JP2019043861A - Composition for improving lactic acid/pyruvic acid ratio - Google Patents

Abstract

To provide compositions capable of improving lactic acid/pyruvic acid ratio by suppressing lowering of pyruvic acid concentration after alcohol intake.SOLUTION: The composition for improving lactic acid/pyruvic acid ratio according to the present invention comprises tryptophan. The composition for improving lactic acid/pyruvic acid ratio further comprises an amino acid selected from the group consisting of glycine, alanine, glutamine, arginine, serine, cysteine, threonine, phenylalanine, proline, asparagine, aspartic acid, methionine, histidine, isoleucine, citrulline, glutamic acid, ornithine, theanine, taurine, tyrosine and valine, as well as at least one saccharide selected from the group consisting of fructose, sucrose, and glucose.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a composition for improving the lactic / pyruvic acid ratio.

  Various substances that promote the metabolism of alcohol consumed in vivo are known. For example, Patent Document 1 describes that glycine accelerates the rate of alcohol elimination in vivo. In addition, Patent Document 2 describes that a food or beverage containing a water-insoluble component derived from tomato fruit and an amino acid such as phenylalanine efficiently lowers the blood alcohol concentration. Furthermore, Patent Document 3 describes that an amino acid composition secreted by the vespidid larva has an improving effect on alcoholic liver dysfunction.

By the way, in humans, the ratio of lactic acid / pyruvic acid in blood is kept almost constant, and the fluctuation is an index showing changes in the state of metabolism, circulation and the like. Relatedly, it is known that intake of alcohol by drinking etc. lowers the concentration of pyruvate and raises the ratio of lactic acid / pyruvate. An increase in the lactate / pyruvate ratio is also taken to represent an increase in the NADH / NAD ⁺ ratio. Here lipids, for sugars, amino acids, metabolic such as nucleic acids are NAD ⁺ dependent, increase in the NADH / NAD ⁺ ratio will be affecting their metabolism, for example, hyperlipidemia, hypoglycemia Is said to be a cause of hyperuricemia etc.

JP 2003-116504 A JP, 2016-042826, A International Publication No. 2002/074302

If reduction of NAD ⁺ to NADH occurs concomitantly with alcohol metabolism, NAD ⁺ will be deficient. Since the reoxidation of NADH to NAD ⁺ accompanies the conversion of pyruvate to lactate, the supply of pyruvate is thought to lead to the supply of NAD ⁺ and promote alcohol metabolism. However, there has not been known a method for efficiently suppressing the decrease in pyruvate concentration after drinking alcohol.

  An object of the present invention is to provide a composition capable of suppressing a decrease in pyruvate concentration after alcohol intake and improving a lactic acid / pyruvate ratio.

  The present invention provides a composition for improving the ratio of lactic acid / pyruvate containing tryptophan.

  In one embodiment, the composition comprises glycine, alanine, glutamine, arginine, serine, cysteine, threonine, phenylalanine, proline, asparagine, aspartic acid, methionine, histidine, isoleucine, citrulline, glutamic acid, ornithine, theanine, taurine, tyrosine And valine, and at least one saccharide selected from the group consisting of fructose, sucrose and glucose.

  In one form, the amino acid is selected from the group consisting of glycine, alanine and glutamine, and the sugar is selected from the group consisting of fructose and sucrose.

  In one embodiment, the content ratio by weight of the amino acid or saccharide to tryptophan is 5 or more and 100 or less.

  In one embodiment, the composition is used to promote alcohol metabolism.

  The present invention also provides a food and drink containing the composition.

  The present invention also provides an alcohol metabolism promoter comprising the composition.

  The present invention also provides an anti-harvest drug comprising the composition.

  ADVANTAGE OF THE INVENTION According to this invention, the fall of the pyruvic acid density | concentration after alcohol intake can be suppressed, and the composition which can improve lactic acid / pyruvic acid ratio can be provided.

It is a figure which shows the pyruvic acid concentration in the blood of the rat after alcohol administration. It is a figure which shows the pyruvic acid concentration in the blood of the rat which alcohol-administered after amino acid or saccharides administration. It is a figure which shows the pyruvic acid concentration in the blood of the rat which carried out alcohol administration after glycine or tryptophan administration. It is a figure which shows the pyruvic acid concentration in the blood of the rat which carried out alcohol administration after fructose or tryptophan administration. It is a figure which shows a time-dependent change of the blood pyruvate concentration in a drinking test. It is a figure which shows the pyruvic acid concentration in the blood 180 minutes after alcohol drinking in a drinking test. It is a figure which shows a time-dependent change of blood lactic acid / pyruvate ratio in a drinking test. It is a figure which shows the lactic acid / pyruvic acid ratio in the blood 180 minutes after alcohol consumption in a drinking test. It is a figure which shows the alcohol elimination rate in the blood in a drinking test.

  In the present specification, when there are a plurality of substances corresponding to each component in the composition, the content of each component in the composition is the total amount of the plurality of substances present in the composition unless otherwise specified. means.

<Composition for improvement of lactic acid / pyruvic acid ratio>
The composition according to the present embodiment contains tryptophan as an active ingredient, and is used to improve the ratio of lactic acid / pyruvic acid in blood. The composition containing tryptophan can be orally administered, for example, to improve the lactic acid / pyruvate ratio that is increased due to alcohol consumption and the like. This can be considered, for example, because administration of a composition containing tryptophan increases the concentration of pyruvate in blood. Here, the improvement of the lactic acid / pyruvic acid ratio in the present specification means bringing the lactic acid / pyruvic acid ratio deviated from the normal state by some factor closer to the normal value. The lactate / pyruvate ratio can be measured in a conventional manner on a blood sample of a subject animal (eg, a mammal, particularly a human).

The composition can effectively improve, in particular, the increase in lactic acid / pyruvate ratio associated with alcohol intake, and alcohol metabolism is effectively promoted. In addition, the composition can improve the ratio of lactic acid / pyruvate deviated from the normal state by its administration, so that the NADH / NAD ⁺ ratio can be improved, and hyperlipidemia, hypoglycemia, high uric acid It is thought that it can contribute to the prevention, amelioration, etc. of pathological conditions such as

  Tryptophan contained in the composition is 2-amino-3-indolylpropionic acid, and may contain at least L-tryptophan. Tryptophan may be racemic but is preferably L-tryptophan. The purity of tryptophan may be any one suitable for administration to the human body, 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, etc., and may be appropriately selected from commercially available products.

  Tryptophan in the composition may be contained as a single substance (free form) or may be contained in the form of a salt. The tryptophan salt is not particularly limited as long as it is a pharmacologically acceptable salt. Specifically, examples include acid addition salts, metal salts, ammonium salts, organic amine addition salts and the like. As acid addition salts, inorganic acid salts such as hydrochlorides, sulfates, nitrates and phosphates, acetates, maleates, fumarates, citrates, malates, lactates, α-ketoglutarates And organic acid salts such as gluconate and caprylate. 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. Ammonium salts include salts such as ammonium and tetramethyl ammonium. Organic amine addition salts include salts of morpholine, piperidine and the like.

  The composition may further comprise an active ingredient other than tryptophan. As active ingredients other than tryptophan, amino acids, saccharides and the like can be mentioned. The amino acid is another amino acid other than tryptophan (hereinafter, also referred to as a second amino acid), and examples thereof include glycogenic amino acids that can be converted to pyruvic acid in vivo. Specific examples of other amino acids include glycine, alanine, glutamine, arginine, serine, cysteine, threonine, phenylalanine, proline, asparagine, aspartic acid, methionine, histidine, isoleucine, citrulline, glutamic acid, ornithine, theanine, taurine, tyrosine, Valine and the like can be mentioned, and from the viewpoint of the improvement effect of the lactic acid / pyruvate ratio, it is preferably at least one selected from the group consisting thereof, at least one selected from the group consisting of glycine, alanine and glutamine More preferably, it is a species, and more preferably it comprises at least glycine. The second amino acid may be a single amino acid or may be a pharmacologically acceptable salt.

  Examples of saccharides include monosaccharides such as fructose and glucose, and disaccharides such as sucrose. The saccharide contained in the composition is preferably at least one selected from the group consisting of fructose, glucose and sucrose from the viewpoint of the improvement effect of the lactic acid / pyruvate ratio, and is selected from the group consisting of fructose and sucrose More preferably, it is at least one of

  When the composition contains a second amino acid, saccharides and the like in addition to tryptophan, its content is, for example, a weight ratio to tryptophan of 5 or more, preferably 10 or more, from the viewpoint of the improvement effect of lactic acid / pyruvate ratio. Preferably it is 15 or more, for example, 100 or less, preferably 60 or less, more preferably 30 or less.

  The total content of the active ingredient in the composition may be appropriately selected depending on the constitution of the composition, the effect expected by administration of the composition, and the like. The total content of the active ingredients in the composition is, for example, 0.0001% by weight or more, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, and for example, 100% by weight or less, preferably 70 % By weight or less, more preferably 50% by weight or less.

  The composition may further contain other ingredients other than the active ingredient, as necessary. Other ingredients include solvents such as water; various vitamins including vitamin B group and the like; sweeteners; flavors; colorants; pharmacologically acceptable carriers, excipients, diluents, salts, pH adjusters , Chelating agents, buffers and the like.

  The composition may be in any form of powder, granules, tablets, capsules, troches, syrups, solutions, injections and the like. The method of administration may be selected from commonly used administration routes depending on the dosage form of the composition and the like. As the administration route, for example, oral administration, nasal administration, rectal administration, intravenous injection, infusion and the like can be mentioned.

  The dose of the composition is usually, for example, 0.01 g or more, preferably 0.1 g or more, and for example, 1.0 g or less, preferably 0.6 or less, more preferably 0. It is 4g or less. Also, the number of administrations per day is, for example, 1 to 3 times.

  In one form, the composition is used to promote alcohol metabolism. The administration of the composition promotes alcohol metabolism to reduce or prevent hangover symptoms caused by excessive alcohol intake and the like. When the composition is used to promote alcohol metabolism, administration of the composition can be, for example, 30 minutes before to 60 minutes before alcohol intake. The composition may also be administered after alcohol intake during alcohol intake.

<Food and Beverage>
The food and drink contain the composition for improving the lactic acid / pyruvate ratio containing tryptophan described above. By taking food and drink, the effects of the composition described above can be obtained. The food and drink containing the composition for improving the ratio of lactic acid / pyruvate according to the present invention includes the composition for improving the ratio of lactic acid / pyruvate as well as health food and drink, functional food and drink, food and drink for sick people, etc. All food and drink products that can be blended are included. Among them, functional food and drink are particularly preferable. “Functional food and drink” means food and drink having certain functionality to a living body, and, for example, food and drink for specified health (including conditional Tokuho [food for specified health and health care)] and nutritional function food and drink Health function food and drink including special use food and drink, nutrition supplement food and drink, health supplement food and drink, supplements (for example, various dosage forms such as tablets, coated tablets, sugar coated tablets, capsules and liquids) and cosmetic food and drinks (for example, diet So-called health food and drink in general such as food and drink). Functional food and drink also include health food and drink to which Health claim (Health claim) based on the food standards of Codex (FAO / WHO Joint Food Standards Committee) is applied.

  The health food etc. may be in the form of a normal food, and may be in the form of supplements (tablets, granules (for example, granules packed in a stick form), fine granules, tablets, chewable tablets, capsules (soft) Capsules, hard capsules, etc.).

  The food and drink may be a fluid beverage. When the food or drink is a beverage, the tryptophan concentration in the beverage is, 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 / ml. It is 100 ml or less, preferably 0.6 g / 100 ml or less, more preferably 0.4 g / 100 ml or less.

  Preferably, the composition that the beverage comprises comprises glycine. When the composition contains glycine, the concentration of glycine in the beverage is, for example, 0.1 g / 100 ml or more, preferably 0.3 g / 100 ml or more, more preferably 0.6 g / 100 ml or more, and for example, 10 g / 100 ml or less Preferably it is 8 g / 100 ml or less, More preferably, it is 7 g / 100 ml or less.

  The beverage comprises, for example, a composition containing tryptophan and a liquid medium such as water and fruit juice. Examples of beverages include green tea, oolong tea, tea beverages such as black tea, soft drinks, jelly beverages, sports beverages, milk beverages, carbonated beverages, vegetable beverages, fruit juice beverages, fermented vegetable beverages, fermented fruit juice beverages, fermented milk beverages (yoghurt etc.) , Lactic acid bacteria drink, milk drink (coffee milk, fruit milk, etc.), powdered drink, cocoa drink, alcoholic drink may be used, may be a drink containing the composition and using milk, purified water etc. as a liquid medium .

  The beverage may contain a sweetener to adjust sweetness. The sweetener may be sugar, and sugar includes sugar, sucrose, fructose, fructooligosaccharide, galactooligosaccharide and the like. Alternatively, instead of sugar, synthetic sweeteners such as aspartame and saccharin may be added.

  The beverage may contain an acidulant. Examples of the acidulant include citric acid, DL-malic acid, L-tartaric acid, lactic acid, phosphoric acid and the like.

  The beverage may contain a flavor. Examples of the flavor include citrus oil such as lemon, lime and orange, orange oil, herb extract and the like. The perfume may be a natural perfume or a synthetic perfume. Natural flavors include, for example, anise oil, angelica oil, allspice oil, orange oil, cassia oil, capsicum oil, guarana extract, cardamom oil, caraway oil, cumin oil, clary sage 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, fenugreek oil, fennel oil, pepper oil, peppermint oil, perilla oil, bergamot oil , Mandarin oil, eucalyptus oil, lemon oil, rosemary oil and the like.

Synthetic perfumes include, for example, anethole, allyl caproate, isoamyl acetate, γ-undecalactone, ethyl vanillin, ethyl butyrate, ethyl phenyl glycidate, eugenol, geraniol, diacetyl, cyclotene, citral, sinamic aldehyde, terpineol Δ-decalactone, decanal, nonanal, γ-nonalactone, vanillin, phenylethyl alcohol, furaneol, furfuryl mercaptan, 2-hexenal, 3-hexenol, heliotropin, perylaldehyde, benzaldehyde, maltol, methyl anthranilate, methyl salicylate , Menthol, α-ionone, linalool and the like.

  When the food or drink is in a form having no fluidity, the food or drink may be in any form such as a tablet, a capsule, a powder, a gel, a stick, a plate or the like. The food and drink may contain the composition such that the intake of tryptophan in one intake is the dose in the composition described above.

  EXAMPLES Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to these examples.

(Reference example)
A Wistar rat (male, 6 weeks old or more) is administered gavage of ethyl alcohol (Alc) at a dose of 1 g / kg, 2 g / kg or 3 g / kg, and blood is collected 3 hours later to give blood pyruvine. The acid concentration (mg / dl) was measured. The results are shown in FIG.

  It can be seen from FIG. 1 that blood pyruvate concentration decreases in a dose-dependent manner by gavage of alcohol into the rat stomach.

Example 1
Administer 1.5 g / kg of various amino acids (all L types except glycine) and saccharides (however, 0.5 g / kg of ornithine and taurine) to Wistar rats (male, 6 weeks old or more), and 30 minutes later Gastric administration of 3 g / kg of alcohol was performed. Blood was collected 3 hours after alcohol administration to measure blood pyruvate concentration (mg / dl). The results are shown in FIG. In addition, the abbreviation in FIG. 2 is as follows. Alcohol non-administration (Alc (-)), alcohol administration (Alc), glycine (Gly), alanine (Ala), glutamine (Gln), arginine (Arg), serine (Ser), cysteine (Cy), threonine (Thr) , Phenylalanine (Phe), proline (Pro), asparagine (Asn), aspartic acid (Asp), methionine (Met), histidine (His), isoleucine (Ile), citrulline (Cit), glutamic acid (Glu), ornithine (Orn) ), Theanine (Tea), taurine (Tau), tyrosine (Tyr). Further, in FIG. 2, the lower left oblique lines indicate the controls (Alc (−), Alc), and the lower right oblique lines indicate that there was a significant difference from the control.

  It can be seen from FIG. 2 that the administration of tryptophan prior to the gavage administration of alcohol can significantly suppress the decrease in blood pyruvate concentration. Since tryptophan significantly suppresses the decrease in pyruvate concentration associated with alcohol intake, it is believed that it can improve the blood lactate / pyruvate ratio and can promote alcohol metabolism. Also, it is understood that glycine, alanine, glutamine, fructose and sucrose can also effectively suppress the decrease in blood pyruvate concentration accompanying alcohol intake.

(Example 2)
To Wistar rats (male, 6 weeks old or more), glycine alone, tryptophan alone, or a mixture of glycine and tryptophan were administered, respectively, and after 30 minutes, 3 g / kg of alcohol was administered via intragastric gavage. Blood was collected 3 hours after alcohol administration to measure blood pyruvate concentration (mg / dl). The results are shown in FIG. The dose of glycine was 1.5 g / kg, and the dose of tryptophan was 0.125 g / kg.

  It can be seen from FIG. 3 that the administration of glycine prior to the gavage administration of alcohol can significantly suppress the decrease in blood pyruvate concentration. Also, it can be seen that even when a small amount of tryptophan is preadministered, it tends to suppress the decrease in blood pyruvate concentration. Furthermore, by simultaneously administering tryptophan and glycine, it is possible to significantly suppress the decrease in blood pyruvate concentration, and it is understood that a synergistic effect is observed in the combined use of tryptophan and glycine. In FIG. 3, the symbols a, b and c indicate that the same symbols have no significant difference.

(Example 3)
To Wistar rats (male, 6 weeks old or more), fructose alone, tryptophan alone, or a mixture of fructose and tryptophan were administered, respectively, and after 30 minutes, 3 g / kg of alcohol was administered by gavage. Blood was collected 3 hours after alcohol administration to measure blood pyruvate concentration (mg / dl). The results are shown in FIG. The dose of fructose was 1.5 g / kg, and the dose of tryptophan was 0.125 g / kg.

  From FIG. 4, it can be seen that the administration of fructose prior to the gavage administration of alcohol can significantly suppress the decrease in blood pyruvate concentration. In addition, it can be seen that the simultaneous administration of tryptophan and fructose tends to be able to more effectively suppress the decrease in blood pyruvate concentration.

(Example 4)
Alcoholic tests were conducted after obtaining informed consent in writing from healthy adult men and women as subjects. Composition containing 6 g (n = 7) of poorly soluble dextrin as a control, 6 g (n = 7) of glycine, 6 g of glycine and 0.1 g of tryptophan (n = 5), composition containing 6 g of glycine and 0.2 g of tryptophan Either n = 7) or a composition (n = 7) containing 6 g of glycine and 0.4 g of tryptophan was orally administered, and after 30 minutes, the caustic soda was consumed at an alcohol amount of 0.32 g / kg. Blood is collected at 60, 120, and 180 minutes after ingestion, before, and at blood pyruvate concentration (mg / dl), blood lactate / pyruvate ratio, and blood alcohol elimination rate (Mg / ml / hr) was measured. The results of measurement of blood pyruvate concentration are shown in FIGS. 5 and 6, the results of measurement of blood lactate / pyruvate ratio are shown in FIGS. 7 and 8, and the results of measurement of blood alcohol elimination rate are shown in FIG. The blood alcohol elimination rate was calculated from the decrease in concentration after reaching the maximum blood alcohol concentration in blood alcohol concentration aging, that is, the slope of the elimination phase.

  FIG. 5 shows time-dependent changes in blood pyruvate concentration, the dotted line shows the control group (slightly soluble dextrin), the solid line shows the composition administration group containing tryptophan and glycine, and the broken line shows the glycine administration group. It can be seen from FIG. 5 that by taking a composition containing tryptophan and glycine before drinking alcohol, the blood pyruvic acid concentration that has been lowered 60 minutes after drinking alcohol is improved over time. Further, it can be seen from FIG. 6 that the intake of the composition containing tryptophan and glycine before drinking tends to promote the recovery of the blood pyruvate concentration lowered by the drinking. In particular, when a composition containing 6 g of glycine and 0.2 g of tryptophan is ingested, it is found that recovery of blood pyruvate concentration is promoted significantly (p = 0.034) with respect to the control group.

  FIG. 7 shows time-course changes in blood lactate / pyruvate ratio, the dotted line is the control group (slightly soluble dextrin), the solid line is the composition administration group containing tryptophan and glycine, and the dashed line is the glycine administration group. It can be seen from FIG. 7 that intake of a composition containing tryptophan and glycine before drinking alcohol suppresses an increase in the ratio of lactic acid / pyruvic acid 60 minutes after drinking alcohol, and further improves over time. It can be seen from FIG. 8 that the intake of the composition containing tryptophan and glycine before drinking tends to promote the improvement of the blood lactate / pyruvate ratio increased by the drinking. In particular, when a composition containing 6 g of glycine and 0.2 g of tryptophan is ingested, improvement of the blood lactate / pyruvate ratio is significantly promoted (p = 0.009) relative to the control group.

  From FIG. 9, it can be seen that alcohol consumption is promoted from the fact that the alcohol elimination rate is increased by ingesting a composition containing tryptophan and glycine before drinking alcohol. In particular, it can be seen that when the composition containing 6 g of glycine and 0.2 g of tryptophan is ingested, the blood alcohol elimination rate is significantly improved (p = 0.034) relative to the control group.

Claims (8)

  Composition for improvement of lactic acid / pyruvic acid ratio containing tryptophan.   An amino acid selected from the group consisting of glycine, alanine, glutamine, arginine, serine, cysteine, threonine, phenylalanine, proline, asparagine, aspartic acid, methionine, histidine, isoleucine, citrulline, glutamic acid, ornithine, theanine, taurine, taurine, tyrosine and valine The composition according to claim 1, further comprising at least one saccharide selected from the group consisting of fructose, sucrose and glucose.   The composition according to claim 2, wherein the amino acid is selected from the group consisting of glycine, alanine and glutamine, and the saccharide is selected from the group consisting of fructose and sucrose.   The composition according to claim 2 or 3, wherein the content ratio by weight of the amino acid or saccharide to tryptophan is 5 or more and 100 or less.   The composition according to any one of claims 1 to 4, which is used for alcohol metabolism promotion.   Food-drinks containing the composition of any one of Claims 1-5.   An alcohol metabolism promoter comprising the composition according to any one of claims 1 to 5.   A hangover inhibitor comprising the composition according to any one of claims 1 to 5.