JPH06219953A - Medicine for preventing and improving diarrhea, food for preventing and improving diarrhea and feed for preventing and improving scours - Google Patents

Abstract

PURPOSE:To provide a medicine for preventing and improving diarrhea, having an effect on prevention and improvement of diarrhea frequently breaking out when an intestinally absorbed medicine for promoting nutrition, a concentrated fluid food, a medicine such as an antibiotic, etc., are administrated and to provide a food and a feed for the same purpose. CONSTITUTION:Cellulose powder is used as the active component and the particle diameter thereof is preferably <=200mum and >=5mum. Celluolose powder containing particles of <=200mum and >=5mum particle diameter in an amount of >=75wt.% based on the whole cellulose powder is more preferably used.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention is effective for the prevention and improvement of diarrhea that often occurs at the time of administration of enteral nutritional supplements, concentrated nutrient liquid foods, etc., or administration of medicines such as antibiotics.
The present invention relates to an orally administrable preventive / improving agent, a diarrhea-preventing / improving food and a diarrhea-preventing / improving feed.

[0002]

2. Description of the Related Art Enteric bacteria of a recipient when a high-nutrition / low-residue diet such as an enteral nutritional supplement, a concentrated nutrient liquid diet, a component nutritional supplement (elemental diet), or a drug such as an antibiotic is administered. It is known that diarrhea often occurs due to changes in the flora. This type of diarrhea is caused by a decrease in residual solids derived from ingested food that is not absorbed and remains in the intestine, or by remarkable intestinal microorganisms that occur especially when oral antibiotics or bile excretion-type intravenous antibiotics are administered. Often due to a large decrease. In any case, due to the relative increase in free water in the intestine, the properties of feces change to watery or mud-like, leading to diarrhea.

With attention paid to the above-mentioned mechanism, attempts have been made to increase the solid content in the intestinal contents to relatively reduce free water and normalize the properties of feces.
Further, in order to increase the solid content, oral administration is possible, and an indigestible or intestinal absorbable substance has been administered alone or in the diet. Examples of the substance include various water-soluble fibers, such as pectin, methoxypectin, galactomannan, alginic acid, the same salt, agar, carboxymethyl cellulose, the same salt or foods containing these substances or various non-water-soluble fibers. , For example, cellulose powder, hemicellulose powder, and mixtures thereof.

However, the physiological or psychological resistance or difficulty of the recipient to the administration of the above substances is unavoidable, and when the administration is accompanied by a slight foreign body sensation, it is effective. Was impossible to administer. In addition, the effective doses of these substances are unexpectedly large, which imposes psychological compulsion on the recipient. Furthermore, the intestinal environment of the recipient differs individually, and it has been difficult to determine in advance the type and dose of the substance to be administered that is suitable for the particular recipient.

[0005] In addition, regarding the knowledge as to what state the maximum effect is observed when the water-insoluble fiber is administered in the intestine, sufficient knowledge has not yet been obtained. .

[0006]

DISCLOSURE OF THE INVENTION The present inventors reexamined the above-mentioned problems existing in the past, and further studied various substances which have been conventionally used from a new viewpoint. In addition, based on new findings obtained from animal experiments and clinical tests described below, the invention relating to a diarrhea prevention / improvement agent, a diarrhea prevention / improvement food and a diarrhea prevention / improvement feed was completed.

That is, the present invention solves the problems in the above-mentioned conventionally used preventive agents and ameliorating agents for diarrhea, prevention and amelioration of diarrhea symptoms, and treatment methods, and is easily accepted by the recipient. An object is to provide an orally administrable diarrhea prevention-improving agent, a diarrhea prevention-improving food and a diarrhea prevention-improving feed, which can be expected to be maximally effective in the smallest possible amount and can be easily prepared.

[0008]

The diarrhea preventive and ameliorating agent according to the present invention comprises a cellulose powder as an active ingredient, preferably a cellulose powder having a particle diameter of 200 microns or less and 5 microns or more as an active ingredient. Is. More preferably, cellulose powder having a particle size of 200 microns or less and 5 microns or more is contained at 75% or more of the total cellulose powder.

Further, in the present invention, as the cellulose powder, a plant-derived powder or a microbial-derived powder is disclosed. Also disclosed is one in which the cellulose powder contains hemicellulose.

Furthermore, in the present invention, not only a diarrhea prevention-improving agent in which the above-mentioned diarrhea-preventing / improving agent is dispersed / blended, preferably a diarrhea-preventing / improving agent in which the above-mentioned diarrhea-preventing / improving agent is uniformly dispersed / blended is used. , A diarrhea prevention-improving food in which the above-mentioned diarrhea prevention-improving agent is dispersed / blended in food, preferably a diarrhea-prevention-improving food in which the above-mentioned diarrhea-preventing / improving agent is uniformly dispersed / blended in food, and the above-mentioned diarrhea Also disclosed is a diarrhea-prevention-improving feed in which a preventive-improving agent is dispersed / blended in a feed, preferably a diarrhea-prevention-improving feed in which the above-mentioned diarrhea-preventing / improving agent is uniformly dispersed / blended in a feed.

[0011]

Although cellulose powder has been used as a diarrhea-improving agent or a constipation-improving agent, it has a specific particle size for preventing or ameliorating diarrhea that occurs especially when a low-residue nutritional diet or antibiotics is administered. There is no finding confirming the effect of the cellulose powder in the range and the dynamic particle size distribution range.

The present inventors questioned the recognition of the effect of the conventional cellulose powder, conducted various experiments and analyzed and examined the results to improve the symptoms of diarrhea of the cellulose powder. Surprisingly, the effects are: 1. It does not depend on the type of cellulose, 2. Having a direct relationship with the distribution of the particle size of the cellulose powder particles, 3. The particle size range is 200 microns or less and 5 microns or more; 4. The effective cellulose powder contains particles in this range as a main category and contains 75% or more of the particles. Furthermore, the particle size distribution is relatively clear, and the presence of particles significantly exceeding 200 microns, which makes the recipient feel a foreign body, is not preferable, and it should not exceed 5% at the maximum. If less than 20% of fine particles are present, the rheology in the oral cavity becomes abnormal,
5. Not as preferable as the case of coarse particles, 6. It has been found that the most effective results are obtained when the administered cellulose powder is present in the intestine as uniformly dispersed as possible.

Therefore, in the present invention, cellulose powder is used as an active ingredient, and preferably cellulose powder having a particle diameter of 200 microns or less and 5 microns or more is used as an active ingredient. More preferably, it contains 75% or more of the cellulose powder having a particle size of 200 microns or less and 5 microns or more of the total cellulose powder, so that it is easily accepted by the recipient and the maximum effect can be expected with the smallest possible amount. In addition, an orally administrable diarrhea-preventing and improving agent for improving and preventing diarrhea that can be easily prepared can be obtained.

The preventive-improving agent of the present invention needs to be orally administrable. However, in order to avoid the foreign body sensation and drug sensation that the recipient tends to feel, normal diet and concentrated nutrition are required. It is advisable to administer it in a liquid diet, enteral nutrient, etc. as uniformly mixed as possible. Of course, when there is no psychological burden on the recipient, it is possible to administer the cellulose powder in a powder state as a suspension syrup, or as a readily degradable or easily degradable tablet. Since the maximum effect is observed when the cellulosic powder is rapidly and uniformly distributed in the intestinal contents after administration, it is administered as a preparation uniformly mixed with the above oral administration before administration. Is appropriate. Further, when the occurrence of diarrhea can be predicted by the administration of meals or drugs, pre-administration of the preventive and amelioration agent of the present invention is effective for the prevention of diarrhea.

The dose of the cellulose powder is determined depending on the symptoms and general condition of the recipient, but is preferably 5 g or more and 40 g or less per adult. In addition, the amount of infants or the elderly may be ½ of the above amount. Further, the administration is started at a small dose at first and then the dose is increased or decreased while observing the improvement state of symptoms. Administration exceeding this range may give the recipient a feeling of foreign body, and in some cases may exacerbate the symptoms of diarrhea. In addition, it is difficult to recognize the effect when administered in a small amount below the range. Furthermore, even if an attempt is made to administer an effective amount of cellulose powder that greatly exceeds the above-mentioned particle size range, psychological resistance is generally large and administration becomes difficult. Moreover, it becomes difficult to prepare a preparation in which cellulose powder is uniformly dispersed at the time of administration.

[0016] In administration, cellulosic
It is desirable to prepare a fresh powder by uniformly mixing the powdered powder with food, liquid food, nutritional supplement, etc., but if it is possible to maintain the homogeneity for a considerable time after adjustment, administer several doses. The amounts may be prepared in bulk. In addition, even when the cellulose powder is administered in the form of powder, suspension syrup, or easily degradable tablet, a suitable dispersion medium should be provided so that the cellulose powder is quickly and uniformly distributed in the intestinal contents after administration. Alternatively, it should be administered in the state of being uniformly mixed and dispersed with a dispersion aid.

The cellulose powder used in the present invention is usually an easily conceivable cellulose powder, for example,
In addition to filter paper powder, purified cellulose powder for pharmaceutical additives, purified cellulose powder for pharmaceutical preparations, purified cellulose powder for addition of ordinary foods or functional foods, purified rayon powder, it contains a considerable amount of hemicellulose. It includes unrefined cellulose, that is, wheat bran powder, barley kernel powder, soybean seed powder, corn kernel powder, cotton linter powder, multifilament vegetable powder, fruit powder refined powder and the like. In addition, in the unpurified cellulose powder, in addition to hemicellulose, a small amount of pectin, chitin,
It also includes the case of containing lignin and the like. Furthermore, in addition to the cellulosic powder derived from these plants, microorganisms such as acetic acid bacteria and Acetobacter xylinum (Acetob) are also available.
cellulosic powder derived from a microorganism produced by Acterxylinum).

[0018]

Examples (Example 1, Animal Experiments 1) SD male rats aged 8 weeks were treated with a concentrated nutrient liquid diet “Mediflu Liquid [Ajinomoto Co., Inc. product]” 40 for 1 week using a drinking water column.
The animals were bred under a restricted diet condition of Kcal / day. After 6 days, the occurrence of watery feces or mud-like feces was observed in all the test animals. After 7 days, the animals were divided into the following 5 groups, each group consisting of 5 animals, and the animals other than the control group were treated with the feed containing 5% by weight of the additive shown in the group name in the liquid diet. The animals were raised for the next week while feeding under the same feeding conditions. In addition,
The feed was prepared daily at 4 pm and fed immediately.
The preparation was carried out by stirring the above liquid food and a predetermined amount of additives with a Waring blender for 1 minute while cooling with ice.

Composition of experimental animals and additives: 1. Control group ----- no additives 2. Pectin group --- A polysaccharide whose main component is methoxypectin. Food additive purity. M. W. , 50 to 10 million 3. Galactomannan group --- A polysaccharide derived from "konjac". For adding functional foods. M. W. , 0.2 to 30 thousand 4. Cellulose group --- A vegetable fiber powder derived from "pulp". 200 to 5 micron classification, 90% or more. Food additive purity. M. W. , 1.0 to 10 million 5. Carrot powder group --- "Carotte" [trade name, product of Ajinomoto Co., Inc.]. The polysaccharide containing M. W. , 60.0-18
0.0 million (MW: average molecular weight distribution of polysaccharide contained in additive)

The experimental results are as follows: Control group -------- Symptoms of diarrhea worsened. During the experimental period, all heads are watery or mud-like stools on all days 2. Pectin group --- No improvement in diarrhea symptoms was observed.
3 out of 5 were worse. Galactomannan group: No improvement in diarrhea symptoms was observed. Four out of five became worse. 4. Cellulose group --- Improvement of diarrhea symptoms is remarkable. All 5 were normal stools during the last 2 days. 4. From the second day after administration, an improvement effect is recognized 5. Carrot powder group --- Some improvement effect is recognized. 2 to 3 normal stools each day during the last 2 days

(Example 2, animal experiment 2) S of 8 weeks old
For 1 week, D strain rats were treated with the antibiotic "cefoperazone sodium; CPZ" aqueous solution, CPZ 1 mg / 100 g
Experimental feed "CRF-1", which was added in an amount equivalent to that of the feed and was in a semi-wet state [trade name, Oriental Yeast Co., Ltd.
The product was raised under free feeding conditions. After the experiment started,
On the second day, about 30% of animals develop watery or mud-like stools,
On the 7th day, all diarrhea showed marked diarrhea. On the 7th day, the animals were sorted into the following 4 groups, each consisting of 5 animals, and for the animals other than the control group, the additives shown in the group name were added to the above feed at 5% by weight per dry matter and mixed. The fed feed was fed under the same feeding conditions as above, and the animals were bred for the next week.
The feed was prepared every day at 4:00 pm and fed immediately. In addition, the amount of food remaining was measured when new feeding was performed.

Composition of experimental animals and additives: 1. Control group ----- no additives 2. Lactic acid bacteria group --- Live lactic acid bacteria (* 1) 3. Soybean oligosaccharide group-soybean oligosaccharide powder (* 2) 4. Cellulose group- "Biocellulose" powder, 20
0 micron to 5 micron classification 90% or more (* 3) (* 1) Wet viable cells obtained by culturing, centrifuging and collecting the lactic acid bacteria separated from commercially available plain yogurt in a glucose whey medium supplemented with milk. (* 2) Dry powder of oligosaccharides separated from soybean whey, which is a by-product of soybean isolated protein production. (* 3) Acetobacter, Acetobacter-Xylinum (Ac
Microbial cellulosic powder obtained by culturing etohobacter xylinum) in a sucrose medium under stirring conditions, collecting the resulting cellulose membrane, drying, and crushing at high speed under cooling with liquid nitrogen.

The experimental results are as follows: Control group -------- Diarrhea symptoms worsened. During the experiment period, all the animals have a large amount of watery or mud-like stools all day. One animal died two days after the start of the experiment and two died on the fourth day. The colonic contents of all the heads were mud-like stool and the adhesion of mucous membrane was remarkable. 2. Lactobacillus group ----- Improvement of diarrhea symptoms is not remarkable. However, only one animal recovered to loose stool. Except for the same animal, all 4 colonic contents were mud-like stools. 3. Soybean oligosaccharide group-Diarrhea is not significantly improved. However, only one animal recovered to loose stool. Except for the same animal, all 4 colonic contents were mud-like stools. 4. Cellulose group--Remarkably improved diarrhea. On the last day, all 5 were normal stools. The effect is recognized from the second day after the start of the experiment. All colonic contents are solid normal stools.

(Control Example 1, Animal Experiment 3) 4. The plant fiber powder administered to the cellulosic group, the remaining sieve-unpassed section obtained by separating the 200-micron to 5-micron section were used in Examples 1, 4. A similar preparation was obtained by adding to the concentrated nutrient liquid food of the same composition used in the cellulose group. While providing this preparation to 10 rats bred under the same conditions as in Example 1 and exhibiting watery or mud-like stools, the following 1
It was raised for a week.

During the experimental period, all heads exhibited watery or mud-like stools all day, and no improvement effect on diarrhea was observed. After 1 week of experimental breeding, the results of autopsy of 5 diarrhea symptoms
All 5 colonic contents were watery stools, and the mucosal attachment was remarkable.

Example 3 Clinical Trial 1 A 45-year-old male patient who underwent subtotal gastrectomy and administration of cephalosporin antibiotics had diarrhea symptoms of soft stool and then watery feces continuously before the operation. I was presenting. After the 3rd day after the operation, a food additive-purified cellulose powder (“pulp” refined product) having a particle size of 200 μm or less and 5 μm or more is skimmed milk powder and other nutrient components containing necessary nutrients as main components. For food, under sterile conditions,
Orally administered after uniformly adding and mixing. The dose of cellulose was 9 g / day on the 3rd day and 12 g / day on the 4th day and thereafter. Improvement of diarrhea symptoms was observed after the 5th day,
By day, she recovered to a loose stool condition similar to normal stool. In addition, the general findings were also improved with the improvement of diarrhea.

(Comparative Example 2, clinical test 2) The remaining non-passage fraction of the 200 μm to 5 μm fraction of the cellulose used in Example 3 was taken as the concentrated nutrient flow of the same composition as in Example 3. The preparation added to the diet and mixed was administered to the same patient on days 8 and 9. At the time of administration on the 8th day, the patient complained of a foreign body sensation in the mouth, but ingested a prescribed amount of nutritional liquid food, but at the time of the administration on the 9th day, the patient barely took about half the amount due to the foreign body sensation. .

On the 8th day, loose stools similar to normal stools were maintained, but on the 9th day and the 10th day, diarrhea was exhibited. Therefore, from the 10th day onward, the same nutrient flux as in Example 3 was applied. A prescribed amount of food preparation was administered. From the 11th day onward, the patient recovered to loose stools, and improvement in diarrhea was noted.

(Example 4, preparation of preventive and ameliorating agent 1) Concentrated nutrition liquid food "Medief Liquid" containing an amino acid mixture, lipid, sugar, vitamins and minerals as main components [Product name: Ajinomoto Co., Inc. product] 50 g of cellulose powder having a particle size of food additive purity of not more than 200 μm and not more than 5 μm was divided into 1 kg and mixed little by little and stirred to obtain a uniform fluid suspension. The mixing was carried out by aseptic stirring in a large Waring blender whose outside was cooled with ice water for 1 minute at a high speed. The obtained fluidized suspension was dispensed in an aseptic vertical transparent glass container in an amount of about 200 ml, sealed, and then stored in a refrigerator kept at an internal temperature of 5 ° C. for 2 days. After 2 days, it was taken out of the room and left to reach room temperature. No precipitate was found in the contents or the components were not separated.

(Example 5 : Preparation of preventive / improving agent 2) In place of the cellulose powder of Example 4, acetic acid bacteria, Acetobacter xylinum (Acetobacter x)
(ylinum) is cultured in a sucrose medium under stirring conditions, and the produced cellulose membrane is collected, dried, and then added with microbial cellulose obtained by high-speed crushing under liquid nitrogen cooling, and homogenized by the same method. A fluid suspension was obtained. This suspension also
Under the same storage conditions and storage period as in Example 4, no precipitation or separation of components was observed.

(Comparative Example 3, Preparation of preventive and ameliorating agent 3) According to the method of Example 4, the remaining cellulose powder of the 200 μm to 5 μm fractions, which was not passed through the sieve fraction, was uniformly mixed. A concentrated nutrient liquid food preparation was obtained. When the preparation was stored according to the storage method of Example 4, a change in state was observed in the upper layer or the lower layer of the container contents in the refrigerator the next morning, and when the container was taken out indoors and left to reach room temperature, Generation of a wavy precipitate was observed in the lower layer and bottom.

[0032]

EFFECTS OF THE INVENTION When the diarrhea prevention / improvement agent, diarrhea prevention / improvement food and diarrhea prevention / improvement feed of the present invention are administered to a patient or animal exhibiting diarrhea symptoms, the diarrhea symptoms can be rapidly improved. In particular, a remarkable effect is often observed in the prevention and amelioration of diarrhea that often occurs during the administration of enteral nutritional supplements and concentrated liquid diets.

Claims (12)

[Claims] 1. A preventive and / or preventive agent for diarrhea containing cellulose powder as an active ingredient. 2. A diarrhea preventive and ameliorating agent comprising a cellulose powder having a particle diameter of 200 microns or less and 5 microns or more as an active ingredient. 3. A preventive and / or preventive agent for diarrhea, which comprises cellulose powder having a particle size of 200 μm or less and 5 μm or more in an amount of 75% or more of the total cellulose powder. 4. The agent for preventing and improving diarrhea according to claim 1, wherein the cellulose powder is derived from a plant. 5. The agent for improving and preventing diarrhea according to claim 1, wherein the cellulose powder is derived from a microorganism. 6. The diarrhea preventive and ameliorating agent according to claim 1, wherein the cellulose powder contains hemicellulose. 7. A diarrhea prevention-improving agent comprising the diarrhea prevention-improving agent according to any one of claims 1 to 6 dispersed and mixed therein. 8. The diarrhea prevention-improving agent according to claim 7, wherein the diarrhea prevention-improving agent according to any one of claims 1 to 6 is uniformly dispersed and blended. Agent. 9. A diarrhea prevention-improving food, comprising the diarrhea prevention-improving agent according to any one of claims 1 to 6 dispersed and mixed in the food. 10. The diarrhea prevention-improving food according to claim 9, wherein the diarrhea prevention-improving agent according to any one of claims 1 to 6 is uniformly dispersed and mixed in the food. Diarrhea preventive improvement food. 11. A diarrhea-preventing and improving feed comprising the diarrhea-preventing and improving agent according to any one of claims 1 to 6 dispersed and mixed in the feed. 12. The diarrhea prevention-improving feed according to claim 11, wherein the diarrhea prevention-improving agent according to any one of claims 1 to 6 is uniformly dispersed and mixed in the feed. Diarrhea prevention feed.