WO2021060264A1 - Composition for improving renal function - Google Patents

Composition for improving renal function Download PDF

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Publication number
WO2021060264A1
WO2021060264A1 PCT/JP2020/035768 JP2020035768W WO2021060264A1 WO 2021060264 A1 WO2021060264 A1 WO 2021060264A1 JP 2020035768 W JP2020035768 W JP 2020035768W WO 2021060264 A1 WO2021060264 A1 WO 2021060264A1
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Prior art keywords
renal function
composition
glycine
tryptophan
improving
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PCT/JP2020/035768
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French (fr)
Japanese (ja)
Inventor
大嶋　俊二
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アサヒグループホールディングス株式会社
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Priority to JP2021548924A priority Critical patent/JPWO2021060264A1/ja
Publication of WO2021060264A1 publication Critical patent/WO2021060264A1/en

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    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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

Definitions

  • the present invention relates to a composition for improving renal function.
  • Kidney disease is a disease in which the function of the kidneys deteriorates due to the deterioration of the functions of the glomeruli, renal tubules, etc. of the kidneys. It is also known that kidney function gradually declines with age. As for the glomeruli of the kidney, when the function of some glomeruli deteriorates, other glomeruli supplement the function, but it is thought that the function of the kidney declines because the glomeruli gradually decrease with aging. There is. Once kidney function is lost, it often cannot be recovered, and there is a risk of developing a condition called chronic renal failure. If renal function declines further and progresses to end-stage renal failure, and recovery of renal function cannot be expected, treatment such as dialysis therapy and kidney transplantation will be required.
  • CKD Chronic kidney disease
  • International Publication No. 2017/002895 proposes a composition having angiotensin converting enzyme inhibitory activity containing an amino acid and a cyclic dipeptide, and is said to have a renal function protecting action.
  • Japanese Patent Application Laid-Open No. 2002-275059 proposes an amino acid composition for improving renal dysfunction containing a specific amino acid.
  • An object of the present invention is to provide a composition for improving renal function.
  • the present invention provides a composition for improving renal function, which comprises glycine and tryptophan, and the content ratio of glycine to tryptophan is more than 10 and less than 60 on a mass basis.
  • the composition has an intake of glycine of 1 g or more and 10 g or less at one time.
  • the present invention also provides a food or drink for improving renal function containing the above composition.
  • the present invention also provides an agent for improving renal function containing the above composition.
  • the present invention is a method for maintaining renal function and a method for maintaining renal function, which comprises administering a composition for improving renal function, which comprises glycine and tryptophan, and the content ratio of glycine to tryptophan is more than 10 and less than 60 on a mass basis.
  • a composition for improving renal function which comprises glycine and tryptophan, and the content ratio of glycine to tryptophan is more than 10 and less than 60 on a mass basis.
  • the content of each component in the composition is the total amount of the plurality of substances present in the composition unless otherwise specified, when a plurality of substances corresponding to each component are present in the composition. means.
  • composition for improving renal function contains glycine and tryptophan as active ingredients, and may further contain other components if necessary.
  • the composition for improving renal function has a content ratio of glycine to tryptophan of more than 10 and less than 60 on a mass basis. Neither glycine nor tryptophan is known to have any effect on renal function. However, renal function in animals can be maintained and improved by ingesting a combination of glycine and tryptophan in a specific mass ratio.
  • the maintenance / improvement of renal function in the present specification includes at least one of maintaining normal renal function and improving decreased renal function, and for example, maintaining an index for evaluating renal function in a normal state. It means to improve the index for evaluating renal function that has deteriorated due to some factor so that it approaches a healthy state.
  • the index for evaluating renal function include glomerular filtration rate (GFR), urinary protein amount, urinary albumin amount, serum creatinine concentration, serum cystatin C concentration and the like.
  • GFR glomerular filtration rate
  • the effect of maintaining / improving renal function can be confirmed by comparing the administration group and the control group with respect to the index for evaluating renal function.
  • factors that worsen the index for evaluating renal function include, for example, lifestyle-related diseases such as aging, drinking and smoking, diseases such as diabetes and hypertension, and dysfunction.
  • the composition for improving renal function is an agent for maintaining / improving at least one index for evaluating renal function selected from the group consisting of GFR, urinary protein amount, urinary albumin amount, serum creatinine concentration and serum cystatin C concentration. May be.
  • GFR is an important index used for diagnosis of CKD together with findings suggestive of renal disorders (urinalysis abnormalities, imaging abnormalities, blood abnormalities, pathological findings, etc.).
  • GFR is generally evaluated as an estimated GFR (eGFR) calculated from the measured value of serum creatine.
  • Serum creatine is known to be affected by muscle mass, gender, age, etc., and eGFR is calculated by an estimation formula that takes these into consideration.
  • the composition for improving renal function according to the present embodiment contains glycine as one of the active ingredients. Glycine is known to be converted to creatine in vivo (see, for example, J. Anim. Sci. 1991. 69: 1532-1550.).
  • the intake of the composition for improving renal function according to the present embodiment will affect the serum creatine concentration, and as a result, the evaluation of GFR will be affected.
  • serum cystatin C is drawing attention as a new GFR marker. Since the serum cystatin C value is not easily affected by muscle mass, diet, exercise, etc., it is said to be useful when it is difficult to evaluate by the GFR estimation formula based on the serum creatine level (see, for example, CKD Medical Treatment Guide 2012). Therefore, in the present specification, eGFR is calculated based on the serum cystatin C concentration to evaluate renal function. Therefore, the composition for improving renal function may be a GFR maintenance / improvement agent, an eGFR maintenance / improvement agent, or an eGFR maintenance / improvement agent based on the serum cystatin C concentration.
  • Glycine contained in the composition is aminoacetic acid and has the simplest structure among amino acids.
  • the purity of glycine may be any one suitable for ingestion by animals, and the purity is, for example, 90% or more, preferably 98% or more.
  • Glycine can be produced by, for example, an extraction method, a microbial fermentation method, or the like, and may be appropriately selected from commercially available products.
  • Tryptophan is 2-amino-3-indrill propionic acid and may contain at least L-tryptophan.
  • the tryptophan may be racemic, but is preferably L-tryptophan.
  • the purity of tryptophan may be as long as it is suitable for ingestion by animals, and the purity is, for example, 90% or more, preferably 98% or more. Tryptophan can be produced by, for example, an extraction method, a microbial fermentation method, or the like, and may be appropriately selected from commercially available products.
  • Glycine and tryptophan may be contained as a simple substance (free form) or may be contained in the form of a salt.
  • the salt of glycine and tryptophan is not particularly limited as long as it is a pharmacologically acceptable salt. Specific examples thereof include acid addition salts, metal salts, ammonium salts and organic amine addition salts. Acid addition salts include inorganic acid salts such as hydrochlorides, sulfates, nitrates and phosphates, acetates, maleates, fumarates, citrates, malates, lactates and ⁇ -ketoglutarates. , Gluconate, organic acid salts such as caprylate, and the like.
  • Examples of the metal salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt, zinc salt and the like.
  • Examples of the ammonium salt include salts such as ammonium and tetramethylammonium.
  • Examples of the organic amine addition salt include salts such as morpholine and piperidine.
  • the mass-based content ratio of glycine to tryptophan in the composition is, for example, more than 10 and less than 60, preferably 12 or more and 45 or less, more preferably 13 or more and 40 or less, still more preferably, from the viewpoint of renal function improving action. Is 14 or more and 35 or less.
  • the mass-based content ratio of glycine to tryptophan may be, for example, greater than 10, preferably 12 or greater, 13 or greater, or 14 or greater.
  • the mass-based content ratio of glycine to tryptophan may be, for example, less than 60, preferably 45 or less, 40 or less, or 35 or less.
  • the composition may further contain other active ingredients in addition to glycine and tryptophan.
  • the other active ingredient may have an effect of maintaining / improving renal function.
  • Other active ingredients include, for example, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, valine, ornithine, citrulline and the like.
  • Other amino acids can be mentioned.
  • the other active ingredient may be at least one selected from the group consisting of these other amino acids.
  • amino acids at least one selected from the group consisting of aspartic acid, aspartic acid, glutamic acid and glutamine is preferable, and at least one selected from the group consisting of aspartic acid, glutamic acid and glutamine is more preferable, and aspartic acid and glutamic acid. At least one selected from the group consisting of is more preferred.
  • the other amino acids may be one kind or a combination of two or more kinds.
  • the composition may be substantially free of other active ingredients other than glycine and tryptophan.
  • substantially free of other active ingredients means that the content of other active ingredients is less than the amount exhibiting the effect of maintaining / improving renal function. Specifically, it means that the content of other active ingredients is, for example, less than 10% by mass, less than 1% by mass, less than 0.1% by mass, or less than 0.01% by mass with respect to glycine. ..
  • the total content of the active ingredient in the composition may be appropriately selected according to the composition of the composition, the effect expected by ingestion of the composition, and the like.
  • the total content of the active ingredient in the composition is, for example, 0.0001% by mass or more, preferably 0.001% by mass or more, more preferably 0.01% by mass or more, still more preferably 0.1% by mass or more, particularly preferably.
  • composition may further contain other ingredients other than the active ingredient, if necessary.
  • Other components include solvents such as water; various vitamins including B vitamins; sweeteners; fragrances; colorants; pharmacologically acceptable carriers, excipients, diluents, salts, pH adjusters. , Chelating agent, buffering agent and the like.
  • the composition may be in any dosage form such as powder, granule, tablet, capsule, troche, syrup, liquid, injection or the like.
  • the ingestion method may be selected from the ingestion routes usually used according to the dosage form of the composition and the like. Examples of the ingestion route include oral administration, nasal administration, rectal administration, intravenous injection, and infusion.
  • the intake amount of the composition may be an amount capable of exerting an action of maintaining / improving renal function, and usually, the intake amount of glycine at one time is, for example, 1 g or more, preferably 2 g or more, more preferably 3 g or more, and further. It may be preferably 5 g or more, and may be, for example, 10 g or less, preferably 8 g or less, and more preferably 7 g or less.
  • the amount of tryptophan ingested at one time may be, for example, 0.01 g or more, preferably 0.1 g or more, more preferably 0.15 g or more, and for example, 1.0 g or less, preferably 0.6 g or less.
  • the intake amount of the composition may be, for example, the intake amount per 60 kg of body weight, and may be appropriately changed according to the body weight of the intake target and the like.
  • the composition can be used for the prevention and / or treatment of diseases in which the pathological condition is improved by the renal function improving action. That is, the composition for improving renal function may be a pharmaceutical composition applied to improve renal function. Examples of such diseases include CKD, diabetic nephropathy, nephrosclerosis, acute nephritis and the like.
  • the composition can also function as a prophylactic agent that suppresses the onset of the above diseases and / or as a therapeutic agent that improves the normal state.
  • the composition can be used for prevention, suppression, etc. of renal function decline.
  • renal dysfunction includes those caused by aging, lifestyle, diseases, dysfunction and the like.
  • the ingestion target of the composition may be any vertebrate having renal function, and can be safely ingested orally or parenterally.
  • the ingestion target of the composition may be, for example, a mammal such as a human, a mouse, a rat, a rabbit, a dog, or a cat.
  • the ingestion target of the composition may be a human or a non-human animal.
  • cats, which are non-human animals, CKD and the like are frequently observed as causes of the disease, death, and the like. Therefore, the composition is suitably used for improving renal function in felines.
  • the composition can also be applied to improve indicators for assessing renal function in healthy humans.
  • Target healthy humans include, for example, humans with normal levels of urinary protein and urinary albumin and a GFR of 90 mL / min / 1.73 m 2 or higher or 60 mL / min / 1.73 m 2 or higher. (For example, see Japan Nephrology Society (eds.), "Evidence-based CKD Practice Guidelines 2018", Tokyo Medical Co., Ltd., June 2018, page 3).
  • the amount of the composition to be ingested is appropriately determined according to the type of the disease, the age, sex, body weight, degree of symptoms, the method of ingestion, and the like. be able to.
  • the total amount of glycine and tryptophan per day is usually 1 g or more, preferably 3 g or more, more preferably 5 g or more, and for example, 10 g or less, preferably 8 g or less. It may be taken once or several times a day, preferably to be 7 g or less.
  • the ingestion period may be, for example, one day or longer, preferably one week or longer, and more preferably one month or longer.
  • the ingestion period may be, for example, one year or less, preferably three months or less.
  • the ingestion period may not be particularly limited.
  • the amount of the composition to be ingested can be appropriately determined according to the age, sex, body weight, ingestion method, and the like of the ingestion target.
  • the total amount of glycine and tryptophan per day is usually 1 g or more, preferably 3 g or more, more preferably 5 g or more, and for example, 10 g or less, preferably 8 g or less. It may be taken once or several times a day, preferably to be 7 g or less.
  • the ingestion period is, for example, one day or longer, preferably one week or longer.
  • the ingestion period may be, for example, one year or less, preferably three months or less.
  • the ingestion period may not be particularly limited.
  • the food and drink contains the above-mentioned composition for improving renal function containing glycine and tryptophan. By ingesting food and drink, the effects of the above-mentioned composition can be obtained.
  • the foods and drinks containing the composition for improving renal function of the present invention include healthy foods and drinks, functional foods and drinks, foods and drinks for the sick, and all foods and drinks to which the above composition for improving renal function can be blended. included. Of these, functional foods and drinks are particularly preferable.
  • “Functional food and drink” means food and drink having a certain functionality with respect to the living body, for example, food and drink for specified health use (including conditional diet [food for specified health use]) and nutritional functional food and drink.
  • Health functional foods and drinks special purpose foods and drinks, nutritional supplement foods and drinks, health supplement foods and drinks, supplements (for example, various dosage forms such as tablets, coated tablets, sugar-coated tablets, capsules and liquids) and beauty foods and drinks (eg diet) It includes all so-called healthy foods and drinks such as foods and drinks.
  • Functional foods and drinks also include healthy foods and drinks to which a Health claim based on the Codex (FAO / WHO Joint Food and Agriculture Organization) food standards applies.
  • the above-mentioned health foods and the like may be in the shape of ordinary foods, and may be in the form of supplements (tablets, granules (for example, granules packed in sticks), fine granules, tablets, chewable tablets, capsules (soft). Capsules, hard capsules), etc.) may be used.
  • supplements tablets, granules (for example, granules packed in sticks), fine granules, tablets, chewable tablets, capsules (soft). Capsules, hard capsules), etc.
  • the food and drink may be a liquid beverage.
  • the glycine concentration in the beverage is, for example, 0.1 g / 100 ml or more, preferably 0.15 g / 100 ml or more, more preferably 0.2 g / 100 ml or more, still more preferably 0.3 g / 100 ml.
  • it may be particularly preferably 0.6 g / 100 ml or more, and for example, it may be 10 g / 100 ml or less, preferably 8 g / 100 ml or less, and more preferably 7 g / 100 ml or less.
  • the tryptophan concentration in the beverage may be, for example, 0.001 g / 100 ml or more, preferably 0.005 g / 100 ml or more, more preferably 0.02 g / 100 ml or more, and for example, 1.0 g / 100 ml or less, preferably 1.0 g / 100 ml or more. It may be 0.6 g / 100 ml or less, more preferably 0.4 g / 100 ml or less.
  • Beverages are composed of, for example, a composition containing glycine and tryptophan, and a liquid medium such as water or fruit juice.
  • Beverages include, for example, tea beverages such as green tea, oolong tea and tea, soft beverages, jelly beverages, sports beverages, milk beverages, carbonated beverages, vegetable beverages, fruit juice beverages, fermented vegetable beverages, fermented fruit juice beverages, fermented milk beverages (yogurt, etc.) , Lactobacillus beverages, milk beverages (coffee milk, fruit milk, etc.), powdered beverages, cocoa beverages, alcoholic beverages, etc., and may be beverages containing a composition and using milk, purified water, etc. as a liquid medium. ..
  • Beverages may contain sweeteners to adjust the sweetness.
  • the sweetener may be sugar, and examples of the sugar include sugar, glucose, fructose, fructooligosaccharide, galactooligosaccharide and the like.
  • synthetic sweeteners such as aspartame and saccharin may be added.
  • Beverages may contain acidulants.
  • the acidulant include citric acid, DL-malic acid, L-tartaric acid, lactic acid, phosphoric acid and the like.
  • Beverages may contain flavors.
  • the fragrance include citrus oils such as lemon, lime and orange, orange oil, herbal extracts and the like.
  • the fragrance may be a natural fragrance or a synthetic fragrance. Natural fragrances include, for example, anis oil, angelica oil, all-spices oil, orange oil, cassia oil, capsicum oil, galana extract, cardamon oil, caraway oil, cumin oil, clarisage oil, grapefruit oil, clove oil, coriander oil.
  • Coffee oil cognac oil, cola nut extract, cinnamon oil, ginger oil, thyme oil, nutmeg oil, peppermint oil, vanilla extract, bitter almond oil, phenuglique oil, fennel oil, pepper oil, peppermint oil, perilla oil, bergamot oil , Mandarin oil, eucalyptus oil, lemon oil, rosemary oil and the like.
  • Synthetic fragrances include, for example, anetol, allyl caproate, isoamyl acetate, ⁇ -undecalactone, ethylvanillin, ethyl butyrate, ethylphenylglycidate, eugenol, geraniol, diacetyl, cycloten, citral, synamic aldehyde, turpineol.
  • ⁇ -decalactone decanal, nonanal, ⁇ -nonalactone, vanillin, phenylethyl alcohol, flaneol, furfuryl mercaptan, 2-hexenal, 3-hexenol, heliotropin, perillaaldehyde, benzaldehyde, maltor, methylanthranilate, methylsalicylate , Mentor, ⁇ -yonon, linalol and the like.
  • the present invention includes a method for maintaining renal function and a method for improving renal function, which comprises administering a composition for improving renal function containing glycine and tryptophan to a subject.
  • another aspect of the present invention is the use of a composition for improving renal function in the production of a composition used for a method for maintaining renal function or a method for improving renal function, a method for maintaining renal function, or a method for improving renal function. It also includes the use of the composition for improving renal function, the composition for improving renal function used in the method for maintaining renal function or the method for improving renal function.
  • Example 1 The study was conducted on 31 healthy adult men and women after obtaining written consent for informed consent.
  • a control containing 5.2 g of dextrin (Cont) or a composition containing 3.0 g of glycine, 0.2 g of tryptophan and 2.0 g of dextrin (GlyTrp) was orally administered once daily for 6 weeks as a test product. Ingested. Blood was collected before and 6 weeks after ingestion of the test product, the serum cystatin C concentration was measured, and eGFR was calculated by a calculation formula based on the measurement. Table 1 shows the mean value and standard deviation of eGFR (in parentheses). Table 1 also shows the results of the t-test regarding the significant difference in changes over time and the significant difference from the target group.
  • eGFR (104 x Cystatin C- 1.019 x 0.996 age ) -8
  • the serum cystatin C concentration increased in the control group, but decreased in the group to which the composition containing glycine and tryptophan was administered. From Table 1 in which eGFR was calculated using the calculation formula, the eGFR was significantly increased over time in the group to which the composition containing glycine and tryptophan was administered, and the eGFR was significantly increased as compared with the control group. Was done. In particular, in the group administered a composition comprising glycine and a tryptophan at low 10 subjects with eGFR value less than 95, 98 mL / min 1.73 m 2 next eGFR from 90 mL / min 1.73 m 2, more pronounced An increase was seen. This indicates that subjects with lower renal function can be expected to have an effect of improving renal function of the composition containing glycine and tryptophan.
  • Example 2 The study was conducted on 16 healthy adult male subjects after obtaining written consent for informed consent. As a control, 6.4 g of dextrin (control group) was prepared. Further, as test products, a composition containing 6.0 g of glycine and 0.4 g of dextrin (Gly), a composition containing 0.4 g of tryptophan and 6.0 g of dextrin (Trp), and 6.0 g of glycine and 0.4 g of tryptophan were used. Each containing composition (GlyTrp (6 + 0.4)) was prepared. Each composition was orally ingested as a single test product.
  • eGFR was calculated by the above formula based on the blood sample.
  • Table 2 shows the mean value and standard deviation of eGFR (in parentheses). Table 2 also shows the results of the t-test for the significant difference from the target group.
  • the eGFR was significantly higher in the group ingesting the composition (GlyTrp (6 + 0.4)) containing glycine and tryptophan and having a glycine content ratio (Gly / Trp) of 15 to tryptophan as compared with the control group. Rose. On the other hand, when glycine alone (Gly) or tryptophan alone (Trp) was administered, no significant difference was observed in eGFR as compared with the control group.
  • Example 3 The study was conducted on 6 healthy adult male subjects after obtaining written consent for informed consent. As a control, 6.4 g of dextrin (control group) was prepared. As test products, a composition containing 6.0 g of glycine, 0.2 g of tryptophan and 0.2 g of dextrin (GlyTrp (6 + 0.2)), and a composition containing 6.0 g of glycine, 0.1 g of tryptophan and 0.3 g of dextrin. The eGFR was calculated and evaluated in the same manner as in Example 2 except that (GlyTrp (6 + 0.1)) was prepared and blood was collected 2 hours after ingestion. The results are shown in Table 3.
  • Example 4 Nine healthy adult male subjects were tested after obtaining written consent for informed consent. As a control, 6.4 g of dextrin (control group) was prepared. As a test product, a composition containing 2.0 g of glycine, 0.4 g of tryptophan and 4.0 g of dextrin (GlyTrp (2 + 0.4)), and a composition containing 3.0 g of glycine, 0.4 g of tryptophan and 3.0 g of dextrin.

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Abstract

Provided is a composition that improves renal function. This composition for improving renal function contains glycine and tryptophan, wherein the content ratio by mass of glycine to tryptophan is more than 10 and less than 60.

Description

腎機能改善用組成物Composition for improving renal function
　本発明は、腎機能改善用組成物に関する。 The present invention relates to a composition for improving renal function.
　腎臓病は、腎臓の糸球体、尿細管等の機能が低下することで腎臓の働きが悪くなる疾病である。また腎臓の機能は加齢により徐々に低下することが知られている。腎臓の糸球体は一部の糸球体の機能が低下すると他の糸球体がその機能を補うが、加齢により糸球体が徐々に減少するため、腎臓の機能が低下していくと考えられている。腎臓の機能は一旦失われると回復できない場合が多く、慢性腎不全といわれる病態に陥るリスクがある。腎臓の機能低下がさらに進んで末期腎不全まで進行し、腎機能の回復が見込めない状態になると透析療法、腎移植といった治療を受けることになる。 Kidney disease is a disease in which the function of the kidneys deteriorates due to the deterioration of the functions of the glomeruli, renal tubules, etc. of the kidneys. It is also known that kidney function gradually declines with age. As for the glomeruli of the kidney, when the function of some glomeruli deteriorates, other glomeruli supplement the function, but it is thought that the function of the kidney declines because the glomeruli gradually decrease with aging. There is. Once kidney function is lost, it often cannot be recovered, and there is a risk of developing a condition called chronic renal failure. If renal function declines further and progresses to end-stage renal failure, and recovery of renal function cannot be expected, treatment such as dialysis therapy and kidney transplantation will be required.
　腎機能の低下、腎臓の障害を所見とする慢性腎臓病（ＣＫＤ：chronic kidney disease）は、末期腎不全、心血管疾患のリスク因子であり、日本では成人の約１３％、１，３３０万人がＣＫＤ患者と言われている。そのため、腎機能を維持・改善できるような技術が切望されている。例えば、国際公開２０１７／００２８９５号には、アミノ酸と環状ジペプチドを含むアンジオテンシン変換酵素阻害活性を有する組成物が提案され、腎機能保護作用を有するとされている。また特開２００２－２７５０５９号公報には、特定のアミノ酸を含む腎機能障害改善用アミノ酸組成物が提案されている。 Chronic kidney disease (CKD), which is a finding of decreased renal function and renal damage, is a risk factor for end-stage renal disease and cardiovascular disease. In Japan, about 13% of adults, 13.3 million people. Is said to be a CKD patient. Therefore, there is an urgent need for technology that can maintain and improve renal function. For example, International Publication No. 2017/002895 proposes a composition having angiotensin converting enzyme inhibitory activity containing an amino acid and a cyclic dipeptide, and is said to have a renal function protecting action. Further, Japanese Patent Application Laid-Open No. 2002-275059 proposes an amino acid composition for improving renal dysfunction containing a specific amino acid.
　本発明は、腎機能を改善する組成物を提供することを目的とする。 An object of the present invention is to provide a composition for improving renal function.
　本発明は、グリシン及びトリプトファンを含み、トリプトファンに対するグリシンの含有比が質量基準で１０を超えて６０未満である腎機能改善用組成物を提供する。 The present invention provides a composition for improving renal function, which comprises glycine and tryptophan, and the content ratio of glycine to tryptophan is more than 10 and less than 60 on a mass basis.
　ある一形態において、前記組成物はグリシンの摂取量が１回当たり１ｇ以上１０ｇ以下である。 In one form, the composition has an intake of glycine of 1 g or more and 10 g or less at one time.
　また本発明は、前記組成物を含む腎機能改善用飲食物を提供する。 The present invention also provides a food or drink for improving renal function containing the above composition.
　また本発明は、前記組成物を含む腎機能改善用剤を提供する。 The present invention also provides an agent for improving renal function containing the above composition.
　さらに本発明は、グリシンとトリプトファンを含み、トリプトファンに対するグリシンの含有比が質量基準で１０を超えて６０未満である腎機能改善用組成物を対象に投与することを含む腎機能の維持方法及び腎機能の改善方法を提供する。 Further, the present invention is a method for maintaining renal function and a method for maintaining renal function, which comprises administering a composition for improving renal function, which comprises glycine and tryptophan, and the content ratio of glycine to tryptophan is more than 10 and less than 60 on a mass basis. Provide a method for improving the function.
　本発明によれば、腎機能を改善する組成物を提供することができる。 According to the present invention, it is possible to provide a composition for improving renal function.
　本明細書において組成物中の各成分の含有量は、組成物中に各成分に該当する物質が複数存在する場合、特に断らない限り、組成物中に存在する当該複数の物質の合計量を意味する。 In the present specification, the content of each component in the composition is the total amount of the plurality of substances present in the composition unless otherwise specified, when a plurality of substances corresponding to each component are present in the composition. means.
＜腎機能改善用組成物＞
　腎機能改善用組成物（以下、単に「組成物」ともいう）は、グリシンとトリプトファンとを有効成分として含み、必要に応じて他の成分をさらに含んでいてもよい。腎機能改善用組成物は、トリプトファンに対するグリシンの含有比が質量基準で１０を超えて６０未満である。グリシン及びトリプトファンのいずれも腎機能に対する作用は知られていない。しかしながら、グリシンとトリプトファンを特定の質量比率で組み合わせて摂取することにより、動物における腎機能を維持・改善することができる。 <Composition for improving renal function>
The composition for improving renal function (hereinafter, also simply referred to as “composition”) contains glycine and tryptophan as active ingredients, and may further contain other components if necessary. The composition for improving renal function has a content ratio of glycine to tryptophan of more than 10 and less than 60 on a mass basis. Neither glycine nor tryptophan is known to have any effect on renal function. However, renal function in animals can be maintained and improved by ingesting a combination of glycine and tryptophan in a specific mass ratio.
　本明細書における腎機能の維持・改善とは、腎機能を正常に維持すること及び低下した腎機能を改善することの少なくとも一方を含み、例えば、腎機能を評価する指標を正常な状態に維持すること、何らかの要因で悪化した腎機能を評価する指標を健康な状態に近づけるよう改善すること等を意味する。腎機能を評価する指標としては、例えば、糸球体濾過量（ＧＦＲ：glomerular filtration rate）、尿タンパク量、尿アルブミン量、血清クレアチニン濃度、血清シスタチンＣ濃度等が挙げられる。腎機能の維持・改善する作用は、腎機能を評価する指標について、投与群と対照群とを比較することで確認することができる。また、腎機能を評価する指標の悪化させる要因としては、例えば、加齢、飲酒、喫煙等の生活習慣、糖尿病、高血圧等の疾患、機能障害等が挙げられる。 The maintenance / improvement of renal function in the present specification includes at least one of maintaining normal renal function and improving decreased renal function, and for example, maintaining an index for evaluating renal function in a normal state. It means to improve the index for evaluating renal function that has deteriorated due to some factor so that it approaches a healthy state. Examples of the index for evaluating renal function include glomerular filtration rate (GFR), urinary protein amount, urinary albumin amount, serum creatinine concentration, serum cystatin C concentration and the like. The effect of maintaining / improving renal function can be confirmed by comparing the administration group and the control group with respect to the index for evaluating renal function. In addition, factors that worsen the index for evaluating renal function include, for example, lifestyle-related diseases such as aging, drinking and smoking, diseases such as diabetes and hypertension, and dysfunction.
　したがって、腎機能改善用組成物は、ＧＦＲ、尿タンパク量、尿アルブミン量、血清クレアチニン濃度及び血清シスタチンＣ濃度からなる群から選択される少なくとも１種の腎機能を評価する指標の維持・改善剤であってよい。 Therefore, the composition for improving renal function is an agent for maintaining / improving at least one index for evaluating renal function selected from the group consisting of GFR, urinary protein amount, urinary albumin amount, serum creatinine concentration and serum cystatin C concentration. May be.
　腎機能を評価する指標のうちＧＦＲは、腎障害を示唆する所見（検尿異常、画像異常、血液異常、病理所見など）とともにＣＫＤの診断に用いられる重要な指標である。ＧＦＲは日常診療においては、血清クレアチンの測定値から算出される推算ＧＦＲ（ｅＧＦＲ）として評価されることが一般的である。血清クレアチンは筋肉量、性別、年齢等に影響を受けることが知られており、これらを考慮した推算式でｅＧＦＲが算出される。ここで、本実施形態に係る腎機能改善用組成物はグリシンを有効成分の１つとして含むものである。グリシンは生体内においてクレアチンに変換されることが知られている（例えば、J. Anim. Sci. 1991. 69:1532-1550．参照）。そのため、本実施形態に係る腎機能改善用組成物の摂取によって血清クレアチン濃度が影響を受け、その結果ＧＦＲの評価が影響を受けることが予想される。一方、新たなＧＦＲマーカーとして血清シスタチンＣが注目されている。血清シスタチンＣ値は筋肉量、食事、運動等の影響を受けにくいため、血清クレアチン値によるＧＦＲ推算式では評価が困難な場合に有用であるとされている（例えば、ＣＫＤ診療ガイド２０１２参照）。そこで本明細書においては、血清シスタチンＣ濃度に基づいてｅＧＦＲを算出し、腎機能を評価することとする。したがって、腎機能改善用組成物は、ＧＦＲの維持・改善剤、ｅＧＦＲの維持・改善剤、又は血清シスタチンＣ濃度に基づくｅＧＦＲの維持・改善剤であってもよい。 Among the indexes for evaluating renal function, GFR is an important index used for diagnosis of CKD together with findings suggestive of renal disorders (urinalysis abnormalities, imaging abnormalities, blood abnormalities, pathological findings, etc.). In daily practice, GFR is generally evaluated as an estimated GFR (eGFR) calculated from the measured value of serum creatine. Serum creatine is known to be affected by muscle mass, gender, age, etc., and eGFR is calculated by an estimation formula that takes these into consideration. Here, the composition for improving renal function according to the present embodiment contains glycine as one of the active ingredients. Glycine is known to be converted to creatine in vivo (see, for example, J. Anim. Sci. 1991. 69: 1532-1550.). Therefore, it is expected that the intake of the composition for improving renal function according to the present embodiment will affect the serum creatine concentration, and as a result, the evaluation of GFR will be affected. On the other hand, serum cystatin C is drawing attention as a new GFR marker. Since the serum cystatin C value is not easily affected by muscle mass, diet, exercise, etc., it is said to be useful when it is difficult to evaluate by the GFR estimation formula based on the serum creatine level (see, for example, CKD Medical Treatment Guide 2012). Therefore, in the present specification, eGFR is calculated based on the serum cystatin C concentration to evaluate renal function. Therefore, the composition for improving renal function may be a GFR maintenance / improvement agent, an eGFR maintenance / improvement agent, or an eGFR maintenance / improvement agent based on the serum cystatin C concentration.
　組成物に含まれるグリシンは、アミノ酢酸のことで、アミノ酸の中で最も単純な構造を有している。グリシンの純度は動物の摂取に適するものであればよく、その純度は例えば９０％以上、好ましくは９８％以上である。グリシンは、例えば抽出法、微生物発酵法等により製造することができ、市販品から適宜選択されてもよい。 Glycine contained in the composition is aminoacetic acid and has the simplest structure among amino acids. The purity of glycine may be any one suitable for ingestion by animals, and the purity is, for example, 90% or more, preferably 98% or more. Glycine can be produced by, for example, an extraction method, a microbial fermentation method, or the like, and may be appropriately selected from commercially available products.
　トリプトファンは、２－アミノ－３－インドリルプロピオン酸のことであり、少なくともＬ－トリプトファンを含んでいればよい。トリプトファンは、ラセミ体であってもよいが、Ｌ－トリプトファンであることが好ましい。トリプトファンの純度は動物の摂取に適するものであればよく、その純度は例えば９０％以上、好ましくは９８％以上である。トリプトファンは、例えば抽出法、微生物発酵法等により製造することができ、市販品から適宜選択されてもよい。 Tryptophan is 2-amino-3-indrill propionic acid and may contain at least L-tryptophan. The tryptophan may be racemic, but is preferably L-tryptophan. The purity of tryptophan may be as long as it is suitable for ingestion by animals, and the purity is, for example, 90% or more, preferably 98% or more. Tryptophan can be produced by, for example, an extraction method, a microbial fermentation method, or the like, and may be appropriately selected from commercially available products.
　グリシン及びトリプトファンは単体（遊離体）として含まれていてもよく、塩の形態で含まれていてもよい。グリシン及びトリプトファンの塩としては薬理学的に許容される塩であれば特に制限はない。具体的には例えば、酸付加塩、金属塩、アンモニウム塩、有機アミン付加塩等が挙げられる。酸付加塩としては、塩酸塩、硫酸塩、硝酸塩、リン酸塩等の無機酸塩、酢酸塩、マレイン酸塩、フマル酸塩、クエン酸塩、リンゴ酸塩、乳酸塩、α－ケトグルタル酸塩、グルコン酸塩、カプリル酸塩等の有機酸塩が挙げられる。金属塩としては、ナトリウム塩、カリウム塩等のアルカリ金属塩、マグネシウム塩、カルシウム塩等のアルカリ土類金属塩、アルミニウム塩、亜鉛塩等が挙げられる。アンモニウム塩としては、アンモニウム、テトラメチルアンモニウム等の塩が挙げられる。有機アミン付加塩としては、モルホリン、ピペリジン等の塩が挙げられる。 Glycine and tryptophan may be contained as a simple substance (free form) or may be contained in the form of a salt. The salt of glycine and tryptophan is not particularly limited as long as it is a pharmacologically acceptable salt. Specific examples thereof include acid addition salts, metal salts, ammonium salts and organic amine addition salts. Acid addition salts include inorganic acid salts such as hydrochlorides, sulfates, nitrates and phosphates, acetates, maleates, fumarates, citrates, malates, lactates and α-ketoglutarates. , Gluconate, organic acid salts such as caprylate, and the like. Examples of the metal salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt, zinc salt and the like. Examples of the ammonium salt include salts such as ammonium and tetramethylammonium. Examples of the organic amine addition salt include salts such as morpholine and piperidine.
　組成物中のトリプトファンに対するグリシンの質量基準の含有比は、腎機能改善作用の観点から、例えば１０を超えて６０未満であり、好ましくは１２以上４５以下、より好ましくは１３以上４０以下、さらに好ましくは１４以上３５以下である。トリプトファンに対するグリシンの質量基準の含有比は、例えば１０を超えていてよく、好ましくは１２以上、１３以上又は１４以上である。また、トリプトファンに対するグリシンの質量基準の含有比は、例えば６０未満であってよく、好ましくは、４５以下、４０以下又は３５以下である。 The mass-based content ratio of glycine to tryptophan in the composition is, for example, more than 10 and less than 60, preferably 12 or more and 45 or less, more preferably 13 or more and 40 or less, still more preferably, from the viewpoint of renal function improving action. Is 14 or more and 35 or less. The mass-based content ratio of glycine to tryptophan may be, for example, greater than 10, preferably 12 or greater, 13 or greater, or 14 or greater. The mass-based content ratio of glycine to tryptophan may be, for example, less than 60, preferably 45 or less, 40 or less, or 35 or less.
　組成物は、グリシン及びトリプトファンに加えて他の有効成分を更に含んでいてもよい。他の有効成分は腎機能を維持・改善する作用を有するものであればよい。他の有効成分としては、例えば、アラニン、アルギニン、アスパラギン、アスパラギン酸、システイン、グルタミン、グルタミン酸、ヒスチジン、イソロイシン、ロイシン、リジン、メチオニン、フェニルアラニン、プロリン、セリン、トレオニン、チロシン、バリン、オルニチン、シトルリンなどの他のアミノ酸が挙げられる。他の有効成分は、これらの他のアミノ酸からなる群から選択される少なくとも１種であってよい。他のアミノ酸のなかでも、アスパラギン酸、アスパラギン、グルタミン酸及びグルタミンからなる群から選択される少なくとも１種が好ましく、アスパラギン、グルタミン酸及びグルタミンからなる群から選択される少なくとも１種がより好ましく、アスパラギン及びグルタミン酸からなる群から選択される少なくとも１種が更に好ましい。他のアミノ酸は１種でもよく、２種以上の組み合わせであってもよい。 The composition may further contain other active ingredients in addition to glycine and tryptophan. The other active ingredient may have an effect of maintaining / improving renal function. Other active ingredients include, for example, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, valine, ornithine, citrulline and the like. Other amino acids can be mentioned. The other active ingredient may be at least one selected from the group consisting of these other amino acids. Among other amino acids, at least one selected from the group consisting of aspartic acid, aspartic acid, glutamic acid and glutamine is preferable, and at least one selected from the group consisting of aspartic acid, glutamic acid and glutamine is more preferable, and aspartic acid and glutamic acid. At least one selected from the group consisting of is more preferred. The other amino acids may be one kind or a combination of two or more kinds.
　組成物は、グリシンとトリプトファン以外の他の有効成分を実質的に含まないものであってよい。他の有効成分を実質的に含まないとは、他の有効成分の含有量が、腎機能を維持・改善する作用を示す量未満であることを意味する。具体的には、他の有効成分の含有量が、例えば、グリシンに対して１０質量％未満、１質量％未満、０．１質量％未満、又は０．０１質量％未満であることを意味する。 The composition may be substantially free of other active ingredients other than glycine and tryptophan. Substantially free of other active ingredients means that the content of other active ingredients is less than the amount exhibiting the effect of maintaining / improving renal function. Specifically, it means that the content of other active ingredients is, for example, less than 10% by mass, less than 1% by mass, less than 0.1% by mass, or less than 0.01% by mass with respect to glycine. ..
　組成物中の有効成分の総含有量は、組成物の構成、組成物の摂取により期待する効果等に応じて適宜選択すればよい。組成物中の有効成分の総含有量は例えば０．０００１質量％以上、好ましくは０．００１質量％以上、より好ましくは０．０１質量％以上、さらに好ましくは０．１質量％以上、特に好ましくは１質量％以上、または５質量％以上であり、また例えば１００質量％以下、好ましくは７０質量％以下、より好ましくは５０質量％以下、または３０質量％以下である。 The total content of the active ingredient in the composition may be appropriately selected according to the composition of the composition, the effect expected by ingestion of the composition, and the like. The total content of the active ingredient in the composition is, for example, 0.0001% by mass or more, preferably 0.001% by mass or more, more preferably 0.01% by mass or more, still more preferably 0.1% by mass or more, particularly preferably. Is 1% by mass or more, or 5% by mass or more, and is, for example, 100% by mass or less, preferably 70% by mass or less, more preferably 50% by mass or less, or 30% by mass or less.
　組成物は、必要に応じて有効成分以外のその他の成分を更に含んでいてもよい。その他の成分としては、水等の溶媒；ビタミンＢ群等を含む各種ビタミン類；甘味料；香料；着色料；薬理学的に許容される担体、賦形剤、希釈剤、塩類、ｐＨ調整剤、キレート剤、緩衝剤等を挙げることができる。 The composition may further contain other ingredients other than the active ingredient, if necessary. Other components include solvents such as water; various vitamins including B vitamins; sweeteners; fragrances; colorants; pharmacologically acceptable carriers, excipients, diluents, salts, pH adjusters. , Chelating agent, buffering agent and the like.
　組成物は、散剤、顆粒剤、錠剤、カプセル剤、トローチ剤、シロップ剤、液剤、注射剤等のいずれの剤形であってもよい。摂取方法は、組成物の剤形等に応じて通常用いられる摂取経路から選択すればよい。摂取経路としては例えば、経口投与、経鼻投与、直腸投与、静脈注射、点滴等を挙げることができる。 The composition may be in any dosage form such as powder, granule, tablet, capsule, troche, syrup, liquid, injection or the like. The ingestion method may be selected from the ingestion routes usually used according to the dosage form of the composition and the like. Examples of the ingestion route include oral administration, nasal administration, rectal administration, intravenous injection, and infusion.
　組成物の摂取量は、腎機能を維持・改善する作用を発揮可能な量であればよく、通常１回につきグリシンの摂取量として例えば１ｇ以上、好ましくは２ｇ以上、より好ましくは３ｇ以上、さらに好ましくは５ｇ以上であってよく、また例えば１０ｇ以下、好ましくは８ｇ以下、より好ましくは７ｇ以下であってよい。また通常１回につきトリプトファンの摂取量として例えば０．０１ｇ以上、好ましくは０．１ｇ以上、より好ましくは０．１５ｇ以上であってよく、また例えば１．０ｇ以下、好ましくは０．６ｇ以下、より好ましくは０．５ｇ以下、さらに好ましくは０．４ｇ以下であってよい。また１日当たりの摂取回数は、例えば１回から３回であってよい。組成物の摂取量は、例えば体重６０ｋｇあたりの摂取量であってよく、摂取対象の体重等に応じて適宜変更してよい。 The intake amount of the composition may be an amount capable of exerting an action of maintaining / improving renal function, and usually, the intake amount of glycine at one time is, for example, 1 g or more, preferably 2 g or more, more preferably 3 g or more, and further. It may be preferably 5 g or more, and may be, for example, 10 g or less, preferably 8 g or less, and more preferably 7 g or less. In addition, the amount of tryptophan ingested at one time may be, for example, 0.01 g or more, preferably 0.1 g or more, more preferably 0.15 g or more, and for example, 1.0 g or less, preferably 0.6 g or less. It may be preferably 0.5 g or less, more preferably 0.4 g or less. The number of intakes per day may be, for example, 1 to 3 times. The intake amount of the composition may be, for example, the intake amount per 60 kg of body weight, and may be appropriately changed according to the body weight of the intake target and the like.
　組成物は、腎機能改善作用によって病態が改善される疾患の予防及び／又は治療用として用いることができる。すなわち、腎機能改善用組成物は、腎機能改善に適用される医薬組成物であってよい。かかる疾患としては、例えば、ＣＫＤ、糖尿病性腎症、腎硬化症、急性腎炎などが挙げられる。組成物は上記疾患の発症を抑制する予防薬として、及び／又は、正常な状態に改善する治療薬としても機能し得る。また、組成物は、腎機能低下の予防用、抑制用等として用いることができる。ここで腎機能低下には、加齢、生活習慣、疾患、機能障害等に起因するものが含まれる。 The composition can be used for the prevention and / or treatment of diseases in which the pathological condition is improved by the renal function improving action. That is, the composition for improving renal function may be a pharmaceutical composition applied to improve renal function. Examples of such diseases include CKD, diabetic nephropathy, nephrosclerosis, acute nephritis and the like. The composition can also function as a prophylactic agent that suppresses the onset of the above diseases and / or as a therapeutic agent that improves the normal state. In addition, the composition can be used for prevention, suppression, etc. of renal function decline. Here, renal dysfunction includes those caused by aging, lifestyle, diseases, dysfunction and the like.
　組成物の摂取対象は、腎機能を有する脊椎動物であればよく、経口又は非経口的に安全に摂取することができる。組成物の摂取対象は、例えば、ヒト、マウス、ラット、ウサギ、イヌ、ネコ等の哺乳動物であってよい。組成物の摂取対象はヒトであってよく、非ヒト動物であってもよい。例えば、非ヒト動物であるネコ科動物においては、その疾患、死亡等の原因としてＣＫＤ等が高頻度で認められる。したがって、組成物はネコ科動物の腎機能改善用として好適に用いられる。また、組成物は健康なヒトにおける腎機能を評価する指標の改善用途に適用することができる。対象となる健康なヒトには、例えば、尿蛋白及び尿アルブミンが正常値であって、ＧＦＲが９０ｍＬ／分／１．７３ｍ２以上又は６０ｍＬ／分／１．７３ｍ２以上であるヒトが含まれる（例えば、一般社団法人日本腎臓学会（編）、「エビデンスに基づくＣＫＤ診療ガイドライン２０１８」、株式会社東京医学社、２０１８年６月、３頁参照）。 The ingestion target of the composition may be any vertebrate having renal function, and can be safely ingested orally or parenterally. The ingestion target of the composition may be, for example, a mammal such as a human, a mouse, a rat, a rabbit, a dog, or a cat. The ingestion target of the composition may be a human or a non-human animal. For example, in cats, which are non-human animals, CKD and the like are frequently observed as causes of the disease, death, and the like. Therefore, the composition is suitably used for improving renal function in felines. The composition can also be applied to improve indicators for assessing renal function in healthy humans. Target healthy humans include, for example, humans with normal levels of urinary protein and urinary albumin and a GFR of 90 mL / min / 1.73 m 2 or higher or 60 mL / min / 1.73 m 2 or higher. (For example, see Japan Nephrology Society (eds.), "Evidence-based CKD Practice Guidelines 2018", Tokyo Medical Co., Ltd., June 2018, page 3).
　組成物を疾患の予防及び／又は治療用医薬として用いる場合、組成物の摂取量は、疾患の種類、摂取対象の年齢、性別、体重、症状の程度、又は摂取方法などに応じて適宜決定することができる。例えば、投与対象に経口摂取する場合には、ヒト成人一日当り、グリシン及びトリプトファンの合計として通常は１ｇ以上、好ましくは３ｇ以上、より好ましくは５ｇ以上、また例えば１０ｇ以下、好ましくは８ｇ以下、より好ましくは７ｇ以下となるように一日一回ないし数回摂取してよい。摂取期間は、例えば１日以上、好ましくは１週間以上、より好ましくは１ヶ月間以上であってよい。また、摂取期間は、例えば１年間以下、好ましくは３ヶ月間以下であってよい。なお、組成物を疾患の予防として用いる場合、摂取期間は特に限られなくてもよい。 When the composition is used as a preventive and / or therapeutic drug for a disease, the amount of the composition to be ingested is appropriately determined according to the type of the disease, the age, sex, body weight, degree of symptoms, the method of ingestion, and the like. be able to. For example, when ingested orally to a human adult, the total amount of glycine and tryptophan per day is usually 1 g or more, preferably 3 g or more, more preferably 5 g or more, and for example, 10 g or less, preferably 8 g or less. It may be taken once or several times a day, preferably to be 7 g or less. The ingestion period may be, for example, one day or longer, preferably one week or longer, and more preferably one month or longer. The ingestion period may be, for example, one year or less, preferably three months or less. When the composition is used for the prevention of diseases, the ingestion period may not be particularly limited.
　組成物を、腎機能低下の予防用、抑制用等として摂取する場合、組成物の摂取量は、摂取対象の年齢、性別、体重、又は摂取方法などに応じて適宜決定することができる。例えば、投与対象に経口投与する場合には、ヒト成人一日当り、グリシン及びトリプトファンの合計として通常は１ｇ以上、好ましくは３ｇ以上、より好ましくは５ｇ以上、また例えば１０ｇ以下、好ましくは８ｇ以下、より好ましくは７ｇ以下となるように一日一回ないし数回摂取してよい。摂取期間は、例えば１日間以上、好ましくは１週間以上である。また、摂取期間は、例えば１年間以下、好ましくは３ヶ月間以下であってよい。なお、組成物を腎機能低下の予防用として摂取する場合、摂取期間は特に限られなくてもよい。 When the composition is ingested for prevention, suppression, etc. of renal dysfunction, the amount of the composition to be ingested can be appropriately determined according to the age, sex, body weight, ingestion method, and the like of the ingestion target. For example, when orally administered to a human adult, the total amount of glycine and tryptophan per day is usually 1 g or more, preferably 3 g or more, more preferably 5 g or more, and for example, 10 g or less, preferably 8 g or less. It may be taken once or several times a day, preferably to be 7 g or less. The ingestion period is, for example, one day or longer, preferably one week or longer. The ingestion period may be, for example, one year or less, preferably three months or less. When the composition is ingested for the prevention of renal dysfunction, the ingestion period may not be particularly limited.
飲食品
　飲食品は、上述したグリシン及びトリプトファンを含む腎機能改善用の組成物を含む。飲食品を摂取することで、上述した組成物の効果を得ることができる。本発明の腎機能改善用組成物を含有する飲食品には、健康飲食品、機能性飲食品、病者用飲食品などの他、上記腎機能改善用組成物を配合できる全ての飲食品が含まれる。なかでも、機能性飲食品はとりわけ好ましい。「機能性飲食品」は、生体に対して一定の機能性を有する飲食品を意味し、例えば、特定保健用飲食品（条件付きトクホ[特定保健用食品]を含む）及び栄養機能飲食品を含む保健機能飲食品、特別用途飲食品、栄養補助飲食品、健康補助飲食品、サプリメント（例えば、錠剤、被覆錠、糖衣錠、カプセル及び液剤などの各種剤形のもの）及び美容飲食品（例えばダイエット飲食品）などのいわゆる健康飲食品全般を包含する。機能性飲食品はまた、コーデックス（FAO/WHO合同食品規格委員会）の食品規格に基づく健康強調表示（Health claim）が適用される健康飲食品を包含する。 Food and beverage The food and drink contains the above-mentioned composition for improving renal function containing glycine and tryptophan. By ingesting food and drink, the effects of the above-mentioned composition can be obtained. The foods and drinks containing the composition for improving renal function of the present invention include healthy foods and drinks, functional foods and drinks, foods and drinks for the sick, and all foods and drinks to which the above composition for improving renal function can be blended. included. Of these, functional foods and drinks are particularly preferable. "Functional food and drink" means food and drink having a certain functionality with respect to the living body, for example, food and drink for specified health use (including conditional diet [food for specified health use]) and nutritional functional food and drink. Health functional foods and drinks, special purpose foods and drinks, nutritional supplement foods and drinks, health supplement foods and drinks, supplements (for example, various dosage forms such as tablets, coated tablets, sugar-coated tablets, capsules and liquids) and beauty foods and drinks (eg diet) It includes all so-called healthy foods and drinks such as foods and drinks. Functional foods and drinks also include healthy foods and drinks to which a Health claim based on the Codex (FAO / WHO Joint Food and Agriculture Organization) food standards applies.
　上記健康食品等は、通常の食品の形状であってもよく、サプリメントの形状（錠剤、顆粒剤（例えば、スティック状に梱包された顆粒剤）、細粒剤、タブレット、チュアブルタブレット、カプセル（軟カプセル、硬カプセル）など）であってもよい。 The above-mentioned health foods and the like may be in the shape of ordinary foods, and may be in the form of supplements (tablets, granules (for example, granules packed in sticks), fine granules, tablets, chewable tablets, capsules (soft). Capsules, hard capsules), etc.) may be used.
　飲食品は流動性を有する飲料であってもよい。飲食品が飲料である場合、飲料中のグリシン濃度は例えば、０．１ｇ／１００ｍｌ以上、好ましくは０．１５ｇ／１００ｍｌ以上、より好ましくは０．２ｇ／１００ｍｌ以上、さらに好ましくは０．３ｇ／１００ｍｌ以上、特に好ましくは０．６ｇ／１００ｍｌ以上であってよく、また例えば１０ｇ／１００ｍｌ以下、好ましくは８ｇ／１００ｍｌ以下、より好ましくは７ｇ／１００ｍｌ以下であってよい。また飲料中のトリプトファン濃度は例えば、０．００１ｇ／１００ｍｌ以上、好ましくは０．００５ｇ／１００ｍｌ以上、より好ましくは０．０２ｇ／１００ｍｌ以上であってよく、また例えば１．０ｇ／１００ｍｌ以下、好ましくは０．６ｇ／１００ｍｌ以下、より好ましくは０．４ｇ／１００ｍｌ以下であってよい。 The food and drink may be a liquid beverage. When the food or drink is a beverage, the glycine concentration in the beverage is, for example, 0.1 g / 100 ml or more, preferably 0.15 g / 100 ml or more, more preferably 0.2 g / 100 ml or more, still more preferably 0.3 g / 100 ml. As mentioned above, it may be particularly preferably 0.6 g / 100 ml or more, and for example, it may be 10 g / 100 ml or less, preferably 8 g / 100 ml or less, and more preferably 7 g / 100 ml or less. The tryptophan concentration in the beverage may be, for example, 0.001 g / 100 ml or more, preferably 0.005 g / 100 ml or more, more preferably 0.02 g / 100 ml or more, and for example, 1.0 g / 100 ml or less, preferably 1.0 g / 100 ml or more. It may be 0.6 g / 100 ml or less, more preferably 0.4 g / 100 ml or less.
　飲料は例えば、グリシン及びトリプトファンを含む組成物と、水、果汁等の液媒体とを含んで構成される。飲料は例えば、緑茶、ウーロン茶及び紅茶などの茶飲料、清涼飲料、ゼリー飲料、スポーツ飲料、乳飲料、炭酸飲料、野菜飲料、果汁飲料、醗酵野菜飲料、醗酵果汁飲料、発酵乳飲料（ヨーグルトなど）、乳酸菌飲料、乳飲料（コーヒー牛乳、フルーツ牛乳など）、粉末飲料、ココア飲料、アルコール飲料などであってよく、組成物を含み、牛乳、精製水などを液媒体とする飲料であってもよい。 Beverages are composed of, for example, a composition containing glycine and tryptophan, and a liquid medium such as water or fruit juice. Beverages include, for example, tea beverages such as green tea, oolong tea and tea, soft beverages, jelly beverages, sports beverages, milk beverages, carbonated beverages, vegetable beverages, fruit juice beverages, fermented vegetable beverages, fermented fruit juice beverages, fermented milk beverages (yogurt, etc.) , Lactobacillus beverages, milk beverages (coffee milk, fruit milk, etc.), powdered beverages, cocoa beverages, alcoholic beverages, etc., and may be beverages containing a composition and using milk, purified water, etc. as a liquid medium. ..
　飲料は、甘みを調整するために、甘味料を含有していてもよい。甘味料は糖であってもよく、糖としては、砂糖、葡萄糖、果糖、フラクトオリゴ糖、ガラクトオリゴ糖等が挙げられる。あるいは、糖の代わりに、アスパルテーム、サッカリン等の合成甘味料が添加されていてもよい。 Beverages may contain sweeteners to adjust the sweetness. The sweetener may be sugar, and examples of the sugar include sugar, glucose, fructose, fructooligosaccharide, galactooligosaccharide and the like. Alternatively, instead of sugar, synthetic sweeteners such as aspartame and saccharin may be added.
　飲料は酸味料を含有していてもよい。酸味料としては、例えば、クエン酸、ＤＬ－リンゴ酸、Ｌ－酒石酸、乳酸、リン酸等が挙げられる。 Beverages may contain acidulants. Examples of the acidulant include citric acid, DL-malic acid, L-tartaric acid, lactic acid, phosphoric acid and the like.
　飲料は香料を含有していてもよい。香料としては、例えば、レモン、ライム、オレンジ等のシトラス油、オレンジ油、ハーブエキス等が挙げられる。香料は天然香料であっても、合成香料であってもよい。天然香料としては、例えば、アニス油、アンゲリカ油、オールスパイス油、オレンジ油、カシア油、カプシカム油、ガラナエキス、カルダモン油、キャラウェイ油、クミン油、クラリセージ油、グレープフルーツ油、クローブ油、コリアンダー油、コーヒー油、コニャック油、コーラナッツエキス、シナモン油、ジンジャー油、タイム油、ナツメグ油、ハッカ油、バニラエキス、ビターアーモンド油、フェヌグリーク油、フェンネル油、ペッパー油、ペパーミント油、ペリラ油、ベルガモット油、マンダリン油、ユーカリ油、レモン油、ローズマリー油等が挙げられる。 Beverages may contain flavors. Examples of the fragrance include citrus oils such as lemon, lime and orange, orange oil, herbal extracts and the like. The fragrance may be a natural fragrance or a synthetic fragrance. Natural fragrances include, for example, anis oil, angelica oil, all-spices oil, orange oil, cassia oil, capsicum oil, galana extract, cardamon oil, caraway oil, cumin oil, clarisage oil, grapefruit oil, clove oil, coriander oil. , Coffee oil, cognac oil, cola nut extract, cinnamon oil, ginger oil, thyme oil, nutmeg oil, peppermint oil, vanilla extract, bitter almond oil, phenuglique oil, fennel oil, pepper oil, peppermint oil, perilla oil, bergamot oil , Mandarin oil, eucalyptus oil, lemon oil, rosemary oil and the like.
　合成香料としては、例えば、アネトール、アリルカプロエート、イソアミルアセテート、γ－ウンデカラクトン、エチルバニリン、エチルブチレート、エチルフェニルグリシデート、オイゲノール、ゲラニオール、ジアセチル、シクロテン、シトラール、シンナミックアルデヒド、ターピネオール、δ－デカラクトン、デカナール、ノナナール、γ―ノナラクトン、バニリン、フェニルエチルアルコール、フラネオール、フルフリルメルカプタン、２－ヘキセナール、３－ヘキセノール、ヘリオトロピン、ペリラアルデヒド、ベンズアルデヒド、マルトール、メチルアンスラニレート、メチルサリシレート、メントール、α－ヨノン、リナロール等が挙げられる。 Synthetic fragrances include, for example, anetol, allyl caproate, isoamyl acetate, γ-undecalactone, ethylvanillin, ethyl butyrate, ethylphenylglycidate, eugenol, geraniol, diacetyl, cycloten, citral, synamic aldehyde, turpineol. , Δ-decalactone, decanal, nonanal, γ-nonalactone, vanillin, phenylethyl alcohol, flaneol, furfuryl mercaptan, 2-hexenal, 3-hexenol, heliotropin, perillaaldehyde, benzaldehyde, maltor, methylanthranilate, methylsalicylate , Mentor, α-yonon, linalol and the like.
　本発明は別の態様として、グリシンとトリプトファンを含む腎機能改善用組成物を対象に投与することを含む腎機能の維持方法及び腎機能の改善方法を包含する。また、本発明は別の態様として、腎機能の維持方法又は腎機能の改善方法に用いられる組成物の製造における腎機能改善用組成物の使用、腎機能の維持方法又は腎機能の改善方法における腎機能改善用組成物の使用、腎機能の維持方法又は腎機能の改善方法に使用される腎機能改善用組成物をも包含する。 As another aspect, the present invention includes a method for maintaining renal function and a method for improving renal function, which comprises administering a composition for improving renal function containing glycine and tryptophan to a subject. In addition, another aspect of the present invention is the use of a composition for improving renal function in the production of a composition used for a method for maintaining renal function or a method for improving renal function, a method for maintaining renal function, or a method for improving renal function. It also includes the use of the composition for improving renal function, the composition for improving renal function used in the method for maintaining renal function or the method for improving renal function.
　以下、本発明を実施例により具体的に説明するが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.
（実施例１）
　健康な成人男女３１名を被験者として、書面でのインフォームドコンセントに同意を得た後に試験を実施した。対照としてのデキストリン５．２ｇ（Ｃｏｎｔ）、又はグリシン３．０ｇとトリプトファン０．２ｇとデキストリン２．０ｇを含む組成物（ＧｌｙＴｒｐ）をそれぞれ、試験品として６週間に渡って毎日１回、経口により摂取させた。試験品の摂取前と６週間後に採血して、血清シスタチンＣ濃度を測定し、それに基づいて算出式によりｅＧＦＲを算出した。表１にｅＧＦＲの平均値と標準偏差（括弧内）を示す。表１には併せて経時変化の有意差と、対象群との有意差についてのｔ検定の結果を示す。 (Example 1)
The study was conducted on 31 healthy adult men and women after obtaining written consent for informed consent. A control containing 5.2 g of dextrin (Cont) or a composition containing 3.0 g of glycine, 0.2 g of tryptophan and 2.0 g of dextrin (GlyTrp) was orally administered once daily for 6 weeks as a test product. Ingested. Blood was collected before and 6 weeks after ingestion of the test product, the serum cystatin C concentration was measured, and eGFR was calculated by a calculation formula based on the measurement. Table 1 shows the mean value and standard deviation of eGFR (in parentheses). Table 1 also shows the results of the t-test regarding the significant difference in changes over time and the significant difference from the target group.
　　ｅＧＦＲ＝（１０４×シスタチンＣ－１．０１９×０．９９６年齢）－８ eGFR = (104 x Cystatin C- 1.019 x 0.996 age ) -8
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　対照群では血清シスタチンＣ濃度が上昇したが、グリシンとトリプトファンを含む組成物を投与した群においては血清シスタチンＣ濃度の低下が認められた。算出式を用いてｅＧＦＲを算出した表１から、グリシンとトリプトファンを含む組成物を投与した群においては、経時的に有意にｅＧＦＲが上昇し、また対照群に比べてｅＧＦＲの有意な上昇が認められた。特に、ｅＧＦＲ値が９５未満の低い被験者１０名ではグリシンとトリプトファンを含む組成物を投与した群において、ｅＧＦＲが９０ｍＬ／分／１．７３ｍ２から９８ｍＬ／分／１．７３ｍ２となり、より顕著な上昇が見られた。これは、腎機能がより低下した対象ほどグリシンとトリプトファンを含む組成物の腎機能改善効果が期待できることを示している。 The serum cystatin C concentration increased in the control group, but decreased in the group to which the composition containing glycine and tryptophan was administered. From Table 1 in which eGFR was calculated using the calculation formula, the eGFR was significantly increased over time in the group to which the composition containing glycine and tryptophan was administered, and the eGFR was significantly increased as compared with the control group. Was done. In particular, in the group administered a composition comprising glycine and a tryptophan at low 10 subjects with eGFR value less than 95, 98 mL / min 1.73 m 2 next eGFR from 90 mL / min 1.73 m 2, more pronounced An increase was seen. This indicates that subjects with lower renal function can be expected to have an effect of improving renal function of the composition containing glycine and tryptophan.
（実施例２）
　健康な成人男性１６名を被験者として、書面でのインフォームドコンセントに同意を得た後に試験を実施した。対照としてのデキストリン６．４ｇ（対照群）を準備した。また試験品として、グリシン６．０ｇとデキストリン０．４ｇを含む組成物（Ｇｌｙ）、トリプトファン０．４ｇとデキストリン６．０ｇを含む組成物（Ｔｒｐ）、及びグリシン６．０ｇとトリプトファン０．４ｇを含む組成物（ＧｌｙＴｒｐ（６＋０．４））をそれぞれ準備した。各組成物をそれぞれ、試験品として経口により単回摂取させた。試験品の摂取前、摂取から１時間後、及び２時間後に採血して、血清シスタチンＣ濃度を測定し、それに基づいて上記算出式によりｅＧＦＲを算出した。表２にｅＧＦＲの平均値と標準偏差（括弧内）を示す。表２には併せて対象群との有意差についてのｔ検定の結果を示す。 (Example 2)
The study was conducted on 16 healthy adult male subjects after obtaining written consent for informed consent. As a control, 6.4 g of dextrin (control group) was prepared. Further, as test products, a composition containing 6.0 g of glycine and 0.4 g of dextrin (Gly), a composition containing 0.4 g of tryptophan and 6.0 g of dextrin (Trp), and 6.0 g of glycine and 0.4 g of tryptophan were used. Each containing composition (GlyTrp (6 + 0.4)) was prepared. Each composition was orally ingested as a single test product. Blood was collected before, 1 hour, and 2 hours after ingestion of the test product, the serum cystatin C concentration was measured, and eGFR was calculated by the above formula based on the blood sample. Table 2 shows the mean value and standard deviation of eGFR (in parentheses). Table 2 also shows the results of the t-test for the significant difference from the target group.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　表２から、対照群に比べて、グリシンとトリプトファンを含み、トリプトファンに対するグリシンの含有比（Ｇｌｙ／Ｔｒｐ）が１５である組成物（ＧｌｙＴｒｐ（６＋０．４））を摂取した群ではｅＧＦＲが有意に上昇した。一方、グリシンのみ（Ｇｌｙ）、又はトリプトファンのみ（Ｔｒｐ）を投与した場合には、対照群と比べてｅＧＦＲに有意差は認められなかった。 From Table 2, the eGFR was significantly higher in the group ingesting the composition (GlyTrp (6 + 0.4)) containing glycine and tryptophan and having a glycine content ratio (Gly / Trp) of 15 to tryptophan as compared with the control group. Rose. On the other hand, when glycine alone (Gly) or tryptophan alone (Trp) was administered, no significant difference was observed in eGFR as compared with the control group.
（実施例３）
　健康な成人男性６名を被験者として、書面でのインフォームドコンセントに同意を得た後に試験を実施した。対照としてのデキストリン６．４ｇ（対照群）を準備した。試験品として、グリシン６．０ｇとトリプトファン０．２ｇとデキストリン０．２ｇを含む組成物（ＧｌｙＴｒｐ（６＋０．２））、及びグリシン６．０ｇとトリプトファン０．１ｇとデキストリン０．３ｇを含む組成物（ＧｌｙＴｒｐ（６＋０．１））を準備したこと、採血を摂取から２時間後としたこと以外は、実施例２と同様にしてｅＧＦＲを算出して評価した。結果を表３に示す。 (Example 3)
The study was conducted on 6 healthy adult male subjects after obtaining written consent for informed consent. As a control, 6.4 g of dextrin (control group) was prepared. As test products, a composition containing 6.0 g of glycine, 0.2 g of tryptophan and 0.2 g of dextrin (GlyTrp (6 + 0.2)), and a composition containing 6.0 g of glycine, 0.1 g of tryptophan and 0.3 g of dextrin. The eGFR was calculated and evaluated in the same manner as in Example 2 except that (GlyTrp (6 + 0.1)) was prepared and blood was collected 2 hours after ingestion. The results are shown in Table 3.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
（実施例４）
　健康な成人男性９名を被験者として、書面でのインフォームドコンセントに同意を得た後に試験を実施した。対照としてのデキストリン６．４ｇ（対照群）を準備した。試験品として、グリシン２．０ｇとトリプトファン０．４ｇとデキストリン４．０ｇとを含む組成物（ＧｌｙＴｒｐ（２＋０．４））、グリシン３．０ｇとトリプトファン０．４ｇとデキストリン３．０ｇを含む組成物（ＧｌｙＴｒｐ（３＋０．４））、及びグリシン４．０ｇとトリプトファン０．４ｇとデキストリン２．０ｇを含む組成物（ＧｌｙＴｒｐ（４＋０．４））を準備したこと、採血を摂取から２時間後としたこと以外は、実施例２と同様にしてｅＧＦＲを算出して評価した。結果を表４に示す。 (Example 4)
Nine healthy adult male subjects were tested after obtaining written consent for informed consent. As a control, 6.4 g of dextrin (control group) was prepared. As a test product, a composition containing 2.0 g of glycine, 0.4 g of tryptophan and 4.0 g of dextrin (GlyTrp (2 + 0.4)), and a composition containing 3.0 g of glycine, 0.4 g of tryptophan and 3.0 g of dextrin. (GlyTrp (3 + 0.4)) and a composition containing 4.0 g of glycine, 0.4 g of tryptophan and 2.0 g of dextrin (GlyTrp (4 + 0.4)) were prepared, and blood collection was performed 2 hours after ingestion. Except for this, eGFR was calculated and evaluated in the same manner as in Example 2. The results are shown in Table 4.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
　表２から４に示されるように、グリシンとトリプトファンを含み、トリプトファンに対するグリシンの含有比が特定の範囲である組成物を摂取することで、ｅＧＦＲが有意に向上し、腎機能が改善される。 As shown in Tables 2 to 4, ingestion of a composition containing glycine and tryptophan and having a specific range of glycine content to tryptophan significantly improves eGFR and improves renal function.
　日本国特許出願２０１９－１７３１４９号（出願日：２０１９年９月２４日）、及び日本国特許出願２０２０－０７９５６６号（出願日：２０２０年４月２８日）の開示はその全体が参照により本明細書に取り込まれる。本明細書に記載された全ての文献、特許出願、及び技術規格は、個々の文献、特許出願、及び技術規格が参照により取り込まれることが具体的かつ個々に記された場合と同程度に、本明細書に参照により取り込まれる。 The disclosures of Japanese Patent Application No. 2019-173149 (Filing Date: September 24, 2019) and Japanese Patent Application No. 2020-079566 (Filing Date: April 28, 2020) are by reference in their entirety. Incorporated into the book. All documents, patent applications, and technical standards described herein are to the same extent as if the individual documents, patent applications, and technical standards were specifically and individually stated to be incorporated by reference. Incorporated herein by reference.

Claims (7)

  1. 　グリシン及びトリプトファンを含み、トリプトファンに対するグリシンの含有比が質量基準で１０を超えて６０未満である腎機能改善用組成物。 A composition for improving renal function containing glycine and tryptophan, and the content ratio of glycine to tryptophan is more than 10 and less than 60 on a mass basis.
  2. 　グリシンの摂取量が１回当たり１ｇ以上１０ｇ以下である請求項１に記載の腎機能改善用組成物。 The composition for improving renal function according to claim 1, wherein the intake of glycine is 1 g or more and 10 g or less at a time.
  3. 　糸球体濾過量、尿タンパク量、尿アルブミン量、血清クレアチニン濃度、及び血清シスタチンＣ濃度からなる群から選択される少なくとも１種の腎機能を評価する指標を維持又は改善する請求項１又は２に記載の腎機能改善用組成物。 According to claim 1 or 2, which maintains or improves an index for evaluating at least one renal function selected from the group consisting of glomerular filtration rate, urinary protein amount, urinary albumin amount, serum creatinine concentration, and serum cystatin C concentration. The above-mentioned composition for improving renal function.
  4. 　請求項１から３のいずれか１項に記載の腎機能改善用組成物を含む腎機能改善用飲食品。 A food or drink for improving renal function containing the composition for improving renal function according to any one of claims 1 to 3.
  5. 　請求項１から３のいずれか１項に記載の腎機能改善用組成物を含む腎機能維持用飲食品。 A food or drink for maintaining renal function containing the composition for improving renal function according to any one of claims 1 to 3.
  6. 　請求項１から３のいずれか１項に記載の腎機能改善用組成物を含む腎機能改善剤。 A renal function improving agent containing the composition for improving renal function according to any one of claims 1 to 3.
  7. 　請求項１から３のいずれか１項に記載の腎機能改善用組成物を含む腎機能維持剤。 A renal function maintaining agent containing the composition for improving renal function according to any one of claims 1 to 3.
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WO2019044348A1 (en) * 2017-08-30 2019-03-07 アサヒグループホールディングス株式会社 Composition for decreasing serum uric acid level

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Publication number Priority date Publication date Assignee Title
WO2019044348A1 (en) * 2017-08-30 2019-03-07 アサヒグループホールディングス株式会社 Composition for decreasing serum uric acid level

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* Cited by examiner, † Cited by third party
Title
NAKAGAWA, TAKAHIKO: "Mechanism of kidney injury and angiopathy caused by uric acid: Significance of URAT1 inhibitors", GOUT AND NUCLEIC ACID METABOLISM, vol. 37, no. 2, 2013, pages 142 - 145, ISSN: 1344-9796 *

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