JP2014234384A - Alcohol metabolism accelerator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide acceleration of metabolism of ingested alcohol and stable reduction of blood alcohol concentration.SOLUTION: The alcohol metabolism accelerator of the invention contains oligopeptides as an effective component. The oligopeptides are obtainable by a production process comprising a first degradation step in which corn gluten meal is treated with alkaline protease for degradation and a second degradation step in which the product of the first degradation step is treated with neutral protease for further degradation. Usually the crude protein content of the oligopeptides thus obtained is 85 wt.% or more and the content of oligopeptides of which molecular weight is 1000 Da or less is 70 wt.% or more.

Description

  The present invention relates to a metabolism promoter, in particular, a metabolism promoter for alcohol taken into the body by drinking or the like.

  Alcohol (ethanol) taken into the body by drinking etc. is partly absorbed in the stomach and mostly in the small intestine and dissolves in the blood, and part is excreted outside the body through sweat, urine and breath, Most is metabolized in the liver. The metabolic process of alcohol in the liver is the first stage in which it is converted to acetaldehyde by being oxidized by alcohol dehydrase (ADH), and this acetaldehyde is further oxidized by aldehyde dehydrogenase (ALDH) to acetic acid. The acetic acid produced through these stages is converted into water and carbon dioxide as it is taken into the blood and circulates throughout the body, and is discharged outside the body through sweat, urine and breath. Is done.

  Alcohol metabolism imposes a heavy burden on the liver, a multifunctional organ that plays an important role in life support, and research on drugs and the like for reducing the burden is ongoing. For example, Patent Document 1 discloses that a peptide obtained by decomposing corn protein (corn gluten meal) by-produced in the process of producing corn starch by a wet milling method with an endo-type alkaline protease (alkaline proteolytic enzyme) is used as an active ingredient. Proposing alcohol metabolism promoters.

  This alcohol metabolism promoter is said to be able to prevent hangover and hangover by taking it immediately before drinking, but it is effective because it tends to temporarily increase blood alcohol concentration after taking alcohol. There is concern that it is unstable and may cause an unexpected burden on the liver.

JP-A-7-285881 (Claims, Table 1 and FIG. 1 etc.)

  The present invention is intended to promote metabolism of ingested alcohol and stably reduce the blood alcohol concentration.

  The alcohol metabolism promoter of the present invention contains an oligopeptide as an active ingredient. The oligopeptide used here is a first decomposition step in which corn gluten meal is decomposed with an alkaline proteolytic enzyme, and a second decomposition step in which the decomposition product in the first decomposition step is further decomposed with a neutral proteolytic enzyme. It is obtained by the manufacturing process containing these.

  This oligopeptide usually has a crude protein content of 85% by weight or more and a oligopeptide having a molecular weight of 1,000 Da or less and a content of 70% by weight or more.

  Since the alcohol metabolism promoter of the present invention contains a specific oligopeptide as an active ingredient, it can promote the metabolism of ingested alcohol and stably reduce the blood alcohol concentration.

The figure which shows the measurement result of the expiration alcohol concentration evaluated in the Example. The figure which shows the measurement result of the alcohol concentration in whole blood evaluated in the Example.

  The alcohol metabolism promoter of the present invention contains a specific oligopeptide as an active ingredient.

  The oligopeptide used here is obtained from corn gluten meal as a raw material. Corn gluten meal is a by-product containing protein as a main component, which is produced when corn starch is produced from corn by a wet milling method, and is usually obtained as a dry yellow powder.

  Corn gluten meal is widely used as a feed and is easily available because it is sold at a low price. However, commercially available corn gluten meal generally contains a large amount of contaminants such as fats and starches, and therefore the protein content is about 60% by weight. For this reason, it is preferable that the commercially available corn gluten meal used as a raw material raises protein content to about 85 weight% by performing refinement | purification processes, such as deoiled fat and destarch.

  In the purification process of corn gluten meal, for example, it is poured into water to prepare a dispersion, and a hydroxide such as sodium hydroxide is added to this dispersion to set the pH in the alkaline region. And after stirring this dispersion while heating, a solid substance is isolate | separated, If this solid content is further washed with water, the refined corn gluten meal can be obtained. In an example of a more specific purification method, a dispersion is prepared by adding corn gluten meal at a rate of 6 to 12 kg with respect to 100 L of water. The pH is adjusted to 8 to 10 by adding an aqueous sodium hydroxide solution to this dispersion, and the mixture is stirred for 20 to 60 minutes while being heated to 50 to 80 ° C. And solid content and a water | moisture content are isolate | separated by the centrifugation method, and a water | moisture content is discarded. Furthermore, about 100L water is added with respect to solid content, it heats to 50-80 degreeC, and solid content is wash | cleaned by stirring for 20-60 minutes, maintaining temperature. When the solid content and the washing water are separated again by a centrifugal separation method and the washing water is discarded, a purified corn gluten meal is obtained.

  In the step for preparing a target oligopeptide from corn gluten meal, first, a first decomposition step of decomposing corn gluten meal with an alkaline proteolytic enzyme is performed. Alkaline proteolytic enzymes are enzymes that can degrade proteins under alkaline conditions, and various commercially available ones, preferably endo-type ones, can be used.

  Specific examples of commercially available alkaline proteolytic enzymes that can be used include Novozymes trade name “Alcalase”, Amano Enzyme trade names “Protin SD-AY10” and “Protease P“ Amano ”3SD”, Danisco Japan Ltd. Company product names “Multifect PR6L” and “Optimase PR89L”, Shin Nippon Chemical Industry Co., Ltd. product name “Sumiteam MP”, DSM Japan Ltd. product name “Delbolase”, Nagase ChemteX Corporation Trade names “Biolase OP”, “Biolase SP-20FG” and “Biolase SP-4FG”, trade name “Orientase 22BF” of HIBI Co., Ltd. and trade name “Aroase XA-10” of Yakult Pharmaceutical Co., Ltd. Can That.

  In the first decomposition step, for example, the concentration of corn gluten meal as a substrate is 4 to 10% by weight, and the amount of alkaline proteolytic enzyme used is 0.5 to 5 with respect to corn gluten meal (in terms of dry weight) used in this step. A weight percent dispersion is prepared and its pH is set in a region where alkaline proteolytic enzymes can function, for example, 7-9. The pH of the dispersion can be adjusted, for example, by adding an aqueous hydroxide salt solution such as an aqueous sodium hydroxide solution. And this dispersion liquid is heated to 45-60 degreeC, temperature is maintained, and it is made to react for 3 to 10 hours. At this time, the dispersion may be stirred.

  Next, the 2nd decomposition process which decomposes | disassembles the degradation product in a 1st decomposition process with a neutral proteolytic enzyme is performed. Neutral proteolytic enzymes are enzymes that can degrade proteins or peptides under neutral conditions (usually in the range of pH 6 to 8), and use various endo-types or exo-types that are commercially available. Can do.

  Specific examples of commercially available neutral proteolytic enzymes that can be used include the product name “Neutrase” from Novozymes, the product name “Promod 223LP” from Kyowa Hakko Bio Co., Ltd., and the product names “Nucleicin” and “Orien” from HBI Corporation. “Tase 10NL” and “Orientase 90N”, trade names “Aroase NS”, “Aroase AP-10” and “Aroase NP-10” from Yakult Pharmaceutical Co., Ltd., trade names “Sumiteam LPL” from Shin Nippon Chemical Industry Co., Ltd. And “Sumiteam LP” and the trade name “Fine Papain for Food” of Nagase ChemteX Corporation.

  In the second decomposition step, for example, the reaction solution after the completion of the first decomposition step is appropriately adjusted so that its concentration is 4 to 10% by weight based on the corn gluten meal (in terms of dry weight) used in the first decomposition step. Water is added or removed, and neutral proteolytic enzymes are added. The amount of neutral proteolytic enzyme added is set to 0.5 to 5% by weight with respect to corn gluten meal (in terms of dry weight) used in the first decomposition step. Furthermore, the pH of the reaction solution is set to a region where neutral proteolytic enzyme can function, usually 6-8. The pH of the reaction solution can be adjusted, for example, by adding hydrochloric acid to the reaction solution. And this reaction liquid is heated to 35-55 degreeC, it stirs, maintaining temperature, and is made to react for 3 to 10 hours.

  The reaction solution after the completion of the first decomposition step is a region different from the region where the alkaline proteolytic enzyme used in the first decomposition step can function, and the neutral proteolytic enzyme used in this step functions. By setting the pH in a possible region, it can be applied to this process as it is.

  The reaction solution after the completion of the second decomposition step is heated to inactivate neutral proteolytic enzyme and alkaline proteolytic enzyme present in the reaction solution, and then centrifuged to separate solids and moisture. To do. And the isolate | separated water | moisture content is filtered and the filtrate is concentrated and dried after applying necessary treatments such as pH adjustment and sterilization treatment. In the filtration treatment, it is usually preferable to use a ceramic filter and a nanofilter in this order. In this case, proteins remaining in water can be removed with a ceramic filter, and low-molecular salts and amino acids remaining in water can be removed with a nanofilter.

  The target oligopeptide obtained in this way is mostly composed of about 2 to 4 amino acids, and the content of crude protein is usually 85% by weight or more, and into the blood through the intestine. It can be obtained as a low molecular weight powder that is easily incorporated efficiently, in particular, as a low molecular weight powder having a molecular weight of 1,000 Da or less and an oligopeptide content of 70% by weight or more.

  The alcohol metabolism promoter of the present invention may be composed of the above-described oligopeptide itself, but may contain other components as long as the efficacy of the oligopeptide is not inhibited. For example, various vitamins, minerals, and other animal and plant-derived components having an alcohol metabolism action may be included. Further, the dosage form of the alcohol metabolism promoter is not particularly limited, but it can be usually provided in a dosage form such as powder, capsule, tablet or solution that can be easily taken orally.

  The alcohol metabolism promoter of the present invention can enhance the activity of alcohol dehydrogenase immediately before drinking (usually within about 30 minutes before drinking) or when taken orally at the same time as drinking. The alcohol concentration in the solvent can be decreased stably and quickly.

  Moreover, since the alcohol metabolism promoter of the present invention is obtained using inexpensive corn gluten meal as a raw material, it can be provided at low cost and mass production is easy.

Example 1
150 g of commercially available corn gluten meal and 2.5 kg of water were uniformly stirred and mixed to prepare a dispersion, and an aqueous sodium hydroxide solution was added thereto to adjust the pH to 8. The dispersion was heated to 60 ° C. and stirred for 60 minutes while maintaining the temperature. And the solid content and the water | moisture content were isolate | separated by centrifuging a dispersion liquid, and the water | moisture content was discarded. 2.5 kg of water was added to the separated solid, and this dispersion was heated to 60 ° C. and stirred for another 60 minutes while maintaining the temperature. The dispersion after stirring was centrifuged again to separate solids and water, and the water was discarded.

  A dispersion was prepared by adding 2.5 kg of water to the separated solid and stirring and mixing so as to be uniform, and an aqueous sodium hydroxide solution was added to the dispersion to adjust the pH to 8. This dispersion was heated to 60 ° C., 1 g of alkaline protease (trade name “Alcalase” from Novozymes) was added, and the mixture was reacted at the same temperature for 3 hours.

  Next, hydrochloric acid was added to the dispersion to adjust the pH to 7, and the mixture was heated to 45 ° C. Then, 1 g of neutral proteolytic enzyme (Novozymes trade name “Neutrase”) was added to the dispersion and reacted at the same temperature for 5 hours.

  After completion of the reaction, the reaction solution was heated at 90 ° C. for 10 minutes to inactivate the alkaline and neutral proteolytic enzymes present in the reaction system. Then, solid content and water | moisture content were isolate | separated by centrifuging a reaction liquid, and the isolate | separated water | moisture content was filtered using the ceramic filter and the nano filter in this order.

  When the solid obtained by concentrating the water after the filtration treatment was dried, 36.7 g of the desired powdery (light brown) oligopeptide was obtained (yield 24%). The resulting oligopeptide has a crude protein content (measured by a nitrogen quantitative conversion method) of 87.3% by weight or more, a fat content (measured by a Soxhlet extraction method) of 1.5% by weight or less, and a PDA method. In the molecular weight distribution measured by (Phase Doppler Particle Measurement System Method), the content of oligopeptides having a molecular weight of 1,000 Da or less was 70% by weight or more.

Example 2
A dispersion liquid was prepared by uniformly stirring and mixing 1,500 g of commercially available corn gluten meal and 15 kg of water, and an aqueous sodium hydroxide solution was added thereto to adjust the pH to 10. The dispersion was heated to 80 ° C. and stirred for 40 minutes while maintaining the temperature. And the solid content and the water | moisture content were isolate | separated by centrifuging a dispersion liquid, and the water | moisture content was discarded. 15 kg of water was added to the separated solid, and this dispersion was heated to 80 ° C. and stirred for an additional 40 minutes while maintaining the temperature. The dispersion after stirring was centrifuged again to separate solids and water, and the water was discarded.

  A dispersion was prepared by adding 25 kg of water to the separated solid content and stirring and mixing so as to be uniform, and an aqueous sodium hydroxide solution was added to the dispersion to adjust the pH to 8. This dispersion was heated to 55 ° C., 15 g of alkaline protease (trade name “Alcalase” from Novozymes) was added, and the mixture was reacted at the same temperature for 4 hours.

  Next, hydrochloric acid was added to the dispersion to adjust the pH to 7.5 and heated to 50 ° C. Then, 15 g of neutral proteolytic enzyme (Novozymes trade name “Neutrase”) was added to the dispersion and reacted at the same temperature for 8 hours.

  After completion of the reaction, the reaction solution was heated at 90 ° C. for 20 minutes to inactivate alkaline proteolytic enzyme and neutral proteolytic enzyme present in the reaction system. Then, solid content and water | moisture content were isolate | separated by centrifuging a reaction liquid, and the isolate | separated water | moisture content was filtered using the ceramic filter and the nano filter in this order.

  When the solid obtained by concentrating the water after the filtration treatment was dried, 326 g of the desired powdery (light brown) oligopeptide was obtained (yield 22.3%). The obtained oligopeptide has a crude protein content (measurement method is the same as in Example 1) of 87.3% by weight or more, and a fat content (measurement method is the same as in Example 1) of 1.5% by weight or less. In the molecular weight distribution measured by the PDA method as in Example 1, the content of oligopeptides having a molecular weight of 1,000 Da or less was 70% by weight or more.

Evaluation and healthy young 30 men the subject groups of 22 to 28 years old, the content of same, crude protein and resulting oligopeptide oligopeptide (Example 1 which is mass-produced in accordance with the method of Example 1 87 Alcohol metabolism of 3 wt% or more, fat content 1.5 wt% or less, and the content of oligopeptide having a molecular weight of 1,000 Da or less in the molecular weight distribution measured by PDA method is 70 wt% or more. The promoting function was evaluated. The test method is as follows.

<Control study>
Within 15 minutes from 8:00 am, 100 mL of Beijing Ninabe white liquor (alcohol content: 38 degrees) was drunk to all subjects. For each person in the subject group, the breath alcohol concentration was measured every 30 minutes from the time immediately after drinking until 180 minutes passed, and the whole blood alcohol concentration was measured after 30 minutes passed since drinking.

<Tests 1-3>
Immediately before drinking, exhalation alcohol concentration and whole blood for each person in the subject group over time was the same as in the control study, except that all the subjects in the same subject group as in the control study took the above oligopeptide orally. The medium alcohol concentration was measured. The dose of oligopeptide in each test is as follows. Tests 1 to 3 were performed with an interval of 24 hours.

Test 1: 1g
Test 2: 2g
Test 3: 3 g

<Measurement method and measurement result of breath alcohol concentration>
This was measured using a breath alcohol content analyzer (model number “WAT89EC-3” manufactured by Shenzhen Weihu Electric Co., Ltd.). The measurement results were analyzed by ANOVA by repeated measurement of a general linear model, and compared between tests by multivariate analysis. The results are shown in Table 1 and FIG.

  According to Table 1 and FIG. 1, the breath alcohol concentrations in Tests 1 to 3 are lower than the results of the control test at a stage of only 30 minutes after drinking, and are stably decreased without increasing thereafter. According to the results of tests 1 to 3, the effect of reducing the concentration of breath alcohol is more remarkable as the dose of oligopeptide increases.

<Measurement method and measurement result of alcohol concentration in whole blood>
1 mL of venous blood was collected from the subject and its alcohol concentration was measured. The total amount of the collected venous blood was added to a test tube to which an anticoagulant and a preservative were added, and the alcohol concentration was measured within 3 days while storing at 4 ° C. In this measurement, a sample was prepared by adding distilled water containing 0.04% by weight of tert-butyl alcohol to 0.1 mL of venous blood taken from a test tube, and mixing the sample with a hydrogen flame photometric detector. Were analyzed using a gas chromatography (Model No. “6890N” manufactured by Agilent Technologies, Inc.). A headspace sampler was used for sample injection. The analysis results were evaluated by one-way analysis of variance. The results are shown in Table 2 and FIG.

  According to Table 2 and FIG. 2, the whole blood alcohol concentration of tests 1 to 3 is significantly lower than that of the control test.

<Correlation / regression analysis result between breath alcohol concentration and whole blood alcohol concentration>
The correlation coefficient between the breath alcohol concentration at 30 minutes after drinking and the alcohol concentration in whole blood was determined by correlation analysis, and r = 0.932 (P <0.001), indicating a strong positive correlation. It was seen. Since the breath alcohol concentration does not increase after drinking and is steadily decreasing, the alcohol concentration in whole blood is considered to follow the same course.

Claims (2)

Containing an oligopeptide as an active ingredient,
The oligopeptide includes a first decomposition step in which corn gluten meal is decomposed with an alkaline proteolytic enzyme, and a second decomposition step in which a decomposition product in the first decomposition step is further decomposed with a neutral proteolytic enzyme. It is obtained by the manufacturing process,
Alcohol metabolism promoter.   The alcohol metabolism promoter according to claim 1, wherein the oligopeptide has a crude protein content of 85% by weight or more and a molecular weight of 1,000 Da or less of the oligopeptide content of 70% by weight or more. .

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