JP6161587B2 - Composition for improving intestinal environment - Google Patents

Description

The present invention relates to a composition for improving the intestinal environment.

  Deterioration of the intestinal environment causes defecation disorders such as constipation and diarrhea and opportunistic infections, and causes a reduction in QOL (Quality of Life). In addition, it has been pointed out that the spoilage products produced by the deterioration of the intestinal environment may damage various organs and may cause onset of diseases such as hypertension and liver damage.

  On the other hand, from the viewpoint of maintaining the intestinal environment, the action of the intestinal bacterial flora on indigestible substances has attracted attention, which promotes the function of the intestinal mucosa through the decomposition of dietary fiber, etc., and suppresses inflammation and allergies. Related things are being revealed.

  Furthermore, it has been suggested that organic acids produced by enteric bacteria may be related to monitoring of nutrient components via the central nervous system (vagus nerve).

  Considering these findings, it can be said that maintaining a good intestinal environment is important in preventing various diseases.

  By the way, daily foods are improved as a general method for keeping a person's health and intestinal environment in a good state. For example, oligosaccharide is known to be a nutrient source for good bacteria in the intestine and is used in cooking and the like. In addition, foods containing bifidobacteria, which are good bacteria that keep the intestinal environment well, are also ingested.

  On the other hand, in addition to normal foods, in order to maintain health, ingestion of health supplements having a specific function is performed, and many such health supplements have been developed.

  For example, Patent Document 1 discloses a health supplement developed based on the idea that foods obtained by fermenting plants contain a large number of enzymes, and the intestinal environment can be improved by ingesting such fermented foods. Is disclosed. In the health supplement of Patent Document 2, the papain enzyme powder obtained by the room temperature extraction method is mixed with the plant enzyme powder obtained through the drying process with respect to the enzyme solution obtained through the ripening process and the fermentation process. It is a blend. And since papain enzyme powder is manufactured by the normal temperature extraction method, it is described that the enzyme maintains activity.

JP 2014-14291 A

  However, although it is described in Patent Document 1 that the enzyme in the papain enzyme powder has activity, the presence or absence of the activity of the papain enzyme powder and the fact that the health supplement of Patent Document 1 has been consumed. Examples showing the effect of improving the intestinal environment are not described. In other words, Patent Document 1 does not describe an example showing the effect of the activity of the enzyme in the papain enzyme powder, that is, the effect of improving the intestinal environment due to the activity of the enzyme. In other words, the technique of Patent Document 1 does not describe any influence of the papain enzyme activity on the intestinal environment.

  In addition, the effects of active enzymes on the intestinal environment are not fully understood at present, and it is also understood what kinds of active enzymes affect the intestinal environment. Absent.

  If it is shown how to take what kind of enzyme having activity and how the intestinal environment is improved, it is effective in maintaining human health.

In view of the above circumstances, an object of the present invention is to provide a composition for improving the intestinal environment that can ingest an enzyme having enzyme activity.

Intestinal environment-improving composition of the first invention is a composition for improving the human intestinal environment, the composition has an enzyme-containing substance containing the enzyme of plant origin, enzyme The contained material includes a protease-containing product containing a protease maintaining enzyme activity, and a cereal fermented product obtained by fermenting a cereal with koji mold, and the protease-containing product dried a papaya fruit. The fermented cereal product includes a fermented germ product obtained by fermenting a germ with koji mold .
The composition for improving the intestinal environment according to the second invention is the composition according to the first invention, wherein the fermented embryo is one or more of rice germ, wheat germ, soybean germ, straw wheat, black soybean and defatted sesame. It is characterized by being obtained by fermenting with.
The composition for improving the intestinal environment of the third invention is characterized in that, in the first invention, the fermented cereal contains a fermented wheat product obtained by fermenting wheat with koji mold.
The composition for improving the intestinal environment of the fourth invention is the composition according to the first, second or third invention, wherein the ratio of the protease-containing material and the fermented cereal product contained in the enzyme-containing substance is 1 to 30% by weight, 10 to 10%, respectively. It is characterized by 95% by weight.
The composition for improving the intestinal environment of the fifth invention is the composition according to the first, second, third or fourth invention, wherein the enzyme-containing substance comprises amylase maintaining enzyme activity and / or lipase maintaining enzyme activity. It is characterized by including.

According to the first invention, the intestinal environment of the ingested person is brought into a healthy state by combining the protease having the enzyme activity of papaya and the fermented cereal containing the fermented germ obtained by fermenting the germ with koji mold. It can be improved and maintained.
According to the 2nd - 3rd invention, since the protease and the cereal fermented material which fermented the predetermined | prescribed grain are ingested simultaneously, the increase effect of bifidobacteria and the increase suppression effect of a clostridial can be made high.
According to the fourth invention, since the protease-containing product and the fermented cereal are blended at an appropriate ratio, the effect of returning the state of the bacterial flora in the human intestine to a healthy state or maintaining the healthy state Can be high.
According to the fifth invention, amylase maintaining enzyme activity and / or lipase maintaining enzyme activity is included, so that amylase is contained as compared with the case of containing only protease maintaining enzyme activity. Since lipase acts on foods together with proteases, the effect of improving the intestinal environment can be enhanced.

It is the figure which showed the flow of the clinical trial in an Example. In an Example, it is the figure which showed the variation | change_quantity of Bifidobacterium and Clostridium cluster IV before and behind ingestion. In an Example, it is the figure which showed the result of the toilet-shaped scale.

Intestinal environment improving composition of the present invention is a composition capable of improving the environment in the intestine by oral ingestion, characterized in that it contains an enzyme that maintains the enzymatic activity Have.

Specifically, the composition for improving the intestinal environment of the present embodiment is a product containing a protease-containing material containing protease and a cereal fermented product obtained by fermenting cereals. In addition, the composition for intestinal environment improvement of this embodiment may contain excipient | filler etc. other than a protease containing material and cereal fermented material. Hereinafter, the composition for improving the intestinal environment of the present embodiment is referred to as the intestinal environment improving substance of the present embodiment or simply the intestinal environment improving substance.

  In the intestinal environment improving substance of the present embodiment, the enzyme contained in the protease-containing material or the fermented cereal is present in a state in which the enzyme activity is maintained. It is desirable that all the enzymes contained in the intestinal environment improving substance have enzyme activity, but it is not always necessary that all enzymes have enzyme activity. However, it is desirable that at least the protease in the protease-containing material maintains the enzyme activity.

  Therefore, if a person takes the intestinal environment-improving substance of this embodiment, the state of the intestinal flora (such as the balance of enteric bacteria) can be maintained in a healthy state.

  In addition, even if the state of the intestinal flora (intestinal bacterial balance, etc.) is broken from a healthy state, if ingested by a person, the state of the intestinal flora can be improved to a healthy state. .

  In particular, if the protease has an enzymatic activity, it is possible to suppress an increase in Clostridium corresponding to bad bacteria while promoting an increase in bifidobacteria corresponding to good bacteria. In other words, compared with the case where only good bacteria are increased by ingesting good bacteria such as bifidobacteria, the effect of returning the intestinal flora to a healthy state or maintaining it in a healthy state. Can be increased.

  In addition, the intestinal environment improving substance of the present embodiment includes a fermented cereal product obtained by fermenting cereals in addition to the protease-containing material. The fermented cereal contains an enzyme that is not included in the protease-containing product. For example, it contains an enzyme such as amylase or lipase. Then, if the enzyme contained in the fermented cereal product maintains the enzyme activity, the protease in the protease-containing product and this enzyme act on the food comprehensively, so that the effect of improving the intestinal environment can be enhanced.

  In particular, it is preferable that the protease-containing product and the cereal fermented product contain amylase maintaining enzyme activity and / or lipase maintaining enzyme activity. In this case, since the effect of degrading carbohydrates and lipids by amylase and / or lipase can be expected, the effect of improving the intestinal environment can be enhanced more than other enzymes.

  In addition, the intestinal environment improving substance of this embodiment may contain vitamins, minerals, lactic acid bacteria, oligosaccharides and the like in addition to the protease-containing substance and the fermented grain product. If vitamins and minerals are included in addition to the protease-containing product and the fermented cereal, the enzyme functions as a coenzyme, which is preferable in that the effect of improving the intestinal environment by the enzyme can be enhanced. If lactic acid bacteria and oligosaccharides are included in addition to the protease-containing material and the fermented cereal, an environment in which good bacteria are increased can be formed, which is preferable in that the effect of improving the intestinal environment by the enzyme can be enhanced.

(State of intestinal environment improving substance of this embodiment)
The state of the intestinal environment improving substance of this embodiment is not particularly limited. For example, it may be in the form of a powder, or may be in the form of a paste or liquid. In addition, the state ingested by humans is not particularly limited, and it may be powdery, pasty, or liquid, or powdered, pasty, or liquid may be hardened into tablets or encapsulated. You may do it.

  In addition, when the intestinal environment improving substance of the present embodiment is powdered, pasted, or liquid, the method for maintaining the enzyme activity is not particularly limited. For example, if the protease-containing product or fermented cereal product is processed without applying heat, the intestinal environment-improving substance maintaining the enzyme activity can be produced.

(Protease-containing material)
The protease-containing material described above is not particularly limited as long as it contains a protease having enzyme activity. For example, since kiwifruit, pineapple, papaya and the like contain protease in the fruit, a protease-containing product containing protease can be produced by processing the fruit by drying or the like.

(About fermented grains)
The grain used as the raw material for the above-mentioned fermented grain product is not particularly limited, and various grains can be used as the raw material. For example, fermented cereals obtained by fermenting raw materials such as rice, wheat, soybeans, straw wheat, black soybeans, and defatted sesame with koji molds can be used. The fermented cereal may be a single cereal or a plurality of cereals. When a plurality of grains are used, it is preferable in that a grain fermented product containing various nutrients is obtained.

  In addition, it is desirable to use a fermented germ obtained by fermenting only the grain germs with Aspergillus as the cereal fermented product, rather than a fermented whole product with Aspergillus. It is desirable to contain fermented wheat.

  Moreover, the method of fermenting the said grain is not specifically limited, A well-known method can be used. However, as described above, fermenting with Aspergillus is preferable in that various enzymes contained in Aspergillus (enzymes that humans do not have such as amylase and lipase) can be obtained.

(Mixing ratio)
In the enzyme-containing substance, the ratios of the protease-containing substance and the fermented cereal product contained in the enzyme-containing substance are preferably 1 to 30% by weight and 10 to 95% by weight, respectively.

  If the weight ratio of the protease-containing material is less than 1% by weight, a sufficient effect of improving the intestinal environment may not be obtained, and if it exceeds 30% by weight, the effect of improving the intestinal environment will change. do not do. Therefore, the weight ratio of the protease-containing material is preferably 1 to 30% by weight, and more preferably 5 to 25% by weight.

  Even if the weight ratio of the fermented cereal is less than 10% by weight, there is a possibility that a sufficient effect for improving the intestinal environment may not be obtained. It does not change. Therefore, the weight ratio of the fermented cereal is preferably 10 to 95% by weight, more preferably 20 to 70% by weight.

(About raw materials for enzyme-containing substances)
In the above example, the case where the enzyme-containing substance is an enzyme-containing substance containing a plant-derived enzyme obtained from a plant as a raw material has been described. The enzyme contained in the enzyme-containing substance may be an animal-derived enzyme or an enzyme derived from a microorganism such as bacteria or fungi. However, in the case of a plant-derived enzyme, a synergistic effect can be expected in the action on food since the action pH and substrate specificity are different from those secreted from the digestive tract.

  In the following, when the intestinal environment-improving substance of the present invention is orally ingested, the intestinal environment-improving substance of the present invention (hereinafter simply referred to as intestinal environment-improving substance) affects the human intestinal environment and QOL associated with bowel movements. The effect was confirmed.

(Test method)
The study employed a double-blind randomized placebo-controlled parallel group comparison study. The test group was divided into two groups: a group ingesting an intestinal environment-improving substance (hereinafter referred to as an enzyme group) and a placebo group ingesting a placebo.
In the test, the intake period of the test food (intestinal environment improving substance or placebo) was 4 weeks. In addition, the visit inspection was conducted twice before ingestion and 4 weeks after ingestion. The overall clinical trial flow is shown in FIG.

(Exam participants)
In the test, adult men and women who tend to have constipation and the number of days of stool was ingested for 4 weeks with intestinal environment-improving substances, and changes in intestinal microflora and stool status were compared with placebo intake.
For the 30 participants who agreed to participate in the study, 20 people with high occupancy of Clostridium were selected as a result of the pre-intake inspection.
The selected 20 people were placed in the placebo group that received the enzyme group and placebo, 10 people in each group using the fully randomized method, provided that the average value and standard deviation of the occupancy of Clostridium were almost uniform. Assigned to 2 groups. Allocation was performed using Excel add-in “Statlight # 11” manufactured by Yukkusu Corporation.

(Food intake)
The intestinal environment-improving substances used in the test were mainly composed of papaya enzyme, gonococcal culture extract concentrate and gonococcal culture extract, which were produced by a drying method that did not apply heat to prevent denaturation.
In addition, the weight ratio of the papaya enzyme (corresponding to the protease-containing product of the above embodiment) in the intestinal environment improving substance, and the koji mold extract and the koji mold extract (corresponding to the cereal fermented product of the above embodiment) The weight ratios were 9% by weight and 56% by weight, respectively. In addition to the above, the intestinal environment-improving substance contains vitamins / minerals and excipients as coenzymes.

  On the other hand, a placebo composed mainly of crystalline cellulose was used as a placebo.

  These intestinal environment-improving substances and placebo were ingested in water or lukewarm water for 6 weeks each 6 minutes before meals in the morning, noon and night.

(Main evaluation items)
In the study, the intestinal bacterial flora in feces was the primary endpoint. Intestinal microbiota is measured using the T-RFLP (Terminal-Restriction Fragment Length Polymorphism) method. Rate was evaluated. The genus Clostridium is classified into several clusters, but the tests evaluated clusterIV, clusterXI, subclusterXIVa, and cluster XVIII that are resident in the human intestine.

The stool samples were collected at home by test participants using a stool collection kit / brush type manufactured by Techno Suruga Labs Co., Ltd. distributed prior to each test. The test participants shipped the stool specimens to the analysis contractor by refrigerated flights within 24 hours after the stool collection.
In the test, the analysis of stool specimens, including spoilage products and ammonia described later, was consigned to Techno Suruga Laboratories.

(Secondary evaluation items)
Defecation and fecal shape evaluation, stool decay products, and fecal ammonia were secondary endpoints.

Japanese version of constipation assessment scale MT version for evaluation of defecation status (Hereinafter CAS-MT) was used. Recall the situation of one week before the inspection date for the 8 items shown in Table 1. Select 2 as “I feel a lot”, 1 as “I feel a little”, 0 as “I don't feel at all”, and select the number that corresponds to me It was. The total score of 8 items was calculated and used as the CAS-MT score. The CAS-MT score takes a value from 0 to 16, and the higher the value, the worse the constipation state.

Table 1 Japanese constipation evaluation scale
* 2: I feel a lot, 1: I feel a little, 0: I do n’t feel at all
The total score of 8 items was used as CAS-MT score.

Toward the evaluation of a toilet form, Kiyoko Fukai. Japanese version of the Constipation Assessment Scale (CAS-J). Palliative care 18; 30-31: 2008., McMillan SC, Williams FA. Validity and reliability of the Constipation Assessment Scale. Cancer Nursing 12; 183-188: 1989.). Regarding the shape of the stool for one week before the examination date, the eight options shown in Table 2 were presented and the number corresponding to itself was selected. The toilet scale has 5 as the most ideal stool state, and the higher the score, the harder the stool, and the lower the score, the watery stool. Evaluation using CAS-MT and the stool scale was performed before ingestion and at the visit examination 4 weeks after ingestion.

Table 2 Toilet Scale Answer Options

In addition, the presence or absence of defecation and sensation during defecation were investigated using the diary method. For the feeling at the time of defecation, the five options shown in Table 3 were presented and the corresponding one was selected. The feeling at the time of defecation means that the higher the score, the easier the stool. The diary entry period was every day from 2 weeks before the start of intake until the end of intake. The results were collected every 2 weeks, 2 weeks before ingestion, 1 to 2 weeks after the start of ingestion, and 3 to 4 weeks after the start of ingestion.

Table 3 Options for “Sense of Defecation” in the Journal

  Indole, skatole, phenol, p-cresol, and ammonia were evaluated as spoilage products in feces.

(Statistical analysis)
Regarding the intestinal environment, defecation, and stool shape, “the test values in each group do not differ before and after intake” and “the amount of change between before and after intake of the test food does not differ between the enzyme group and the placebo group The null hypothesis was verified, and if there was a significant difference, it was concluded that the null hypothesis was rejected. Then, when a normality test (normality of Kolmogorov-Smirnov) was performed, normality could not be assumed for some items.
Therefore, the comparison before and after ingestion was performed using the Wilcoxon sign rank sum test, and the comparison between groups before and after the intervention was performed using the Mann-Whitney U test.
In addition, Pearson's chi-square test was performed for the variation of the toilet scale. The significance level was 5% (p <0.05) by two-sided test, and 5% or more and less than 10% (p <0.10) was judged to have a tendency. IBM SPSS Ver.18.0 was used for the test.

(Experimental result)
Of the 20 people who participated in the study, all completed the study. The intake rate throughout the intake period averaged 98.7%, and none of the intake rates fell below 90%. Of the 20 people, one of the enzyme group had a cold during the intake period and was taking antibiotics, so we excluded it from the analysis considering the effect of antibiotics on the intestinal flora.
In addition, for one person in the placebo group, the occupancy rate of the genus Clostridium was given top priority as defined in the protocol, and as a result of comprehensive examination of the intestinal environment such as other bacterial species and intestinal spoilage products, Selected as a participant. However, when the data of the questionnaire was confirmed during the analysis, it was determined that the initial inclusion criteria were not fully met and it could not be determined that there was a tendency to constipate.
Therefore, the final analysis target was 18 (male: 5; female: 13; average age: 54.8 ± 8.1 years) and 9 enzyme groups (male: 2; female: 7) ) And 9 placebo groups (3 men, 6 women).

(Intestinal flora)
Table 4 shows the results of intestinal flora. FIG. 2 shows the amount of change in Bifidobacterium and Clostridium cluster IV before and after ingestion.
The proportion of Bifidobacterium increased from 7.1 ± 6.7% to 11.6 ± 9.7% in the enzyme group and decreased from 10.3 ± 9.7% to 8.9 ± 9.0% in the placebo group compared to 4 weeks after ingestion. The proportion of Clostridium cluster IV decreased from 8.6 ± 3.7% to 7.5 ± 6.2% in the enzyme group and increased from 9.4 ± 3.3 to 13.3 ± 5.0% in the placebo group compared to 4 weeks after ingestion.
Using the Wilcoxon sign rank sum test, in the enzyme group, the occupancy rate of Bifidobacterium was significantly increased 4 weeks after ingestion compared with that before ingestion (p = 0.015).
On the other hand, in the placebo group, the occupancy rate of Clostridium cluster IV significantly increased after 4 weeks of ingestion compared with that before ingestion (p = 0.038). When the amount of change from before intake to 4 weeks after intake was compared by Mann-Whitney U test, Bifidobacterium (p = 0.015) and Clostridium cluster IV (p = 0.031), the enzyme group and placebo group There was a significant difference between them.
In summary, the amount of change in Bifidobacterium was significantly greater in the enzyme group compared to the placebo group. On the other hand, the amount of change in Clostridium cluster IV was significantly greater in the placebo group than in the enzyme group.

Table 4 Mean values and standard deviations of intestinal flora

(Defecation and bowel state)
Table 5 shows the results of defecation status (CAS-MT). In addition, FIG. 3 shows the results of the toilet form state (toilet scale), and Table 6 shows the results of the bowel log. Regarding the score of CAS-MT, the enzyme group significantly decreased after 4 weeks of intake (p = 0.028) compared to before the intake, and no significant change was observed in the placebo group. There was no significant difference between the enzyme group and the placebo group in the amount of change from before ingestion to 4 weeks after ingestion.
In the enzyme group, those who answered 5 after 4 weeks of ingestion in the enzyme group increased significantly, and the result of the chi-square test was also significant (p = 0.044). In the placebo group, there was no significant change in response trends before and 4 weeks after ingestion.
In the enzyme group, the number of days of bowel movement tends to increase compared to 2 weeks before inoculation in the first 2 weeks after the start of ingestion (p = 0.051). Significantly increased (p = 0.012). In the placebo group, it significantly increased (p = 0.027) from 3 to 4 weeks after the start of ingestion compared to 2 weeks before inoculation. Regarding the amount of change, no significant difference was observed between the enzyme group and the placebo group.
Defecation sensation was significantly increased in the enzyme group 3 to 4 weeks after the start of ingestion compared to 2 weeks before inoculation (p = 0.028). In the placebo group, there was a significant increase between 1 and 2 weeks after ingestion compared to 2 weeks before inoculation (p = 0.036), but between 3 and 4 weeks after ingestion and 2 weeks before inoculation. There was no significant difference. Regarding the amount of change, no significant difference was observed between the enzyme group and the placebo group.

Table 5 CAS-MT mean and standard deviation

Table 6 Average values and standard deviations of stool logbooks

(Fecal spoilage and fecal ammonia)
Table 7 shows the results of fecal spoilage products and fecal ammonia. In the enzyme group, no significant change was observed before and after inoculation for any of the items. In the placebo group, indole (p = 0.021) and ammonia (p = 0.008) decreased significantly after 4 weeks of ingestion compared to before ingestion.

Table 7 Mean and standard deviation of fecal spoilage products and fecal ammonia

(Discussion)
As a result of ingesting the test food for 4 weeks, characteristic results were observed in Bifidobacterium and Clostridium cluster IV in the intestinal flora. Bifidobacterium in the enzyme group was significantly elevated compared to the placebo group. Bifidobacterium is said to have the action as a good bacterium, such as protection against intestinal infection, enhancement of immune function, suppression of spoilage product formation, and intestinal regulation. On the other hand, Clostridium cluster IV in the placebo group was significantly elevated compared to the enzyme group.

  In the enzyme group, Clostridium cluster IV decreased as Bifidobacterium increased. Since a negative correlation has been reported between Bifidobacterium and Clostridium leptum group, also known as Clostridium cluster IV, there is a similar correlation between Bifidobacterium and Clostridium cluster IV in the enzyme group. Estimated.

  In summary, it was suggested that taking the intestinal environment-improving substance of the present invention for 4 weeks may change the balance of the intestinal microflora and improve the human intestinal environment.

  So far, oral administration of Aspergillus fermented burdock powder to rats and feeding of Aspergillus oryzae degradation products made from rice bran have been reported to increase Bifidobacterium. Combining these previous studies with the results of the tests, it was shown that the substance that improves the intestinal environment could proliferate Bifidobacterium in the human intestine and improve the intestinal environment.

  The intestinal environment improving substance of the present invention is suitable as a substance for improving constipation and the like.

Claims (5)

A composition for improving the intestinal environment of a person,
The composition is
It has an enzyme-containing substance that contains a plant-derived enzyme,
The enzyme-containing substance is
A protease-containing product containing a protease maintaining enzyme activity, and a fermented cereal obtained by fermenting a cereal with koji mold,
The protease-containing material is
It is a dried papaya fruit,
The cereal fermented product is
A composition for improving the intestinal environment , comprising a fermented germ product obtained by fermenting a germ with koji mold . The embryo fermented product is
Rice germ, wheat germ, soybean germ, koji wheat, intestinal environment improving of claim 1, wherein the one or more of the black soybean and defatted sesame is obtained by fermenting with Aspergillus Composition. The cereal fermented product is
Wheat intestinal environment improving composition according to claim 1, characterized in that it contains wheat fermented product obtained by fermenting with Aspergillus. Protease content and cereal fermented product contained in the enzyme-containing material,
The composition for improving the intestinal environment according to claim 1, 2 or 3, which is 1 to 30% by weight and 10 to 95% by weight, respectively. The enzyme-containing substance is
5. The composition for improving the intestinal environment according to claim 1, 2, 3, or 4 , comprising amylase maintaining enzyme activity and / or lipase maintaining enzyme activity.