JP2015151389A - Salivation accelerator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a salivation accelerator which can be used continuously for a long period of time, and has an excellent improving effect of xerostomia (dry mouth) and the like by reduced salivation.SOLUTION: The present invention provides a salivation accelerator containing the component obtained by the mixed culture of Lactic acid bacteria, Bacillus natto, and yeast.

Description

  The present invention relates to a salivary secretion promoter that improves dryness in the oral cavity. More specifically, the present invention relates to a salivary secretion promoter comprising a component obtained by mixing and cultivating lactic acid bacteria, natto bacteria, and yeast, and a medicine, quasi-drug, food and feed containing the same.

  In recent years, xerostomia in which the amount of saliva secreted is reduced due to various causes and the oral cavity is dry, particularly a disease called dry mouse, has become a problem. Known causes of decreased salivary secretion include autoimmune diseases, side effects of drugs, various diseases such as diabetes, radiation therapy, aging, stress, and exercise.

  As saliva secretion decreases, in addition to dryness in the oral cavity, discomfort such as stickiness in the oral cavity, symptoms such as caries, tongue coating, bad breath, and periodontal disease are observed, and quality of life (QOL) If it decreases and progresses, it is known that it develops into severe symptoms such as glossodynia, dysphagia, articulation disorder, stomatitis, stomatitis, severe halitosis, caries, and periodontal disease.

Traditionally, gargle, troches, artificial saliva, internal medicine, etc. were used to promote saliva secretion, but artificial saliva has problems such as short action time and inability to use during sleep. However, since it is used for symptomatic treatment, the use is limited due to side effects and interaction problems in the case of various causes and the elderly (patent documents 1 to 4).
Therefore, an active ingredient that is safe and can be used easily for a long period of time is desired even for elderly people, sick people, and healthy people who have become dry mice due to stress or the like.

Japanese Patent No. 3690442 JP 2009-173564 A JP 2009-184927 A JP 2011-68642 A

  In the present invention, a salivary secretion promoter that is safe and can be used continuously for a long period of time and has an excellent improvement effect on xerostomia (dry mouth) caused by reduced salivary secretion is provided. Aimed to do.

  As a result of diligent studies to solve the above problems, the present inventors have found that a component obtained by mixing and cultivating lactic acid bacteria, natto bacteria, and yeast (effective component in the present invention) has a salivary secretion promoting effect, and dry mice The present invention has been completed by finding that it is effective for various symptoms associated therewith.

That is, the present invention relates to the following [1] to [7].
[1] A salivary secretion promoter containing a component obtained by mixed culture of lactic acid bacteria, natto bacteria, and yeast.
[2] The saliva secretion promoter according to [1] above, which contains a fermentation broth obtained by culturing lactic acid bacteria, natto bacteria, and yeast in a medium containing rice bran extract and glucose.
[3] The salivary secretion promoter according to [1] or [2] above, wherein the lactic acid bacterium is Lactobacillus paracatheis.
[4] The salivary secretion promoter according to any one of [1] to [3] above, wherein the Bacillus natto is Bacillus pamilus.
[5] The salivary secretion promoter according to any one of [1] to [4] above, wherein the yeast is one or more selected from Saccharomyces cerevisiae and Pichia membranfaciens.
[6] The saliva secretion promoter according to any one of [1] to [5] above, which is used for improving dry mice.
[7] The salivary secretion promoter according to any one of [1] to [6] above, which is blended in a composition for oral cavity or oral administration.

According to the present invention, since salivary secretion decline is improved, unpleasant symptoms in the dry mouse, oral cavity, bad breath, periodontal disease, stomatitis and the like can be improved.
Moreover, since the active ingredient of the present invention is a naturally derived ingredient, it can be safely administered for a long time.
Furthermore, according to the present invention, since saliva secretion is improved, digestive tract disorders such as dysphagia and indigestion can be improved, and diarrhea can be improved and appetite can be enhanced.
Since the active ingredient in the present invention is tasteless and odorless, it can be added to foods and the like without limitation.
The present invention can be easily used not only for humans but also for pets and the like, and can improve bad breath, periodontal disease and stomatitis.

Shows the percentage of people who feel the mouth is moist after taking an oral care tablet. Percentage of people who feel that the feeling of stickiness in the mouth after taking an oral care tablet has improved. Shows the percentage of people who feel that dryness in the mouth has improved after taking oral care tablets. Shows the percentage of people who felt saliva increased after taking oral care tablets. Shows the percentage of people who feel that the environment in their mouth has improved after taking oral care tablets. Percentage of people who felt that bad breath after taking oral care tablets improved. Shows the percentage of people who feel that plaque has decreased after taking oral care tablets. The change of the intestinal vagal nerve activity (intestinal vagal nerve activity, intestinal vagal-NA) when the 10,000 times dilution liquid solution or control of LBS culture is intragastric administration is shown. The vertical axis shows the percentage of the nerve activity of intestinal vagal-NA before the start of intragastric administration (0 minutes) as 100%, and the horizontal axis shows time (minutes).

  The saliva secretion promoter of this invention contains the component obtained by carrying out mixed culture of lactic acid bacteria, natto bacteria, and yeast.

  In the present invention, the component (also referred to as component in the present invention) obtained by mixing and cultivating lactic acid bacteria, natto and yeast is the component obtained by mixing and cultivating lactic acid bacteria, natto and yeast, ie, each of the above-mentioned bacteria Ingredients obtained from fermented cultures, including live bacteria of the bacteria, dead bacteria after heating, secreted products secreted by the bacteria into the culture medium during culture, mixtures thereof, and ingredients obtained from these . Among them, a culture solution obtained by mixing culture of lactic acid bacteria, natto bacteria and yeast (also referred to as a mixed culture solution in the present invention) and a product obtained by removing dead bacteria from the mixed culture solution are preferable. Moreover, the mixed culture solution is preferably a soluble component obtained by filtering dead bacteria after heat treatment.

  Examples of the medium used for the mixed culture in the present invention include a medium containing rice bran, water, glucose, honey, broth, malt juice, meat extract and the like. A medium containing rice bran, glucose and water is preferable.

  Although the kind of rice bran which is a composition component of a culture medium is not specifically limited, For example, what was generated when brown rice was polished can be used. The composition ratio of rice bran, glucose and water is usually 1: 0.5-4: 10-40 by weight, preferably 1: 0.5-3: 10-30, and 1: 1: 20. More preferred. Moreover, you may add the other component useful for culture | cultivation of said each microbe to the said culture medium.

  In the present invention, lactic acid bacteria, natto bacteria and yeast are mixed and used.

  The lactic acid bacteria used in the present invention are not particularly limited as long as they are bacteria involved in lactic acid fermentation, but Lactobacillus, Bifidobacterium, Enterococcus, Lactococcus And the like. Of these, the genus Lactobacillus is preferable, and Lactobacillus paracasei is more preferable.

  The Bacillus natto used in the present invention is not particularly limited as long as it belongs to the genus Bacillus, but Bacillus pumilus is preferable.

  The yeast in the present invention is not particularly limited as long as it is a fungus that exhibits unicellularity in a certain period of the life cycle and proliferates mainly by budding, but includes microorganisms belonging to the genus Saccharomyces and Pichia. Of these, Saccharomyces cerevisiae and Pichia membranifaciens are preferable.

  In the present invention, one or more selected from Lactobacillus paracasei, Bacillus pumilus, Saccharomyces cerevisiae and Pichia membranifaciens are mixed. It is particularly preferable to culture as Lactobacillus paracasei, Bacillus pumilus, Saccharomyces cerevisiae and Pichia membranifaciens. Most preferred.

  The component in this invention can be manufactured as follows, for example. First, for example, a medium for mixed culture of the lactic acid bacteria, natto bacteria and yeast is prepared as follows.

First, rice bran and water are mixed and the mixture is filtered. Glucose is added to the filtrate, heated and mixed, and then the mixture is filtered. Water is further added to the filtrate, sterilized and cooled, and the obtained medium is subjected to mixed culture.
Next, the medium is inoculated with the lactic acid bacteria, natto and yeast, and cultured as follows to obtain a mixed culture. That is, primary culture is performed by aeration culture. The culture temperature is usually 32 to 40 ° C, preferably 35 to 37 ° C. The culture time is 36 to 60 hours, preferably 40 to 55 hours.
Next, secondary culture is performed by cold and warm aging. The culture temperature is usually 2 to 15 ° C, preferably 5 to 8 ° C. The culture period is 30 to 60 days, preferably 40 to 50 days.
Subsequently, the culture solution obtained by the secondary culture is sterilized. The sterilization method is not particularly limited, and is usually performed by heat sterilization, electromagnetic wave sterilization, filter sterilization, or the like, and among them, sterilization by heating is preferable. In the case of heat sterilization, the sterilization temperature is usually 110 to 130 ° C, preferably 120 to 121 ° C. The sterilization time is 10 to 60 minutes, preferably 16 to 17 minutes. The sterilized culture solution thus obtained or the solution obtained by filtering the culture solution to remove the cells (dead bacteria) is used as a component in the present invention.

The components in the present invention prepared as described above may be directly contained in the salivary secretion promoter, but further concentrated or fractionated by purification treatment such as decolorization, deodorization, desalting, column chromatography, etc. It can also be used after processing. Moreover, it can also be used by freeze-drying and pulverizing, or suspending this powder in a solvent and making it into a paste.
As the powder, commercially available “LBS Culture (registered trademark)” (manufactured by Ritani Bioscience Co., Ltd.) may be used.

  The salivary secretion promoter of the present invention may be only the active ingredient in the present invention, but may be a mixture of other components and additives. Other specific ingredients that may be included include binders such as tragacanth, gum arabic, corn starch and gelatin; excipients such as microcrystalline cellulose, crystalline cellulose; corn starch, pregelatinized starch, Bulking agents such as alginic acid and dextrin; lubricants such as magnesium stearate; fluidity improvers such as fine silicon dioxide and methylcellulose; lubricants such as glycerin fatty acid esters; such as sucrose, lactose and aspartame Sweetening agents; peppermint, vanilla flavoring and flavoring agents such as cherry or orange; emulsifiers such as monoglyceride, polyglycerin fatty acid ester, sucrose fatty acid ester, lecithin and the like.

The saliva secretion-promoting agent of the present invention can promote secretion of saliva in the oral cavity by oral administration or application to the oral cavity.
The oral dose of the active ingredient in the present invention is appropriately set according to the age and sex of the subject, the degree of symptoms of the subject, the form of the preparation, and the like. For example, if the saliva secretion promoter of the present invention is applied to an adult, the dose of the agent per adult is usually 15 to 100 mg, preferably 25 to 75 mg of the active ingredient of the present invention. Preferably, the amount corresponding to 40 to 60 mg is exemplified. Moreover, about the frequency | count of administration of the saliva secretion promoter of this invention, the said dosage is normally 1 time or more per day, Preferably it is 1-3 times, More preferably, it is 2-3 times.
The amount of the active ingredient of the present invention applied to the oral cavity is appropriately set according to the degree of symptoms of the subject, the form of the preparation, and the like. For example, if the salivary secretion promoter of the present invention is applied to an adult, the active ingredient of the present invention is usually 15 to 100 mg, preferably 25 to 75 mg as the amount of the agent applied per adult. Preferably, the amount corresponding to 40 to 60 mg is exemplified. Moreover, about the frequency | count of administration of the saliva secretion promoter of this invention, the said dosage is normally 1 time or more per day, Preferably it is 1-3 times, More preferably, it is 2-3 times.

In the salivary secretion promoter of the present invention, the administration period is not particularly limited, and since the ingredient is a naturally derived ingredient, it can be administered for a long time, but usually 3 days to 1 year, preferably 4 weeks to 4 months. It is.
Administration is preferably after meals, and ingestion before going out in the morning and before going to bed at night is effective. It is also effective for ingestion before daytime meetings and before interviews.

The saliva secretion promoter of the present invention is also included in the present invention in the form of a pharmaceutical composition, a quasi-drug composition, a food composition, a feed composition, etc. by adding various additives as necessary. .
The pharmaceutical composition or quasi-drug composition is a pharmaceutically acceptable carrier, excipient, binder, swelling agent, lubricant, sweetener, flavoring agent, antiseptic, and the like. It is provided by formulating with an agent, an emulsifier, a coating agent, etc.
There are no particular restrictions on the dosage form of the above composition. Examples of the dosage form include tablets (orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets), granules, powders, pills, capsules. Oral solutions (elixirs, suspensions, emulsions, fragrances, limonase agents), syrups, oral jelly preparations, etc., oral tablets (gum, sublingual tablets, troches, drops) , Buccal tablets, adhesive tablets), intraoral sprays, semi-solid oral preparations, mouthwashes, ointments, and the like.
Of these, preparations for oral administration such as chewable tablets, preparations for oral application such as oral sprays and gums are preferable, and chewable tablets are more preferable.

  In the above pharmaceutical composition or quasi-drug composition, the mixing ratio of the salivary secretion promoter of the present invention is appropriately set according to the application amount of the agent, the form and use of the composition, etc. The active ingredient in the present invention is usually contained in an amount of 1 to 30% by weight, preferably 2 to 20% by weight, more preferably 5 to 20% by weight. By satisfying such a blending ratio, the salivary secretion promoting effect can be effectively achieved and the feeling of taking and the feeling of use can be satisfied.

  When the dispensing unit form is a capsule, a liquid carrier such as fats and oils can be further contained in the above type of material.

  Various other materials can also be included to change the physical form of the dispensing unit. Examples of the coating agent for tablets include shellac, sugar, or both. A syrup or elixir can contain, for example, sucrose as a sweetening agent, methylparaben and propylparaben as preservatives, a pigment, a cherry or orange flavor, and the like. In addition, various vitamins and various amino acids may be contained.

  When an enteric preparation is used, for example, an aqueous solution of hydroxylphenylmethylcellulose may be used as a coating pretreatment agent, and an aqueous solution of hydroxypropylmethylcellulose phthalate and an aqueous solution of polyacetin may be used as a coating agent to form an enteric preparation by a conventional method.

  When the salivary secretion promoter of the present invention is blended in food as a food additive, it is prescribed in the health foods and health functional food systems ingested by paying attention to the specific functions of the present invention in addition to general foods. It means food for specified health use and food with functional nutrition, and also includes dietary supplements. The amount of the active ingredient of the present invention contained in the food is not particularly limited, but it is preferable that the amount of food and drink per day be in the same range as the above dose of the active ingredient in the present invention. The form of the health functional food of the salivary secretion promoter of the present invention is not particularly limited.

  In the above food composition, the proportion of the salivary secretion promoter of the present invention is appropriately set according to the application amount of the agent, the form and use of the composition, etc. It is contained in an amount of 1 to 30% by weight, preferably 2 to 20% by weight, more preferably 5 to 20% by weight. By satisfying such a blending ratio, the salivary secretion promoting effect can be effectively achieved and the feeling of taking and the feeling of use can be satisfied.

  The food in the present application is a form in which the active ingredient in the present invention is packaged in the form of an ingestion unit amount per serving, or a beverage in which the active ingredient in the present invention is suspended or dissolved in a form of a drink per serving etc. The form filled in is mentioned. The dose per meal may be the daily dose shown above.

  Specifically, in the unit packaging form per serving, the intake amount of the active ingredient in the present invention per unit is usually 10 mg to 100 mg, preferably 15 mg to 100 mg, more preferably 25 mg to 75 mg, more preferably 40 mg ˜60 mg is particularly preferred. For example, in the case of taking twice a day, the intake amount of the active ingredient in the present invention in the unit is usually preferably 10 mg to 100 mg, 15 mg to 100 mg, more preferably 25 mg to 75 mg, more preferably 40 mg to 60 mg. Particularly preferred.

  The form of the food composition in which the salivary secretion promoter of the present invention is blended is not particularly limited, and may be appropriately set to a commonly used preparation form according to the application. For example, a solid agent, a semi-solid agent, and a liquid agent are mentioned, Preferably a solid agent and a liquid agent are mentioned. Specifically, tablets (orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets), granules, powders, pills, capsules, oral solutions (elixirs, suspensions, emulsions, aromatic waters) Preparations, limonase preparations, artificial saliva), syrup preparations, oral jelly preparations, oral preparations, oral tablets (gum, sublingual tablets, troches, drops, buccal tablets, adhesive tablets), oral sprays And preparations applied to the oral cavity such as oral semi-solid preparations, gargles, ointments and the like. Among these, chewable tablets and gums are preferable, and chewable tablets are more preferable from the viewpoint of more effectively exerting the salivary secretion promoting effect.

  In the above-mentioned food composition for promoting saliva secretion, in addition to the saliva secretion-promoting agent of the present invention, for the ingredients to be blended, depending on the use and formulation form of the composition, etc. What is necessary is just to select suitably from the inside. Such components are not particularly limited, but include, for example, excipients, lubricants, disintegrants, binders, antiseptic / antibacterial agents, pH adjusters, chelating agents, antioxidants, cooling agents, Coating agents, solubilizers or solubilizers, disintegration aids, stabilizers, suspending agents, fluidizing agents, emulsifiers, thickeners, thickeners, surfactants, buffers, antifoaming agents, Examples include foaming agents, solvents, isotonic agents, sweeteners, fragrances, colorants, dispersants, adsorbents, wetting agents, and moisture-proofing agents.

In addition to the active ingredient in the present invention, the pharmaceutical, quasi-drug, and food of the present invention may further contain any other active ingredient.
For example, drugs having salivary secreting action such as menthol, alginic acid, polyglutamic acid, organic acids, carbohydrates and the like can be mentioned.

  The saliva secretion-promoting agent of the present invention can be used as it is or by blending various additives into the above composition to administer dry mouth (xerostomia), caries, tongue coating, bad breath, periodontal disease, It is possible to improve dysphagia, stomatitis, stomatitis, and the like.

  Furthermore, the salivary secretion promoter of the present invention is a feed composition for the purpose of improving dry mice such as pets (xerostomia), caries, tongue coating, halitosis, periodontal disease, dysphagia, stomatitis, stomatitis, etc. Can also be provided.

  A salivary secretion promoter, particularly an oral or oral composition, to be incorporated into the pharmaceutical composition, quasi-drug composition, food composition and feed composition, comprising the active ingredient of the present invention Salivary secretion promoters for blending into products are also included in the present invention.

When the salivary secretion promoter is produced in medicines, quasi drugs, foods, etc., a method commonly used in the technical field may be used as it is or appropriately applied depending on the type of preparation. For example, in the case of tablets, granulation methods commonly used in the art (for example, extrusion granulation method, pulverization granulation method, dry compaction granulation method, fluidized bed granulation method, rolling granulation method, high speed granulation method, Agitation granulation method, etc.), tableting method (for example, wet tableting method, direct tableting method, etc.) and the like can be appropriately combined according to the purpose. In the case of a liquid preparation, for example, the above-mentioned components are used by using a base such as water (purified water, etc.), alcohol, vegetable oil (olive oil, soybean oil, sesame oil, cottonseed oil, etc.) and an additive such as a surfactant. Can be dissolved or suspended and produced by methods commonly used in the art.
Similarly, when a feed composition is produced, it can be produced by a method commonly used in the art depending on the target animal.

  Further, the present invention will be described in detail by examples. First, preparation examples of components in the present invention are shown.

[Preparation Example of Components in the Present Invention]
1. Preparation of medium: First, 450 g of raw rice bran and 9 L of water were mixed and stirred for 1 to 1.5 hours to obtain an aqueous extract of 5% by weight of rice bran. Next, this rice bran extract was filtered with a cotton cloth. This filtration can be performed using, for example, a suction machine or a filter press in addition to the cotton cloth. And while removing the residue (salt) after filtration, 450g of glucose was added to the filtrate, and also it heated at 100 degreeC for 10 minute (s), and prepared the mixed solution. Next, the heated mixed solution was filtered with a cotton cloth. The filtration in this case can also be performed using a suction machine or a filter press in addition to the cotton cloth. While removing the residue after filtration, the filtrate was supplemented with about 3 L of water to prepare a 9 L mixed solution. This solution was sterilized at 121 ° C. for 17 minutes and then cooled to obtain a medium. In addition, as raw rice bran, what was generated at the time of brown rice polishing was used, and tap water was used as water.

  2. Preparation of the culture solution: In the medium prepared as described above, Lactobacillus paracasei, Saccharomyces cerevisiae, Pichia membranifaciens and Bacillus pumilus 4 types of bacteria were added and mixed. Next, aeration culture was performed at 37 ° C. for 48 hours (primary culture). After the primary culture, cold aging was performed at 5 ° C. for 1.5 months (secondary culture). After this secondary culture, the mixture was sterilized at 121 ° C. for 17 minutes, and then filtered to remove the cells to obtain a mixed culture solution. This mixed culture was stored refrigerated at 5 ° C.

  In the following examples according to the present invention, “LBS culture” (manufactured by Ritanial Bioscience Co., Ltd.) was used as a component in the present invention. This product is obtained by removing the cells after the heat sterilization treatment in the mixed culture solution described in the above preparation example.

[Example 1] Effect of improving the dry mouth of ingredients in the present invention Various additives shown in Table 1 were weighed so as to contain 5% of LBS culture bulk powder as an ingredient in the present invention, and compressed into tablets by a conventional method. A 300 mg oral care tablet was prepared, and the improvement effect was evaluated for dry mice and other symptoms. The evaluation was conducted by a test conducted by 42 subjects of 20 to 60 years old who were very concerned about dry mice (Group A), interested (Group B), and so much interested (Group C). went.
Subject is
・ Toothpaste less than 2 times a day as a lifestyle ・ As a lifestyle, a person who satisfies the above condition of not using the mouthwash more than 4 times a week was selected, and the use of the mouthwash was discontinued during the test.
Each subject was allowed to hold 1 tablet (1 tablet 300 mg) 3 times a day for 3 minutes or more in the oral cavity and ingested for 3 days or more, and then the effect was evaluated.

The question of whether the mouth feels moist compared to before and after taking an oral care tablet was evaluated according to the following criteria.
I don't think at all
I don't think so much
There was no change
I think so
I think so
I think very much

  Table 2 shows the number of subjects in each group evaluated.

  The proportion of subjects who made each evaluation is shown in FIG.

  The above criteria were used to evaluate the question of whether the feeling of stickiness in the mouth was improved before and after taking the oral care tablet.

  Table 3 shows the number of subjects in each group evaluated.

  The percentage of subjects who made each evaluation is shown in FIG.

  The question of whether or not dryness in the mouth was thought to have improved compared to before and after taking oral care tablets was evaluated according to the above criteria.

  Table 4 shows the number of subjects in each group for each evaluation.

  The number of subjects who made each evaluation is shown in FIG.

  The question of whether or not saliva increased compared to before and after taking oral care tablets was evaluated according to the above criteria.

  Table 5 shows the number of subjects in each group evaluated.

   The percentage of subjects who made each evaluation is shown in FIG.

  When asked whether the environment in the mouth was better compared to before and after taking the oral care tablet, the above criteria were used.

  Table 6 shows the number of subjects in each group evaluated.

   FIG. 5 shows the ratio of subjects who made each evaluation.

  The question of whether the bad breath was thought to have improved compared to before and after taking oral care tablets was evaluated according to the above criteria.

  Table 7 shows the number of subjects in each group evaluated.

  FIG. 6 shows the ratio of subjects who made each evaluation.

  The above criteria were used to evaluate the question of whether plaque was reduced before and after taking an oral care tablet.

  Table 8 shows the number of subjects in each group for each evaluation.

  The number of subjects who made each evaluation is shown in FIG.

[Example 2] Examination of the effect of intragastric administration on the activity of the rat intestinal vagus (parasympathetic) nerve centrifuge branch (1) Experimental method The experiment was conducted under a light / dark cycle (lighted from 8 o'clock to 20 o'clock) every 12 hours Wistar male rats (about 9 weeks old) having a body weight of about 300 g and kept in a constant temperature animal room at 24 ° C. for 1 week or more were used. On the day of the experiment, fasting for 3 hours followed by urethane anesthesia, inserting a cannula for intragastric administration, lifting the intestinal vagus (parasympathetic) nerve centrifuge branch with a silver electrode, and the method described previously (Shen J, et al. Neurosci. Lett. 383188-193, 2005, Tanida M, et al., Neurosci. Lett. 389: 109-114, 2005). At the time when this measured value settled (around 13:00), 1 ml / 300 g body weight of a 10,000-fold diluted LBS culture solution was intragastrically administered via a cannula, and changes in these nerve activities were measured electrophysiologically. As a control experiment, the change in the nerve activity was measured when the medium solution 1 ml / 300 g body weight used for the culture of LBS culture was intragastrically administered by the same method. A tube was inserted into the trachea from the start of surgery to the end of the measurement to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a heat retaining device. Intestinal vagus nerve activity data is expressed as a percentage, with the average value of the firing frequency per 5 seconds (pulse / 5 s) every 5 minutes and the value for 5 minutes (0 minute value) before the start of administration as 100%. did. The mean ± standard error is calculated from the data, and the statistical significance of the group is tested by analysis of variance (ANOVA) with repeated measures. The neuronal activity before the start of intragastric administration (0 min) The test of statistical significance between absolute values was performed by Mann-Whitney U-test.

(2) Results Figure 8 shows the intestinal vagal nerve activity (intestinal vagal-NA) when a 10,000-fold diluted solution or 1 ml / 300g body weight of the medium solution of LBS culture was administered into the stomach. Measured data is shown. In FIG. 8, the nerve activity of intestinal vagal-NA before the start of intragastric administration (0 minutes) is shown as a percentage with 100%. Intestinal vagal-NA slightly increased 5 minutes after administration of 1 ml / 300g body weight of the medium solution as a control experiment, and the intestinal vagal-NA value reached the maximum value of 104.3 ± 5.4%, and then slowly The intestinal vagal-NA value decreased to the lowest value of 90.3 ± 5.0% 55 minutes after administration (FIG. 8). In contrast, intestinal vagal-NA increased slowly and gradually, and the intestinal vagal-NA value reached the highest 45 minutes after administration when a 1/300 g body weight of a 1 / 10,000-fold diluted LBS culture medium solution was administered into the stomach. The value increased to 115.6 ± 6.8%, and after that it decreased slightly, but remained in the vicinity (Fig. 8).
Statistical differences between intestinal vagal-NA values between the control medium solution administration group and the LBS culture undiluted solution diluted 10,000-fold dilution group between 5 and 60 minutes after the start of intragastric administration Examination reveals that the intestinal vagal-NA value in the LBS culture administration group is significantly higher (P <0.0005, F = 57.6 by ANOVA with repeated measures) than the intestinal vagal-NA value in the control medium solution application group became.
There was no statistically significant difference by Mann-Whitney U-test between the absolute values of intestinal vagal-NA before the start of administration (0 minutes) in the LBS culture administration group and the control medium solution administration group.

From the above experiment, in the anesthetized rat, the intragastric administration of 1 ml / 300 g body weight of the LBS culture undiluted solution was performed in the intestinal vagus as compared to the intragastric administration of 1 ml / 300 g body weight of the medium solution as a control experiment. (Parasympathetic) It was revealed that the activity of the nerve centrifuge branch (intestinal vagal-NA) was significantly increased.
If the intestinal vagus (parasympathetic) nerve is promoted, digestion and absorption capacity, gastrointestinal motility (peristalsis) and salivation are promoted, and diarrhea is improved and appetite is increased. (Parasympathetic) It was suggested to promote nerves and promote salivation.

Example 3: Examples of various compositions (1) Oral care tablet containing saliva secretion promoter (chewable tablet)
According to the following composition, an oral care tablet containing the saliva secretion promoter described in the present invention was prepared.
LBS culture bulk 20%, anhydrous citric acid 11.54%, sodium bicarbonate 13%, yogurt powder YP-A 7%, dry coat yogurt # 177 4%, sun sweet SU-200 0.1%, mirasui 200 1%, Partec SI150 40.86%, calcium stearate 2%, aloezil 200FAD 0.5%

(2) Oral care tablet containing saliva secretion promoter (chewable tablet)
According to the following composition, an oral care tablet containing the saliva secretion promoter described in the present invention was prepared.
LBS Culture Bulk 10%, Partec SI150 50%, Xyrit Fine Powder 33.6%, Viva Pure 102 33.6%, Calcium Stearate 3.0%, Aloesil 200FAD 0.3%, Dry Court Menthol # 32-D 0.1%

(3) Oral products containing saliva secretion promoter A mouthwash containing the saliva secretion promoter according to the present invention was prepared according to the following composition.
LBS culture bulk 5%, moisture 68.98%, sorbitol 5%, sodium benzoate 0.02%

(4) Food containing saliva secretion promoter (candy)
According to the following composition, a candy containing the saliva secretion promoter described in the present invention was prepared.
LBS Culture raw powder 2.6%, Minamata 97.3%, Fragrance (tea flavor) 0.1%

(5) Food containing a saliva secretion promoter (chewing gum)
According to the following composition, the chewing gum containing the salivary secretion promoter described in the present invention was prepared.
LBS culture bulk powder 5%, gum base 87%, calcium stearate 2%, sucrose fatty acid ester 1.5%, flavor 2%, vitamin C 2%, citric acid 0.5%

  The salivary secretion-promoting agent of the present invention can improve dry mice, make the oral cavity a desirable environment, and increase QOL. It can also be used safely and for a long time for elderly people, sick people, healthy people and children.

Claims (7)

  The salivary secretion promoter containing the component obtained by mixing culture of lactic acid bacteria, natto bacteria, and yeast.   The saliva secretion promoter of Claim 1 containing the fermented liquor obtained by culture | cultivating lactic acid bacteria, Bacillus natto, and yeast with the culture medium containing a rice bran extract and glucose.   The salivary secretion promoter according to claim 1 or 2, wherein the lactic acid bacterium is Lactobacillus paracasei.   The salivary secretion promoter according to any one of claims 1 to 3, wherein the Bacillus natto is Bacillus pamilus.   The salivary secretion promoter according to any one of claims 1 to 4, wherein the yeast is at least one selected from Saccharomyces cerevisiae and Pichia membranifasiens.   The salivary secretion promoter according to any one of claims 1 to 5, which is used for improving dry mice.   The saliva secretion promoter of any one of Claims 1-6 for mix | blending with the composition for oral cavity or oral administration.