be a cause.
  • Pigmentation worsened in the placebo group whereas pigmentation did not change in the Profec-containing acidic drink group.
  • the number and area of pigmentation were significantly improved before and after ingestion. This suggests that yogurt components including lactic acid bacteria may have contributed to the improvement of pigmentation.
  • the activation of macrophages of immune cells contributes to the improvement of pigmentation such as spots. It is suggested that the significant improvement in the number and area of pigmentation may be a result of activation of immune cells including macrophages in the components contained in yogurt including lactic acid bacteria.
  • 4 weeks which is one turnover of human skin, was set as the intake period.
  • the evaluation of skin with food usually sets an intake period of 8 to 12 weeks, so the intake period may be short to fully evaluate the effect. Nevertheless, since the effects described above were observed, Profec's improvement effect on the skin is considered to be very high.
  • the melanin production inhibitory effect of DHNA and ACNQ contained in Profec manufactured by Meiji Co., Ltd. was examined from the viewpoint of the tyrosinase activity inhibitory effect and the melanin production inhibitory effect by melanoma cells.
  • Reagent preparation (Tyrosinase activity inhibition test) DHNA and ACNQ dissolved in DMSO as a sample, PTU (phenylthiourea) dissolved in DMSO as a positive control, kojic acid and arbutin (Arubutin) dissolved in 0.1 M phosphate buffer (pH 6.8), Each sample was prepared at 2 ⁇ M to 200 mM at a concentration before addition (ACNQ only 2 ⁇ M to 20 mM) and used for the experiment. Concentration or final concentration in the reaction solution are each 0.1 ⁇ 10000 ⁇ M (ACNQ only 0.1 ⁇ 1000 ⁇ M), DMSO concentration in the reaction solution is 5%.
  • assay medium As a basal medium, 10% FCS-EMEM (containing antibiotics) was used. Media containing samples (DHNA, ACNQ) and positive controls (PTU, Arubutin, Kojic acid), negative controls (PBS, DMSO) have final concentrations of 1 nM-100 ⁇ M for DHNA, 1 nM-10 ⁇ M for ACNQ, and positive controls It was prepared by diluting with basal medium so that 100 ⁇ M and the negative control were 0.1%.
  • Tyrosinase (derived from mushroom, Sigma) adjusted to 100 unit / mL with 0.1 M Phosphate buffer (pH 6.8) was added and incubated at 37 ° C. for 15 minutes, and then the absorbance (405 nm) was measured.
  • Example 5 Preparation of tablets of propionic acid bacteria culture (1) 721 parts by weight of fish scale collagen peptide, 8.1 parts by weight of fermented glucosamine, 4.1 parts by weight of arginine, 32.9 parts by weight of reduced maltose, and 200 parts by weight of powdered propionic acid bacteria culture (DHNA: 81 ⁇ g / g), Prepare a pullulan aqueous solution in which 3.0 parts by weight of pullulan is dissolved in 100 parts by weight of hot water after mixing and heating in a fluidized bed granulator (Freund Sangyo Co., Ltd.) and spray the pullulan aqueous solution in the granulator. And granulated.
  • DHNA powdered propionic acid bacteria culture
  • the product was dried until the water content became 3%, cooled, and passed through a 14 mesh sieve to remove large granules. Then, 20 parts by weight of glycerin fatty acid ester having an HLB value of 2.1 and 10.9 parts by weight of sodium L-ascorbate were added thereto and mixed uniformly.
  • the obtained mixed powder is compression-molded with a tableting machine (manufactured by Hata Kogyo Co., Ltd.) to a hardness of 3 kgf, and a circular tablet (tablet) with a weight of 0.25 g and a diameter of 8 mm Manufactured. As a result of the follow-up of the produced tablets at 23 ° C.
  • Example 6 Production of tablets of propionic acid bacteria culture (2) 706 parts by weight of fish scale collagen peptide, 8.1 parts by weight of fermentation glucosamine, 4.1 parts by weight of arginine, 21.9 parts by weight of reduced maltose, and 200 parts by weight of powdered propionic acid bacteria culture (DHNA: 81 ⁇ g / g), A pullulan solution prepared by dissolving 3.0 parts by weight of pullulan, 10.9 parts by weight of orange fruit juice and 5.0 parts by weight of carotene pigment in 100 parts by weight of hot water is prepared in a fluidized bed granulator (Freund Sangyo Co., Ltd.). The pullulan solution was sprayed in a granulator and granulated.
  • DHNA powdered propionic acid bacteria culture
  • the product was dried until the water content became 3%, cooled, and passed through a 14 mesh sieve to remove large granules. Then, 20 parts by weight of glycerin fatty acid ester having an HLB value of 2.1, 10.9 parts by weight of sodium L-ascorbate and 10 parts by weight of powdered orange flavor were added and mixed uniformly.
  • the obtained mixed powder is compression-molded with a tableting machine (manufactured by Hata Kogyo Co., Ltd.) to a hardness of 10 kgf, and a circular tablet (tablet) with a weight of 1.0 g and a diameter of 15 mm Manufactured.
  • Example 7 Production of tablets of propionic acid bacteria culture (3) 721 parts by weight of fish scale collagen peptide, 8.1 parts by weight of fermented glucosamine, 4.1 parts by weight of arginine, 51.0 parts by weight of reduced maltose, 200 parts by weight of powdered propionic acid bacteria culture (DHNA: 81 ⁇ g / g), silicon dioxide 16.0 parts by weight were added and mixed uniformly with a V-shaped mixer.
  • DHNA powdered propionic acid bacteria culture
  • the resulting mixed powder is compression-molded with a tableting machine (manufactured by Hata Kogyo Co., Ltd.) to a hardness of 8.0 kgf, and a circular tablet (tablet with a weight of 0.25 g and a diameter of 8 mm) (tablet ) Was manufactured.
  • a tableting machine manufactured by Hata Kogyo Co., Ltd.
  • a circular tablet tablette with a weight of 0.25 g and a diameter of 8 mm
  • composition containing the culture of propionic acid bacteria provided based on the present invention can be used as an agent for improving skin condition, particularly as an inhibitor of pigment formation, by oral administration.
  • the compositions of the present invention formulated into foods such as nutrients and yogurt, can also be utilized as a composition for oral ingestion it can be expected the improvement of the skin condition.
  • the component which comprises the composition of this invention is comprised with the component demonstrated that it was excellent in safety
  • the composition of the present invention can additionally contain a milk fermentation component.
  • the composition of the present invention can be expected to have an intestinal regulating effect in addition to the skin condition improving effect by ingesting the composition.

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Abstract

Selon la présente invention, il est démontré que le produit de bactéries propioniques cultivées a pour effet d'améliorer l'état de la peau. Une composition contenant le produit de bactéries propioniques cultivées améliore l'état de la peau et, en particulier, inhibe la pigmentation. La composition est formée à partir de composants éprouvés depuis de nombreuses années de consommation comme étant excellents en termes de sécurité et de goût, et la consommation à long terme de la composition est possible. Des composants de fermentation du lait peuvent en outre être ajoutés à la composition. Lorsqu'elle est ingérée, la composition devrait avoir un effet régulateur sur la fonction intestinale ainsi qu'un effet améliorant l'état de la peau.
PCT/JP2011/061695 2010-05-21 2011-05-20 Composition pour améliorer l'état de la peau Ceased WO2011145737A1 (fr)

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CN201180035694.7A CN103025338B (zh) 2010-05-21 2011-05-20 用于改善皮肤状态的组合物
JP2012515953A JP5954828B2 (ja) 2010-05-21 2011-05-20 皮膚状態の改善用組成物
SG2012081121A SG185410A1 (en) 2010-05-21 2011-05-20 Composition for improving condition of skin
HK13106302.5A HK1178465B (en) 2010-05-21 2011-05-20 Composition for improving condition of skin

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JP2010-117487 2010-05-21

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WO2014080784A1 (fr) * 2012-11-20 2014-05-30 大蔵製薬株式会社 Préparation pharmaceutique aqueuse d'olanzapine présentant une stabilité à long terme
WO2014163031A1 (fr) * 2013-04-01 2014-10-09 株式会社明治 Régulateur intestinal instantané
US10117910B2 (en) * 2014-05-20 2018-11-06 Hainan Meihetai Biotechnology Co., Ltd. Composition of natural vitamin C and fish scale collagen peptide and preparation method thereof
CN113365646A (zh) * 2019-01-15 2021-09-07 诺维信公司 用于调节真皮和真皮下特性的基于孢子的益生菌组合物
JP7531261B2 (ja) 2017-02-17 2024-08-09 株式会社明治 インターロイキン－２３産生促進用組成物

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CN104988104B (zh) * 2015-08-13 2017-12-26 山东凤凰生物有限公司 一株具有吸附或降解肠毒素功能的乳酸菌及其应用
SG11201807875XA (en) * 2016-03-24 2018-10-30 Meiji Co Ltd Composition for improving oral cavity environment
WO2018174369A1 (fr) * 2017-03-24 2018-09-27 주식회사 팜스킨 Produit de colostrum fermenté par des bactéries lactiques et composition cosmétique l'utilisant
TWI676684B (zh) * 2017-06-15 2019-11-11 財團法人食品工業發展研究所 乳酸桿菌、使用其製備色素之方法、乳酸桿菌培養物與包括其之色素組成物
KR101927988B1 (ko) * 2018-08-23 2018-12-12 주식회사 지놈앤컴퍼니 신규의 큐티박테리움 그래뉼로섬 균주, 및 이러한 균주 또는 이의 배양물을 포함하는 여드름 예방 또는 치료용 조성물
KR101925135B1 (ko) * 2018-08-23 2018-12-04 주식회사 지놈앤컴퍼니 신규의 큐티박테리움 아비덤 균주, 및 이러한 균주 또는 이의 배양물을 포함하는 아토피 피부염 예방 또는 치료용 조성물
WO2020067663A1 (fr) * 2018-09-28 2020-04-02 주식회사 엘지생활건강 Composition favorisant le renouvellement cellulaire et l'excrétion mélanique
CN110066749A (zh) * 2019-04-25 2019-07-30 杭州师范大学 一种微生物复合菌制剂及其应用
CN112386618A (zh) * 2019-08-14 2021-02-23 百岳特生物技术（上海）有限公司 普蒂亚花萃取物用于制备皮肤抗老化的组合物的用途
KR102214820B1 (ko) * 2020-02-13 2021-02-10 씨제이제일제당 (주) 피부 상태 개선용 조성물
KR102380211B1 (ko) * 2020-06-04 2022-03-30 주식회사 이뮤니스바이오 면역세포배양액을 포함한 항균효과를 가지는 화장료 조성물
TWI895625B (zh) * 2022-08-05 2025-09-01 彩宸生活事業股份有限公司 乳酸菌醱酵上清液及其用於製備增強肌膚保護力、保濕及美白之化粧品組成物的用途

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Publication number Priority date Publication date Assignee Title
WO2014080784A1 (fr) * 2012-11-20 2014-05-30 大蔵製薬株式会社 Préparation pharmaceutique aqueuse d'olanzapine présentant une stabilité à long terme
WO2014163031A1 (fr) * 2013-04-01 2014-10-09 株式会社明治 Régulateur intestinal instantané
CN105073107A (zh) * 2013-04-01 2015-11-18 株式会社明治 速效性整肠剂
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CN113365646A (zh) * 2019-01-15 2021-09-07 诺维信公司 用于调节真皮和真皮下特性的基于孢子的益生菌组合物

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JP5954828B2 (ja) 2016-07-20
SG185410A1 (en) 2012-12-28
JP2016164144A (ja) 2016-09-08

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