JP2018184481A - Functional gastrointestinal disorders preventive and/or improvement agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral ingestion agent or the like capable of preventing and/or improving functional gastrointestinal disorders for both persons positive to and persons negative to pylori.SOLUTION: A functional gastrointestinal disorders prevention and/or improvement agent is for persons positive to and persons negative to helicobacter pylori, and contains lactic acid bacterium as an active ingredient. It is preferable to use a genus Lactobacillus lactic acid bacterium as a lactic acid bacterium, and it is more preferable to use Lactobacillus gasseri OLL 2716 (FERM BP-6999).SELECTED DRAWING: None

Description

  The present invention relates to an oral intake agent for preventing and / or improving functional gastrointestinal disorders such as functional dyspepsia.

Despite advances in endoscopic diagnosis, upper digestive symptoms such as upper abdominal pain and discomfort, stomach sag after meals, upper abdominal bloating, nausea / vomiting, epigastric pain, and epigastric burning There are many cases of findings that cannot explain symptoms in response to complaints. FD (functional dyspepsia), a state in which there are no complaints of elucidation of symptoms due to the general examination including endoscopy, although there is a complaint of such digestive symptoms Abdominal indefinite complaints, postprandial complaints, epigastric pain or functional gastroenteropathy).
Since these symptoms do not appear in organic diseases, they may be overlooked or misdiagnosed. For this reason, the QOL of a person having a functional gastrointestinal tract disorder in which a clear diagnosis of a disease name is not made despite such discomfort is lowered.
As a method for improving these symptoms, it is known to administer a drug for releasing serotonin and nitric oxide. However, since administration of these drugs has side effects, it has been expected to prevent or improve functional gastrointestinal disorders by a method without side effects.

Various proposals have been made so far in order to prevent or improve functional gastrointestinal disorders by methods without side effects.
For example, Patent Document 1 and Patent Document 2 describe that functional gastrointestinal disorders were improved by administration of glutamic acid, 5′-nucleotide, and the like (each claim 1).

  Patent Document 3 describes a functional gastrointestinal tract preventive / ameliorating agent containing glutamic acid and arginine as active ingredients. This preventive / ameliorating agent is easy to manufacture, low in cost and high in safety, especially in upper areas such as functional gastroenteropathy (FD) such as abdominal pain, stomach upset, heartburn and gastroesophageal reflux disease (GERD) It is said to be effective for digestive tract disorders (summary).

  Further, as a technique for preventing or improving functional gastrointestinal tract disorders using lactic acid bacteria, for example, Patent Document 4 has a sterilizing action of Helicobacter pylori (hereinafter sometimes referred to as H. pylori). There is a description of Bifidobacterium bifidum (hereinafter sometimes referred to as bifidobacteria) that is highly viable even under aerobic conditions such as in fermented milk beverages, and fermentation containing this bifidobacteria Ingestion of milk beverages has been shown to improve indefinite stomach complaint syndrome (paragraphs 0011, 0096).

  Patent Document 5 shows that the Lactobacillus gasseri MCC 1183 strain has a sterilizing action against Helicobacter pylori. An anti-inflammatory agent, an anti-ulcer agent, and a stomach sag used for the prevention or treatment of gastritis applying this finding. (Paragraphs 0023 and 0052).

  Patent Document 6 describes a Lactobacillus lactic acid bacterium such as Lactobacillus acidophilus (Lactobacillus gasseri), a Streptococcus lactic acid bacterium such as Streptococcus faecalis, and a gastrointestinal function enhancer containing aloe (Claim 1). , 2, paragraph 0012), it is described that the enhancement of gastrointestinal function includes improvement of stomach sag and abdominal bloating (paragraph 0043).

  That is, a technique for improving functional gastrointestinal disorders by sterilizing H. pylori using fermented milk beverages containing lactic acid bacteria such as bifidobacteria has already been known. In addition, it has already been proposed to sterilize Helicobacter pylori using Lactobacillus gasseri MCC1183 strain to improve stomach upset. Furthermore, it has already been proposed to improve stomach sag and abdominal bloating by a gastrointestinal function enhancer containing Lactobacillus lactic acid bacteria, Streptococcus lactic acid bacteria, and aloe.

International Publication No. 2006/030980 Pamphlet Japanese Patent No. 5067145 International Publication No. 2009/113594 Pamphlet Japanese Patent No. 4881304 Japanese Patent No. 5300772 JP 2012-126700 A Japanese Patent No. 4509250

On the other hand, as described in Patent Document 7, the applicant of the present invention relates to a Helicobacter pylori sterilization and / or infection prevention pharmaceutical agent containing Lactobacillus gasseri OLL2716 strain, which is a lactic acid bacterium having high sterilization ability of H. pylori as an active ingredient. Has a patent right. This document describes that the pharmaceutical agent is used as an anti-gastritis agent or an anti-ulcer agent (claims 1 and 3).
However, it was not clear whether Lactobacillus gaselli OLL2716 strain was effective as a functional gastrointestinal tract disorder preventing and / or ameliorating agent.

Therefore, the present inventors have conducted intensive research and found that Lactobacillus gasseri OLL2716 strain is effective in preventing and / or improving functional gastrointestinal disorders.
In addition, at this time, as a result of studying the correlation between the effect of preventing and / or improving functional gastrointestinal tract disorders by Lactobacillus gasseri OLL2716 and the sterilizing effect of Helicobacter pylori, surprisingly, Lactobacillus gaseri The OLL2716 strain was found to be able to prevent and / or ameliorate functional gastrointestinal disorders irrespective of the eradication of Helicobacter pylori.
Furthermore, it was found that the Lactobacillus gasseri OLL2716 strain can prevent and / or ameliorate functional gastrointestinal disorders even for H. pylori-negative individuals.

That is, it has been clarified that the Lactobacillus gasseri OLL2716 strain has an effect of preventing and / or improving functional gastrointestinal dysfunctions not only against H. pylori positive but also H. pylori negative.
On the other hand, regarding improvement of functional gastrointestinal tract disorders using only lactic acid bacteria as active ingredients, as described in Patent Documents 4 and 5, it is assumed that Helicobacter pylori is eradicated (decreased). There was no suggestion that an effect could be expected even in the negative.

  The present invention has been made in view of the above circumstances, and can prevent and / or improve functional gastrointestinal disorders for both positive and negative persons with H. pylori, such as an oral ingestion agent, etc. The purpose is to provide.

In order to achieve the above object, the functional gastrointestinal tract disorder preventive and / or ameliorating agent of the present invention is for Helicobacter pylori positive and negative persons and contains lactic acid bacteria as an active ingredient.
In the present invention, lactic acid bacteria and Lactobacillus lactic acid bacteria are preferably used, and Lactobacillus gasseri OLL 2716 (FERM BP-6999) is more preferably used as the Lactobacillus lactic acid bacteria.
Furthermore, the present invention is preferably used as an agent for preventing and / or improving functional gastrointestinal tract disorders for H. pylori negative persons.

Further, in the present invention, it is preferable that the daily dose of the lactic acid bacteria to humans is 2 × 10 ^{7 to} 5 × 10 ¹⁰ , and 10 ⁷ or more per 1 g of the lactic acid bacteria culture. When lactic acid bacteria are included, the daily dose of the culture of lactic acid bacteria to humans is preferably 5 to 1000 g.
Moreover, the functional gastrointestinal tract preventive and / or ameliorating agent of the present invention has a rapid effect, and the rapid effect exhibits a functional gastrointestinal tract disorder improving effect 4 weeks after ingestion.
Furthermore, examples of functional gastrointestinal tract disorders include a feeling of stomach sag or abdominal bloating.
In addition, it is also preferable that the functional gastrointestinal tract disorder preventing and / or improving agent of the present invention is provided as a functional food such as a health supplement, health functional food, or supplement.

  ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to provide the oral intake etc. which can prevent and / or improve a functional gastrointestinal tract disorder | damage | failure with respect to both the positive person and negative person of Helicobacter pylori.

It is a figure which shows the correlation of (DELTA) fecal H. pylori antigen (OD value) by the intake of the functional gastrointestinal tract disorder | damage | failure prevention and / or ameliorating agent which concerns on embodiment of this invention, and (DELTA) stomach feeling of leanness (VAS score). It is a figure which shows the feeling of stomach stagnation (VAS score) (population with which fecal H. pylori antigen (OD value) decreased) by ingestion of the functional gastrointestinal tract disorder prevention and / or the improving agent which concerns on embodiment of this invention. It is a figure which shows the feeling of stomach sag (VAS score) by the intake of the functional gastrointestinal tract disorder prevention and / or ameliorating agent according to an embodiment of the present invention (a group in which fecal H. pylori antigen (OD value) has not decreased). . It is a figure which shows the correlation of (DELTA) fecal H. pylori antigen (OD value) and (DELTA) abdominal fullness (VAS score) by ingestion of the functional gastrointestinal tract disorder | damage | failure prevention and / or improving agent which concerns on embodiment of this invention. It is a figure which shows the abdominal bloating feeling (VAS score) (group in which the fecal H. pylori antigen (OD value) decreased) by ingestion of the functional gastrointestinal tract disorder prevention and / or the improvement agent which concerns on embodiment of this invention. It is a figure which shows the feeling of abdominal bloating (VAS score) by the intake of the functional gastrointestinal tract disorder prevention and / or ameliorating agent according to the embodiment of the present invention (a group in which fecal H. pylori antigen (OD value) has not decreased). .

Hereinafter, preferred embodiments of the present invention will be described in detail.
The functional gastrointestinal tract disorder preventing and / or improving agent (hereinafter sometimes referred to as FD improving agent) according to an embodiment of the present invention is for positive and negative persons of H. pylori, and uses lactic acid bacteria as an active ingredient. It is characterized by containing.
According to the embodiment of the present invention, it is possible to provide an FD improving agent having a lactic acid bacterium as an active ingredient which generally has a eating habit and has few side effects. For example, according to the embodiment of the present invention, an FD improving agent can be provided even for H. pylori negative persons.

Lactic acid bacteria are generally used in fermented foods such as yogurt, cheese, butter, and pickles, and some have a familiar flavor and are easy to take.
As long as lactic acid bacteria in the embodiment of the present invention produce lactic acid by assimilating saccharides, the genus, species and origin thereof are arbitrary. Among these, lactic acid bacteria belonging to the genus Lactobacillus, in particular, Lactobacillus gasseri are preferable, and Lactobacillus gasli OLL 2716 (FERM BP-6999) can be suitably used.

Functional gastrointestinal disorders in the embodiments of the present invention include no organic diseases such as peptic ulcer and cancer symptoms, gastrointestinal tract, stomach sag, abdominal bloating, nausea / vomiting, upper abdominal pain, It refers to the pathological condition followed by upper abdominal indefinite complaints such as loss of appetite or abnormal bowel movements, and is a symptom in which reproducible gastrointestinal symptoms that reduce the patient's QOL are observed even if no organic diseases of the digestive tract are observed. Such functional gastrointestinal dysfunction is a disease that has been diagnosed as chronic gastritis or gastritis, and is characterized by symptoms such as abdominal pain, stomach upset, heartburn. Such functional gastrointestinal tract disorders do not show organic diseases of the gastrointestinal tract. As a cause, abnormal transmission of the nervous system due to stress, microscopic inflammation that cannot be detected by endoscopes, etc. There are various theories, such as the existence and decline of the motor function of the digestive tract, but it is not clear.
The digestive tract refers to a luminal organ involved in a series of digestion from the oral cavity to the anus. Examples include the pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), and large intestine. The upper digestive tract refers to the pharynx, esophagus, stomach, and duodenum.

In the embodiment of the present invention, the number of lactic acid bacteria as an active ingredient in the FD improving agent is preferably 2 × 10 ^{7 to} 5 × 10 ¹⁰ as an effective amount (intake amount) per day for humans. 5 × 10 ^{7 to} 5 × 10 ¹⁰ , more preferably 1 × 10 ^{8 to} 5 × 10 ¹⁰ , more preferably 5 × 10 ^{8 to} 5 × 10 ¹⁰ , and even more preferably 5 × 10 It is desirable to make it contain so that it may be ingested by ^{8 to} 2 × 10 ¹⁰ pieces.
When the FD improving agent is incorporated so that the number of lactic acid bacteria is less than 2 × 10 ⁷ , it is difficult to prevent and / or improve the functional gastrointestinal tract disorder in humans. This is because even if the number of bacteria is contained so as to be ingested more than 5 × 10 ¹⁰ , the effect is not greatly changed.

In addition, in the embodiment of the present invention, when 10 ⁷ or more lactic acid bacteria are included per 1 g of lactic acid bacteria culture as effective amount (intake amount) per day for humans, the culture of lactic acid bacteria is included in the FD improving agent. Preferably 5 to 1000 g, more preferably 10 to 1000 g, still more preferably 50 to 500 g, more preferably 70 to 300 g, more preferably 70 to 250 g, particularly preferably 80 to 200 g. It is desirable to make it. Here, in the embodiment of the present invention, the effective amount (intake amount) per day may be taken for a human in one time, or may be taken in two or more times.
The number of lactic acid bacteria included per 1 g of the lactic acid bacteria culture may be 10 ⁷ or more, and may be 10 ⁷ , 10 ⁸ , 10 ⁹ or the like. If the number of lactic acid bacteria included per gram of the lactic acid bacteria culture is increased, the effective amount of the lactic acid bacteria culture can be reduced while including the effective number of lactic acid bacteria in the FD improving agent. By taking a smaller amount of food, it is possible to obtain the same effect of preventing and / or improving functional human digestive tract disorders.

  The culture of lactic acid bacteria in the embodiment of the present invention can be obtained by culturing (growing) lactic acid bacteria with known medium components. Moreover, the number of lactic acid bacteria per unit weight of a culture solution can be raised by centrifuging the obtained culture solution of lactic acid bacteria. The lactic acid bacterium in the embodiment of the present invention may be in a state of just being cultured (proliferated), may be mixed with a cryoprotectant or the like, may be frozen, or may be lyophilized. In addition, the lactic acid bacteria in the embodiment of the present invention may be live or dead, and preferably live.

  Moreover, you may use the commercial item containing the lactic acid bacteria in embodiment of this invention for convenience. For example, in the case of Lactobacillus gasseri OLL 2716 (FERM BP-6999), lactic acid bacteria can be isolated from “Meiji Probio Yogurt LG21” sold by Meiji Co., Ltd. When lactic acid bacteria and other ingestible components in the embodiment of the present invention are ingested together, the other ingestible components are not limited, but for example, dairy components are preferably used. The dairy component means a composition containing milk itself or a milk component obtained by processing milk, for example, raw milk (such as milk), reduced milk (milk powder, cream, butter), fermented milk (yogurt, cheese), milk Including all ingredients including milk components such as preparations (whey, casein, lactose, whey minerals, permeates), the origin and form are not particularly limited.

In addition, the FD improving agent according to the embodiment of the present invention has a rapid action, and particularly has a functional gastrointestinal disorder improving effect in 4 weeks. Of course, this does not restrict the continuous intake of the FD improving agent according to the embodiment of the present invention for longer than 4 weeks, and it is preferable to continuously take it for 4 weeks or more. It is more preferable to continuously take the above, more preferably to take continuously for 12 weeks or more, still more preferably to take continuously for 16 weeks or more, and even more preferably to take continuously for 20 weeks or more.
Furthermore, the FD improving agent according to the embodiment of the present invention is not particularly limited in the intake method and the intake frequency. In the examples described later, an FD improving agent is taken daily as an example, and the preferred number of lactic acid bacteria per day is shown in the above embodiment, but if not taken every day, the embodiment of the present invention is used. It does not mean that FD improvement effects are not recognized. As long as the effect is recognized, the intake frequency is changed to, for example, once every two days, once every three days, once every four days, once every five days, once every seven days (one week), and every ten days. Times, once a month, etc.

The FD improving agent according to the embodiment of the present invention can be composed of a unit packaging form per serving, and can also be a form including the number of effective lactic acid bacteria per unit packaging.
For example, it is preferable to contain lactic acid bacteria, which are active ingredients, per unit package so that 2 × 10 ^{7 to} 5 × 10 ¹⁰ can be ingested, and 5 × 10 ^{7 to} 5 × 10 ¹⁰ ingested. More preferably, it is contained so as to be ingested at 1 × 10 ^{8 to} 5 × 10 ¹⁰ , and further preferably contained so as to be ingested at 5 × 10 ^{8 to} 5 × 10 ¹⁰ . It is more preferable that it is contained so as to be ingested at 5 × 10 ⁸ to 2 × 10 ¹⁰ .
In addition, for example, when 10 ⁷ or more lactic acid bacteria are included per 1 g of lactic acid bacteria culture, it is preferable that 5 to 1000 g of lactic acid bacteria culture as an active ingredient is contained per unit package. More preferably, it is contained so that it is ingested at ˜1000 g, more preferably, it is contained so that it is ingested at 50 to 500 g, and more preferably, it is contained so that it is ingested at 70 to 300 g. It is more preferable to make it contain so that it may be ingested by 250g, and it is especially preferable to make it contain so that it may be ingested by 80-200g.

  When the FD improving agent according to the embodiment of the present invention is packaged per unit package, a known package can be used. For example, paper, plastic, glass, nylon, stainless steel, aluminum, iron, copper, silver, bamboo, etc. are not particularly limited. However, in view of the fact that lactic acid bacteria are facultative anaerobic bacteria, it is preferable that the lactic acid bacteria do not come into contact with air or oxygen. For example, in the manufacturing process and packaging process of the FD improving agent according to the embodiment of the present invention, it is preferable to provide a process for removing the possibility of exposure to oxygen, and the packaging material that does not allow oxygen to permeate into the package during storage after packaging. Is preferably selected.

In the embodiment of the present invention, the method of ingesting the FD improving agent is not particularly limited, and all of the known ingestion forms such as oral, tube, enteral, vascular injection, coating, suppository, etc. can be applied. Ingestion can be suitably used.
In the embodiment of the present invention, the temperature of the FD improving agent when ingesting the FD improving agent is preferably −30 to 50 ° C., more preferably −20 to 45 ° C., and 0 to 45 ° C. More preferably, it is more preferably 0 to 30 ° C, still more preferably 0 to 20 ° C, and particularly preferably 0 to 10 ° C.
In the embodiment of the present invention, the FD improving agent may contain other ingestible components, various additives, raw materials for pharmaceuticals, and the like as components other than lactic acid bacteria.

  Hereinafter, although the test implemented in order to confirm the effect of embodiment of this invention is demonstrated in detail, this invention is not limited to the following structures.

(Example 1)
A solid FD improving agent containing Lactobacillus gasseri OLL 2716 (FERM BP-6999) as an active ingredient was prepared by the following method. Using raw material milk, skim milk powder, and water, adjust the milk fat content to 3.0% by weight and non-fat milk solid content to 9.2% by weight, and homogenize the resulting mixture by the usual method. Then, sterilization and cooling treatment were performed. Then, inoculated with Lactobacillus bulgaricus, Streptococcus thermophilus and Lactobacillus gasseri OLL 2716 (FERM BP-6999) isolated from Meiji Co., Ltd. "Meiji Probio Yogurt LG21" The obtained culture was designated as Example 1 (FD improving agent). In addition, this FD improving agent takes lactic acid bacteria containing an active ingredient as it is for convenience.
In this FD improving agent, the number of Lactobacillus gasseri OLL 2716 (FERM BP-6999) lactic acid bacteria per gram was approximately 10 ⁷ .

(Comparative Example 1)
A solid placebo (placebo) not containing Lactobacillus gasseri OLL 2716 (FERM BP-6999) was prepared by the following method. Using raw material milk, skim milk powder, and water, adjust the milk fat content to 3.0% by weight and non-fat milk solid content to 9.2% by weight, and homogenize the resulting mixture by the usual method. Then, sterilization and cooling treatment were performed. Thereafter, Lactobacillus bulgaricus and Streptococcus thermophilus isolated from Meiji Co., Ltd. “Meiji Probio Yogurt LG21” were inoculated and cultured in the usual manner, and the resulting culture was used as Comparative Example 1 (placebo).
Therefore, this placebo does not contain Lactobacillus gasseri OLL 2716 (FERM BP-6999) lactic acid bacteria contained in Example 1, and Lactobacillus gasseri OLL 2716 (FERM BP-6999) per gram in the placebo. The number of lactic acid bacteria is 0.

(Test method 1)
Using the FD improving agent of Example 1 and the placebo of Comparative Example 1 (hereinafter, these may be referred to as test samples), a randomized placebo-controlled double-blind intervention study was performed.
Specifically, a group of subjects who randomly ingest the H. pylori-infected persons who are 30 years of age or older and who do not have an organic disease and who ingest the FD improving agent of Example 1 (hereinafter sometimes referred to as an FD improving agent group). And a group of subjects taking the placebo of Comparative Example 1 (hereinafter sometimes referred to as a placebo group). During the test period, all the subjects and the tester were controlled so that the group to which each subject belonged was not known.
The subjects in the FD improving agent group received FD improving agents, and the subjects in the placebo group received placebo 90 g daily for 12 weeks.

  In addition, functional gastrointestinal dysfunction (subject symptoms: feeling of stomach sag, abdominal bloating) was evaluated using a visual analog scale (VAS). This VAS evaluation was performed by summing up the subjects' VAS scores, assuming that the maximum feeling of stomach sag and abdominal bloating was 100, and the case of no feeling of stomach sag and abdominal bloating was 0. VAS evaluation was performed before ingestion of the test sample, 4 weeks after ingestion, 8 weeks after ingestion, and 12 weeks after ingestion.

  Moreover, the fecal H. pylori antigen (OD value) of each test subject was confirmed by a conventional method. Confirmation of fecal H. pylori antigens was performed before and 12 weeks after ingestion of the test sample.

(Change in stomach feeling)
Spearman's rank correlation coefficient was calculated based on these VAS evaluation results and fecal H. pylori antigen test results, and Δ fecal H. pylori antigen (OD value) (change in the number of H. pylori in the stomach) Correlation with ΔVAS score (change in stomach feeling) was verified. The result is shown in FIG.
As the absolute value of the correlation coefficient γ is closer to 1, it is determined that there is a stronger correlation. However, in the graph of the figure, the correlation coefficient γ shows −0.100, and Δfecal H. pylori antigen The result that there was no correlation between (OD value) and ΔVAS score was obtained.
That is, it can be seen from the graph in the figure that the increase or decrease in the feeling of stomach sag occurs regardless of the increase or decrease in the fecal H. pylori antigen (OD value).

Next, for each of the FD improving agent group and the placebo group in the population in which the fecal H. pylori antigen (OD value) decreased, the test sample before ingestion, 4 weeks after ingestion, 8 weeks after ingestion, and 12 weeks after ingestion The VAS score of later feeling of stomach sag was tabulated. The result is shown in FIG.
In addition, in the group in which the fecal H. pylori antigen (OD value) did not decrease, for each of the FD improving agent group and the placebo group, before ingestion of the test sample, 4 weeks after ingestion, 8 weeks after ingestion, and 12 ingestion. VAS scores of stomach feeling after a week were tabulated. The result is shown in FIG.

As shown in FIG. 2, in the population in which the fecal H. pylori antigen (OD value) is reduced, that is, in the population in which the H. pylori in the stomach has been sterilized and the number of bacteria is reduced, It can be seen that the feeling of stomach sag is reduced.
In contrast, in the placebo group, there was almost no reduction in the feeling of stomach sag compared to before the ingestion.
Further, as shown in FIG. 3, in the group in which the stool H. pylori antigen (OD value) did not decrease, that is, in the group in which the H. pylori in the stomach did not decrease, It can be seen that the feeling is reduced.
In contrast, in the placebo group, there was a large variation in the feeling of stomach sag, and no clear reduction was observed.

From these results, it can be seen that, in the FD improving agent group of Example 1, not only subjects who had Helicobacter pylori decreased, but also subjects who did not have Helicobacter pylori had reduced stomach feeling.
That is, it was found that the effect of improving the feeling of stomach sag by the functional gastrointestinal tract disorder preventing and / or improving agent according to the embodiment of the present invention does not depend on the sterilization of H. pylori.
Therefore, it can be expected that this effect is similarly exerted on H. pylori negative persons.

  Also, as shown in FIGS. 2 and 3, according to the FD improving agent of Example 1, the feeling of stomach sag is greatly reduced in 4 weeks after ingestion. That is, it was revealed that the FD improving agent of Example 1 has an effect of improving functional gastrointestinal tract disorders 4 weeks after ingestion. Since it takes about 12 weeks until the effect of improving the functional gastrointestinal tract is obtained by the oral ingestion agent or the like, the functional gastrointestinal tract disorder preventing and / or improving agent according to the embodiment of the present invention is excellent in rapid action. It was found to have sex.

(Change in abdominal fullness)
Spearman's rank correlation coefficient was calculated in the same manner as in the evaluation of the change in the feeling of stomach sag, Δ fecal H. pylori antigen (OD value) (change in the number of H. pylori in the stomach) and ΔVAS score (abdominal fullness) Change). The result is shown in FIG.
In the graph of the figure, the correlation coefficient γ is 0.069. Therefore, it was obtained that there was no correlation between Δfecal H. pylori antigen (OD value) and ΔVAS score.
That is, it can be seen from the graph in the figure that the increase or decrease in abdominal fullness occurs regardless of the increase or decrease in fecal H. pylori antigen (OD value).

Next, for each of the FD improving agent group and the placebo group in the population in which the fecal H. pylori antigen (OD value) decreased, the test sample before ingestion, 4 weeks after ingestion, 8 weeks after ingestion, and 12 weeks after ingestion The VAS score of the subsequent abdominal fullness was tabulated. The result is shown in FIG.
In addition, in the group in which the fecal H. pylori antigen (OD value) did not decrease, for each of the FD improving agent group and the placebo group, before ingestion of the test sample, 4 weeks after ingestion, 8 weeks after ingestion, and 12 ingestion. VAS scores of abdominal fullness after a week were tabulated. The result is shown in FIG.

As shown in FIG. 5, in the population in which the fecal H. pylori antigen (OD value) was reduced, that is, in the population in which the H. pylori bacteria were eradicated and the number of bacteria was reduced, It can be seen that the feeling of fullness of the abdomen is reduced by 8 weeks after ingestion.
In contrast, in the placebo group, there was a large variation in abdominal bloating compared to before ingestion, and no clear reduction was seen.
In addition, as shown in FIG. 6, in the group in which the fecal H. pylori antigen (OD value) did not decrease, that is, in the group in which the H. pylori in the stomach did not decrease, the FD improving agent group had abdominal distension It can be seen that the feeling is reduced.
In contrast, in the placebo group, there was a large variation in abdominal bloating compared to before ingestion, and no clear reduction was seen.

From these results, it can be seen that the FD improver of Example 1 reduced the feeling of abdominal fullness not only in subjects whose H. pylori decreased, but also in subjects whose H. pylori did not decrease.
That is, it has been clarified that the effect of improving the feeling of abdominal distension by the functional gastrointestinal tract disorder preventing and / or improving agent according to the embodiment of the present invention does not depend on the sterilization of H. pylori.

(Test method 2)
Using the FD improving agent of Example 1, a test using an F-scale questionnaire for gastroesophageal reflux disease (GERD) (Frequency Scale for the Symptoms of GERD, hereinafter sometimes referred to as FSSG) was performed.
Specifically, 24 patients taking a gastric acid secretion inhibitor (23 H. pylori-negative and 1 H. pylori-positive) were taken as a group of subjects taking the FD improving agent of Example 1.
And the test subject of this group was made to ingest 118g of FD improvement agents per day continuously for 12 weeks.

In addition, functional gastrointestinal dysfunction (subject symptoms: acid reflux related symptoms (Reflux), dyskinesia (dysmotility)) was evaluated using an F-scale questionnaire for gastroesophageal reflux disease (GERD). This FSSG evaluation was performed by summing up the scores of subjects for each predetermined item, assuming that the case where the symptom was felt was 4 and the case where the symptom was not felt was 0.
Evaluation of FSSG acid reflux-related symptoms are as follows: Question 1 (Do you suffer from heartburn?), Question 2 (Do you rub your chest unexpectedly with your palm?), Question 3 (After eating, heartburn may occur) ), Question 4 (Is there a sense of discomfort in the throat (burning, etc.)?), Question 5 (Can I use it if I swallow things up), Question 6 (Bitter water (stomach acid) may rise) Is there any ??) and Question 7 (Do you get heartburn when you lean forward?)
In addition, the evaluation of FSSG dyskinetic symptoms was as follows: Question 8 (Do you sometimes feel hungry?), Question 9 (Do you have a heavy stomach after eating?), Question 10 (Eating) After that, I added up the total of Question 11 (Do you feel full during the meal?) And Question 12 (Do you often get gop?).
Furthermore, in the comprehensive evaluation of FSSG, the total of the above questions 1 to 12 was tabulated.
These FSSG evaluations were performed before and 12 weeks after ingestion of the test sample. Moreover, FSSG evaluation was represented with the average value and standard deviation of the score for every test subject, and judged by the significant difference (P value).

(Evaluation of FSSG acid reflux-related symptoms)
The total of questions 1 to 7 was totaled for each subject, and the average value and standard deviation were calculated. Before ingestion of the test sample, the average value of the total score was 6.2 and the standard deviation was 6.2. On the other hand, after 12 weeks of ingestion of the test sample, the average value of the total score was 4.8, and the standard deviation was 4.7. A significant difference test of the total score before the test sample ingestion and 12 weeks after the test sample ingestion was performed. As a result, the P value was 0.008, and it was found that the score was significantly reduced by the ingestion of the test sample.

(Evaluation of FSSG dyskinetic symptoms)
The total of questions 8 to 12 was counted for each subject, and the average value and standard deviation were calculated. Before ingestion of the test sample, the average of the total score was 4.6 and the standard deviation was 3.8. On the other hand, after 12 weeks of ingestion of the test sample, the average value of the total score was 3.6 and the standard deviation was 2.5. A significant difference test was performed between the total score before intake of the test sample and 12 weeks after intake of the test sample. As a result, the P value was 0.021, and it was found that the score significantly decreased due to the intake of the test sample.

(FSSG comprehensive evaluation)
The total of questions 1 to 12 was totaled for each subject, and the average value and standard deviation were calculated. Before taking the test sample, the average of the total score was 10.8 and the standard deviation was 0.5. On the other hand, after 12 weeks of ingestion of the test sample, the average value of the total score was 8.4 and the standard deviation was 6.6. A significant difference test of the total score before the test sample ingestion and 12 weeks after the test sample ingestion was performed. As a result, the P value was 0.005, and it was found that the score was significantly reduced by the ingestion of the test sample.

From these results, according to the FD improving agent of Example 1, even in a group where there are 23 H. pylori-negative persons among 24 subjects, in the state where the secretion of gastric acid is stopped with a gastric acid secretion inhibitor, That is, it can be seen that subjective symptoms of gastroesophageal reflux disease (GERD) (acid reflux-related symptoms and dyskinetic symptoms) that occur without depending on gastric acid secretion could be reduced.
That is, the functional gastrointestinal tract disorder preventing and / or ameliorating agent according to the embodiment of the present invention has an effect of improving the functional gastrointestinal tract disorder, particularly in the upper abdomen such as the esophagus. It turned out that it did not depend on the secretion suppression of bacteria and gastric acid.

  The present invention can be suitably used for preventing or improving functional gastrointestinal disorders by a method without side effects.

Although several embodiments and / or examples of the present invention have been described in detail above, those skilled in the art will appreciate that these exemplary embodiments and / or embodiments are substantially without departing from the novel teachings and advantages of the present invention. It is easy to make many changes to the embodiment. Accordingly, many of these modifications are within the scope of the present invention.
The contents of the documents described in this specification and the specification of the Japanese application that is the basis of Paris priority of the present application are all incorporated herein.

Claims (8)

  A functional gastrointestinal tract preventive and / or ameliorating agent for helicobacter pylori positive and negative persons and containing lactic acid bacteria as an active ingredient.   The functional GI tract disorder preventive and / or ameliorating agent according to claim 1, wherein the lactic acid bacterium is a Lactobacillus lactic acid bacterium.   3. The functional gastrointestinal tract disorder preventing and / or improving agent according to claim 1, wherein the Lactobacillus lactic acid bacterium is Lactobacillus gasseri OLL 2716 (FERM BP-6999).   The functional gastrointestinal tract disorder preventing and / or ameliorating agent according to any one of claims 1 to 3, wherein the agent is for Helicobacter pylori negative. 5. The functional gastrointestinal tract disorder prevention according to claim 1, wherein the daily dose of the lactic acid bacteria to a human is 2 × 10 ^{7 to} 5 × 10 ^10. / Or improver. When 10 ⁷ or more lactic acid bacteria are included per 1 g of the lactic acid bacteria culture, the daily dose of the lactic acid bacteria culture to a human is 5 to 1000 g. The agent for preventing and / or improving functional gastrointestinal tract disorders according to claim 1.   The functional gastrointestinal tract disorder preventing and / or improving agent according to any one of claims 1 to 6, wherein the functional GI tract disorder improving effect is exhibited in 4 weeks after ingestion.   The agent for preventing and / or improving functional gastrointestinal tract according to any one of claims 1 to 7, wherein the functional gastrointestinal tract disorder is a feeling of stomach sag or abdominal fullness.