JPH10179087A - Food composition for liver disease patient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a food compsn. which has decreased side effects, is effectual, is easy to drink or take in and is capable of decreasing the various symptoms of liver disease patients by incorporating a specific ratio of raffinose into the compsn. SOLUTION: The raffinose is incorporated at least at 1wt.% and more preferably 3 to 15wt.% into the compsn. The raffinose-contg. oligosaccharide mixture produced as a soybean oligosaccharide in addition to the raffinose obtd. from beet roots, soybean whey, etc., may be compounded with the compsn. at the weight corresponding to the desired raffinose content.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a food composition to be administered to a patient with liver disease, which relates to raffinose or a food composition for patients with liver disease containing raffinose and lactulose.

[0002]

2. Description of the Related Art For the treatment of various liver diseases such as viral hepatitis, cirrhosis, alcoholic liver disease, and fatty liver, treatments for controlling nutritional metabolism by diet therapy and exercise therapy have been mainly performed. For alcoholic liver disease, include abstinence, balanced diet, diet-reducing therapy for hypertrophic fatty liver, and administration of hyperbranched amino acid preparations for liver failure mainly due to decompensated cirrhosis (Meiji Watanabe and Misako Okita, "Liver Diseases and Therapeutic Nutrition", Daiichi Shuppan, 1992).

[0003] Conventionally, many food compositions for various liver diseases are known. However, the present inventors have found that spoilage products produced by intestinal putrefactive bacteria such as ammonia can be used to improve liver function in patients with liver disease. From the viewpoint that it is most important to improve the intestinal flora and reduce the burden of putrefaction products in food compositions administered to patients with liver disease, Further detailed studies were conducted on known lactulose, various oligosaccharides, and the like.

[0004] Lactulose is a non-digestible oligosaccharide having a wide range of assimilation properties for bifidobacteria, and various similar oligosaccharides such as galactooligosaccharides, various fructooligosaccharides, and raffinose are known. These oligosaccharides have the effects of improving the intestinal environment, improving convenience, and suppressing the production of intestinal putrefaction products as bifidobacteria growth factors, and are widely used mainly in foods (Monthly Food Chemical, No. 10, Vol. 79-84, 1986).

[0005] However, among these oligosaccharides, only lactulose and lactitol as drugs for ameliorating hepatic encephalopathy or hyperammonemia have been used in patients with liver diseases (Japanese clinical practice, vol. 52). , First
No. 110-118, 1994).

[0006] Lactulose is assimilated by a wide variety of bifidobacteria, which grows bifidobacteria,
It is metabolized to organic acids, lowering the pH in the intestinal tract, inhibiting the absorption of ammonia produced by putrefactive bacteria from the intestinal tract, and promoting peristaltic movement of the intestinal tract to shorten the intestinal retention time of intestinal contents. It is known to promote defecation (Japanese clinical practice, vol. 46, extra number, 1077-10th
83, 1988). Due to these effects, it has been reported that the absorption of various toxic substances including ammonia from the intestinal tract and the production of ammonia in the intestinal tract itself have recently been suppressed [Hepatology, Vol. 1133 pages, 1986
Year] .

[0007] However, lactulose is also utilized by Escherichia coli, Clostridium, and the like, and may exhibit some difficulty in the selective utilization of useful bacteria such as Bifidobacterium.
Depending on the dose, diarrhea may be induced and abdominal distension may be caused. In addition, there is a problem that the sweetness is strong and it is difficult for some patients to take a large amount. Furthermore, since lactulose is a reducing sugar, when it is mixed with a substance having an amino group or the like and processed, it tends to turn brown, so that care must be taken when adding it to foods containing proteins, amino acids and the like.

[0008] On the other hand, lactitol is a substance belonging to sugar alcohol, and its properties are similar to those of oligosaccharides, and like lactulose, it is also used for the treatment of hepatic encephalopathy and hyperammonemia (clinical). Pharmaceutical Sciences, Vol. 11, No. 7, pp. 1439-1473, 1995). However, assimilation by human-derived bifidobacteria,
It has the disadvantage of being restricted to special bacteria (Bifidus, Vol. 9, No. 1, pages 19-26, 1995).
Years), the improvement of the intestinal flora becomes insufficient, and the effect may not be obtained depending on the patient.

As described above, lactulose and lactitol, which are conventionally known drugs administered to liver diseases, have room for improvement in the intestinal environment and the like for the purpose of improving the symptoms of liver diseases. In particular, there has been a long-awaited demand for imparting the above-mentioned improvement effect to food compositions for patients with liver diseases which are taken as food.

[0010] Next, raffinose, which has recently been studied from the viewpoint of improving the intestinal environment, will be described. Raffinose is not assimilated by as wide a range of bifidobacteria as lactulose, but hardly assimilated by spoilage and ammonia-producing bacteria, and is known to be an excellent oligosaccharide as a selective sugar source for the growth of bifidobacteria. In addition, the effects of suppressing the production of intestinal putrefaction products and improving the convenience are also clarified (Japan Food Science, No. 9, pp. 34-40, 1993).

Conventionally, raffinose has been mostly used as a food utilizing processing characteristics, an edible dehydrating agent utilizing hygroscopicity, a stabilizer of a transplanted organ transport solution, a stabilizer of a probiotic agent, and the like. There (Japan Food Science, No. 9,
Pp. 34-40, 1993).

In addition, as a composition for improving the intestinal environment, a composition comprising a combination of galactooligosaccharides such as raffinose and stachyose and dietary fiber is useful for treating hepatic dysfunction and colorectal cancer.
In addition, it is disclosed that the composition is effective for prevention (Japanese Patent Application Laid-Open No. 3-151854), but the effect of the composition is limited to the reduction of the amount of intestinal putrefaction products, and the effect on liver disease is not clear. Was not intended for use as a food for liver disease. In addition, the publication clearly states that when only oligosaccharides are administered, an intestinal flora improving effect cannot be found. It has also been disclosed that a liquid food containing an indigestible oligosaccharide such as raffinose and polydextrose has an effect of improving bowel movement (Japanese Patent Application Laid-Open No. 62-220169). Was limited to improving bowel movements.
Furthermore, foods mainly comprising a saccharide mixture of oligosaccharides containing raffinose and edible dietary fiber have an intestinal action,
It is disclosed that it is effective for promoting health (Japanese Unexamined Patent Publication No.
However, the effect of the food on liver disease was not yet known.

As described above, the conventionally known food compositions for patients with liver disease do not have a food composition which is mainly intended to improve the intestinal environment and exhibit the effect of improving the symptoms of liver disease. As an oligosaccharide used for
Oligosaccharides that are effective and easy to drink or ingest have been desired.

[0014]

SUMMARY OF THE INVENTION In view of the above-mentioned prior art, the present inventors have proposed a composition containing a desired oligosaccharide alone and a desired oligosaccharide mixture in order to improve various symptoms of a liver disease patient. The present inventors have found that the use of is possible to improve the intestinal environment of patients with liver disease, to be effective, to reduce various symptoms, and to improve various symptoms, thereby completing the present invention.

[0015] It is an object of the present invention to provide a food composition for a liver disease patient which can improve various symptoms occurring in the liver disease patient.

[0016]

Means for Solving the Problems A first invention of the present invention for solving the above-mentioned problems is to provide a food composition to be administered to a patient with a liver disease, wherein the raffinose content in the composition is at least 1% (by weight). It is a desirable food composition for a liver disease patient, wherein the raffinose content in the composition is preferably 3 to 15% (by weight).

According to a second aspect of the present invention, there is provided a food composition to be administered to a patient with liver disease, wherein the total content of raffinose and lactulose in the composition is at least 1% (by weight). A food composition for a liver disease patient, wherein the total content of raffinose and lactulose in the composition is 3 to 15% (weight), and at least 1 part (weight) of raffinose with respect to 10 parts (weight) of lactulose. ) Is also a desirable mode.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION Next, the present invention will be described in detail. First, constituent elements common to the first and second inventions of the present invention will be described.

The raffinose used in the first and second inventions of the present invention is, for example, one produced from beet root by a known method (for example, Japanese Patent Application Laid-Open No. 54-49345). A method known from whey (for example,
Raffinose produced according to JP-A-59-179064) can also be used. In addition, the raffinose-containing oligosaccharide mixture produced as soybean oligosaccharide can be directly used by blending it in an amount corresponding to a desired raffinose content in the food composition of the present invention.

In addition to raffinose used in the first and second inventions of the present invention, other components as a food composition are as follows. Proteins include, for example, milk proteins,
Soy protein, wheat flour, corn protein, etc., and protein degradation products, peptides, amino acids, etc. can be added to the protein.

The lipids include various known oils and fats, oil and fat compositions, fatty acid compositions, and the like, and these can be used by appropriately mixing them. In addition, carbohydrates, other than oligosaccharides other than raffinose and lactulose, glucose,
Various known saccharides such as sugar, dextrose, and starch can be exemplified, and can be appropriately used as needed for the purpose of adjusting sweetness, stabilizing tissue, and the like.

Examples of the minerals to be blended include sodium chloride, potassium chloride, calcium chloride, magnesium sulfate, calcium glycerophosphate, iron citrate and the like. Examples of the vitamins to be blended are vitamin A, Examples include vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , niacin, folic acid, vitamin C, vitamin D, vitamin E, vitamin K, calcium pantothenate, nicotinamide, choline chloride, and the like.

Further, various additives include guar gum, pectin, locust bingham, carrageenan, carboxymethyl cellulose and the like as stabilizers, benzoic acid and its salts, sorbic acid and its salts as preservatives, thaumatin as a sweetener, Stevia, saccharin, amino acid derivatives, lactitol, etc., as antioxidants, polyphenols, β-carotene, ascorbic acid derivatives, etc., as cell components Bifidobacterium powder, lactic acid powder, various cell wall components, etc., respectively. If necessary, known excipients, extenders, emulsifiers, fragrances, coloring agents, preservatives and the like can also be added.

In addition, the food composition for liver disease patients of the present invention may be mixed with and / or processed with widely used food materials as a therapeutic food for liver disease to be administered to patients with liver disease. Good.

In order to enhance the preservability of the food composition for a liver disease patient of the first and second inventions of the present invention or to prepare a dosage form, a shape-retaining agent, an excipient, etc. are added by an ordinary method, It can be processed into liquid, powder, granule, etc.

According to the first invention of the present invention, the above raffinose is contained in the final composition in an amount of 1% (by weight, hereinafter the same unless otherwise specified), preferably 3 to 15%, particularly preferably 5 to 15%. 10% by weight of a food composition for a liver disease patient, wherein raffinose as an active ingredient of the food composition is administered in a range of 3 g or more per person per day for a liver disease patient, preferably 5 to 10 g per day. You.

The second invention of the present invention has an essential requirement that it contains the above-mentioned raffinose and lactulose, but the lactulose to be used is produced by subjecting lactose to alkali isomerization by a known method, and is in the form of syrup or powder. Any of the dosage forms such as solid and granular forms can be used. However, since there are few by-products, for example, JP-B-52-210
Preferably manufactured by the method described in JP-A No. 63-63.

The food composition for a liver disease patient according to the second invention of the present invention contains the above raffinose and lactulose in a final composition in a total amount of 1% or more, preferably 3 to 15%, particularly preferably 5 to 10%. %, And the ratio of raffinose to lactulose is preferably at least 1 part relative to 10 parts of lactulose (weight; hereinafter the same unless otherwise specified), more preferably 6 parts of raffinose. 1 part lactulose
The range is 12 parts. The dose of the food composition to a liver disease patient is 3 g or more, preferably 1 g / day, per person, as a total amount of the active ingredients raffinose and lactulose.
5-10 g per day.

The food composition for a patient with liver disease of the present invention produced as described above can improve various symptoms of liver disease as described later.

Next, the present invention will be described in detail with reference to test examples. The problem of the tests that have been carried out to develop a composition for a conventional liver disease is that the intestinal environment of a liver disease patient has not been sufficiently grasped and reflected, as described above. The effects of the products on improving the symptoms of liver disease were insufficient.

The present inventors, when selecting an oligosaccharide in a composition assuming the intestinal tract of a liver disease patient, have a wide range of assimilation to the main constituent bifidobacteria in the intestine and a growth rate. Fast, and the added oligosaccharides are rarely used by other spoilage bacteria. A high amount of acid production in the intestinal tract as a result of the added oligosaccharide being sufficiently utilized by useful bacteria such as Bifidobacterium. The pH value in the intestinal tract is reduced as much as possible as a result of the added oligosaccharide being sufficiently utilized by useful bacteria such as bifidobacteria. However, it was considered to be an important factor for examining the effect of improving the intestinal environment and various symptoms of liver disease.

When the above conditions are satisfied, the production of toxic substances such as ammonia, indole and skatole by putrefactive bacteria in the intestinal tract can be surely and effectively suppressed, and the burden on liver function can be reduced. Therefore, it is considered that the present invention certainly exerts the effect of improving various symptoms of liver disease. Therefore, the present inventors decided to carry out a preliminary test under conditions as close as possible to these three points.

As an experimental means, in order to accurately select a desired composition under conditions most suitable for patients with liver disease, assimilation and proliferation of major intestinal bifidobacteria mixed with various oligosaccharides alone and in combination. A method of comprehensively evaluating each index of speed, acid generation, and pH value was adopted.

Preliminary test 1 This test was conducted to determine the growth promoting effect of added oligosaccharides on a mixed culture system of various Bifidobacteria frequently detected in the human intestinal tract. The test was performed to select oligosaccharides in the composition to be administered to improve the symptoms of the above.

(1) Test strains In order to examine the effect of oligosaccharides on the intestinal environment in patients with liver disease, the following three strains of bifidobacteria, which are frequently detected in adults and elderly people in Japan, are shown below. And a mixed culture system of these three bacterial species was used assuming the intestinal flora.

[0036] Bifidobacterium adolescentisBB-102, Bifidobacterium bifidum
BB-225), Bifidobacterium longum (Bifidob)
acterium longum BB-536) These strains were isolated from the stool of healthy adults by the usual method [Tomota Mitsuoka, “Study on Bifidobacteria”, pp. 40-60, Japan Bifidobacterium Center, 1994]. The strain is an identified bifidobacterium strain, which has been preserved by the present inventors and can be distributed as needed.

In particular, Bifidobacterium bifidum is one of the representative Bifidobacteria usually established in the human intestine, but lacks the ability to assimilate many oligosaccharides. When estimating the growth promoting effect of various bifidobacteria, these strains are intentionally excluded from the test.

(2) Test method 1) Preparation of basal medium and preculture solution 0.5% yeast extract, 0.5% meat extract, glucose 2
%, Monopotassium phosphate 0.1%, dipotassium phosphate 0.
1%, anhydrous sodium acetate 0.2%, cystine 0.05
%, Tween 80 0.05%, and purified water (ion-exchanged water) 96.5%
The solution was autoclaved at 15 ° C. for 15 minutes and used as a basal medium.

The basal medium was dispensed in an amount of 10 ml, and 1 ml of the bifidobacterium storage slant was added to a sterilized test tube medium.
A platinum loop was inoculated, 2 ml of sterilized liquid paraffin was overlaid, anaerobic conditions were set, and anaerobically cultured at 37 ° C. for 24 hours to obtain a pre-culture solution.

2) Preparation of Test Medium Instead of glucose in the base medium, various oligosaccharides such as lactulose (manufactured by Morinaga Milk Industry Co., Ltd.), raffinose (manufactured by Nippon Sugar Beet Co., Ltd.), lactitol (manufactured by Wako Pure Chemical Industries, Ltd.), And galacto-oligosaccharides (manufactured by Nissin Sugar Co., Ltd.) were each used alone to prepare a medium using 2%, and each was placed in a test tube at 10 m.
Each of these was dispensed and sterilized to obtain a test medium.

3) Methods of culture and measurement In order to comprehensively evaluate the effects of the various oligosaccharides used on the mixed culture system of Bifidobacteria, the growth was intended to improve the intestinal environment of the above-mentioned liver disease patients. Speed, medium acidity,
Investigations were made from three points: medium pH.

That is, for each of the four test media described above, 0.2 ml of each of the precultures of the three kinds of bifidobacteria was mixed and inoculated in a total of 0.6 ml, and three test tubes were immediately sterilized with liquid paraffin. Overlay 2 ml and in a regular incubator at 37 ° C., 3
One of them was cultured for 12 hours and the other for 48 hours. The turbidity of another medium without liquid paraffin was measured immediately using a spectrophotometer (manufactured by Hitachi, Ltd.) at a wavelength of 660 nm, a quartz cell, and an optical path length of 10 mm.

In the test tube medium cultured for 12 hours, the turbidity was measured after culturing under the same conditions as described above, and the increase in turbidity after 12 hours was measured and used as an index of the growth rate. The turbidity was measured after 12 hours of cultivation, because the added oligosaccharide was assimilated by the bifidobacterium as quickly as possible to determine whether or not it could grow. The culture time was set.

In the medium cultured for 48 hours,
The pH of this medium was measured with a pH meter (manufactured by Horiba, Ltd.), and the remaining one medium was subjected to centrifugation to obtain a medium supernatant, and 5 ml of the supernatant was subjected to medium with 0.1 N NaOH using phenolphthalein as an indicator. 0.1N required for sum titration and titration
The number of ml of NaOH was defined as the acidity of the medium. The reason why the pH and the acidity were measured 48 hours after the culture was to compare and study the acid production amount and the pH value at the maximum use of the oligosaccharide added to the medium by culturing for a long time.

4) Evaluation method Evaluation was based on the growth activity value calculated by the following equation.

Growth activity value = (medium turbidity increase) × (medium acidity) / (medium pH) In the above equation, “medium turbidity increase” means the degree of rapid growth of the main bifidobacteria. The “acidity of the culture medium” means the acid generating ability for the added oligosaccharide, and the “pH of the culture medium” means the pH lowering ability by utilizing the added oligosaccharide, and the growth activity value is determined by the above formula. These are compiled to comprehensively determine the effects of the three factors.

(3) Test Results The results of this test are as shown in Table 1. As is clear from Table 1, from the comprehensive evaluation results under the three conditions of the growth of the bifidobacteria in the mixed culture system, the increase in the acidity, and the decrease in the pH,
Raffinose had the highest growth activity value, followed by lactulose. However, the growth activity values of lactitol and galactooligosaccharide were low.

The same test as described above was carried out for other known oligosaccharides, such as fructooligosaccharides, xylo-oligosaccharides, lactosucrose, and isomaltooligosaccharides. ,
The effect was also inferior to raffinose and lactulose, and no good effect was observed for any of these oligosaccharides tested.

[0049]

[Table 1]

Preliminary Test 2 Next, it was confirmed by a test whether or not the “composition for improving the intestinal environment” described in JP-A-3-151854 matches the purpose of the composition of the present inventors.

(1) Test method As a test medium, the composition used in Experimental Example 3 of the above-mentioned publication, 6.6 parts by weight of soybean oligosaccharide (manufactured by Calpis Food Industry Co., Ltd.) 2.0 parts by weight of soluble hemicellulose (SANEI The following mixture corresponding to the composition used in Example 2 was also used as the composition A, and the following mixture corresponding to the composition used in Example 2: 1.25 parts by weight of polydextrose (manufactured by Carter Food Science) Stachyose 1 0.5 part by weight (manufactured by Nacalai Tesque, Inc.) Raffinose 0.5 part by weight (manufactured by Nippon Sugar Beet Co., Ltd.) was used as composition B, and 2% of each composition was added instead of glucose added to the medium. Except for the above, the test was performed by the same test method and evaluation method as the preliminary test 1.

(2) Test Results As a result, the growth activity value of composition A was 1.5, and the growth activity value of composition B was 1.6. From these values, the "composition for improving the intestinal environment" described in Japanese Patent Application Laid-Open No. 3-151854, in which an oligosaccharide was used in combination with dietary fiber, showed that the present inventor compared the results of preliminary test 1 with raffinose and lactulose. According to these evaluations, it was confirmed that no clear effect was exhibited on liver disease.

Preliminary Test 3 According to Preliminary Test 1, even when raffinose alone was used alone as an oligosaccharide used in a food composition for a patient with liver disease,
Although it was clear that it exceeded the known lactulose, the effect of the combination use of raffinose and lactulose was further examined by the same test method as in the preliminary test 1.

(1) Test method As a test medium, instead of glucose added to the medium,
The test was performed by the same test method and the same evaluation method as in Preliminary Test 1, except that thirteen types of culture media to which raffinose and lactulose were added in combination at the ratios shown in Table 2 (total 2%) were prepared and used.

(2) Test Results The results of this test are as shown in Table 2. If the growth activity values in Table 2 are determined by comparing with the growth activity values of raffinose and lactulose alone obtained in Preliminary Test 1,
From 1 part of raffinose to 10 parts of lactulose,
Up to 1 part lactulose for 10 parts raffinose,
Especially lactulose 1 to 12 for 6 parts of raffinose
It was found that by using both oligosaccharides in combination at a ratio of parts, a high growth activity value was obtained and the intestinal environment could be reliably improved.

[0056]

[Table 2]

Test Example 1 In this test, the food composition for a liver disease patient of the present invention was administered to a healthy adult, and the number of bifidobacteria in the feces and the occupancy rate of the bifidobacteria, fecal pH, fecal pH and blood It was performed to examine the amount of putrefaction products and the effect on liver function.

(1) Test Method A drink for a liver disease patient manufactured by the same method as in Example 1 was used for 20 healthy adults (age 29-59, average 49)
Was ingested twice a day (200 ml) for 2 weeks, and feces and blood of each subject were collected before and after the ingestion.

The measurement of the fecal flora and the measurement of the pH were performed according to the method of Mitsuoka (Toshimitsu Mitsuoka, “The World of Intestinal Bacteria”, Sosobunsha, 198
0 years). As shown in Table 3, stool decay products include ammonia, phenol, indole, skatole, etc., blood decay products include ammonia and indole, and blood hepatic function test.
OT and GPT were measured.

Ammonia was measured by a colorimetric method using an ammonia measurement kit (manufactured by Wako Pure Chemical Industries, Ltd.). Phenol, indole, skatole and other putrefaction products were quantified by the method of Yoshihara [Agricultural and
Agricultural and Bio
logical Chemistry), Vol. 45, 1873-1875
Page, 1981]. GOT and GPT were measured using a measurement kit (manufactured by Wako Pure Chemical Industries, Ltd.).

(2) Test Results The results of this test are as shown in Table 3. As is clear from Table 3, in all fecal measurement items such as phenol, indole, skatole, and ammonia, which were measured in feces, a decrease in fecal content was observed two weeks after ingestion. This indicates that the intestinal flora changed to a bifidobacteria-dominant flora, and that spoilage bacteria such as clostridium decreased, and that the growth of anaerobic bacteria such as Peptococcus and Bacteroides involved in the production of ammonia was suppressed. It is shown that. The results of the analysis of the microflora also showed an increase in the number of bifidobacteria and a significant increase in the occupancy of the bifidobacteria relative to the total number of bacteria 2 weeks after the administration, indicating a tendency consistent with the decrease in spoilage products. In addition, a decrease in the pH of feces was also apparent, suggesting that the absorption of ammonia from the intestinal tract was suppressed.

Also, the amount of spoilage products in blood is significantly reduced,
It became clear that these putrefaction products absorbed into the body were reduced. Regarding liver function, although the subjects were healthy adults, the measured values tended to decrease, confirming that they were effective in improving liver function. This is considered to be because the burden on the liver function was reduced due to the reduction of various toxins absorbed into the body.

Furthermore, all the 20 participants who participated in the test did not complain of any side effects such as diarrhea, abdominal pain and abdominal bloating during the period of ingesting the food composition (beverage) for patients with liver disease of Example 1. .

As described above, by administering the food composition for a liver disease patient of the present invention, it is possible to prevent hepatic encephalopathy and hyperammonemia in a liver disease patient by improving the intestinal environment without worrying about side effects. It has been clarified that it is also possible to improve the liver function associated with various liver diseases.

[0065]

[Table 3]

Test Example 2 This test was conducted to examine the inhibitory effect of the food composition for liver disease patients of the present invention on liver damage using an experimental animal model of liver damage due to drug administration.

(1) Test Method Eighty male Wistar rats weighing about 250 g (manufactured by Charles River Japan) were divided into the following two groups, and the following diets were administered. A continuous mixture of olive oil (manufactured by Nacalai Tesque) and carbon tetrachloride (manufactured by Nacalai Tesque) in an equal volume of 0.2 ml per 100 g body weight was intraperitoneally administered for 12 weeks. Every four weeks from the start of carbon tetrachloride administration, 10 mice were arbitrarily extracted from each group, and blood was collected by cardiac blood sampling under ether anesthesia, and plasma was obtained by centrifugation.

As a liver function test, GOT, GPT, total bilirubin, albumin, and total cholesterol were measured from the obtained plasma samples using a measurement kit (manufactured by Wako Pure Chemical Industries, Ltd.), and the degree of hepatocellular damage was measured. Tested.

1) Group 1 Protein (casein) 25%, fat (soy oil) 6%, carbohydrate (corn starch, cellulose, granulated sugar) 64
%, A mineral mixture (AIN-76 formulation) 3.5%, a vitamin mixture (AIN-76 formulation) 1%, methionine 0.3%, choline chloride 0.2%, a commercial feed (manufactured by Oriental Yeast Co., Ltd.) ) 95 parts were fed a diet to which 5 parts of corn starch was further added.

2) Group 2 A diet prepared by adding 5 parts of raffinose (manufactured by Nippon Sugar Beet Co., Ltd.) to 95 parts of the above commercial feed was administered.

(2) Test Results The results of this test are as shown in Table 4. As is clear from Table 4, at all test points, the rats in the second group had less liver damage than the rats in the first group, and the rats mixed with raffinose were administered with a diet mixed with raffinose. It is clear that liver injury due to carbon tetrachloride was suppressed.

Therefore, by administering the food composition for liver disease patients of the present invention, it is possible to prevent liver damage caused by various toxic substances and protect the damaged liver. Became clear.

The same test was carried out using 5 parts of an equal mixture of raffinose and lactulose (manufactured by Morinaga Milk Industry Co., Ltd.) instead of 5 parts of raffinose used as the diet to be administered to the second group. Almost the same results were obtained.

[0074]

[Table 4]

Test Example 3 In this test, a food composition for a patient with liver disease of the present invention was administered to a healthy adult, and raffinose, which was an active ingredient thereof,
And a mixture of raffinose and lactulose,
Perform to determine the desired daily dose, stool, fecal bifidobacteria count and bifidobacteria occupancy,
Fecal pH, GOT and GPT in blood, and physical condition after drinking were tested.

(1) Preparation of Sample A liquid food (liquid food A) in which the saccharide composition of the same liquid food for liver disease patients as in Example 4 was dextrin 4.5% and raffinose 10%, and dextrin 4. 5%, raffinose 5% and lactulose 5% were changed to a liquid food (liquid food B), and produced by the same method as in Example 4,
Used for testing.

(2) Test method Twelve healthy adults (age 35-59 years, average 50 years) were
Liquid food A was randomly divided into 6 groups of 2 persons each, and 10 ml, 30 ml, 50 ml, and 100 m of liquid diet A were given per day per week, respectively.
1, 150 ml and 200 ml in the morning from 9:00 to 1
At 2:00, they were allowed to drink continuously at an appropriate time. One week after the end of drinking of the liquid food A, the same 12 persons were again divided into 6 groups of 2 persons at random again, and the liquid food B was divided into 10 groups, 30 ml, 50 ml, 100 ml, and 15 groups per day per week, respectively.
In the amount of 0 ml and 200 ml, they were drunk continuously from 9:00 to 12:00 in the morning at an appropriate time.

Before and after the administration of the liquid diet A and before and after the administration of the liquid diet B, feces and blood of each subject were collected, and the flora, pH, GOT and GPT in the feces were measured.
The stool and physical condition (subjective symptoms) after administration of each liquid diet were investigated.

The measurement of each item of feces and blood was performed in Example 1.
The procedure was performed in the same manner as described above.

(3) Test Results The administration results of Liquid Meal A and Liquid Meal B are shown in Tables 5 and 6, respectively, as an average of one set of two persons. As is clear from Tables 5 and 6, in the groups in which 10 ml of liquid food A and B were ingested, the change in each measured value before and after drinking was small, and at least 30 ml (3 g as an active ingredient) or more, particularly 5 g or more per day was administered. It turned out to be desirable.

In addition, liquid food A and liquid food B were both 50
ml (5 g as an active ingredient) or more
Up to the group that drank 0 ml (20 g as an active ingredient), significant improvement was observed in the numerical values of each test item almost according to the dose. In addition, neither liquid food A nor liquid food B showed any noticeable side effects such as physical condition at any dose.

On the other hand, in preparing the tested liquid foods and various food compositions described in the other examples, the content of the oligosaccharide was adjusted to 15% in order to appropriately mix proteins, fats and other components as foods. If the concentration is too high, there is a high possibility that adverse effects on production such as collapse of nutritional balance, excessive sweetness, lack of stability as a composition, and generation of browning due to high-temperature heat treatment will occur.

Accordingly, in view of the results of this test and the above-mentioned problems in production, one of the food compositions for patients with liver diseases of the present invention
It has been found that a daily dose in the range of 3 to 15 g, especially 5 to 10 g, is desirable.

[0084]

[Table 5]

[0085]

[Table 6]

[0086]

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

Example 1 2.0 kg of skim milk powder, 8.5 kg of sucrose, caramel 0.1 kg
2kg, Raffinose 1.5kg, Stabilizer (CMC)
0.35 kg of citric acid and 0.35 kg of citric acid in 87.1 water
The resulting mixture was mixed and dissolved in water, sterilized on a plate at 95 ° C. for 10 seconds, cooled, filled into a 100 ml bottle, and 950 nonfermented acid milk type beverages for patients with liver diseases were produced.

Except for raffinose (manufactured by Nippon Sugar Beet Co., Ltd.), all commercial products were used.

Example 2 A cookie for a liver disease patient having the following composition was produced by a conventional method. Wheat flour 25 (g / 100 g) whole egg 5.0 skim milk powder 2.5 soy protein 1.5 margarine 16 butter 12 powdered sugar 20 raffinose 10 lactulose 1 crystalline cellulose 3 salt 0.1 iron citrate 0.005 vitamins 0. 5 Emulsifiers, spices, etc. Trace amounts In addition, all commercial products were used except for raffinose (manufactured by Nippon Sugar Beet Sugar Co., Ltd.) and lactulose (manufactured by Morinaga Milk Industry Co., Ltd.)

Example 3 2 kg of raffinose (manufactured by Nippon Sugar Beet Co., Ltd.), 12 kg of lactulose powder (manufactured by Morinaga Milk Industry Co., Ltd.), and 100 bifidobacterium powder (manufactured by Morinaga Milk Industry Co., Ltd., 10 ¹⁰ cells / g of bifidobacteria)
g, DHA powder (manufactured by NOF Corporation) 200 g, vitamins (commercially available, a mixture of vitamins A, D, E, and K) 15 g,
In addition, a total of 85 kg of dextrin (manufactured by Asahi Foods) as an excipient, sucrose fatty acid ester (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), a sour agent and a flavor as a binder are uniformly mixed,
After tableting, about 1 tablet. 5 g of nutritional supplement for patients with liver disease 6
I got ten thousand.

Example 4 A liquid diet for patients with liquid liver disease having the following composition was produced by a conventional method. Protein Milk protein 1.5 (g / 100 ml) Protein degradation product 2.0 Branched chain amino acid mixture 1.0 Arginine 0.3 Lipid Regulated fat 2.0 Carbohydrate dextrin 11.5 Raffinose 1.5 Lactulose 1.5 Vitamins 0.3 Minerals 0.6 Others (flavors, etc.) Trace amounts All commercial products were used except for raffinose (manufactured by Nippon Sugar Beet Sugar Co., Ltd.) and lactulose (manufactured by Morinaga Milk Industry Co., Ltd.).

Example 5 800 g of a hot cake mix sieved three times, 60 g of raffinose, 40 g of lactulose, 100 raisins
g and water (800 g) were mixed, divided into 80 pieces, and steamed with high heat using a steamer to obtain about 20 g of steamed bread for a patient with liver disease of about 20 g.

Raffinose (manufactured by Nippon Sugar Beet Sugar Co., Ltd.)
Except for lactulose (manufactured by Morinaga Milk Products), all commercial products were used.

[0094]

Industrial Applicability As described above in detail, the present invention relates to a food composition to be administered to a patient with a liver disease, wherein the raffinose content in the composition is at least 1% (by weight). And a food composition for a liver disease patient, wherein the total content of raffinose and lactulose in the composition is at least 1% (by weight) in a composition to be administered to a patient with a liver disease. The effects that can be achieved are as follows. 1) The food composition for liver disease patients of the present invention can reduce the burden of liver function by effectively improving the intestinal environment of liver disease patients. 2) The food composition for liver disease patients of the present invention can suppress the generation of toxic substances such as ammonia in the intestinal tract and the absorption of toxic substances from the intestinal tract into the body. 3) The food composition for a liver disease patient of the present invention can suppress hepatocyte damage. 4) The food composition for liver disease patients of the present invention has no side effects such as diarrhea and loose stool. 5) The food composition for a liver disease patient of the present invention has low sweetness and is easy to ingest. 6) The food composition for liver disease patients of the present invention can be processed into various foods such as, for example, fluid foods and nutrients.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI A23L 2/38 A23L 2/38 P A61K 31/70 ACS A61K 31/70 ACS A23L 2 / 00F (72) Inventor Toshio Ohashi Kanagawa 5-1-83 Higashihara, Zama City, Japan Morinaga Milk Industry Food Research Laboratory Co., Ltd. (72) Inventor Mitsunori Takase 5-1-83 Higashihara, Zama City, Kanagawa Prefecture Morinaga Milk Industry Nutrition Science Research Institute Co., Ltd. (72) Inventor Hirohiko Nakamura Kanagawa 5-183 Higashihara, Zama City, Japan Morinaga Milk Industry Nutrition Science Research Institute, Inc. (72) Inventor Koji Sayama Inada-cho, Inada-cho, Hokkaido

Claims (5)

[Claims] 1. A food composition to be administered to a patient with liver disease, wherein the raffinose content in the composition is at least 1%.
(Weight) a food composition for a liver disease patient. 2. The composition according to claim 1, wherein the raffinose content is 3 to 1.
The food composition for a liver disease patient according to claim 1, which is 5% (by weight). 3. A food composition to be administered to a patient with liver disease, wherein the total content of raffinose and lactulose in the composition is at least 1% (by weight). 4. The food composition for a liver disease patient according to claim 3, wherein the total content of raffinose and lactulose in the composition is 3 to 15% (weight). 5. The method according to claim 3, wherein the raffinose is at least 1 part by weight based on 10 parts by weight of lactulose.
And the food composition for liver disease patients according to claim 4.