JP5631721B2 - Gastrointestinal hypersensitizer - Google Patents

Description

  The present invention relates to a composition having an action of enhancing gastrointestinal function such as an action of enhancing intestinal contraction.

  In recent years, due to stress, westernization of eating habits, lack of exercise, etc., an increasing number of people complain of symptoms due to disorders of gastrointestinal function such as constipation, heartburn, stomach upset and indigestion. For example, constipation is not only one of the unpleasant symptoms that plague many modern people, but it also indirectly causes stiff shoulders, headaches, loss of appetite, and cosmetic problems such as rough skin. ing.

  Gastrointestinal disorders such as constipation, heartburn, stomach upset and indigestion are said to occur easily if the stomach or intestinal peristalsis is weak. Conventionally, it has been known that useful bacteria such as lactic acid bacteria and plants such as aloe have an effect of improving gastrointestinal function. Lactic acid bacteria improve the intestinal microflora, have a laxative action, and are used to improve constipation. Aloe is said to have a manic action by increasing the amount of water in the large intestine and causing peristalsis.

  Patent Document 1 discloses an oral composition containing an extract of a plant belonging to the genus Salacia and at least one of a component having an anti-constipation action or a component having an anti-diarrheal action. Patent Document 2 discloses a composition obtained from asparagus, and one or more substances selected from the group consisting of methylmethionine and / or its derivatives, niacin and / or its derivatives, vitamin B2, aloe, mucin and lactic acid bacteria. Foods and drinks having an action to improve and prevent gastrointestinal disorders are disclosed. Patent Document 3 discloses an adsorbent obtained by supporting a plant extract such as aloe extract on the surface of activated carbon, and a defecation deodorant containing bifidobacteria as an intestinal regulating substance.

Patent Document 4 discloses a food for improving constipation containing dead lactic acid bacteria and aloe. Patent Document 5 discloses a food having an effect of improving constipation in which a processed kale product and at least one selected from lactic acid bacteria, bifidobacteria, dietary fiber, aloe and the like are blended. Patent Document 6 discloses lactic acid bacteria, aloe, and the like as materials containing components having an effect of improving constipation. Patent Document 7 discloses a composition that improves the decrease in gastric emptying ability, which may contain carnitine chloride and may contain aloe, lactic acid bacteria, and the like.
However, the above-described composition has room for contrivance so that a stronger gastrointestinal function enhancing action can be exerted.

JP 2009-215276 A Japanese Patent Laid-Open No. 2008-19170 JP 2005-247784 A JP 2004-81105 A JP 2002-204669 A JP 2002-51731 A JP-A-8-259445

  An object of the present invention is to provide a safe gastrointestinal function-enhancing agent that can effectively enhance the gastrointestinal function by effectively enhancing the contraction of the stomach or intestinal tract and has no side effects and can be taken for a long time. And

The inventors of the present invention have made extensive studies in view of the above problems. When (a) two or more kinds of lactic acid bacteria and (b) aloe or a processed product thereof are used in combination, intestinal contraction is caused by their synergistic action. It was found that can be effectively enhanced. Since intestinal contraction occurs due to contraction of intestinal smooth muscle, the use of (a) two or more lactic acid bacteria and (b) aloe or processed products thereof acts on the smooth muscle of the digestive tract such as the stomach, small intestine and large intestine. The contraction can be enhanced. That is, the peristaltic movement of the digestive tract can be activated. Therefore, when (a) two or more kinds of lactic acid bacteria and (b) aloe or a processed product thereof are used, the gastrointestinal function can be enhanced by enhancing the contraction of the digestive tract. Using such a composition having an action of enhancing the contraction of the gastrointestinal tract can activate, for example, gastric peristalsis, thereby improving the digestive action in the stomach and facilitating the delivery of food from the stomach to the intestines. it can. Moreover, when intestinal tract contraction is enhanced, the movement of the intestines is activated and an excellent constipation-resolving effect can be exhibited.
The present inventors have further studied based on the above findings and have completed the present invention.

That is, the present invention relates to the following (1) to (8).
(1) A gastrointestinal function enhancer comprising (a) two or more lactic acid bacteria, and (b) aloe or a processed product thereof.
(2) The gastrointestinal function enhancer according to (1) above, wherein the lactic acid bacterium comprises two or more types of bacteria selected from the genus Lactobacillus and the genus Streptococcus.
(3) Gastrointestinal function enhancement according to (1) or (2) above, wherein the lactic acid bacterium comprises at least one lactic acid bacterium belonging to Lactobacillus acidophilus and at least one lactic acid bacterium belonging to Streptococcus faecalis Agent.
(4) The lactic acid bacteria according to any one of (1) to (3), wherein the lactic acid bacteria include at least Lactobacillus acidophilus KS-13 and Streptococcus faecalis 129 BIO 3B (Streptococcus faecalis 129 BIO 3B). The gastrointestinal hypersensitivity agent described.
(5) The above (1) to (4), wherein the aloe is Cape Aloe (Aloe ferox Miller), or a hybrid of Cape Aloe (Aloe ferox Miller) and Aloe africana Miller or Aloe spicata Baker ) The gastrointestinal hyperfunction agent according to any one of the above.
(6) The agent for enhancing gastrointestinal function according to any one of (1) to (5), wherein the processed product of aloe is a dried product of aloe leaf juice.
(7) The gastrointestinal function enhancer according to any one of (1) to (6), wherein the gastrointestinal hyperfunction is enhancement of intestinal contraction.
(8) An intestinal tract contraction enhancer comprising the gastrointestinal function enhancer according to any one of (1) to (7).

  In the present specification, a lactic acid bacterium classified as a genus Streptococcus in taxonomy before 1984 is referred to as a genus Streptococcus (for example, Schleifer, KH and R. Kilpper-Balz. 1984. Int. J. Syst. Bacteriol. 34: 31-34.). A part of the genus Streptococcus has become a lactic acid bacterium classified as Enterococcus genus after 1984, which is currently used for classification of lactic acid bacteria (for example, Schleifer, KH and R. Kilpper-Balz. 1984. Int. J. Syst. Bacteriol. 34: 31-34 (same as above)). For example, Streptococcus faecalis such as Streptococcus faecalis 129 BIO 3B described herein are lactic acid bacteria that are currently classified as Enterococcus faecium. In the present invention, as the lactic acid bacterium belonging to the genus Streptococcus, it is preferable to use a lactic acid bacterium classified into the genus Enterococcus since 1984, which is currently used for classification of lactic acid bacteria.

  In the present specification, a lactic acid bacterium classified as Lactobacillus acidophilus in taxonomy before 1980 is referred to as Lactobacillus acidophilus (for example, Lauer, E. and O. Kandler). 1980. Zbl.Bakt., I.Abt.Orig.C1: 75-78.). A part of this Lactobacillus acidophilus has become a lactic acid bacterium classified as Lactobacillus gasseri on the taxonomy after 1980, which is currently used for classification of lactic acid bacteria (for example, Lauer, E. and O. Kandler. 1980. Zbl. Bakt., I. Abt. Orig. C1: 75-78 (same as above)). Lactobacillus acidophilus such as Lactobacillus acidophilus KS-13 described herein is a lactic acid bacterium classified as Lactobacillus gasseri according to the current taxonomy It is.

  The classification system of lactic acid bacteria was classified by cell morphology, cell sequence, lactic acid fermentation format, sugar utilization, DNA-DNA homology, etc. until around 1980, but now it has chemical taxonomic properties and bases of 16S rRNA gene. Due to the active use of sequence-based genetic methods to propose new genera and reclassify known genera, Streptococcus faecalis 129 BIO 3B is now Enterococcus faecium in the current taxonomy. , Lactobacillus acidophilus KS-13 (Lactobacillus acidophilus KS-13) belongs to Lactobacillus gasseri, respectively.

  When the gastrointestinal function enhancer of the present invention is used, the contraction of the gastrointestinal tract can be enhanced, so that gastrointestinal dysfunction such as constipation can be effectively improved. In addition, the gastrointestinal function enhancer of the present invention is safe without side effects even when taken for a long time.

FIG. 1 is a diagram illustrating an example of a spray drying apparatus having a four-fluid nozzle. FIG. 2 is a schematic diagram showing the structure of the Magnus tank used in the examples.

The gastrointestinal function enhancer of the present invention contains (a) two or more lactic acid bacteria, and (b) aloe or a processed product thereof.
The aloe used in the present invention only needs to be used in crude drugs. Preferably, as aloe, Cape Aloe (Aloe ferox Miller) or a hybrid of Cape Aloe (Aloe ferox Miller) and Aloe africana Miller or Aloe spicata Baker (Aloe spicata Baker) is used.

  Examples of the processed aloe include aloe leaf powder, aloe powder, and aloe extract that is an extract of aloe. Aloe powder or aloe extract is preferable, and aloe powder is more preferably used. The aloe powder is usually a powder of dried aloe leaf juice. For example, aloe powder from the Japanese Pharmacopoeia is preferably used. Aloe extract is usually obtained by adding a suitable leachate such as water to the aloe powder, leaching for a certain period of time by the cold immersion method, digestion method or percolation method, filtering the leachate, and concentrating or drying by an appropriate method. can get. Of the aloe extract thus obtained, the soft extract has a syrupy consistency, and the dry extract is a hard mass, granule or powder that can be crushed.

  Aloe can usually be obtained as a commercially available product as aloe powder or as an extract of aloe. In the gastrointestinal function enhancer of the present invention, aloe powder may be blended as it is, or may be blended in the form of an aloe extract.

  The lactic acid bacteria in this invention are not specifically limited, For example, what is necessary is just 2 or more types of bacteria selected from lactic acid bacteria, such as a bifidobacterium, a lactobacillus, and a lactic acid bacterium.

The lactic acid bacteria used in the present invention include, for example, Bifidobacterium bifidum, B. longum, B. breve, B. adolescentis, B. infantis, B. pseudolongum, B. thermophilum and the like Bifidobacterium genus Bifidobacterium Lactobacillus acidophilus, L. casei, L. gasseri, L. plantarum, L. delbrueckii subsp bulgaricus, L. delbrueckii subsp lactis, L. fermentum, L. helveticus, L. johnsonii, L. paracasei subsp. Paracasei, Lactobacillus of the genus Lactobacillus such as L. reuteri, L. rhamnosus, L. salivarius, L. brevis; (Enterococcus) hirae, Streptococcus thermophilus and other Streptococcus genus (currently classified as Enterococcus genus), Lactococcus lactis, L. cremoris Lactococcus genus such as Tetragenococcus halophilus, Tetragenococcus genus, Pediococcus acidilactici, P. pentosaceus etc. Pediococcus genus, Oenococcus oeni etc. Etc.
These cells can be easily obtained from, for example, an organization such as ATCC or IFO or the Japan Bifidobacteria Center. Moreover, what is marketed can also be used suitably.

  In the present invention, the two or more kinds of lactic acid bacteria preferably include two or more kinds of bacteria selected from the genus Lactobacillus and the genus Streptococcus. As described above, the lactic acid bacteria belonging to the genus Streptococcus are preferably lactic acid bacteria classified into the genus Enterococcus since 1984, which is currently used for classification of lactic acid bacteria. More preferably, at least one lactic acid bacterium selected from the genus Lactobacillus and at least one lactic acid bacterium selected from the genus Streptococcus are used. As a lactic acid bacterium belonging to the genus Lactobacillus, Lactobacillus acidophilus is preferable. As a lactic acid bacterium belonging to the genus Streptococcus, Streptococcus faecalis is preferable. More preferably, the lactic acid bacteria in the present invention include at least one lactic acid bacterium belonging to Lactobacillus acidophilus and at least one lactic acid bacterium belonging to Streptococcus faecalis. Furthermore, it is most preferable to use two kinds of Lactobacillus acidophilus KS-13 (Lactobacillus acidophilus KS-13) and Streptococcus faecalis 129 BIO 3B (Streptococcus faecalis 129 BIO 3B) as essential.

As long as the effects of the present invention are exhibited, useful bacteria such as saccharifying bacteria and butyric acid bacteria may be included in addition to the above lactic acid bacteria. For example, saccharifying bacteria such as Bacillus subtilis, Bacillus mesentericus, Bacillus polyformenticus; for example, sporic lactic acid bacteria such as Bacillus coagulans; Bacillus toyoi, B. et al. Examples include butyric acid bacteria such as licheniformis and Clostridium butyricum; and other useful bacteria.
These cells can be easily obtained from, for example, an organization such as ATCC or IFO or the Japan Bifidobacteria Center. Moreover, what is marketed can also be used suitably.

  The said microbial cell can be obtained by culture | cultivating on well-known conditions or the conditions according to it. For example, in the case of lactic acid bacteria, one or more of the above lactic acid bacteria is usually preferred at about 25 to 45 ° C. for about 4 to 72 hours in a liquid medium containing glucose, yeast extract, peptone and the like. Aerial or anaerobic culture is performed, and the cells are collected from the culture solution and washed to obtain wet cells. In the case of saccharifying bacteria, aerobic culture is usually carried out at about 25 to 45 ° C. for about 4 to 72 hours in an agar medium containing meat extract, casein peptone, sodium chloride and the like. Then, the cells are collected from the medium and washed to obtain wet cells.

  The lactic acid bacterium used in the present invention is preferably a living bacterium, but a processed product of the bacterium may be used. The treated product of bacteria refers to a product obtained by adding some treatment to lactic acid bacteria, and the treatment is not particularly limited. Specific examples of the treated product include a disruption solution of the microbial cells by ultrasonic waves, a culture solution or a culture supernatant of the microbial cells, and a solid residue obtained by separating them by solid-liquid separation means such as filtration or centrifugation. It is done. In addition, a treatment solution obtained by removing a cell wall by an enzyme or mechanical means, a protein complex (protein, lipoprotein, glycoprotein, etc.) or a peptide complex (peptide, glycopeptide, etc.) obtained by trichloroacetic acid treatment or salting-out treatment, etc. ) Etc. are also mentioned as the treated product. Furthermore, these concentrates, these dilutions, or these dried products are also included in the treated product. In addition, the treated product in the present invention includes those obtained by further adding, for example, various chromatographic separations to the disrupted solution of the bacterial cells by ultrasonic waves, the cell culture solution or the culture supernatant. . Dead cells of lactic acid bacteria are also included in the treated product in the present invention. The dead cells can be obtained by, for example, enzyme treatment, heat treatment at about 100 ° C., treatment with drugs such as antibiotics, treatment with chemicals such as formalin, treatment with radiation such as γ rays. it can.

  The lactic acid bacterium used in the present invention may be a dried product (bacterial cell dried product), and the microbial cell dried product is preferably a single micron dried cell product. The dried microbial cell usually refers to a dried individual microbial cell or a collection of dried microbial cells. Single micron means 1-10 μm by rounding off the first decimal place. When a single-micron dried microbial cell product is used as the lactic acid bacterium used in the present invention, the viable cell ratio in the preparation increases, and as a result, the intestinal contraction enhancing action and the like increase, resulting in an enhanced action of gastrointestinal function.

A preferred method for producing a dried microbial cell product will be described. The said microbial cell is disperse | distributed to a solvent and it is set as a microbial cell liquid. As the solvent, a known solvent used in the art may be used, but water is preferable. If desired, ethanol may be added. By adding ethanol, ethanol is vaporized first, and then water is vaporized, so that stepwise drying is possible. Further, the bacterial cell liquid may be a suspension. The solvent may be the same as shown above. When suspending, a suspending agent such as sodium alginate may be used.
Moreover, you may add the additive generally used in this industry, such as a protective agent, an excipient | filler, a binder, a disintegrating agent, or an antistatic agent, to the said microbial cell liquid by a normal compounding ratio.

The bacterial cell liquid is subjected to a drying operation by a spray dryer in order to produce a dried bacterial cell product. The spray drying apparatus is preferably a spray drying apparatus equipped with a atomizing apparatus capable of forming single micron spray droplets. When spray droplets having a very small particle diameter are used, the surface area per unit mass of the spray droplets is increased, and contact with dry hot air is efficiently performed, so that productivity is improved.
Here, the droplet of single micron means that the particle size of the spray droplet is 1 to 10 μm rounded to the first decimal place.

Examples of the spray drying device include a spray drying device in which the atomization device is, for example, a rotary atomizer (rotary disk), a pressurized nozzle, or a two-fluid nozzle or a four-fluid nozzle using the force of compressed gas.
The spray drying apparatus may be any spray drying apparatus of the above type as long as it can form single micron spray droplets, but it is preferable to use a spray drying apparatus having a four-fluid nozzle.

In a spray drying apparatus having a four-fluid nozzle, the four-fluid nozzle has a gas flow channel and a liquid flow channel as one system, which are provided symmetrically at the two-system nozzle edge. It constitutes the slope that becomes the surface.
Also, an external mixing type apparatus that gathers compressed gas and liquid from one side toward the collision focus at the tip of the nozzle edge is preferable. With this method, it is possible to spray for a long time without nozzle clogging.

  A spray drying apparatus having a four-channel nozzle will be described in more detail with reference to FIG. At the nozzle edge of the four-channel nozzle, the bacterial cell liquid that springed out from the liquid channel 3 or 4 was thinly stretched and stretched on the fluid flow surface 5 by the high-speed gas flow exiting from the gas channel 1 or 2. The liquid is atomized by a shock wave generated at the collision focal point 6 at the tip of the nozzle edge to form a single micron spray droplet 7.

As the compressed gas, for example, an inert gas such as air, carbon dioxide, nitrogen gas, or argon gas can be used. In particular, when spray-drying a material that is easily oxidized, it is preferable to use an inert gas such as carbon dioxide, nitrogen gas, or argon gas.
The pressure of the compressed gas is usually about 1 to 15 kgf / cm ² , preferably about 3 to 8 kgf / cm ² .
The gas amount in the nozzle is usually about 1 to 100 L / min, preferably about 10 to 20 L / min per 1 mm of the nozzle edge.

Usually, after that, in the drying chamber, the sprayed droplets are brought into contact with dry hot air to evaporate the water and obtain a dried bacterial cell product.
The entrance temperature of the drying chamber is usually about 2 to 400 ° C, preferably about 5 to 250 ° C, more preferably about 5 to 150 ° C. Even if the inlet temperature is about 200 to 400 ° C., the temperature in the drying chamber is not so high due to the heat of vaporization due to the evaporation of moisture, and the residence time in the drying chamber is shortened to Damage can be suppressed to some extent.
The outlet temperature is usually about 0 to 120 ° C, preferably about 5 to 90 ° C, more preferably about 5 to 70 ° C.

In the spray drying apparatus having a four-channel nozzle, since there are two liquid channels, two different types of bacterial cell liquids or bacterial cell liquids and other solutions or suspensions are sprayed simultaneously from the respective liquid channels. Thus, a dried microbial cell product in which these are mixed can be produced.
For example, by simultaneously spraying two different types of bacterial cell solutions, a dried bacterial cell product containing the two types of bacterial cells can be obtained.

By reducing the particle size of the dried bacterial cell as described above, there is an advantage that the viable cell rate is increased and a preparation having a high viable cell rate can be provided.
That is, it is preferable to spray single micron spray droplets in order to obtain a single micron dried cell. When the particle size of the spray droplets is reduced, the surface area per unit mass of the spray droplets increases, so that contact with the dry hot air is performed efficiently, and killing or damaging the cells due to the heat of the dry hot air as much as possible. Can be suppressed. As a result, the viable cell rate is increased and a dried cell body having a large number of viable cells is obtained.

  The gastrointestinal function-enhancing agent of the present invention is easily produced by mixing (a) two or more kinds of lactic acid bacteria and (b) aloe or a processed product thereof with other components. Other components are not particularly limited as long as the effects of the present invention are exhibited. The gastrointestinal function enhancer of the present invention can be used in the form of pharmaceuticals, quasi drugs, foods and drinks, feeds and the like. Such a pharmaceutical comprising the gastrointestinal function-enhancing agent of the present invention is also one aspect of the present invention.

  The dosage form of the gastrointestinal hypersensitivity agent of the present invention may be a dosage form suitable for administration in consideration of the physicochemical properties, biological properties and the like of each component. In the case of a pharmaceutical, it is suitable for oral administration and is preferably an internal preparation. Examples of the internal dosage form include tablets, pellets, fine granules, powders, granules, pills, chewables, troches, liquids, suspensions and the like. Among these, tablets or powders are preferable. Furthermore, the gastrointestinal function-enhancing agent of the present invention includes (a) two or more kinds of lactic acid bacteria, and (b) aloe or a processed product thereof, as well as excipients (for example, lactose, starch, crystalline cellulose, sodium phosphate, etc. ), Binders (eg starch, gelatin, carmellose sodium, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone etc.), disintegrants (eg starch, carmellose sodium etc.), lubricants (eg talc, stearin) Magnesium sulfate, calcium stearate, macrogol, sucrose fatty acid ester, etc.), stabilizer (sodium bisulfite, sodium thiosulfate, sodium edetate, sodium citrate, ascorbic acid, dibutylhydroxytoluene, etc.), colorant, flavoring agent , Brightener, etc. Known additives such as a may contain appropriately used in the industry. The total amount of two or more lactic acid bacteria contained in the preparation can be determined by appropriately selecting from the range of about 0.000001 to 99% by mass in the final preparation. The amount of aloe contained in the preparation or processed product thereof can be determined by appropriately selecting from the range of about 0.0001 to 99% by mass in the final preparation.

Preparation of the composition containing (a) 2 or more types of lactic acid bacteria, and (b) aloe or its processed material can be manufactured by mixing components by a conventional method of preparation. In that case, the blending ratio of (a) two or more lactic acid bacteria and (b) aloe or processed product thereof in the composition is (a) two or more types relative to the mass 1 of aloe or processed product thereof. The total number of lactic acid bacteria is preferably about 4 × 10 ² to 2 × 10 ^9, more preferably about 4 × 10 ³ to 1 × 10 ⁹ . In two or more types of lactic acid bacteria, the blending ratio of each lactic acid bacterium is not particularly limited. For example, when Lactobacillus acidophilus and Streptococcus faecalis are used, about 0.001 to 1000 Streptococcus faecalis are viable with respect to 1 viable Lactobacillus acidophilus. It is preferable to use about 0.1-10 Streptococcus faecalis in terms of the number of viable bacteria per 1 viable bacteria of Lactobacillus acidophilus.

  Lactic acid bacteria are generally anaerobic and are weak against air or oxygen in the dry state, and are vulnerable to high temperatures and humidity. Therefore, in the formulation of the composition, in the presence of an inert gas or in a vacuum at a low temperature as much as possible. It is preferable to process.

  When a composition containing (a) two or more kinds of lactic acid bacteria and (b) aloe or a processed product thereof is made into a solid preparation, the powders may be simply mixed by a drying method, or the powder may be compressed. It may be made into granules or tablets. When granules and tablets are produced by a wet method, they can be kneaded and dried using an aqueous solution of a binder to obtain a desired solid agent. Furthermore, the powder or granule obtained in this way can be filled into a capsule to form a capsule.

  For example, when manufacturing a tablet, it is good to use a well-known tableting machine. Examples of the tableting machine include a single-shot tableting machine and a rotary tableting machine. Moreover, the manufacturing method of a pill, a chewable agent, or a troche agent may be performed in accordance with a well-known method, for example, can be made with the same means as manufacturing a tablet.

In order to obtain a uniform mixture by mixing a small amount of active ingredients (two or more kinds of lactic acid bacteria and aloe or processed product thereof) with a large amount of other powders, a so-called stepwise mixing method is preferably employed. For example, the active ingredient can be mixed with 100 to 200 times its volume of powder to obtain a uniform powder, and this can be mixed with the remaining powder to obtain a uniform powder.
For drying from the hydrated material, means such as L-drying, freeze-drying and spray-drying can be employed. In order to obtain dry cells of lactic acid bacteria, the bacteria can be suspended in a neutral buffer solution containing an appropriate stabilizer such as monosodium glutamate or adonitol and dried by a method known per se. .

In the present invention, the dose of two or more lactic acid bacteria is usually about 10 ³ to 10 ¹² cells / adult / time, preferably 10 in terms of the number of live bacteria for each lactic acid bacterium. ⁵ to 10 ¹⁰ pieces / adult / time, more preferably 10 ⁶ to 10 ¹⁰ pieces / adult / time. It is effective to orally administer this amount for each bacterium, usually with aloe or a processed product thereof 2 to 4 times a day, preferably about 1 hour before meal to about 2 hours after meal. Here, the measurement of the number of viable bacteria in the preparation varies depending on the bacterial cells, but can be easily measured by, for example, each bacterial cell quantification method described in the Japanese Pharmacopoeia Pharmaceutical Standards.

  In the present invention, the dose of aloe or a processed product thereof is usually about 5 to 380 mg / adult / dose, preferably about 5 to 250 mg / adult / dose, more preferably about 10 to 250 mg / adult as the amount of aloe powder. / Times. The dose of aloe or a processed product thereof is, for example, the amount of aloe powder used in the production of aloe extract when using aloe extract.

The gastrointestinal function-enhancing agent of the present invention is particularly preferably used for enhancing digestive tract contraction, particularly enhancing intestinal tract contraction.
The gastrointestinal function-enhancing agent of the present invention can be suitably applied to, for example, an individual (animal) having symptoms caused by gastrointestinal dysfunction or gastrointestinal function deterioration. Moreover, since the gastrointestinal function-enhancing agent of the present invention has no side effects and is safe, it can be administered for a prophylactic purpose for a long time. For this reason, it can be suitably applied not only to individuals who develop symptoms caused by the above gastrointestinal dysfunction or gastrointestinal function, but also to healthy individuals, individuals (animals) that may develop the symptoms, and the like. Especially, it applies especially suitably to the individual who developed the symptoms caused by the above gastrointestinal dysfunction or gastrointestinal dysfunction.
Symptoms caused by gastrointestinal dysfunction and gastrointestinal dysfunction are not particularly limited, and include constipation, stomach sag, heartburn, indigestion, abdominal bloating, abdominal pain, acid reflux, hard stool, residual stool, and the like. Among these, it is preferably applied to constipation. As the individual, mammals such as humans, mice, rats, rabbits, dogs, cats, cows, horses, pigs and monkeys are preferable, and humans are particularly preferable.

  The gastrointestinal function-enhancing agent of the present invention can effectively enhance contraction of the digestive tract such as stomach, small intestine, large intestine, etc. by using (a) two or more lactic acid bacteria in combination with (b) aloe or a processed product thereof. Therefore, it is effective for the prevention, improvement or treatment of gastrointestinal dysfunction, the administration method is simple, and there are almost no side effects.

The gastrointestinal function-enhancing agent of the present invention can be suitably used as an intestinal contraction enhancing agent or a constipation improving agent.
The intestinal contraction enhancing agent containing the gastrointestinal function enhancing agent of the present invention is also one aspect of the present invention. The constipation improving agent containing the gastrointestinal hyperfunction agent of the present invention is also one aspect of the present invention.
Preferred embodiments of the intestinal contraction enhancing agent and constipation improving agent of the present invention are the same as those of the aforementioned gastrointestinal function enhancing agent.

  The agent for enhancing gastrointestinal function of the present invention can be used as a pharmaceutical as described above, and can also be used as a food or drink such as a functional food, a food for specified health use, or a drink. A food / beverage composition for enhancing gastrointestinal function, a food / beverage composition for enhancing intestinal contraction, and a food / beverage composition for improving constipation are also one aspect of the present invention. By ingesting the food and beverage composition according to the present invention to a mammal including a human who has suffered from, or is likely to suffer from, gastrointestinal dysfunction such as constipation or gastrointestinal dysfunction, Can be prevented or ameliorated. The total amount of two or more kinds of lactic acid bacteria contained in the food / beverage product composition can usually be determined by appropriately selecting from the range of about 0.000001 to 99% by mass in the final composition. The amount of aloe contained in the food / beverage product composition or a processed product thereof can usually be determined by appropriately selecting from the range of about 0.0001 to 99% by mass in the final composition.

  When the gastrointestinal function enhancer of the present invention is used as a food or drink composition, its form is not particularly limited. Moreover, food-drinks compositions can also be made into processing forms, such as a natural liquid food, a semi-digested nutrient food, a component nutrient food, or a drink agent. Furthermore, the food-drinks composition concerning this invention is good also as an easily soluble formulation added to an alcoholic beverage or mineral water at the time of use. More specifically, the food / beverage composition according to the present invention includes, for example, confectionery such as biscuits, cookies, cakes, candy, chocolate, chewing gum, Japanese confectionery; bread, noodles, cooked rice or processed products thereof; sake, medicinal liquor, etc. Fermented foods; livestock farming foods such as yogurt, ham, bacon, sausage, mayonnaise; beverages such as fruit juice drinks, soft drinks, sports drinks, alcoholic drinks, and tea.

  In addition, the food / beverage composition according to the present invention, for example, under the control of a dietitian based on a doctor's meal, adds the food / beverage composition of the present invention to any food at the time of cooking in a hospital meal, It can also be given to patients in the form of food prepared in The food / beverage composition of the present invention may be liquid or solid such as powder or granule.

  The food-drinks composition which concerns on this invention may contain the auxiliary component conventionally used in the foodstuff field | area. Examples of the auxiliary component include lactose, sucrose, liquid sugar, honey, magnesium stearate, oxypropylcellulose, various vitamins, trace elements, citric acid, malic acid, fragrance, and inorganic salt.

  The amount of intake of the food and beverage composition according to the present invention varies depending on the lifestyle-related disease state, age, sex, etc. of the mammal to be ingested, so it cannot be generally stated, but (a) two or more lactic acid bacteria, and ( b) It is preferable to take the same amount of aloe or its processed product as in the case of the above-mentioned pharmaceuticals.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. In this example, “%” means “% by mass” unless otherwise specified.

<Example 1>
(Preparation of dried lactic acid bacteria and measurement of the number of viable bacteria in the dried bacteria)
1. Preparation Method of Fungus (3B: Streptococcus faecalis 129 BIO 3B) The dry product of 3B cells was prepared as follows. That is, after the 3B cryopreserved strain (Biofermin Pharmaceutical Co., Ltd.) was allowed to stand at 37 ° C. for 24 hours, this was added to the liquid medium for lactamine test (2) (described in the Japanese Pharmacopoeia Pharmaceutical Standards “Lactamine” section). The cultured bacterial solution was inoculated at a ratio (volume ratio) of 1 with respect to the liquid medium for lactamine test (2) 100, followed by stationary culture at 37 ° C for 18 hours. The obtained culture solution is centrifuged, washed three times with water, an appropriate amount of water is added, and 0.1 kg of glutamate and 0.5 kg of dextrin are added to 1 kg of wet cells, and the mixture is added to the spray drying apparatus. The cells were dried. In addition, 3B stock | strain is contained as components, such as a biopharmaceutical compound biopharmaceutical powder (brand name, Biofermin Pharmaceutical Co., Ltd.), and can be obtained by refine | purifying from this powder etc. by the method performed normally.

The above-mentioned liquid medium for lactamine test (2) is mixed with the following components according to the method described in the section of the Japanese Pharmacopoeia Standard “Lactamine”, and heated at 121 ° C. for 15 minutes using a high-pressure steam sterilizer. And prepared by sterilization.
Yeast extract 5g
Casein peptone 20g
Glucose 20g
Meat extract 15g
Tomato juice ^* 200mL
Polysorbate 80 3g
L-cysteine hydrochloride 1g
800 mL of purified water
pH 6.8 ± 0.1
Tomato juice ^* was prepared by adding an equal amount of purified water to tomato juice, boiled with occasional stirring, adjusted to pH 6.8, and filtered.

2. Measurement of the number of viable bacteria in the dried microbial cell body The measurement was performed according to the lactamine determination method described in the section of the Japanese Pharmacopoeia Pharmaceutical Standards “Lactamine”. That is, weigh accurately 5 g of the dried bacterial cell product, add it to 30 mL of diluent (2), shake vigorously, add the same diluent to make exactly 50 mL, shake well, and accurately measure 1 mL of this bacterial solution. Then, the operation (10-fold dilution method) of addition into 9 mL of the same diluted solution that was accurately dispensed was repeated, and diluted so that the number of viable bacteria in 1 mL was 20 to 200. 1 mL of this solution was placed in a Petri dish, and 20 mL of a lactamine test agar medium (2) maintained at 50 ° C. was added thereto and quickly mixed to solidify. This was subjected to aerobic culture at 37 ° C. for 24-48 hours, and the number of viable bacteria in the dried microbial cells was determined from the number of colonies that appeared and the dilution rate. The above-described 1. The cell count of the dried microbial cell product obtained in 1 was 6.4 × 10 ¹¹ CFU / g viable count.

The preparation method of the diluent (2) used in the examples is shown below.
Preparation of Diluent (2) In accordance with the method described in the Japanese Pharmacopoeia Standards for Drugs “Lactamine”, the following ingredients are mixed and sterilized by heating at 121 ° C. for 15 minutes using a high-pressure steam sterilizer. Prepared.
Anhydrous sodium monohydrogen phosphate 6.0 g
4.5g potassium dihydrogen phosphate
Polysorbate 80 0.5g
L-cysteine hydrochloride 0.5g
Kang 1.0g
Purified water 1000mL
pH 6.8-7.0

  The agar medium for lactamine test (2) was prepared by adding 20 g of agar to the liquid medium for lactamine test (2) and sterilizing by heating at 121 ° C. for 15 minutes using a high-pressure steam sterilizer.

<Example 2>
(Preparation of dried lactic acid bacteria and measurement of the number of viable bacteria in the dried bacteria)
1. Preparation method of fungus (LA: Lactobacillus acidophilus KS-13) Preparation of a dry cell of LA was performed as follows. That is, a cryopreserved strain of LA (Biofermin Pharmaceutical Co., Ltd.) was allowed to stand at 37 ° C. for 24 hours, and then this cultured bacterial solution was added to the lactamine test liquid medium (2) 100. And then inoculated at a ratio of 1 (volume ratio) and cultured at 37 ° C. for 18 hours. The obtained culture solution is centrifuged, washed three times with water, an appropriate amount of water is added, and 0.1 kg of glutamate and 0.5 kg of dextrin are added to 1 kg of wet cells, and the mixture is added to the spray drying apparatus. The cells were dried. In addition, LA strain | stump | stock is contained as components, such as a new biofermin S tablet (brand name, Biofermin Pharmaceutical Co., Ltd.) of an over-the-counter medicine, and it can obtain by refine | purifying with the method performed normally from this tablet.

2. Measurement of the number of viable bacteria in the dried microbial cell body The measurement was performed according to the lactamine determination method described in the section of the Japanese Pharmacopoeia Pharmaceutical Standards “Lactamine”. That is, weigh accurately 5 g of the dried bacterial cell product, add it to 30 mL of diluent (2), shake vigorously, add the same diluent to make exactly 50 mL, shake well, and accurately measure 1 mL of this bacterial solution. Then, the operation (10-fold dilution method) of addition into 9 mL of the same diluted solution that was accurately dispensed was repeated, and diluted so that the number of viable bacteria in 1 mL was 20 to 200. 1 mL of this solution was placed in a Petri dish, and 20 mL of a lactamine test agar medium (2) maintained at 50 ° C. was added thereto and quickly mixed to solidify. This was subjected to aerobic culture at 37 ° C. for 24-48 hours, and the number of viable bacteria in the dried microbial cells was determined from the number of colonies that appeared and the dilution rate. The above-described 1. The cell count of the dried microbial cell product obtained in 1 was 6.8 × 10 ¹¹ CFU / g viable cells.

<Example 3>
(Intestinal contraction enhancing effect by combined use of lactic acid bacteria and aloe)
Aloe powder (manufactured by Nippon Powder Chemical Co., Ltd.) was used as the aloe, and 3B and LA cell bodies obtained by the methods of Examples 1 and 2 were used as the lactic acid bacteria.

  After purchasing male SD rats at the age of 8 weeks (purchased from Japan SLC), under conditions of room temperature 22 ± 5 ° C., humidity 55 ± 5%, and 12-hour cycle lighting (7: 0 to 19:00), CE-2 (manufactured by CLEA Japan) and waterworks were freely ingested and bred. Preliminary breeding was performed for one week or more, and rats having a body weight of 300 to 400 g were used for the test.

Rats were exsanguinated under anesthesia and immediately laparotomized to remove the lower colon. The intestinal contents, surrounding fat and outer membrane were removed to prepare a 1.5 cm tubular specimen.
A Tyrode solution (NaCl (8.0 g / L), KCl (0.2 g / L), MgCl ₂ (0.1 g / L), CaCl ₂ (0.2 g) previously heated to 37 ° C. in a 10 mL capacity Magnus tank. / L), NaHCO ₃ (1.0 g / L), NaH ₂ PO ₄ (0.05 g / L), glucose (1.0 g / L)) 10 mL, and the extracted specimen is loaded with 1 g load. And suspended on an isometric transducer (FD-pickup TB-611T, manufactured by Nihon Kohden Co., Ltd.) as shown in FIG. The intestinal tract movement of the specimen was recorded with a recorder (WT645G, manufactured by Nihon Kohden) through an amplifier (AD-632J, manufactured by Nihon Kohden). The specimens were equilibrated for 1 hour or more at 37 ° C. under aeration. During this time, the Tyrode solution was changed about every 20 minutes. After equilibration, the specimen was added to the Magnus tank when stabilized.

A schematic diagram showing the structure of the Magnus tank used in the examples is shown in FIG. The Magnus tank 11 includes a gas supply unit 12, a circulating water supply port 14 and a circulating water discharge port 19, and an infusion injection port 16 and an infusion discharge port 21.
Air 13 is supplied from the gas supply unit 12 to the Tyrode solution 23 in the Magnus tank. The circulating water 15 for maintaining the temperature in the Magnus tank is supplied from the circulating water supply port 14, and the water 20 circulated in the Magnus tank is discharged from the circulating water discharge port 19. In the examples, water 15 at 37 ° C. was supplied from the circulating water supply port 14. A Tyrode solution 17 is injected from the infusion port 16 into the tube. A Tyrode solution (modified Tyrode solution) 22 used in the experiment is discharged from the infusion port 21. When the tubular specimen 24 suspended in the Tyrode solution 23 contracts, the strength of contraction is detected by an isometric transducer (FD-pickup TB-611T, manufactured by Nihon Kohden Co., Ltd.) installed in the direction of the arrow 18.

As the specimen, an aloe solution in which methanol was dissolved to 160 mg / mL was used. The lactic acid bacterium used was suspended in Tyrode solution and heated at 37 ° C. for 30 minutes so that the bacterium was 2.5 × 10 ¹⁰ cfu / mL based on the measured viable count. In addition, when using 2 types of lactic acid bacteria, each suspension was mixed and used for each equivalent. Acetylcholine was used by dissolving in Tyrode solution so as to be 10 ⁻⁶ M and 10 ⁻⁵ M. As the amount of each specimen added, 15 μL of the aloe solution, 100 μL of each of the lactic acid bacteria suspension and acetylcholine were added to 10 mL of Tyrode solution filled in the Magnus tank. That is, the concentration of each specimen in the Magnus tank is Aloe 0.24 mg / mL, lactic acid bacteria 2.5 × 10 ⁸ cfu / mL, acetylcholine 10 ⁻⁸ M and 10 ⁻⁷ M. The concentration and combination of the specimens to be treated were carried out according to the following (i) to (ix).

(i) Aloe (0.24mg / mL)
(ii) LA (2.5 × 10 ⁸ cfu / mL)
(iii) 3B (2.5 × 10 ⁸ cfu / mL)
(iv) LA (1.25 × 10 ⁸ cfu / mL) + 3B (1.25 × 10 ⁸ cfu / mL)
(v) Aloe (0.24 mg / mL) + LA (2.5 × 10 ⁸ cfu / mL)
(vi) Aloe (0.24 mg / mL) + 3B (2.5 × 10 ⁸ cfu / mL)
(vii) Aloe (0.24 mg / mL) + LA (1.25 × 10 ⁸ cfu / mL) + 3B (1.25 × 10 ⁸ cfu / mL)
(viii) Acetylcholine (10 ⁻⁸ M)
(ix) Acetylcholine (10 ⁻⁷ M)

  In accordance with the above (i) to (ix), the intestinal motility of the specimen when the specimen was treated was the maximum tension for 1 minute after the specimen addition indicated by the waveform recorded in the recorder, that is, the intestinal contraction strength.

(result)
Table 1 shows the waveform of the intestinal motility when treating (i) to (ix) at the lower part of the isolated colon and the tension (g) as the maximum intestinal contraction force for 1 minute after the addition of the specimen. As is apparent from Table 1, the intestinal contraction effect was recognized by adding aloe to the Magnus tank. Intestinal contractile action was also observed in lactic acid bacteria (LA, 3B and LA + 3B). Furthermore, when these aloe and lactic acid bacteria are added in combination, a strong intestinal contraction effect is observed when they are used together, and this reaction results in a stronger intestinal contraction effect in the case of two lactic acid bacteria than in the case of one kind. It became. Furthermore, when the intestinal contraction strength is compared from the values of tension (g) shown in Table 1, the enhancement of the intestinal contraction force when Aloe and two types of lactic acid bacteria are added in combination is a synergistic effect. Admitted. Moreover, the intestinal contraction reaction by the combination of aloe and lactic acid bacteria was similar to the intestinal contraction by acetylcholine that promotes defecation by stimulating parasympathetic nerves. From the above results, it was shown that the combined use of aloe and at least two or more lactic acid bacteria enhances the intestinal contractile action and leads to promotion of defecation.
Intestinal tract contraction occurs due to contraction of intestinal smooth muscle. Therefore, it is considered that the use of aloe and two kinds of lactic acid bacteria acts on smooth muscle to enhance the contraction. Therefore, when aloe and two types of lactic acid bacteria are used, the contraction of the gastrointestinal tract such as the stomach, small intestine and large intestine can be enhanced, and the gastrointestinal function can be enhanced.

  The gastrointestinal function-enhancing agent of the present invention is useful for preventing or improving symptoms caused by gastrointestinal dysfunction such as constipation, indigestion, stomach sag, and indigestion, or decreased gastrointestinal function.

DESCRIPTION OF SYMBOLS 1, 2 Gas flow path 3 to which compressed gas is supplied, 4 Liquid flow path to which a liquid including a dry body is supplied 5 Fluid flow surface 6 Collision focal point 7 Spray droplet 11 Magnus tank 12 Gas supply part 13 Air 14 Ring Flowing water supply port 15 Water (circulating water)
16 Infusion port 17 Tyrode solution 18 Arrow 19 Circulating water outlet 20 Water (circulating water)
21 Infusion outlet 22 Modified Tyrode solution 23 Tyrode solution 24 Tubular specimen

Claims (5)

(A) lactic acid bacteria containing at least Lactobacillus acidophilus KS-13 (Lactobacillus acidophilus KS-13) and Streptococcus faecalis 129 BIO 3B (Streptococcus faecalis 129 BIO 3B) , and (b) containing aloe or a processed product thereof Gastrointestinal hypersensitizer. 2. The gastrointestinal function-enhancing agent according to claim 1 , wherein the aloe is Cape Aloe (Aloe ferox Miller) or a hybrid of Cape Aloe (Aloe ferox Miller) with Aloe africana Miller or Aloe spicata Baker. . The agent for enhancing gastrointestinal function according to claim 1 or 2 , wherein the processed product of aloe is a dried product of aloe leaf juice. The gastrointestinal hyperfunction agent according to any one of claims 1 to 3 , wherein the gastrointestinal hyperfunction is intestinal contraction enhancement. The intestinal tract contraction enhancer containing the gastrointestinal function enhancer according to any one of claims 1 to 4 .