WO1986005094A1 - Agent antiobesite et composition - Google Patents

Agent antiobesite et composition Download PDF

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Publication number
WO1986005094A1
WO1986005094A1 PCT/JP1985/000118 JP8500118W WO8605094A1 WO 1986005094 A1 WO1986005094 A1 WO 1986005094A1 JP 8500118 W JP8500118 W JP 8500118W WO 8605094 A1 WO8605094 A1 WO 8605094A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
lactic acid
phenyl
composition
producing
Prior art date
Application number
PCT/JP1985/000118
Other languages
English (en)
Japanese (ja)
Inventor
Takao Matsuo
Satoshi Horii
Nobuyuki Kitamori
Original Assignee
Takeda Chemical Industries, Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Takeda Chemical Industries, Ltd. filed Critical Takeda Chemical Industries, Ltd.
Priority to PCT/JP1985/000118 priority Critical patent/WO1986005094A1/fr
Priority to DK97986A priority patent/DK97986A/da
Priority to EP86301506A priority patent/EP0194794A3/fr
Priority to AU54271/86A priority patent/AU596961B2/en
Priority to NO860826A priority patent/NO165662C/no
Priority to JP61051053A priority patent/JPH072647B2/ja
Priority to FI860967A priority patent/FI860967A/fi
Priority to CA000503581A priority patent/CA1255591A/fr
Publication of WO1986005094A1 publication Critical patent/WO1986005094A1/fr

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Classifications

    • 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
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • 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
    • A61K31/13—Amines
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof

Definitions

  • Anti-obesity agent and anti-obesity composition are provided.
  • the present invention relates to an anti-obesity agent comprising a combination of an ⁇ -glucosidase inhibitor which is an anti-obesity agent and a non-pathogenic live lactic acid-producing bacterium, and an anti-obesity composition comprising both of them.
  • the present inventors have conducted intensive studies on a method for suppressing side effects such as diarrhea and flatulence resulting from the administration of the above-mentioned anti-obesity drug. It was found that the objective of the period was achieved. A In other words, the above-mentioned side effects such as diarrhea and flatulence do not occur because a large amount of oligosaccharides and disaccharides stay in the intestinal tract.I-Lactic acid-producing bacteria that utilize and remove these sugars to convert to lactic acid When lactic acid is administered, the lactic acid produced thereby is rapidly absorbed into the living body, so that the occurrence of osmotic diarrhea can be prevented.
  • a homo-lactic lactic acid fermentation bacterium produces only lactic acid without generating carbon dioxide gas, thereby preventing both diarrhea and flatulence at the same time.
  • the produced lactic acid is absorbed into the living body through the intestinal tract wall, but unlike the case where glucose is absorbed, it does not stimulate insulin secretion, so that adipocyte hypertrophy does not occur. The original anti-fertility effect is maintained as it is.
  • Examples of -dalcosidase inhibitory substances used in the present invention include, for example, JP-A-57-200335, JP-A-58-59946, JP-A-58-162597, JP-A-58-216U5, JP-A-59-73549 and JP-A-59-95297.
  • A is a hydroxyl group, phenol, phenyl, phenyl, pyridyl, cyclohexyl, an optionally substituted phenyl-containing chain hydrocarbon group having 1 to ⁇ carbon atoms, a hydroxyl group, It represents a cyclic hydrocarbon group having 5 or 6 carbon atoms or a ⁇ residue which may have a droxymethyl group, a methyl group or an amino group.
  • N-substituted variolamine derivative represented by the general formula [I] include:
  • Such as NH NH Such as NH NH.
  • A is a hydroxyl group, a phenyl group, a phenyl group, a phenyl group, a cycloalkyl group, an optionally substituted phenyl group having 1 to 10 carbon atoms, a hydroxyl group, a hydroxymethyl group. Having a methyl group and an amino group
  • A is a hydroxyl group, phenoxy, phenyl, furyl, pyridyl, cyclohexyl, an optionally substituted phenyl hydrocarbon group having 1 to 10 carbon atoms, a hydroxyl group, a hydroxymethyl group, It represents a C5 or C6 cyclic hydrocarbon group or sugar residue that may have a methyl or amino group.
  • the ⁇ -substituted derivative of validinin represented by the formula [1] is also suitably used as the ⁇ -dalcosidase inhibitory substance of the present invention.
  • the non-pathogenic lactic acid-producing bacteria that can be used in the present invention include not only lactic acid bacteria in a narrow sense, but also lactic acid bacteria in a broad sense, for example, bacteria of the genus Sporolabacillus sp. Contains live bacteria of the genus if idobacterium. Those that do not generate gas that causes flatulence during growth and reproduction can be used more advantageously.
  • Lactic acid-producing bacteria that can be used in the present invention include Lactobacillus acidophilus (Lactobacillus acidophilus), L. salivarius (L.
  • Bacterial microorganisms of the genus Bacillus are derived from two molecules of glucose by fermentation. Produces two molecules of lactic acid and three molecules of acetic acid to produce B. idobacterium um bif iduin, B. infantis, B. adolescent is, B. Longum (B.
  • microorganisms resident in the intestine such as Streptococcus faecalis, Lactobacillus acidophilus, and Bifidobacterium bifidobacter, as lactic acid-producing bacteria, disrupts the intestinal bacterial flora. There is no advantage.
  • the dose of the single glucosidase inhibitor is 0.05-500 mg / adult Z, preferably ⁇ . ⁇ ⁇ ! ⁇ Adults / time, usually 2 or 4 times daily, preferably between 1 hour before meals and 2 hours after meals.
  • the dalcosidase inhibitor is a variolamine derivative represented by the general formula [I]
  • the number of viable non-pathogenic lactic acid-producing bacteria used in combination with the above inhibitor is 10 3 to 10 12 cells / adult / time, preferably 10 5 to ⁇ 01 1 in terms of the number of viable cells. It is effective to take a preparation containing Z doses per adult, usually 2 to 4 times a day, preferably 1 hour before meals to 2 hours after meals.
  • -As a method of administering a combination of a glucosidase inhibitor and a non-pathogenic lactic acid-producing bacterium, a preparation containing the inhibitory substance and a preparation containing the lactic acid-producing bacterium are separately prepared, and both preparations are simultaneously prepared. Or at a different time There is a method of administering the active ingredient and a method of administering a composition containing both the inhibitory substance and the lactic acid-producing bacterium. It is often more convenient to administer a composition containing both components.
  • the dosage form of a glucosidase-inhibiting substance, a preparation containing lactic acid-producing bacteria alone, and a composite preparation containing both at the same time take into account the physicochemical properties, biological properties, etc. of each component.
  • Dosage forms convenient for administration may be tablets, pellets, granules, granules, powders and capsules.
  • excipients, coloring agents, fragrances, stabilizers, brighteners, etc. which are commonly used in the preparation. May be used.
  • An anti-obesity composition containing a glucosidase-inhibiting substance and a non-pathogenic lactic acid-producing bacterium can be prepared by mixing both components according to a conventional method of preparation.
  • the compounding ratio of the a-dalcosidase inhibitory agent and the non-pathogenic lactic acid-producing bacterium is preferably 10 3 to 10 12 in the former case and 5 to 500 mg in the former case, and 1.0 to 10 in the latter case. 50mg
  • lactic acid-producing bacteria are generally anaerobic and are susceptible to air or oxygen when dry, and are susceptible to high temperatures and humidity. It is preferable to process at low temperature.
  • the powder When the composition of the present invention is formed into a solid preparation, the powder may be simply mixed together by a drying method, or the powder may be compressed into granules or tablets. When granules and tablets are produced by a wet method, they can be kneaded using an aqueous solution of a binder and dried to obtain a target solid preparation. Further, the powder or granules thus obtained can be filled into capsules to give capsules. In order to mix a small amount of the active ingredient with a large amount of other powders to obtain a uniform mixture, it is better to employ a so-called stepwise mixing method. For example, the active ingredient
  • a uniform powder is obtained by mixing with 100 to 200 times the volume of powder, and a uniform powder is obtained by mixing this with the remaining powder.
  • Drying from hydrated materials can be performed by L-drying, freeze-drying, spray drying, or other means.
  • the cells can be suspended in a neutral buffer solution containing an appropriate stabilizer, for example, monosodium glutamate salt, adnitol, etc., and dried by a method known per se. Is preferred.
  • an appropriate stabilizer for example, monosodium glutamate salt, adnitol, etc.
  • composition of the present invention is effective in preventing obesity by using a small amount thereof, and the administration method is simple and has almost no side effects.
  • diarrhea is caused by indigestion, abnormal intestinal fermentation, or disturbance of the intestinal flora.
  • antibiotics herbal medicines, lactic acid bacteria, and medicinal charcoal are used. ⁇
  • lactic acid bacteria have been claimed to be effective for normalizing intestinal bacteria that have been disrupted by diarrhea or for treating indigestion, but the mechanism of action is well understood. Not.
  • medicated charcoal is used in anticipation of adsorption of gas produced by abnormal fermentation in the digestive tract, adsorption of harmful substances in self-poisoning, and detoxification.
  • diarrhea and flatulence are prevented by blending a lactic acid-producing bacterium which selectively assimilates saccharides retained in the intestinal tract by inhibiting the digestion of carbohydrates by the antifertilizer.
  • a lactic acid-producing bacterium which selectively assimilates saccharides retained in the intestinal tract by inhibiting the digestion of carbohydrates by the antifertilizer.
  • Can be prevented, and this milk Acid-producing bacteria are resident in the intestine and are harmless, and the lactic acid produced by their reproduction is completely harmless to humans, so it is extremely safe.
  • — 14252 is a powdered lg of 10 12 cells (iOg as cell powder) and N- (1,3-dihydroxy-2-propyl) paliolamine (hereinafter referred to as AO-128).
  • AO-128 N- (1,3-dihydroxy-2-propyl) paliolamine
  • AO-128 tablet a compressed tablet containing AO-128 5mg per iOOmg (hereinafter referred to as AO-128 tablet). . )made.
  • a bacterial tablet (Hereinafter referred to as a bacterial tablet).
  • One AO-128 tablet was orally administered to each of three beagle dogs 30 minutes before feeding, and one microbial tablet was orally administered immediately before feeding, and diarrhea was observed in all dogs observed for 24 hours. Did not.
  • the tablets prepared in this way were orally administered to each of six beagle dogs immediately before the lined diet, and observed up to 48 hours after the administration. No diarrhea was observed in any dog.
  • the same tablets were administered to 3 healthy boys, 1 tablet each, just before lunch, and observed for 10 hours. As a result, some flatulence was observed and no diarrhea was observed.
  • lactic acid-producing bacteria-free tablets (1 tablet lO) obtained by the same procedure as above using 20 g of lactose, 74 g of corn starch, 5 g of AO-128 powder and 1 g of magnesium stearate were used. Containing 5 mg of A0-128 in Omg).
  • one tablet was administered to the same person under the same conditions, flatulence and diarrhea were observed for 5 to 8 hours after administration.
  • A0-128 granules containing 5 mg of AO-128 and 3 mg of hydroxypropyl cellulose in 100 mg (hereinafter referred to as A0-128 granules) were prepared by a wet kneading method.
  • G.5g was thoroughly mixed and formed into a flat tablet having a weight of liOmg and a diameter of 6.5 mm using a tableting machine. One tablet each was orally administered to each of three beagles immediately before feeding and observed for 48 hours. No diarrhea was observed.
  • AO-128 granules]; 00 g and magnesium stearate (1 g) were mixed to form a flat tablet having a weight of 101 mg and a diameter of 6.5 dragons in the same manner as described above.
  • AO-128 granules]; 00 g and magnesium stearate (1 g) were mixed to form a flat tablet having a weight of 101 mg and a diameter of 6.5 dragons in the same manner as described above.
  • Example 1 1 g of the mixture obtained in Example 1 or a mixture containing other cells obtained in the same manner as in Example 1 was mixed with 99 g of a commercially available powdered feed (CE-2) to prepare a test mixture. Feed was prepared. This diet was fed to male J cl: SD rats (6 animals per group) at the age of 7 weeks, and the state of feces after 36 to 48 hours was observed. The control group was fed a diet mixed with 10 mg of AO-128 and 100 g of powdered diet. Table 1 shows the results. Table 1
  • Soil Feces are observed, but water diffusion is observed on the absorbent paper. -: Feces are observed, and no water diffusion is observed on the absorbent paper.
  • a test feed was prepared using two or more types of bacteria according to the method of Reference Example 1. However, the amount of potato starch was reduced by an amount corresponding to the increase in the amount of cells, to prepare a composition containing AO-128 and the cells, and this was mixed with the feed.
  • the diet was fed to a 7-week-old Jci: SD rat (5 mice per group), and the state of feces was observed 36 to 48 hours later.
  • the control group received a diet in which 10 mg of AO-128 was mixed with 100 g of powdered diet. Table 2 shows the results. Table 2
  • composition of the present invention reduces diarrhea
  • changes in hyperglycemia and hyperinsulinemia inhibitory action and antifertilization action after ingestion of diet may occur. Was considered.
  • the anti-obesity agent and the anti-obesity composition according to the present invention prevent or treat the fertilization of humans and animals by oral administration without substantially reducing side effects such as diarrhea without reducing food consumption. It is useful as an agent for preventing and treating obesity in humans and animals.

Abstract

Agent antiobésité comprenant une combinaison d'un inhibiteur d'alpha-glucosidase et de bactéries non pathogènes produisant de l'acide lactique, et composition antiobésité les contenant. Il est possible de prévenir ou de traiter l'obésité sans suivre de régimes, par administration orale de l'agent ou de la composition. L'absorption de ces composés n'est virtuellement pas accompagnée des symptomes de diarrhée, météorisme, etc., induits par l'administration de l'inhibiteur d'alpha-glucosidase.
PCT/JP1985/000118 1985-03-08 1985-03-08 Agent antiobesite et composition WO1986005094A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
PCT/JP1985/000118 WO1986005094A1 (fr) 1985-03-08 1985-03-08 Agent antiobesite et composition
DK97986A DK97986A (da) 1985-03-08 1986-03-04 Middel til inhibering af fordoejelse af sakkarid
EP86301506A EP0194794A3 (fr) 1985-03-08 1986-03-04 Composition inhibant la digestion de saccharides
AU54271/86A AU596961B2 (en) 1985-03-08 1986-03-04 Saccharide digestion inhibiting composition
NO860826A NO165662C (no) 1985-03-08 1986-03-05 Fremgangsmaate for fremstilling av en sakkaridnedbrytningsinhiberende sammensetning.
JP61051053A JPH072647B2 (ja) 1985-03-08 1986-03-07 糖消化抑制剤および糖消化抑制組成物
FI860967A FI860967A (fi) 1985-03-08 1986-03-07 Fetma motverkande medel.
CA000503581A CA1255591A (fr) 1985-03-08 1986-03-07 Compose inhibant la digestion des saccharides

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP1985/000118 WO1986005094A1 (fr) 1985-03-08 1985-03-08 Agent antiobesite et composition

Publications (1)

Publication Number Publication Date
WO1986005094A1 true WO1986005094A1 (fr) 1986-09-12

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1985/000118 WO1986005094A1 (fr) 1985-03-08 1985-03-08 Agent antiobesite et composition

Country Status (1)

Country Link
WO (1) WO1986005094A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5571796A (en) * 1995-06-06 1996-11-05 Alberta Research Council Administration of valienamine-related disaccharide compounds in reducing inflammation in a sensitized mammal arising from exposure to an antigen
JP2006280263A (ja) * 2005-03-31 2006-10-19 Snow Brand Milk Prod Co Ltd ビフィズス菌菌体粉末
JP2015507629A (ja) * 2011-12-29 2015-03-12 ヒルズ・ペット・ニュートリシャン・インコーポレーテッド 消化管フローラを改良する組成物および方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS51106725A (fr) * 1975-03-13 1976-09-21 Takeda Chemical Industries Ltd
JPS51118827A (en) * 1975-04-09 1976-10-19 Nisshin Flour Milling Co Ltd A preventive method and treatment of dog's diarrhea
JPS5435214A (en) * 1977-08-25 1979-03-15 Nisshin Flour Milling Co Ltd Remedy and prophylaxis of scours of calf
EP0049981A1 (fr) * 1980-10-06 1982-04-21 Takeda Chemical Industries, Ltd. Dérivés de valiénamine, leur production et leur utilisation
EP0056194A1 (fr) * 1981-01-05 1982-07-21 Takeda Chemical Industries, Ltd. Pseudo-aminosucres N-substitués, leur préparation et leur utilisation
EP0063456A1 (fr) * 1981-04-13 1982-10-27 Takeda Chemical Industries, Ltd. Pseudoaminosucres, leur préparation et utilisation
EP0069950A1 (fr) * 1981-07-13 1983-01-19 Metallgesellschaft Ag Procédé de phosphatation de surfaces métalliques
EP0089812A1 (fr) * 1982-03-19 1983-09-28 Takeda Chemical Industries, Ltd. Pseudo-aminosucres-N-substitués, leur fabrication et emploi

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS51106725A (fr) * 1975-03-13 1976-09-21 Takeda Chemical Industries Ltd
JPS51118827A (en) * 1975-04-09 1976-10-19 Nisshin Flour Milling Co Ltd A preventive method and treatment of dog's diarrhea
JPS5435214A (en) * 1977-08-25 1979-03-15 Nisshin Flour Milling Co Ltd Remedy and prophylaxis of scours of calf
EP0049981A1 (fr) * 1980-10-06 1982-04-21 Takeda Chemical Industries, Ltd. Dérivés de valiénamine, leur production et leur utilisation
EP0056194A1 (fr) * 1981-01-05 1982-07-21 Takeda Chemical Industries, Ltd. Pseudo-aminosucres N-substitués, leur préparation et leur utilisation
EP0063456A1 (fr) * 1981-04-13 1982-10-27 Takeda Chemical Industries, Ltd. Pseudoaminosucres, leur préparation et utilisation
EP0069950A1 (fr) * 1981-07-13 1983-01-19 Metallgesellschaft Ag Procédé de phosphatation de surfaces métalliques
EP0089812A1 (fr) * 1982-03-19 1983-09-28 Takeda Chemical Industries, Ltd. Pseudo-aminosucres-N-substitués, leur fabrication et emploi

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5571796A (en) * 1995-06-06 1996-11-05 Alberta Research Council Administration of valienamine-related disaccharide compounds in reducing inflammation in a sensitized mammal arising from exposure to an antigen
US5814616A (en) * 1995-06-06 1998-09-29 Alberta Research Council Administration of valienamine-related disaccharide compounds in reducing inflammation in a sensitized mammal arising from exposure to an antigen
JP2006280263A (ja) * 2005-03-31 2006-10-19 Snow Brand Milk Prod Co Ltd ビフィズス菌菌体粉末
JP2015507629A (ja) * 2011-12-29 2015-03-12 ヒルズ・ペット・ニュートリシャン・インコーポレーテッド 消化管フローラを改良する組成物および方法

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