WO2017014153A1 - Composition contre l'obésité comprenant un dipeptide cyclique - Google Patents

Composition contre l'obésité comprenant un dipeptide cyclique Download PDF

Info

Publication number
WO2017014153A1
WO2017014153A1 PCT/JP2016/070864 JP2016070864W WO2017014153A1 WO 2017014153 A1 WO2017014153 A1 WO 2017014153A1 JP 2016070864 W JP2016070864 W JP 2016070864W WO 2017014153 A1 WO2017014153 A1 WO 2017014153A1
Authority
WO
WIPO (PCT)
Prior art keywords
cyclo
gly
pro
obesity
glu
Prior art date
Application number
PCT/JP2016/070864
Other languages
English (en)
Japanese (ja)
Inventor
典正 金川
山本　憲司
仁 小貫
翔太 野中
Original Assignee
サントリーホールディングス株式会社
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 サントリーホールディングス株式会社 filed Critical サントリーホールディングス株式会社
Priority to JP2017529858A priority Critical patent/JP6671367B2/ja
Publication of WO2017014153A1 publication Critical patent/WO2017014153A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to an anti-obesity composition. More specifically, an anti-obesity composition containing an amino acid-containing cyclic dipeptide or a salt thereof as an active ingredient, use of a cyclic dipeptide or a salt thereof for preventing or improving obesity, and a cyclic dipeptide or a salt thereof
  • the present invention relates to a method for preventing or ameliorating obesity.
  • Obesity is one of the major problems in modern society, but the main factor is the increase in the intake of high-fat food accompanying the westernization of Japanese lifestyles. Further, it is known that excessive intake of fat not only leads to obesity but also various diseases caused by obesity such as diabetes, hyperlipidemia, hypertension, arteriosclerosis and the like. Therefore, prevention or improvement of obesity is extremely important for preventing the onset of various diseases related to obesity.
  • Patent Document 1 discloses that an epigallocatechin multimer contained in oolong tea or the like has an inhibitory action on lipase activity, thereby suppressing dietary fat absorption.
  • Patent Documents 2 and 3 non-polymer catechins have an action of increasing the expression of ⁇ -oxidation-related genes in the liver and an action of increasing the total ketone body concentration in the blood. It is disclosed that a metabolic promotion effect is exhibited.
  • Patent Documents 4 and 5 it is also reported that collagen or the like exhibits a lipid metabolism regulating action or a body fat content reducing action.
  • Patent Document 6 discloses that a dipeptide composed of tryptophan and histidine has an AMP kinase activating action, thereby obtaining an effect of preventing or treating obesity.
  • An object of the present invention is to provide a composition for anti-obesity that can be more easily produced and is highly safe, excellent in absorbability into the body, and expected to have a high effect, use of a material for preventing or improving obesity, And providing a method for preventing or ameliorating obesity.
  • a cyclic dipeptide is a dipeptide having a cyclic structure formed by dehydration condensation of an amino group and a carboxyl group present at the end of a linear dipeptide.
  • various physiological activities have received attention.
  • the present inventors take a combination of specific cyclic dipeptides to suppress weight gain, suppress body fat accumulation, suppress visceral fat accumulation, increase body energy consumption, decompose fat in the body. It has been found that a promoting action and the like are exhibited, and thereby an anti-obesity effect such as prevention or improvement of obesity can be obtained, and the present invention has been completed.
  • An anti-obesity composition containing, as an active ingredient, a cyclic dipeptide having an amino acid as a structural unit or a salt thereof, Cyclic dipeptides include cycloglycylarginine (Cyclo (Gly-Arg)), cycloglycylproline (Cyclo (Gly-Pro)), cycloglycylalanine (Cyclo (Gly-Ala)), cyclohydroxyprolylalanine (Cyclo (Hyp-Ala)], cycloglycylhydroxyproline [Cyclo (Gly-Hyp)], cycloglycyllysine [Cyclo (Gly-Lys)], cycloglycylserine [Cyclo (Gly-Ser)], cycloprolyl Glutamic acid (Cyclo (Pro-Glu)), cycloglycylvaline (
  • the anti-obesity composition according to (1) wherein the total amount of the cyclic dipeptide or a salt thereof is 20 mg / 100 g / Brix or more.
  • the anti-obesity composition according to (1) or (2) which prevents or ameliorates obesity through promotion of decomposition of fat in the body.
  • the anti-obesity composition according to (7) which has an action of increasing the expression level of acyl CoA oxidase.
  • the composition for anti-obesity according to (7) which has an action of increasing the expression level of carnitine palmitoyltransferase 1A.
  • the composition for anti-obesity according to (7) which has an action of increasing the expression level of medium-chain acyl CoA dehydrogenase.
  • Function indications are “prevent obesity”, “improve obesity”, “suppress body weight gain”, “suppress body fat accumulation”, “suppress visceral fat accumulation” , “Increasing energy consumption in the body”, “Promoting the breakdown of fat in the body”, “Easy to consume fat”, “Promoting fat burning", and “Promoting metabolism”
  • Cyclic dipeptides include cycloglycylarginine (Cyclo (Gly-Arg)), cycloglycylproline (Cyclo (Gly-Pro)), cycloglycylalanine (Cyclo (Gly-Ala)), cyclohydroxyprolylalanine (Cyclo (Hyp-Ala)], cycloglycylhydroxyproline [Cyclo (Gly-Hyp)], cycloglycyllysine [Cyclo (Gly-Lys)], cycloglycylserine [Cyclo (Gly-Ser)], cycloprolyl Glutamic acid (Cyclo (Pro-Glu)), cycloglycylvaline (Cyclo (Gly-Val)), cycloglycyl Glutamic acid (Cyclo (Pro-Glu)), cycloglycylvaline (Cyclo (Gly-Val)), cyclogly
  • a composition having a very effective anti-obesity action can be provided. Since the cyclic dipeptide or a salt thereof contained in the anti-obesity composition of the present invention has high safety, it can be said that the anti-obesity composition of the present invention has high utility value in the market. Further, by taking the anti-obesity composition of the present invention, it is possible to suppress body weight gain, suppress body fat accumulation, suppress visceral fat accumulation, increase body energy consumption, and promote body fat degradation. Can be effectively used to prevent or improve obesity.
  • One embodiment of the present invention is an anti-obesity composition containing, as an active ingredient, a cyclic dipeptide having an amino acid as a structural unit or a salt thereof.
  • Cyclic dipeptide or salt thereof is characterized by having an amino acid as a structural unit, and having a diketopiperazine structure formed by dehydration condensation of an amino group and a carboxyl group of an amino acid. It refers to a dipeptide. Therefore, the cyclic dipeptide is distinguished from the chain dipeptide.
  • cyclic dipeptides or salts thereof may be collectively referred to simply as cyclic dipeptides.
  • any order thereof may be used, for example, [Cyclo (Gly-Arg)] and [Cyclo (Arg-Gly)] and Represent the same cyclic dipeptide.
  • cyclic dipeptides In cyclic dipeptides, the terminal portions of two amino acids are linked via an amide bond (that is, the cyclic dipeptide has a cyclic structure formed by the amide bond between the amino terminus and the carboxy terminus. Therefore, cyclic dipeptides are more lipophilic than linear dipeptides with polar carboxyl groups or amino groups exposed at the molecular end (particularly linear dipeptides of the same amino acid composition). It has the characteristics. Therefore, cyclic dipeptides are superior in gastrointestinal permeability and membrane permeability compared to linear dipeptides. This is also clear from the results of compound permeation tests using rat inverted intestinal tracts reported in the past (J. Pharmacol, 1998, 50: 167-172). Cyclic dipeptides are also considered to have increased resistance to various peptidases due to their specific structure.
  • the cyclic dipeptide or a salt thereof contained in the anti-obesity composition of the present invention is not particularly limited, and examples thereof include cycloglycylarginine [Cyclo (Gly-Arg)], cycloglycylproline [Cyclo (Gly-Pro)], Cycloglycylalanine [Cyclo (Gly-Ala)], cyclohydroxyprolylalanine [Cyclo (Hyp-Ala)], cycloglycylhydroxyproline [Cyclo (Gly-Hyp)], cycloglycyllysine [Cyclo (Gly-Ala)] Lys)], cycloglycylserine (Cyclo (Gly-Ser)), cycloprolyl glutamic acid (Cyclo (Pro-Glu)), cycloglycyl valine (Cyclo (Gly-Val)), cycloglycyl glutamic acid (Cyclo ( Gly
  • cyclic dipeptides or salts thereof is not particularly limited, but, for example, 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, 15 or more, 20 or more selected from the aforementioned cyclic dipeptides Or 30 or more.
  • the kind of the plurality of cyclic dipeptides or salts thereof included in the anti-obesity composition of the present invention is not particularly limited, but it is preferable to select and include a cyclic dipeptide or a salt thereof having a high anti-obesity effect.
  • the anti-obesity effect includes the effect of increasing the expression level of ⁇ -oxidation enzymes such as acyl CoA oxidase and medium chain acyl CoA dehydrogenase, the effect of increasing the expression level of carnitine palmitoyltransferase 1A, the effect of suppressing body weight gain, and the accumulation of body fat. It can be determined based on an inhibitory effect, an effect of suppressing the accumulation of visceral fat, an effect of increasing energy consumption in the body, an effect of promoting the degradation of fat in the body, or the like.
  • the cyclic dipeptide or a salt thereof contained in the anti-obesity composition of the present invention is cycloglycylarginine [Cyclo (Gly-Arg)], cycloglycylproline [Cyclo (Gly-Pro).
  • cyclic dipeptide salt refers to any pharmacologically acceptable salt (including inorganic salts and organic salts) of the cyclic dipeptide, such as sodium salt and potassium salt of the cyclic dipeptide. , Calcium salt, magnesium salt, ammonium salt, hydrochloride, sulfate, nitrate, phosphate, organic acid salt (acetate, citrate, maleate, malate, oxalate, lactate, succinate , Fumarate, propionate, formate, benzoate, picrate, benzenesulfonate, trifluoroacetate, and the like), but are not limited thereto. Cyclic dipeptide salts can be readily prepared by those skilled in the art by any method known in the art.
  • the cyclic dipeptide used in the present invention can be prepared according to a method known in the art. For example, it may be produced by a chemical synthesis method, an enzymatic method, or a microbial fermentation method, or may be synthesized by dehydration and cyclization of a linear peptide. JP 2003-252896 A, Journal of Peptide ⁇ Science, 10, 737-737, 2004.
  • an animal and plant derived peptide heat-treated product rich in cyclic dipeptide can be obtained by further heat-treating an animal and plant derived peptide obtained by subjecting a raw material containing animal and plant derived protein to enzyme treatment or heat treatment. From these points, the cyclic dipeptide or salt thereof used in the present invention may be chemically or biologically synthesized, or may be obtained from an animal or plant derived peptide.
  • Animal and Plant Derived Peptide in the present specification is not particularly limited.
  • soybean peptide, tea peptide, malt peptide, milk peptide, placenta peptide, collagen peptide and the like can be used.
  • Animal and plant-derived peptides may be prepared and used from animal or plant-derived proteins or raw materials containing proteins, but commercially available products may also be used.
  • Soybean peptide refers to a low molecular weight peptide obtained by subjecting soy protein to enzyme treatment or heat treatment to lower the molecular weight of the protein. Soybeans (scientific name: Glycine max) used as a raw material can be used without restriction of varieties and production areas, and can also be used in processed products such as pulverized products.
  • tea peptide refers to a low molecular weight peptide derived from tea obtained by subjecting a tea (including tea leaves or tea husk) extract to enzyme treatment or heat treatment to lower the protein.
  • a tea leaf used as an extraction raw material, a tea leaf (scientific name: Camellia sinensis) manufactured tea leaf leaf, stem, etc. that can be extracted and used can be used.
  • the form is not limited to large leaves or powders. The harvest time of tea leaves can also be selected appropriately according to the desired flavor.
  • malt peptide refers to a malt-derived low molecular weight peptide obtained by subjecting an extract obtained from malt or a pulverized product thereof to enzymatic treatment or heat treatment to lower the molecular weight of the protein.
  • malt peptide used as a raw material can be used without restriction of varieties and production areas, barley malt obtained by germinating barley seeds is particularly preferably used. In the present specification, barley malt may be simply referred to as “malt”.
  • milk peptide is a product obtained by decomposing milk protein, which is a component derived from natural milk, into a molecule in which at least several amino acids are bound. More specifically, it is obtained by hydrolyzing milk protein such as whey (whey protein) or casein with an enzyme such as proteinase, and filtering and sterilizing and / or concentrating and drying the filtrate. Examples include whey peptides and casein peptides.
  • placenta peptide placenta is the placenta of mammals and has been used as a health food, cosmetics, and pharmaceutical material in recent years because of its excellent functionality.
  • placenta peptide refers to a placenta that has been solubilized and reduced in molecular weight by enzyme treatment or subcritical treatment.
  • extracts obtained from plant placenta are used in health foods, cosmetics, etc. as having a physiological effect equivalent to placenta derived from placenta. be called.
  • the “placenta peptide” in the present specification includes those obtained by subjecting plant placenta to enzyme treatment or subcritical treatment, solubilization and low molecular weight.
  • Collagen peptide refers to a low molecular peptide obtained by subjecting collagen or a pulverized product thereof to enzymatic treatment or heat treatment to lower the molecular weight of collagen.
  • Collagen is a major protein in animal connective tissue and is the most abundant protein in mammalian bodies including humans.
  • high-temperature heat treatment means that the treatment is performed for a certain period of time at a temperature of 100 ° C. or higher and a pressure exceeding atmospheric pressure.
  • a pressure-resistant extraction device As the high-temperature and high-pressure treatment device, a pressure-resistant extraction device, a pressure cooker, an autoclave, or the like can be used according to conditions.
  • the temperature in the high-temperature heat treatment is not particularly limited as long as it is 100 ° C or higher, but is preferably 100 ° C to 170 ° C, more preferably 110 ° C to 150 ° C, and still more preferably 120 ° C to 140 ° C.
  • this temperature shows the value which measured the exit temperature of an extraction column, when using a pressure-resistant extraction apparatus as a heating apparatus, and when using an autoclave as a heating apparatus, it is the temperature of the center temperature in a pressure vessel. The measured value is shown.
  • the pressure in the high-temperature heat treatment is not particularly limited as long as it is a pressure exceeding atmospheric pressure, but is preferably 0.101 MPa to 0.79 MPa, more preferably 0.101 MPa to 0.60 MPa, and even more preferably 0.101 MPa to 0. 48 MPa.
  • the high-temperature heat treatment time is not particularly limited as long as a processed product containing a cyclic dipeptide is obtained, but is preferably about 15 minutes to 600 minutes, more preferably about 30 minutes to 500 minutes, and even more preferably about 60 minutes to 300 minutes. It is.
  • the high-temperature heat treatment conditions for the animal and plant derived peptides are not particularly limited as long as a processed product containing a cyclic dipeptide is obtained, but preferably [temperature: pressure: time] is [100 ° C. to 170 ° C .: 0.101 MPa to 0.001. 79 MPa: 15 minutes to 600 minutes], more preferably [110 ° C. to 150 ° C .: 0.101 MPa to 0.60 MPa: 30 minutes to 500 minutes], even more preferably [120 ° C. to 140 ° C .: 0.101 MPa to 0 48 MPa: 60 minutes to 300 minutes].
  • the specific cyclic dipeptide in the heat-treated product of animal and plant derived peptides does not satisfy the desired content, the specific cyclic dipeptide that is deficient may be appropriately added using other animal or plant derived peptides, commercial products, or synthetic products. it can.
  • Anti-obesity composition 4-1 Composition for anti-obesity containing cyclic dipeptide or salt thereof as active ingredient
  • One embodiment of the present invention is an anti-obesity composition containing as an active ingredient a cyclic dipeptide containing amino acid as a constituent unit or a salt thereof.
  • the anti-obesity composition of the present invention comprises cycloglycylarginine [Cyclo (Gly-Arg)], cycloglycylproline [Cyclo (Gly-Pro)], cycloglycylalanine [Cyclo (Gly-Ala)], cyclohexane.
  • the number of cyclic dipeptides or salts thereof contained in the anti-obesity composition of the present invention is not particularly limited, but in the present invention, two or more, three or more, four or more selected from the aforementioned cyclic dipeptides or salts thereof are used. Preferably, 5 or more, 10 or more, 15 or more, 20 or more, or 30 or more are included.
  • the kind of several cyclic dipeptide or its salt contained in the composition for anti-obesity of this invention is not specifically limited, It is preferable to select and include the cyclic dipeptide or its salt with a high anti-obesity effect.
  • the anti-obesity composition of the present invention comprises cycloglycylarginine [Cyclo (Gly-Arg)], cycloglycylproline [Cyclo (Gly-Pro)], cycloglycylalanine [ Cyclo (Gly-Ala)], cyclohydroxyprolylalanine (Cyclo (Hyp-Ala)), cycloglycylhydroxyproline (Cyclo (Gly-Hyp)), cycloglycyllysine (Cyclo (Gly-Lys)), cyclo Glycylserine [Cyclo (Gly-Ser)], Cycloprolylglutamic acid [Cyclo (Pro-Glu)], Cycloglycylvaline [Cyclo (Gly-Val)], Cycloglycylglutamic acid [Cyclo (Gly-Glu)] Cycloglycylthreonine
  • the total amount of the cyclic dipeptide or a salt thereof contained in the anti-obesity composition of the present invention is not particularly limited as long as the desired effect of the present invention can be obtained in consideration of its administration form, administration method and the like. Is not to be done.
  • the total amount of the cyclic dipeptide or a salt thereof contained in the anti-obesity composition of the present invention is 200 ppm / Brix or more, more preferably 300 ppm / Brix or more, and 5000 ppm / Brix or less, more preferably, per Brix.
  • Is 4000 ppm / Brix or less typically 200 ppm / Brix to 5000 ppm / Brix, and more preferably 300 ppm / Brix to 4000 ppm / Brix.
  • the individual content of each cyclic dipeptide or salt thereof contained in the anti-obesity composition of the present invention is 1 ppm / Brix or more, more preferably 3 ppm / Brix or more, and 3000 ppm / Brix or less, more preferably 2000 ppm / Brix or less, typically 1 ppm / Brix to 3000 ppm / Brix, and more preferably 3 ppm / Brix to 2000 ppm / Brix.
  • ppm ppm of weight / volume (w / v).
  • composition of the present invention can contain any additive and any commonly used component in addition to the aforementioned cyclic dipeptide or a salt thereof, depending on the form.
  • additives and / or ingredients include vitamins such as vitamin E and vitamin C, bioactive ingredients such as minerals, nutritional ingredients, and fragrances, as well as solvents, dispersants, and disintegrations incorporated in the formulation.
  • a coating agent etc. are mentioned, it is not limited to these.
  • acyl-CoA oxidase (Acyl-CoA oxidase (ACO)) which is a peroxisome ⁇ -oxidase, carnitine palmitoyl involved in lipid transport into mitochondria
  • transferase 1A carnitine palmitoyltransferase 1A (CPT1A)
  • MCAD medium-chain acyl-CoA dehydrogenase
  • one embodiment of the present invention is an anti-obesity composition having an acyl CoA oxidase expression promoting action, a carnitine palmitoyltransferase 1A expression promoting action, or a medium chain acyl CoA dehydrogenase expression promoting action.
  • one embodiment of the present invention is to prevent or improve obesity by suppressing body weight gain, suppressing body fat accumulation, suppressing visceral fat accumulation, increasing body energy consumption, or promoting degradation of body fat. It is also an anti-obesity composition.
  • the anti-obesity composition of the present invention is formulated into a solid agent such as a tablet, granule, powder, powder, or capsule, or a liquid agent such as a normal solution, suspension, or emulsion according to a known method. can do. These compositions can be taken with water or the like as it is. Moreover, after preparing the form (for example, powder form and granule form) which can be mix
  • the present invention can be provided in the form of a composition as an example, but is not limited to this form, and may be provided in the form of an agent, for example.
  • the said agent can also be provided as a composition as it is, or as a composition containing the said agent.
  • it can be provided in the form of a medicine or the like, but is not limited to this form.
  • the composition of the present invention include, but are not limited to, a pharmaceutical composition, a food / beverage product composition, a food composition, a beverage composition, a cosmetic composition, and the like.
  • Non-limiting examples of food compositions include functional foods, health supplements, functional nutrition foods, special foods, foods for specified health use, dietary supplements, diet foods, health foods, supplements, food additives, etc. Can be mentioned.
  • the anti-obesity composition of the present invention can be applied to any therapeutic use (medical use) or non-therapeutic use (non-medical use).
  • Specific examples include use as pharmaceuticals, quasi-drugs, and cosmetics, and they are not included in the Pharmaceutical Affairs Law, but obesity prevention effects, obesity improvement effects, weight gain inhibition effects, body Examples thereof include use as a composition that explicitly or implicitly promotes the effect of inhibiting the accumulation of fat, the effect of inhibiting the accumulation of visceral fat, the effect of increasing energy consumption in the body, the effect of promoting the degradation of fat in the body, and the like.
  • the present invention relates to the anti-obesity composition, which is labeled with a function exhibited by an anti-obesity action.
  • Such display or function display is not particularly limited. For example, “prevent obesity”, “improve obesity”, “suppress body weight gain”, “suppress body fat accumulation”, “internal organs” ⁇ Suppress fat accumulation '', ⁇ Increase energy consumption in the body '', ⁇ Promote the breakdown of fat in the body '', ⁇ Make fat easier to consume '', ⁇ Promote fat burning '', ⁇ Metabolism "Promote".
  • indications such as the indication and the function indication may be attached to the composition itself, or may be attached to a container or packaging of the composition.
  • the anti-obesity composition of the present invention can be taken by an appropriate method according to the form.
  • ingestion methods include internal (oral), external, and injection methods, but the method is not particularly limited as long as the desired effect of the present invention is exhibited.
  • ingestion is used to include all aspects of ingestion, taking, drinking, and the like.
  • the intake amount of the anti-obesity composition of the present invention is set at appropriate times according to its form, intake method, intended use, and age, weight, and symptom of the subject patient or animal, and is not constant.
  • the effective human intake of the cyclic dipeptide or a salt thereof in the present invention is not constant, but is preferably 10 mg or more, more preferably 100 mg or more, per day for a human having a body weight of 50 kg. Further, administration may be performed once or several times within one day within a desired intake range.
  • the intake period is also arbitrary.
  • the effective human intake of the cyclic dipeptide or a salt thereof in the present invention means the total intake of the cyclic dipeptide or a salt thereof showing an effective effect in humans.
  • the ingestion target of the anti-obesity composition of the present invention is preferably a human, but domestic animals such as cattle, horses, goats, pet animals such as dogs, cats, rabbits, or mice, rats, guinea pigs, monkeys, etc. It may be a laboratory animal.
  • the amount used per day for about 20 g per mouse is the content of the active ingredient in the composition, the state of the ingested subject, body weight, sex, age, etc.
  • the total amount of the cyclic dipeptide or a salt thereof is preferably 10 mg / kg or more, more preferably 100 mg / kg or more, although it varies depending on conditions.
  • cyclic dipeptide or salt thereof for preventing or ameliorating obesity
  • cycloglycylarginine [Cyclo (Gly-Arg)]
  • cycloglycylproline [Cyclo (Gly-Pro)]
  • cycloglycylalanine [Cyclo (Gly-Ala)]
  • cyclohydroxyprolylalanine [Cyclo ( Hyp-Ala)]
  • cycloglycyl lysine [Cyclo (Gly-Lys)]
  • cycloglycyl serine [Cyclo (Gly-Ser)]
  • cycloprolyl glutamic acid (Cyclo (Pro-Glu)
  • cycloglycylvaline Cyclo (Gly-Val)
  • cycloprolyl glutamic acid Cyclo (Pro-Glu)
  • the number of cyclic dipeptides or salts thereof is not particularly limited, but 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, 15 or more, 20 or more selected from the aforementioned cyclic dipeptides or salts thereof It is preferable to use the above or more than 30 kinds for preventing or improving obesity.
  • the kind of the plurality of cyclic dipeptides or salts thereof used in the use of the present invention is not particularly limited, but it is preferable to select and use a cyclic dipeptide or a salt thereof having a high anti-obesity effect.
  • cycloglycylarginine [Cyclo (Gly-Arg)], cycloglycylproline [Cyclo (Gly-Pro)], cycloglycylalanine [Cyclo (Gly-Ala)], cyclohydroxy Prolylalanine (Cyclo (Hyp-Ala)), cycloglycylhydroxyproline (Cyclo (Gly-Hyp)), cycloglycyllysine (Cyclo (Gly-Lys)), cycloglycylserine (Cyclo (Gly-Ser)) ], Cycloprolyl glutamic acid (Cyclo (Pro-Glu)), cycloglycyl valine (Cyclo (Gly-Val)), cycloglycyl glutamic acid (Cyclo (Gly-Glu)), cycloglycyl threonine [Cyclo (Gly-Arg)], cycloglycyl
  • the use of the present invention includes, for example, suppression of body weight increase, suppression of body fat accumulation, suppression of visceral fat accumulation, increase of energy consumption in the body, promotion of decomposition of fat in the body, prevention of obesity, improvement of obesity, etc.
  • the use is a use in a human or non-human animal, and may be a therapeutic use or a non-therapeutic use.
  • “non-therapeutic” is a concept that does not include a medical act, that is, a treatment act on the human body by treatment.
  • One embodiment of the present invention provides a method for preventing or ameliorating obesity using the aforementioned cyclic dipeptide or a salt thereof as an active ingredient in a subject in need of prevention or amelioration of obesity. Is.
  • cycloglycylarginine [Cyclo (Gly-Arg)], cycloglycylproline [Cyclo (Gly-Pro)], cycloglycylalanine [Cyclo (Gly-Ala)], cyclohydroxyprolylalanine [Cyclo ( Hyp-Ala)], cycloglycyl hydroxyproline [Cyclo (Gly-Hyp)], cycloglycyl lysine [Cyclo (Gly-Lys)], cycloglycyl serine [Cyclo (Gly-Ser)], cycloprolyl glutamic acid (Cyclo (Pro-Glu)), cycloglycylvaline (Cyclo (Gly-Val)), cycloglycylglutamic acid (Cyclo (Gly-Glu)), cycloglycylthreonine [Cyclo (Gly-Thr)], cyclohydroxy Proly
  • the number of cyclic dipeptides or salts thereof is not particularly limited, but 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, 15 or more, 20 or more selected from the aforementioned cyclic dipeptides or salts thereof A method for preventing or improving obesity using the above or 30 or more cyclic dipeptides or salts thereof as an active ingredient is preferred.
  • the kind of the plurality of cyclic dipeptides or salts thereof used in the method of the present invention is not particularly limited, but it is preferable to select and use a cyclic dipeptide or a salt thereof having a high anti-obesity effect.
  • cycloglycylarginine [Cyclo (Gly-Arg)], cycloglycylproline [Cyclo (Gly-Pro)], cycloglycylalanine [Cyclo (Gly-Ala)], cyclohydroxy Prolylalanine (Cyclo (Hyp-Ala)), cycloglycylhydroxyproline (Cyclo (Gly-Hyp)), cycloglycyllysine (Cyclo (Gly-Lys)), cycloglycylserine (Cyclo (Gly-Ser)) ], Cycloprolyl glutamic acid (Cyclo (Pro-Glu)), cycloglycyl valine (Cyclo (Gly-Val)), cycloglycyl glutamic acid (Cyclo (Gly-Glu)), cycloglycyl threonine [Cyclo (Gly-Arg)], cycloglycyl
  • the subject requiring prevention or improvement of obesity is the same as the subject to which the anti-obesity composition of the present invention is applied.
  • the amount of the cyclic dipeptide or salt thereof used in the above method is not particularly limited, but is preferably an effective amount or more.
  • the effective amount refers to an amount capable of preventing or improving obesity when the subject is ingested with the anti-obesity composition of the present invention as compared to a subject who is not ingested. That is.
  • the anti-obesity composition of the present invention when the anti-obesity composition of the present invention is ingested by the above-mentioned subject, compared with a subject not ingested, the amount that can suppress the increase in body weight, the amount that can suppress the accumulation of body fat, The amount that can suppress the accumulation, the amount that can increase the energy consumption in the body, or the amount that can promote the decomposition of fat in the body.
  • the specific effective amount is set in a timely manner according to the ingestion form, the ingestion method, the purpose of use and the age, weight, symptoms, etc. of the subject and is not constant.
  • the aforementioned cyclic dipeptide or a salt thereof may be ingested as it is or as a composition containing the aforementioned cyclic dipeptide or a salt thereof so that the therapeutically effective amount is obtained.
  • obesity can be prevented or ameliorated without causing side effects.
  • Example 1 Evaluation of anti-obesity effect by a mixture of 32 kinds of cyclic dipeptides 8 Eight-age male C57BL / 6J mice were divided into 4 groups of 8 mice, each with a low-fat purified feed (AIN93M) and a high-fat purified feed (D12451) , And a high-fat refined feed supplemented with 1.3% cyclic dipeptide 32 species mixture for 8 weeks.
  • Table 1 shows the mixing ratio of each cyclic dipeptide in the cyclic dipeptide mixture.
  • the feed composition is shown in Table 2.
  • ACO oxidase
  • CPT1A carnitine palmitoyltransferase 1A
  • MCAD medium chain acyl CoA dehydrogenase
  • VO 2 oxygen consumption of 00 approximately
  • VCO 2 carbon dioxide emissions
  • Respiration exchange ratio carbon dioxide emissions (VCO 2 ) / oxygen consumption (VO 2 )
  • Example 3 Evaluation of ⁇ -oxidation-related gene elevating action by 32 kinds of cyclic dipeptide mixture
  • Human hepatoma-derived cells HepG2: RCB1889
  • DMEM medium 10% FBS, 2 mM glutamine, 1% antibiotics added
  • RNA was extracted from the cells using NucleoSpin (registered trademark) RNA (Takara Bio).
  • cDNA was synthesized using PrimeScript (registered trademark) RT Master Mix (Takara Bio), and acyl CoA oxidase (by Takara Bio) was subjected to real-time PCR using SYBR (registered trademark) Premix Ex Taq (trademark) II (Takara Bio). ACO) and carnitine palmitoyltransferase 1A (CPT1A) mRNA expression levels were measured.
  • the comparative Ct method using gapdh gene as an internal standard gene was applied. The expression level of the gene was expressed as a relative expression level with respect to the control group (group not added with the collagen peptide heat-treated product). Data were expressed as mean ⁇ standard error. The results are shown in Table 8.
  • the present invention provides an anti-obesity composition containing a cyclic dipeptide or a salt thereof as an active ingredient.
  • the present invention is a new safe and effective for the prevention or improvement of obesity by suppressing body weight gain, body fat accumulation, visceral fat accumulation, increasing body energy consumption, promoting the degradation of body fat, etc. Since it provides a means, industrial applicability is high.

Abstract

L'invention fournit une composition contre l'obésité, une application d'une substance destinée à une prévention ou à une amélioration concernant l'obésité, et un procédé de prévention ou amélioration concernant l'obésité. Selon l'invention, un dipeptide cyclique spécifique ou un sel de celui-ci, possède un effet contre l'obésité. Plus précisément, l'invention fournit un nouveau moyen destiné à une prévention ou à une amélioration concernant l'obésité par inhibition d'une augmentation du poids, inhibition de l'accumulation de graisses de l'organisme, inhibition de l'accumulation de graisses viscérales, accroissement de la consommation énergétique dans le corps, accélération de la dégradation des graisses dans le corps, ou similaire.
PCT/JP2016/070864 2015-07-17 2016-07-14 Composition contre l'obésité comprenant un dipeptide cyclique WO2017014153A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2017529858A JP6671367B2 (ja) 2015-07-17 2016-07-14 環状ジペプチド含有抗肥満用組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015142654 2015-07-17
JP2015-142654 2015-07-17

Publications (1)

Publication Number Publication Date
WO2017014153A1 true WO2017014153A1 (fr) 2017-01-26

Family

ID=57835066

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/070864 WO2017014153A1 (fr) 2015-07-17 2016-07-14 Composition contre l'obésité comprenant un dipeptide cyclique

Country Status (3)

Country Link
JP (1) JP6671367B2 (fr)
TW (1) TW201716067A (fr)
WO (1) WO2017014153A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018117000A1 (fr) * 2016-12-21 2018-06-28 サントリーホールディングス株式会社 Aliments et boissons contenant de la cyclo(aspartyl-glycine), du glucose et du maltose

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5418218A (en) * 1992-07-10 1995-05-23 The University Of Maryland At Baltimore Histidyl-proline diketopiperazine (cyclo his-pro) a cns-active pharmacologic agent
JP2013537195A (ja) * 2010-09-07 2013-09-30 ディエムアイ アクイジション コーポレイション 疾患の治療

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5418218A (en) * 1992-07-10 1995-05-23 The University Of Maryland At Baltimore Histidyl-proline diketopiperazine (cyclo his-pro) a cns-active pharmacologic agent
JP2013537195A (ja) * 2010-09-07 2013-09-30 ディエムアイ アクイジション コーポレイション 疾患の治療

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JUNG E.Y. ET AL.: "Glucose Tolerance and Antioxidant Activity of Spent Brewer's Yeast Hydrolysate with a High Content of Cyclo-His- Pro (CHP", JOURNAL OF FOOD SCIENCE, vol. 76, 2011, pages C272 - C278, XP055348462 *
PRASAD C.: "Bioactive Cyclic Dipeptides", PEPTIDES, vol. 16, no. 1, 1995, pages 151 - 164, XP002477201 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018117000A1 (fr) * 2016-12-21 2018-06-28 サントリーホールディングス株式会社 Aliments et boissons contenant de la cyclo(aspartyl-glycine), du glucose et du maltose

Also Published As

Publication number Publication date
TW201716067A (zh) 2017-05-16
JPWO2017014153A1 (ja) 2018-04-26
JP6671367B2 (ja) 2020-03-25

Similar Documents

Publication Publication Date Title
JP5334448B2 (ja) グルタチオン産生促進剤およびグルタチオンの欠乏に起因する疾患の予防・治療剤
JP6796487B2 (ja) 環状ジペプチド高含有組成物
WO2015194447A1 (fr) Agent améliorant le métabolisme du glucose
JP6669750B2 (ja) 環状ジペプチド含有血清カルノシン分解酵素阻害用組成物
JP5403942B2 (ja) グルタチオン産生促進剤およびグルタチオンの欠乏に起因する疾患の予防・治療剤
TWI744240B (zh) 含有環狀二肽及甜味料之組成物
WO2017119481A1 (fr) Composition contenant un dipeptide cyclique pour la prévention de maladie neurologiques
WO2016133157A1 (fr) Inhibiteur de lipase
JP6666912B2 (ja) Ｔｒｐｖ１刺激用組成物
JP6671367B2 (ja) 環状ジペプチド含有抗肥満用組成物
WO2017002840A1 (fr) Composition pour antagoniste de récepteur d'endothéline
JP6786490B2 (ja) 抗肥満用組成物
CN107922458B (zh) 含有氨基酸及环状二肽的组合物
JP6661597B2 (ja) α−グルコシダーゼ阻害剤
WO2017119476A1 (fr) Composition pour prévenir des maladies neurologiques
JP6687619B2 (ja) メラニン凝集ホルモン受容体拮抗用組成物
JP2007176837A (ja) 痩身用組成物
JP2022129479A (ja) 肝機能向上剤および肝機能向上用経口組成物
WO2017002765A1 (fr) Composition pour réduire les calories

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16827713

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2017529858

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16827713

Country of ref document: EP

Kind code of ref document: A1