JP7200298B2 - Suppressant for diarrhea-type irritable bowel syndrome and food composition - Google Patents

Description

NPMD NITE P-1537

The present invention relates to an agent for suppressing diarrhea-type irritable bowel syndrome and a food composition.

Irritable Bowel Syndrome (IBS) is
It is a disease in which constipation or diarrhea continues for a long period of time, accompanied by abdominal pain and discomfort, even though no obvious abnormalities such as inflammation or ulcers are observed on examination. Irritable bowel syndrome is classified into constipation type, diarrhea type, alternation type, and unclassifiable type according to the state of bowel movements.

Diarrhea-type irritable bowel syndrome (hereinafter sometimes referred to as “diarrhea-type IBS”) is accompanied by abdominal pain and discomfort, and causes sudden diarrhea. In addition, constipation-type irritable bowel syndrome (hereinafter sometimes referred to as "constipation-type IBS") causes intestinal spasm and stool stagnation.
Too much water is taken from the stool, making it difficult to defecate. Alternating irritable bowel syndrome (hereinafter sometimes referred to as "alternating IBS") is characterized by alternating constipation and diarrhea. The unclassifiable type is one that does not fit into any of the above categories.

In particular, in diarrhea-type IBS, the sudden urge to defecate and the frequent need to defecate reduce the quality of private life and labor productivity.

It is said that 10 to 15% of the general public have IBS-like symptoms. However, the number of "patients" who require hospital visits is small, and 75% of those with IBS-like symptoms have mild symptoms and do not visit hospitals.

Although IBS lowers the quality of life (QOL, hereinafter sometimes referred to as "QOL"), it is not a life-threatening serious condition. Therefore, for mild IBS or IBS-like symptoms, it is desired to improve self-medication to relieve symptoms with over-the-counter medicines and supplements.

Under these circumstances, there are many research reports suggesting that probiotics such as lactic acid bacteria are effective against weak inflammation of the large intestine, which is considered to be one of the causes of IBS.
Because of its low cost and high safety, it is expected to be an effective means for controlling IBS-like symptoms. For example, in Patent Document 1, Lactobacillus brevis K
There is described an enteritis inhibitor containing cells of strain B290 or a fermented product thereof as an active ingredient.

JP 2014-166972 A

However, the effect of the colitis suppressant described in Patent Document 1 is only examined using colitis model mice in which colitis is induced by administration of trinitrobenzenesulfonic acid. For this reason, it was unclear whether the enteritis suppressant described in Patent Document 1 is effective in humans, and whether it is effective in improving diarrhea-type IBS among multiple types of IBS. Accordingly, an object of the present invention is to provide a diarrhea-type IBS inhibitor and a food composition that improve diarrhea-type IBS in humans.

The present invention includes the following aspects.
(1) Lactobacillus brevis strain KB290 (accession number NITE P-1537)
and β-carotene as active ingredients, a diarrhea-type IBS inhibitor.
(2) The diarrhea-type IBS inhibitor according to (1), wherein the Lactobacillus brevis strain KB290 cells are administered at a rate of 1×10 ¹⁰ cells or more per day.
(3) The diarrhea-type IBS inhibitor according to (1) or (2), wherein 4 mg or more of β-carotene is administered per day.
(4) The diarrhea-type IBS inhibitor according to any one of (1) to (3), wherein the Lactobacillus brevis strain KB290 is a viable cell.
(5) The antidiarrheal IBS inhibitor according to any one of (1) to (4), which is administered for 7 weeks or more.
(6) Lactobacillus brevis strain KB290 (accession number NITE P-1537)
and β-carotene as active ingredients for suppressing diarrhea-type IBS.
(7) The food composition for suppressing diarrhea-type IBS according to (6), which is used so that 1×10 ¹⁰ or more cells of Lactobacillus brevis strain KB290 are ingested per day.
(8) β-carotene is used so that 4 mg or more is taken per day, (6) or (
The food composition for suppressing diarrhea-type IBS according to 7).
(9) The food composition for suppressing diarrhea-type IBS according to any one of (6) to (8), wherein the Lactobacillus brevis strain KB290 is a viable cell.
(10) The food composition for suppressing diarrhea-type IBS according to any one of (6) to (9), which is used so as to be ingested for 7 weeks or longer.
(11) The food composition for suppressing diarrhea-type IBS according to any one of (6) to (10), which is a supplement.
(12) The food composition for suppressing diarrhea-type IBS according to any one of (6) to (11), which is a food with function claims.
(13) The food composition for suppressing diarrhea-type IBS according to any one of (6) to (11), which is a food for special use.
(14) The food composition for suppressing diarrhea-type IBS according to (13), which is a food for sick people.
(15) The food composition for suppressing diarrhea-type IBS according to (13), which is a food for specified health uses.
(16) Lactobacillus brevis strain KB290 (accession number NITE P-1537
) and β-carotene as active ingredients, a supplement for suppressing diarrhea-type irritable bowel syndrome.
(17) Lactobacillus brevis strain KB290 (accession number NITE P-1537
) and a composition containing β-carotene as active ingredients.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a diarrhea-type IBS inhibitor and a food composition that improve diarrhea-type IBS in humans.

It is a figure which shows a test schedule. 4 is a graph showing the amount of change in evaluation results of abdominal pain intensity. It is a graph which shows the amount of change of the evaluation result of defecation frequency. (a) is a graph showing the percentage of subjects whose absentee rate due to IBS-like symptoms was 0%. (b) is a graph showing the percentage of subjects whose IBS-like symptoms affected the decrease in labor productivity during work at 0%. (c) is a graph showing the proportion in which the overall rate of IBS-like symptoms affecting labor productivity (total labor productivity loss rate) was 0%. (d) is a graph showing the ratio of patients whose IBS-like symptoms interfered with daily life (rate of disability to daily life) was 0%. 1 is a graph showing the amount of change in interleukin-10 concentration in serum.

[Diarrhea-type IBS inhibitor]
In one embodiment, the present invention provides a diarrhea-type IBS inhibitor containing cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene as active ingredients.

As will be described later in Examples, the agent for suppressing diarrhea-type IBS of the present embodiment can suppress diarrhea-type IBS in humans. In the present specification, "suppressing diarrhea-type IBS" can also be referred to as "improving diarrhea-type IBS", "treating diarrhea-type IBS", or the like. Therefore, the antidiarrheal IBS inhibitor of this embodiment can also be called an antidiarrheal IBS improving agent, an antidiarrheal IBS therapeutic agent, or the like.

As used herein, diarrhea-type IBS includes diarrhea-type IBS that requires hospitalization, and milder symptoms similar to diarrhea-type IBS that do not require hospitalization. That is, diarrhea-type IBS means a symptom that suddenly causes diarrhea accompanied by abdominal pain and discomfort, although there is a difference in severity and mildness.

In the present specification, diarrhea-type IBS symptoms that require treatment with pharmaceuticals, etc., and diarrhea-type IBS-like symptoms that do not require treatment with pharmaceuticals, etc., but are accompanied by abdominal pain and abdominal discomfort are also used. There may be symptoms.

The antidiarrheal IBS inhibitor of this embodiment can be used not only for patients with diarrhea-type IBS who require medical treatment, but also for diarrhea accompanied by abdominal pain and abdominal discomfort (diarrhea-type IBS-like symptoms), although medical treatment is not necessary. ) can be taken by those who are worried about it.

As will be described later in Examples, ingestion of the diarrhea-type IBS inhibitor of this embodiment can reduce the intensity of abdominal pain. Therefore, it can also be said that the antidiarrheal IBS inhibitor of this embodiment is an abdominal pain intensity reducing agent.

In addition, as will be described later in Examples, the frequency of defecation can be reduced by ingesting the diarrhea-type IBS inhibitor of the present embodiment. Therefore, diarrhea-type IBS of this embodiment
The inhibitor can also be said to be a defecation frequency reducing agent.

In addition, as will be described later in Examples, labor productivity can be improved by ingesting the diarrhea-type IBS inhibitor of the present embodiment. Therefore, diarrhea type IB of this embodiment
S inhibitors can also be said to be labor productivity enhancers.

Here, the improvement of labor productivity means reducing the absentee rate due to diarrhea-type IBS-like symptoms, reducing the decrease in labor productivity during work due to diarrhea-type IBS-like symptoms, etc. means.

The antidiarrheal IBS inhibitor of the present embodiment is a composition containing the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene as active ingredients, and is used for improving diarrhea-type IBS-like symptoms. It is based on the finding that it is effective for

(Lactobacillus brevis strain KB290)
Lactobacillus brevis strain KB290 (accession number NITE P-1537) is
It was deposited on February 13, 2013 at the National Institute of Technology and Evaluation Patent Microorganism Depositary Center (2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture).

In the diarrhea-type IBS inhibitor of the present embodiment, the cells of the Lactobacillus brevis strain KB290 may be viable cells or dead cells. In addition, when using live bacteria, some dead bacteria may be mixed. In addition, Lactobacillus brevis KB290
It may be used in a state in which the shape of the cells does not remain, such as a crushed product of the strain, an extract, or the like.

In the diarrhea-type IBS inhibitor of the present embodiment, it is preferable to administer 1×10 ¹⁰ or more cells of Lactobacillus brevis strain KB290 per day. This daily amount can be administered at once or divided into several times, and the timing may be before, after or between meals.

As will be described later in Examples, it has been confirmed that administration of a diarrhea-type IBS inhibitor containing the above amount of cells of Lactobacillus brevis strain KB290 to a subject has an effect of improving diarrhea-type IBS symptoms. there is

When Lactobacillus brevis strain KB290 is used as a diarrhea-type IBS suppressant in a state where no bacterial cells remain, it is necessary to administer an amount corresponding to 1×10 ¹⁰ or more bacterial cells per day. good.

There is no particular upper limit to the dose of Lactobacillus brevis strain KB290 strain cells per day, but even if 6×10 ¹⁰ cells or more are administered per day, the effect of improving diarrhea-type IBS symptoms tends not to increase any further. Therefore, the upper limit of the dose of Lactobacillus brevis strain KB290 cells may be, for example, 6 × ¹⁰ cells per day, or 4 × 1 cells per day.
It may be 0 ¹⁰ or 2×10 ¹⁰ per day.

The cells of the Lactobacillus brevis strain KB290 used in this embodiment can be prepared by a well-known method. In obtaining the cells, Lactobacillus brevis KB29
It is preferable to preculture the 0 strain before use. Pre-culture may be performed by a known method. For example, commercially available lactic acid bacteria medium (de Man, Rogosa, Sharpe medium, manufactured by Oxoid) is dissolved in distilled water to a predetermined concentration, and autoclave sterilized. and a method of inoculating Lactobacillus brevis strain KB290 and pre-cultivating for a predetermined period of time.
The cells of the Lactobacillus brevis strain KB290 used in the present embodiment can also be used as a powder obtained by drying the cells. Drying of the cells is preferably carried out by freeze-drying, spray-drying, or the like, since the cells are less likely to be denatured. For example, the cells of the Lactobacillus brevis strain KB290 are suspended in a liquid medium or the like, concentrated by centrifugation or the like, and then lyophilized to obtain a cell powder.

(β-carotene)
β-carotene is not particularly limited, and may be a natural component or a synthetic one. When β-carotene is added as a natural component, it may be added in the form of carrots containing β-carotene, its juice, algae, etc., and β-carotene extracted and purified from these raw materials
Carotene may be added. It may also be used in the form of retinol, retinal, or retinoic acid, which are produced when β-carotene is absorbed and decomposed in the body.

In the diarrhea-type IBS inhibitor of the present embodiment, β-carotene is 4 mg or more per day,
For example, it is preferably administered 4.3 mg or more, such as 4.5 mg or more, such as 4.8 mg or more. This daily amount can be administered at once or divided into several times, and the timing may be before, after or between meals.

As will be described later in Examples, it has been confirmed that administration of a diarrhea-type IBS inhibitor containing 4 mg or more of β-carotene per day to a subject has an effect of improving diarrhea-type IBS symptoms.

Although there is no particular upper limit to the daily dose of β-carotene, administration of 15 mg or more per day tends not to further improve the diarrhea-type IBS symptoms. Therefore, β
- the upper limit of carotene dosage may be, for example, 15 mg per day, or 1
It may be 0 mg or 6 mg per day.

The diarrhea-type IBS inhibitor of this embodiment is preferably administered for 7 weeks or more, for example 8 weeks or more, for example 9 weeks or more, for example 10 weeks or more, for example 12 weeks or more.

As will be described later in Examples, continuous administration of the diarrhea-type IBS inhibitor of the present embodiment for 7 weeks or longer tends to make the effect of improving diarrhea-type IBS more pronounced.

The diarrhea-type IBS inhibitor of this embodiment may be a pharmaceutical composition containing cells of Lactobacillus brevis strain KB290, β-carotene, and a pharmaceutically acceptable carrier. The above pharmaceutical composition is preferably administered orally, and is preferably formulated into a dosage form for oral use. Dosage forms for oral use include, for example, tablets, capsules, elixirs, microcapsules and the like.

Pharmaceutically acceptable carriers include, for example, binders such as gelatin, corn starch, gum tragacanth and gum arabic; excipients such as starch and crystalline cellulose; swelling agents such as alginic acid and the like.

The pharmaceutical composition may contain additives. Additives include calcium stearate,
Lubricants such as magnesium stearate; Sweeteners such as sucrose, lactose, saccharin and maltitol; Flavoring agents such as peppermint and red oil; Stabilizers such as benzyl alcohol and phenol; Buffering agents such as phosphate and sodium acetate solubilizers such as benzyl benzoate and benzyl alcohol; antioxidants; preservatives and the like.

The pharmaceutical composition can be formulated by appropriately combining the above carriers and excipients and admixing them in a unit dose form generally required for pharmaceutical practice. The pharmaceutical composition may be formulated for oral administration, eg, once daily.

[Food composition for suppressing diarrhea-type IBS]
In one embodiment, the present invention provides a food composition for suppressing diarrhea-type IBS, containing cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene as active ingredients. As will be described later in Examples, ingestion of the food composition of the present embodiment can improve diarrhea-type IBS in humans.

In the food composition of the present embodiment, Lactobacillus brevis strain KB290 and β-
As the carotene, the same ones as those in the diarrhea-type IBS inhibitor described above can be used.

In the food composition of the present embodiment, the bacterial cells of the Lactobacillus brevis strain KB290 are the same as in the diarrhea-type IBS inhibitor described above, and live bacteria may be used.
Killed bacteria may be used. In addition, when using live bacteria, some dead bacteria may be mixed. In addition, the lysate, extract, etc. of Lactobacillus brevis strain KB290 may be used in a state in which the shape of the cells does not remain.

In the food composition of the present embodiment, the Lactobacillus brevis strain KB290 cells are preferably used so that 1×10 ¹⁰ cells or more are ingested per day. Moreover, when the Lactobacillus brevis strain KB290 is used in a state in which the shape of the cells does not remain, it should be used in an amount corresponding to 1×10 ¹⁰ cells or more per day. This daily amount can be ingested at once or divided into several times, and the timing may be before, after or between meals. In addition, "1 × 10 ¹ per day
⁰ or more", which varies depending on the form of the food composition, the recommended daily intake displayed,
In the case of a drink that is usually consumed at one time, it refers to the amount contained in one bottle.

In addition, the upper limit of the intake of the Lactobacillus brevis KB290 strain cells per day is the same as described above.

In the food composition of the present embodiment, β-carotene is 4 mg or more per day, for example 4
. It is preferably used so that 3 mg or more, such as 4.5 mg or more, such as 4.8 mg or more, is taken. This daily amount can be taken at once or divided into several times,
The timing may be before meals, after meals, or between meals. In addition, "4m per day
"greater than or equal to g" refers to the recommended daily intake indicated on the label, or the amount contained per bottle in the case of a drink that is normally consumed at one time, depending on the form of the food composition. is. Also, the upper limit of the daily dose of β-carotene is the same as described above.

The food composition of the present embodiment is preferably ingested for 7 weeks or more, for example 8 weeks or more, for example 9 weeks or more, for example 10 weeks or more, for example 12 weeks or more.

As will be described later in Examples, continuous ingestion of the food composition of the present embodiment for 7 weeks or longer tends to result in a more pronounced effect of improving diarrhea-type IBS.

The food composition of the present embodiment may be in the form of, for example, a supplement, a yogurt, a beverage, or a gel food. It may be in the form of any cooked food or the like. The shape of the supplement includes, for example, the shape of capsules used in the examples.

The food composition of this embodiment may be a food with function claims. "Foods with functional claims" means foods that have been notified to the Consumer Affairs Agency as having functional claims on product packages based on scientific evidence. Examples of such indications include "functionality to suppress diarrhea and abdominal pain due to diarrhea/repeated diarrhea/stress", "functionality to prevent diarrhea and abdominal pain due to diarrhea/repeated diarrhea/stress", "diarrhea/repeated diarrhea/stress-induced Functionality that helps improve the eating habits of people who are concerned about diarrhea and abdominal pain", "Functionality that suppresses sudden abdominal insertion/abdominal pain and discomfort", "Sudden abdominal insertion/abdominal pain and Functionality to prevent discomfort", "functionality to help improve eating habits for those who are concerned about sudden stomach insertion/abdominal pain and discomfort", "functionality to relieve sudden stomach urgency and upset""Functionality to prevent sudden stomach urgency and upset", "Functionality to help improve eating habits for people who are concerned about sudden stomach urgency and upset", "Toilet anxiety" functionality that helps improve the eating habits of people who cannot concentrate on work or study,” and “functionality that helps improve the eating habits of people who are concerned about sudden plugging in when commuting to work or school.” is not limited to In addition, it is conceivable to manufacture and sell foods that do not have any functional labeling by claiming such functionality through fliers, e-mails, or verbally. As will be described later in Examples, it has been confirmed that ingestion of the food composition of the present embodiment improves diarrhea-type IBS.

The food composition of this embodiment may be a food for special use. Foods for special dietary uses are foods labeled as suitable for the growth, maintenance and recovery of health of infants, young children, expectant and nursing mothers, and the sick, etc., under the permission of the government.

The food composition of the present embodiment may be a food for sick people among special purpose foods. As described later in Examples, the food composition of the present embodiment has been confirmed to have an effect of improving diarrhea-type IBS.

The food composition of the present embodiment may be a food for specified health use among foods for special dietary uses. Foods for Specified Health Uses means foods that are scientifically recognized as being useful for maintaining and improving health, and whose effects are permitted to be labeled. The government examines the indicated effects and safety, and the Director General of the Consumer Affairs Agency approves each food product. As described later in Examples, the food composition of the present embodiment has been confirmed to have an effect of improving diarrhea-type IBS.

[supplement]
In one embodiment, the present invention provides a supplement for suppressing diarrhea-type IBS, containing cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene as active ingredients. Diarrhea-type IBS can be improved by ingesting the supplement of this embodiment.

As the Lactobacillus brevis strain KB290 and β-carotene in the above supplement, the same ones as those in the food composition for suppressing diarrhea-type IBS can be used. Also, the contents of Lactobacillus brevis strain KB290 and β-carotene may be the same as those in the aforementioned food composition for suppressing diarrhea-type IBS.

[Method for suppressing diarrhea-type IBS]
In one embodiment, the present invention provides a method for suppressing diarrhea-type IBS, comprising the step of ingesting a composition containing, as active ingredients, cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene. (excluding medical treatment of humans). Here, the medical practice means the practice of treating a human by a doctor (including a person who has been instructed by a doctor).

As the Lactobacillus brevis strain KB290 and β-carotene, the same ones as those in the aforementioned food composition for suppressing diarrhea-type IBS can be used. In addition, the content of Lactobacillus brevis strain KB290 and β-carotene is also the diarrhea type IB described above.
The same content as in the food composition for suppressing S may be used.

As will be described later in Examples, diarrhea-type IBS can be suppressed by ingesting a composition containing the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene as active ingredients. can.

The period of ingestion of the composition containing the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene as active ingredients is 7 weeks or longer.
For example, it is preferably 8 weeks or more, such as 9 weeks or more, such as 10 weeks or more, such as 12 weeks or more.

[Other embodiments]
In one embodiment, the present invention provides diarrhea-type IBS, comprising administering an effective amount of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene to a patient in need of treatment. provides a method of treatment for

In one embodiment, the present invention provides a composition for the treatment of diarrhea-type IBS, comprising cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β
- to provide a composition containing carotenes;

In one embodiment, the present invention provides Lactobacillus brevis strain KB290 (accession number NITE P-1537) for producing a diarrhea-type IBS inhibitor (diarrhea-type IBS therapeutic agent).
) and β-carotene.

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

A randomized, placebo-controlled, double-blind, parallel-group study was conducted on subjects suffering from diarrhea accompanied by abdominal pain and discomfort. A randomized, placebo-controlled, double-blind, parallel-group study is a study in which both doctors and subjects are asked which is a medicinal "experimental drug" and which is ineffective, in order to eliminate the placebo effect (belief effect) caused by the placebo. It is one of the ways to proceed with the trial without knowing whether it is a placebo. The double-blind study means that the treatment assigned to each subject is unknown not only to the subject and investigator, but also to staff such as researchers engaged in the study.

[Production of Capsules of Examples]
Example capsules were produced. Cell powder of Lactobacillus brevis strain KB290,
β-Carotene and excipients were encapsulated to produce the capsules of the Examples. Excipients are
It contained starch, reduced maltose starch syrup and calcium stearate. The capsule ingredients also included hydroxypropyl methylcellulose and a coloring agent (titanium dioxide).

The capsules of the example contained 1×10 ¹⁰ cells of Lactobacillus brevis strain KB290 per capsule. The capsules of the examples also contained 4.0-4.5 mg of β-carotene per capsule.

[Production of Capsules of Comparative Example]
Subsequently, comparative capsules were produced. Only excipients were enclosed in capsules similar to those used in Examples to produce capsules for Comparative Examples. Comparative encapsulated excipients included starch and calcium stearate.

[Implementation of test]
There were 44 subjects. Forty-four subjects selected as subjects were divided into a group ingesting the capsule of the example and a group ingesting the capsule of the comparative example, with 22 subjects each. In addition, from the subjects,
Those (patients) who were judged to require medical treatment by the principal investigator were excluded. Disclosure of allocation results and study capsule linkages to investigators and investigators was made after all data were available.

Interviews, physiological tests, biochemical tests, hematological tests, and urinalysis were performed for subject selection and physical condition management.

Subsequently, tests were conducted using the capsules of Examples and Comparative Examples. FIG. 1 is a diagram showing a test schedule. Subjects were selected for a one-week screening period, as shown in FIG. After that, a pre-ingestion observation period was provided for 3 weeks. After that, from 4 weeks after the start of the study to 16
Subjects were allowed to ingest the capsules of Examples or Comparative Examples for the 12 weeks leading up to Week 12. Thereafter, an observation period after ingestion was provided for 4 weeks from the 16th week to the 20th week after the start of the test.

For ingestion of capsules, the capsule of the example or comparative example assigned to each subject was taken once daily.
ingested the capsule. Also, in order to make sure you do not forget to take it, the timing of taking it is once a day.
time, from waking up to breakfast. If you could not take it from waking up to breakfast,
It was decided that it should be taken on the same day. The capsules were stored in an aluminum pouch with the mouth closed. In addition, the subjects were asked to fill in a diary.

[Test evaluation]
The effects of ingestion of the capsules were evaluated for the following evaluation items.

(Evaluation of stool properties)
The stool properties were evaluated by questionnaire. The subject's stool properties were measured using Bristol sto
1 (rabbit stool), 2 (lumpy stool), 3 (slightly hard stool), 4 (regular stool), 5 (soft stool), 6 (muddy stool), 7 (watery stool) based on the ol scale. A 7-point score was recorded by the subject for each bowel movement.

(Evaluation of abdominal pain intensity)
Abdominal pain intensity was evaluated using a questionnaire. The subjects themselves rated and recorded "the intensity of the most painful abdominal pain in the last 24 hours" with an 11-point score from 0 to 10 based on the Lickert scale every day.

(Evaluation of other IBS-like symptoms)
Other IBS-like symptoms were evaluated by questionnaire. Specifically, the subject himself
Defecation urgency, stomach discomfort, bloating, incomplete bowel movements, straining during defecation, farting, and rumbling were scored and recorded daily on a 5-point scale of 1-5.

(Evaluation of obstacles to labor productivity and daily life)
A questionnaire was used to evaluate labor productivity and obstacles to daily life. Specifically, the subjects themselves recorded, on a weekly basis, how many hours they had missed from work due to IBS-like symptoms, how much their IBS-like symptoms affected their productivity at work, and the like. The questionnaire is the existing WPAI Japanese version
The [Work Productivity and Disability Questionnaire: General Health V2.2 (WPAI: GH)] was used with modifications. In other words, the description of “health problems” was changed to “abdominal symptoms”, and “physical and mental problems and symptoms” were changed to “diarrhea, abdominal pain, stomach discomfort, bloating, urgency to defecate.” , feeling of incomplete bowel movement, straining during defecation, farts, stomach rumbling, etc.”

(Evaluation of quality of life (QOL))
QOL was evaluated by questionnaire. Specifically, SF-8 (trademark) (Internet <URL: https://www.sf-36.jp/qol/sf8.
html>. ), a questionnaire was given to the subjects.

(Evaluation of inflammatory markers in serum)
Inflammatory markers in the serum, which are said to reflect colonic inflammation, were evaluated. Serum was prepared from the blood collected from the subject at the start of the ingestion period, the end of the ingestion period, and the end of the post-intake observation period.
There is a case. ) and interleukin-12 (hereinafter sometimes referred to as “IL-12”), and an inhibitory cytokine interleukin-10 (hereinafter, “IL-1
0” in some cases. ) was measured.

For the measurement of IL-1β, a commercially available kit (Human IL-1β/IL-1F2 Qu
Antikine HS ELISA Kit, R&D Systems) was used. In addition, for the measurement of IL-12, a commercially available kit (Human IL-12 p70 Quant
ikene ELISA Kit, R&D Systems) was used. Also, IL-10
A commercially available kit (Human IL-10 Ultrasensitive
ELISA Kit, Thermo Fisher Scientific) was used.

(statistical analysis)
Subjects with a capsule intake rate of 80% or more and a diary entry rate of 80% or more were selected as subjects for analysis. Differences at each time point in the evaluation results between the group ingesting the capsules of the example and the group ingesting the capsules of the comparative example were analyzed by Student's t-test.

[Test results]
Of the 22 subjects assigned to the group ingesting the example capsules, 2 subjects dropped out due to relocation. Thus, the study was completed with a group of 20 people who took the capsules of the example and a group of 22 people who took the capsules of the comparative example. Table 1 shows the test results. Efficacy is defined as “
○”, and those in which no effect was observed were evaluated as “×”. As a result, abdominal pain intensity,
Significant effects were observed on stool frequency, impairment of work productivity and daily living, and inflammatory markers.

(Regarding Abdominal Pain Intensity)
FIG. 2 is a graph showing changes in abdominal pain intensity evaluation results. In the figure, the white circles represent the average value of the group ingesting the capsules of the comparative example, and the black circles represent the average value of the group ingesting the capsules of the example. Error bars represent standard deviation. The symbol "§" indicates that there is a significant difference at a risk rate of less than 10%, and the symbol "*" indicates that there is a significant difference at a risk rate of less than 5%. As shown in FIG. 2, it was revealed that the abdominal pain intensity score was significantly reduced in the group ingesting the capsules of the example. In particular, a significant difference was observed after about 7 weeks from the start of ingestion of the capsules of the Examples.

(Regarding defecation frequency)
FIG. 3 is a graph showing the amount of change in evaluation results of defecation frequency. In the figure, the white circles represent the average value of the group ingesting the capsules of the comparative example, and the black circles represent the average value of the group ingesting the capsules of the example. Error bars represent standard deviation. The symbol "§" indicates that there is a significant difference at a risk rate of less than 10%, and the symbol "*" indicates that there is a significant difference at a risk rate of less than 5%. As shown in FIG. 3, it was found that the frequency of defecation was significantly reduced in the group ingesting the capsules of the example.

In particular, the results showed a significant difference in the post-ingestion observation period. This is because the ingestion of the placebo (comparative example) capsule has a placebo effect on IBS-like symptoms, so no significant difference was observed between the example and the comparative example in terms of the capsule intake period. However, the placebo effect disappeared after the ingestion observation period began, and the effect of ingesting the capsules of the example became clearer, suggesting that a significant difference was recognized.

(Regarding obstacles to labor productivity and daily life)
FIG. 4(a) is a graph showing the percentage of subjects with an absentee rate of 0%. Here, those who had an absentee rate of 0% were those who answered that they did not absent from work due to stomach symptoms as a result of a questionnaire asking whether they had absent from work due to stomach symptoms. is the ratio of

Moreover, FIG. 4(b) is a graph showing the percentage of subjects whose IBS-like symptoms affected the decrease in labor productivity during work at 0%. Here, those who had a rate of 0% that IBS-like symptoms affected the decline in labor productivity during work were the results of a questionnaire survey of subjects on how much their stomach symptoms affected productivity during work. , is the percentage of those who answered that stomach symptoms did not affect their work.

In addition, FIG. 4(c) is a graph showing the ratio of those whose IBS-like symptoms affected the decline in labor productivity (total loss of labor productivity) to 0%. . Here, those who had a total labor productivity loss rate of 0% were those who had an absentee rate of 0% and who had an IB
This is the ratio of those whose S-like symptoms affected the decline in labor productivity during work to 0%.

FIG. 4(d) is a graph showing the percentage of patients whose IBS-like symptoms interfered with daily life (percentage of obstacles to daily life) was 0%. Here, the disability rate to daily life is 0%
Percentage of subjects who responded that their stomach symptoms did not affect their daily activities as a result of a questionnaire survey on how much their stomach symptoms affected their daily activities other than work. is.

In FIGS. 4(a) to (d), the white bars represent the average values of the group ingesting the capsules of the comparative example, and the black bars represent the average values of the group ingesting the capsules of the example. Error bars represent standard deviation. "§"
The symbol of indicates that there is a significant difference at a risk rate of less than 10%, and the symbol of "*" indicates that there is a significant difference at a risk rate of less than 5%.

As a result, as shown in FIGS. 4(a) to 4(d), it is clear that the group ingesting the capsules of the example showed a significant improvement effect on labor productivity and obstacles to daily life. became.

(Regarding inflammatory markers)
As a result of evaluating inflammatory markers in the serum of subjects, IL-10, an inhibitory cytokine
A significant difference was observed between the groups ingesting the capsules of Examples and Comparative Examples.

FIG. 5 is a graph showing changes in serum IL-10 concentration. In the figure, the white circles represent the average value of the group ingesting the capsules of the comparative example, and the black circles represent the average value of the group ingesting the capsules of the example. Error bars represent standard deviation. The symbol "*" indicates that there is a significant difference at a risk rate of less than 5%. As a result, as shown in FIG. 5, it was revealed that the IL-10 concentration was significantly increased in the group ingesting the capsules of the example.

These results indicate the possibility that the anti-inflammatory action of IL-10 is involved in the mechanism by which the ingestion of the capsules of the Examples reduces the intensity of abdominal pain among diarrhea-type IBS-like symptoms. .

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a diarrhea-type IBS inhibitor and a food composition that improve diarrhea-type IBS in humans.

NITE P-1537

Claims (12)

An agent for improving diarrhea-type IBS-like symptoms,
The active ingredients contained therein are the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene,
The dosage of the cells of the Lactobacillus brevis strain KB290 is 1×10 ¹⁰ cells or more per day, and
The dose of β-carotene is 4 mg or more per day. The agent of claim 1,
The subject of administration is a human suffering from diarrhea accompanied by abdominal pain or discomfort. A food composition for improving diarrhea-type IBS-like symptoms,
Contributing components it contains are the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene,
The intake amount of the Lactobacillus brevis strain KB290 cells is 1×10 ¹⁰ cells or more per day, and
The intake of β-carotene is 4 mg or more per day. The food composition of claim 3,
The intake subjects are humans suffering from diarrhea accompanied by abdominal pain or discomfort. Abdominal pain intensity reducing agent,
The active ingredients contained therein are the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene,
The dosage of the cells of the Lactobacillus brevis strain KB290 is 1×10 ¹⁰ cells or more per day, and
The dose of β-carotene is 4 mg or more per day. The agent of claim 5,
The subject of administration is a human suffering from diarrhea accompanied by abdominal pain or discomfort. A food composition for reducing the intensity of abdominal pain,
Contributing components it contains are the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene,
The intake amount of the Lactobacillus brevis strain KB290 cells is 1×10 ¹⁰ cells or more per day, and
The intake of β-carotene is 4 mg or more per day. The food composition of claim 7,
The intake subjects are humans suffering from diarrhea accompanied by abdominal pain or discomfort. A defecation frequency reducing agent,
The active ingredients contained therein are the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene,
The dosage of the cells of the Lactobacillus brevis strain KB290 is 1×10 ¹⁰ cells or more per day, and
The dose of β-carotene is 4 mg or more per day. The agent of claim 9,
The subject of administration is a human suffering from diarrhea accompanied by abdominal pain or discomfort. A food composition for reducing the frequency of defecation,
Contributing components it contains are the cells of Lactobacillus brevis strain KB290 (accession number NITE P-1537) and β-carotene,
The intake amount of the Lactobacillus brevis strain KB290 cells is 1×10 ¹⁰ cells or more per day, and
The intake of β-carotene is 4 mg or more per day. 12. The food composition of claim 11,
The intake subjects are humans suffering from diarrhea accompanied by abdominal pain or discomfort.

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