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WO2012008474A1 - Inhibiteur d'absorption de fructose - Google Patents

Inhibiteur d'absorption de fructose Download PDF

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Publication number
WO2012008474A1
WO2012008474A1 PCT/JP2011/065927 JP2011065927W WO2012008474A1 WO 2012008474 A1 WO2012008474 A1 WO 2012008474A1 JP 2011065927 W JP2011065927 W JP 2011065927W WO 2012008474 A1 WO2012008474 A1 WO 2012008474A1
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WO
WIPO (PCT)
Prior art keywords
monoterpene
fructose
gellanate
geraniol
group
Prior art date
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Ceased
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PCT/JP2011/065927
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English (en)
Japanese (ja)
Inventor
大輔 宮城
秀幸 青山
純也 菊石
富田　実
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Tomita Pharmaceutical Co Ltd
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Tomita Pharmaceutical Co Ltd
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Priority to JP2012524570A priority Critical patent/JP5843169B2/ja
Publication of WO2012008474A1 publication Critical patent/WO2012008474A1/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
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • 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
    • 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
    • A61K31/11—Aldehydes
    • 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
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

  • the present invention relates to a fructose absorption inhibitor containing monoterpene as an active ingredient and a preventive or therapeutic agent for diseases or symptoms caused by excessive intake of fructose.
  • Glucose a kind of monosaccharide, is metabolized by an enzyme group called glycolytic system after digestion and absorption. Glucose is metabolically regulated at the stage of phosphofructokinase among these enzymes, so that conversion to fat is controlled.
  • glucose is the most important monosaccharide in mammalian biochemistry and is the main energy source for various tissues.
  • the brain normally uses glucose as the only energy source. Therefore, it is a safety problem to strongly inhibit the absorption of glucose.
  • fructose monosaccharide fructose
  • fructose is metabolized in a system that does not undergo metabolic regulation through a metabolic pathway different from that of glucose. Therefore, it is easily converted into fat in the liver and easily promotes obesity.
  • fructose causes various diseases such as hyperlipidemia, arteriosclerosis, myocardial infarction, obstructive arteriosclerosis, aortic aneurysm, stroke, fatty liver and obesity due to its large intake.
  • NASH nonalcoholic steatohepatitis
  • the best way to prevent obesity in the case of excessive intake of carbohydrates is to specifically inhibit the absorption of fructose in the intestinal tract.
  • Patent Documents 1 and 2 eucalyptus extracts and plant-derived extracts such as banaba, olive, and guava have been reported as substances that specifically inhibit the in vivo absorption of fructose.
  • Patent Documents 1 and 2 since these extracts are a mixture of various components having different structures and properties, they are difficult to handle, and depending on the type of plant as a raw material, the production area, and the growth state, There are problems such as large fluctuations in activity, reduced ability due to interaction, and the possibility of containing toxic substances.
  • An object of the present invention is to provide a fructose absorption inhibitor comprising a single component monoterpene as an active ingredient and a preventive or therapeutic agent for diseases or symptoms caused by excessive intake of fructose.
  • the present inventors have found that monoterpenes are excellent in inhibiting fructose absorption from the intestinal tract and suppressing blood triglyceride elevation, and have completed the present invention. It was. That is, the present invention includes the following: [1] A triglyceride elevation inhibitor containing monoterpene. [2] The triglyceride elevation inhibitor according to the above [1], wherein the monoterpene contains a chain monoterpene. [3] The triglyceride elevation inhibitor according to the above [1], wherein the monoterpene includes a cyclic monoterpene.
  • Monoterpenes are ( ⁇ )- ⁇ -pinene, ( ⁇ )- ⁇ -pinene, 1.8-cineole, (R)-(+)-limonene, (R) -limonene oxide, terpineol, ⁇ -
  • the monoterpene according to any one of [10] to [12] above, wherein the monoterpene includes a monoterpene having at least one group selected from a hydroxyl group, a carbonyl group, a carboxyl group, an ester bond and an ether bond.
  • a prophylactic or therapeutic agent for lipemia [14] The high of [10] or [11], wherein the monoterpene contains at least one selected from geraniol, linalool, citral, citronellal, nerol, lavandol, ocimene, citronellol, gellanic acid and gellanate.
  • a prophylactic or therapeutic agent for lipemia is provided.
  • Monoterpenes are ( ⁇ )- ⁇ -pinene, ( ⁇ )- ⁇ -pinene, 1.8-cineole, (R)-(+)-limonene, (R) -limonene oxide, terpineol, ⁇ -
  • the prophylactic or therapeutic agent for hyperlipidemia according to any one of [10] and [12] above, comprising at least one selected from terpinene, (S)-(+)-carvone and (R) -pulegone .
  • the monoterpene contains at least one selected from geraniol, linalool, citral, citronellal, nerol, lavandol, ocimene, citronellol, gellanic acid and gellanate Absorption inhibitor.
  • Monoterpenes are ( ⁇ )- ⁇ -pinene, ( ⁇ )- ⁇ -pinene, 1.8-cineole, (R)-(+)-limonene, (R) -limonene oxide, terpineol, ⁇ -
  • the fructose absorption inhibitor according to any one of [19] and [21] above, comprising at least one selected from terpinene, (S)-(+)-carvone and (R) -pulegone.
  • the fructose absorption inhibitor of the present invention exhibits a high fructose absorption inhibitory action from the intestinal tract and a triglyceride rise inhibitory action, various diseases or symptoms caused by excessive intake of fructose such as hyperlipidemia, arteriosclerosis, It can be used as a preventive or therapeutic agent for myocardial infarction, obstructive arteriosclerosis, aortic aneurysm, stroke, fatty liver and obesity.
  • the fructose absorption inhibitor of the present invention does not contain various components having different structures and properties as in conventional extracts, and the monoterpene, which is a single component, is used as an active ingredient, so it is easy to handle. There is no activity variation due to the difference in raw materials as seen in the extract.
  • the fructose absorption inhibitor containing monoterpene as an active ingredient and the preventive or therapeutic agent for diseases or symptoms caused by excessive intake of fructose (hereinafter collectively referred to as “fructose absorption inhibitor of the present invention”) are simple. Although monoterpene which is one component is an active ingredient, monoterpenes can generally be classified into chain monoterpenes and cyclic monoterpenes.
  • the “chain monoterpene” in the present invention is a hydrocarbon having a basic skeleton with 10 carbon atoms (2 isoprene structural units) having isoprene as a structural unit, or an oxygen-containing functional group (hydroxyl group, carbonyl group). , A derivative having a carboxyl group, an ester bond, and an ether bond) and having no cyclic structure.
  • chain monoterpenes include geraniol, linalool, citral, citronellal, nerol, lavandol, ocimene, citronellol, gellanic acid, gellanate, and gellanate.
  • gellanate examples include alkali metal salts of gellan acid, such as potassium gellanate, sodium gellanate, calcium gellanate, magnesium gellanate, ammonium gellanate, and the like. Examples include methyl and ethyl gellanate.
  • chain monoterpenes those having at least one group selected from a hydroxyl group, a carbonyl group, a carboxyl group, an ester bond and an ether bond are preferable.
  • examples thereof include geraniol, linalool, citral, citronellal, nerol, lavandol, citronellol, gellanic acid, and gellanate.
  • geraniol, gellanic acid, potassium gellanate, citronellol, citral and nerol are preferable, and geraniol, gellanic acid and potassium gellanate are particularly preferable.
  • the chain monoterpene is a natural substance contained in essential oils derived from herb plants such as rose, palmarosa, lemongrass, and daidai. From these materials, conventional means (extraction, isolation, purification, etc.) are used. Obtainable. It can also be synthesized artificially from various starting materials using conventional organic synthesis methods. Since the chain monoterpene is commercially available, it can be obtained from each supplier.
  • the “cyclic monoterpene” in the present invention is a hydrocarbon having a basic skeleton having 10 carbon atoms (2 isoprene structural units) having isoprene as a structural unit, or an oxygen-containing functional group (hydroxyl group, carbonyl group, A compound having a cyclic structure with a derivative having a carboxyl group, an ester bond, or an ether bond.
  • Examples of such cyclic monoterpenes include ( ⁇ )- ⁇ -pinene, ( ⁇ )- ⁇ -pinene, 1.8-cineole, (R)-(+)-limonene, (R) -limonene oxide, Examples include terpineol, ⁇ -terpinene, (S)-(+)-carvone, and (R) -pregon.
  • cyclic monoterpenes those having at least one group selected from a hydroxyl group, a carbonyl group, a carboxyl group, an ester bond and an ether bond are preferable.
  • terpineol, (S)-(+)-carvone and (R) -pulegone are preferred.
  • cyclic monoterpene is a natural substance contained in the skins derived from citrus plants such as lemons and plants such as laurels and rosemary. From these materials, conventional means (extraction, isolation, purification, etc.) are used. Obtainable. It can also be synthesized artificially from various starting materials using conventional organic synthesis methods. Since cyclic monoterpenes are commercially available, they can be obtained from various suppliers.
  • the monoterpene in the present invention may be each enantiomer (R isomer or S isomer), may be a mixture containing R isomer and S isomer in an arbitrary ratio, and equimolar amounts of R isomer and S isomer. It may be a racemate. Moreover, in this invention, monoterpene may be used independently and may be used in combination of 2 or more type.
  • the fructose absorption inhibitor of the present invention can be appropriately set depending on the form, administration method, purpose of use, and age, weight, and symptoms of the patient to whom the pharmaceutical is administered.
  • the dosage of monoterpene contained in the preparation is preferably 0.1 to 2000 mg / kg body weight, preferably 1 to 1000 mg / kg body weight per day for an adult.
  • the dose may vary depending on various conditions, and an amount smaller than the above dose may be sufficient, or an amount larger than the above dose may be required.
  • the fructose absorption inhibitor of the present invention may be performed once in a day or divided into several times within a desired dosage range.
  • the fructose absorption inhibitor of the present invention can be administered before, during and after fructose intake.
  • the fructose absorption inhibitor for example, It is desirable to administer 10 to 120 minutes before or at the time of ingestion.
  • the intake of fructose here is not limited to the intake of fructose itself or a composition containing fructose (for example, an edible composition, that is, food, beverage, supplement or feed), but is decomposed in vivo.
  • fructose absorption inhibitor of the present invention can be administered as it is (especially orally administered) as it is, or added to any food or drink and taken daily.
  • the form of the fructose absorption inhibitor of the present invention is not particularly limited as long as it contains monoterpene as an active ingredient.
  • it may contain only a monoterpene or a composition containing a monoterpene and other components.
  • a composition include a pharmaceutical composition containing a monoterpene and a pharmaceutically acceptable carrier, and an edible composition (that is, food, beverage or feed).
  • the said pharmaceutical composition can be manufactured by the well-known method in the formulation field
  • the pharmaceutically acceptable carrier used in the pharmaceutical composition can be selected according to the administration form and dosage form of the pharmaceutical composition.
  • the pharmaceutically acceptable carrier various organic or inorganic carrier materials that can be used as a pharmaceutical material are used.
  • the carrier material is an excipient, lubricant, binder, or disintegrant in a solid formulation. Or it can mix
  • the excipient is not particularly limited, and examples thereof include lactose, sucrose, D-mannitol, xylitol, sorbitol, erythritol, starch, and crystalline cellulose.
  • the lubricant is not particularly limited, and examples thereof include magnesium stearate, calcium stearate, talc, colloidal silica, and the like.
  • the binder include, but are not limited to, pregelatinized starch, methylcellulose, crystalline cellulose, sucrose, D-mannitol, trehalose, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, and polyvinylpyrrolidone.
  • starch, carboxymethylcellulose, low substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, carboxymethyl starch sodium, etc. are mentioned.
  • solubilizing agent is not particularly limited, and examples thereof include polyethylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like. Can be mentioned.
  • the suspending agent is not particularly limited, for example, a surfactant such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, or Examples thereof include hydrophilic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose.
  • a surfactant such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, or Examples thereof include hydrophilic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, methyl cellulose,
  • tonicity agent For example, sodium chloride, glycerol, D-mannitol, etc. are mentioned.
  • buffer solutions such as a phosphate, acetate, carbonate, a citrate, etc. are mentioned.
  • preservative For example, paraoxybenzoic acid ester, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid etc. are mentioned.
  • antioxidant For example, sulfite, ascorbic acid, etc. are mentioned.
  • the monoterpene content in the pharmaceutical composition can be set in consideration of the administration form, administration method, etc.
  • the monoterpene dosage is 0.1 to 2000 mg / kg body weight per day for an adult, preferably Can be set to 1 to 1000 mg / kg body weight. Specifically, for example, it is 0.01 to 90% by weight, preferably 0.1 to 70% by weight, and most preferably 1 to 50% by weight of the whole composition. In some cases, other pharmaceutically acceptable carriers may constitute the remainder of the composition.
  • Examples of the form of the pharmaceutical composition include tablets, capsules (including soft capsules and microcapsules, preferably sustained release), powders, granules, syrups and the like, or injections. It can be an agent for parenteral administration such as suppositories, suppositories, pellets, and drops.
  • the pharmaceutical composition can be administered orally or parenterally.
  • parenteral refers to intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous, and intraarticular injections and infusions, transdermal, nasal, transpulmonary, enteral, vaginal, etc. Refers to the mode of administration including.
  • the pharmaceutical composition is in the form of an oral administration agent
  • starch lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, inorganic salt, etc.
  • a pharmaceutical carrier for example, starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, inorganic salt, etc.
  • a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a corrigent, a colorant, a fragrance and the like may be further blended.
  • the pharmaceutical composition is in the form of a parenteral agent, distilled water as a diluent, physiological saline, aqueous glucose solution, vegetable oil, sesame oil, peanut oil, soybean oil, It can be prepared by dissolving or suspending the active ingredient of the present invention in corn oil, propylene glycol, polyethylene glycol or the like, and adding a bactericidal agent, stabilizer, isotonic agent or the like, if desired.
  • the edible composition (food, beverage, supplement or feed) containing the monoterpene of the present invention is not particularly limited.
  • confectionery for example, chewing gum, candy, jelly, biscuit, chocolate, gummy, rice confectionery
  • Dairy products eg, yogurt
  • health foods eg, capsules, tablets, powders
  • beverages eg, soft drinks, milk beverages, vegetable / fruit juice drinks, tea
  • livestock feeds eg, pet foods, Cat food, dog food.
  • the edible composition is not particularly limited as long as it contains a monoterpene, and includes, for example, orally ingestible shapes such as tablets, granules, and capsules.
  • the method for producing the edible composition is not particularly limited, and examples thereof include cooking, processing, and production by a generally used method for producing food or beverage.
  • a monoterpene is added to the produced food or beverage. It should just be contained.
  • the edible composition may contain fructose and a substance that decomposes in vivo to produce fructose (for example, sucrose).
  • the monoterpene content in the edible composition is not particularly limited as long as it contains an effective amount for expressing its physiological action.
  • the monoterpene dose is 0. It can be set to 1 to 2000 mg / kg body weight, preferably 1 to 1000 mg / kg body weight.
  • Fructose is metabolized in a system that does not undergo metabolic regulation through a metabolic pathway different from that of glucose, so it is easily converted into fat in the liver by overdose of fructose, increasing triglycerides in the blood, It becomes a factor that causes diseases such as obesity, hyperlipidemia, and fatty liver. Therefore, since the fructose absorption inhibitor of the present invention exhibits a high fructose absorption inhibitory action from the intestinal tract and a triglyceride rise inhibitory action, various diseases caused by excessive intake of fructose such as obesity, hyperlipidemia, It can be used as a preventive or therapeutic agent for liver and the like.
  • treatment means significantly improving the symptoms of a target disease, such as treatment, alleviation, reduction, or suppression.
  • Example 1 Chain monoterpene Wine yeast (Saccharomyces cerevisiae NBRC2260) was used as a test substance. A fermentation inhibition test using potassium acid was conducted. First, wine yeast was cultured and collected, and a cell suspension was prepared so that the number of cells was about 1 ⁇ 10 8 per mL. 1.0 mL of this bacterial cell suspension was measured into a test tube, and 0.1 mL of 0.1 M potassium phosphate buffer solution, 0.5 mL of 1% magnesium aqueous solution, 1.0 mL of the test substance solution shown in Table 1, 1.0 mL of a mixed solution of glucose and fructose (both containing 10% by weight) was added, and water was added to 5 mL to obtain a fermentation solution.
  • a mixed solution of glucose and fructose both containing 10% by weight
  • the fermentation solution was fermented in a 30 ° C. water bath for 4 hours. Thereafter, the fermentation solution was centrifuged to separate cells, and the amount of fructose was quantified using this supernatant to measure the residual rate of fructose in the fermentation solution. Further, a test was carried out using farnesol, which is a chain sesquiterpene, and geranylgeraniol, which is a chain diterpene. The measurement results are shown in Table 1.
  • the chain monoterpene has a fructose absorption inhibition effect due to a high residual rate of fructose.
  • a low molecular chain monoterpene having at least one group selected from a hydroxyl group, a carbonyl group, a carboxyl group, an ester bond and an ether bond such as geraniol, citral, nerol, citronellol, gellan acid and potassium gellanate is low. It was suggested that the concentration also has a high inhibitory effect.
  • farnesol which is a chain sesquiterpene
  • geranylgeraniol which is a chain diterpene, have significantly lower fructose absorption inhibitory effects than chain monoterpenes.
  • Example 2 Cyclic monoterpene
  • Wine yeast Sacharomyces cerevisiae NBRC2260
  • cyclic monoterpenes (-)- ⁇ -pinene, (-)- ⁇ -pinene, 1.8-cineole as test substances
  • a fermentation inhibition test using (R)-(+)-limonene, (R) -limonene oxide, terpineol, ⁇ -terpinene, (S)-(+)-carvone, (R) -pulegone was performed.
  • wine yeast was cultured and collected, and a cell suspension was prepared so that the number of cells was about 1 ⁇ 10 8 per mL.
  • the cyclic monoterpene has an effect of inhibiting fructose absorption because the residual rate of fructose is high.
  • a cyclic monoterpene having at least one group selected from a hydroxyl group, a carbonyl group, a carboxyl group, an ester bond and an ether bond such as terpineol, (S)-(+)-carvone and (R) -pulegone It was suggested that even at low concentrations, it has a high inhibitory effect.
  • Example 3 Absorption inhibitory effect of fructose by geraniol The fructose absorption inhibitory effect by geraniol was confirmed using SD-type SPF rats (male: 3 mice in each group). Geraniol 0.5 g / kg was orally administered to rats fasted for 18 hours, and after 10 minutes, fructose 1.0 g / kg was orally administered (geraniol group). Ten minutes later, blood was collected from the portal vein, and the fructose concentration in the portal vein blood was measured. In addition, the group which performed the same operation without administering geraniol was set as the control group. The measurement results are shown in FIG.
  • Table 3 shows the average value of fructose concentration in portal blood 10 minutes after administration of fructose
  • FIG. 1 shows the transition.
  • the increase in plasma fructose concentration was suppressed as compared with the Control group, suggesting that geraniol inhibited fructose absorption.
  • Table 4 shows the average value of fructose concentration in portal blood 10 minutes after administration of fructose, and FIG. 2 shows the transition.
  • the increase in plasma fructose concentration was suppressed in the potassium gellanate group as compared to the Control group, suggesting that potassium gellanate inhibited fructose absorption.
  • Example 4 Absorption inhibitory effect of fructose by repeated administration of geraniol The absorption inhibitory effect of fructose by repeated administration of geraniol was confirmed using SD type SPF rats (male: 3 mice in each group). The test group (geraniol group) was given 0.5% geraniol mixed feed and 30% fructose mixed feed freely. The group fed with the normal feed is the Control group, and the group fed with the 30% fructose mixed feed containing no geraniol. It was set as the Control group. Blood was collected from the subclavian vein immediately before the start of test substance administration and 14 days after administration, and the triglyceride concentration in plasma was measured. The measurement results are shown in Table 5 and FIG.
  • Table 5 shows the triglyceride concentration in plasma, and FIG. 3 shows the transition.
  • the Geraniol group is The increase in triglyceride concentration is suppressed as compared with the Control group. This suggests that geraniol inhibits the absorption of fructose in the intestinal tract and thereby suppresses triglyceride synthesis in the liver.
  • Table 6 shows the plasma triglyceride concentration
  • FIG. 4 shows the transition.
  • the gellan acid and potassium gellanate groups are P.I.
  • the increase in triglyceride concentration is suppressed as compared with the Control group. This suggests that, like geraniol, gellanic acid and potassium gellanate inhibit the absorption of fructose in the intestinal tract and thereby suppress triglyceride synthesis in the liver.

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Abstract

L'invention concerne un inhibiteur d'absorption de fructose qui a un monoterpène en tant que principe actif, et un agent préventif ou thérapeutique pour des symptômes ou des maladies provoquées par une surconsommation de fructose ; plus particulièrement, l'invention concerne un agent préventif ou thérapeutique pour l'hyperlipidémie, un agent de suppression d'augmentation du taux de triglycérides et un inhibiteur d'absorption de fructose contenant un monoterpène.
PCT/JP2011/065927 2010-07-14 2011-07-13 Inhibiteur d'absorption de fructose Ceased WO2012008474A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013237656A (ja) * 2012-05-17 2013-11-28 Kao Corp ＰＰＡＲγ活性抑制剤
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CN106668050A (zh) * 2017-01-22 2017-05-17 新乡医学院 治疗动脉粥样硬化的药物组合物及应用
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Publication number Priority date Publication date Assignee Title
JP2013237656A (ja) * 2012-05-17 2013-11-28 Kao Corp ＰＰＡＲγ活性抑制剤
JP2015074647A (ja) * 2013-10-11 2015-04-20 有限会社 坂本薬草園 ステロール調節因子結合タンパク質１ｃ遺伝子発現抑制剤
CN106668050A (zh) * 2017-01-22 2017-05-17 新乡医学院 治疗动脉粥样硬化的药物组合物及应用
WO2019002500A1 (fr) 2017-06-30 2019-01-03 Unilever Plc Composition comestible
WO2019002499A1 (fr) 2017-06-30 2019-01-03 Unilever Plc Composition comestible
WO2019002498A1 (fr) 2017-06-30 2019-01-03 Unilever Plc Composition comestible
WO2019159434A1 (fr) * 2018-02-15 2019-08-22 理恵 堤 Composition contenant du yuko

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