JP6193176B2 - Vitality and / or concentration improver - Google Patents

Description

  The present invention relates to a vitality and / or concentration improver.

  Vigor and concentration are the source of human life. As means for improving vitality, there is exercise (Non-Patent Document 1). As means for improving concentration, there is meditation (Non-Patent Document 2).

Reliability and validity of vitality index, and the relationship between vitality index and aging and exercise Tsunekazu Kanzaki, Hisashi Murata, Reiko Kikuchi, Yoichi Sugiyama, Hiroshi Hasegawa, Akihiro Igata, Kenji Toba The Japan Geriatrics Society Magazine Vol. 45 (2008) No. 2) Efforts to reduce stress as a living technology Sadako Tokumaru, Miyoko Ishizawa, Kazuo Naka Japan Abstracts of Home Economics Education Conference, Regular Meeting, Seminar Presentation Vol. 55 (2012)

  However, conventional vitality improvers and concentration improvers have not been able to sufficiently improve vitality and concentration.

  An object of the present invention is to provide a new agent that promotes improvement of vitality and / or concentration.

The present invention provides the following inventions.
[1] A vitality and / or concentration improver containing sake yeast and / or a culture thereof.
[2] Sake yeast and / or its culture is sake yeast and / or its culture containing methylthioadenosine and / or its salt, and the content of methylthioadenosine and / or its salt in sake yeast and its culture The agent of Claim 1 whose is 1 mass%-50 mass%.
[3] Sake yeast and / or its culture is sake yeast and / or its culture containing methylthioadenosine and / or its salt, and the amount of methylthioadenosine skeleton contained in the sake yeast and its culture is 1.5. The agent of Claim 1 which is mass%-80 mass%.

Moreover, this invention can provide the following embodiment in other aspects.
(1) A method for improving vitality and / or concentration by administering sake yeast and / or a culture thereof.
(2) The method according to (1) above, wherein the sake yeast and / or culture thereof is orally administered.
(3) Use of sake yeast and / or a culture thereof for producing a vitality and / or concentration improver.

  According to the present invention, vitality and / or concentration can be improved.

FIG. 1 is a graph showing evaluation of SF-8 (registered trademark) of the example. FIG. 2 is a graph showing an evaluation result of the concentration reduction frequency score of the example.

  The agent of the present invention contains sake yeast and / or a culture thereof as an active ingredient.

  Sake yeast is yeast used for sake brewing. Yeasts used for sake brewing are mainly classified into S. cerevisiae. As sake yeast, association 6 yeast (K-6), association 7 yeast (K-7), association 9 yeast (K-9), association 601 yeast (K-601), association 701 yeast ( K-701), Association No. 901 yeast (K-901), Association No. 1001 yeast (K-1001), Association No. 1501 yeast (K-1501) (all of which are distributed by the Japan Brewing Association). Sake yeast may be either live cells or dead cells.

  The sake yeast culture means a mixture obtained by culturing sake yeast. The mixture usually contains yeast cells, cell components (parts of cells such as crushed cells), products metabolized by yeast, medium components, and the like.

  The sake yeast and the culture thereof preferably contain methylthioadenosine and / or a salt thereof. Methylthioadenosine means 5'-deoxy-5'-methylthioadenosine. 5'-deoxy-5'-methylthioadenosine may be in either the anti-type or the syn-type. Sake yeast and cultures thereof contain methylthioadenosine and / or a salt thereof, usually as a metabolite or degradation product of yeast. Hereinafter, methylthioadenosine and / or a salt thereof may be abbreviated as MTA in the present specification.

  The salt of methylthioadenosine is not particularly limited as long as it is a pharmacologically acceptable salt, and may be selected according to the dosage form and the like. Suitable salts of methylthioadenosine include, for example, acid addition salts. The acid addition salt may be any of an inorganic acid addition salt and an organic acid addition salt. For example, hydrochloride, sulfate, nitrate, carbonate, phosphate, formate, oxalate, citrate , Ascorbate, methanesulfonate, 1,4-butanedisulfonate, 1,5-pentanesulfonate and p-toluenesulfonate.

  The content of methylthioadenosine and / or its salt in sake yeast and its culture can be expressed as the content of methylthioadenosine per dry mass of the yeast culture. The content (content rate) of methylthioadenosine per dry mass means the percentage of the ratio of the net mass of methylthioadenosine contained in the yeast culture to the total amount of the yeast culture. If the yeast culture contains methylthioadenosine salt, the “net mass of methylthioadenosine” does not include the mass of the salt portion of methylthioadenosine salt. The content of methylthioadenosine and / or a salt thereof per dry mass of the yeast culture is preferably 1% by mass or more, more preferably 2% by mass or more, and further preferably 4% by mass or more. preferable. Thereby, sake yeast and its culture | cultivation can exhibit the vitality and / or concentration improvement effect efficiently. The upper limit of the content of methylthioadenosine and / or its salt per dry mass of the yeast culture is usually 50% by mass or less, preferably 20% by mass or less, more preferably 10% by mass or less. The content of methylthioadenosine and / or a salt thereof per dry mass of the yeast culture is preferably 1% by mass to 50% by mass, more preferably 2% by mass to 20% by mass, and more preferably 4% by mass. More preferably, it is 10 mass%.

  The methylthioadenosine content per dry mass in sake yeast and its culture can be defined by the following formula (1), for example.

[Formula (1)]
Methylthioadenosine content per dry mass of sake yeast or its culture = (a / b) × 100

  In the formula (1), a is the methylthioadenosine content (not including the mass of the salt portion of the methylthioadenosine salt) (g) in a certain amount collected from sake yeast and its culture. Quantification as methylthioadenosine can be performed by liquid chromatography. b is the dry weight (g) after 24 hours of freeze-drying (trap cooling temperature −75 ° C.) of the same amount of yeast culture collected at the time of the above a measurement.

  In the sake yeast culture, the yeast may contain methylthioadenosine and / or a salt thereof, or may contain methylthioadenosine and / or a salt thereof outside the cells.

  The sake yeast and the culture thereof may contain S-adenosylmethionine or a salt thereof, and preferably contain it. S-adenosylmethionine has a structure in which adenosine and methionine are linked via a methylsulfonyl bond. The optical isomers of methionine include L-form, D-form, and DL-form. In the present invention, methionine in the structure of S-adenosylmethionine may be any of the optical isomers, but is preferably L-form. Sake yeast and its cultures usually contain S-adenosylmethionine or a salt thereof as a yeast metabolite. Hereinafter, in this specification, S-adenosylmethionine and / or a salt thereof may be abbreviated as SAMe.

  The salt of S-adenosylmethionine is not particularly limited as long as it is a pharmacologically acceptable salt, and can be selected according to the dosage form and the like. Suitable salts of S-adenosylmethionine include, for example, acid addition salts and halides, and specifically include hydrochloride, sulfate, p-toluenesulfonate (tosylate), sulfuric acid / p. -Toluenesulfonate, methanesulfonate, trifluoromethanesulfonate, 1,4-butanedisulfonate, 1,5-pentanesulfonate, phosphate, chloride, bromide and the like. Of these, hydrochloride or tosylate is preferred.

  In the present invention, sake yeast and its culture may contain any one of methylthioadenosine and / or a salt thereof and S-adenosylmethionine or a salt thereof, or both. It is preferable to include both.

  The amount of methylthioadenosine skeleton in sake yeast and its culture is preferably 1.5% by mass or more. Thereby, a high vitality improvement and concentration improvement effect are acquired. The upper limit is preferably 80% by mass or less. The skeleton amount is preferably 1.5% by mass to 80% by mass, more preferably 4% by mass to 50% by mass, and still more preferably 7% by mass to 20% by mass. The amount of methylthioadenosine skeleton means the total amount of 5'-deoxy-5'-methylthioadenosine in the structure. The amount of methylthioadenosine skeleton can be determined by conversion from the molecular weight. That is, taking S-adenosylmethionine as an example, the molecular weight of methylthioadenosine is 297.3, and the molecular weight of S-adenosylmethionine is 398.4. The amount of methylthioadenosine skeleton of S-adenosylmethionine can be obtained by multiplying 297.3 and dividing by 398.4. The amount of methylthioadenosine skeleton in the case of containing both methylthioadenosine and S-adenosylmethionine can be determined by adding the mass of methylthioadenosine and the amount of methylthioadenosine skeleton of S-adenosylmethionine determined by the above method. Quantification of methylthioadenosine and other components can be performed by liquid chromatography or ion chromatography according to a conventional method.

  Sake yeast may be cultured in a conventional manner according to culture conditions suitable for sake yeast. There is no restriction | limiting in particular in the culture medium used for culture | cultivation, The component utilized for the culture medium utilized for culture | cultivation of normal microorganisms, such as a carbon source, a nitrogen source, an inorganic salt, may be contained. Examples of the carbon source include glucose, sucrose, acetic acid, ethanol, molasses, sulfite pulp waste liquid, and the like. Examples of the nitrogen source include nitrogen-containing inorganic salts such as urea, ammonia, ammonium sulfate, ammonium chloride, and ammonium phosphate, and nitrogen-containing organic substances such as corn steep liquor (CSL), casein, yeast extract, and peptone. Examples of inorganic salts include phosphates such as lime superphosphate and ammonium phosphate; potassium salts such as potassium chloride and potassium hydroxide; magnesium salts such as magnesium sulfate and magnesium hydrochloride; zinc; copper; manganese; Can be mentioned. The medium may further contain components such as vitamins, nucleic acid-related substances, and amino acids. The medium preferably contains at least ethanol and an amino acid (for example, methionine). When the medium is a solid medium, agar or the like is usually added.

  The medium may be a solid medium or a liquid medium. Examples of the culture mode in the case of a liquid medium include batch culture, fed-batch culture, continuous culture and the like, and any of these may be adopted.

  The culture temperature may be any temperature as long as it is between 6 ° C and 35 ° C, usually 20 ° C to 35 ° C, and preferably 25 ° C to 32 ° C. The culture time may usually be 1 day or more and preferably 2 days or more and 10 days or less.

  The sake yeast containing methylthioadenosine and / or a salt thereof may be a yeast originally containing methylthioadenosine and / or a salt thereof, or may be added to a yeast not originally containing methylthioadenosine and / or a salt thereof. Yeast obtained by producing can be used. Alternatively, methylthioadenosine and / or a salt thereof may be produced in the yeast culture by heat-treating the yeast culture that produces a substance having the structure of methylthioadenosine. An example of a method for producing yeast with methylthioadenosine and / or a salt thereof is a method in which yeast is cultured to produce methylthioadenosine and / or a salt thereof in the yeast (intracellular). In the case of such a method, the obtained culture broth may be used as it is as a yeast culture containing methylthioadenosine and / or a salt thereof, and the yeast recovered after the cultivation contains methylthioadenosine and / or a salt thereof. You may use as yeast to do. Furthermore, a dried yeast culture obtained by drying the culture medium after culturing as it is or after collecting the bacteria may be used. In the present invention, it is preferable to use a yeast culture containing methylthioadenosine and / or a salt thereof in a dry state.

  In addition, components such as a stabilizer and an excipient may be added to the yeast culture weighed by the formula (1), and then the following heating operation may be performed.

  Conditions for heating the yeast culture are not particularly limited. The temperature is 40 ° C or higher, preferably 50 ° C or higher, more preferably 60 ° C or higher, and still more preferably 80 ° C or higher. The upper limit is usually 200 ° C. or lower, preferably 180 ° C. or lower, more preferably 160 ° C. or lower, and still more preferably 120 ° C. or lower. Usually, it is 40 ° C or higher and 200 ° C or lower, preferably 50 ° C or higher and 180 ° C or lower, more preferably 60 ° C or higher and 160 ° C or lower, and further preferably 80 ° C or higher and 120 ° C or lower. The treatment time may be adjusted according to the degree of formation of methylthioadenosine and / or a salt thereof.

  There is no particular limitation on the heating method. As a heating method in the case of a liquid yeast culture, for example, a method in which a container in which the yeast culture is put is heated while stirring in a heating apparatus such as an electric heater or an electric heater, and a container in which the yeast culture is put in a hot water bath. , A method of heating in an oil bath or the like while stirring, a method of heating the yeast culture in a water jacketed container and heating it through hot water or steam in the water jacket, and a container containing the yeast culture with a heat exchange type plate heater Heating method, sealing the container containing the yeast culture, heating the container with hot water, heating with electromagnetic waves (microwave oven), heating with spray drying, heating with autoclave, fluidized bed The method of heating with dryers, such as a dryer and a shelf dryer, etc. are mentioned. Examples of the heating method in the case of a solid yeast culture such as powder include a method of heating in an autoclave, a method of heating a sealed container with hot water, a fluidized bed dryer, a rotary aeration dryer, and a shelf dryer. And a method of heating with a dryer such as a method of heating with a roaster.

  A yeast culture with a high content of methylthioadenosine and / or a salt thereof can be obtained by drying the yeast culture following the heat treatment. The method for drying the culture is not particularly limited, and any of the methods commonly used for preparing dry yeast cells may be used. For example, freeze-drying method, spray-drying method And drum drying method. Furthermore, the yeast culture excellent in the handleability can be obtained by processing the obtained dry yeast culture into a powder form.

  The agent of the present invention can improve vitality. Vitality means the power to move or work, which means activity and vitality, and is sometimes expressed by the word spirit. The improvement of vitality includes increasing vitality, sustaining high vitality, and suppressing reduction of vitality as compared with a contrasted state (for example, a state before administration of the agent of the present invention).

  The agent of the present invention can improve concentration. Concentration means not only focusing attention on one thing, but also paying attention in a balanced manner, including the necessary range of things, and avoiding being distracted by irrelevant things. This also includes a reduction in the frequency with which concentration is reduced. Concentration improvement improves the concentration, maintains a high concentration, and suppresses a decrease in concentration compared to a contrasted state (for example, the state before administration of the agent of the present invention). Including that.

  In addition to sake yeast and / or its culture, the agent of the present invention may be mixed or used in combination with a component capable of improving vitality and a component capable of improving concentration.

  The agent of the present invention is a preparation substantially consisting only of sake yeast and / or culture thereof, or sake yeast and / or culture thereof, and one or more components other than sake yeast and culture thereof It can be set as the formulation containing these.

  Components (arbitrary components) other than sake yeast and its culture are not particularly limited as long as the effects of the present invention are not essentially impaired. Optional ingredients include excipients, disintegrants, binders, lubricants, coating agents, colorants, color formers, flavoring agents, flavoring agents, antioxidants, preservatives, flavoring agents, acidulants, sweetness Examples include pharmacologically acceptable additives such as agents, reinforcing agents, vitamins, swelling agents, thickeners, and surfactants. From these, select additives that do not impair the effects of improving vitality and concentration, the properties required for the formulation (eg, formulation stability), and the final product dosage form. obtain. The optional component may be one type or a combination of two or more types.

  The dosage form of the agent of the present invention is not particularly limited as long as it can contain sake yeast and its culture as active ingredients. Examples of dosage forms for oral administration include liquid (liquid), syrup (syrup), solid (tablet), capsule (capsule), powder (granule, fine granule), soft capsule ( Soft capsules), semi-liquid, cream, and paste. Examples of dosage forms for parenteral administration include liquids (injections, nasal drops), mists (sprays, inhalants) and the like. These preparations can be prepared by mixing sake yeast and / or its culture with a pharmacologically acceptable medium.

  The dosage of the agent of the present invention is not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately adjusted depending on factors such as the age and condition of the administration target organism. The preferable dosage for obtaining the desired effect is as follows.

  The intake (mg / day) of sake yeast and culture per day is usually 10 mg or more, preferably 100 mg or more, and more preferably 200 mg or more. The upper limit is usually 20000 mg or less, preferably 16000 mg or less, more preferably 10,000 mg or less, and still more preferably 8000 mg or less. The intake is usually 10 mg to 20000 mg, preferably 100 mg to 16000 mg, more preferably 100 mg to 10000 mg, and still more preferably 200 mg to 8000 mg.

  When the sake yeast or culture contains methylthioadenosine and / or its salt, the lower limit of the daily dose of methylthioadenosine and / or its salt (mg / day) is preferably 0.01 mg or more, more preferably It is 0.1 mg or more, More preferably, it is 1 mg or more, The upper limit becomes like this. Preferably it is 1000 mg or less, More preferably, it is 500 mg or less, More preferably, it is 100 mg or less. The lower limit of the dose (mg / week) of methylthioadenosine and / or its salt per week is preferably 30 mg or more.

  The total dose (mg / day) of methylthioadenosine or a salt thereof per day is preferably 1 mg or more, more preferably 10 mg or more, and more preferably 15 mg or more as the amount of methylthioadenosine skeleton. Further preferred. The upper limit is preferably 10,000 mg or less, more preferably 1000 mg or less, and still more preferably 70 mg or less. The amount of the skeleton is preferably 1 mg to 10000 mg, more preferably 10 mg to 1000 mg, and still more preferably 15 mg to 70 mg. The total dose (mg / week) of methylthioadenosine or a salt thereof per week is preferably 3 mg or more, more preferably 30 mg or more, and more preferably 45 mg or more as the total amount of each skeleton. More preferably it is. The upper limit is preferably 30000 mg or less, more preferably 3000 mg or less, and even more preferably 250 mg or less. The amount of the skeleton is preferably 3 mg to 30000 mg, more preferably 30 mg to 3000 mg, and further preferably 45 mg to 250 mg.

  The measurement of the amount of methylthioadenosine can be performed, for example, by liquid chromatography or ion chromatography.

  The agent of the present invention is preferably administered continuously. Continuing means being administered at a specific dosing interval. Examples of the administration interval include administration of 1 to 3 times a day three times or more a week, and administration of once a day is preferably performed 3 to 7 days a week.

  The administration period of the agent of the present invention is not particularly limited, but is preferably 2 days or more, more preferably 4 days or more, further preferably 1 week or more, and further preferably 4 weeks or more. Is more preferable. Thereby, vitality and / or concentration can be further improved.

  The dosage form of the agent of the present invention is not particularly limited. For example, oral administration (eg, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.) and the like can be mentioned. Among these, a less invasive dosage form is preferable, and oral administration is more preferable.

  Although the administration time of the agent of the present invention is not particularly limited, it is usually preferably administered 10 hours before to immediately before bedtime, and preferably administered 1 hour before to bedtime.

  The subject of taking the agent of the present invention is usually a human. The ingestion target person is not particularly limited. Examples of ingestion subjects include subjects who have a subjectively reduced vitality, subjects who want to improve their vitality subjectively, subjects who have a subjectively reduced concentration, The target person who wants to improve is mentioned. In addition, subjects who do not have any particular problems can be ingested on a daily basis for the purpose of improving, maintaining, concentrating and maintaining vitality.

  The agent of the present invention may be used as an additive for food and drink, a pharmaceutical additive, or an quasi-drug additive. Thereby, a vitality and / or concentration improvement effect can be provided to food and drink, medicine, and quasi drug.

  The agent of the present invention relates to food and drink, for example, health food, functional food, nutritional supplement (supplement), food for specified health use, medical food, food for sick people, food for infants, food for care, elderly It can be used by blending with foods for use.

  There is no particular limitation on foods and drinks that can be mixed with the agent of the present invention, for example, beverages (soft drinks, carbonated drinks, nutritional drinks, powdered drinks, fruit drinks, milk drinks, jelly drinks, etc.), confectionery (cookies, cakes, Gum, candy, tablet, gummy, bun, gourd, pudding, jelly, ice cream, sherbet, etc.), processed fishery products (kamaboko, chikuwa, hanpen, etc.), processed livestock products (hamburger, ham, sausage, winner, cheese, butter) , Yogurt, fresh cream, margarine, fermented milk, etc.), soup (powder soup, liquid soup, etc.), staple foods (rice, noodles (dried noodles, raw noodles), bread, cereal, etc.), seasonings (mayonnaise, shortening) , Dressing, sauce, sauce, soy sauce, etc.).

  In addition to these, the agent of the present invention can be combined with one or more components suitable for internal use to form an internal use composition. According to the internal use composition of this invention, the component which improves vitality and / or concentration can be obtained easily by oral ingestion. The form of the internal use composition should just be a form suitable for internal use. The internal use composition can be obtained by mixing the agent of the present invention and a pharmacologically acceptable medium that can be used internally. Definitions, examples, and preferred examples of pharmaceutically acceptable orally acceptable media are the same as those of the optional components described for the agent of the present invention.

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited to the following Example.

Example 1 and Comparative Example 1
Four subjects were ingested daily for 1 week before going to bed for a period of 4 weeks for 6 subjects (Example 1). The same subject was allowed to take placebo tablets instead of the specimen for 4 weeks other than the above 4 weeks (Comparative Example 1). The breakdown of the sexes of the 6 subjects was 4 males and 2 females, and the ages were 26-51 years old. The specimen was a tablet containing sake yeast and was prepared as follows: sake yeast powder (Mitsubishi Gas Chemical), crystalline cellulose (Asahi Kasei Chemicals), CMC-Ca (Daicel Chemical Industries) were mixed. Thereafter, stearic acid Ca (manufactured by Taihei Chemical Industrial Co., Ltd.) was added and mixed, and tableting was performed by a direct compression method using a rotary tableting machine (LIBURA2 manufactured by Kikusui Seisakusho Co., Ltd.).

  Placebo tablets were prepared using crystalline cellulose instead of sake yeast.

  The content of sake yeast in the tablet was 500 mg / 4 grains, and the content of MTA in the sake yeast was about 4% by mass. The amount of MTA skeleton was 7% by mass. The amount of MTA skeleton taken per day and the amount taken per week were 35 mg / day and 245 mg / week, respectively.

  Each subject's concentration was evaluated during and before and after the intake period. The evaluation was performed using SF-8 (registered trademark) and a concentration reduction frequency score.

  SF-8 (registered trademark) is a health-related QOL evaluation index provided by the NPO Health and Medical Evaluation and Research Organization, and includes 8 areas of health (body function, daily role function (body), body pain, overall It is a scale that can measure health, vitality, social life function, daily role function (mind), mental health).

  The concentration reduction frequency score is one of the scores obtained from the results of the examination by the questionnaire of POMS (Profile of Mood States: registered trademark) which is a psychological test. 5 = 0 = no, 1 = little, 2 = fair, 3 = quite 4 = very much.

  Each evaluation was performed in each period of 1 week before ingestion, 1st week and 4th week after ingestion start, 1st week and 2nd week after ingestion end. Questionnaires of SF-8 (registered trademark) and concentration reduction frequency score were conducted on two days of each week, and an average value was calculated. The results of SF-8 (registered trademark) and concentration reduction frequency score are shown in FIGS. 1 and 2, respectively.

  As is clear from FIG. 1, vitality, mental health, and overall health are all better during the intake period than before and after the intake period, and in particular, the vitality (p <0. 05), mental health (p <0.1) was significantly different from that before ingestion. As apparent from FIG. 2, there was a tendency that it was difficult to concentrate during the intake period. A significant difference was observed between before intake and 4 weeks after the start of intake and 1 week after the end of intake (p <0.05). The concentration reduction frequency score in Example 1 in each period was as follows: 1 week before intake: 1.5; 1 week after start of intake: 1.0; 4 weeks after start of intake: 0.5 And after completion of intake (week 1): 0.43. In Comparative Example 1, there was no change in either SF-8 (registered trademark) or concentration reduction frequency score.

  These results show that sake yeast and / or cultures thereof are useful as active ingredients of vitality improvers and concentration improvers in the present invention.

Claims (2)

Sake yeast containing methylthioadenosine and / or salt thereof and / or culture thereof, containing methylthioadenosine skeleton contained in sake yeast and culture thereof is 1.5% by mass to 80% by mass, and administration interval Is a vitality and / or concentration-improving agent , wherein 1 to 3 times a day is 3 to 7 times a week, and the administration period is one week or more .   The sake yeast and / or its culture is sake yeast and / or its culture containing methylthioadenosine and / or its salt, and the content of methylthioadenosine and / or its salt in sake yeast and its culture is 1 mass. The agent of Claim 1 which is% -50 mass%.

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