JPH07308151A - Apparatus for producing composition effective for improving intestinal bacterial flora and its system - Google Patents

Abstract

PURPOSE:To provide a preparation apparatus provided with a vessel main body for culturing microorganism on a culture medium and a heater placed on the bottom of the main body, effective for uniformly proliferating the microorganism on the whole area of the medium and useful for the preparation of a composition containing microorganisms useful e.g. for the improvement of intestinal bacterial flora. CONSTITUTION:This apparatus for the preparation of a composition containing the objective microorganism is provided with a vessel main body 10 for culturing microorganism on a medium and consisting of an outer vessel 12 and an inner vessel 14 inserted into the outer vessel 12 interposing a proper gap therebetween, nichrome wire heaters placed between the inner wall of the outer vessel 12 and the outer wall of the inner vessel 14 and between the bottom of the outer vessel 12 and the bottom of the inner vessel 14 and a timer circuit connected to the vessel main body 10. The apparatus is preferably used for the cultivation of human intestinal bacteria belonging to the genus Streptococcus, etc.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is an anti-allergic agent by improving the intestinal flora by fermenting the intestinal flora on an edible medium (may be referred to as bacterial growth or culture). The present invention relates to an apparatus and a system for producing a composition (food or drug) that achieves an action. Specifically, edible media (eg milk products such as milk, other nutrient media such as soymilk) contained in the container body are mixed with microorganisms and fermented to produce products such as foods containing microorganisms. To do.

[0002]

2. Description of the Related Art Allergies such as hay fever and atopic dermatitis, which have been rapidly increasing in recent years, have been considered as diseases of the immune system. However, since the cause and the mechanism of its onset are not known yet, a fundamental and effective treatment method has not been established, and the reality is that the treatment is symptomatic.

In recent years, the relationship between the immune system and other organs has been gradually clarified, and it has come to be considered that the immune system functions while being closely related to other organs.

[0004] For example, it is known that the immune system is affected by the cranial nervous system via hormones, and that the activity of natural killer (NK) cells is reduced under conditions of high mental stress (Matsuda). , Hirano, Brain and Immunity (Metabolism, Vol. 26, Special Issue, pages 45 to 61), R. Ader
Et al. Interactions betw-ee
n the brain and the immune system) Annual Report of Pharmacology and Toxicology (Annu. Rev. Phama-col. Toxicol.) 1990.30, 561.
602).

The Peyer's patches present in the intestine are important tissues that control the immune system by the antigen components present in the digestive organs, and it is considered that the intestinal tract and immune functions are deeply involved.

Regarding allergies, it is necessary to comprehensively consider the relationship with other organs and the relationship with the living environment. From the above viewpoints, the present inventors have been treating patients with allergic diseases for many years, and have obtained the following findings.

Noget Ear Examination (Blu Dior Translated by Yukio Nagasu Ear Needle Method-P. Nozier's Theory and Clinical (Published by Enterprise Co., Ltd. in 1985), Nozier Ikuhiro Fukuda Translation of Auricles, 1989 Issued by Taniguchi Shoten , Min Han Cho, Theory and Clinic of Ear Needle Method in Europe and America in 1979.
Although many have no subjective symptoms, they have abnormalities in the digestive organs, mainly the intestinal tract, and at the same time are in a state of being mentally stressed by an interview. That is, there are many people who have constipation or its tendency, or conversely, are likely to have diarrhea, and excrete stool or gas having an abnormally strong odor.

In summary, it has been found that many patients with allergic diseases actually have abnormalities in the intestinal flora and intestinal damage. The intestinal flora and gastrointestinal epithelium easily become abnormal due to mental stress and are easily damaged.

The present inventor has treated various diseases caused by autonomic imbalance by means of electrification from the ear and cured extremely excellent treatment results. However, in allergic diseases, electrification and anti-inflammatory to skin. Although a therapeutic effect was obtained by applying the agent and its combined use, it often took a long treatment period.

In recent years, it has been often pointed out that pesticides, antibiotics, synthetic antibacterial agents and the like, which are frequently used in the fields of agriculture, fisheries and livestock, remain in foods, and these are also enteric. It is a factor that damages the flora. Modern people are in a situation where intestinal bacteria are prone to abnormalities. It is considered that abnormalities of intestinal microbiota and damage to the mucosal epithelium adversely affect the immune system, nervous system, and metabolic system, causing various damages of allergic diseases in a cyclical manner.

Conventionally, there are intestinal regulating agents containing intestinal bacterial flora, but these are insufficient in improving the intestinal bacterial flora due to a small number of bacterial species or a small number of bacteria. Therefore, no consideration is given to allergic diseases.

[0012]

Therefore, the present invention, for the purpose of providing a composition capable of treating and preventing allergic diseases by improving the intestinal flora, applied for a patent in 1993. No. 339097 was proposed. Among these, the present inventors have described that such a composition is preferably a fermented edible normal medium using enterobacteria.

Conventionally, as an apparatus for realizing this type of fermentation, there has been an apparatus for producing yogurt by adding lactic acid bacteria to milk. This type of device is configured such that the container is covered with a heat insulating lid and the contents in the container can be heated at a constant temperature.

In order to produce yogurt using this apparatus, milk is first put in a pan or the like and sterilized by boiling,
Put the pan and water in a bowl filled with water and cool the heated milk to about 40 to 45 ° C. Next, the lactic acid bacterium is put into milk in a pan and stirred, and this is put into an inner container of a yogurt maker and heated at a fermentation temperature for a predetermined time.
Then, after fermentation, it is cooled in a refrigerator.

Since the conventional device is such,
It requires time and labor to boil and disinfect milk, and it is very inconvenient and troublesome to clean up the pan and the like.

Therefore, as disclosed in Japanese Utility Model Publication No. 60-38382, the main body is divisible into an upper body and a lower body, and the inside is 1000 cc in a state where both are connected.
A yogurt making machine has been proposed which can store a packed milk pack and can store a 500 cc milk pack in the lower body in a state where the both are divided.

Therefore, according to this conventional apparatus, the milk pack can be opened, mixed with the fermenting bacteria, and then immediately sealed and set in the main body as it is. Therefore, as in the conventional case, the milk is put in another pan and boiled. Not only does it need to be cooled, but since it does not use a pan, it can save the trouble of disinfecting with hot water and cleaning up.

However, in this type of conventional apparatus, the milk that is the medium cannot be heated uniformly,
There is a problem that fermentation (culture or growth of bacteria) proceeds in the heated portion, whereas fermentation does not proceed in the insufficiently heated portion. Therefore, there is a problem in that the properties of the product after fermentation become uneven, such as milk partially becoming yogurt-like.

Of course, it is conceivable to lay a heater in all the areas in contact with the milk pack, but this causes an increase in the size of the manufacturing apparatus and an increase in cost.

The present invention has been made for the purpose of solving the technical problems described here. That is, the present invention, an apparatus for producing a microorganism-containing composition capable of uniformly heating a mixture of the nutrient medium and the microorganism when culturing the microorganism in a medium that serves as a nutrient for the growth of the microorganism, and The purpose is to provide a system for.

[0021]

Means and Actions for Solving the Problems The present inventor has found that in allergic diseases such as atopic dermatitis and hay fever that are not known to cause, stress coming from cranial nerves and abnormal intestinal bacterial flora present in the digestive tract It was found that and are often interrelated, and it was found that ingestion of intestinal bacteria has a great effect on the treatment or prevention of allergies.

Here, the enterobacteria mean various non-pathogenic bacteria existing in the human intestinal tract, such as Streptococcus, Enterococcus, Bifidobacterium,
The bacterium is preferably included in at least one genus of Lactobacillus and Clostridium. More preferably, it includes bacteria of all these genera.

By ingesting or taking these intestinal bacteria, the intestinal microflora is improved and it becomes possible to treat or prevent allergic diseases. In this application, the anti-allergic action includes not only the treatment of allergies but also the prevention of allergies (maintaining the state where allergies are treated).

The antiallergic action is atopic dermatitis,
It provides good therapeutic and preventive effects against various allergic diseases such as hay fever, respiratory diseases such as allergic rhinitis, and allergies caused by drugs, or symptoms that may cause them.

The improvement of intestinal flora means not only normalizing intestinal bacteria (number of intestinal bacteria, balance of intestinal bacterial species, etc.) but also normal intestinal flora. It also includes actively maintaining or supplementing intestinal bacteria. The improvement of the intestinal microflora itself leads to the antiallergic effect as described above, and also leads to a wide range of effects such as intestinal regulating action, nourishing and tonic action, physical strength promotion / maintenance, and beauty and health. The intestinal bacterium is preferably 100 billion or more in daily intake.

As the bacterial species belonging to any one of the genus Streptococcus, the genus Enterococcus, the genus Bifidobacterium, the genus Lactobacillus and the genus Clostridium (the bacterial species belonging to the present invention), Enterococcus faecalis, Enterococcus faecium, Enterococcus -Durans, Enterococcus evium, Streptococcus salivarius, Streptococcus bovis, Streptococcus iknuus, Lactobacillus acidophilus, Lactobacillus gasserie, Lactobacillus salivarius, Lactobacillus reutivarii, Lactobacillus reuteribacillus, Lactobacillus reuteri, Lactobacillus Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium adresene Offices, Bifidobacterium Infantes, can be exemplified Bifidobacterium bifidum and the like.

The intestinal bacteria may include other intestinal bacteria such as known yogurt bacteria. Examples of such yogurt bacteria include at least one of Streptococcus thermophilus and Lactobacillus bulgaricus.

Specific examples of strains are Enterococcus faecalis ATCC 19433, Enterococcus faecium ATCC 19434 and Enterococcus durans.
IID 677, Streptococcus salivarius IID 5223
, Enterococcus hirae ATCC 8043, Enterococcus hirae ATCC 9790, Lactobacillus acidophilus ATCC 4356, Lactobacillus arabinosus A
TCC 8014, Lactobacillus fermentum IAM 114
8, Lactobacillus casei ATCC 393, Bifidobacterium adresentis ATCC 15705, Bifidobacterium longum JCM 1217, Bifidobacterium bifidum JCM 1254, Bifidobacterium breve JCM 1192, Enterococcus hirae ATCC 80
43, the Clostridium butyricum ATCC 6015.
All of these strains are easily available. These strains are managed and stored in the following microorganism preservation institutions. These institutions distribute the lots on request. The English letter IAM for the strain indicates the Institute for Applied Microbiology, University of Tokyo (currently Institute for Molecular and Cellular Biology), and IID
Indicates the Institute of Medical Science, University of Tokyo, and ATCC is The Am
erican Type Culture Collection, JCM is Japa
Indicates nCollection of Microorganisms. The numbers after these English letters are numbers for identifying the strain. In short, regardless of whether they are Japanese citizens, these strains can be easily obtained because they are offered for distribution to the institutions shown here or are commercially available.

These preservation organizations are the Japanese Federation of Preservation Machines (JFCC).
Since I am a member of the Ollection of Microorganisms),
JFCC Catalog of Cu
ltuers, 1966 and 1968), you can find out in which conservation institution the desired fungus is stored.

The contacts (addresses) of the above organizations are as follows.

Research Institute for Applied Microbiology, University of Tokyo: 1-1-1 Yayoi, Bunkyo-ku, Tokyo ATCC: 12301 Parklawn Drive, Rockville, Md. 20852 ,
USA JCM: 2-1 Hirosawa, Wako-shi, Saitama Life Sciences Bio-Biological Department In addition, as other preservation organizations that preserve the above strains,
Fermentation Research Institute (Address: Jusannishinomachi, Higashiyodogawa-ku, Osaka-shi, Osaka), The Northern Regional Research Laborato
ry, Peoria, Illinois, USA, Centraalbureau voor sc
himmelcultur-es, Baar, Netherlands.

The ATCC strains described here are the strains issued in 1989.
ATCC catalog (17th edition), JCM strains in JCM catalog issued in 1992, other strains in 1979 or
It is described in the JFCC catalog issued in 1992.

Known culture techniques can be applied to the culture of these strains. The following are all examples of culture methods.

Culturing of the genus Enterococcus, the genus Streptomyces, and the genus Lactobacillus is carried out aerobically using a Rogosa medium. Cultivation of the genus Bifidobacterium and the genus Clostridium is anaerobic and is performed using, for example, a GAM medium (manufactured by Nissui Pharmaceutical Co., Ltd.).

In a preferred embodiment of the above composition, viable cells are separated from this culture solution, and the viable cells are freeze-dried with the culture solution and excipients such as skim milk, glucose, lactose and starches. It consists of dried cells.

The composition containing intestinal bacteria can be powdered using a known formulation technique, if necessary, together with an excipient, etc.
It can be provided in the form of tablets, liquid preparations, granules or fine granules. The viable cell count in the obtained composition was 10 ^{9 to} 10 ¹² /
It is preferably g.

The effective amount of this composition is tentatively based on the amount that can be ingested from 100 billion to 10 trillion per day in viable cell count. However, even if ingesting less than or more than this amount of viable bacteria, the effect is observed in most cases. No acute toxicity was observed with this composition.

This composition may contain a culture obtained by culturing the intestinal bacterium in an edible medium. Thereby, the nutrition of the edible medium can be simultaneously ingested together with the ingestion of the composition of the present invention. In addition, it is preferable that the number of bacteria in the composition is increased by culturing in an edible medium, and then it can be ingested. Examples of such an edible medium include milk and soy milk. The device and system according to the present invention realize suitable production of a composition obtained by culturing intestinal flora in an edible medium.

The above-mentioned bacterium is preferably cultured in an edible medium at the optimum growth temperature, and in the case of the above-mentioned strain, it is preferably 40 ± 4 ° C (36 to 44 ° C). In the aggregate of all the above-mentioned strains, particularly preferably 37 to 40 ° C. When the culturing temperature is within this range, the enterobacteria can be grown, proliferated, and cultivated while preventing the growth of various bacteria other than the enterobacteria of the present invention. The culturing time at this time is preferably about 8 to 15 hours. Adjusting the culturing time means that the growth of bacteria (may be referred to as growth and growth), the fermentation of an edible medium (the growth of bacteria in an edible medium) are allowed to proceed to a desired range, and It can be said that it is desirable from the viewpoint of setting the properties (mouthfeel, fluidity, taste, etc.) of the edible medium (nutrient medium) within a desired range or preventing the growth of various bacteria.

It is effective for this composition to contain a component for improving the growth of bacteria in the composition. This improves the growth of the bacteria on the edible medium and helps to evenly grow on the edible medium. Oligosaccharides are preferred as this component. This is because this oligosaccharide selectively grows intestinal bacteria. Even when ingested by humans, this oligosaccharide is not digested by digestive enzymes and reaches the large intestine as it is to be used for the growth of intestinal bacteria. Such oligosaccharides include lactosucrose (milk fruit oligosaccharide),
Includes isomaltooligosaccharide and galactooligosaccharide (raffinose, soybean oligosaccharide). Other similar ingredients include skim milk.

By adding this oligosaccharide to the above composition, ingested intestinal bacteria can grow better even in the human intestinal tract. The content of oligosaccharides added to the composition is not particularly limited, but usually, it may be added to the composition so that the daily intake of humans is 10 mg to 100 g of oligosaccharides. In addition, components such as oligos may be directly added to the edible medium (nutrient medium).

The composition has uses as a health food, a functional food, or a drug. In addition, it is preferable to apply a known acid-resistant coating (enteric coating, enteric coating) to the dry cells to prevent decomposition by gastric acid when ingested. Such coating includes covering dry cells with a fat composed of fatty acids (stearic acid, palmitic acid, etc.) and wax (slack, etc.), or coating dry cells with proteins such as zein. Be done. These dressings are
It may be applied directly to the dried cells or dissolved in a solvent (alcohol such as ethanol) and applied or sprayed on the dried cells.

A composition obtained by culturing these enterobacteria in an edible medium is produced by the apparatus and production system described in the claims. The apparatus is not limited to fermentation by enterobacteria and culture of enterobacteria, but is applicable to culture, growth, or fermentation of possible microorganisms. That is, the present invention is
The present invention is characterized by comprising a container body for culturing microorganisms on a medium, and a heating device provided on at least a bottom surface of the container body to produce a composition or product containing the microorganisms.

For example, for producing a composition containing intestinal bacteria, the intestinal bacteria described in detail above are used as microorganisms, and edible medium such as milk is used as the nutrient medium. A device or system is provided.
The device of the present invention provides more favorable results when multiple intestinal bacteria are used simultaneously.

The heating device is preferably further provided on at least one side surface of the container body. In a preferred embodiment, a heating device is provided on one of the bottom surface and the side surface (particularly the back surface) of the container. However, it does not prevent the heating devices from being arranged on two or more side surfaces (for example, the back surface and the front surface). In the present invention, it is also preferable to form a slope on the bottom surface. This inclination is formed, for example, from the front surface to the back surface of the container body.

The heating device includes, for example, an electric heating device (for example, a resistance wire such as a nichrome wire or a far infrared heater). In addition, the edible medium (which may be referred to as a nutrient medium) is a basis for causing a phenomenon of microbial growth such as fermentation, and particularly, dairy products such as milk and various other products. Food can be illustrated.

Further, the heating device has a temperature control circuit for maintaining the temperature of the mixture of the medium and the microorganisms at a temperature suitable for the growth of the microorganisms. An example of such a control circuit is a thermoswitch made of bimetal.

The manufacturing apparatus of the present invention may further include a heating time setting circuit (timer circuit). This makes it possible to set a time suitable for culturing the microorganism. The suitable time for culturing the intestinal bacterium is as described above. The microorganisms mixed with the edible medium are mainly the intestinal bacteria described above. However, it is not limited to these bacteria.

The amount of bacteria inoculated into the edible medium is not particularly limited and is selected from the most suitable range depending on the type of bacteria and / or the components of the medium or the amount thereof. In addition, the heating by the heating device is preferably adjusted to a temperature suitable for growth (fermentation, etc.) of the mixture, but is appropriately selected depending on the type of bacteria. For intestinal bacteria, the temperature may be about 36 to 44 ° C. Also, Streptococcus thermophilus, which is often used for yogurt and cheese, is optimal at about 45 ° C, but may be 35 to 46 ° C. In addition, the genus Leuconostoc (leuconostoc, mescentroides), which is an inoculum often detected in other fermented foods (eg pickles), has a temperature of 25 to 30 ° C.
The temperature of Lactococcus cremoris is preferably 30 to 37 ° C.

In the present invention, the nutrient medium is supplied into the container body as a pack (for example, milk pack) or transferred to another container.

Further, it is desirable that the heating device of the present invention is provided on the side surface of the container body so that substantially the entire area of the side surface of another container accommodating the nutrient medium can be heated. Further, the metal foil strip is attached to the container body across the side surface provided with the heating device and the side surface not provided with the heating device.

The heating device may include one that is inserted into the nutrient medium and heats it from the inside. An example of such a material is a stainless steel tube in which a nichrome wire is built. This can be placed in a milk pack to heat the milk. By doing so, the medium is also heated from the inside, so that the entire medium is uniformly heated (heated).

In the present invention, the duration of heating is preferably the time until fermentation (growth of microorganisms) reaches almost all regions of the nutrient medium.

According to the present invention, since the mixture of the nutrient medium and the microorganism is heated from the bottom surface of the container body, convection for mixing the heated portion and the non-heated portion in the mixture is sequentially performed. The heat is distributed almost evenly in the mixture (medium). Therefore, the microorganisms grow almost evenly over almost the entire mixture. Therefore, the fermentation also proceeds evenly throughout the mixture.

The present invention provides a suitable system in which the optimum temperature for growth must be adjusted within a predetermined range. The present invention provides a system for suitably growing (or may be referred to as culture or fermentation) the above-mentioned intestinal bacteria in a medium and uniformly growing the same in the medium.

If the heating device is provided on the bottom surface or the bottom surface and the back surface of the container body, the size of the device is not increased and the cost is not increased. Since the heating device is present on the bottom surface and the side surfaces including the back surface, the above-mentioned uniform heating is achieved more effectively.

The advantage that the apparatus and system of the present invention can uniformly heat the medium is also shown in the following. If the medium is not heated evenly, for example, the growth of the bacteria will progress where heating is progressing and the growth ability of the bacteria will remain low where heating is insufficient. There are places where the bacteria grow partially and places where the bacteria do not grow. This leads to partial differences in the fluidity of the medium. As confirmed by the present inventor, when a commercially available milk is used as the medium, for example, the milk becomes yogurt-like at a location where the growth of the bacteria, that is, the fermentation (cultivation of the bacteria) is advanced, and thus the fluidity is reduced. To do. After that, if heating is continued as it is, convection of the medium becomes difficult, so that the cells are divided into areas where the growth of bacteria is progressing and areas where the growth is not sufficient. If the culturing time is selected based on the portion where the growth of the bacterium is low, the culturing time becomes long and the fermentation of the medium in the heated portion may proceed excessively, for example, lumps may be formed. On the other hand, if the culturing time is selected based on the part where the growth of the bacterium is progressing, the culturing time will be shortened, and the fermentation of the medium will be insufficient at the place where the heating is low. In any case, the properties of the product after completion of fermentation cannot be achieved to be uniform properties, such as partial lumps and non-lumps because the medium is not heated uniformly.

This is a further problem when a plurality of strains or species are used as bacteria. The device or system of the present invention is advantageous in that it can uniformly heat a medium in which a plurality of strains or strains are inoculated. The optimum temperature for growth varies depending on the strain or species. If the medium cannot be heated uniformly, it will be difficult to grow all strains or species, and for example, some bacteria will partially grow and some will not. This can occur due to slight temperature differences. When a plurality of strains or bacterial species are grown on a common medium, it is preferable to select and maintain a range of optimum growth temperature common to the bacterial strains or bacterial species. The ability to evenly warm the medium makes this possible. Moreover, the bacteria are evenly grown in the medium. That is, the medium is fermented uniformly. This allows
The properties of the product including the components after fermentation including the bacterium and the medium can be made uniform.

In particular, the apparatus and system of the present invention bring more preferable results when culturing (growing) a plurality of strains shown in Table 1 below in milk (nutrient medium or edible medium). .

[0060]

【Example】

(Production of Composition) Cultivation of bacteria contained in the genus Enterococcus, Streptococcus, or Lactobacillus is aerobically carried out at 37 ° C. using Rogosa culture. Cultivation of bacteria contained in the genus Bifidobacterium or Clostridium is anaerobically performed at 37 ° C. using a GAM medium (manufactured or sold by Nissui Pharmaceutical Co., Ltd.).

The culture medium was previously autoclaved for 121
Apply sterilization for 15 minutes at 0 ° C. Dry cells were obtained by the following method for each strain shown in Table 1.

The medium was inoculated with each strain shown in Table 1 (10 ⁶
/ Ml), after culturing for 15 hours, the culture is centrifuged at 12,000 rpm to collect the cells, and the cells are dispersed in 10% skim milk (1/20 of the culture) and freeze-dried. The viable cell count of the dried cells was 10 ^{9 to} 10 ¹² / g. The viable cell count of each strain is shown in Table 1.

Rogosa medium: 10 g of tryptic case, 5 g of yeast extract, 3 g of tryptose, 3 g of K ₂ HPO _4, 3 g of KH ₂ PO _4, 2 g of ammonium citrate, 1 g of Tween 80, 20 g of glucose, 0.2 g of cystine in 1 liter of water. Salt solution 5 ml Salt solution: MgSO ₄ .7H ₂ O 11.5 g, FeSO ₄ .7H ₂ O 0.
68 g MnSO ₄ .7H ₂ 0 2.4 g (Anti-allergic test 1) Next, for patients with atopic dermatitis, the above-mentioned energization treatment and anti-inflammatory ointment (Shiunkaku: Nagakura Pharmaceutical Co., Ltd.) or When only Matsuura Pharmaceutical Co., Ltd. manufactures or sells the application treatment, this treatment and a commercially available anti-bacterial agent (Levenin: Wakamoto Pharmaceutical, Biosley:
Experiments were carried out on the antiallergic effect when the dry bacterial cells shown in Table 1 were ingested as compared with the case where the drug was taken according to the usage of Toa Pharmaceutical Co., Ltd.). The results are shown in Table 2.

Experimental Example 1. Dried bacterial cells of the strains shown in Table 1 are mixed in equal amounts to give a mixed dried bacterial cell powder. This was packed in a gelatin capsule at a dose of 500 mg and taken 3 times daily.

Experimental Example 2. The dried bacterial cells of Experimental Example 1 were added to 1 liter of commercially available milk that had been refrigerated, placed in a warmer, and kept at about 40 ° C. for 8 to 12 hours. Milk coagulates weakly, but this was refrigerated and taken in an amount of 500 ml daily. At the time of administration, sugar, aspartame and other sweetening amounts were added, or jam and fruit sugar were added according to taste, and they were seasoned appropriately before eating. Experimental example 3. 500 mg of dried bacterial cells of Enterococcus hirae ATCC 9790 was packed in a gelatin capsule and taken 3 times daily.

Experimental Example 4. 500 mg of dry cells of Lactobacillus acidophilus JCM 1217 was packed in a gelatin capsule and taken 3 times daily.

Example 5. Bifidoacterium longum JCM 1217 500 mg of dried bacterial cells was packed in a gelatin capsule and taken 3 times daily.

The energization treatment method and the application treatment of an anti-inflammatory ointment (purple plaster), this treatment and the administration of a commercially available rectifying intestinal medicine, and each of the experimental examples were carried out for 3 months. Place the dried cells or a serratin capsule filled with dried cells in a sealed bottle 4
Stored below ℃.

The results are shown in Table 2. With regard to the composition of the present invention, an obvious antiallergic action was observed. Moreover, a high antiallergic action was observed for the composition containing a plurality of strains. In addition, D to H shown in Table 2
As a result of an interview with the patients in the group, an intestinal regulating effect was observed in the constipated person.

(Anti-allergic test 2) A patient (12-year-old girl) suffering from allergic purpura and having internal hemorrhage from the end of March 1993 to the beginning of April of the same year, and then, based on Example 2, When the composition was taken, internal bleeding began to disappear about 1 week after the administration, and when the composition was further taken, no bleeding was observed until the end of August 1994.

As described above, it was confirmed that the composition of the present invention has an antiallergic action against various allergic diseases including atopic dermatitis.

Incidentally, dried bacterial cells containing oligosaccharide (composition)
Can provide the dried bacterial cells of each strain shown in Table 2 with the following composition, for example.

Lactose oligosaccharide 1.0 g Crystalline cellulose 1.5 g Lactose 0.5 g Dry cell 0.02 g As described above, this composition was found to have an excellent antiallergic effect.

[0074]

[Table 1]

[0075]

[Table 2]

Next, an embodiment of the manufacturing apparatus (system) of the present invention will be described.

FIG. 1 is a sectional view of the container body of this apparatus, and FIG.
2 is a sectional view taken along line AA of FIG. This embodiment includes a container body, a heating device provided in the container body, and a timer circuit connected to the container body.

The container body forms a space for containing the mixture of the nutrient medium and the microorganism in the manufacturing apparatus. That is, as shown in FIGS. 1 and 2, the container body 10 has a rectangular shape having a space 11 having a rectangular cross section inside. The container body 10 is composed of an outer container 12 facing the outside and an inner container 14 forming an inner part.

The upper surface of the outer container 12 is open, and the support legs 16 are integrally formed on the bottom surface so as to project in four U-shapes evenly. The outer container 12 has a space 18 having a rectangular cross section inside, and an inner container 14 having a second space having a rectangular cross section is accommodated in the space 18. The outer wall portion of the inner container 14 is formed to be slightly narrower than the width of the space 18 of the outer container so that the inner container 14 can be stored in the outer container 12, and the space between the inner wall of the outer container 12 and the outer wall of the inner container 14 is increased. A gap 22 is formed.

As shown in FIG. 2, the gap 24 is formed wider between the inner wall of the outer container 12 and the outer wall of the inner container 14 corresponding to the back surface 10A of the container body 10 than the other portions. In this wide gap (hereinafter referred to as "wide gap"), a nichrome wire heater as a heating device described later is arranged.

On the other hand, the bottom surface 26 of the inner container 14 is the outer container 12
Is located above the bottom surface 28 of the
It is fastened by a connecting mechanism composed of 0A and a nut 30B. That is, from the bottom surface 26 of the inner container 14 to the outer container 1
2 and from the bottom surface 28 of the outer container 12 toward the inner container 14, cylindrical projecting pieces 32A and 32B are provided so as to project at the respective central positions, and the inner container 14 is inserted into the outer container 12. At this time, the tip surfaces of both are aligned with each other. A cylindrical bolt hole 30A is formed in each of the projecting pieces 32A and 32B, and the bolt 31 is inserted from the inner container 14 into the bolt hole.
It is inserted into 2A and 32B. Next, the nut 30B is screwed onto the tip of the bolt 31 from the outer container 12 side. In this way, the inner container 14 is fixed in the outer container 12.

FIG. 3 is an enlarged sectional view of the connecting mechanism, in which an O-ring 34 for sealing is provided between the two protruding pieces 32A and 32B.
Is installed. In this way, the two protrusions 32
A and 32B can be completely fixed and sealed without rattling.

As shown in FIGS. 1 and 2, the inner container 14
The upper end portion of the outer container 12 protrudes upward from the upper end of the outer container 12 in a state where the inner container 14 is fixed in the outer container 12, and further bends toward the bottom surface direction and outward, and the tip thereof is the outer container. It ends at the upper end of 12.

As shown in FIG. 4, a portion of the inner container 14 which faces the inner side in the radial direction is notched along the circumferential direction with a thickness of about half, and the outer container 12 has a leading end portion on its outer wall. It is cut out along the circumference with almost half the wall thickness. Therefore, the tip of the inner container 14 and the tip of the outer container 12 are engaged with each other when the inner container 14 is fixed in the outer container 12. An annular packing 3 serving as a seal member for waterproofness is preferably provided between the two.
6 around. Alternatively, both may be directly sealed with an adhesive (material).

FIGS. 5 to 7 are enlarged views of the inner container 14. The back surface 38 (the portion facing the wide gap 24) and the bottom surface 26 (see FIG. 7) of the inner container 14 serve as a heating device. The nichrome wire heater 40 of FIG. The nichrome wire heater 40 is continuously arranged so that the back surface meanders in the length direction and the bottom surface part also meanders, and these two surfaces can be simultaneously and widely heated.

Further, on the back surface 38, the left and right side surfaces, and the front surface of the inner container 14, heat transfer means for keeping heat and for applying heating by the nichrome wire heater 40 provided on the back surface to other surfaces than the back surface. Double layer aluminum foil 4 as
4 is wound in series so as to cover the nichrome wire heater 40. The aluminum foil 44 is also attached to the bottom surface 26.

In the middle of the nichrome wire heater 40, a TRS (thermo switch: a switch that closes when the temperature exceeds a preset temperature and opens when the temperature is lower than the preset temperature) 46 is provided as a temperature control means. Since the nichrome wire heater 40 provided on the back surface 38 of the inner container 14 is housed in the wide gap 24, the nichrome wire heater 40 is brought into contact with the inner wall of the outer container 12 when the inner container 14 is housed in the outer container 12. The insertion of the inner container 14 is not hindered.

FIG. 8 is a perspective view showing the entire outer container 12, and a magnet type cord receiving port 48 for energizing the nichrome wire heater 40 is present on the back surface portion thereof. The receiving port 48 is configured to be electrically connected to the nichrome wire heater 40 when the inner container 14 is set in the outer container 12, and the power cord 50 shown in FIG. 9 can be set in the receiving port 48. Has become.

The power cord 50 is provided at its tip with a plug-in portion 52 that can be attached to and detached from the magnet type receptacle 48, and at the other end with a plug 54 that can be plugged into a household power source.
A timer circuit 56 is provided on the way. A timer knob 58 for setting the energization time to the heating device is provided on the front surface of the timer circuit.

FIG. 10 shows a circuit diagram of an electric circuit. Therefore, by connecting the insertion portion 52 to the receptacle 48 and setting the timer knob 58 to a desired time, the nichrome wire heater 40 can be energized during that time.

Reference numeral 60 shown in FIGS. 1 and 2 indicates a container for storing milk as a nutrient medium (edible medium), preferably a container capable of containing 1000 cc of milk. The space inside the inner container 14 of the container body 10 is formed in a shape and volume capable of accommodating such a container. Further, as shown in FIG. 11, the inner container 14 may be formed so that the milk pack 62 containing 1000 cc can be stored as it is.

As shown in FIG. 5, the nichrome wire heater 40
Inner container 14 so that these containers can be heated sufficiently.
Is provided from the bottom to the top of the back surface 38 of the. The height of the container body 10 can be changed as appropriate. Further, as shown in FIG. 12, the container body 10 may be covered with a lid 64 for the purpose of keeping heat. It should be noted that reference numeral 60 in FIGS. 1 and 2 and reference numeral 15 in FIG. 12 indicate a different container mainly made of resin different from the milk pack, and the milk in the commercially available milk pack can be used by transferring it to the container. .

Next, the operation of this embodiment will be described. In this example, the dried bacterial cells of Experimental Example 1 and 1 liter of commercially available packed milk were used. The operation in this example is a detailed version of the description of Experimental Example 2. The dried bacterial cells are usually packaged in an amount to be applied to each 1 liter milk pack. These strains are preferably stored in a cool dark place (preferably several degrees Celsius or less).

A milk pack (containing 1000 cc of milk) mixed with bacteria according to Experimental Example 2 was inserted into the inner container 14 of the container body 10, and the timer knob 58 was set to a time suitable for the growth (fermentation) of microorganisms. To do. Usually, it is 5 to 20 hours. In the case of this embodiment, it is 8 to 15 hours.
During this period, the nichrome wire heater 40 is energized to heat the milk to a temperature suitable for fermentation by the nichrome wire heater 40, and at a suitable temperature for fermentation by the temperature maintaining means 46 (in the case of the above-mentioned intestinal bacteria, 36). To 44 ° C, preferably 3
7 ° C to 40 ° C).

At the time of this heating, the nichrome wire heater 40
However, since it is provided in a wide area of the bottom surface 26 of the inner container 14, the milk in the pack is heated from almost the entire surface of the bottom surface 26. The heated milk becomes lighter in specific gravity and successively convects with the unheated milk on the upper part of the milk, and the whole milk pack is uniformly heated to a temperature suitable for the growth of microorganisms. Moreover, since the back surface 38 of the inner container 14 is also provided with the nichrome wire heater 40, the temperature suitable for fermentation can be reached in a short time.

Therefore, the nutrient medium (milk) is heated from the height direction by the nichrome wire heater 40 provided on the back surface 38 of the inner container 14 and the nichrome wire heater provided on the bottom surface 26 of the inner container 14. By 40,
By heating in the radial direction as well, the entire mixture of the nutrient medium and the bacteria can be heated uniformly and rapidly. Moreover, the nichrome wire heater 40 is attached to the inner container 14
Since it is only provided on the bottom surface 26 and the back surface 38 of the device, the device is not oversized and the cost is not increased.

FIG. 14 shows the characteristics when the device 10 of this embodiment is used. Fig. 14 shows the heating time and 10
The relation with the temperature in the predetermined position in the 00cc milk pack is shown by a graph. FIG. 15 shows the same characteristics when the device described in Japanese Utility Model Publication No. 60-38382 described as a conventional technique is used. 14 and 15 are time-temperature relationship curves corresponding to the position A (upper part of the container) of FIG. 13, BB is the same relationship curve at the position B (middle part of the container), and CC is the value of C. It is a similar relationship curve at the position (bottom of container).

In the apparatus described in Japanese Utility Model Publication No. 60-38382, unlike the apparatus of this embodiment, since the heater is not provided on almost the entire bottom surface, the heating of the milk pack is localized and the milk is fermented. (Proliferation of bacteria) partially progresses.
Since the fluidity decreases in the fermented part and the heating progresses in this state even after that, as shown in FIG. 15, it is about between the part with the highest temperature (CC) and the part with the lowest temperature (AA). A difference of 15 to 17 ° C occurs. In the hottest part, the temperature exceeds the optimum temperature for the growth of bacteria. When observing the product after it was made, many lumps were partially observed.

On the other hand, in the apparatus of this embodiment, as described above, since the medium is heated uniformly during the fermentation of milk (edible medium), as shown in FIG. 14, [AA] [BB ]
The characteristics as shown in [CC] were obtained. According to this characteristic, the temperature difference between the highest temperature part ([CC]) and the lowest temperature part ([AA]) could be reduced to about 7 ° C. or less. Even at the highest temperature, the optimum temperature for growth of the bacteria was not exceeded. This indicates that the milk in the pack was actually heated almost uniformly over the whole by the manufacturing apparatus of the present invention. Observation of the resulting product confirmed that it had uniform properties (viscosity, fluidity, etc.) from the bottom to the top of the milk pack.

According to the manufacturing apparatus of this embodiment, the heat quantity from the heating apparatus is prevented from escaping toward the outer container by the aluminum foil 44, and the heat quantity of the nichrome wire heater 40 on the back surface 38 of the inner container is controlled. , The left and right side surfaces and the front surface of the inner container 14 can also be affected. Further, since the nichrome wire heater 40 is provided only on the bottom surface and the back surface of the inner container 14, the device does not become large and the cost does not increase.

The container body 10 of the present invention is preferably made of resin. The inner container 14 is preferably made of a material having good thermal conductivity (for example, vinyl chloride resin, polypropylene, polyethylene resin), and the outer container 12 is made of a material having excellent heat insulating property (for example, polystyrene, ABS). It is desirable to configure.

The device or system according to the present invention is
It can be appropriately changed within the scope of the present invention. For example,
As shown in FIG. 16, the bottom surface 26 of the inner container 14 may be formed in an inclined shape having an upslope from the front surface to the back surface 38. According to this, by increasing the area of the bottom surface of the inner container, it is possible to widely heat the medium,
Moreover, heat convection can be improved. In this example, a container (pack) containing a nutrient medium
When inserting, the bottom shape of the container (pack) is preferably matched with the bottom shape of the inner container.

As the heating device, there is far infrared ray generating means in addition to the nichrome wire heater 40. The far infrared ray generating means is configured as follows. That is, the inner container 1
The far infrared ray generating ceramics may be fixed to at least one surface (a part or most of this surface) of the outer container 12 side and the surface of the inner space 20 side of No. 4. Radia echo powder manufactured by Nippon Sheet Glass Co., Ltd. can be used as such ceramics. If this ceramic is preliminarily formed into a plate shape (card shape) and is adhered to the surface of the inner container 14, it is possible to obtain preferable results such as easy manufacture.

It is more preferable that this ceramic is provided on a part or all of at least one of the inner surface and the outer surface of the separate container 15 shown in FIG. and again,
The side surface of the separate container 15 may have a double structure with a space inside, and a structure in which ceramics are arranged in this space.

In this case, the ceramic is
It has the advantage of being easy to maintain without having direct contact with the nutrient medium. The far-infrared ceramic emits far-infrared rays when heated by the nichrome wire heater 40. Far infrared rays penetrate into the nutrient medium and can heat it effectively. Therefore, the heating time can be shortened and the heating can be performed in a wide range. The amount of far infrared rays generated can be increased by increasing the area or volume provided with the ceramics.

As shown in FIG. 17, the arrangement pattern of the nichrome wire heaters 40 is reciprocated (may be meandering) in the width direction of the inner container 14 to narrow the interval between the adjacent nichrome wire heaters 40. Thereby, the nutrient medium can be heated in a wide range.

Further, in order to improve the heat transfer efficiency from the inner container 14 to another container 60 (a milk pack, see FIG. 1) housed in the inner container 14, it is laid on the back surface 38 of the inner container 14. The laying density of the nichrome wire heaters 40 (see FIG. 5) is improved (that is, the distance between the adjacent nichrome wire heaters 40 is reduced), or the inner container 14
It is preferable to minimize the gap between the back surface 38 and the separate container 60. For this reason, a plurality of hemispherical projections projecting toward the back side of the inner container 14 are evenly arranged (for example, three places) from the upper part to the bottom part of the container front, and another container 60 is attached to the inner container 14. It is preferable to urge the back side to be in close contact. The heating or heating with far infrared rays as described above is also for improving the efficiency of heat transfer to the separate container 60.

The height of the inner container 14 is preferably set to the height of the milk pack 1000 cc. But 5
You may make it the height of a 00cc pack. When the inner container 14 is formed at the former height, the container body 10 is set to 500
By covering the cc pack from above, the device of the present invention can be used regardless of the size of another container (milk pack or the like). In addition, you may put milk etc. in the inner container 14 directly. In this case, by providing a lid that covers the container body 10, milk or the like in the inner container 14 can be heated uniformly.

Further, according to the present invention, since the nutrient medium (milk, soy milk, etc.) can be uniformly heated or heated, the optimum temperature of the fermenting bacteria mixed with the nutrient medium in the medium can be adjusted. Can be adjusted appropriately. The advantages of adjusting the nutrient medium to the optimum temperature of the fermenting bacteria can be understood, for example, from the following points. In a preferred embodiment of the present invention, a mixture of a plurality of the above-mentioned intestinal bacteria is used as the fermenting bacterium, but in this case, the nutrient medium is maintained in the optimum temperature range common to the plurality of bacteria.

As shown in FIG. 14, according to the present invention, almost the entire nutrient medium can be heated uniformly, so that the entire nutrient medium can be maintained at a common optimum temperature. On the other hand, according to the conventional manufacturing apparatus, as shown in FIG. 15, in the medium at the bottom of the container where the temperature rises, the optimum temperature of one or more bacteria is exceeded, and these bacteria die or grow. May not. Fermented products containing all active ingredients can be obtained by uniformly fermenting the nutrient medium by growth of all of the plurality of bacteria.

The duration of the fermentation of milk according to this example is preferably such that the fermentation covers all areas in the milk pack. This time is preferably about 8 to 15 hours using a 1 liter milk pack as described above.

The duration of fermentation can be adjusted not only by adjusting the heating time but also by detecting the temperature difference in the milk pack. That is, when fermentation starts in the milk pack, a temperature difference occurs between the upper, lower, middle, and lower parts of the pack. Referring to FIG. 14, a temperature difference occurs after a lapse of about 8 hours. In the range of 10 to 14 hours when the degree of fermentation is considered to be almost good, a temperature difference of about 6 to 10 ° C is observed below and above the milk pack. Therefore,
The end of heating can be known by detecting this temperature difference with a thermometer such as a thermocouple placed in the milk pack. For example, put temperature sensors in the upper and lower parts of the milk pack, turn off the switch of the circuit that energizes the nichrome wire when the microcomputer receiving the signal of this sensor judges that the preset temperature difference has been reached. Just do it.

[0113]

As described above, according to the apparatus or system of the present invention, the mixture of the edible medium and the microorganism is heated from the bottom surface of the container body, so that the heating is almost evenly distributed in the mixture. become. Therefore, the microorganism
It grows almost evenly over almost the entire mixture. Therefore,
Fermentation proceeds evenly throughout the mixture. As a result, it is possible to provide a product having uniform properties from the bottom to the top of the product.

Since the heating device is formed only on one of the bottom surface and the side surface (preferably the back surface) of the container body, such an effect can be obtained, so that the device is not enlarged.
Moreover, there is no increase in cost.

Moreover, according to the device or system of the present invention, the intestinal bacterial flora is grown in a good condition, and the bacterial cells of such bacteria are contained to improve or maintain the intestinal bacterial flora, and further A microorganism-containing product having anti-allergic properties can be provided.

[Brief description of drawings]

FIG. 1 is a sectional view of a container body of a manufacturing apparatus and a manufacturing system according to an embodiment of the present invention.

FIG. 2 is a sectional view taken along line AA of FIG.

FIG. 3 is an enlarged cross-sectional view of a connection mechanism of the container body.

FIG. 4 is a cross-sectional view of a joint portion between the outer container and the inner container of the container body.

FIG. 5 is a perspective view of the inner container of the embodiment.

FIG. 6 is a partial cross-sectional view of the inner container cut in the radial direction.

FIG. 7 is a partial perspective view of the inner container as viewed from the bottom.

FIG. 8 is a perspective view of an outer container.

FIG. 9 is a perspective view of a power cord for energizing the container body.

FIG. 10 is a circuit diagram showing an electric circuit for heating.

FIG. 11 is a cross-sectional view of the container body showing a state in which a milk pack is stored.

FIG. 12 is a cross-sectional view of the container body showing a state where the lid is placed on the inner container of the container body.

FIG. 13 is a schematic diagram showing the relationship between the height position of a milk pack and each code.

FIG. 14 is a characteristic diagram showing a relationship between heating temperature and heating time.

FIG. 15 is a characteristic diagram showing a relationship between heating temperature and heating time in a conventional device.

FIG. 16 is a conceptual diagram showing another embodiment of the bottom shape of the inner container.

FIG. 17 is a conceptual diagram showing another arrangement pattern of heating devices.

[Explanation of symbols]

 10 Container body 12 Outer container 14 Inner container 40 Nichrome wire heater

Claims (15)

[Claims] 1. An apparatus for producing a composition containing a microorganism, which comprises a container body for culturing a microorganism on a medium, and a heating device provided on at least a bottom surface of the container body. 2. The device according to claim 1, wherein the heating device is further provided on at least one side surface of the container body. 3. The apparatus according to claim 2, wherein the heating device is provided on a bottom surface and a back surface of the container body. 4. The apparatus according to claim 1, further comprising temperature control means for maintaining the heating by the heating device at a temperature suitable for fermentation of the microorganism. 5. The container body according to claim 1, wherein the container body includes an outer container and an inner container arranged in the outer container, and the heating device is arranged on a surface of the inner container. The device according to claim 1. 6. The apparatus according to claim 2, wherein the heating device is provided on the side surface of the container body so that substantially the entire area of the side surface of another container for storing the edible medium can be heated. 7. The apparatus according to claim 1, wherein the bottom surface of the container body is formed to have an inclination. 8. The apparatus according to claim 5, wherein the metal foil strip is attached over the side surface of the inner container where the heating device is provided and the side surface where the heating device is not provided. 9. The medium according to claim 1, which comprises an edible component.
The described device. 10. A composition containing a microorganism comprising human intestinal bacteria, a container body for culturing the intestinal bacteria in an edible medium, and a heating device provided on at least a bottom surface of the container body. A system for manufacturing things. 11. The system according to claim 10, wherein the intestinal bacterium is one or more bacteria belonging to at least one of Streptococcus, Enterococcus, Bifidobacterium, Lactobacillus, and Clostridium. . 12. The system according to claim 10 or 11, wherein the edible medium is a dairy product. 13. A bacterium belonging to any one of the genus Streptococcus, Enterococcus, Bifidobacterium, Lactobacillus, and Clostridium is Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus ebium. , Streptococcus salivarius, Streptococcus bovis, Streptococcus ikuinus, Lactobacillus acidophilus, Lactobacillus gasserie, Lactobacillus salivarius, Lactobacillus fermentum, Lactobacillus reuteri, Lactobacillus arabinus burebidobacterium, Bifidobacterium. , Bifidobacterium longum, Bifidobacterium adrensetis, Bifidobactere 11. The method of claim 11 or 1, which is Lium infantes or Bifidobacterium bifidum.
2. The system described in 2. 14. A specific strain of the strain is Enterococcus faecalis ATCC 19433, Enterococcus faecium ATCC 19434, Enterococcus durans IID 677, Streptococcus salivarius IID.
5223, Enterococcus hirae ATCC 9790, Lactobacillus acidophilus ATCC 4356, Lactobacillus arabinosus ATCC 8014, Lactobacillus fermentum IAM 1148, Lactobacillus casei ATCC 39
3, Bifidobacterium adrescentis ATCC 15
705, Bifidobacterium longum JCM 1217, Bifidobacterium bifidum JCM 1254, Bifidobacterium breve JCM 1192, Enterococcus hirae ATCC 8043, Clostridium butyricum A
14. The system of claim 13, which is TCC 6015. 15. The culture temperature of the intestinal bacterium is 36 to 4
15. The system of claims 10-14, which is at 4 ° C.