JP6885757B2 - QOL improver - Google Patents

Description

The present invention relates to a QOL improver containing a sulfur-containing amino acid.

In recent years, the awareness of long-term care and nursing has increased, and the index called QOL has come to be used frequently. QOL is an abbreviation for quality of life and is often used to mean something like "quality of life" or "quality of life." QOL depends on the subjectivity, values, and outlook on life of an individual, and even in the same environment, the level of QOL can change depending on how the individual perceives it.

In this way, QOL can change by personal subjectivity, and it is difficult to measure its degree, but recently, as a relatively objective scale, an evaluation scale that analyzes from the answers of many question items. Has appeared, and some have been scientifically proven to be valid. As such an evaluation scale, SF-36 (registered trademark) (MOS Short-Form 36-Item Health Survey), EQ-5D and the like are known. In particular, the former was created in connection with the Medical Outcom Study (MOS) in the United States, translated in Japan and other countries around the world, and is the most widely used in the world, and its reliability, validity, and reaction. It has been proven to have sufficient properties in sex.

By using such an evaluation scale, it is possible to observe the current state of an individual's QOL and changes in the QOL associated with various behaviors. In addition, by using this evaluation scale as an index, it becomes possible to screen behaviors, foods and drinks, drugs, etc. that improve QOL. If there is a food or drink that can improve QOL by ingesting it on a daily basis, it is extremely useful. For example, Patent Document 1 describes that the Lactobacillus ONRICb0240 strain, which is one of the lactic acid bacteria, improved the overall health and vitality of SF-36 (registered trademark) and significantly improved the physical health. Has been done.

Sulfur-containing amino acids are a general term for amino acids that have a sulfur atom in the molecule. It is known that it is abundantly contained in plants of the genus Allium, cycloallyin having a sulfur atom as a heteroatom of a ring structure, S-alkyl-L-cysteine sulfoxide or S-alkenyl- having a sulfur atom as a sulfoxide. There are L-cysteine sulfoxide and its analogs. Examples of cysteine sulfoxide contained in onion include S-methylcysteine sulfoxide (MCSO), S-propylcysteine sulfoxide, S-allyl-L-cysteine sulfoxide, and S-1-propenyl-L. -Cysteine sulfoxide (PeCSO) and the like can be mentioned.

Patent Document 2 reports that cycloalliin has a fibrin-dissolving action, a blood glucose lowering action, and a blood lipid lowering action. In addition, Patent Document 3 reports that PeCSO has a testosterone-increasing effect, and is expected to have an effect on the prevention and treatment of diseases in which testosterone is effective, such as prevention of aging of male sexual function. There is a description. However, Patent Documents 2 and 3 do not describe any effect on improving QOL.

International release WO2012 / 133533 Japanese Patent No. 361178 Japanese Patent No. 4172488

An object of the present invention is to provide a QOL improving agent for improving human mental health, particularly mental health, which is low in cost, safe and easy to ingest.

The above problem can be solved by a QOL improving agent containing a sulfur-containing amino acid.

The QOL improving agent of the present invention has an effect of improving the score of SF-36 (registered trademark) by ingesting it, and has an effect of reducing physical pain, increasing mental health, and improving QOL. Shown. Further, according to the present invention, since the effect is obtained by the sulfur-containing amino acid derived from a safe plant of the genus Allium, it is simple and highly safe, so that it can be continuously ingested.

The sulfur-containing amino acid which is the active ingredient of the present invention is the above-mentioned cycloalliin, cysteine sulfoxide, and analogs thereof. For these, synthetic products may be used, or commercially available reagents may be used. Alternatively, a composition containing a sulfur-containing amino acid produced by extraction, purification or the like from a natural product such as an animal or plant containing the above-mentioned sulfur-containing amino acid can also be used. Preferably, cycloallyin and S-methylcysteine sulfoxide (MCSO), S-propylcysteine sulfoxide, S-allyl-L-cysteine sulfoxide, S-1 extracted from Allium plants such as onions. Examples include compositions containing sulfur-containing amino acids selected from -propenyl-L-cysteine sulfoxide (PeCSO).

Among them, since PeCSO and MCSO, which are abundantly contained in onions, are highly effective, onion extracts, which are sulfur-containing amino acid compositions derived from onions, are most preferable. However, onions contain CS lyase (alliinase), which is an enzyme that converts PeCSO and MCSO into sulfenic acid. Therefore, when plant tissues are destroyed by operations such as extraction and cooking, the action of the enzyme causes PeCSO and MCSO in the plant are lost. Therefore, PeCSO and MCSO are hardly contained in the extract of the above-mentioned plant and the cooked food containing the above-mentioned plant obtained by the conventional usual method.

Therefore, when PeCSO and MCSO are prepared from onions, it is preferable to heat-treat the plant before cutting it to inactivate CS lyase and then perform extraction treatment. As such a method, a method for preparing cysteine sulfoxide from onions described in Patent Document 2 can be adopted. More specifically, uncut plants of the genus Allium are heat-treated at a pressure of 1 to 5 atm and a temperature of 40 to 150 ° C. for 5 to 120 minutes to remove sulfur-containing amino acids contained in the plants. Inactivates the degrading CS lyase. Then, the heat-treated product of the obtained onion is extracted with alcohol and concentrated under reduced pressure to obtain a heat-treated post-treatment extract containing an L-cysteine sulfoxide derivative.

Preferably, the cysteine sulfoxides used in the present invention, especially PeCSO and MCSO, (i) heat the onion, (ii) treat the heated onion with a γ-glutamyl bond cleaving enzyme, and then (iii). It can be prepared by subjecting the obtained enzyme-treated product to ion exchange chromatography. The detailed procedure of this method will be described below using an onion as an example.

The steps (i) to (iii) are preferably carried out under acidic pH conditions in order to prevent alteration of PeCSO and MCSO, unless required for an enzymatic reaction or the like. The preferred pH is pH 5.5 or less, more preferably pH 4.5 or less.

In step (i), the onions are heated. The heating inactivates the enzyme CS lyase, which decomposes PeCSO and MCSO contained in onions. The heating conditions are not particularly limited as long as the CS lyase can be inactivated without altering the target PeCSO and MCSO, but for example, the pressure is 1 to 5 atm and the temperature is 40 to 150 ° C. 5 to 120 minutes, more preferably 15 to 40 minutes at a pressure of 1 to 2 atm and a temperature of 80 to 120 ° C.

When the inside of an onion is exposed to the air by cutting, crushing, perforating or the like, the contained PeCSO and MCSO are decomposed and the content thereof is reduced. Therefore, the heating is preferably performed on the undivided onions. Here, an "unsubdivided" onion is either not cut, divided, crushed, perforated, scratched, etc., or is processed, but the sulfur-containing amino acid content is increased by the processing. Those that are not significantly reduced, for example, those that can achieve a final yield of sulfur-containing amino acids of 80% or more with respect to intact onions.

Step (ii) is a step of treating the onion heated in the above step (i) with γ-glutamyl bond cleaving enzyme. Since a part of PeCSO and MCSO in the onion exists as a glutamyl form, glutamic acid is cleaved from the glutamyl form by enzymatic treatment to release PeCSO and MCSO. In order to allow the enzymatic reaction to proceed sufficiently, it is preferable to cut, crush, shred, etc. the onion heated in the above step (i) before the enzymatic treatment. The subdivided onions are further diluted with an aqueous liquid such as water, acidic water, or alkaline water about 2 to 20 times. The pH of the aqueous liquid is adjusted to the optimum pH of the γ-glutamyl bond-cleaving enzyme to be used later or its vicinity.

Examples of the γ-glutamyl bond-cleaving enzyme used for the enzyme treatment include γ-glutaminase, γ-glutamyl transferase, γ-glutamyl transpeptidase, γ-glutamyl peptidase and the like. These enzymes may be extracted from animals, plants, microorganisms, etc., or may be commercially available products. Examples of commercially available products include glutaminase SD-C100S manufactured by Amano Enzyme. The conditions for the enzyme treatment may be appropriately set according to the optimum conditions for the enzyme, the type of Allium plant to be used, the site to be used, the size, the state of subdivision, and the like. Generally, the amount of the enzyme added is 0.001 to 1% by mass, preferably 0.01 to 0.1% by mass, based on the total amount of the onion. The reaction conditions may be the optimum pH of the enzyme, about 1 to 24 hours at a temperature of 15 to 65 ° C., preferably about 2 to 6 hours at 35 to 60 ° C. After the completion of the enzyme treatment, it is preferable to inactivate the γ-glutamyl bond-cleaving enzyme by heating, pH adjustment, or the like. If necessary, the reaction product obtained by the above enzyme treatment may be filtered, centrifuged, squeezed or the like to separate the solution containing PeCSO and MCSO. Further, the obtained solution may be concentrated.

In step (iii), the reaction product obtained by the enzyme treatment in step (ii) above is subjected to ion exchange chromatography. The ion exchange resin for the ion exchange chromatography may be a cation exchange resin, but a strongly acidic cation exchange resin is preferable, and a sulfonic acid type strongly acidic cation exchange resin is more preferable. Commercially available products can be used as the ion exchange resin, for example, Diaion (registered trademark) UBK-550, Diaion (registered trademark) SK1B (manufactured by Mitsubishi Chemical Corporation), Amberlite (registered trademark) IR120B, Amber. Preferably used are Wright (registered trademark) 200C, Dowex (registered trademark) MSC-1 (The Dow Chemical Company), Duolite C26 (Rohm and Haas), LEWATTI (registered trademark) SP-112 (LANXESS Distribution GmbH), etc. Can be done. Ion exchange chromatography may be performed according to a usual procedure. The eluate containing PeCSO and MCSO obtained by ion exchange chromatography may be used as it is in the present invention, but concentration or further desalting treatment is preferable because the purity of PeCSO and MCSO is increased.

By the above method, a fraction containing a high amount of PeCSO and MCSO can be obtained from the onion. The obtained fraction can be dried as it is and contained in the QOL improving agent of the present invention. Further, if necessary, in addition to or in place of the above drying, treatments such as freeze-drying, solidification, granulation, powdering, granulation, and tableting may be performed.

The content of sulfur-containing amino acids in the QOL improving agent of the present invention is preferably 5 to 1000 mg, more preferably 6 to 200 mg, still more preferably 6 to 200 mg, based on the daily intake of adults as the content of PeCSO and MCSO. Is 7 to 50 mg, most preferably 9 to 25 mg. Specifically, when the QOL improving agent of the present invention is in the form of granules or tablets, the content of sulfur-containing amino acids is, for example, 0.2 to 10% by mass, preferably 0. It is 5 to 5% by mass.

The QOL improving agent of the present invention can be contained in foods, feeds or cosmetics. When used as food or feed, it is preferable to include PeCSO and MCSO so that the daily intake is within the above range, but in consideration of long-term intake, 1 The content may be such that the daily intake is less than 5 mg.
When used as cosmetics, for example, face or body emulsions, cosmetics, creams, lotions, essences, facial masks, sheets and the like are preferable. The content of the onion-containing composition of the present invention in cosmetics is not particularly limited, but is 0.001 to 60% by mass, preferably 0.01 to 40% by mass, based on the weight of the cosmetic base material. The range is appropriate.

The quality of life improver of the present invention is for improving the subscale score of SF-36 (registered trademark) regarding mental health, particularly for improving the score of mental health, for improving mental health, or for improving SF-36 (registered). It may be a medicine, a food or drink, etc. for improving or treating a decrease in QOL associated with a decrease in mental health of the trademark). Agents of the present invention may be applied to human.

Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples.

(Production Example) Production of onion extract After washing and dehulling 5000 g of onion (Kita Momiji 2000), the whole onion was heat-treated in a hot water bath at 95 ° C. for 20 minutes without cutting. The heat-treated onions were crushed using a mixer (manufactured by Oster), and 1 mL of water was added and dispersed per 1 g of the onions. Glutaminase (glutaminase SD-C100S; manufactured by Amano Enzyme) was added to the obtained dispersion in an amount of 0.025% by mass based on the total amount of onions in the solution, and the reaction was carried out at 60 ° C. for 2 hours to complete the reaction. After that, the enzyme was inactivated by heating at 90 ° C. for 15 minutes. The obtained reaction solution was centrifuged at 6,000 rpm for 30 minutes, suction-filtered, and then freeze-dried to obtain about 500 g of an onion crude heat-treated extract containing about 3% by mass of sulfur-containing amino acids.
Distilled water was added to the extract after the rough heat treatment of the onion to obtain a 30% (w / v) aqueous solution. 1000 mL of this aqueous solution was used as a sample solution and passed through 500 mL of a strongly acidic cation exchange resin (Diaion SK1B, manufactured by Mitsubishi Chemical) regenerated with hydrochloric acid. Then, the sample solution remaining in the column was washed out with 3000 mL of distilled water. Then, 1000 mL of a 5% sodium hydroxide solution (pH = 14) was passed through the column to elute the sulfur-containing amino acids adsorbed on the ion exchange resin. Further, 2000 mL of distilled water was added to elute the liquid remaining in the column. The eluate eluted with the sodium hydroxide solution and the eluate eluted with distilled water are combined, concentrated with an evaporator (manufactured by Tokyo Rikaki), desalted, and further lyophilized to obtain sulfur-containing amino acids. A powdered onion extract contained was obtained. This powder contained about 2.2% by mass of PeCSO and about 0.72% by mass of MCSO.

(Example 1)
The onion extract of the production example was blended so as to contain 30 mg of sulfur-containing amino acids per 3 tablets per day, and after adding excipients and the like, tablets were tableted using a tableting machine to produce tablets. After that, it was confirmed that the appearance, flavor, and properties were indistinguishable by coating, and the mixture was blinded and used in the test.

(Comparative Example 1)
Excipients were blended in place of the onion extract, and tablets with the same raw materials were produced as placebo tablets. Further, in the same manner as in Example 1, it was confirmed that the appearance, flavor, and properties could not be distinguished by coating, and the mixture was blinded and used in the test.

(Test Example 1)
The subjects were 60 healthy Japanese men aged 50 to 80 years. The 60 subjects were assigned by the stratified block randomization method and divided into 2 groups (30 subjects in each group). The study was a placebo-controlled randomized, double-blind, parallel-group comparative study in which 3 tablets of Example 1 and Comparative Example 1 were ingested daily with water or lukewarm water. The intake period was 4 weeks, and 4 subscales related to mental health (vitality, social function, daily role) were used to evaluate health-related quality of life using the SF-36v2 questionnaire before and 4 weeks after the start of intake. A total of four subscales of function (mental) and mental health) were evaluated.
The score values at the start and after ingestion for 4 weeks are shown in Table 1 as average values. In addition, the difference between the average score at the start and after 4 weeks of ingestion is calculated and shown in Table 1.

Of the four subscales, the tablet containing the sulfur-containing amino acid of the present invention of Example 1 scored against Comparative Example 1 in all items of vitality, social life function, daily role function (mental) and mental health. The effect of improving the value was shown. In particular, regarding mental health, an increase of 3 points or more was shown with respect to the score difference of Comparative Example 1, and a particularly remarkable improvement was observed.

Claims (7)

A QOL improver for improving human mental health containing one or more sulfur-containing amino acids selected from S-methylcysteine sulfoxide and S-1-propenyl-L-cysteine sulfoxide. Containing 5~1000mg as daily intake of one or more sulfur containing amino acid selected from the S- methyl cysteine sulfoxide and S-1- propenyl -L- cysteine sulfoxide, according to claim 1 QOL improver. Claim 1 or 2 in which one or more sulfur-containing amino acids selected from S-methylcysteine sulfoxide and S-1-propenyl-L-cysteine sulfoxide are contained in the onion extract. QOL improvement agent according to. Mental human health is either one or more selected from a healthy active Chikara及beauty heart, QOL improving agent according to any one of claims 1-3. A preventive or ameliorating agent for human mental health deterioration containing one or more sulfur-containing amino acids selected from S-methylcysteine sulfoxide and S-1-propenyl-L-cysteine sulfoxide. The fifth aspect of claim 5, wherein one or more sulfur-containing amino acids selected from S-methylcysteine sulfoxide and S-1-propenyl-L-cysteine sulfoxide are contained in a daily intake of 5 to 1000 mg. Preventive or ameliorating agent. Claim 5 or 6 in which one or more sulfur-containing amino acids selected from S-methylcysteine sulfoxide and S-1-propenyl-L-cysteine sulfoxide are contained in the onion extract. The preventive or improving agent described in.