JPH03151854A - Composition for improving intestinal environment - Google Patents

Abstract

PURPOSE:To obtain a composition effective in improving the pH environment in digestive tracts and decreasing putrefaction product and having excellent remedying and preventing effect against hepatic encephalopathy, colon cancer, colon diseases, etc., by mixing an oligosaccharide and dietary fibers. CONSTITUTION:The objective composition for improving intestinal environment is produced by mixing (A) an oligosaccharide (e.g. raffinose or stachyose) and (B) dietary fibers (e.g. hemicellulose or high-methoxy pectin) as active components. The composition lowers the pH in intestine in high efficiency, improves the intestinal environment and decreases the putrefaction products. The composition may be compounded with a sweetener, a thickener, a binder, fruit juice, nutrient, etc., in addition to the components A and B.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention relates to a composition that improves the intestinal environment, which plays an important role in treating/preventing hepatic encephalopathy and/or colorectal cancer. It is something.

More specifically, the present invention aims to reduce intestinal PH throughout the entire intestinal tract.
and putrefactive products, thereby treating, preventing, and/or alleviating the symptoms of hepatic encephalopathy and/or colon cancer.

Therefore, the composition according to the present invention is a nutritional food.

Health agent 1: Extremely useful as a functional food or medicine.

(Prior Art and Problems) It is already well known that there are many types of bacteria in the human intestinal tract, and that there are bacterial species (genus) called good bacteria and bad bacteria.゛Bifidobacterium is a representative of good bacteria.
) bacteria produce lactic acid and acetic acid in the large intestine, and the pH in the large intestine
is lowering. A decrease in pH prevents infection by pathogenic bacteria and also advances peristalsis. It is also said that the growth of bad bacteria is suppressed, and as a result, the production of putrefactive products such as carcinogens such as ammonia, phenols, indoles, and nitroso compounds is suppressed, and the absorption of these putrefactive products is also reduced. These substances directly stimulate the intestinal lining and contribute to carcinogenesis, and indirectly, they are absorbed and transported in the blood, increasing the stimulation or load on organs such as the liver, kidneys, and brain. It is believed that

Among these substances, for example, ammonia and lower fatty acids (isobutyric acid, isovaleric acid, etc.) in the blood are produced by intestinal bacteria and are known to be factors that induce hepatic encephalopathy. ”17:117-13g (19
84) : r Clinician J 9(12) 22 : 22
48-24:2450 (1983)).

It goes without saying that colon cancer is thought to be primarily caused by direct irritation of the intestinal wall by a single carcinogen, and other colon diseases include ulcerative colitis.

Crohn's disease and diverticular disease of the large intestine are considered to be incurable diseases of unknown cause. However, although the triggering factors are unknown, it is predicted that all of them are closely related to the intestinal environment.

Therefore, in any disease, there is a need in the art to suppress harmful substances in the intestinal tract as soon as possible.

However, as mentioned above, the pH of the intestinal environment decreases due to the proliferation of Bifidobacterium spp.
There is a need for substances that can be utilized as specifically as possible by bacteria of the genus Bifidobacterium, and some oligosaccharides have been
It is already commercially available as a growth factor for the genus actarium or a growth factor for the genus actarium. It is true that these oligosaccharides efficiently bind Bifidobacter to varying degrees.
It is assimilated by bacteria of the genus Erium and lowers the pH, and also suppresses the growth of bad bacteria that produce putrefactive products.

However, as a result of research conducted by the present inventors, it has been found that indigestible oligosaccharides are normally consumed from the cecum to the ascending colon, and are difficult to remain in the lower part of the large intestine. Furthermore, the produced lactic acid and acetic acid are absorbed while passing through the large intestine, and Na
It has been found that when the retention is significant, the pH of the intestinal contents increases due to neutralization with 1 tCO, etc. Therefore, even if only oligosaccharides are ingested,
(Of course, the premise is that it passes through the small intestine without being absorbed.) However, it has been found that it is difficult to constantly control the pH drop throughout the intestine, especially in the lower part of the large intestine.

On the other hand, in addition to oligosaccharides, ingestion of 0 dietary fiber, which is known to improve the intestinal environment, increases fecal volume, restores peristaltic movement, and improves intestinal contents. It is known that because the intestinal transit time is shortened, the production of putrefactive products and carcinogens produced in the intestinal tract, especially the large intestine, is reduced, and carcinogenesis is suppressed because the time of contact with the intestinal membrane is reduced. There is.

It has been conventionally believed that dietary fiber is an indigestible polymer compound that cannot be broken down by human digestive enzymes, but it has recently been found that it is insufficient to consider human digestive enzymes alone. In other words, it has become clear that dietary fiber is also assimilated and degraded by bacterial groups present in the human intestinal tract. In particular, when the molecular weight of conventional dietary fiber is broken down into a small soluble dietary fiber, it becomes easily assimilated and degraded by intestinal bacteria.

Therefore, regarding dietary fiber, it is necessary to investigate what kind of intestinal bacteria utilize it and what kind of dietary fiber serves as a nutrient source for the growth of useful bacteria. In particular, dietary fiber that feeds bad bacteria is undesirable because even if it has an advantage in intestinal transit time, it can be used by bad bacteria and produce substances that have a negative impact on the intestinal wall. If this were to happen, the original effect would be diminished.

In this way, improvement of the human intestinal environment must be considered from a comprehensive perspective, but there have been only a few successful examples of this, which have not been previously known. Although a health food for promoting intestinal regulation consisting of a mixture is known (Japanese Unexamined Patent Publication No. 63-63366), this food
"Oligosaccharides can compensate for the deficiencies in taste and texture that dietary fiber alone has, and at least approach the taste and texture of oligosaccharides alone, making them practical as food." No.1 It does not have any effect beyond the traditional effects of dietary fiber, such as intestinal regulation and bowel movement effects.

In contrast, the present invention uses oligosaccharides and dietary fiber in combination to actively and efficiently lower the pH in the intestinal tract, especially throughout the lower small intestine and large intestine, improve the intestinal environment, and improve the production of putrefied products. This has been successful in contributing to the treatment, prevention, and/or alleviation of symptoms of hepatic encephalopathy and colorectal cancer. This is a newly developed application.

(Means for solving problems) Prevention of hepatic encephalopathy, colorectal cancer and the aforementioned colorectal diseases.

For treatment, the pH is efficiently lowered throughout the large intestine,
The present invention has been made for the purpose of improving the intestinal environment and reducing the amount of putrefaction products, so that the advantages of each substance can be sufficiently or synergistically exerted.

As a result of a comprehensive study, we found that, completely unexpectedly, the combined use of oligosaccharides and dietary fiber allowed Bihydrobacterium bacteria to survive and proliferate throughout the large intestine, improving the intestinal environment, which is a novel and useful drug. I gained a lot of knowledge.

The present invention was made based on this new knowledge, and relates to compositions and products in which the functions of oligosaccharides and dietary fibers are shared, and which specifically contribute to beneficial bacteria. The present invention relates to a composition comprising an oligosaccharide that can be converted into an oligosaccharide and a dietary fiber, preferably a dietary fiber that is not assimilated by harmful bacteria.

The composition according to the present invention is very effective in improving the intestinal environment in daily life, as is clear from what will be described later. The composition according to the present invention is also very suitable for use as a composition for preventing or treating colon cancer and hepatic encephalopathy.

By applying the composition according to the present invention, beneficial bacteria grow actively in the upper part of the large intestine, lactic acid and acetic acid are sufficiently produced, and the pH of the contents in the intestine is lowered. And the pH
The reduced contents are distributed to the colon and rectum while maintaining an appropriate PL and suppressing putrefaction products harmful to the human body as much as possible, maintaining the environment of the entire large intestine in a good condition. It is possible.

Various beneficial bacteria have already been reported in the literature, and although they cannot be generally defined, the beneficial bacteria referred to in the present invention include Bifidobacterium.
It refers to the genus erium and the genus Lactobacillus, and more specifically, B, longum, B,
Brave.

B. bifidum; B. adolescenti
S, B., 1nfantis, L.

5alivarius, L. acidophilu
S, L, gasseri, etc.

The bad bacteria referred to in the present invention include Clostridium genus,
and Enterobacteriaceae, such as the genus Escherichia (
Enterobacteriacea), specifically Coperfringens, C. diff.
icile, C. paraputrificum.

E. coli, etc.

In the present invention, the quality of oligosaccharides and dietary fibers is determined using the assimilation ability by these bacteria as a marker.

Assimilation ability can be examined by conventional methods. for example,
Pepton-Yeast-Fildas 5olut
After adding 0.5% of the test substance to an ion semi-solid agar medium and inoculating the test bacteria, anaerobic culture was carried out at 37°C for 96 hours. Determine the presence or absence. Alternatively, it can be appropriately determined by a known method such as measuring absorbance.

Oligosaccharides in the present invention refer to oligosaccharides that are used specifically or selectively by good bacteria and are assimilated by bad bacteria as much as possible. Examples of such oligosaccharides include raffinose, stachyose, etc. Examples include galactooligosaccharides, fructooligosaccharides, maltotriose, maltotetraose, maltopentaose, etc., and mixtures thereof. Among these, beneficial bacteria prefer and easily assimilate oligosaccharides composed of galactose, such as stachyose, raffinose, or a mixture thereof.
It is particularly suitable in that there are few types of bacteria that assimilate harmful bacteria in general.

The content of oligosaccharide in the composition of the present invention is determined depending on the use of the composition. That is, the content differs depending on whether the amount is taken once or multiple times per day. Therefore, a total daily intake of 1.0 to 10 g is generally preferred for adults (60 g).

Since oligosaccharides themselves are highly safe foods, there is no upper limit on their use.
The amount to be added is naturally limited in terms of ease of handling, taste, etc.

If the desired effect is desired immediately, a larger amount may be used, for example, 15 to 20 g. However, if the amount is too large, undesirable effects such as diarrhea may occur. In short, it is important to determine the respective concentrations in consideration of the number of times the composition is ingested per day and the weight per volume. When the drug is administered in several doses, it is usually administered 2 to 4 times a day.

The dietary fiber referred to in the present invention refers to human digestive enzymes.

In particular, it refers to macromolecular compounds in food that are not digested by digestive enzymes in the small intestine, and includes plant and animal compounds. In addition, one physical property of dietary fiber is that it lowers the molecular weight,
Those that are soluble in water systems.

Those with lower viscosity can also be used. When the soluble dietary fiber is made into a composition having a form such as a beverage type,
It is convenient to handle and is a preferred material.

In the present invention, dietary fibers include cellulose polysaccharides such as cellulose and hemicellulose, pectins, lignin, chitin, gums such as guar gum, seaweed-derived polysaccharides such as alginic acid, galactomannan, glucomannan, etc., or chemical Examples include modified and synthesized edele starch, polydextrose, methyl cellulose, etc., and those that are not assimilated by bad bacteria are used. Particularly preferred are those that cannot be assimilated by bad bacteria, such as cellulose.

Hemicellulose, polydextrose, lignin.

Examples include those made soluble by reducing the molecular weight of dietary fiber such as high methoxy pectin.

Solubility here refers to the property of being uniformly dispersed in water and not forming a precipitate even if left for a long time.

The content of the fibers used in the composition of the present invention can be determined as appropriate depending on the form and use of the composition. For compositions in the form of drinks, the upper limit of the content is naturally determined from the viewpoint of viscosity and handling.For compositions in the form of tablets, the content can be increased, so the upper limit of the content is determined by the texture. have a major impact on

In general, an average of 20 to 35 centimeters per day for adults. It is said that it is necessary to ingest fiber of 1 to 10 g per adult per day, although it varies depending on the intake amount around day 0 when used in combination with the oligosaccharide referred to in the present invention, compared to the case of fiber alone. 10 because the rate of passage of intestinal contents is increased.
If the amount is more than g, diarrhea symptoms are likely to occur.

When the composition according to the present invention is used for daily health considerations or for the prevention of hepatic encephalopathy or colorectal cancer, it is preferable to use a low content, and when a rapid improvement of the intestinal environment is expected. It is preferable that the content be in the form of strips. Therefore, the content of the composition can be appropriately determined by considering the number of times of intake per day, the form of the composition, etc.

The composition according to the present invention contains oligosaccharides and dietary fiber as active ingredients, and although these ingredients may be taken directly, other raw materials may be blended to form various foods and drinks or nutritional supplements. The oligosaccharides and dietary fibers may be used in their crude form without being purified, or their contents may be used.

To this end, the other raw materials listed above include sweeteners, thickeners,
Binders, excipients, fruit juices, vegetable juices.

Coffee extract, other animal and plant extracts, fragrances, colorants,
It may be formulated into a formulation or into the form of various food and drink products in accordance with conventional methods using various ingredients commonly used in the preparation of pharmaceuticals such as seasonings, nutritional supplements, and food and drink products.

In addition, when used as a drink or other beverage, commonly used raw materials such as glucose, sucrose, liquid sugar, lactose 1 artificial sweetener, amino acids, proteins, vitamins, lactic acid bacteria drinks, plant extracts, and flavorings are added. May be added.

Experimental examples and examples of the present invention will be described below.

Experimental example 1 We investigated the assimilation ability of typical fibers by intestinal bacteria.

The test bacterial strain was pure cultured on EG agar medium, and subcultured twice in modified CAM broth and anaerobic culture at 37°C for 24 hours.This culture was transferred to PYF semi-solid agar medium with various test fibers at a final concentration of 0. After adding it to a concentration of 5% and sterilizing it, 1.
0.03mM inoculation per 5mM. After culturing anaerobically at 37°C for 4 days, the pH was measured.

The 0 criterion for determining assimilation is the presence or absence, or strength or weakness, of assimilation based on how much the pH has decreased.

It is as follows.

P) 16.0≦p)1 5.5≦p)l (6,0± 5.0≦pH<5.5 + 4.5≦pH<5.0 + age pH (4,5◆+÷ Typical test fibers include cellulose, MC (methylcellulose), HC (hemicellulose), po (polydextrose), GG (guar gum decomposition product), and GM.
(galactomannan decomposition product), DX (1! Digestible dextrin), and AA (alginic acid) were used.

The results are shown in Table 1, and in this experiment, cellulose, methylcellulose, and hemicellulose.

It was found that polydextrose is not particularly assimilated by bad bacteria.

Experimental Example 2 CD rats (3 weeks old, male) obtained from Charles River were divided into 4 groups of 6 rats each. Basal feed: casein 23.0% excluding dietary fiber, starch 61.7%, granulated sugar 5.0%, soybean oil 5.0%, vitamin mixture 1
．． 0%, mineral mixture 4.0%, DL-methionine 0
．． A powdered feed with a composition of 3% was used.

The control group (CNT) was a group in which this powdered feed was used as it was, and the group in which 1.6% of hemicellulose was replaced with the same amount of starch in the above composition was the control group (CNT).
HC), similarly soybean oligosaccharide powder (23% stachyose, 7% raffinose, 44% monosaccharide, glucose,
The plot in which 7.0% starch was substituted for 13% fructose, 10% other sugars, and 3% water was compared to the plot in which soybean oligosaccharide alone was added (SO
E), and the mixed area (MI
X).

After raising the rats for one week using each of these four types of feed, the rats were sacrificed, the intestines were removed, and the PH values of the contents of the cecum and the lower part of the large intestine were measured.

The results are shown in Figure 1.

As is clear from the figure, in the MIX area, the entire large intestine (
It can be seen that the pH value in the shaded area) has decreased overall compared to other areas.

Experimental example 3 The effects of the composition of the present invention were investigated on healthy subjects.

That is, 6.6 g of soybean oligosaccharide powder (of which about 2 g of effective oligosaccharides) and 2 g of soluble hemicellulose were mixed together to make one pack, and 4 healthy boys and 2 girls aged 22 to 52 years old
The subjects were asked to take 1 batch per day for 10 consecutive days. After 10 days, stool was collected and the following measurements were performed. In addition, feces were collected from the same person before ingestion and analyzed for the same items.

This was used as a control.

Ammonia was measured using an ion meter. For p-cresol, after adjusting the sample to pH 8.0, steam distillation is performed, and the resulting fraction is distilled into 5E-30 (14% Clo T-
'//l/BW, l-DMC: 60-80, IL
y (manufactured by Gascro Industries) as a carrier. Quantitative analysis was performed by gas chromatography. Organic acid (isobutyric acid (i
C,), isovaleric acid (ici)) is PEG-60
Quantitative analysis was performed by gas chromatography using 00 (80-100 mesh, manufactured by Gascro Kogyo Co., Ltd.) as a carrier. The results are shown in Table 2.

Table 2 Control 10th day of intake PH 6,65 ± 0.63 5.78 ± 0.33 Table 2
As is clear from the above, after ingesting the composition of the present invention, the pH of the stool decreases, and harmful putrefactive products such as ammonia, p-cresol, and is.

butylic acid, iso valeric
It was found that acid was significantly reduced.

Example 1 Brix 5.8% liquid sugar 100 votes Q, stachyose 1.4%, soluble hemicellulose 1.5%, sucrose 1.9%, L-ascorbic acid 0.1%, citric acid (crystal) 0.23%, sodium citrate 0.04%
, 1000 mg of taurine was dissolved. This beverage type composition is useful as a solution for people who have or are at risk of having diseases in the liver and large intestine.

Example 2 1.25 parts by weight of polydextrose, 1.25 parts by weight of stachyose.
0 parts by weight, 0.5 parts by weight of raffinose, 0.1 parts by weight of bifidobacteria powder, 0.15 parts by weight of ascorbic acid, and 0.5 parts by weight of powdered sucrose were thoroughly and uniformly mixed in a powder mixer. 3.5 g each was filled into laminated sticks. This product is useful as a powder-type composition to be ingested multiple times per day for people who are at risk of developing hepatic encephalopathy.

(Effects of the Invention) The present invention utilizes the combined use of oligosaccharides and dietary fiber for purposes that are completely different from the conventional simple intestinal regulation effect, that is, to lower the pH throughout the intestinal tract and improve the intestinal environment. We have succeeded in developing a completely new application that improves the quality and reduces the amount of spoiled products.

Therefore, the composition according to the present invention can be widely and safely used in functional foods, drinks, nutritional foods, medicines, etc. for the treatment, prevention, and/or symptom relief of hepatic encephalopathy, colorectal cancer, and other colorectal diseases. can do.

[Brief explanation of the drawing]

No. 1111 shows the pH values of the cecum and large intestine contents of rats fed each diet.

Claims (1)

[Scope of Claims] 1. Oligosaccharides and A composition characterized by being mixed with dietary fiber. 2. The composition according to claim 1, wherein the dietary fiber is soluble dietary fiber. 3. The composition according to claim 1 or 2, wherein the oligosaccharide is a galactooligosaccharide. 4. The composition according to claim 3, wherein the galactooligosaccharide is raffinose or/and stachyose.