JP2012031132A - Composition for ameliorating fatigue - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for ameliorating fatigue with significant effects to unidentified complaints caused by fatigue, such as (1) daily tiredness, (2) fatigability or recoverability from tiredness, (3) shoulder stiffness, (4) headaches, (5) clear mind of awakening, (6) recovery from fatigue, including recovery from eye fatigue, (7) dryness of eyes, (8) ameliorating a disposition to catch a cold, (9) forgetfulness, (10) depressed feeling, (11) sagging skin, and (12) thinning hair.SOLUTION: There is provided a composition for ameliorating fatigue containing a soybean saponin B group.

Description

  The present invention relates to a fatigue improving composition.

  The present applicant has continued research and development focusing on the characteristics of soybean components. First, it was found that the soybean saponin B group has an abnormal protein removing action, and Patent Document 1 was proposed. Further, when the applicant further continued research and development, he found that the soybean saponin B group has a blood flow improving function and proposed Patent Document 2.

JP 2006-124327 A JP 2010-59142 A

  An object of this invention is to provide the fatigue improvement composition.

The main configuration of the present invention is as follows.
(1) A fatigue improving composition comprising soybean saponin B group.
(2) The soybean saponin B group is derived from a soybean extract, and is a soybean extract containing 30 to 100 parts by weight of soybean saponin B group out of 100 parts by weight of soybean extract (1) The fatigue improving composition as described.
(3) The soybean saponin B group is derived from a soybean extract, and is a soybean extract containing 50 to 100 parts by weight of soybean saponin B group out of 100 parts by weight of soybean extract (1) 2. The fatigue improving composition according to 1.
(4) Soy saponin B group-containing materials include Soyasaponin I, II, III, IV, V as saponin B group or acetylated forms thereof, and Soyasaponin A1, A2, A3, A4, A5, A6 as soybean saponin A group. The fatigue-improving composition according to any one of (1) to (3), wherein Ac, Ad or an acetyl form thereof is contained.
(5) The fatigue improving composition according to any one of (1) to (4), wherein the fatigue improvement is an improvement in stiff shoulders, a headache, or a refreshing feeling.
(6) A fatigue improving food comprising the fatigue improving composition according to any one of (1) to (5).
(7) A fatigue improving feed or veterinary medicine comprising the fatigue improving composition according to any one of (1) to (4).

  The composition containing soy saponin B group includes (1) daily fatigue, (2) ease of fatigue, ease of fatigue, (3) stiff shoulders, (4) headache, and (5) refreshing awakening. (6) Fatigue recovery such as eye recovery, or even (7) Drying of eyes, (8) Improving ease of catching cold, (9) Forgetfulness, (10) Depressed mood, (11) Skin (12) It has a remarkable effect on indefinite complaints associated with fatigue, such as hair volume.

The graph which showed the improvement situation of fatigue after taking a tablet by change (physical condition) of VAS A graph showing the improvement of daily fatigue after ingestion of tablets in a stage evaluation of effect sensitivity A graph that shows the improvement in ease of fatigue after ingestion of tablets and the improvement status of fatigue recovery speed in a stage evaluation of the effect sensitivity A graph showing the improvement status of stiff shoulders after ingestion of tablets in a stage evaluation of effect sensitivity A graph showing the improvement of head feeling after ingestion of tablets in a stage evaluation of effect sensitivity A graph showing the level of improvement in the awakening feeling after taking a tablet in a stage evaluation of the effect sensitivity The graph which shows the result of the double blind test which confirmed the fatigue recovery by administering the formulation containing soybean saponin B The graph which shows the result of the double blind test which confirmed the change of the parameter | index of fatigue recovery by administering the formulation containing soybean saponin B The graph which shows the result of the double blind test which confirmed the real feeling of the fatigue recovery by administering the formulation containing soybean saponin B

The present invention is described in detail below.
Soybean-derived saponins are widely distributed in seed coats, cotyledons, hypocotyls or leaves, stems, roots, etc. in soybean seeds. The structure is similar to that of glycyrrhizin, but the triterpenoid skeleton has a sugar chain composed of 2 to 5 sugars. Soy saponins are classified into four groups (A, B, E, and DDMP groups) according to the structure of aglycon (non-sugar part), and all groups of saponins have a variety of sugar chain structures.
To date, eight types of A groups, two types of E groups, five types of B groups, and six types of DDMP groups, each having Soyasapogenol A, B, E, and DDMP as aglycons, have been identified. The saponin A group is a bisdesmoside-type saponin with sugar chains bound at two positions, C-3 and C-22, of Soyasapogenol A. It is distributed only in soybean seed hypocotyl and has an unpleasant taste (bitterness, astringency). It is the main cause. There are currently two names for the saponin A group, SoyasaponinA1 and SoyasaponinAb are the same compound, A2 is Af, A3 is Ah, A4 is Aa, A5 is Ae, and A6 is Ag. Ac and Ad are not known.

  In contrast, the saponin B group and the E group are monodesmoside saponins in which one sugar chain is bonded only at the C-3 position. The saponin DDMP group can be purified by extraction under mild conditions (Non-patent Document Agric Biol Chem, 57 546-550 (1993)), but is converted to the saponin B group under heating and alkaline conditions. Therefore, most of the saponins present in soybeans are the saponin A group and the saponin DDMP group, the saponin B group is small, and the saponin B group is an artifact component that is mostly produced from the saponin DDMP group during extraction. It is estimated that there is. There are many saponin B groups in soybean hypocotyls and cotyledons. Currently, there are two names for saponin B group, Soyasaponin I and Soyasaponin Bb are the same compound, II is Bc, III is Bb ', IV is Bc' V is Ba (Non-Patent Document BBB 62 (12) 2291-2299, 1998).

In general, many saponins are hemolytic. However, it has been reported that soybean saponin has almost no hemolytic property (Non-patent Document Basics and Clinical Vol.15 No.5 1981). Moreover, when the present inventors measured the hemolysis index | exponent with respect to the 2% blood suspension of the rabbit of the soybean saponins obtained from soybean, it is 100 or less like ginseng saponin, and does not have hemolysis like other reports. It has been found. Further, as disclosed in Patent Document 1, the present inventors tested mutagenicity and acute toxicity, and it was confirmed that none of them was abnormal and the soybean saponin B group had high safety.
A composition containing the soybean saponin B group of the present invention in a high content (hereinafter sometimes referred to as “high-content soybean saponin B group”) can be obtained by the following steps.

[Extraction of saponin]
The raw soybean hypocotyl can be used either defatted in advance with an organic solvent or the like, but not defatted from the viewpoint of saponin extraction efficiency. The method for extracting saponin from the raw material soybean hypocotyl is generally a method of adding 5 to 10 times the volume of extraction solvent to the raw material at room temperature to 80 ° C. and stirring, but saponin can be sufficiently extracted. If it is conditions, it will not specifically limit. The ion exchange resin in the present invention is not particularly limited as long as it is a weakly basic anion exchange resin containing a tertiary amine, and a resin having a non-uniform particle size such as Diaion WA-30 manufactured by Mitsubishi Kasei can also be used. However, those having a uniform particle size having a particle size distribution of 90% or more in the range of the average particle size ± 10% are preferable.

[Elution and purification of saponin]
After distilling off the solvent from the saponin extract by distillation, adsorbing the saponin solution diluted with water onto the ion exchange resin, washing the resin with water, alcohol or hydrous alcohol, then using acid or alkali The saponin adsorbed on the resin is eluted. The crude soy saponin product obtained by drying the eluted saponin solution as it is has a low purity of 20 to 50% by weight, contains many impurities other than saponin, and the ratio of the highly bioactive soybean saponin B group is also about 20 to 30% by weight. And low.

  In order to increase the purity of saponin, the eluted saponin is diluted with water as it is, and the saponin is adsorbed on a nonpolar synthetic adsorbent. Examples of non-polar synthetic adsorbents include styrene / divinylbenzene type resins, such as Mitsubishi Chemical, Diaion HP-20, and Rum and Haas Amberlite XAD-2. . The alcohol concentration in the hydrous alcohol used when adsorbing to the synthetic adsorbent varies depending on the type of alcohol, but it is preferably 0 to 50% by weight in the case of methanol and 0 to 30% by weight in the case of ethanol. Next, after the resin is washed with water or water-containing ethanol, it can be eluted with water-containing alcohol having a higher alcohol concentration than that at the time of washing to obtain a saponin-rich solution.

[Post-processing]
After adjusting the pH of the obtained saponin-rich solution using a pH adjuster as necessary, the saponin-rich solution is dried by a method such as heat drying, reduced pressure heat drying, spray drying, freeze drying, etc. Obtainable.
Through the above steps, a high-concentration soybean saponin having a purity of 70% by weight or more can be obtained efficiently and inexpensively, and the highly active soybean saponin B group can be concentrated to a concentration of 50% by weight or more. The soy saponin B group ratio can be increased to 70% by weight or more. For example, Japanese Patent Application Laid-Open No. 2006-124324 discloses a manufacturing method.

  As the order of purification with resin, after treatment with anion exchange resin, purification with non-polar synthetic adsorbent is performed. When treated with a synthetic adsorbent first, low-polar substances and the like are strongly adsorbed to the synthetic adsorbent, and the resin deteriorates even when subjected to normal resin regeneration such as alkali treatment, and the resin capacity gradually decreases. On the other hand, low-polar substances can be removed in addition to soybean isoflavones and oligosaccharides by first refining soybean saponin with an anion exchange resin, and the subsequent processing capacity of non-polar synthetic adsorbents Is improved and deterioration is less likely to occur. In that case, the anion exchange resin can be repeatedly used many times by treatment with alkali.

It was confirmed that the composition prepared with rich soybean saponin B group has a fatigue recovery effect.
Examples of forms utilizing such effects include pharmaceuticals, foods, beverages, supplements, food additives, feeds, feed additives, animal drugs, and the like. Oral or parenteral provision is also possible. Although the high content soybean saponin B group can be used for various purposes as it is, it can be mixed with various other components in advance or added to foods, feeds or veterinary drugs according to the purpose.

  As food, it can be used directly or with various nutritional components added. For example, after adding suitable auxiliaries such as starch, lactose, maltose, vegetable oil powder, cocoa butter powder, stearic acid, etc., using conventional means, edible forms such as granules, granules, tablets , Capsules, pastes, etc., may be used for food as health supplements, health functional foods, etc., and various foods, for example, processed foods such as ham and sausage, fishery processed foods such as kamaboko and chikuwa , Bread, confectionery, butter, powdered milk, fermented dairy products, and may be used by adding to beverages such as water, fruit juice, milk, and soft drinks. Such agents and foods can be produced by a formulation technique that is usually employed.

  As an application method as a medicine, either oral administration or parenteral administration can be adopted. In administration, the active ingredient can be mixed with a solid or liquid nontoxic pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration, and injection, and administered in the form of a conventional pharmaceutical preparation.

  It can be conveniently used when it is in a composition mixed with a bulking agent. Examples of bulking agents include sugars such as glucose, lactose, maltose and sucrose, sugar alcohols such as sorbitol, processed starches such as dextrin and cyclodextrin, starches such as wheat starch and corn starch, proteins such as casein and soy protein, Polymer stabilizers such as gum, sodium alginate, sodium caseinate, gelatin, pectin, powdered cellulose, carboxymethylcellulose, emulsifiers such as lecithin, sucrose fatty acid ester, propylene glycol fatty acid ester, glycerin fatty acid ester, calcium powder, and the like can be used.

  The fatigue improving composition of the present invention can contain a compound having an antioxidant action in addition to the above-described high-content soybean saponin B group. Although the compound which shows an antioxidant action is not specifically limited, For example, various vitamins, various polyphenols, such as silymarin, tocotrienol, coenzyme Q10, and the natural component containing them are mentioned.

  The composition of the present invention can be applied in the form of, for example, a solution such as an aqueous solution, an oil, an emulsion, a suspension, a semi-solid agent such as a gel or a cream, a solid agent such as a powder, a granule, a tablet, or a capsule. . It can be prepared in these forms by a conventionally known method to form various dosage forms.

  The fatigue-improving composition of the present invention can contain additives such as a pharmaceutically acceptable diluent or carrier as required, in addition to containing the high-content soybean saponin B group as a main active ingredient. Moreover, the composition of this invention can contain the other medicinal component with high pharmacological activity if needed.

In addition, the following can be added according to a use and a dosage form.
Examples of the oils and fats include liquid oils such as camellia oil, evening primrose oil, macadamia nut oil, olive oil, rapeseed oil, corn oil, sesame oil, jojoba oil, germ oil, wheat germ oil, rice oil, glycerin trioctanoate, and cocoa butter , Coconut oil, hydrogenated coconut oil, palm oil, palm kernel oil, molasses, mollusc kernel oil, hydrogenated oil, hydrogenated castor oil, beeswax, candelilla wax, cotton wax, nuta wax, lanolin, lanolin acetate, liquid lanolin And waxes such as sugarcane wax.

  Examples of the thickener include carrageenan, gum tragacanth, quince seed, casein, dextrin, gelatin, CMC, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxyvinyl polymer, guar gum, xanthan gum, bentonite and the like.

The medicinal ingredient, for example, vitamin A oil, vitamin A such as retinol, vitamin B ₂ such as riboflavin, vitamin B ₆ such as pyridoxine hydrochloride, vitamin B _12, folic acid, L- ascorbic acid, L- ascorbic Vitamin C such as acid phosphate ester, L-ascorbic acid monopalmitate, L-ascorbic acid dipalmitate, L-ascorbic acid-2-glucoside, pantothenic acid such as calcium pantothenate, vitamin D ₂ , Vitamin Ds such as calciferol; vitamins such as vitamin E such as α-tocopherol, tocopherol acetate, nicotinic acid and α-tocopherol can be mentioned.

  Whitening agents such as placenta extract, glutathione, and yukinoshita extract, skin activators such as royal jelly, linden extract, capsaicin, gingeron, cantalis tincture, ictamol, caffeine, tannic acid, blood circulation promoters such as γ-oryzanol, glycyrrhizic acid Derivatives, glycyrrhetinic acid derivatives, anti-inflammatory agents such as azulene, amino acids such as arginine, serine, leucine and tryptophan, maltose sucrose condensates of resident bacteria control agents, lysozyme chloride and the like.

  In addition, chamomile extract, parsley extract, beech extract, wine yeast extract, grapefruit extract, honeysuckle extract, rice extract, grape extract, hop extract, rice bran extract, loquat extract, buckwheat extract, yakuinin extract, assembly extract, merirot extract, birch extract, licorice extract , Peony extract, bonito extract, loofah extract, capsicum extract, lemon extract, gentian extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, tea extract, seaweed extract, cucumber extract, clove extract, carrot extract, Examples include various extracts such as maroni extract, hamamelis extract and mulberry extract.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples etc.

Example 1
First, the prescription of the fatigue improving composition used in Example 1 of the present invention will be described.
<Adjustment of soy saponin>
As for the soybean saponin used in the present invention, it is desirable to use 30 to 100 parts by weight of soybean saponin B group out of 100 parts by weight of soybean extract, and it can be obtained by the above production method. Also, commercially available products can be obtained by using saponin B manufactured by J-Oil Mills.
The content of soybean saponin obtained by the above production method and product is 50% or more.

<Prescription>
In this example, an experiment was conducted by orally administering to a subject a tablet containing collagen, CoQ10, soy isoflavone, hyaluronic acid, and royal jelly in addition to soy saponin. Table 1 shows the blending amount of the tablets.

<Intake method>
Two capsules were taken with water etc. twice a day after meals in the morning and evening.

<Subject>
(1) Selection criteria Women over 45 years old (2) Exclusion criteria Those who meet any of the following conditions were excluded as subjects in this study.
A: Person with severe gastrointestinal disease, liver disease, kidney disease or heart disease suspected or has a history of it B: Allergies or idiosyncrasies to food (especially gelatin, collagen, soybean, wheat, bee) Person who possesses c: Person who already uses similar products (supplements containing collagen, CoQ10, isoflavone, saponin, hyaluronic acid). However, those who were able to discontinue these supplements 1 week before the start of intake were allowed to participate.

<Test method>
The study design was an open study in which everyone took active drugs. The ingestion period was 8 weeks, and the test tablets were ingested twice a day with water after breakfast and dinner. During the monitoring period, intake of supplements corresponding to the above c) was prohibited. Other supplements were allowed to continue, but no new supplements were allowed to start during monitoring.
In addition, drinking, smoking, and regular exercise in daily life were free.

<Investigation method>
The questionnaire was conducted a total of 4 times before the start of intake (week 0), 2 weeks after intake, 4 weeks after intake, and 8 weeks after intake.

<Evaluation methods and items>
(1) Evaluation by VAS method VAS (Visual Analogue Scale) is, for example, an evaluation of whether there is pain, draw a straight line of 10 cm, the left end is “no pain”, the right end Let the patient (subject) place a mark (x) to indicate where the current pain is, and measure the length from the left edge to the mark. It is a method to evaluate the strength of the. The items evaluated by the VAS method are as follows.
・ Daily fatigue ・ Easy to get tired, easy to get tired ・ Stiff shoulder ・ Heavy head ・ Feeling of getting up in the morning

(2) Stage evaluation of actual effect sensitivity Depending on the degree of improvement, the subjects were asked to select the effect as “I did not feel it at all”, “I did not feel it much”, “I felt a little”, or “I felt it” The following points were given to each.
0 points: I did not feel at all 1 point: I did not feel much 2 points: Somewhat felt 3 points: I felt

In addition, since it was originally not worried, when it was not possible to evaluate, “Non-evaluation” was selected, and in the case of statistics, processing was performed except those who selected “Non-evaluation”. The items evaluated by the stage evaluation of effect sensitivity are as follows.
・ Improves daily fatigue ・ Improves “ease of fatigue”, improves fatigue recovery speed ・ Improves shoulder stiffness ・ Improves head feeling ・ Improves a refreshing feeling of awakening

<Statistical test method>
The VAS measurement data was expressed as an average value ± standard error for each item, with the highest point being 100 points. The improvement actual sensitivity was counted for each item by selecting “not evaluated”, 0 points, 1 point, 2 points, and 3 points for each item. No significant difference test was performed.

<Result>
The change in evaluation by the VAS method is shown in FIG. As can be seen from the figure, when taking tablets containing soybean saponin, improvements were observed in all evaluation items. In particular, “daily fatigue”, “easy to get tired and easy to get rid of”, “stiff shoulders”, and “feeling when waking up in the morning” showed significant improvements before and 8 weeks after ingestion.

Next, with regard to the statistical results of the stage evaluation of the effect sensitivity, “Daily fatigue is improved” is shown in FIG. 2, “Improvement of“ Fatigue ”and fatigue recovery speed is improved” in FIG. 4 is shown in FIG. 4, “Improved head feeling” is shown in FIG. 5, and “Improved refreshing feeling of waking” is shown in FIG.
In any of the evaluation items, 2 weeks after ingestion, those who answered “2 points: felt a little” or “3 points: felt” divided the majority by about 30% to about 40%. After 8 weeks after ingestion, those who answered “2 points: felt a little” or “3 points: felt” were about 57% to about 66%, greatly exceeding the majority. It was found that the subjects gained a feeling that their physical condition was greatly improved by taking tablets containing the saponin B group.

Example 2
<Prescription>
A soft capsule formulation was prepared using soybean saponin B group prepared in the same manner as in Example 1. The prescription for soft capsules was as follows.
Formulation 1: Saponin AZ-B (manufactured by J-Oil Mills) 100 mg (50 mg as soybean saponin B) / day Formulation 2: Placebo (containing only oil)

<Test method>
A parallel-blind double-blind method with placebo as a control was adopted.

<Subject>
Targeting 30 healthy men and women with an average age of 47 years, after randomly assigning them to two groups, it was confirmed that the age and gender were not biased.

<Test intake and intake method>
Ingestion period: 12 weeks Intake amount: 2 tablets / day
Ingestion method: Ingest with water

<Evaluation of administration test effect>
Actual evaluation by questionnaire was performed 3 times, 4 weeks, 8 weeks and 12 weeks after ingestion. The evaluation index items for fatigue or fatigue recovery include: “body weight to feel normally”, “easy to recover from fatigue”, “ease of fatigue”, “bad morning awakening”, “stiff shoulders”, “daily fatigue” "Feeling", "bad sleep", "feeling when waking up in the morning", "volume of hair", "fatigue of eyes (including frequency and degree)", "blurred eyes (including frequency and degree)" , "Dry eyes (including frequency and degree)", "Forget things (including frequency and degree)", "Ease of catching a cold", "Depressed mood", "Sag slack", "Stairs 17 items of “feeling rising” were adopted as questions. For each item, “1. improved”, “2. somewhat improved”, “3. did not change”, “4. worsened”, “5. The subjects were asked to answer in a five-step evaluation. In addition, as a comprehensive evaluation, we received answers in four stages: “1. I felt improvement”, “2, I felt a little”, “3, I didn't feel much”, and “4. I didn't feel at all”. In the analysis, the responses of the subjects who evaluated “5. Originally not interested” were excluded from the effect evaluation.

<Statistical test method>
The survey responses were evaluated as “1. Improved” or “2. Slightly improved”. The number of subjects was counted as “Actual effect”, and “3. No change” or “4. The number of subjects was counted as “no effect”. The appearance rate of each evaluation is shown in FIG. Moreover, chi-square test was performed about evaluation of each item, and it was evaluated whether it was statistically significant. In the overall evaluation, Mann-Whitney U test was performed in four stages: felt, slightly felt, not felt much, or not felt at all.

<Result>
As shown in FIG. 7, the evaluation of the soybean saponin B administration group was high in most survey items. In particular, as shown in FIG. 8, the soybean saponin administration group showed a statistically significant effect on the placebo administration group in terms of the improvement of “normal body weight” and “morning awakening”. It was confirmed that In addition, regarding the overall evaluation of the subjects, as shown in the nonparametric rank sum test shown in FIG. 9, it was revealed that the soybean administration group had an effect of recovery from fatigue. Furthermore, as shown in FIG. 8, it was confirmed that the two items of “ease of recovery from fatigue” and “ease of fatigue” increase as the administration period elapses.
As described above, in the double blind test in which soybean saponin B was administered, it was confirmed that the soybean saponin B administration group significantly recovered from fatigue.

Claims (7)

  A fatigue improving composition comprising soybean saponin B group.   2. The fatigue according to claim 1, wherein the soybean saponin B group is derived from the soybean extract and is a soybean extract containing 30 to 100 parts by weight of the soybean saponin B group out of 100 parts by weight of the soybean extract. Improvement composition.   2. The fatigue according to claim 1, wherein the soybean saponin B group is derived from a soybean extract and is a soybean extract containing 50 to 100 parts by weight of the soybean saponin B group out of 100 parts by weight of the soybean extract. Improvement composition.   Soy saponin B group-containing materials include Soyasaponin I, II, III, IV, V as saponin B group, or their acetylated form, Soyasaponin A1, A2, A3, A4, A5, A6, Ac, Ad as soybean saponin A group Or those acetylated bodies are contained, The fatigue improvement composition of Claims 1-3 characterized by the above-mentioned.   The fatigue improving composition according to any one of claims 1 to 4, wherein the fatigue improvement is an improvement in stiff shoulders, a headache feeling, or a refreshing feeling of awakening.   A fatigue improving food comprising the fatigue improving composition according to any one of claims 1 to 5. A fatigue improving feed or veterinary medicine comprising the fatigue improving composition according to any one of claims 1 to 4.