HK1225637A1

HK1225637A1 - Prophylactic and/or therapeutic agent for functional gastrointestinal disorders

Info

Publication number: HK1225637A1
Application number: HK16114045.8A
Authority: HK
Inventors: 古贺泰裕; 高木敦司; 大津俊广
Original assignee: 株式会社明治; 学校法人东海大学
Priority date: 2014-02-28
Filing date: 2015-02-27
Publication date: 2017-09-15
Also published as: CN106029081A; WO2015129281A1; JPWO2015129281A1; JP2018184481A; SG11201604840TA; JP6781887B2

Abstract

　Provided is an oral agent or the like capable of preventing and/or improving functional gastrointestinal disorders in both persons positive and negative for Helicobacter pylori. The problem is solved by a prophylactic and/or therapeutic agent for functional gastrointestinal disorders, the agent containing lactobacilli as an active ingredient, to be used in persons positive and negative for Helicobacter pylori. Lactobacilli of the genus Lactobacillus are preferably used as the lactobacilli, more preferably Lactobacillus gasseri OLL 2716 (FERM BP-6999).

Description

Agent for preventing and/or ameliorating functional digestive tract disorder

Technical Field

The present invention relates to an oral intake preparation and the like for preventing and/or ameliorating functional digestive tract disorders such as functional dyspepsia.

Background

In spite of the progress of endoscopic diagnosis, a large number of cases in which symptoms cannot be described have been observed in the upper digestive organ symptoms such as epigastric pain and/or discomfort, epigastric fullness after meals, epigastric fullness, nausea, seed vomiting, epigastric pain, and epigastric burning sensation. A state in which organic lesions cannot be observed by a routine examination including an endoscope and an observation result of analyzable symptoms cannot be obtained due to the presence of such digestive organ symptoms is referred to as FD (functional dyspepsia), unidentified complaints of the upper abdomen, complaints after meals, pain in the upper abdominal region, or functional gastroenteritis).

Since these symptoms do not appear in organic lesions, the symptoms may be overlooked or misdiagnosed. Therefore, the quality of life (QOL) of persons suffering from such functional gastrointestinal disorders accompanied by discomfort but with no clear diagnosis of the disease name is reduced.

As a method for improving these symptoms, it is known to administer a drug for releasing 5-hydroxytryptamine and nitric oxide. However, since administration of these drugs is accompanied by side effects, prevention and improvement of functional digestive tract disorders by a method free from side effects are desired.

In order to prevent and improve functional digestive tract disorders by a method free from side effects, various proposals have been made up until now.

For example, patent documents 1 and 2 describe that functional digestive tract disorders are ameliorated by administration of glutamic acid, 5' -nucleotide, and the like (each according to claim 1).

Patent document 3 describes a functional digestive tract disorder preventing and seed improving agent containing glutamic acid, arginine and the like as active ingredients. The prophylactic/therapeutic agent is said to be easily produced, to be low in cost and to be highly safe, and to be effective especially against upper gastrointestinal disorders such as functional gastroenteritis (FD) including abdominal pain, gastrectasia, and heartburn, and gastroesophageal reflux disease (GERD) (abstract).

As a technique for preventing and ameliorating functional digestive tract disorders using lactic acid bacteria, for example, patent document 4 describes a technique related to bifidobacterium (hereinafter, sometimes referred to as Lactobacillus bifidus), which has a bactericidal activity against Helicobacter Pylori (hereinafter, sometimes referred to as Helicobacter Pylori), and shows: the fermented milk beverage has high survivability even under aerobic conditions as in the fermented milk beverage, and ingestion of the fermented milk beverage containing the Lactobacillus bifidus improves the symptom of unidentified gastric complaints (paragraphs 0011 and 0096).

Patent document 5 shows that lactobacillus gasseri MCC1183 strain has a bactericidal action against helicobacter pylori, and there are related descriptions of an anti-inflammatory agent, an anti-ulcer agent and a food and drink suitable for gastric distention, which are used for preventing or treating gastritis by applying this finding (paragraphs 0023 and 0052).

Patent document 6 describes a gastrointestinal hyperactivity agent containing lactobacillus such as lactobacillus acidophilus (lactobacillus gasseri), streptococcus such as streptococcus faecalis, and aloe vera (claims 1 and 2, paragraph 0012), and further describes improvement of gastrointestinal hyperactivity including bloating and abdominal distension (paragraph 0043).

That is, a technique for removing helicobacter pylori and improving functional digestive tract disorders by fermented milk drinks containing lactic acid bacteria such as lactobacillus bifidus is known. In addition, the use of Lactobacillus gasseri MCC1183 strain for the removal of helicobacter pylori and the improvement of gastric distention has also been proposed. Further, it has been proposed to improve the feeling of stomach distension and abdominal distension by a gastrointestinal function-promoting agent containing lactic acid bacteria belonging to the genus Lactobacillus, lactic acid bacteria belonging to the genus Streptococcus, and aloe.

Documents of the prior art

Patent document

Patent document 1: international publication No. 2006/030980 pamphlet

Patent document 2: japanese patent No. 5067145

Patent document 3: international publication No. 2009/113594 pamphlet

Patent document 4: japanese patent No. 4881304

Patent document 5: japanese patent No. 5300772

Patent document 6: japanese patent laid-open No. 2012 and 126700

Patent document 7: japanese patent No. 4509250.

Disclosure of Invention

Problems to be solved by the invention

On the other hand, as described in patent document 7, the present applicant has patented a pharmaceutical preparation for the sterilization and/or infection prevention of helicobacter pylori, which contains as an active ingredient a lactic acid bacterium having a high capability of sterilizing helicobacter pylori, i.e., lactobacillus gasseri OLL2716 strain. This document describes that the pharmaceutical preparation is used as an anti-gastritis agent or an anti-ulcer agent (according to claims 1, 3).

However, it is not clear whether or not the L.gasseri OLL2716 strain is effective as a functional digestive tract disorder preventing and/or improving agent.

Thus, the present inventors have conducted intensive studies and found that the L.gasseri OLL2716 strain is effective for preventing and/or improving functional digestive tract disorders.

In addition, at this time, the correlation between the effect of preventing and/or improving functional digestive tract disorders by the L.gasseri OLL2716 strain and the bactericidal effect of helicobacter pylori was studied, and as a result, it was surprisingly found that: the L.gasseri OLL2716 strain can prevent and/or improve functional digestive tract disorders, and is not related to the sterilization of helicobacter pylori.

Further, it was found that: the L.gasseri OLL2716 strain can prevent and/or improve functional digestive tract disorders even in the case of helicobacter pylori-negative persons.

Namely, it is clear that: the L.gasseri OLL2716 strain has an effect of preventing and/or ameliorating functional digestive tract disorders not only in the case of positive H.pylori but also in the case of negative H.pylori.

On the other hand, regarding the improvement of functional digestive tract disorders by using only lactic acid bacteria as an active ingredient, as described in patent documents 4 and 5, it is assumed that helicobacter pylori is eliminated (reduced), and no effect is expected even in a case where helicobacter pylori is negative.

The present invention has been made in view of the above circumstances, and an object thereof is to provide an oral intake preparation or the like which can prevent and/or ameliorate functional digestive tract disorders for both positive and negative subjects of helicobacter pylori.

Detailed Description

In order to achieve the above object, the agent for preventing and/or ameliorating a functional digestive disorder of the present invention is used for positive and negative subjects of helicobacter pylori, and comprises a lactic acid bacterium as an active ingredient.

In the present invention, lactic acid bacteria and lactic acid bacteria belonging to the genus Lactobacillus are preferably used, and Lactobacillus gasseri (Lactobacillus gasseri) OLL2716 (FERM BP-6999) is more preferably used as the lactic acid bacteria belonging to the genus Lactobacillus.

Further, the present invention is preferably formulated as a preventive and/or ameliorating agent for functional digestive tract disorders in a helicobacter pylori-negative person.

Further, in the present invention, the number of bacteria of the lactic acid bacteria is preferably 2 × 10 relative to the single daily dose of human⁷~5×10¹⁰An average of 1g of the culture of the above-mentioned lactic acid bacteria contains 10⁷In the case of more than one lactic acid bacterium, the culture of the lactic acid bacterium is preferably administered in an amount of 5 to 1000g per day.

In addition, the agent for preventing and/or improving functional gastrointestinal disorders of the present invention has a quick-acting property, which has an effect of improving functional gastrointestinal disorders 4 weeks after ingestion.

Further, examples of the functional gastrointestinal disorder include a feeling of stomach distension or a feeling of abdominal distension.

Further, it is preferable that the agent for preventing and/or improving a functional digestive tract disorder of the present invention is supplied in the form of a functional food such as a health supplement, a health functional food, and a nutritional supplement.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, an oral intake preparation and the like can be provided which can prevent and/or ameliorate functional digestive tract disorders for both positive and negative subjects of helicobacter pylori.

Drawings

FIG. 1 is a graph showing the correlation between helicobacter pylori antigen (OD value) and Δ bloating sensation (VAS score) in Δ stool by ingestion of the functional gastrointestinal disorder preventing and/or improving agent according to the embodiment of the present invention.

FIG. 2 is a schematic view of a feeling of bloating (VAS score) (a group in which helicobacter pylori antigen (OD value) is decreased in stool) caused by ingestion of the functional gastrointestinal disorder-preventing and/or-ameliorating agent according to the embodiment of the present invention.

FIG. 3 is a schematic view of a feeling of bloating (VAS score) (a group in which helicobacter pylori antigen (OD value) is not decreased in stool) caused by ingestion of the functional gastrointestinal disorder-preventing and/or-ameliorating agent according to the embodiment of the present invention.

FIG. 4 is a graph showing the correlation between the helicobacter pylori antigen (OD value) and the.DELTA.bloating sensation (VAS score) in the.DELTA.stool by ingestion of the functional gastrointestinal disorder preventing and/or ameliorating agent according to the embodiment of the present invention.

FIG. 5 is a schematic view of the feeling of abdominal distension (VAS score) (the group in which helicobacter pylori antigen (OD value) is decreased in stool) caused by ingestion of the functional gastrointestinal disorder-preventing and/or-ameliorating agent according to the embodiment of the present invention.

FIG. 6 is a schematic view of the feeling of abdominal distension (VAS score) (the group in which the helicobacter pylori antigen (OD value) in the stool is not decreased) caused by ingestion of the functional gastrointestinal disorder-preventing and/or-ameliorating agent according to the embodiment of the present invention.

Detailed Description

Hereinafter, preferred embodiments of the present invention will be described in detail.

The functional gastrointestinal disorder-preventing and/or-ameliorating agent (hereinafter, sometimes referred to as FD-ameliorating agent) according to an embodiment of the present invention is used for positive and negative subjects of helicobacter pylori, and contains lactic acid bacteria as an active ingredient.

According to the embodiment of the present invention, an FD improving agent containing a lactic acid bacterium having a usual eating habit and substantially no side effect as an active ingredient can be provided. For example, according to an embodiment of the present invention, even a negative person against helicobacter pylori can provide an FD improving agent.

Lactic acid bacteria are generally used in fermented foods such as yogurt, cheese, butter, and pickles, and have a common taste and are easily ingested.

The lactic acid bacteria in the embodiment of the present invention may be any of the genus, species, source, and the like as long as they assimilate a saccharide to produce lactic acid. Among them, lactic acid bacteria of the genus Lactobacillus, particularly Lactobacillus gasseri (Lactobacillus gasseri), are preferable, and can be suitably used for Lactobacillus gasseri OLL2716 (FERM BP-6999).

The functional digestive tract disorder in the embodiment of the present invention is: organic lesions such as peptic ulcer and cancer are not confirmed, but a disease state in which upper and lower abdomen are not responsible for complaints, such as digestive tract, stomach distension, abdominal distension, nausea, vomiting, epigastric pain, loss of appetite, or abnormal defecation, persists means that a symptom of digestive organ symptoms with reproducibility is confirmed by lowering QOL of a patient even if no organic lesions of the digestive tract are observed. This functional gastrointestinal disorder has been hitherto diagnosed as a chronic gastritis or gastritis, and is characterized by showing symptoms such as abdominal pain, gastrectasia, heartburn, and the like. In addition, since organic lesions of the digestive tract are not observed in such functional digestive tract disorders, the following hypothesis is assumed as the cause of the lesions: abnormal conduction of the nervous system due to stress or the like, slight inflammation to the extent that detection by an endoscope or the like is impossible, and a decrease in the motor function of the digestive tract, etc. are not known.

The digestive tract refers to a series of organs of the digestive tract from the mouth to the anus, and examples thereof include the throat, esophagus, stomach, small intestine (duodenum, jejunum, ileum), and large intestine. The upper digestive tract refers to the throat, esophagus, stomach, and duodenum.

In addition, in the embodiment of the present invention, it is desirable that the number of bacteria taken in the FD improving agent is preferably 2 × 10 in terms of a single daily effective dose (intake amount) of human⁷~5×10¹⁰And more preferably 5 × 10⁷~5×10¹⁰More preferably 1 × 10⁸~5×10¹⁰And more preferably 5 × 10⁸~5×10¹⁰More preferably still 5 × 10⁸~2×10¹⁰The mode of (a) contains lactic acid bacteria as an active ingredient.

This is because the number of bacteria taken in the FD improver is less than 2 × 10⁷The mode (2) above, when containing lactic acid bacteria, it is difficult to obtain an effect of preventing and/or improving functional digestive tract disorders in humans even if the number of bacteria taken in the FD improving agent is more than 5 × 10¹⁰The mode of the present invention contained lactic acid bacteria, and no significant change in the effect was observed.

In addition, in the embodiment of the present invention, an average of 10 g of lactic acid bacteria culture is contained in an effective amount (intake amount) per day for a human⁷In the case of more than one lactic acid bacterium, it is desirable that the FD improver contains a culture of the lactic acid bacterium such that it is ingested preferably in an amount of 5 to 1000g, more preferably in an amount of 10 to 1000g, still more preferably in an amount of 50 to 500g, still more preferably in an amount of 70 to 300g, still more preferably in an amount of 70 to 250g, and particularly preferably in an amount of 80 to 200 g. In the embodiment of the present invention, the effective amount (intake amount) per day of a human may be taken 1 time, or may be taken a plurality of times in 2 or more times.

The number of lactic acid bacteria contained in 1g of the lactic acid bacteria culture on average was 10⁷More than one, or 10⁷、10⁸1, 10⁹And so on. If the number of lactic acid bacteria contained in an average of 1g of the lactic acid bacteria culture is increased, the FD improving agent can contain an effective amount of the lactic acid bacteria culture and can reduce the effective amount of the lactic acid bacteria culture, and the same effect of preventing and/or improving functional digestive tract disorders in humans can be obtained by ingesting a smaller amount of the lactic acid bacteria culture.

The lactic acid bacteria culture according to the embodiment of the present invention can be obtained by culturing (growing) lactic acid bacteria with a known medium component. Further, the number of lactic acid bacteria per unit weight of the culture solution can be increased by subjecting the culture solution of the obtained lactic acid bacteria to centrifugal separation or the like. The lactic acid bacteria in the embodiment of the present invention may be in a state immediately after culturing (growth), may be in a state of being mixed with a cryoprotectant or the like and frozen, or may be in a freeze-dried state. The lactic acid bacteria in the embodiment of the present invention may be live bacteria or dead bacteria, and preferably live bacteria.

In addition, commercially available products containing the lactic acid bacteria according to the embodiments of the present invention can be conveniently used. For example, in the case of Lactobacillus gasseri (Lactobacillus gasseri) OLL2716 (FERM BP-6999), lactic acid bacteria can be isolated from "Meiji ProbioYogurt LG 21" which is sold by Kogyo K.K.K.K.K.K.K.K.K.K.K.K.K.. When the lactic acid bacterium according to the embodiment of the present invention and other ingestible ingredients are taken together, the other ingestible ingredients are not limited, and for example, milk ingredients are suitably used. The milk component refers to milk itself or a composition containing a milk component obtained by processing milk, and includes all components containing a milk component such as raw milk (e.g., cow milk), reconstituted milk (e.g., milk powder, cream, butter), fermented milk (e.g., yogurt, cheese), and dairy products (e.g., whey, casein, lactose, whey minerals, Permeate), and the source and form thereof are not particularly limited.

The FD improving agent according to an embodiment of the present invention is characterized by having a fast-acting property, and particularly has an effect of improving functional digestive tract disorders for 4 weeks. Of course, this is not limited to continuous intake of the FD improving agent according to the embodiment of the present invention for longer than 4 weeks, but continuous intake is preferably 4 weeks or longer, more preferably 8 weeks or longer, still more preferably 12 weeks or longer, still more preferably 16 weeks or longer, and still more preferably 20 weeks or longer.

Further, the method and frequency of taking the FD improving agent according to the embodiment of the present invention are not particularly limited. In the examples described below, the FD improving agent is taken daily as an example, and the preferred number of lactic acid bacteria per day is shown in the above embodiments, but the FD improving effect according to the embodiments of the present invention is not necessarily observed until the lactic acid bacteria are taken every day. Within the range in which this effect is observed, the frequency of ingestion may be appropriately adjusted to, for example, 2 days 1 time, 3 days 1 time, 4 days 1 time, 5 days 1 time, 7 days (1 week) 1 time, 10 days 1 time, 1 month 1 time, and the like.

The FD improving agent according to the embodiment of the present invention may be in the form of a unit package containing 1 meal on average, or may be in the form of a unit package containing the number of effective lactic acid bacteria.

For example, the unit package is preferably packaged for ingestion 2 × 10⁷~5×10¹⁰The form of the tablet contains lactic acid bacteria as an active ingredient, and more preferably, it is ingested in an amount of 5 × 10⁷~5×10¹⁰The form of the tablet contains lactic acid bacteria as an active ingredient, and preferably 1 × 10⁸~5×10¹⁰The form of the tablet contains lactic acid bacteria as an active ingredient, and more preferably 5 × 10⁸~5×10¹⁰The mode of the preparation contains lactic acid bacteria as an active ingredient, and further preferably comprises intake of 5 × 10⁸~2×10¹⁰The mode of (a) contains lactic acid bacteria as an active ingredient.

In addition, for example, 10 is contained in 1g of the culture of lactic acid bacteria on average⁷In the case of more than one lactic acid bacterium, the unit package contains the lactic acid bacterium culture as an active ingredient by taking 5 to 1000g, more preferably 10 to 1000g, still more preferably 50 to 500g, still more preferably 70 to 300g, still more preferably 70 to 250g, and particularly preferably 80 to 200g of the lactic acid bacterium culture as an active ingredient.

When the FD improving agent of the embodiment of the present invention is packaged in a unit package, a known package can be used. Examples of the metal material include, but are not limited to, paper, plastic, glass, nylon, stainless steel, aluminum, iron, copper, silver, and bamboo. Among them, lactic acid bacteria are preferably in a form not in contact with air or oxygen, because they are facultative anaerobes. For example, in the manufacturing process and the 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 contact with oxygen, and it is preferable to select a packaging material which does not allow oxygen to penetrate into the inside of the package during storage after packaging.

In the embodiment of the present invention, the method for ingesting the FD improving agent is not particularly limited, and any known ingestion form such as oral, tube, intestinal, vascular injection, liniment, suppository, and the like can be used, and oral ingestion is particularly preferably used.

In the embodiment of the present invention, the temperature of the FD improver when the FD improver is ingested is preferably-30 to 50 ℃, more preferably-20 to 45 ℃, still more preferably 0 to 30 ℃, still more preferably 0 to 20 ℃, and particularly preferably 0 to 10 ℃.

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.

Examples

Hereinafter, a test performed to confirm the effects of the embodiment of the present invention will be described in detail, but the present invention is not limited to the following configuration.

(example 1)

A solid FD improving agent containing Lactobacillus gasseri (Lactobacillus gasseri) OLL2716 (FERM BP-6999) as an active ingredient was prepared by the following method. The raw milk, skim milk powder and water were appropriately prepared so that the milk fat content was 3.0 wt% and the fat-free milk solid content was 9.2 wt%, and the obtained mixture was homogenized by a usual method, sterilized and cooled. Thereafter, Lactobacillus bulgaricus, Streptococcus thermophilus and Lactobacillus gasseri (Lactobacillus gasseri) OLL2716 (FERM BP-6999) isolated from MeijiProbio LG21 K.K., K.were inoculated and cultured by a usual method, and the resulting culture was used as example 1 (FD improving agent). For convenience, the FD improving agent is regarded as a substance directly ingested by a lactic acid bacterium containing an active ingredient.

The average number of Lactobacillus gasseri OLL2716 (FERM BP-6999) lactic acid bacteria in 1g of the FD improving agent is about 10⁷And (4) respectively.

Comparative example 1

A solid blank (placebo) without Lactobacillus gasseri OLL2716 (FERM BP-6999) was prepared by the following method. The raw milk, skim milk powder and water were appropriately prepared so that the milk fat content was 3.0 wt% and the fat-free milk solid content was 9.2 wt%, and the obtained mixture was homogenized by a usual method, sterilized and cooled. Thereafter, lactobacillus bulgaricus and streptococcus thermophilus isolated from MeijiProbio Yogurt LG21, ltd, were inoculated and cultured by a usual method, and the resulting culture was used as comparative example 1 (placebo).

Therefore, the placebo contains no Lactobacillus gasseri OLL2716 (FERM BP-6999) lactic acid bacteria contained in example 1, and the number of the Lactobacillus gasseri OLL2716 (FERM BP-6999) lactic acid bacteria in 1g of the placebo is 0 on average.

(test method 1)

The FD improving agent of example 1 and the blank control agent of comparative example 1 (hereinafter, these may be referred to as test samples) were used to perform an intervention test by a random blank control-dual blind test method.

Specifically, 131 subjects aged 30 years or older and free from organic lesions and infected with helicobacter pylori were randomly divided into a subject group taking the FD improving agent of example 1 (hereinafter sometimes referred to as FD improving agent group) and a subject group taking the blank control agent of comparative example 1 (hereinafter sometimes referred to as blank control agent group). In the course of the test, all the subjects and the test performers were managed in such a manner that the groups to which the subjects belong were not known.

The FD-improving agent was administered to the subjects in the FD-improving agent group and the placebo group to the subjects in the placebo group so that the FD-improving agent was administered at 90g for 1 day for 12 weeks.

In addition, functional digestive tract disorders (subjective symptoms: feeling of fullness in the stomach, feeling of fullness in the abdomen) were evaluated using a Visual Analogue Scale (VAS). In this VAS evaluation, the most severe feeling of fullness and distension was taken as 100, the less feeling of fullness and distension was taken as 0, and the VAS scores of the subjects were counted and evaluated. VAS evaluation was performed before intake of test samples, after 4 weeks of intake, after 8 weeks of intake, and after 12 weeks of intake.

In addition, helicobacter pylori antigen (OD value) in feces of each subject was confirmed by a conventional method. The confirmation of H.pylori antigen in the stool was performed before and 12 weeks after the intake of the test sample.

(Change in feeling of stomach distention)

Based on these VAS evaluation results and examination results of helicobacter pylori antigens in stool, rank correlation coefficients of spearman were calculated, and the correlation of the helicobacter pylori antigen in Δ stool (OD value) (change in the number of helicobacter pylori in stomach) with the Δ VAS score (change in bloating) was verified. The results are shown in FIG. 1.

The closer the absolute value of the correlation coefficient γ is to 1, the more significant the correlation is judged to be, but in the graph of the figure, the correlation coefficient γ is represented by-0.100, and a result in which the helicobacter pylori antigen (OD value) in Δ stool and the Δ VAS score are not correlated can be obtained.

That is, as can be seen from the graph of the drawing: the increase or decrease in the sensation of fullness produced was independent of the increase or decrease in helicobacter pylori antigen (OD value) in the stool.

Next, VAS scores of bloating before intake of the test sample, after intake of 4 weeks, after intake of 8 weeks, and after intake of 12 weeks were counted for the FD improving agent group and the blank control agent group, respectively, in the group in which the helicobacter pylori antigen (OD value) in stool was reduced. The results are shown in FIG. 2.

In addition, VAS scores of bloating before intake of the test sample, after intake of 4 weeks, after intake of 8 weeks, and after intake of 12 weeks were counted for the FD improving agent group and the blank control agent group, respectively, in the group in which the helicobacter pylori antigen (OD value) in feces was not reduced. The results are shown in FIG. 3.

As shown in fig. 2, it can be seen that: the bloating sensation in the FD-improving agent group was reduced in the group in which the helicobacter pylori antigen (OD value) was reduced in stool, that is, the group in which the number of helicobacter pylori in the stomach was reduced by sterilization.

In contrast, in the placebo group, no substantial decrease in the feeling of bloating was observed compared to before ingestion.

In addition, as shown in fig. 3, it can be seen that: the bloating sensation was reduced in the FD-improving agent group in the group in which helicobacter pylori antigen (OD value) was not decreased in stool, that is, in the group in which helicobacter pylori was not decreased in stomach.

In contrast, the blank control group had a large variation in the feeling of bloating, and no clear decrease was observed.

From these results, it can be seen that: in the FD-improving agent group of example 1, not only the feeling of bloating was reduced in subjects with reduced helicobacter pylori, but also the feeling of bloating was reduced in subjects without reduced helicobacter pylori.

Thus, the following results are obtained: the effect of improving the feeling of fullness by the functional gastrointestinal disorder-preventing and/or-ameliorating agent of the present embodiment does not depend on the sterilization of helicobacter pylori.

Therefore, it is expected that the same effect will be obtained also in a case of a helicobacter pylori-negative person.

As shown in fig. 2 and 3, the FD-improving agent of example 1 significantly reduced the feeling of fullness 4 weeks after ingestion. Namely, it is clear that: the FD improving agent of example 1 has an effect of improving functional digestive tract disorders by 4 weeks after ingestion. Since it takes about 12 weeks to obtain an effect of improving functional gastrointestinal disorders by an oral ingestion agent or the like, it is understood that the agent for preventing and/or improving functional gastrointestinal disorders according to the embodiment of the present invention has an excellent rapid-acting property.

(Change in Abdominal distension feeling)

In the same manner as the evaluation of the change in the feeling of fullness, the rank correlation coefficient of spearman was calculated, and the correlation between the helicobacter pylori antigen (OD value) in Δ stool (change in the number of helicobacter pylori in the stomach) and the Δ VAS score (change in the feeling of fullness) was verified. The results are shown in FIG. 4.

In the graph of the figure, the correlation coefficient γ is shown as 0.069. Therefore, results were obtained in which the H.pylori antigen (OD value) in the Δ stool had no correlation with the Δ VAS score.

That is, as can be seen from the graph of the drawing: the increase and decrease in the sensation of abdominal distension produced was independent of the increase and decrease in helicobacter pylori antigen (OD values) in the stool.

Next, VAS scores of abdominal distension before intake of the test sample, after intake of 4 weeks, after intake of 8 weeks, and after intake of 12 weeks were counted for the FD improving agent group and the blank control agent group, respectively, in the group in which the helicobacter pylori antigen (OD value) in stool was reduced. The results are shown in FIG. 5.

In addition, VAS scores of abdominal distension before intake of the test sample, after intake of 4 weeks, after intake of 8 weeks, and after intake of 12 weeks were counted for the FD improving agent group and the blank control agent group, respectively, in the group in which the helicobacter pylori antigen (OD value) in feces was not decreased. The results are shown in FIG. 6.

As shown in fig. 5, it can be seen that: in the group in which the helicobacter pylori antigen (OD value) was decreased in the stool, that is, the group in which the number of helicobacter pylori in the stomach was decreased by sterilization, the abdominal distension in the FD-improving agent group was decreased up to 8 weeks after ingestion.

In contrast, in the placebo group, the abdominal distension sensation varied greatly from that before ingestion, and no clear decrease was observed.

As shown in fig. 6, it can be seen that: in the group in which helicobacter pylori antigen (OD value) was not decreased in the stool, that is, the group in which helicobacter pylori was not decreased in the stomach, the abdominal distension in the FD improving agent group was decreased.

From these results, it can be seen that: in the FD-improving agent of example 1, not only the abdominal distension of the subject with reduced helicobacter pylori but also the abdominal distension of the subject without reduced helicobacter pylori were reduced.

Thus, the method can be clear: regarding the effect of improving the feeling of abdominal distension by the functional gastrointestinal disorder-preventing and/or-ameliorating agent of the embodiment of the present invention, there is no dependence on sterilization by helicobacter pylori.

(test method 2)

The FD-improving agent of example 1 was used to carry out an experiment on the Frequency scale for gastroesophageal reflux disease (GERD) (Frequency scales of the Symptoms of GERD, hereinafter sometimes referred to as FSSG).

Specifically, 24 patients (23 subjects who were negative to helicobacter pylori and 1 subject who was positive to helicobacter pylori) who were taking gastric acid secretion inhibitors were used as the subject group who took the FD improving agent of example 1.

The subjects in this group were allowed to take the FD improving agent at 118g for 1 day for 12 consecutive weeks.

In addition, functional digestive tract disorders (subjective symptoms: acid Reflux-related symptoms (Reflux), motor disturbance (dyskinesia) symptoms (dyskinesia)) were evaluated using a frequency scale for gastroesophageal Reflux disease (GERD). In the FSSG evaluation, the case where the symptom was most severe was denoted by 4, and the case where the symptom was not felt was denoted by 0, and the scores of the subjects for the respective predetermined items were counted to perform the evaluation.

In the evaluation of the symptoms related to acid reflux of FSSG, statistics are performed on the total of problem 1 (heartburn.

In the evaluation of the dyskinesia symptoms of FSSG, the evaluation was performed by counting the total of the questions 8 (with or without abdominal distension.

Further, in the comprehensive evaluation of FSSG, statistics are made for the total of the above problems 1 to 12.

These FSSG evaluations were performed before intake of the test samples and after intake for 12 weeks. In addition, FSSG evaluation was expressed as mean score and standard deviation for each subject, judged as significant difference (P-value).

(evaluation of acid reflux-related symptoms of FSSG)

The total of questions 1 to 7 was counted for each subject, and the average value and standard deviation thereof were calculated. The average of the total scores before intake of the test specimens was 6.2 with a standard deviation of 6.2. On the other hand, the average value of the total score 12 weeks after the intake of the test sample was 4.8, and the standard deviation was 4.7. When the total score before and after 12 weeks of taking the test sample was tested for significance: p value was 0.008 and by taking the test sample, the score was significantly reduced.

(evaluation of symptoms of dyskinesia of FSSG)

The total of questions 8 to 12 was counted for each subject, and the average value and standard deviation thereof were calculated. The average of the total scores before intake of the test specimens was 4.6 with a standard deviation of 3.8. On the other hand, the average value of the total score 12 weeks after the intake of the test sample was 3.6, and the standard deviation was 2.5. When the total score before and after 12 weeks of taking the test sample was tested for significance: p value was 0.021, and by taking the test sample, the score was significantly reduced.

(comprehensive evaluation of FSSG)

The total of questions 1 to 12 was counted for each subject, and the average value and standard deviation thereof were calculated. The average of the total scores before intake of the test specimens was 10.8 with a standard deviation of 0.5. On the other hand, the average value of the total score 12 weeks after the intake of the test sample was 8.4, and the standard deviation was 6.6. When the total score before and after 12 weeks of taking the test sample was tested for significance: the P value was 0.005, and the score was significantly reduced by taking the test sample.

From these results, it can be seen that: the FD improving agent according to example 1 can reduce subjective symptoms (acid reflux-related symptoms and dyskinesia symptoms) of gastroesophageal reflux disease (GERD) which occur in a state where gastric acid secretion is terminated with a gastric acid secretion inhibitor, that is, under a condition where gastric acid secretion is not involved, even in a group of 23 helicobacter pylori-negative subjects among 24 subjects.

Thus, the following results are obtained: the effect of improving functional digestive tract disorders, particularly upper abdominal functional digestive tract disorders such as esophagus, in particular, upper stomach, by the functional digestive tract disorder preventing and/or improving agent of the embodiment of the present invention is independent of the sterilization of helicobacter pylori and the inhibition of gastric acid secretion.

Industrial applicability

The present invention can be suitably used for preventing and ameliorating functional digestive tract disorders by a method free from side effects.

While several embodiments and/or examples of the present invention have been described in detail, it will be apparent to those skilled in the art that various changes can be made in these embodiments and/or examples without substantially departing from the novel teachings and effects of the present invention. Accordingly, these various modifications are also encompassed within the scope of the present invention.

The entire contents of the documents described in this specification and the japanese application specification which forms the basis of the priority of the paris convention of the present application are incorporated herein by reference.

Claims

1. A preventive and/or ameliorating agent for functional gastrointestinal disorders, which is used for positive and negative subjects of helicobacter pylori and contains lactic acid bacteria as an active ingredient.

2. The agent for preventing and/or ameliorating functional digestive tract disorders according to claim 1, wherein the lactic acid bacterium is a lactic acid bacterium belonging to the genus Lactobacillus.

3. The agent for preventing and/or ameliorating functional digestive tract disorders according to claim 1 or 2, wherein the lactobacillus is lactobacillus gasseri (lactobacillus gasseri) OLL2716 (FERM BP-6999).

4. The agent for the prevention and/or amelioration of functional digestive tract disorders according to any one of claims 1 to 3, wherein it is used for a negative person of helicobacter pylori.

5. The agent for preventing and/or ameliorating a functional digestive disorder according to any one of claims 1 to 4, wherein the number of lactic acid bacteria per single-day dose of human is 2 × 10⁷~5×10¹⁰And (4) respectively.

6. The agent for preventing and/or ameliorating a functional digestive disorder according to any one of claims 1 to 4, wherein the lactic acid bacteria are contained in an amount of 10 g per 1g of the culture⁷When the lactic acid bacteria are more than one, the daily dose of the culture of lactic acid bacteria to human is 5-1000 g.

7. The agent for preventing and/or ameliorating a functional gastrointestinal disorder according to any one of claims 1 to 6, wherein the agent exerts an effect of ameliorating a functional gastrointestinal disorder 4 weeks after ingestion.

8. The agent for preventing and/or ameliorating a functional gastrointestinal disorder according to any one of claims 1 to 7, wherein the functional gastrointestinal disorder is a feeling of gastric or abdominal distension.