WO2019054491A1

WO2019054491A1 - Food/drink item or preparation for improving tear secretion performance/tear stability

Info

Publication number: WO2019054491A1
Application number: PCT/JP2018/034218
Authority: WO
Inventors: 一男坪田; 松本　光晴
Original assignee: 協同乳業株式会社; 学校法人慶應義塾
Priority date: 2017-09-14
Filing date: 2018-09-14
Publication date: 2019-03-21
Also published as: JP7336105B2; JPWO2019054491A1; JP2022163118A; JP7150282B2

Abstract

The present invention provides a food/drink item or preparation for improving tear secretion performance/tear stability, a water-soluble indigestible component having been added to the food/drink item or preparation. This food/drink item or preparation can be used to prevent or mitigate dry eye.

Description

Food or drink or preparation for improving tear secretion ability and tear stability

The present invention relates to a food or drink or a preparation for improving lacrimation ability and / or lacrimal stability, which is formulated with a water-soluble indigestible component.

Tears play various roles in covering and protecting the surface of the eye.

Dry eye refers to a state in which the ability to moisturize the surface of the eye is reduced (a decrease in tear fluid stability) due to a decrease in tear secretion (decrease in lacrimal secretion ability) or a decrease in tear quality. Causes of dry eye include diseases such as aging, stress, Sjogren's syndrome and the like. In addition to these factors, the number of dry eye patients also tends to increase in recent years due to the use of personal computers and smartphones, the use of contact lenses, and the use of air conditioners.

As mentioned above, the environment in which modern people are placed contains many factors that are likely to become dry eye, and not only dry eye patients, but also ordinary consumers who are concerned about preventing dry eye high.

On the other hand, indigestible carbohydrates such as inulin are known to suppress the rise of glucose in the blood by raising the ratio of the microflora of the gastrointestinal tract relative to the phyrite tract of the Bacteroides. Although the possibility of treating dry eye syndrome has been suggested (Patent Document 1), there is no specific description.

Japanese Patent Application Publication No. 2014-528925

The present invention provides a food or drink or a preparation which is a composition for improving lacrimal secretion ability and / or lacrimal stability.

As a result of intensive studies, the present inventors have found that water-soluble indigestible components (including oligosaccharides and sugar alcohols) are effective in improving lacrimal secretion ability and / or lacrimal stability. The present invention has been completed based on the findings.

That is, in one aspect, the present invention may be as follows.

[1] A food or drink for improving lacrimal secretion ability and / or lacrimal stability comprising maltitol, galactooligosaccharides, glucomannan, lactose, fructooligosaccharides, isomaltooligosaccharides, cellobiose, xylooligosaccharides, xylitol, The above food and drink containing one or more water-soluble indigestible components selected from the group consisting of sorbitol, erythritol, mannitol, pectin, resistant starch, resistant digestive dextrin and reduced resistant digestive dextrin.

[2] The food or drink as described in the above-mentioned [1] for preventing or reducing dry eye.

[3] The water-soluble indigestible ingredients to be incorporated into food and drink are as follows:
(A) one or more water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(B) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(C) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides and glucomannan;
(D) maltitol, galactooligosaccharides, glucomannan and lactose; or (e) maltitol, galactooligosaccharides and glucomannan;
Food-drinks as described in said [1] or [2] which is it.

[4] The above-mentioned [1] to [3], wherein the water-soluble indigestible component is contained in 0.01% w / w to 20% w / w in food and drink selected from liquid, suspension and emulsion Food and drink described in any one of the above.

[5] The food or drink according to any one of the above [1] to [4], wherein the food or drink is a dairy product or a soft drink.

[6] The food or drink according to [5] above, wherein the dairy product is selected from the group consisting of milk drinks, cheese, fermented milk, lactic acid bacteria drinks and ice creams.

[7] The above-mentioned [1] or [2], wherein a combination of two or all of the water-soluble indigestible ingredients selected from the group consisting of maltitol, galactooligosaccharides and glucomannan is blended in milk or a milk beverage Food and drink described in].

[8] The food or drink according to any one of the above [1] to [3], further comprising a probiotic.

[9] A preparation for improving lacrimal secretion and / or lacrimal stability, which comprises maltitol, galactooligosaccharide, glucomannan, lactose, fructooligosaccharide, isomaltooligosaccharide, cellobiose, xylooligosaccharide, xylitol, sorbitol The above-mentioned preparation comprising one or more water-soluble indigestible components selected from the group consisting of erythritol, mannitol, pectin, resistant starch, resistant digestive dextrin and reduced resistant digestive dextrin.

[10] The water-soluble indigestible ingredients are as follows:
(A) one or more water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(B) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(C) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides and glucomannan;
(D) maltitol, galactooligosaccharides, glucomannan and lactose; or (e) maltitol, galactooligosaccharides and glucomannan;
The formulation according to the above [9], which is

[11] The preparation according to the above [9] or [10], further comprising a probiotic.

[12] Maltitol, galactooligosaccharides, glucomannan, lactose, fructooligosaccharides, isomaltooligosaccharides, cellobiose, xylooligosaccharides, xylitol, sorbitol, erythritol, mannitol, pectin, resistant starch, resistant digestible dextrin and reduced resistant digestible dextrin An agent for preventing, treating or ameliorating a disease or symptom having lacrimal secretion and / or lacrimal fluid stability disorder, comprising as an active ingredient one or more water-soluble indigestible components selected from the group consisting of:

[13] The disease or condition having tear secretion and / or tear stability disorder is dry eye (including dry keratoconjunctivitis), dry eye syndrome, VDT syndrome or Sjogren's syndrome as described above [12] The preventive or therapeutic / improvement agent described.

The food / beverage products or preparations of the present invention are useful as those capable of improving lacrimation ability and / or lacrimal stability.

FIG. 1 is a graph showing the evaluation results of the lacrimal secretion improving effect of milk added with a water-soluble indigestible ingredient mixture (galactooligosaccharide, maltitol, glucomannan). FIG. 2 is a graph showing inter-group differences in VAS score by stratification analysis for the results of Example 2. FIG. 3 is a graph showing intra-group changes of VAS score by stratification analysis with respect to the results of Example 2.

The present invention will be specifically described below, but the present invention is not limited thereto. Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art.

In the present specification, the water-soluble indigestible component means a component which is difficult to be degraded by human digestive enzymes among components contained in food and is water-soluble. In the present specification, "water-soluble indigestible component" is a concept which means a component including oligosaccharides, disaccharides, sugar alcohols, etc. centering on water-soluble dietary fibers which can not be degraded by human digestive enzymes. is there. As used herein, “water-soluble resistant ingredient” means either alone or in combination, unless otherwise specified.

(Food and drink)
One aspect of the present invention relates to a food and drink for improving lacrimation ability and / or lacrimal stability, which is formulated with a water-soluble indigestible component.

The water-soluble indigestible components contained in the food and drink of the present invention include maltitol, galactooligosaccharides, glucomannan, lactose, fructooligosaccharides, isomaltooligosaccharides, cellobiose, xylooligosaccharides, xylitol, sorbitol, erythritol, mannitol, pectin, register It is one or more water-soluble indigestible components selected from the group consisting of starch starch, indigestible dextrin and reduced indigestible dextrin. Preferably, the water-soluble indigestible component contained in the food and drink of the present invention may be a combination of two or more types of water-soluble indigestible components selected from the above group.

In one preferred embodiment, the water-soluble indigestible component contained in the food and drink of the present invention is
(A) one or more water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(B) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(C) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides and glucomannan;
(D) maltitol, galactooligosaccharides, glucomannan and lactose; or (e) maltitol, galactooligosaccharides and glucomannan;
It may be

The food and drink of the present invention may contain other ingredients in addition to the above-mentioned water-soluble indigestible ingredients. Such other components include, for example, turmeric, fructan, lactulose, raffinose, soy oligosaccharides, milk oligosaccharides, chitosan oligosaccharides, cyclic oligosaccharides, palatinose and the like.

Maltitol is 4-O-α-D-glucopyranosyl-D-glucitol, also called reduced maltose.

The galactooligosaccharide is 4'-galactosyl lactose.

Glucomannan is a polysaccharide in which glucose and mannose are linked in a linear manner with β-1,4-linkage in a ratio of about 2: 3. The degree of polymerization of glucomannan used in the present invention is not particularly limited.

Fructooligosaccharides are polysaccharides in which one or more D-fructoses are linked via β-2,1-glycosidic bonds to the fructose portion of sucrose (sugar in which glucose and fructose are α-1,2-glycosidic bond). The degree of polymerization of the fructooligosaccharide used in the present invention is not particularly limited. Preferred fructooligosaccharides for use in the present invention include kestose, nystose and fructosyl nystose.

The isomalto-oligosaccharide is a polysaccharide having glucose as a basic constitutional unit, and contains one or more α-1,6-linkage, α-1,4-linkage, and α-1,3-linkage. The degree of polymerization of the isomaltooligosaccharide used in the present invention is not particularly limited. Preferable isomaltoligosaccharides used in the present invention include isomaltose, isomaltoliose and panose.

The xylooligosaccharide is a polysaccharide having a structure in which about 2 to 7 xylose are β-1,4-linked.

Pectin is a complex polysaccharide composed mainly of polygalacturonic acid in which galacturonic acid is α-1,4-linked. The molecular weight of pectin which can be used in the present invention is not particularly limited.

Resistant starch is a generic term for starch and starch degradation products that reach the large intestine without being digested in the digestive tract up to human small intestine. Resistant starch (RS) is classified into four types according to its characteristics. Type 1 (RS1) is a starch that does not act on digestive enzymes such as α-amylase such as grain with low purification degree, type 2 (RS2) is starch with high amylose content, and type 3 (RS3) is glued by cooking etc. Aging starch which has changed its structure in the course of cooling after cooling, type 4 (RS4) is a modified starch (chemically modified starch). In the present invention, any type of resistant starch may be used.

Indigestible dextrin is a dietary fiber purified by adding a trace amount of acid to starch, hydrolyzing at high temperature, and hydrolyzing with α-amylase and glucoamylase. The indigestible dextrin is a glucan having an average molecular weight of about 2,000, and in addition to the inherent alpha-1,4- and alpha-1,6-linkages of starch, alpha-1,2-linkage and alpha-1 , 3-bonds, etc., and have a branched and developed structure as compared to the raw material starch. Reduced indigestible dextrin is obtained by subjecting indigestible dextrin to reduction treatment.

Although the addition amount of the water-soluble indigestible component or the combination of the water-soluble indigestible components in the food and drink of the present invention is not particularly limited, preferably, the combination of the water-soluble indigestible components or the water-soluble indigestible components is preferably 0 .01% w / w to 20% w / w, preferably 0.5% w / w to 15% w / w, more preferably 1% w / w to 10% w / w.

When the combination of the water-soluble indigestible component is blended in the food and drink, the ratio of each component of the water-soluble indigestible component is not particularly limited, and can be appropriately set by those skilled in the art. For example, each component of the water-soluble indigestible component is preferably contained in a ratio of at least 1% or more, 10% or more, 20% or more with respect to the whole of the water-soluble indigestible component. Each component of the water-soluble indigestible component may be contained in an equal amount to the whole of the water-soluble indigestible component.

Preferred examples of combinations of water-soluble indigestible components according to the invention are maltitol, galactooligosaccharides, glucomannan and lactose; or maltitol, galactooligosaccharides and glucomannan.

The addition amount of the water-soluble indigestible component in the food and drink of the present invention is not particularly limited, but if the amount is too large, there is a possibility of side effects of diarrhea. The combination of the sex component or the water-soluble indigestible component is 0.2 g to 40 g, preferably 1 g to 30 g, more preferably 2 g to 20 g. In the case of 200 ml of beverage, 0.1% w / w to 20% w / w, preferably 0.5% w / w to 15% w / w, more preferably 1% w, based on the total weight / W to 10% w / w is included. In the case of 200 ml of beverage, for example, the concentration of maltitol contained in the beverage is 0.1% w / w to 3% w / w, preferably 0.5% w / w to 2.5% w / w, The concentration of galactooligosaccharides contained in the beverage may be from 0.1% w / w to 3% w / w, preferably 0.5% w / w. W / w to 2.5% w / w, 0.8% w / w to 1.5% w / w, and the concentration of glucomannan contained in the beverage is 0.05% w / w It may be ̃3.0% w / w, preferably 0.1% w / w to 2.5% w / w, more preferably 0.1% w / w to 2.0% w / w, The concentration of lactose contained in the beverage is preferably 1% w / w to 10% w / w. The above concentration is the concentration relative to the weight of the beverage. The daily intake amount is preferably one or two times of the above intake amount, and it is also possible to divide the amount per time into two times and so on.

The food and drink of the present invention may contain probiotics in addition to the water-soluble indigestible component. As used herein, probiotics refers to living microorganisms that produce beneficial effects in humans upon ingestion. The probiotics contained in the food and drink of the present invention are not particularly limited, but belong to a microorganism understood as a lactic acid bacterium in the art, for example, a microorganism belonging to Lactobacillus, Bifidobacterium. Microorganisms, Lactococcus lactis, Enterococcus faecalis, Pediococcus pentosaceus may be mentioned. The probiotics may comprise a single strain of the above mentioned microorganism, or it may comprise a combination of multiple species or strains.

Examples of the microorganism belonging to the genus Lactobacillus include Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus rhamnosus, Lactobacillus gasseri, Lactobacillus deliburerikki, Lactobacillus helveticus, Lactobacillus paracasei. , Lactobacillus acidophilus, Lactobacillus reuteri, but not limited thereto.

Examples of microorganisms belonging to the genus Bifidobacterium include Bifidobacterium animalis animalis, Bifidobacterium animalis lactis, Bifidobacterium pseudocatenulatam, bifidobacterium catenulatam, bifidobacterium. Examples include, but are not limited to, um bifidum, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis and bifidobacterium addresscensis. Among these, Bifidobacterium animalis lactis can be preferably used. As one embodiment of Bifidobacterium animalis lactis, the LKM 512 strain can be used. The LKM 512 strain can be obtained from the trust organization (NITE Patent Organism Depositary) under the accession number FERMP-21998.

The amount of probiotics contained in the food or drink of the present invention is not particularly limited, and for example, 2 × 10 ³ to 8 × 10 ¹² cfu, preferably 2 × 10 ⁵ to 8 × 10 ¹¹ cfu, per 100 g of food or beverage More preferably, it can be formulated to contain 2 × 10 ⁷ to 8 × 10 ¹⁰ cfu. As used herein, cfu refers to colony forming units. The cfu may be measured using any method known to the person skilled in the art, for example by diluting the microorganism with phosphate buffer (PBS) and spreading the dilution on MRS medium at 37 ° C. After 48 hours of anaerobic culture, it can be measured by counting the number of grown colonies.

The food and drink of the present invention is not particularly limited as long as it is a food or a beverage, but is preferably a dairy product or a western-style confection, or a soft drink. The dairy product is not particularly limited as long as it is a food or beverage using raw milk or processed milk as a raw material, and includes, for example, milk drinks, cheese, fermented milk, lactic acid bacteria drinks and ice creams. Preferred dairy products are milk drinks or lactic acid bacteria drinks. There is no particular limitation on the western-style confectionery, but includes products using dairy products as raw materials, such as pudding. The soft drink is not particularly limited as long as it is a drink other than a dairy product and a lactic acid bacteria drink and contains less than 1% of alcohol content, for example, juice (fruit drink and / or vegetable drink), coffee drink, tea system Beverages, carbonated beverages, sports drinks, mineral water, soy milk, etc. are included.

In one aspect, the food and drink of the present invention may be a health food, and may be classified as, for example, a special purpose food, a health functional food (a food for specified health use, a nutritional function food or a functional indication food) .

The food and drink of the present invention can improve the lacrimal secretion ability and tear stability of a subject who has ingested it. The effect of improving tear secretion ability and tear stability of the food and drink of the present invention can be confirmed by evaluating changes in tear secretion ability and tear stability before and after ingestion of the food and drink. The tear secretion ability and tear stability can be confirmed, for example, by the evaluation of tear volume and the evaluation of tear layer destruction time (BUT). As a method of measuring the amount of tears, for example, a Schirmer test using a cotton thread / filter paper for tears test may be mentioned. The evaluation of tear film rupture time is to measure the time for the tear film to dry in a state in which eyelids are instilled with fluorescein dye and eyes are not opened.

In one aspect, the food or drink according to the present invention is a food or drink for preventing or alleviating a disease or symptom having a disorder of lacrimal secretion such as dry eye (including dry keratoconjunctivitis), dry eye syndrome, VDT syndrome, Sjogren's syndrome Can be. The subject to which the food and drink of the present invention is to be ingested is not particularly limited. Not only patients who are diagnosed with dry eye, but also ordinary consumers, such as subjects with a tendency to dry eye (dry eye reserve group) (referred to as dry eye syndrome) and subjects who wish to prevent dry eye It can be a target.

In the present invention, "dry eye" means that tear film stability is reduced in a state in which the ability to moisturize the surface of the eye is reduced due to a decrease in tear secretion or a decrease in tear quality. And BUT is 5 seconds or less and there is a subjective symptom. The "dry eye reserve group" refers to a case where the dry eye condition does not correspond to the above-mentioned dry eye condition, but it indicates a symptom that satisfies one of the conditions.

(Formulation)
One aspect of the present invention relates to a formulation for improving lacrimal secretion comprising a water-soluble resistant ingredient or a combination of water-soluble resistant ingredients. The water-soluble indigestible component or the combination of the water-soluble indigestible component contained in the preparation of the present invention is as defined in the item of food and drink described above.

The amount of the water-soluble indigestible ingredient or the combination of the water-soluble indigestible ingredients in the preparation of the present invention is not particularly limited, but preferably, the water-soluble indigestible ingredient or water-soluble indigestible ingredient per intake or administration. The combination of the sex components is formulated to contain 0.1 g to 20 g, preferably 0.5 g to 20 g, more preferably 1 g to 10 g. In another embodiment, the formulation of the present invention comprises 0.01% of a water-soluble resistant ingredient or a combination of water-soluble resistant ingredients in a formulation, in particular when it is a liquid, a suspension or an emulsion w / w to 20% w / w, preferably 0.5% w / w to 15% w / w, more preferably 1% w / w to 10% w / w It may be. However, since glucomannan is poorly soluble in water, preferably 0.01% w / w to 1% w / w in the preparation, more preferably 0.1% w / w to 1% w in the preparation / W may be included.

When the combination of the water-soluble indigestible component is blended in the preparation of the present invention, the ratio of each component of the water-soluble indigestible component is not particularly limited, and can be appropriately set by those skilled in the art. The ratio of each component of the water-soluble indigestible component is not particularly limited, and can be appropriately set by those skilled in the art. For example, each component of the water-soluble indigestible component is preferably contained in a ratio of at least 5% or more, 10% or more, 20% or more with respect to the whole of the water-soluble indigestible component. Each component of the water-soluble indigestible component may be contained in an equal amount to the whole of the water-soluble indigestible component.

The formulation of the present invention may contain other ingredients in addition to the above-mentioned water-soluble indigestible ingredients. Examples of such other components include the components described above in the section of food and drink.

The formulation of the present invention may further contain probiotics. The probiotics contained in the preparation of the present invention are as defined above in the section of food and drink. In this aspect, the formulation of the present invention may be one wherein the water-soluble indigestible ingredient or the combination of the water-soluble indigestible ingredient and the probiotics are contained in the same composition, or the water-soluble indigestible It may be a composition comprising a composition comprising a combination of a sex component or a water soluble resistant ingredient and a composition comprising a probiotic. In the case of combination compositions, the composition comprising the water soluble resistant ingredient or the combination of the water soluble resistant ingredient and the composition comprising the probiotics may be taken or administered simultaneously, or separately It may be taken or administered.

The amount of probiotics in the preparation of the present invention is not particularly limited, but 2 × 10 ³ to 8 × 10 ¹² cfu, preferably 2 × 10 ⁵ to 8 × 10 ¹¹ cfu, more preferably 2 × 10 ³ to 8 × 10 ¹² cfu per intake or administration. Can be formulated to contain 2 × 10 ⁷ to 8 × 10 ¹⁰ cfu.

The formulations of the present invention may be pharmaceuticals or quasi drugs. Thus, the formulations of the present invention may be pharmaceutical compositions. Alternatively, the preparation of the present invention may be a food such as a supplement. The supplements may be classified into special purpose foods, health functional foods (specific health food, nutritive functional foods or functional labeling foods), but are not limited thereto.

The form of the preparation of the present invention is not particularly limited as long as it is a form suitable for human consumption or administration to humans, for example, liquid, suspension (dispersion liquid), emulsion, semisolid, paste, It may be in the form of powder, granules, tablets, capsules, jellies or pills. Here, when the preparation of the present invention is a liquid, a suspension or an emulsion, the preparation may be in the form of a solution, an internal solution and / or a drink.

The formulation of the present invention may also contain additives such as sweeteners, preservatives, coloring agents, antioxidants, or flavors, or pharmaceutically acceptable excipients or carriers. As used herein, "pharmaceutically acceptable" is a component that does not produce toxic, irritating, allergic or other adverse reactions when administered to an animal, such as a human, and is other than the other components of the formulation. It means an ingredient that is compatible with the ingredient. Pharmaceutically acceptable excipients or carriers can utilize ingredients commonly used in the art.

The tear secretion ability and / or tear stability improving effect of the preparation of the present invention can be confirmed by the method described in the item of food and drink. In one aspect, the preparation of the present invention can be a preparation for preventing or alleviating a disease or condition having tear secretion and / or tear stability disorder such as dry eye. Further, subjects to which the preparation of the present invention is to be ingested or administered are also as described above in the section of food and drink.

(Method for improving tear secretion ability and / or tear stability)
The present invention also relates to a method for improving the lacrimal ability and / or lacrimal stability of a subject, which comprises ingesting or administering the food or drink or the preparation of the present invention to the subject.

The present invention is also directed to a food or beverage formulated with a combination of a water soluble resistant ingredient or a combination of water soluble resistant ingredients as described above for use in a method of improving lacrimal secretion ability and / or tear fluid stability of a subject Products or preparations. The present invention further relates to the use of the above-mentioned water-soluble resistant ingredient or a combination of water-soluble resistant ingredients for the preparation of a food or drink or a preparation having improved lacrimal secretion ability and / or tear liquid stability.

In one aspect, improving lacrimation ability may be to prevent or treat a disease or condition having lacrimation and / or tear stability disorders such as dry eye.

As used herein, a "subject" is a mammal, preferably a human.

Having generally described the invention, specific embodiments are provided herein, to which reference may be made for a further understanding. However, these are for the purpose of illustration and do not limit the present invention.

(Example 1: Evaluation of tear secretion improvement effect by water-soluble indigestible component)
<Method>
Seven-week-old female C57BL / 6 mice (Charles River Japan, Inc.) were divided into 3 groups (n = 4 / group), and the following groups were administered.
Group 1: 5% (w / w) lactose (aqueous solution dissolved in distilled water)
Group 2: 5% (w / w) lactose + 1% (w / w) galactooligosaccharide + 1% (w / w) maltitol + 1% (w / w) glucomannan (aqueous solution dissolved in distilled water)
Group 3 (control): distilled water The above solution was repeatedly administered by oral gavage with 0.5 mL / animal twice a day (morning, afternoon) for 19 days.

Two weeks after administration, stress treatment was performed for 4 days. The stress treatment was performed as follows. It was restrained for 4 hours a day in a 50 ml polypropylene centrifuge tube subjected to respirable / excretable treatment. During restraint, air was blown to the face of the mouse at a wind speed of 0.5 to 1.0 m / s. Food and drink were kept ad libitum in the cage except during restraint treatment time.

Measurement of lacrimal secretion was performed as follows before administration, 2 weeks after administration (before stress loading), on day 2 of stress loading, and on day 5 of stress loading. Insert a cotton thread (ZONE-QUICK (registered trademark), Showa Pharmaceutical Co., Ltd.) for 15 seconds in the left and right outer eye corners of the mouse, and measure the length of the cotton thread that turned brown due to the penetration of tears with an accuracy of 0.5 mm. did. The average value of the results obtained for the left and right eyes was taken as the tear secretion of the individual.

<Result>
The results are shown in FIG. In the third group, which was a control, it was observed that the amount of tear secretion decreased due to stress. In the first group to which 5% lactose was administered, a slight decrease in tear secretion was observed, but no decrease in tear secretion was observed as in the control group. In the second group, which received a solution containing a combination of 5% lactose and other water-soluble indigestible components, the tear output was maintained to the same extent as before stress loading. This result indicates that the water-soluble indigestible component or the combination of the water-soluble indigestible component is effective in improving lacrimal secretion ability.

In addition, although the body weight of each mouse was also measured in the measurement of lacrimal secretion ability, almost no weight loss was observed throughout the test period.

(Example 2: Evaluation of dry eye preventive effect by water-soluble indigestible component)
<Method>
1. subject
Blood pressure and pulse rate measurement, tear film breakup time (BUT), Schirmer test, to 118 healthy Japanese men and women who routinely perform VDT (Visual Display Terminals) work between 20 and 60 years old The subjects were asked a questionnaire on eye symptoms, and the results showed that the subject had a dry eye reserve group (BUT should show a symptom that satisfies the condition of less than 5 seconds or one of the symptoms or less) that is expected to develop in the future. Elected as

However, those who are treating the eye (including those who had eye surgery within 3 months of the study), taking medications, foods etc that may affect the study within 3 months of the study Those who did were excluded. The selected 54 subjects were randomly assigned, and 27 subjects were tested drink group and the remaining 27 subjects were placebo group. After the test, subjects whose test drink frequency was over 10% of the total frequency of the protocol intake were excluded from data analysis as protocol violation.
The background of the subject subjected to data analysis is as shown in Table 1 below.

2. Test beverage Ingredients prepared by adding 1.5% (w / w) of galactooligosaccharide, 1.0% (w / w) of maltitol, and 0.1% (w / w) of glucomannan as active ingredients based on non-adjusted milk and skimmed milk powder As an active ingredient, lactose in milk was also contained in a 5% (w / w) amount) as a test beverage (= dietary fiber added milk). The placebo used sucrose, a milk protein raw material, a flavor, etc., and the texture, the flavor, and the taste produced the drink almost the same as a test drink. After sterilizing, all were sealed in a white paper pack without a label at 200 mL / tube for test.

3. Study Design This study is a randomized, double-blind, parallel-group, controlled trial conducted from November to December when dry eye symptoms worsen. The test drink group and the placebo group ingested 200 mL of each drink once a day for 3 weeks. BUT examinations were performed with the left eye of the subject prior to the study (Week 0) and at 3 weeks of study drink or placebo intake (Week 3). At Week 0, the above test was performed after taking 200 ml of water in order to measure the basic value before taking the test drink. Questionnaire tests were conducted before taking the test drink or placebo (Week 0), 1 week (Week 1), 2 weeks (Week 2), 3 weeks (Week 3).

The schedule on the day of measurement was fasting for 13 hours or more from the previous day (water was freely taken during fasting period), and each beverage was ingested at 9:00 am on the day of the test. We prohibited VDT work from 1 hour before BUT examination and prohibited reading from 10 minutes before examination. During the study period, I was asked to maintain the lifestyle before the start of the study, but prohibited the intake of milk and dairy products other than the test drink.

4. Ophthalmic examination BUT evaluated keratoconjunctival epithelial disorder based on the fluorescein staining score of the cornea (Ocul Surf 14, 255-63 (2016)). That is, after instilling 2 μL of 1% fluorescein dye without preservative into the eye with a micropipette to avoid changes in tear fluid dynamics, the time from tearing up to tearing of the tear film is measured three times, The average value was calculated. In Schirmer test, test paper for tear function examination (Tear production measuring strips; hereinafter, Schirmer paper) was placed on the outer third of the lower conjunctival fornix of the eye for 5 minutes. After 5 minutes, the test paper was removed and the wet length was measured. In order to avoid interference with conjunctival staining, Schirmer tests were performed at intervals of 10 minutes after BUT measurement when measuring background values.

5. Evaluation of subjective symptoms of eyes using questionnaire The subjective symptoms of eyes were performed a total of 4 times in Week 0, Week 1, Week 2 and Week 3 in Visual analogue scale (VAS) evaluation. There are 12 questions for VAS evaluation, and the subject is 100mm horizontal straight line for each question (one end "does not mind the symptoms at all (score = 0)" and the other end can not stand (score = 100) Marked the level of subjective symptoms in). The length from score = 0 was measured and scored in mm using a ruler. The questions are as follows: Dry eyes, open eyes, hard eyes, painful eyes, red eyes, tears, tears, itchy eyes, itchy eyes, blurred eyes, dazzling eyes Heavy, tired eyes.

<Result>
1. BUT change BUT value is the Week 3 value minus the Week 0 value in the BUT change amount (0.17 ± 0.28 seconds) in the test drink group (0.69 ± 0.39 seconds) significantly ((0.69 ± 0.39 seconds)) p <0.05) showed a high value (Table 2). In addition, regarding the intra-group change from Week 0 to Week 3, a significant decrease (deterioration) was observed only in the placebo group. These show that the test beverage suppressed the deterioration of tear fluid stability (decrease in BUT value) accompanying the seasonal variation from November to December, and made it BUT value and recover 0.17 points from the time of Week 0. Show.

2. Subjective symptoms of eye Stratified analysis was performed excluding the subjects who had BUT at Week 0 and Schirmer test score of 10 or more (normal value). Figure 2 shows differences between groups. In the item of “eye-rolling”, at Week 3, the test drink group showed a significantly (p <0.05) lower value than the placebo group (FIG. 2A). Also, in the items of “eyeache” and “red eyes” in Week 2, the test drink group showed significantly lower values (p <0.01 and p <0.05, respectively) compared to the placebo group (FIG. 2B And C). Figure 3 shows intra-group changes observed at Week 0 and after intake (Week 1 to Week 3). "Drying eyes" (Week 1 to 3), "Winging eyes" (Week 3), "Winging eyes" (Week 2), "Winging eyes" (Week 1), "Winging eyes" (Week) 1) In the items of “Blur” (Week 3), no change was observed in the placebo group, but only the test drink group significantly improved.

Claims

Food and drink for improving lacrimal secretion ability and / or lacrimal stability, comprising maltitol, galactooligosaccharides, glucomannan, lactose, fructooligosaccharides, isomaltooligosaccharides, cellobiose, xylooligosaccharides, xylitol, sorbitol, erythritol The above food and drink containing one or more water-soluble indigestible components selected from the group consisting of mannitol, pectin, resistant starch, indigestible dextrin, and reduced indigestible dextrin.
Food / beverage products of Claim 1 for preventing or reducing dry eye.
The water-soluble indigestible ingredients to be incorporated into food and drink are as follows:
(A) one or more water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(B) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(C) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides and glucomannan;
(D) maltitol, galactooligosaccharides, glucomannan and lactose; or (e) maltitol, galactooligosaccharides and glucomannan;
Food-drinks of Claim 1 or 2 which are these.
The water-soluble resistant substance according to any one of claims 1 to 3, comprising 0.01% w / w to 20% w / w in food and drink selected from liquid, suspension and emulsion. Food and drink described.
The food or drink according to any one of claims 1 to 4, wherein the food or drink is a dairy product or a soft drink.
The food and drink according to claim 5, wherein the dairy product is selected from the group consisting of milk drink, cheese, fermented milk, lactic acid bacteria drink and ice cream.
The food or drink according to claim 1 or 2, wherein a combination of two or all of the water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides and glucomannan is incorporated in milk or a milk beverage. .
The food or drink according to any one of claims 1 to 3, further comprising probiotics.
A formulation for improving lacrimal secretion ability and / or lacrimal fluid stability, which comprises maltitol, galactooligosaccharide, glucomannan, lactose, fructooligosaccharide, isomaltooligosaccharide, cellobiose, xylooligosaccharide, xylitol, sorbitol, erythritol, The above-mentioned preparation comprising one or more water-soluble indigestible components selected from the group consisting of mannitol, pectin, resistant starch, indigestible dextrin and reduced indigestible dextrin.
The water soluble resistant ingredients are as follows:
(A) one or more water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(B) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides, glucomannan and lactose;
(C) A combination of two water-soluble indigestible components selected from the group consisting of maltitol, galactooligosaccharides and glucomannan;
(D) maltitol, galactooligosaccharides, glucomannan and lactose; or (e) maltitol, galactooligosaccharides and glucomannan;
The formulation according to claim 9, which is
The formulation according to claim 9 or 10, further comprising probiotics.
A group consisting of maltitol, galactooligosaccharides, glucomannan, lactose, fructooligosaccharides, isomaltoligosaccharides, cellobiose, xylooligosaccharides, xylitol, sorbitol, erythritol, mannitol, pectin, resistant starch, resistant digestive dextrin and reduced resistant digestive dextrin An agent for preventing, treating or ameliorating a disease or symptom having tear secretion and / or tear stability disorder, comprising, as an active ingredient, one or more kinds of water-soluble indigestible components selected from among the above.
The prevention or disorder according to claim 12, wherein the disease or condition having lacrimal secretion and / or lacrimal stability disorder is dry eye (including dry keratoconjunctivitis), dry eye syndrome, VDT syndrome or Sjogren's syndrome. Therapeutic and improving agent.