JP6671652B2 - Body temperature raising agent - Google Patents

Description

  The present invention relates to a body temperature increasing agent.

  In recent years, it has been noted that the number of children and elderly people with hypothermia is increasing. In addition, many people suffer from cold, such as cold end, even if their body temperature is normal. Hypothermia and cold cause various discomforts and are also thought to cause various diseases. Therefore, a temperature increasing agent capable of increasing body temperature is useful for health. For example, Patent Literature 1 describes that a lactic acid bacterium Lactobacillus paracasei ST11 strain has a body temperature increasing effect.

JP 2011-523407 A

  The strain described in Patent Literature 1 describes that the body temperature rises by about 1.5 ° C. in a short time of about 60 minutes after ingesting the strain. With such a degree of increase in body temperature, when a person with normal fever ingests the above strain, the body temperature rises to a fever state, and is not suitable as a body temperature increasing agent.

  In addition, under stress such as stress-related sleep disorders, lifestyle disorders, excessive cooling, etc., a decrease in body temperature may be observed, but strains of lactic acid bacteria that can suppress such a decrease in body temperature have so far been reported. Not known to

  Therefore, an object of the present invention is to provide a novel body temperature increasing agent having a moderate body temperature increasing effect.

  The present inventors have found that a strain of Lactobacillus brevis SBC8803, which is a lactic acid bacterium, or a treated product thereof itself has an action of appropriately increasing body temperature. The present invention is based on this new finding.

  That is, the present invention provides a body temperature increasing agent containing, as an active ingredient, a cell of SBC8803 belonging to Lactobacillus brevis or a processed product thereof.

  According to the above body temperature increasing agent, the body temperature can be increased appropriately. Therefore, for example, it is effective for raising the body temperature of a person who is hypothermic to an appropriate body temperature.

  The Lactobacillus brevis SBC8803 strain was obtained from the National Institute of Advanced Industrial Science and Technology, Patent Organism Depositary on June 28, 2006 (1-1 1-1 Higashi, Tsukuba, Ibaraki, Japan, Chuo No. 6 (zip code 305-8566)). ) Is the strain of FERM BP-10632 deposited under Accession No. In this specification, this strain is also referred to as “SBL88 strain”.

  In addition, since the above-mentioned body temperature increasing agent has the above-described effects, it can be used as, for example, a cold improving agent.

  The present inventors have also found that the strain of SBL88 strain or the treated product itself has an action of suppressing a decrease in body temperature at the time of a body temperature disorder due to disturbance of lifestyle, excessive cooling, etc. under stress such as stress sleep disorder. Also found. Therefore, the above-mentioned body temperature increasing agent can also be used as a body temperature decrease inhibitor.

  Lactobacillus brevis is a kind of lactic acid bacterium that has been used for fermented foods for a long time, and its safety to living organisms has been established. Therefore, the body temperature increasing agent of the present invention is highly safe for living bodies and can be taken continuously for a long period of time. Therefore, it can be used as a pharmaceutical component, a food and drink component, a food and drink additive, and the like.

  According to the present invention, a novel body temperature increasing agent having a moderate body temperature increasing effect is provided. In addition, there are provided pharmaceuticals, foods and drinks, food and drink additives, etc., containing the above body temperature increasing agent.

It is a graph which shows transition of the average body temperature of the mouse | mouth of a SBL88 group and a control group in a non-stress breeding period and a stress breeding period.

  Hereinafter, preferred embodiments of the present invention will be described in detail.

  The body temperature increasing agent of the present invention contains, as an active ingredient, a cell of SBC8803 belonging to Lactobacillus brevis or a processed product thereof.

  As the body temperature increasing agent of the present invention, the above-mentioned cells and the treated product of the above-mentioned cells may be used alone or in combination of two or more.

  The cells may be live cells or dead cells. The cells can be produced in large quantities by culturing live cells. The medium may be either a liquid medium or a solid medium, but preferably contains a nitrogen source and a carbon source. As a nitrogen source, meat extract, peptone, gluten, casein, yeast extract, amino acid, etc., and as a carbon source, glucose, xylose, fructose, inositol, maltose, water candy, koji juice, starch, bagasse, bran, Molasses, glycerin and the like can be used. As inorganic substances, ammonium sulfate, potassium phosphate, magnesium chloride, salt, iron, manganese, molybdenum, and the like can be added, and vitamins and the like can be further added. Suitable media include MRS medium, LBS medium, Rogosa medium, WYP medium, GYP medium and the like.

  The culture of the above strain can be performed according to a culture method commonly used for culturing strains belonging to Lactobacillus brevis. For example, the culture temperature is usually 20 to 50C, preferably 25 to 40C, more preferably 30C. The culture time is usually 6 to 62 hours, preferably 12 to 48 hours, and more preferably 15 to 30 hours. The pH of the medium is usually 3 to 8, preferably 4 to 7, and more preferably 6 to 7. The culture may be performed in an incubator, and the culture may be performed with aeration and shaking.

  Examples of the processed product of the cells include a processed product obtained by subjecting the above cells (live cells or dead cells) to heat, pressure, drying, pulverization, crushing, destruction, or self-lysis. . These processes may be used in combination of two or more. As a treated product of the cells, for example, a treated product obtained by heating the cells at 100 ° C. or more for several minutes or more (for example, subjecting the cells to an autoclave treatment at a temperature of 105 to 125 ° C. for 10 minutes or more) Treated product), a processed product obtained by subjecting cells to freeze-drying, spray-drying, or the like, a processed product obtained by contacting the cells with an organic solvent (acetone, ethanol, etc.), and transforming the cells with acid or A treated product obtained by contacting with an alkali solution, a treated product obtained by enzymatically crushing the cells, or a treated product obtained by physically destroying the cells with an ultrasonic wave, a French press or the like can be used. Such treated cells are preferable in that they are easier to handle than untreated cells (especially live cells).

  The body temperature increasing agent of the present invention may be in any form of solid (eg, powder obtained by freeze-drying), liquid (water-soluble or fat-soluble solution or suspension), paste and the like, Any dosage form such as powders, pills, granules, tablets, syrups, troches, capsules and the like may be used.

  The above-mentioned various preparations may be composed of only the above-mentioned cells as an active ingredient or a processed product thereof, and for example, can be prepared by molding the cells or a processed product thereof into the above-mentioned dosage form. . The above-mentioned various preparations may also contain the above-mentioned active ingredient and pharmaceutically acceptable additives (excipient, binder, lubricant, disintegrant, emulsifier, surfactant, base, solubilizer, suspension) And a molding agent. In this case, the content of the active ingredient is, for example, 0.5 to 50% by mass based on the total amount of the preparation.

  For example, excipients include lactose, sucrose, starch, dextrin and the like. Examples of the binder include polyvinyl alcohol, gum arabic, tragacanth, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidone. Lubricants include magnesium stearate, calcium stearate, talc and the like. Disintegrators include crystalline cellulose, agar, gelatin, calcium carbonate, sodium bicarbonate, dextrin and the like. Examples of the emulsifier or the surfactant include Tween 60, Tween 80, Span 80, and glyceryl monostearate. Examples of the base include cetostearyl alcohol, lanolin, polyethylene glycol, rice bran oil, fish oil (DHA, EPA, etc.), olive oil and the like. Examples of the solubilizer include polyethylene glycol, propylene glycol, sodium carbonate, sodium citrate, Tween 80, and the like. Examples of the suspending agent include Tween 60, Tween 80, Span 80, glyceryl monostearate, polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxymethyl cellulose, sodium alginate and the like.

  The body temperature increasing agent of the present invention may be administered to humans or non-human mammals. The dose and the administration method can be appropriately determined depending on the condition, age, etc. of the individual to be administered. Suitable administration methods include, for example, oral administration. As an example of the dosage and the administration method, there can be mentioned a method of orally administering a body temperature-increasing agent once a day in an amount such that the active ingredient amount is 0.5 mg to 500 mg.

  The body temperature increasing agent of the present invention can be used as a pharmaceutical component, a food and drink component, a food and drink additive, a feed component, a feed additive and the like.

  For example, the body temperature increasing agent of the present invention is water, soft drink, fruit drink, milk drink, alcoholic drink, bread, noodles, rice, tofu, dairy product, fermented food, fermented milk, soy sauce, miso, confectionery Etc. can be used as an additive to foods and drinks. These foods and drinks may further contain other additives commonly used in the art, such as, for example, bitterness, flavoring, apple fiber, soy fiber, meat extract, black extract. Vinegar extract, gelatin, corn starch, honey, animal and vegetable fats and oils; monosaccharides such as glucose and fructose; disaccharides such as sucrose; polysaccharides such as dextrose and starch; sugar alcohols such as erythritol, xylitol, sorbitol, and mannitol; Vitamins. The body temperature increasing agent of the present invention can also be used as an ingredient of foods for specified health use, special use foods, dietary supplements, health foods, functional foods, foods for patients, and the like. The food or drink can be obtained by a production method including a step of adding the body temperature increasing agent of the present invention. The food or beverage containing the body temperature increasing agent of the present invention may be a fermented product obtained by fermenting milk, skim milk, soy milk, vegetables, fruit juice, grains, processed products thereof, and the like with the above strain.

  The body temperature increasing agent of the present invention has an effect of appropriately increasing body temperature. That is, according to the body temperature increasing agent of the present invention, for example, the temperature can be increased by 0.05 to 0.50 ° C. Therefore, even if a person with normal fever ingests, the body temperature does not rise to a fever state, so that it can be used, for example, as a cold improving agent for improving symptoms such as cold.

  Further, the body temperature increasing agent of the present invention has an effect of suppressing a decrease in body temperature at the time of a body temperature disorder due to disturbance of lifestyle, excessive cooling or the like under stress such as stress sleep disorder. At the time of these body temperature disorders, the body temperature tends to decrease compared to the normal state. However, by taking the body temperature increasing agent of the present invention, the decrease in the body temperature can be suppressed and the body temperature closer to the normal state can be maintained. Therefore, the body temperature increasing agent of the present invention can be used as a body temperature decrease inhibitor.

  Hereinafter, the present invention will be described more specifically based on examples and the like. However, the present invention is not limited to the following examples.

[Example 1]
(Test method)
<Preparation of treated cells>
The SBL88 strain was inoculated into a medium (composition: maltose 2% by mass, yeast extract 1.4% by mass, sodium acetate 0.5% by mass, manganese sulfate 0.005% by mass, pH 6.5 to 7.0), and 30 The culture was allowed to stand at room temperature for 1 day. The obtained culture solution (about 8 × 10 ⁸ cfu / ml) was centrifuged at 8,000 rpm for 10 minutes to collect the cells. The collected cells were resuspended in distilled water and centrifuged at 8,000 rpm for 10 minutes to collect the cells. This operation was repeated twice. The collected cells were suspended in distilled water, heat-treated at 105 ° C. for 10 minutes, and freeze-dried to obtain heat-treated cell powder (cell-treated product).

<Preparation of mouse feed>
Mouse feed containing 0.5% by mass of the treated cells of SBL88 strain was added to powdered feed AIN-93M (manufactured by Oriental Yeast Co., Ltd.) and then pelleted to contain a mouse feed containing the treated cells (AIN-93M feed containing SBL88). Was prepared. As a control, powdered feed AIN-93M was pelletized to prepare a mouse feed (AIN93M feed) containing no treated cells.

<Mouse rearing>
Throughout the entire period, the mice were kept in a rotating basket (SW-15S, Merquest Limited). The activity of the mice was measured using a chronobiology kit (Stanford Software Systems, CA).

  Mice of the C3H / HeN strain (male, 6 weeks old, 13 mice, Japan SLC, Inc.) were bred for 10 days. Three days after the start of acclimatization, a temperature data logger (manufactured by Thermocron SL KN Laboratory) was implanted in the abdominal cavity of the mouse. After acclimation, the mice were divided into two groups in the order of the total amount of activity, and AIN-93M feed was fed as a diet to 6 mice in the control group, and AIN-93M containing SBL88 was fed as a diet to 7 mice in the test group (SBL88 group). They were fed and fed ad libitum.

<Measurement of average body temperature>
One day after starting to feed the AIN-93M diet or the AIN-93M diet containing SBL88, measurement of body temperature was started using a data logger. The measurement was performed every 15 minutes, and the average body temperature for one day (24 hours) was determined. The average body temperature of each group was determined as the average body temperature of the mice of each group. The presence or absence of a significant difference was compared by the Tukey's method after the multiple comparison test.

<Stress on mice>
In the SBL88 group and the control group, the period from the start of measurement of body temperature (day 0) to the 26th day was the non-stress breeding period, and the stress breeding period was started from the 27th day. As a stress loading method, stress sleep disorder was continuously induced for 2 weeks by physically shielding the mouse so that the mouse could not get off the wheel.

<Result>
FIG. 1 is a graph showing changes in the average body temperature of the mice of the SBL88 group and the control group during the non-stress breeding period and the stress breeding period. In FIG. 1, data marked with * indicates that p <0.05, and data marked with ** indicates that p <0.01. During the non-stress breeding period (0-26 days), the average body temperature of the SBL88 group showed a high value with a statistically significant difference compared to the control group.

  Even during the stress breeding period (day 27 to 41), the SBL88 group showed a high mean body temperature with a statistically significant difference from the control group. Moreover, in the stress rearing period, the difference in the average body temperature between the SBL88 group and the control group was more remarkable than in the non-stress rearing period. In the control group, it was observed that when stress was applied, the average body temperature gradually decreased significantly compared to the non-stress breeding period. On the other hand, in the SBL88 group, even under stress, the decrease in body temperature was suppressed, and body temperature closer to normal was maintained. The difference between the average body temperature of the SBL88 group and the control group was 1 ° C. or less under both non-stress and stress conditions. That is, the administration of the treated product of SBL88 could raise the body temperature appropriately. In addition, in the stress-loaded state, the decrease in body temperature could be suppressed by administration of the treated product of SBL88.

Claims (4)

A body temperature increasing agent as a body temperature lowering inhibitor, comprising, as an active ingredient, a dead cell of a strain SBC8803 (Accession number: FERM BP-10632) belonging to Lactobacillus brevis. A medicament for suppressing a decrease in body temperature , which contains dead cells of a strain SBC8803 (accession number: FERM BP-10632) belonging to Lactobacillus brevis and which is a heat-treated product as an active ingredient. A food or drink for suppressing a decrease in body temperature , which contains dead cells of a SBC8803 (accession number: FERM BP-10632) strain belonging to Lactobacillus brevis and which is a heat-treated product as an active ingredient. A food and drink additive for suppressing a decrease in body temperature , which contains dead cells of a strain SBC8803 (Accession No .: FERM BP-10632) belonging to Lactobacillus brevis and which is a heat-treated product as an active ingredient.

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