WO2014163031A1 - Régulateur intestinal instantané - Google Patents

Régulateur intestinal instantané Download PDF

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Publication number
WO2014163031A1
WO2014163031A1 PCT/JP2014/059404 JP2014059404W WO2014163031A1 WO 2014163031 A1 WO2014163031 A1 WO 2014163031A1 JP 2014059404 W JP2014059404 W JP 2014059404W WO 2014163031 A1 WO2014163031 A1 WO 2014163031A1
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Prior art keywords
intestinal
effect
immediate
propionic acid
present
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PCT/JP2014/059404
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English (en)
Japanese (ja)
Inventor
圭介 堰
ナダー シーワナーソン
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株式会社明治
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Priority to JP2015510071A priority Critical patent/JPWO2014163031A1/ja
Priority to SG11201508154QA priority patent/SG11201508154QA/en
Priority to CN201480019256.5A priority patent/CN105073107A/zh
Publication of WO2014163031A1 publication Critical patent/WO2014163031A1/fr
Priority to HK16105265.9A priority patent/HK1217290A1/zh

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    • 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
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives

Definitions

  • the present invention relates to an immediate-acting intestinal agent having a low physical burden unlike conventional intestinal-regulating agents.
  • the present invention includes a propionic acid bacteria culture, DHNA (1,4-dihydroxy-2-naphthoic acid) or an analog thereof as an active ingredient.
  • the present invention relates to an immediate-acting intestinal agent with a small physical burden.
  • probiotics for example, live bacteria such as lactic acid bacteria and bifidobacteria
  • prebiotics for example, indigestible
  • intestinal preparations that adjust the intestinal environment by ingesting continuously. Oligosaccharides, dietary fibers, sterilized microorganisms, etc. are known. These intestinal preparations have a mild intestinal effect and are extremely unlikely to cause side effects such as abdominal pain and diarrhea that are problematic with the laxatives described above.
  • Profec (Meiji, trade name; “Profec” is a registered trademark of Meiji Meiji Co., Ltd.) is “tummy vitality tablet (tablet containing Profec)” and “tummy vitality milk (milk drink containing Profec)” (Meiji's “Onaka Vitality” is a commercialized product such as “Meiji Meiji Co., Ltd.”), which is known as prebiotics, and has received approval for foods for specified health use.
  • Profec is a whey fermented product of Propionibacterium freudenreichii ET-3 strain isolated from Emmental cheese and developed as a material containing components that promote the growth of bifidobacteria, among the main enteric bacteria.
  • Non-Patent Document 1 It has been clarified that when humans ingest Profec in 2 to 4 weeks, the effect of intestinal regulation is exhibited (Non-patent Documents 2 to 4, 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. It has also been clarified that administration of DHNA to colitis model animals exerts an improvement / prevention effect on enteritis (Non-patent Document 5).
  • Patent Documents 2 and 3 (2) Among bowel control effects, the effect of improving bowel movement (for example, increase in the number of bowel movements or increase in the volume of bowel movement) is often not recognized significantly (Patent Document 2), (3) bowel movement improvement effect There is a known problem that a person with a tendency to constipation needs to take or ingest (administer) the material continuously. That is, at present, there are few known intestinal regulating agents having both immediate effect, sustainability and safety.
  • An object of the present invention is to provide an intestinal regulating agent that has a low physical burden, is highly safe, has an immediate effect, and is durable.
  • the present invention is based on the discovery of a new fast-acting and long-lasting intestinal effect related to Profec, which has not been known for a long time.
  • An immediate-acting intestinal regulating agent comprising at least one component of a culture of propionic acid bacteria, or DHNA or an analog thereof.
  • the immediate-acting intestinal agent of [1] wherein the propionic acid bacterium is Propionibacterium freudenreichii.
  • the intestinal effect lasts for 1 week, preferably 1.5 weeks, more preferably 2 weeks after the discontinuation of ingestion (administration), [1] to [4] Any of the immediate-acting intestinal agents.
  • Daily intake (dose) is 5 ⁇ g or more (for example, 5 ⁇ g to 100 ⁇ g), preferably 6 ⁇ g or more (for example, 6 ⁇ g to 50 ⁇ g), more preferably 6.5 ⁇ g or more (for example, 6.5 ⁇ g to 20 ⁇ g), the immediate-acting intestinal agent according to any one of [1] to [5].
  • the content per packaging form is 5 ⁇ g to 100 ⁇ g, preferably 6 ⁇ g to 50 ⁇ g, more preferably 6.5 ⁇ g to 20 ⁇ g, using the converted amount (content) of DHNA or an analog thereof as an index.
  • the immediate-acting intestinal regulating agent according to any one of [1] to [6].
  • the rapid-acting intestinal agent according to any one of [1] to [7] which is taken (administered) together with a collagen peptide.
  • a method for producing an immediate-acting intestinal preparation comprising a step of blending (using) at least one component of a culture of propionic acid bacteria or DHNA or an analog thereof, preferably propionic acid bacteria Is Propionibacterium freudenreichii, and a fast-acting intestinal preparation is a fast-acting bowel movement improving agent.
  • a fast-acting intestinal preparation is a fast-acting bowel movement improving agent.
  • Daily intake (dose) is 5 ⁇ g or more (for example, 5 ⁇ g to 100 ⁇ g), preferably 6 ⁇ g or more (for example, for example) using the equivalent amount (intake) of DHNA or an analog thereof as an index.
  • the content per packaging form is 5 ⁇ g to 100 ⁇ g, preferably 6 ⁇ g to 50 ⁇ g, more preferably 6.5 ⁇ g to 20 ⁇ g, using the converted amount (content) of DHNA or an analog thereof as an index.
  • the present invention further relates to the following aspects.
  • [B-1] Use of a culture of propionic acid bacteria or DHNA or an analog thereof for the production of a rapid-acting intestinal agent, preferably, the propionic acid bacteria is Propionibacterium freudenreichii And an immediate-acting intestinal preparation is an immediate-acting bowel movement improving agent.
  • [B-2] Use of [B-1], wherein an intestinal regulating effect is obtained within 7 days, preferably within 2 days, more preferably within 1 day after ingestion (after administration).
  • [B-3] The intestinal effect is sustained for (at least) 1 week, preferably 1.5 weeks, more preferably 2 weeks after cessation of ingestion (administration), [B-1] Or use of [B-2].
  • Daily intake (dose) is 5 ⁇ g or more (for example, 5 ⁇ g to 100 ⁇ g), preferably 6 ⁇ g or more (for example, for example) using the converted amount (intake) of DHNA or an analog thereof as an index. 6 ⁇ g to 50 ⁇ g), more preferably 6.5 ⁇ g or more (for example, 6.5 ⁇ g to 20 ⁇ g), the use according to any one of [B-1] to [B-3].
  • the content per packaging form is 5 ⁇ g to 100 ⁇ g, preferably 6 ⁇ g to 50 ⁇ g, more preferably 6.5 ⁇ g to 20 ⁇ g, using the converted amount (content) of DHNA or an analog thereof as an index. The use of any one of [B-1] to [B-4].
  • the present invention further relates to the following aspects.
  • [C-1] A culture of propionic acid bacteria or DHNA or an analog thereof for use in the expression of an immediate intestinal regulating effect.
  • the propionic acid bacteria is Propionibacterium (Propionibacterium). freudenreichii), an immediate effect of bowel control is an immediate effect of improving bowel movement.
  • [C-2] Propionic acid of [C-1], wherein an intestinal regulating effect is obtained within 7 days, preferably within 2 days, more preferably within 1 day after ingestion (after administration) Fungal culture or DHNA or analogs thereof.
  • the intestinal regulating effect lasts for 1 week, preferably 1.5 weeks, more preferably 2 weeks after cessation of ingestion (administration), [C-1] Or a culture of propionic acid bacteria of [C-2] or DHNA or an analog thereof.
  • the daily intake (dose) is 5 ⁇ g or more (for example, 5 ⁇ g to 100 ⁇ g), preferably 6 ⁇ g or more (for example, for example) using the converted amount (intake) of DHNA or an analog thereof as an index.
  • the content per packaging form is 5 ⁇ g to 100 ⁇ g, preferably 6 ⁇ g to 50 ⁇ g, more preferably 6.5 ⁇ g to 20 ⁇ g, using the converted amount (content) of DHNA or an analog thereof as an index.
  • the present invention further relates to the following aspects.
  • a method for producing an immediate intestinal regulating effect comprising a step of ingesting (administering) an effective amount of at least one component of a culture of propionic acid bacteria or DHNA or an analog thereof.
  • the propionic acid bacterium is Propionibacterium freudenreichii
  • the immediate effect of intestinal regulation is an immediate effect of improving bowel movement.
  • Immediate effect of [D-1] characterized in that an intestinal regulating effect can be obtained within 7 days, preferably within 2 days, more preferably within 1 day after ingestion (after administration) Of intestinal regulation effect.
  • the intestinal effect lasts for (at least) 1 week, preferably 1.5 weeks, more preferably 2 weeks after cessation of ingestion (administration), [D-1] Or [D-2] a method for producing the immediate effect of intestinal regulation.
  • the daily intake (dose) is 5 ⁇ g or more (for example, 5 ⁇ g to 100 ⁇ g), preferably 6 ⁇ g or more (for example, for example) using the equivalent amount (intake) of DHNA or an analog thereof as an index. 6 ⁇ g to 50 ⁇ g), more preferably 6.5 ⁇ g or more (for example, 6.5 ⁇ g to 20 ⁇ g), exhibiting an immediate intestinal regulating effect of any of [D-1] to [D-3] How to make.
  • [D-5] The content per packaging form is 5 ⁇ g to 100 ⁇ g, preferably 6 ⁇ g to 50 ⁇ g, more preferably 6.5 ⁇ g to 20 ⁇ g, using the converted amount (content) of DHNA or an analog thereof as an index.
  • probiotics and prebiotics have been known as materials that maintain the intestinal environment by continuously ingesting them, thereby producing an intestinal regulating effect. Therefore, they have been recognized as a material for the main purpose and intended use of preventing constipation.
  • the rapid-acting intestinal adjuster of the present invention can be produced by blending ingredients (such as raw materials) that have been ingested (administered) by humans as foods and the like. Therefore, the immediate action intestinal preparation of the present invention has already been guaranteed high safety and can be taken continuously (continuously).
  • the immediate-acting intestinal agent of the present invention has a plurality of advantageous effects such as the immediate effect of conventional laxatives and the sustainability and safety of conventional probiotics and prebiotics. It has been clarified that it can be provided as a new means with a small physical burden for obtaining an intestinal effect.
  • Wm-n means the n-th day of the m-th week, for example, W3-1 (the first day of the third week) means the first day after taking the test meal. It is a graph which shows a subject's difficulty of defecation. “*” And “* ⁇ ” indicate that there is a significant difference at p ⁇ 0.01 and p ⁇ 0.05, respectively, compared with the second week (Week2). It is a graph which shows the time required for a test subject's defecation. “*” And “* ⁇ ” indicate that there is a significant difference at p ⁇ 0.01 and p ⁇ 0.05, respectively, compared with the second week (Week2).
  • “*” And “* ⁇ ” indicate that there is a significant difference at p ⁇ 0.01 and p ⁇ 0.05, respectively, compared with the second week (Week2). It is a graph which shows the satisfaction to the characteristic of a test subject's defecation. “*” And “* ⁇ ” indicate that there is a significant difference at p ⁇ 0.01 and p ⁇ 0.05, respectively, compared with the second week (Week2). It is a graph which shows a test subject's satisfaction with the defecation habit. “*” And “* ⁇ ” indicate that there is a significant difference at p ⁇ 0.01 and p ⁇ 0.05, respectively, compared with the second week (Week2).
  • the horizontal axis indicates the number of days after taking the test meal, and the day of intake is the 0th day.
  • the bar graph shows the number of subjects who first felt the bowel control effect
  • the line graph shows the cumulative percentage of subjects who felt the bowel regulation effect.
  • the present invention provides a rapid-acting intestinal regulating agent comprising at least one active ingredient of a culture of propionic acid bacteria or DHNA or an analog thereof.
  • the “intestinal regulating effect” includes a bowel movement improving effect, a constipation improving effect, an intestinal environment improving effect, and a fecal improvement effect, and preferably a bowel movement improving effect. Therefore, in the present specification, the “intestinal regulating agent” includes a bowel movement improving agent, a constipation improving agent, an intestinal environment improving agent, and a fecal improvement agent, and is preferably a bowel movement improving agent.
  • “improvement of bowel movement” means increase in the number of bowel movements, increase in the volume of bowel movement, improvement in difficulty of bowel movement, reduction in time required for bowel movement, improvement in feeling during bowel movement, improvement in frequency of bowel movement, bowel movement characteristics Means improvement of stool and / or improvement of defecation habits, and can also be expressed as “facilitation of bowel movement”.
  • immediate effect means within 7 days, within 6 days, within 5 days, within 4 days, or within 3 days after ingestion (after administration), preferably within 2 days after ingestion, more Preferably, it means the property of exhibiting a predetermined effect within one day after ingestion, and “expression of immediate effect of intestinal regulation” can also be expressed as “expression of intestinal effect in a short period of time”. .
  • “improved in a short period” means within 7 days, 6 days, 5 days, 4 days, or 3 days after ingestion (after administration), preferably within 2 days after ingestion, Preferably, it means improving the condition within one day after ingestion.
  • the term “persistence” means the property of maintaining a predetermined effect for at least 1 week, preferably 1.5 weeks, more preferably 2 weeks after cessation of administration (administration). .
  • “maintaining a predetermined effect” means that the effect after stopping the intake of a predetermined (active) component is 30% or more, preferably 50% or more, more preferably 70% compared to the effect during intake. It means that it is maintained at% or more.
  • “intake” can also be expressed as “administration”.
  • immediate effective intestinal adjuster does not mean only pharmaceutical products or quasi-drugs that are used to develop an immediate effective intestinal regulating effect.
  • health supplements for example, health supplements, health functions It also means foods (special health foods or functional foods for nutrition), functional foods such as supplements, food additives, and the like.
  • the quick-acting intestinal preparation of the present invention is characterized by a small physical burden. Therefore, the rapid-acting intestinal regulating agent of the present invention can be used for constipation prone persons of a wide age group. That is, it can be preferably used for women, elderly people, infants, infants, or sick persons (patients) who have been difficult or impossible to use conventional laxatives because the physical burden is not small.
  • the immediate-acting intestinal agent of the present invention can be preferably used by women because it can be expected to improve beauty.
  • the immediate-acting intestinal preparation of the present invention is preferably an immediate-acting intestinal with a low degree or frequency of side effects, and more preferably an immediate-acting intestinal with no side effects.
  • the rapid-acting intestinal regulating agent of the present invention includes 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.
  • the rapid-acting intestinal regulating agent of the present invention can be blended (added) with the following microorganism culture. Namely, Propionibacterium freudenreichii, Propionibacterium toeni (P. thoenii), Propionibacterium ashidipropionici (P. acidipropionici), Propionibacterium genseny (P. jensenii) and the like.
  • 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 granulosum (P. granulosam) is there.
  • a method for isolating these propionic acid bacteria from nature or fermented milk is known.
  • These propionic acid bacteria may be microorganisms used for manufacturing Swiss cheese 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.
  • the conditions described in WO03 / 016544A1 and the like can be applied. For example, if a suitable medium is inoculated with Propionibacterium freudenreichii and cultured under conditions where propionic acid bacteria can grow, a culture of propionic acid bacteria can be obtained.
  • the rapid-acting intestinal regulating agent of the present invention can be blended with other components (materials, etc.) after sterilizing the culture of propionic acid bacteria after completion of the culture.
  • the immediate-acting intestinal regulating agent of the present invention can be sterilized after blending a culture of propionic acid bacteria with other components (materials, etc.) after completion of the culture.
  • sterilization methods and the like are stipulated in a ministerial ordinance such as milk, and low temperature long time sterilization, high temperature short time sterilization, and ultra high temperature (instant) sterilization can be used as general heat sterilization treatment. .
  • the sterilization method equivalent to the case of milk or heat sterilization treatment can be applied to the culture of propionic acid bacteria of the present invention or the immediate action intestinal preparation containing the same.
  • These heat sterilization treatments may be a batch type (batch unit) or a continuous type.
  • 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 culture of propionic acid bacteria or the rapid-acting intestinal regulating agent containing the same is continuously maintained in an inert gas atmosphere and / or injected with an inert gas as necessary ( Bubbling) is preferred.
  • the inert gas include nitrogen gas, argon gas, carbon dioxide gas, etc., but they are present in large quantities in the air, the cost is relatively low, safety is confirmed, and the flavor and quality of food and drink Nitrogen gas is particularly desirable because it does not affect the process.
  • the culture of propionic acid bacteria or the rapid-acting intestinal preparation containing the same is maintained in a vacuum (reduced pressure) atmosphere and / or allowed to pass through the vacuum atmosphere as necessary. It is preferable.
  • the vacuum state include reduced-pressure degassing treatment.
  • the inventors of the present invention have confirmed that an immediate intestinal regulating effect is maintained in the sterilized product of the propionic acid bacteria culture. That is, in the present invention, the immediate effect of intestinal regulation of the culture of propionic acid bacteria is maintained even after sterilization of the culture.
  • microorganisms such as lactic acid bacteria
  • Probiotics and prebiotics have been reported to improve the intestinal environment and stimulate immunity.
  • probiotics refer to microorganisms that give a beneficial effect to the host by being introduced into the intestine of the host in a living state.
  • prebiotics refer to substances that have beneficial effects on the host by acting on microorganisms that originally lived in the intestines.
  • microorganisms such as lactic acid bacteria and bifidobacteria
  • probiotics that exhibit an intestinal regulating action in human tests.
  • these microorganisms function as probiotics and act on live bacteria, their production and quality control have not been easy.
  • live bacteria preparations have limited storage stability. For example, after producing a live bacteria preparation, the original activity (stability) cannot be maintained over a long period even if stored at a low temperature. There were many.
  • the culture of propionic acid bacteria of the present invention not only functions as probiotics but also functions as prebiotics. To do. At this time, in 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 immediate effect of intestinal regulation.
  • the culture of propionic acid bacteria of the present invention or the immediate-acting intestinal preparation containing the same is a prebiotic that acts even when killed, so that its production and quality control are easy. Furthermore, the preparations and the like based on the present invention can maintain their original activity (stability) over a long period even when stored at room temperature.
  • the effect of oral administration it often depends on the action of living microorganisms (such as lactic acid bacteria and bifidobacteria), and the influence of gastric acid must be considered. This is because gastric acid reduces the number of viable microorganisms and a sufficient amount of viable bacteria cannot be delivered into the intestine.
  • the culture of propionic acid bacteria of the present invention or the sterilized product thereof can be processed into any form such as liquid, paste, gel, powder, granule, solid and the like.
  • an appropriate excipient is added (mixed) to the culture of the propionic acid bacterium of the present invention or the sterilized product thereof to adjust the solid content concentration to 30% to 40%, followed by spray drying or freeze drying. And can be pulverized.
  • known excipients can be used, for example, skim milk powder, whey powder, raw starch, dextrin, etc., and in addition, WPC, WPI, modified starch, etc. are used as necessary. be able to.
  • a publicly known method can be used for spray drying and freeze drying, for example, a method of spray-drying or freeze-drying a culture of the propionic acid bacterium of the present invention or a sterilized product thereof as it is, Alternatively, the culture of the propionic acid bacterium of the present invention, or a sterilized product thereof and a reducing solution of excipients are mixed and concentrated to a solids concentration of 30% to 40%, followed by spray drying or freeze drying. A method can also be used.
  • oxygen removal treatment (addition of nitrogen, addition of oxygen scavenger, etc.)
  • it can be processed into a triturated preparation (0.2% powdered powder) for easy use in foods.
  • modified starch of excipient for example, in addition to dextrin, acetylated adipic acid cross-linked starch, acetylated phosphoric acid cross-linked starch, acetylated oxidized starch, octenyl sodium succinate starch, acetic acid starch, oxidized starch, hydroxypropyl starch Hydroxypropylated phosphoric acid crosslinking starch, phosphoric acid monoesterified phosphoric acid crosslinking starch, phosphorylated starch, phosphoric acid crosslinking starch and the like can be used.
  • the culture of the propionic acid bacterium of the present invention or the sterilized product thereof may be ingested together with the collagen peptide, or may be formulated together with the collagen peptide.
  • a culture of propionic acid bacteria has an effect of promoting the growth of lactic acid bacteria.
  • a culture of propionic acid bacteria having such an action, or a processed product thereof (bacteria, concentrate, dried product, etc.) is also referred to as “Bifidogenic Growth Stimulator: BGS”.
  • BGS Bacthelial Growth Stimulator
  • a whey fermentation product by the propionic acid bacterium is preferable.
  • reduced whey aqueous whey powder solution
  • Propionibacterium freudenreichii ET-3 producing BGS The culture of propionic acid bacteria obtained in this way can be used (included) as an active ingredient in the rapid-acting intestinal regulating agent of the present invention.
  • Such a culture of propionic acid bacteria containing BGS is also called “Profec”.
  • this Profec specifically increases the number of bifidobacteria in the human intestine (Bifidobacterium ⁇ : ⁇ Bifidobacterium), so it has been approved as an ingredient involved in specific health foods (ILSI, No. 80, 5- 13 (2004)).
  • BGSpowder made by Meiji, trade name
  • tummy vitality tablet made by Meiji, trade name; “tummy vitality” is a registered trademark of Tsubaki Meiji Co., Ltd.
  • tummy vitality is a registered trademark of Tsubaki Meiji Co., Ltd.
  • “B.G.S.powder”, “tummy vitality tablet” or “tummy vitality milk” can also be used as the immediate-acting intestinal regulating agent of the present invention.
  • the culture of propionic acid bacteria whey fermented product by propionic acid bacteria
  • a culture of propionic acid bacteria, which is a prebiotic has an excellent immediate-effect intestinal effect that is manifested in short-term use.
  • BGS contained in Profec includes, for example, 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).
  • This 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 metabolic process of bifidobacteria energy.
  • any of the following components (i), (i ′) and (ii), (ii ′), or two or more thereof can be used as the culture of the propionic acid bacterium of the present invention. That is, the present invention provides either (i) 1,4-dihydroxy-2- naphthoic acid (DHNA) and (ii) 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ) or both.
  • DHNA 1,4-dihydroxy-2- naphthoic acid
  • ACNQ 2-amino-3-carboxy-1,4-naphthoquinone
  • an immediate-acting intestinal adjusting agent containing as an active ingredient.
  • 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.
  • This DHNA can be synthesized, for example, according to the method described in JP-A-2007-284449, but is not limited thereto.
  • this ACNQ can be synthesized according to the methods described in, for example, JP-A No. 07-289273, Japanese Patent No. 3265193, Japanese Patent No. 2003-089683, Japanese Patent No. 4072430, Japanese Patent No. 3532226, but is not limited thereto.
  • these DHNAs and ACNQs can be used as they are as the immediate-acting intestinal regulating agent of the present invention by blending these synthesized products or fractions of the active ingredients thereof.
  • these DHNA and ACNQ can be purified and used as the rapid-acting intestinal regulating agent of the present invention.
  • the present invention also provides an immediate-acting intestinal preparation containing as an active ingredient either (i ′) an analog of DHNA and (ii ′) an analog of ACNQ, or both.
  • These analogs of DHNA and ACNQ include 1, 4-naphthoquinone, 2-methyl-1, 4-naphthoquinone, 4-amino-2-methyl-1-naphthol, 2-amino-3-chloro-1, Examples thereof include, but are not limited to, 4-naphthoquinone.
  • These DHNA analogs and ACNQ analogs are known to be produced in cultures of microorganisms used for the production of fermented milk, for example, according to the method described in JP-A-07-289273. .
  • these DHNA analogs and ACNQ analogs can be used as they are as the rapid-acting intestinal regulating agent of the present invention by blending the culture of these microorganisms or fractions of the active ingredients thereof.
  • the DHNA analog and ACNQ analog can be purified and used together with DHNA and ACNQ as the immediate-acting intestinal adjuster of the present invention.
  • the daily dose (ingestion amount) for humans (adults) Is generally in the range of 0.01 ⁇ g / kg ⁇ body weight to 100 mg / kg ⁇ body weight, using the converted amount (intake amount) of DHNA or an analog thereof contained in the culture of propionic acid bacteria as an index.
  • the daily dose (ingestion amount) for humans (adults) may be sufficient even if the dose is less than this, depending on the age, physique, sex, etc. of humans. Conversely, higher doses may be required.
  • the daily intake (dose) is not particularly limited, but for example, 5 ⁇ g or more (for example, 5 ⁇ g) using the converted amount (intake) of DHNA or an analog thereof as an index.
  • the daily intake (dose) is, for example, 0.5 mg or more (for example, 0.5 mg) using the converted amount (intake) of the culture of propionic acid bacteria as an index. ⁇ 10 mg), preferably 0.6 mg or more (0.6 mg to 5 mg), more preferably 0.65 mg or more (0.65 mg to 2 mg).
  • the content per packaging form for humans (of adults) is, for example,
  • the converted amount (content) of DHNA or an analog thereof contained in the culture of propionic acid bacteria is used as an index, and generally ranges from 0.01 ⁇ g / kg ⁇ body weight to 100 mg / kg ⁇ body weight.
  • the content per packaging form for humans (adults) may be sufficient even if it is less than this depending on the age, physique, gender, etc. of humans. In some cases, higher doses may be required.
  • the content per packaging form is not particularly limited. For example, 5 ⁇ g to 100 ⁇ g, preferably 6 ⁇ g to 50 ⁇ g, using the converted amount (content) of DHNA or an analog thereof as an index. More preferably, it is 6.5 ⁇ g to 20 ⁇ g.
  • the content per packaging form is, for example, 0.5 mg to 10 mg, preferably 0.6 mg to 5 mg, using the converted amount (content) of the culture of propionic acid bacteria as an index. More preferably, it is 0.65 mg to 2 mg.
  • the administration frequency (intake frequency) for humans (adults) can be divided into several times (eg 2 to 4 times) per day, for example.
  • the daily dose (ingestion amount) for humans (adults) means the amount necessary to develop an immediate effect of intestinal regulation, and the person (ingestion) of human age, physique, gender, etc. And the like, the administration route, the degree of intestinal effect expected actually, and the like.
  • the administration route (intake route) for human (adult) is preferably oral administration (oral intake) or enteral administration (enteral intake), and oral administration (oral intake). Is more preferable.
  • the rapid-acting intestinal preparation of the present invention can be prepared by blending a culture of propionic acid bacteria at, for example, 0.001 to 20% by weight, preferably 0.01 to 15% by weight, more preferably 0.05 to 10% by weight.
  • the rapid-acting intestinal regulating agent of the present invention can be processed into any dosage form such as liquid, paste, gel, powder, granule, solid and the like. Specifically, it can be formulated into tablets, capsules, granules, powders, syrups and the like.
  • the main ingredients are excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspending agents, coating agents, solvents, isotonic agents, antioxidants, stabilization.
  • the rapid-acting intestinal preparation of the present invention is prepared by blending (mixing) propionic acid bacteria with components (milk fermentation components, etc.) suitable for oral administration (oral intake), pharmaceutically acceptable carriers, and the like. And can be provided.
  • the immediate-acting intestinal adjuster of the present invention is obtained by adding (dispersing) a propionic acid bacterium culture to a component (such as a milk fermentation component) suitable for oral administration (oral intake), a pharmaceutically acceptable carrier, or the like.
  • vitamins, minerals, organic acids (including fatty acids such as short chain fatty acids), saccharides, amino acids, peptides (for example, collagen peptides) and the like can be blended in appropriate amounts.
  • the present inventors selected (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) at least one component selected from the group consisting of ACNQ or an analog thereof. It has been found that immediate intestinal regulating effects are expressed in ingested (oral administration, etc.) humans. That is, the present invention comprises (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, (c) at least one component selected from the group consisting of ACNQ or an analog thereof, It relates to an intestinal regulating agent.
  • the present invention provides an animal ingesting (orally) at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof. And the like, and the like.
  • animals include mammals, birds, amphibians, and reptiles, but mammals are preferred, humans are more preferred, and humans are even more preferred.
  • the present invention also relates to a rapid-acting intestinal agent of at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof.
  • a rapid-acting intestinal agent of at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof.
  • the present invention provides an immediate-acting intestinal adjustment of at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof. It relates to use in the manifestation of effects.
  • the present invention comprises a step of using at least one component selected from (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof.
  • the present invention relates to a method for producing a sex adjusting agent.
  • the present invention is a group comprising (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, (c) ACNQ or an analog thereof for use in the development of an immediate effect of regulating the intestine. Relates to at least one component selected.
  • the immediate-acting intestinal agent of the present invention includes pharmaceuticals, quasi drugs, health supplements, health functional foods (specific health foods or nutritional functional foods), functional foods (supplements, etc.), other foods, food additives, etc. It can be used in the form of In supplements and the like, for example, a tablet is a preferable form from the viewpoint of good storage stability and the ability to reliably take an effective amount.
  • “food” includes “beverage”.
  • the rapid-acting intestinal adjuster of the present invention can also be used in biological standards of pharmaceuticals, foods and drinks (foodstuffs such as infant formulas, infant formulas, and lactating formulas).
  • Examples of the rapid-acting intestinal adjuster of the present invention include various propionic acid bacteria suspensions, propionic acid bacteria, propionic acid culture supernatant (including medium components), propionic acid fermentation products, and the like. Can be included.
  • the immediate-acting intestinal adjuster of the present invention can be ingested alone (oral administration), or can be ingested (oral administration) in combination (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 intestinal effect, it is effective in the expression and improvement of the immediate effect of intestinal effect.
  • the immediate-acting intestinal preparation of the present invention includes milk, dairy products, soft drinks, powdered drinks, fermented milk, lactic acid bacteria drinks, acidic drinks, yogurt, cheese, bread, biscuits, crackers, pizza crusts, formula milk powder, Examples include liquid foods, foods for patients, nutritional foods, frozen foods, food compositions, processed foods, and other commercially available foods.
  • the immediate-acting intestinal adjuster of the present invention can be set to, for example, a pH of 2 to 6, preferably 3 to 5, as an acidic pharmaceutical or food form.
  • the immediate-acting intestinal regulating agent of the present invention as shown in the Examples described later, exhibited an immediate-acting intestinal regulating effect when ingested as an ingredient of a culture of propionic acid bacteria.
  • the present invention provides a functional food containing at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof. Or let a pharmaceutical composition be one of the preferable aspects.
  • the present invention provides at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof, as a functional food or a pharmaceutical.
  • the present invention relates to a method for producing a functional food or a pharmaceutical composition that expresses an immediate effect of regulating the intestine, including a step of blending with a chemically acceptable carrier.
  • the present invention includes, in a functional food, at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof.
  • the present invention relates to a method for imparting a functional food with the ability to develop an immediate effect of regulating the intestine, including the step of:
  • the present invention provides pharmaceutically acceptable at least one component selected from the group consisting of (a) a culture of propionic acid bacteria, (b) DHNA or an analog thereof, and (c) ACNQ or an analog thereof.
  • a pharmaceutical composition prepared by blending with a carrier.
  • an additional component for example, collagen peptide
  • it can be prepared by mixing saccharides (for example, maltodextrin) and the like homogeneously as a carrier, and blended with vitamin C and the like as a stabilizer. May be.
  • the immediate action intestinal agent of the present invention is a protein derived from a culture of propionic acid bacteria, for example, 1% by weight or more of saccharides, preferably 10% by weight or more of saccharides, more preferably 30% by weight or more of saccharides. More preferably, it can be prepared by blending so that the ratio is 70% by weight or more of the saccharide.
  • the immediate-acting intestinal adjuster of the present invention should be set to, for example, 0.1 to 3 kcal, preferably 0.3 to 2.5 kcal, more preferably 0.5 to 2 kcal per mL as a form of a pharmaceutical enteral nutrient or liquid food. Can do.
  • Subjects The subjects were 76 Thai women aged 18 to 49 years with mild constipation (slow or irregular bowel movements). Subject characteristics are shown in Table 1 (numbers are average values ⁇ standard deviation).
  • Test meal 1.5 g / pack of BGS powder (composition containing Profec, dextrin and glucose) was used as the test meal.
  • Profec is a composition in which whey is fermented with Propionibacterium freudenreichii ET-3 (propionic acid bacterium ET-3) and then sterilized.
  • One BGS powder 1.5 g contained DHNA (1,4-dihydroxy-2-naphthoic acid) in an amount of 6.5 ⁇ g to 6.6 ⁇ g.
  • Test schedule The subject ingested the test meal (BGS powder) at 1 packet / day at any time. During the first two weeks (Week 1 and Week 2) of the start of the study, the subjects did not take the test meal during the pre-intake period (pre-intake period) and in the next 2 weeks (Week 3 and Week 4) During the ingestion period (intake period), the subject took the test meal, and in the next two weeks (Week 5, Week 6), the subject took the test meal as the period after ingestion (post intake period). Did not take.
  • Subjects were 128 Japanese women aged 18 to 64 whose number of bowel movements was approximately 4 or less per week.
  • Test meal 7 g of “Amino Collagen Profec” (manufactured by Meiji Co., Ltd.) was used as a test meal.
  • “Amino Collagen Profec” is composed of fish collagen peptide (gelatin), maltodextrin, whey fermented product (milk-derived), vegetable oil, vitamin C, glucosamine, arginine, thickener (gum arabic), and flavoring.
  • 7 g of “collagen profec” contained 6.6 ⁇ g or more of DHNA derived from the whey fermentation product.
  • Test schedule The subjects took the test meal at 7 g / day for an arbitrary time for 25 days. Regarding the number of days after ingestion, the first ingestion day was defined as “Day 0”.
  • FIG. 11 and Table 2 show the distribution of the number of days after ingestion in which the subjects realized the effect of regulating the intestines.
  • the cumulative proportion of subjects who realized the bowel regulation effect was found that more than half (about 54%) of the subjects felt the bowel regulation effect on the fourth day after ingestion and About 72% of the subjects on day 6 and 80% or more (about 82%) of the intestinal effect realized on day 7 after ingestion.
  • the 24th day after ingestion all the subjects felt the intestinal effect, and the average number of days when the intestinal effect was first felt was about 4.9 days.
  • the rapid-acting intestinal preparation containing the propionic acid bacteria culture provided as an active ingredient based on the present invention can exhibit an intestinal effect (especially an effect of improving bowel movement) in a short period of time by ingesting it. it can.
  • the immediate-acting intestinal preparation of the present invention is composed of ingredients that have been proven to be excellent in safety and taste from a long dietary experience, have a low physical burden, and take it over a long period of time You can also.

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Abstract

La présente invention concerne un régulateur intestinal instantané caractérisé par les éléments suivants : il contient une culture de Propionibacteriaceae, de DHNA ou de leur analogue en tant que principe actif ; il présente des effets de régulation de l'intestin en l'espace d'un jour après sa prise ; et il présente des effets de régulation de l'intestin plus prononcés en deux jours après sa prise. L'invention porte en outre sur un régulateur intestinal instantané, qui contient une culture de Propionibacteriaceae, de DHNA ou de leur analogue en tant que principes actifs et maintient les effets de régulation de l'intestin pendant deux semaines après sa prise.
PCT/JP2014/059404 2013-04-01 2014-03-31 Régulateur intestinal instantané WO2014163031A1 (fr)

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JP2015510071A JPWO2014163031A1 (ja) 2013-04-01 2014-03-31 即効性の整腸剤
SG11201508154QA SG11201508154QA (en) 2013-04-01 2014-03-31 Instantaneous intestinal regulator
CN201480019256.5A CN105073107A (zh) 2013-04-01 2014-03-31 速效性整肠剂
HK16105265.9A HK1217290A1 (zh) 2013-04-01 2016-05-09 速效性整腸劑

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Publication number Priority date Publication date Assignee Title
WO2021015107A1 (fr) * 2019-07-19 2021-01-28 株式会社明治 Composition

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WO2003016544A1 (fr) * 2001-08-10 2003-02-27 Meiji Dairies Corporation Procede d'elaboration d'acide 1,4-dihydroxy-2-naphtoique
WO2008088008A1 (fr) * 2007-01-17 2008-07-24 Meiji Dairies Corporation Agent prophylactique et/ou thérapeutique pour dyspepsie fonctionnelle
WO2011145737A1 (fr) * 2010-05-21 2011-11-24 株式会社明治 Composition pour améliorer l'état de la peau

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JP4974473B2 (ja) * 2005-03-30 2012-07-11 小林製薬株式会社 パチュリー油及び食物繊維を含有する排便促進用経口組成物
JP2009215276A (ja) * 2008-02-12 2009-09-24 Fujifilm Corp サラシア属植物を含有する経口用組成物
JP2011057641A (ja) * 2009-09-11 2011-03-24 Toyo Shinyaku Co Ltd 便通改善剤
TWI476000B (zh) * 2009-12-10 2015-03-11 Meiji Co Ltd Production of Propionic Acid Bacteria in the Preparation of Preventive Agents for Influenza Infectious Diseases and Induction Promoters for Neutralizing Antibodies

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WO2003016544A1 (fr) * 2001-08-10 2003-02-27 Meiji Dairies Corporation Procede d'elaboration d'acide 1,4-dihydroxy-2-naphtoique
WO2008088008A1 (fr) * 2007-01-17 2008-07-24 Meiji Dairies Corporation Agent prophylactique et/ou thérapeutique pour dyspepsie fonctionnelle
WO2011145737A1 (fr) * 2010-05-21 2011-11-24 株式会社明治 Composition pour améliorer l'état de la peau

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021015107A1 (fr) * 2019-07-19 2021-01-28 株式会社明治 Composition
JP2021017414A (ja) * 2019-07-19 2021-02-15 株式会社明治 組成物
JP7402628B2 (ja) 2019-07-19 2023-12-21 株式会社明治 組成物

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