JP2014208600A - Composition comprising useful component in turmeric - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition which can inhibit the symptom of hangover, comprising natural compounds obtained from food materials with high safety and a rich history of use in foods as active ingredients.SOLUTION: This invention provides a composition to be orally administered, the composition comprising 0.5 mg or more of Bisacurone per oral dose.

Description

  The present invention relates to a bisaclone-containing composition capable of suppressing the symptoms of hangover.

  Turmeric (Curcuma longa LINNE) is a medicinal plant belonging to the genus Turmeric in the tropical and subtropical regions of the world, mainly in Southeast Asia.

  Turmeric rhizomes contain 3-5% curcumin (yellow pigment). Various utilities are known for turmeric extract and curcumin. For example, Non-Patent Document 1 suggests that a turmeric extract-containing beverage has an action of preventing sickness while appropriately expressing the “sickness” inherent in alcohol by ingesting together with alcohol.

  Patent Document 1 discloses a pharmaceutical composition for the prevention and treatment of hangover, comprising turmeric or an extract thereof in combination with duck or an extract thereof, oren or an extract thereof and ginger or an extract thereof. Has been.

  Patent Document 2 discloses a pharmaceutical composition containing turmeric together with a processed garlic product and having an action of improving unpleasant symptoms such as irritations after drinking alcohol, nausea, and hangover.

  On the other hand, there is still a need for an effective therapeutic agent and preventive agent for hangover symptoms, and there is a need for a therapeutic agent and prophylactic agent that has abundant dietary experience and a highly safe naturally-derived component as an active ingredient. Yes.

JP 2003-226650 A WO 2005/032569

Takuya Hamano et al., “Examination of the effect of turmeric extract on alcohol metabolism in healthy adults”, Applied Pharmacology, 72 (1/2), 31-38 (2007)

  An object of this invention is to provide the composition which can suppress the symptom of a hangover which uses the natural compound obtained from the food material with abundant food experience with high safety as an active ingredient.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that bisaclone contained in the turmeric extract has an action to suppress hangover symptoms, and have completed the present invention.

That is, the present invention has the following features.
[1] A composition that is orally ingested and contains 0.5 mg or more of bisaclone per oral intake.
[2] The composition according to [1], wherein bisaclone is derived from a turmeric extract.
[3] The composition of [1] or [2], further comprising curcumin.
[4] The composition according to any one of [1] to [3], which is a food or drink or a pharmaceutical product.
[5] The composition according to [4], which is a liquid composition.
[6] The composition according to [5], wherein the pH is 3.1 or more.
[7] A packaged beverage containing the composition according to [5] or [6].
[8] An agent for suppressing hangover symptoms, comprising bisaclone as an active ingredient.
[9] The inhibitor of [8], wherein the symptoms of hangover are a head sensation, a hangover feeling, a feeling of remaining alcohol, and / or a stomach discomfort.

  ADVANTAGE OF THE INVENTION According to this invention, the composition which can suppress the symptom of a hangover which uses a natural compound as an active ingredient can be provided.

FIG. 1 shows the effect of bisaclone on blood ethanol concentration. FIG. 2 shows the effect of bisaclone and curcumin on blood ethanol concentration. FIG. 3 shows the effect of suppressing hangover symptoms by taking bisaclone (0.5 mg or 0.25 mg). FIG. 4 shows the results of a storage test for bisaclone in beverages with different pH values.

本明細書におけるビサクロンとは上記化合物の光学異性体も包含する概念である。 1. Bisaclone In the present invention, bisaclone refers to a compound represented by the following formula or a salt thereof, and is a compound classified as a bisaborane-type sesquiterpene:

Bisaclone in the present specification is a concept including optical isomers of the above compounds.

  Bisacron may be extracted or purified from plant materials or artificially synthesized, but from the viewpoint of safety, it may be extracted or separated / purified from plant materials. preferable.

  The plant raw material is preferably a ginger family plant, particularly preferably Curcuma longa (Curcuma), Curcuma aromatica, Curcuma zedoaria, Curcuma phaeocaulis, Curcuma kwangsiensis, Curcuma wenyujin, Curcuma xanthorrhiza. Appropriate parts such as rhizomes of plant raw materials can be used as raw materials for the manufacture of bisaclone in the original form, in a form cut into an appropriate size or shape, or in the form of a pulverized product. These raw materials may be appropriately dried.

  The extraction method of bisaclone from plant materials is not particularly limited. For example, a solvent capable of dissolving bisaclone such as water, ethanol, methanol, isopropanol, propylene glycol, diethyl ether, petroleum ether, hexane, acetone, acetonitrile, ethyl acetate, animal and vegetable fats and oils, or a mixture of two or more thereof. Is used to extract solvent-soluble components from plant materials. As the extraction solvent, water and / or a hydrophilic extraction solvent, specifically, alcohol or water is preferable. Ethanol is preferred as the alcohol. The mixing ratio when using a mixture of alcohol and water is not particularly limited, but for example, the weight ratio is preferably in the range of 10:90 to 90:10, and more preferably in the range of 20:80 to 50:50.

  The obtained plant raw material extract is further subjected to purification means such as solvent fractionation, chromatography (column chromatography, high performance liquid chromatography (HPLC), etc.) and / or recrystallization, if necessary, and bisaclone May be separated or purified. For example, bisaclone obtains a methanol extract of turmeric as a plant raw material, elutes the extract with a silica gel column using methanol and chloroform, and more than curcuminoids (mixture of curcumin, demethoxycurcumin, bisdemethoxycurcumin) It can be separated or purified from the highly polar fraction using a preparative HPLC column.

  In the composition of the present invention or the inhibitor of hangover symptoms, 0.5 mg or more of bisaclone is preferably added per one oral intake. Bisaclone may be in the form of an extract of plant material, or may be in a form separated / purified from the extract of plant material. That is, an extract of a plant material containing a predetermined amount of bisaclone can be blended in the composition of the present invention or the hangover symptoms inhibitor.

  The amount of bisaclone in the composition is determined by mixing the composition with ethyl acetate and centrifuging the supernatant from the supernatant to remove ethyl acetate under reduced pressure. It can obtain | require by attaching | subjecting to chromatography (HPLC).

  In the present invention, the term “single oral intake” means the amount of the composition of the present invention or the hangover symptom inhibitor that is orally ingested at a time, or a short time interval (for example, 10 minutes or less, preferably 5 minutes or less). ) Means the total amount taken orally several times continuously. When the composition of the present invention or the hangover symptoms inhibitor is in the form of a liquid composition, for example, 50 ml to 500 ml (typically 50 ml, 100 ml, 150 ml, 200 ml, 250 ml, 300 ml, 350 ml, 400 ml, 450 ml or 500ml) is the amount, and in the case of other forms such as semi-solid (such as jelly) or solid, for example 50g to 500g (typically 50g, 100g, 150g, 200g, 250g, 300g, 350g, 400g, 450g or 500g) is the amount. Hereinafter, “single oral intake” is used in this sense.

  Further, in the present invention, “bisaclone 0.5 mg or more” means that at least when the composition of the present invention or the hangover symptom suppressant is completed, that is, the composition of the present invention or the hangover symptom suppressor is a finished product. At least at the stage of shipment of the manufacturing plant, it means “containing 0.5 mg or more of bisaclone”.

2. Other Components The composition of the present invention or the inhibitor of hangover symptoms may contain a turmeric pigment. Turmeric pigment is obtained by extracting from the rhizome part of turmeric with hot ethanol, hot oil or propylene glycol, or room temperature to hot hexane or acetone. The pigment mainly contains curcumin. The amount of turmeric pigment in the bisaclone-containing beverage of the present invention is blended with turmeric pigment in an amount of 3 to 50 mg, more preferably 5 to 40 mg, particularly preferably 6 to 30 mg of curcumin per single oral intake. Is good.

  In addition to the bisaclone and turmeric pigments, the composition of the present invention or the hangover symptom suppressor is an ingredient that is acceptable in the final form of foods and drinks, pharmaceuticals, etc., and can be taken orally Can be included.

  In particular, when the composition of the present invention or the hangover symptom suppressor is in the form of a liquid composition or a semi-solid composition (such as a jelly), in addition to the above components, fructose-glucose liquid sugar, Cyclic oligosaccharides, acidulants, thickeners, inositol, fragrances, niacin, antioxidants, vitamins, sweeteners, starch, agar, etc. can be added.

  Cyclic oligosaccharides, acidulants, thickening polysaccharides, and sweeteners adjust the flavor of plant material extracts and turmeric pigments to reduce unpleasant tastes (bitterness, astringency, etc.) to the extent that they do not cause discomfort can do.

  Examples of the acidulant include citric acid, malic acid, gluconic acid, tartaric acid, and salts thereof, and one or a mixture of two or more of these can be used. The pH value of the composition of the present invention or the hangover symptom inhibitor can be adjusted by appropriately adjusting the amount of acidulant added. Preferably, the pH value of the composition of the present invention or the hangover symptom suppressor is 3.1 or more, more preferably 3.2 or more, and still more preferably 3.5 or more. In the present invention, the pH value refers to a value measured at a product temperature of 20 ° C. Bisaclone is a very unstable substance in an acidic aqueous solution, and when included in a liquid composition or semi-solid composition (such as a jelly) having a low pH value, it immediately decomposes and its amount is remarkably reduced. On the other hand, when the pH value of the liquid composition or semi-solid composition is preferably 3.1 or more, more preferably 3.2 or more, still more preferably 3.5 or more, and still more preferably 3.7 or more, the pH value increases as the pH value increases. The stability of bisaclone contained in the liquid composition or semi-solid composition is improved, and the decomposition of bisaclone contained in the liquid composition or semi-solid composition is suppressed. As a result, the liquid composition or semi-solid composition can maintain the action and effect of bisaclone for a long time. In the present invention, “the stability of bisaclone is improved” and “the decomposition of bisaclone is suppressed” means that the decomposition rate of bisaclone in a liquid composition or a semisolid composition is less than pH 3.1. This means that the decomposition rate of bisaclone in the liquid composition or semi-solid composition is slow, and the decomposition of bisaclone does not necessarily have to stop completely. In addition, the upper limit of the pH value is preferably 5 or less from the viewpoint of suppressing unpleasant taste such as “bitterness” and “astringency” caused by the extract of the plant raw material.

Thickeners include thickening polysaccharides such as gellan gum, xanthan gum, pectin, guar gum and the like.
Examples of the sweetener include sugars such as fructose, glucose, and liquid sugar, and high-intensity sweeteners such as honey, sucralose, acesulfame potassium, thaumatin, and aspartame.

Examples of the antioxidant include vitamin C, enzyme-treated rutin, tocopherol (vitamin E), catechin and the like.
Vitamins include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin E, niacin, inositol and the like.

3. Composition and use thereof The composition of the present invention is a food or drink composition having an action of reducing so-called hangover symptoms (especially head sensation, hangover feeling, feeling of remaining alcohol, stomach discomfort) upon waking up after alcohol consumption. It can be used as a pharmaceutical composition.

  The form of the composition of the present invention is not particularly limited, but a liquid, solid, or semi-solid composition suitable for oral intake is preferable, and a liquid composition or a solid composition is particularly preferable.

  The liquid composition may be provided as a liquid food (beverage) or a liquid pharmaceutical for oral administration, but is preferably a beverage. The liquid composition is a composition based on water, and can be produced by mixing the above components with water. The amount of each component is as described above. Such a liquid composition can be contained in a container used as a beverage container. Examples of beverage containers include polyethylene terephthalate (PET) containers, so-called PET bottles, metal can containers, and the like. The form of the container is not particularly limited. Further, the capacity of the container is not particularly limited, but for example, 50 ml to 500 ml (typically 50 ml, 100 ml, 150 ml, 200 ml, 250 ml, 300 ml, 350 ml, 400 ml, 450 ml or 500 ml), preferably 100 ml to 200 ml. it can. The means for accommodating the liquid composition in the container is arbitrary.

  The solid composition is provided as, for example, a pharmaceutical having a form such as a granule, capsule, tablet, fine granule, caplet, powder, pill, health food, nutritional supplement (supplement) and the like. Solid composition mixes active ingredients such as bisaclone and turmeric pigments (the amount of each component is as described above) with auxiliary agents such as excipients, extenders, binders, disintegrants, lubricants, etc. However, it can be molded and produced according to a conventional method.

I. Effect of bisaclone on blood ethanol concentration The effect of bisaclone on blood ethanol concentration was tested as follows.

1. Test animals For each test object, 7-week-old male SD rats (7 animals) were used.

2. Test object control: Dextrin (Matsuya Chemical Co., Ltd.)
Bisaclon: The rhizome part of curcuma longa was extracted with water, and the resulting water extract was re-extracted with methanol, and purified from the resulting methanol extract using a preparative column. I used something.
Bisaclone was dissolved in 0.5 w / v% methylcellulose (Wako Pure Chemical Industries).

3. Test method Preliminary breeding was acclimatized for one week from the arrival of the test animals to the day before the start of the breeding.
The test object was forcibly administered intragastrically using a gastric sonde to the following dosage. Ethanol was administered by the same route at the same time so that the following dose was obtained.
Dextrin (control): Dextrin 2010mg / kg
Bisaclone: Bisaclone 250mg / kg + dextrin 1760mg / kg
Ethanol: 2g / kg
After ethanol administration, heparinized blood was collected from the tail vein at 10, 30, 60, 120, 180, and 240 minutes, and blood ethanol concentration at each time point was determined using F-kit ethanol (JK International) according to the manufacturer's instructions. Was measured.

4). Test results The results are shown in FIG. Each result shows the total area under the blood concentration-time curve (AUC) at each time point. It was confirmed that blood ethanol concentration can be reduced by administering bisaclone.

II. Effect of bisaclone and curcumin on blood ethanol concentration The effect of bisaclone and curcumin on blood ethanol concentration was tested as follows.

1. Test animals For each test object, 7-week-old male SD rats (8 animals) were used.

2. Test object control: Dextrin (Matsuya Chemical Co., Ltd.)
Curcumin: Turmeric Color HJK (Inabata Fragrance Co., Ltd.)
Bisaclon: The rhizome part of curcuma longa was extracted with water, and the resulting water extract was re-extracted with methanol, and purified from the resulting methanol extract using a preparative column. I used something.
Curcumin and bisaclone were dissolved in 0.5 w / v% methylcellulose (Wako Pure Chemical Industries) (hereinafter referred to as “0.5% MC”).

3. Test method Preliminary breeding was acclimatized for one week from the arrival of the test animals to the day before the start of the breeding.
The test object was forcibly administered intragastrically using a gastric sonde to the following dosage. Ethanol was administered by the same route at the same time so that the following dose was obtained.
Curcumin only: 125mg / kg
Curcumin + bisaclone: Curcumin 125mg / kg + bisaclone 20mg / kg
Ethanol: 2g / kg
After ethanol administration, heparinized blood was collected from the tail vein at 10, 30, 60, 120, 180, and 240 minutes, and blood ethanol concentration at each time point was determined using F-kit ethanol (JK International) according to the manufacturer's instructions. Was measured.

4). Test results The results are shown in FIG. Each result shows the total area under the blood concentration-time curve (AUC) at each time point. It was shown that blood ethanol concentration can be further reduced by administering a mixture of curcumin and bisaclone rather than curcumin alone, and it was confirmed that bisaclone has an effect of lowering blood ethanol concentration.

III. Effect on hangover symptoms The effect of bisaclone on hangover symptoms was tested as follows.

1. Test beverage A test beverage containing bisaclone (Example A) is prepared by mixing ingredients other than water (powder raw material), adding and dissolving in water to make a 100 mL aqueous solution, and heating it to 93 ° C in a metal can. Made. Comparative Example a was prepared in the same manner as in Example A except that it was hot-packed and then stored at 40 ° C. for one week. The pH value of each test beverage was 3.1. Bisaclone is very unstable in an acidic aqueous solution, and storage at 40 ° C. promotes decomposition and can reduce the amount of bisaclone.

  The turmeric pigment is obtained by extracting the rhizome part of turmeric (Curcuma longa) with acetone and evaporating the acetone under reduced pressure. This turmeric pigment contained 30% by weight of curcumin, and each test beverage contained 30 mg of curcumin.

Bisaclone was used in the form of turmeric extract. The turmeric extract is obtained by extracting the rhizome part of curcuma longa with water. The amount of bisaclone in each test beverage was determined by high-performance liquid chromatography using a solution obtained by mixing the test beverage with ethyl acetate and centrifuging the supernatant and distilling off ethyl acetate under reduced pressure and then dissolving in acetonitrile. It was determined by attaching to a graphic (HPLC). HPLC was performed under the following conditions.

  Example A and Comparative Example a had the following compositions. Bisaclone was contained in Example A in an amount of 0.5 mg and Comparative Example a in an amount of 0.25 mg.

2. Test subjects The test subjects were 10 selected from men and women aged 20 to 65 who can drink alcoholic beverages. Those who could not drink alcoholic beverages (self-reported), those who were in the hospital, those who were taking medication, those who were ill with kidney / liver disease, and those with various types of hypersensitivity were excluded from the study subjects.

3. Test Method The hangover suppression effect was confirmed for each test beverage by the following procedure.
The following test was conducted twice in a week.

  After ingesting the above Example A or Comparative Example a on the day before the test, alcohol was consumed while eating for 2 hours (no limitation on the type of alcohol or intake. However, the alcohol intake was recorded every hour, The two trials consumed almost the same amount of alcohol.)

  I went to bed after drinking, and took 7 hours as a guide. The amount of water that can be consumed after drinking was up to 200 mL. After getting up, a questionnaire about hangover was conducted.

The following matters were prohibited:
Ingestion of medicines and foods to improve hangover

4). Test schedule The test (first test) ingesting Example A as a test beverage was performed on five test subjects, and then the test (second test) was performed on Comparative Example a. Moreover, the said test (1st test) which ingests the comparative example a as a test drink was performed with respect to the remaining 5 test subjects, and the said test (2nd test) was then performed about Example A. .

5. Evaluation items by questionnaire In the questionnaire, each test subject was asked to fill in the self-assessment results by the VAS method for seven items: headache, headache, nausea, malaise, hangover, residual alcohol, and stomach discomfort.

  The VAS (Visual Analog Scale) method is a test that evaluates the degree of subjective symptoms by quantifying. In this method, the highest possible state is set to the right end and the lowest is set to the left end in a straight line. It is also widely used in clinical medicine for subjective evaluation, and is used especially for comparison of the condition before and after administration between subjects.

6). Test result For each evaluation item in the test ingesting each test beverage, an average value was obtained by summing up the VAS entry values of all the subjects. The results are shown in FIG. A t-test was performed between Example A and Comparative Example a, and p <0.1 was determined to be significant.

  In Example A containing bisaclone 0.5 mg, significant suppression of head sensation, hangover sensation, alcohol lingering feeling, and stomach discomfort among the hangover symptoms was observed compared to Comparative Example a containing bisaclone 0.25 mg. In particular, it was confirmed that the effect of suppressing “head feeling” was significantly high.

IV. Storage test
The storage stability of bisaclone according to pH value was tested as follows.
Example 1-6 was used for the test.

The turmeric pigment used was obtained by the method described in “III. Effect on hangover symptoms”.
Bisaclone was used in the form of turmeric extract. The turmeric extract used was obtained by the method described in “III. Effect on hangover symptoms”. The amount of bisaclone in the turmeric extract was determined by mixing the extract with ethyl acetate, centrifuging the ethyl acetate from the supernatant obtained by centrifugation, and then using the solution dissolved in acetonitrile as the analysis sample. In the same manner as the method for measuring the amount of bisaclone in the test beverage described in “Effect on hangover symptoms”, the measurement was performed using high performance liquid chromatography (HPLC).

The pH value of each beverage was adjusted using citric acid and / or trisodium citrate. The pH value in the table refers to the value measured at a product temperature of 20 ° C.
Each beverage was prepared by mixing ingredients other than water (powder raw material), adding and dissolving in water, adding the liquid raw material into a 100 mL aqueous solution, and hot-packing it into a metal can that was heated to 93 ° C. . Four bottles were prepared for each beverage.

  After each test beverage was stored at 93 ° C before heating, after 93 ° C heating / hot-packing, and at 40 ° C for 7 days, 14 days, and 30 days, the amount of bisaclone in each beverage was It was measured in the same manner as in the experiment of “III. Effect on hangover symptoms”. The bisaclone content of each sample was calculated as a percentage when the bisaclone content of the sample before heating at 93 ° C. was taken as 100%.

  The results are shown in FIG. It was shown that when the pH value of the beverage is 3.1 and 3.3 or higher, the decay rate (graph inclination) of the amount of bisaclone in the beverage is moderate as compared with the beverage having a pH value of 2.9. It is also shown that the rate of decay of the amount of bisaclone in the beverage (graph slope) is more gradual when the pH value of the beverage is 3.5 or higher than when the pH value of the beverage is 3.1 and 3.3. It was. That is, when the pH value of the beverage is 3.1 or more, it is confirmed that the decomposition of bisaclone in the beverage can be suppressed and the bisaclone can be stably contained, and when the pH value of the beverage is 3.5 or more, It was confirmed that the decomposition of bisaclone was further suppressed and bisaclone could be stably contained.

Claims (9)

  A composition that is orally ingested and contains 0.5 mg or more of bisaclone per oral intake.   The composition of claim 1, wherein the bisaclone is derived from a turmeric extract.   The composition according to claim 1, further comprising curcumin.   The composition of any one of Claims 1-3 which is food-drinks or a pharmaceutical.   The composition according to claim 4, which is a liquid composition.   The composition according to claim 5, wherein the pH is 3.1 or more.   A packaged beverage in which the composition according to claim 5 or 6 is contained.   An inhibitor of hangover symptoms containing bisaclone as an active ingredient.   The suppressant according to claim 8, wherein the hangover symptom is a head sensation, a hangover feeling, a feeling of remaining alcohol, and / or a stomach discomfort.

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