Composition for promoting saliva secretion

Abstract

The purpose of the present invention is to provide a novel composition for promoting saliva secretion. According to the present invention, provided is a composition for promoting saliva secretion, the composition comprising a fructooligosaccharide as an active ingredient. According to the present invention, an effect of promoting secretion of saliva and IgA in saliva is provided, and the present invention is advantageous in terms of high safety without concern about side effects when continuously ingested over a long period of time, and is particularly useful for oral care of a person of middle age or an elderly person with reduced levels of saliva and IgA secretion. According to the present invention, secretion of IgA (viral cross-reactive IgA) having cross-reactivity to a previously unexposed virus can be promoted. Therefore, the present invention is also advantageous in terms of contribution to prevention of viral infection.

Description

Composition for promoting saliva secretion REFERENCE TO RELATED APPLICATIONS

[0001] This application benefits from the priority of an earlier Japanese application, Patent Application No. 2023-136952 (filing date: August 25, 2023), the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a composition for promoting saliva secretion. The present invention also relates to a composition for promoting IgA secretion in saliva.

[0003] Saliva has important physiological functions, such as preventing dry mouth and self-cleaning the oral cavity by digesting food residue. Therefore, a decrease in saliva secretion facilitates bacterial proliferation, increasing the risk of halitosis and tooth decay, and ultimately leading to a weakened immune system. Furthermore, saliva secretion can be reduced not only by illness but also by stress and physical condition. Therefore, maintaining an appropriate level of saliva secretion is extremely important for maintaining a healthy oral environment (Non-Patent Document 1).

[0004] Furthermore, a decrease in salivary IgA is known to increase the risk of upper respiratory tract infections (Non-Patent Document 2), and pneumonia, which is a leading cause of death among Japanese people, is closely related to the condition of the oral cavity. Furthermore, with the global spread of the novel coronavirus (SARS-CoV-2), there has been growing public interest in the treatment and prevention of SARS-CoV-2 infection (COVID-19). Under these circumstances, since pathogens such as viruses and bacteria enter the body through the mouth and are transmitted via the nasal and pharyngeal mucosa, there is hope for improving mucosal immunity in the oral cavity, which is the entry point for these pathogens.

[0005] Llena-Puy C., Med Oral Patol Oral Cir Bucal., 2006; 11(5): E449-55.Moreira A, et al., J Strength Cond Res., 2014; 28(2): 467-73.

[0006] An object of the present invention is to provide a novel composition for promoting saliva secretion and a novel composition for promoting IgA secretion in saliva.

[0007] The present inventors have now found in human studies that ingestion of fructooligosaccharides promotes the secretion of saliva at rest and IgA (particularly cross-reactive IgA) in saliva. The present invention is based on these findings.

[0008] The present invention provides the following inventions. [1] A composition for promoting cross-reactive IgA secretion in saliva or an agent for promoting IgA secretion in saliva, comprising fructooligosaccharide as an active ingredient. [2] A composition or agent according to the above item [1], for use in preventing or reducing the risk of viral infection. [3] A composition or agent according to the above item [1] or [2], wherein the virus is a coronavirus. [4] A composition or agent according to any of the above items [1] to [3], wherein the virus is a betacoronavirus. [5] A composition or agent according to any of the above items [1] to [4], wherein the virus binds to the ACE2 receptor. [6] A composition or agent for promoting resting saliva secretion, comprising fructooligosaccharide as an active ingredient. [7] A composition or agent according to the above item [6], for use in oral care. [8] A composition or agent according to any of the above items [1] to [7], for use in enhancing oral immunity. [9] The composition or agent according to any one of [1] to [8] above, wherein the fructooligosaccharide is a mixture of 1-kestose, nystose, and 1-fructofuranosyl-D-nystose.

[10] The composition or agent according to [9] above, wherein the ratio of 1-kestose, nystose, and 1-fructofuranosyl-D-nystose in the mixture is 10-50:20-70:1-20.

[11] The composition or agent according to any one of [1] to

[10] above, wherein the subject is a human.

[12] The composition or agent according to

[11] above, wherein the human is 50 years of age or older.

[13] The composition or agent according to

[11] or

[12] above, wherein the effective daily intake for a human is 1-60 g.

[14] The composition or agent according to any one of [1] to

[13] above, wherein the composition or agent is taken continuously for one week or more.

[15] The composition or agent according to any one of [1] to

[14] above, wherein the composition or agent is a food composition.

[16] A method for promoting secretion of virus-cross-reactive IgA in saliva or a method for promoting resting saliva secretion, comprising the step of having a subject in need thereof ingest an effective amount of a fructooligosaccharide or a composition containing the same.

[17] A method for oral care by promoting saliva secretion at rest, or a method for preventing or reducing the risk of viral infection that can be prevented by promoting the secretion of virus-cross-reactive IgA in saliva, comprising a step of having a subject in need thereof ingest an effective amount of fructooligosaccharide or a composition containing same.

[18] Use of fructooligosaccharides as a salivary cross-reactive IgA secretion promoter or a resting saliva secretion promoter for the manufacture of a salivary cross-reactive IgA secretion promoter or a resting saliva secretion promoter, or in a method for promoting saliva secretion at rest.

[19] Use of fructooligosaccharides as an oral care agent by promoting resting saliva secretion or a preventive or risk-reducing agent for viral infections that can be prevented by promoting saliva secretion at rest, or as an oral care agent by promoting saliva secretion at rest or a preventive or risk-reducing agent for viral infections that can be prevented by promoting saliva secretion at rest, or in a method of oral care by promoting saliva secretion at rest or a method for preventing or risk-reducing viral infections that can be prevented by promoting saliva secretion at rest.

[0009] In this specification, the compositions of [1] to

[15] above may be referred to as "compositions of the present invention." Furthermore, in this specification, the agents of [1] to

[15] above may be referred to as "agents of the present invention."

[0010] The active ingredient of the present invention is fructooligosaccharide, which has long been used as a food ingredient. Therefore, the compositions and agents of the present invention are effective in promoting the secretion of saliva and salivary IgA (especially cross-reactive IgA) at rest, and are advantageous in that they are highly safe and can be taken continuously over a long period of time without the risk of side effects. They are particularly useful for oral care for middle-aged and elderly people, whose saliva and IgA secretion levels decline. The present invention is also advantageous in that it can promote the secretion of IgA (cross-reactive IgA) that is cross-reactive with viruses that have not previously been infected, thereby contributing to the prevention of viral infections.

[0011] Figure 1 shows the salivary secretion rate (mL / min) (Figure 1A), salivary IgA concentration (μg / mL) (Figure 1B), salivary IgA secretion rate (μg / min) (Figure 1C), salivary SARS-COV-2 cross-reactive IgA concentration (ng / mL) (Figure 1D), and salivary SARS-COV-2 cross-reactive IgA secretion rate (ng / min) (Figure 1E) before the start of fructooligosaccharide intake (week 0), and 4 weeks (week 4) and 8 weeks (week 8) after the start of intake. Figure 2 shows the increase rate of saliva secretion rate (Figure 2A), the increase rate of salivary IgA concentration (Figure 2B), the increase rate of salivary IgA secretion rate (Figure 2C), the increase rate of salivary SARS-COV-2 cross-reactive IgA concentration (Figure 2D), and the increase rate of salivary SARS-COV-2 cross-reactive IgA secretion rate (Figure 2E) for each subject before the start of fructooligosaccharide intake (week 0), 4 weeks after the start of intake (week 4), and 8 weeks after intake (week 8). Specific Description of the Invention

[0012] The compositions and agents of the present invention contain fructooligosaccharides as active ingredients. The compositions and agents of the present invention may contain only fructooligosaccharides as the active ingredient, or may consist of fructooligosaccharides as the active ingredient. In the present invention, "fructooligosaccharides (FOS)" refers to oligosaccharides in which one to three fructose molecules are bound to sucrose. FOS include 1-kestose, in which one fructose molecule is bound to the fructose residue of sucrose via a β-2,1 bond; nystose, in which two fructose molecules are bound to the fructose residue of sucrose via a β-2,1 bond; and 1-fructofuranosyl-D-nystose, in which three fructose molecules are bound to the fructose residue of sucrose via a β-2,1 bond.

[0013] FOS is synthesized by β-fructofuranosidase. In the present invention, any of 1-kestose, nystose, and 1-fructofuranosyl-D-nystose can be used as the fructooligosaccharide. In the present invention, a mixture of two or more fructooligosaccharides selected from the group consisting of 1-kestose, nystose, and 1-fructofuranosyl-D-nystose can also be used, and a mixture of 1-kestose, nystose, and 1-fructofuranosyl-D-nystose (for example, a commercially available product such as Mei Oligo P manufactured by Meiji Food Materials Co., Ltd.) is preferred. In the present invention, the mixture of 1-kestose, nystose, and 1-fructofuranosyl-D-nystose preferably has a mass ratio of 1-kestose:nystose:1-fructofuranosyl-D-nystose of 10-50:20-70:1-20, more preferably 20-45:30-60:3-18, and particularly preferably 30-40:45-55:5-15.

[0014] The compositions and agents of the present invention may be provided as fructooligosaccharides themselves, or may be provided as a mixture of fructooligosaccharides and other ingredients.

[0015] The content of fructooligosaccharides in the compositions and agents of the present invention can be determined arbitrarily depending on the purpose, use, form, dosage form, symptoms, body weight, etc., and the present invention is not limited thereto. However, the content (solid content equivalent) relative to the total amount can be determined as follows: That is, the lower limit of the fructooligosaccharide content in the compositions and agents of the present invention (not less than or greater than) can be, for example, 0.5%, 1%, 2%, 3%, 4%, or 5% by mass. The upper limit of the content (not more than or less than) can be 100% by mass, or 99%, 90%, 80%, 70%, or 60% by mass. These lower and upper limits can be arbitrarily combined, and the content range can be, for example, 0.5 to 100% by mass, 1 to 99% by mass, 2 to 90% by mass, or 5 to 60% by mass.

[0016] The content of fructooligosaccharides in the compositions and preparations of the present invention can be measured by high performance liquid chromatography (HPLC). For example, the content of fructooligosaccharides can be measured under the following analytical conditions (see Appendix 3 of the Specified Health Food (Standards and Criteria Type) System, Regarding Labeling Approval for Foods for Specified Health Uses (October 30, 2014, Food and Drug Administration No. 259)). Detector: differential refractometer; Column packing: 5 μm chemically modified aminopropylsilylated silica gel; Column tube: stainless steel tube with an inner diameter of 4 mm and a length of 25 cm; Column temperature: 40° C.; Mobile phase: acetonitrile / water mixture (70:30); Flow rate: 1.0 mL / min.

[0017] As shown in the Examples below, fructooligosaccharides have the effect of promoting saliva secretion at rest. That is, the composition and agent of the present invention can be used to promote saliva secretion at rest. Saliva has functions such as mucosal protection, lubrication, self-cleaning, water balance, buffering, antibacterial properties, digestion, tissue repair, and remineralization, so by promoting saliva secretion, it can be used for oral care or oral hygiene. The composition and agent of the present invention can also be used to enhance oral immunity (especially mucosal immunity) because the above functions of saliva enhance oral immunity.

[0018] The amount of saliva can be measured by a known method. For example, as shown in the Examples below, saliva can be collected using a saliva collection device (e.g., a salivet) and the amount of saliva collected can be measured.

[0019] As shown in the examples below, fructooligosaccharides have the effect of promoting IgA secretion in saliva. That is, the composition and agent of the present invention can be used to promote IgA secretion in saliva. Furthermore, because fructooligosaccharides promote the secretion of IgA that cross-reacts with viruses (sometimes referred to as "virus-cross-reactive IgA" in this specification), the composition and agent of the present invention can be used to prevent viral infection. Here, in the present invention, saliva containing IgA refers to resting saliva. In the present invention, "prevention of viral infection" is used to mean a reduction in the risk of viral infection, and a reduction in the risk of viral infection means a reduction in the probability of a subject contracting or developing a viral infection. The composition and agent of the present invention can also be used to enhance oral immunity (particularly mucosal immunity) because promoting IgA secretion in saliva enhances oral immunity.

[0020] The amount or concentration of IgA in saliva can be measured by known methods, such as immunoassays using antibodies or aptamers, including enzyme immunoassays (ELISA and EIA), radioimmunoassays (RIA), fluorescent immunoassays (FIA), fluorescence polarization immunoassays (FPIA), chemiluminescent immunoassays, and Western blots, with ELISA and EIA being preferred from the standpoint of rapid and simple detection.

[0021] In the present invention, the virus is not particularly limited as long as it cross-reacts with IgA, but is preferably a coronavirus. Examples of coronaviruses include alphacoronaviruses (e.g., HCoV-229E, HCoV-NL63), betacoronaviruses (e.g., HCoV-OC43, SARS-CoV, HCoV-HKU1, MERS-CoV, SARS-CoV-2), gammacoronaviruses, and deltacoronaviruses, more preferably betacoronaviruses, and even more preferably SARS-CoV-2. Coronaviruses also include those that bind to ACE receptors, and examples of ACE receptor-binding coronaviruses include HCoV-NL63, SARS-CoV, and SARS-CoV-2, preferably SARS-CoV and SARS-CoV-2, and more preferably SARS-CoV-2. Infection with HCoV-NL63, SARS-CoV and SARS-CoV-2 begins when the spike protein (S protein) binds to the ACE2 receptor on the cell membrane.

[0022] Subjects to which the compositions and agents of the present invention are administered or taken include humans and non-human mammals (e.g., pets such as dogs and cats, and livestock such as cows and horses), preferably humans. In the present invention, the subject also includes healthy subjects.

[0023] Here, taking into consideration that the secretion of saliva and IgA in saliva is known to decrease with age in humans, it is preferable that the subjects to be ingested or administered with the compositions and agents of the present invention are middle-aged or elderly people, and examples of such ages include those aged 50 or older, 55 or older, 60 or older, 65 or older, 70 or older, 75 or older, 80 or older, or 85 or older.

[0024] Subjects receiving or receiving the compositions and agents of the present invention may be those with reduced saliva secretion or salivary IgA secretion (including not only those with chronically reduced functions but also those with temporarily reduced functions). Reduced salivary secretion is known to be caused by anxiety, tension, Sjögren's syndrome, salivary gland disorders, dehydration, cirrhosis, diabetes, and side effects of medications (such as antipsychotics and antihypertensives). Examples of subjects with reduced saliva secretion or salivary IgA secretion include middle-aged and elderly people, as well as those with these factors. Subjects receiving or receiving the compositions and agents of the present invention may also be those who are at risk of or are at high risk of reduced saliva secretion or salivary IgA secretion, even if they are not necessarily in a state where the functions of saliva secretion or salivary IgA secretion are reduced.

[0025] In the present invention, a subject with reduced saliva secretion or reduced IgA secretion in saliva can be identified using, for example, the amount of saliva secretion or the amount of IgA secretion in saliva as an index. For example, if saliva is collected from a subject before the start of intake or administration, and the amount of saliva secretion or the amount of IgA secretion in saliva is low compared to a reference value, the subject can be identified as having reduced saliva secretion or reduced IgA secretion in saliva.

[0026] In the present invention, the "reference value" can be determined, for example, by calculating the saliva volume or the IgA secretion volume in saliva of a subject (normal subject) with normal saliva secretion or IgA secretion in saliva. In the above-mentioned method for determining the reference value, the mean value, median value, percentile value, maximum value, or minimum value of the normal subject can be used. The percentile value can be any value selected, for example, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 75, 80, 85, 90, or 95. When calculating the reference value, it is preferable to use multiple normal subjects, for example, 2 or more, 5 or more, 10 or more, 20 or more, 50 or more, or 100 or more. The reference value is a value used to identify subjects with reduced saliva secretion or IgA secretion in saliva, and in this sense, it can be referred to as a cutoff value or boundary value.

[0027] In the present invention, the "reference value" can also be calculated based on the saliva volume or IgA secretion volume in saliva of a subject with normal saliva secretion or IgA secretion function in saliva (normal subject) and the saliva volume or IgA secretion volume in saliva of a subject with reduced saliva secretion or IgA secretion function in saliva (reduced subject). For example, the reference value can be set by performing statistical analysis such as ROC (Receiver Operating Characteristic) analysis using the saliva volumes or IgA secretion volumes in saliva of normal subjects and reduced subjects. Methods for creating ROC curves and setting reference values ​​based on ROC curves are well known, and can be set appropriately by those skilled in the art from the perspective of sensitivity and specificity.

[0028] In the present invention, a subject can be identified as having reduced saliva secretion or salivary IgA secretion function when, for example, the saliva volume or IgA secretion volume in saliva of a subject is lower than the average value of the saliva volume or IgA secretion volume in saliva of a normal subject, or is about 0.9 times or less, about 0.85 times or less, about 0.8 times or less, about 0.75 times or less, about 0.7 times or less, about 0.65 times or less, about 0.6 times or less, about 0.55 times or less, about 0.5 times or less, about 0.45 times or less, about 0.4 times or less, or about 0.35 times or less compared to the average value.

[0029] The compositions and agents of the present invention can be provided in the form of pharmaceuticals and quasi-drugs (e.g., pharmaceutical compositions), foods (e.g., food compositions), feeds (e.g., pet foods), etc., and can be implemented according to the description below.

[0030] The compositions and agents of the present invention can be orally administered or ingested by humans and non-human mammals. That is, the compositions and agents of the present invention can be orally administered or ingested compositions and agents. Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. These preparations can be formulated using pharmaceutically acceptable carriers by methods commonly used in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, flavorings, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc.

[0031] When the compositions and agents of the present invention are provided as foods, fructooligosaccharides can be directly incorporated into the food, and the food contains an effective amount of fructooligosaccharides. Here, "containing an effective amount" of fructooligosaccharides refers to a content such that the fructooligosaccharide intake range described below is achieved when the individual food is ingested in the amount normally consumed. Furthermore, the term "food" is used to include health foods, functional foods, health-related foods (e.g., foods with specified health uses, nutrient-functional foods, and foods with functional claims), dietary supplements, food supplements, medical foods, special-use foods (e.g., foods for infants, foods for pregnant women, and foods for the sick) and supplements. Here, dietary supplements refer to products (excluding tobacco) intended to supplement the diet, as defined by the Federal Food, Drug, and Cosmetic Act, that contain one or more vitamins, minerals, herbs or other botanicals, amino acids, etc., and are labeled as dietary supplements. A food supplement is a concentrated form of nutrients or other substances, either alone or in combination, that supplements the normal diet and has a nutritional or physiological effect, and is labeled as such. A medical food, as defined in the U.S. Food and Drug Administration (FDA) Medical Foods Guidance Documents & Regulatory Information, is a food formulated to be taken or administered enterally under physician supervision for the specific dietary management of a disease or condition for which unique nutritional requirements have been established based on accepted scientific principles through medical evaluation.

[0032] The form of the "food" is not particularly limited, and may be, for example, a food or supplement that is taken daily, a drink, a semi-liquid or gel form, or a solid form. The agent of the present invention can also be used as a food additive.

[0033] For example, when fructooligosaccharides are orally administered or ingested as a food, the daily dose (in terms of solid content) for a human can be 1 to 60 g, preferably 3 to 50 g, and more preferably 10 to 20 g. In the present invention, fructooligosaccharides can be administered once a day, or can be taken multiple times a day (e.g., two or more times, three or more times).

[0034] The compositions and agents of the present invention can further enhance the effects of promoting IgA secretion in saliva and preventing viral infections by being used in combination with materials or compositions that are expected to have the effect of promoting IgA secretion in saliva or the effect of preventing viral infections. Examples of such materials or compositions include fermented milk prepared using lactic acid bacteria, beverages or compositions containing one or more selected from lactic acid bacteria, bifidobacteria, and yeast, tea beverages (green tea, black tea, roasted green tea, herbal tea) or tea extracts, fruit juice, vegetable juice, polyphenols, lactoferrin, lactoperoxidase, casein peptides, rice bran, and herbal medicines.

[0035] The composition and agent of the present invention can be provided as a composition and agent comprising a daily intake amount of fructooligosaccharide effective for promoting the secretion of saliva and IgA (particularly virus-cross-reactive IgA) in saliva. In this case, the composition and agent of the present invention may be packaged so that the effective daily intake amount can be ingested, and the form thereof is not particularly limited as long as the effective daily intake amount can be ingested.

[0036] Typically, the compositions and agents of the present invention can be provided in unit intake forms, and a subject can ingest one or more unit intake forms to receive a daily effective intake amount. Here, the term "unit intake form" refers to a form containing a predetermined amount of an active ingredient suitable for one intake, and examples include processed forms such as sticks, tablets, capsules, chocolates, ice cream, candies, and fermented milk, as well as packaged forms.

[0037] When the compositions and agents of the present invention are provided in unit intake forms, it is desirable to provide information on the intake amount so that the effective intake amount for one day can be taken. Furthermore, when the effective intake amount for one day is provided in multiple unit intake forms, for convenience of intake, multiple unit intake forms corresponding to the effective intake amount for one day can be provided as a set, and even multiple unit intake forms corresponding to the effective intake amount for multiple days can be provided as a set.

[0038] When the composition and agent of the present invention are provided in a packaged form, it is desirable that the package has instructions regarding the amount of intake so that a daily effective intake can be taken, or that a document with such instructions is provided together with the composition and agent. Furthermore, when a daily effective intake is provided in multiple packages, multiple packages containing a daily effective intake can be provided as a set for convenience of intake.

[0039] The packaging form for providing the composition and agent of the present invention is not particularly limited as long as it is a form that specifies a certain amount, and examples include wrapping paper, bags, soft bags, paper containers, cans, bottles, capsules, and other containers that can accommodate the composition and agent of the present invention.

[0040] The compositions and agents of the present invention can be taken continuously for at least one week to better exert their effects, and the intake and administration period is preferably two weeks or more (e.g., 2 to 14 weeks), more preferably three weeks or more (e.g., 3 to 21 weeks), even more preferably four weeks or more (e.g., 4 to 28 weeks), and even more preferably one month or more (e.g., 1 to 6 months). Here, "continuously" means daily administration or administration at least once every two days. When the compositions and agents of the present invention are provided in a packaged form, they may be provided as a set containing an effective intake amount for a certain period (e.g., one week) for continuous intake.

[0041] The food of the present invention may be labeled to indicate that it has the effect of promoting the secretion of either or both of saliva and IgA in saliva (particularly cross-viral IgA). In this case, in order to make the labeling easy for consumers to understand, the food of the present invention may be labeled with, for example, some or all of the following: - Prepares the oral environment - Improves the oral environment - Helps improve the oral environment - Maintains a good oral environment - Maintains a clean oral environment - Cares for the oral cavity - Oral immune care - Maintains oral mucosal immunity - Oral mucosal immune care - Maintains oral mucosal immunity - Stops / blocks the invasion of coronavirus

[0042] Another aspect of the present invention provides a method for promoting saliva secretion (preferably a method for promoting resting saliva secretion) and a method for promoting IgA secretion in saliva (preferably a method for promoting virus-cross-reactive IgA secretion in saliva), which comprises ingesting or administering an effective amount of a fructooligosaccharide or a composition containing the same to a subject in need thereof (e.g., a human or non-human mammal). The method for promoting saliva secretion and the method for promoting IgA secretion of the present invention can be carried out according to the description of the compositions and agents of the present invention. Note that, since the subjects to be ingested or administered the present invention may be those with reduced saliva secretion or reduced IgA secretion in saliva, the method may further include a step of determining the subject to be ingested or administered prior to ingestion or administration. Such a determination step can be carried out according to the description of the compositions or agents of the present invention.

[0043] Another aspect of the present invention provides a method for oral care by promoting saliva secretion (preferably promoting resting saliva secretion), and a method for preventing and reducing the risk of viral infection that can be prevented by promoting IgA secretion in saliva (preferably promoting cross-viral IgA secretion in saliva), which comprises ingesting or administering an effective amount of a fructooligosaccharide or a composition containing the same to a subject in need thereof (e.g., a human or non-human mammal).The oral care method and the prevention and risk reduction methods of the present invention can be carried out according to the description of the compositions and agents of the present invention.

[0044] According to another aspect of the present invention, there are provided the use of fructooligosaccharides for the manufacture of saliva secretion stimulants (preferably resting saliva secretion stimulants), salivary IgA secretion stimulants (preferably viral cross-reactive IgA secretion stimulants in saliva), and oral care agents by promoting saliva secretion (preferably resting saliva secretion), as well as the use of fructooligosaccharides as saliva secretion stimulants and the use of fructooligosaccharides as salivary IgA secretion stimulants (preferably viral cross-reactive IgA secretion stimulants in saliva). The present invention also provides the use of fructooligosaccharides for the production of oral care agents that promote saliva secretion (preferably promoting resting saliva secretion) and preventive agents and risk-reducing agents for viral infections that can be prevented by promoting IgA secretion in saliva (preferably promoting cross-viral IgA secretion in saliva), and the use of fructooligosaccharides as oral care agents that promote saliva secretion (preferably promoting resting saliva secretion) and the use of fructooligosaccharides as preventive agents and risk-reducing agents for viral infections that can be prevented by promoting IgA secretion in saliva (preferably promoting cross-viral IgA secretion in saliva).

[0045] Another aspect of the present invention provides fructooligosaccharides for use in promoting saliva secretion (preferably promoting resting saliva secretion), fructooligosaccharides for use in promoting salivary IgA secretion (preferably promoting cross-viral IgA secretion in saliva), fructooligosaccharides for use in oral care by promoting saliva secretion (preferably promoting resting saliva secretion), and fructooligosaccharides for use in preventing and reducing the risk of viral infections that can be prevented by promoting IgA secretion in saliva (preferably promoting cross-viral IgA secretion in saliva). The above-mentioned fructooligosaccharides can be used in accordance with the description of the compositions and agents of the present invention.

[0046] The methods and uses of the present invention may be used in mammals, including humans, and are intended to be both therapeutic and non-therapeutic. As used herein, "non-therapeutic" means not including surgical, therapeutic, or diagnostic procedures for humans (i.e., medical procedures for humans), and specifically does not include methods of surgical, therapeutic, or diagnostic procedures for humans performed by a physician or a person under the direction of a physician.

[0047] The present invention will be described in more detail based on the following examples, but the present invention is not limited to these examples.

[0048] Example 1: Evaluation of the effect of fructooligosaccharides on saliva secretion and salivary IgA secretion In Example 1, the effect of fructooligosaccharide intake on saliva secretion and salivary IgA secretion was evaluated in a human study.

[0049] (1) Methods A. Subjects The subjects were 27 people who met the selection criteria shown in Table 1 (average age 63 years, age range 51-87 years).

[0050]

[0051] B. Fructooligosaccharide intake period and daily intake The subjects were administered fructooligosaccharides for 8 weeks, with a daily intake of 15 g (5 g of Mei Oligo P (Meiji Food Materia) granules taken three times a day). Mei Oligo P (Meiji Food Materia) contains 1-kestose, nystose, and 1-fructofuranosyl-D-nystose as fructooligosaccharides, with a fructooligosaccharide content of 95% or more and a 35:50:10 ratio of 1-kestose, nystose, and 1-fructofuranosyl-D-nystose.

[0052] C. Saliva Samples Saliva samples were collected three times: before the start of intake (week 0), four weeks after the start of intake (week 4), and eight weeks after the start of intake (week 8) (Location: Tsukui Holdings Co., Ltd. (332 Mutsugawa 1-chome, Minami-ku, Yokohama, Kanagawa Prefecture)). Samples were collected in the morning. Subjects were not allowed to brush their teeth or eat or drink for 30 minutes before collection. After resting for at least 30 minutes, saliva was collected by holding a Salivet in their mouths for one minute. If the amount of saliva collected was less than 0.2 g, it was collected for an additional minute. The Salivet was then centrifuged at 2000 rpm for two minutes to prepare the saliva sample.

[0053] Calculation of saliva secretion rate The saliva secretion rate was calculated by dividing the amount of saliva collected by the collection time.

[0054] Measurement of total IgA concentration and calculation of secretion rate Total IgA concentration was measured by diluting saliva samples 5000-fold with assay diluent (LABISKOMA) and using a Human IgA ELISA Core Kit (LABISKOMA) according to the kit manual. Total IgA secretion rate was calculated by dividing the amount of total IgA by the time saliva was collected.

[0055] Measurement of SARS-CoV-2 cross-reactive IgA concentration and calculation of secretion rate. SARS-CoV-2 cross-reactive IgA concentration was measured by diluting saliva samples 50-fold with sample buffer (EUROIMMUN) and using Anti-SARS-CoV-2 ELISA (IgA) (EUROIMMUN) according to the kit manual. This kit uses the S1 domain of the SARS-CoV-2 spike protein as the antigen. Since this measurement was semi-quantitative, a calibration curve was created using Anti-2019-nCoV S-IgA Neutralizing Antibody (Elabscience) as an anti-SARS-CoV-2 IgA standard, and quantitative values ​​were calculated. The secretion rate of SARS-CoV-2 cross-reactive IgA was calculated by dividing the amount of SARS-CoV-2 cross-reactive IgA by the time the saliva was collected.

[0056] (2) Results: Excluding two subjects who received influenza vaccinations during the study period, saliva samples from 25 subjects were analyzed. The results are shown in Figures 1 and 2. The results in Figure 1 confirmed that the saliva secretion rate (Figure 1A), salivary IgA secretion rate (Figure 1C), and salivary SARS-COV-2 cross-reactive IgA secretion rate (Figure 1E) significantly increased at 4 and 8 weeks after the start of supplementation compared to week 0. The results in Figure 2 confirmed that the salivary secretion rate increase rate (Figure 2A), salivary IgA secretion rate increase rate (Figure 2C), and salivary SARS-COV-2 cross-reactive IgA secretion rate increase rate (Figure 2E) significantly increased at 4 and 8 weeks after the start of supplementation compared to week 0. These results indicated that ingestion of fructooligosaccharides promoted saliva secretion, salivary IgA secretion, and salivary SARS-COV-2 cross-reactive IgA secretion.

[0057] According to the present invention, it is possible to provide a method for producing a food for promoting IgA secretion in saliva, which contains fructooligosaccharide as an active ingredient.

Claims

1. A composition for promoting the secretion of virus-cross-reactive IgA in saliva, comprising fructooligosaccharide as an active ingredient.

2. The composition of claim 1 for use in preventing or reducing the risk of viral infection.

3. The composition according to claim 1 or 2, wherein the virus is a coronavirus.

4. The composition described in claim 1 or 2, wherein the virus is a betacoronavirus.

5. The composition according to claim 1 or 2, wherein the virus binds to the ACE2 receptor.

6. A composition for promoting resting saliva secretion, comprising fructooligosaccharide as an active ingredient.

7. The composition according to claim 6 for use in oral care.

8. A composition according to claim 1 or 6 for use in enhancing oral immunity.

9. The composition of claim 1 or 6, wherein the fructooligosaccharide is a mixture of 1-kestose, nystose and 1-fructofuranosyl-D-nystose.

10. The composition according to claim 9, wherein the ratio of 1-kestose, nystose and 1-fructofuranosyl-D-nystose in the mixture is 10-50:20-70:1-20.

11. The composition according to claim 1 or 6, wherein the subject to be ingested is a human.

12. The composition of claim 11, wherein the human is 50 years of age or older.

13. The composition according to claim 11, wherein the effective daily intake for humans is 1 to 60 g.

14. The composition according to claim 1 or 6, which is taken continuously for one week or more.

15. The composition of claim 1 or 6 which is a food composition.

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