JPS62263128A - Capsule containing useful enteric bacteria - Google Patents

Abstract

PURPOSE:To obtain the titled capsule containing bacteria in improved storage stability, by separating useful enteric bacteria encapsulated in a capsule from the wall of the capsule with a hydrophobic substance which is nonfluid at normal temperature. CONSTITUTION:A capsule containing useful enteric bacteria separated from the wall of the capsule with a hydrophobic substance which is nonfluid at normal temperature (e.g. animal oil or fat). Encapsulation of useful enteric bacteria (e.g. bifidus bacteria, lactobacilli, etc.) has been attempted for the administration of active amount of the bacteria, however, the bacteria or bacteria-supporting powder are stirred and moved in a liquid oil by shaking and successively brought into contact with water taken up from atmosphere into the capsule wall, resulting in extermination of the bacteria. The contact of the bacterial cell with the capsule wall can be restricted by the present process to suppress the absorption and migration of moisture and keep the bacterial cell in stable state.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to capsules containing stable intestinal beneficial bacteria.

[Conventional technology]

A large number of bacteria reside in the human intestine, and their activities are involved in the chemical reactions of substances in the human intestinal tract, and have a major impact on the function of the intestine and, ultimately, on the state of human health. well known. Among these bacteria, B. bifidus and lactic acid bacteria do not have any harmful effects on their own, but when they multiply, they suppress the proliferation of other bacteria that have harmful effects, causing harmful effects such as abnormal intestinal fermentation. It is desirable to allow Bifidobacteria and lactic acid bacteria to grow in the intestines, as they have the function of preventing the production of harmful products.

In general, during infancy, humans mainly consume amino I, such as N-acetylglucosamine, from breast milk. The so-called bifidus
By supplying components called factors, Bacteria bifidus and lactic acid bacteria proliferate in the intestines, and these bacteria are said to account for more than 90% of the intestinal bacteria, forming an extremely favorable bacterial flora. However, as children grow older and stop ingesting breast milk, the supply of bifidus factors decreases, resulting in a decrease in these beneficial intestinal bacteria and a deterioration of the bacterial flora.

Therefore, attempts have been made to improve the bacterial flora by orally administering useful intestinal bacteria, and for this purpose, lactic acid bacteria preparations and foods and drinks containing Bifidus bacteria are commercially available. However, it is difficult to ensure an effective amount of -II when ingested only from conventional foods and drinks, and furthermore, a considerable portion of the useful bacteria are killed by gastric juice.

As a result, intestinal function declines, especially due to deterioration of the bacterial flora.
For patients exhibiting symptoms such as abnormal fermentation or diarrhea, it is necessary to administer the drug in a well-controlled manner so that an effective dose reaches the intestines.

However, the useful bacteria mentioned above are anaerobic and have the property of dying when they absorb moisture. In addition, useful bacteria'
If the salinity is increased, the bacteria will be killed by the action of self-produced lactic acid, so it is difficult to maintain a high concentration. Therefore, it is necessary to encapsulate the necessary number of useful bacteria in a capsule to administer an effective dose. At present, satisfactory results have not been obtained in the formulation of this drug.

Therefore, the present inventors first proposed the patent application No. 61-43651.
In this issue, we proposed an intestine-beneficial bacteria-containing product in which a capsule with a diameter of 3 mm or less is filled with oil in which intestine-beneficial bacteria or powder carrying them is dispersed. The enteric bacteria in this capsule had excellent storage stability, as is clear from the examples in the above specification.

[Problem that the invention seeks to solve]

However, in this storage test, the capsules were wrapped in aluminum foil to prevent moisture and left in a constant temperature bath. However, it has been revealed that if the capsules are left in the atmosphere and further shaken from time to time for storage, storage stability deteriorates significantly.

Of course, this does not deny that the invention of the above application is useful, since it is customary to store it in a moisture-proof manner and leave it still. However, especially when stored by end consumers, it is difficult to ensure complete moisture resistance, and some degree of shaking is unavoidable, so it is desirable that the product is stable even when stored under such conditions. This is also important from the perspective of improving quality.

The present inventors have arrived at the present invention as a result of intensive research on this point.

An object of the present invention is to provide a technology that can improve the storage stability of beneficial bacteria in capsules containing enteric bacteria.

[Means for solving problems]

The outline of the present invention is to isolate the encapsulated intestinal beneficial bacteria from the capsule coating via a non-flowing hydrophobic substance at room temperature.

[Effect]

According to the above means, it is possible to prevent beneficial intestinal bacteria from directly contacting the capsule coating, and it is also possible to prevent moisture etc. from penetrating into the interior through the capsule coating.
The beneficial bacteria in the intestines can be prevented from being affected by moisture, etc., and the above object can be achieved.

The present inventors found that by storing without moisture protection and shaking occasionally, bacteria are killed because the capsule coating absorbs moisture from the atmosphere, and furthermore, shaking causes bacteria and the powder carrying them to become liquid. It is presumed that this is because all the bacterial cells absorb the moisture in the capsule coating as they are stirred and moved in the oil, come into contact with the capsule coating one after another, and absorb moisture. On the other hand, when the capsule is covered with water and left to stand still, there is relatively little moisture in the capsule coating, and only a small portion of the bacterial cells are in contact with the capsule coating, while the rest are submerged in oil. It is thought that it remains stable because the water absorption and transfer is slow.

Based on this hypothesis, the present inventors created a capsule containing bacteria useful for the intestines with the above-mentioned structure in order to prevent water from being absorbed into the bacterial cells.

With the above configuration, the storage stability of intestinal useful bacteria is significantly improved, the above hypothesis has been verified, and the present invention has been completed.

Intestinal useful bacteria that can be used in the present invention include B.
bifidum SB, long+a % R, ad
olescentislB, breves B, 1nf
Bifido-bacLe, such as Bifido antis.
riua+), L, acidophilus, L, 1a
ctis, L. casei.

Lactobacilli such as L. bulgaricus
act 1lus) and 5treptococcus
1actis and the like. These bacteria can be used as they are or as a powder supported on skim milk powder, starch, or the like.

Seamless capsules are usually suitable as capsules, and their coating materials include gelatin, alginic acid, carrageenan, pectin, etc. In the present invention, various methods can be used to isolate the capsule coating from beneficial intestinal bacteria. The following are possible.

Next, some examples are shown.

(1) A first nozzle located in the center, a second nozzle located outside of the first nozzle, and a third nozzle located outside of the second nozzle.
Prepare a triple nozzle consisting of nozzles.

A dispersion obtained by dispersing useful intestinal bacteria or a powder supporting them in oil that is liquid even at room temperature is passed through the first nozzle, and a liquid obtained by heating and melting an oil that is insoluble in the oil and solid at room temperature is passed through the second nozzle. Then, a capsule coating forming material such as an aqueous gelatin solution is simultaneously ejected from a third nozzle to form a three-layered droplet, and the droplet is dropped into a hardening bath for the outer layer of the droplet, which is made of cold oil or the like. do. As a result, upon cooling, a seamless capsule film made of gelatin gel or the like is formed on the outermost layer, and an intermediate layer made of solid fat (a non-flowable hydrophobic substance) is formed inside the film.
Furthermore, a three-layer capsule containing beneficial bacteria for the intestinal tract is formed inside of the capsule, in which a liquid oil in which beneficial bacteria for the intestinal tract are dispersed is sealed.

(2) In the above method 111, a method in which glycerin, polyglycerin, or a liquid ester thereof is used as a dispersion medium for the suspension jetted from the first nozzle.

(3) A double nozzle consisting of a first nozzle in the center and a second nozzle on the outside is used. Fats and oils that are solid at room temperature (
A dispersion of bacteria or their supported powder dispersed in a melt of a hydrophobic substance (hydrophobic substance) is simultaneously ejected from the first nozzle and a capsule coating forming material such as an aqueous gelatin solution is ejected from the second nozzle to form 2111 drops. , the outer layer of the droplet is dropped into a curing bath to form a capsule. This capsule has a two-layer structure consisting of an outer capsule coating and a solid fat sealed in the capsule, and useful bacteria are dispersed in the solid fat.

(4) A method in which powder carrying beneficial intestinal bacteria is compressed by a method such as tabletting, and the powder is coated as is or after being impregnated with oil or the like, coated with solid oil, and then covered with a capsule film.

The present invention is not limited to the method described above, and it goes without saying that methods other than the above may be used.The key point is that the bacteria and the capsule membrane are separated by a non-flowable hydrophobic substance. Any method that can do this is fine.

As a non-flowing hydrophobic substance for isolating the capsule coating and beneficial intestinal bacteria, any substance that maintains a non-flowing state such as a solid at the temperature during storage and has hydrophobic properties may be used. Specifically, oil or wax can be used. Examples of the fats and oils include animal fats and oils such as lard and het, butter, and hydrogenated oils. As the wax, roasted wax or beeswax can be mentioned.

Note that the present invention is not limited to these specific examples.

In addition, among the various embodiments described above, various solid fats and oils may be used in the method of dispersing bacterial powder in solid fats and oils. Can be done. However, in the case of a three-layer capsule containing a dispersion liquid in the center, the solid fat must be one that does not dissolve the dispersion medium in the center layer, and both of these components must be This must be taken into account when making a selection. For example, when glycerin is used as the dispersion medium in the center layer, almost all solid fats and oils can be used, but when vegetable oil is used, hydrogenated human oil can be used. etc. are preferable. However, if melted fats and oils need to be used in the manufacturing process, they must be melted at a temperature that will not kill beneficial intestinal bacteria.

[Example 1] FIG. 1 is a schematic cross-sectional view showing a capsule containing bacteria useful for the intestines, which is an example of the present invention.

The capsule containing useful intestinal bacteria in Example 1 is a so-called membraneless capsule with a three-layer structure. That is, the first FJl in the center contains lactic acid bacteria (Lac tobac i -1
This is a dispersion liquid made of glycerin in which supported powder 2 in which P. 1us acidphilus is supported on starch is dispersed.

The outer layer 213 is made of wax (a non-flowing hydrophobic substance), and the outermost third layer 4 is made of gelatin gel (capsule coating).

The capsule of Example 1 can be manufactured by the method (2). That is, from the first nozzle of the triple nozzle (not shown), the number of viable bacteria is 6°5xto'/
200g of lactic acid bacteria-supported starch powder and 800g of glycerin
A dispersion liquid uniformly dispersed in water is simultaneously jetted out from the second nozzle, and a 20% gelatin water solution is jetted out from the third nozzle. In addition, at the time of ejection, each liquid ejected from the triple nozzle is heated to about 55°C. Then, two droplets with a three-layer structure are ejected and formed.
It was dropped into a soybean oil bath (hardening bath) at 0° C. and cooled to obtain capsules of Example 1 having a diameter of about 31 mm.

In Comparative Example 1, the capsule of Example 1 does not have the second layer made of wax, and the dispersion of the first layer is added to the gelatin gel (capsule coating) of the third layer. It is something that is in direct contact.

This was produced in the same manner as in Example 1 by using a double nozzle and simultaneously ejecting the dispersion liquid from the first nozzle and the 20% aqueous gelatin solution from the second nozzle.

(Storage Test) The capsules obtained in Example 1 and Comparative Example 1 were subjected to a storage test in which they were lightly shaken once a day at a temperature of 37° C. and a relative humidity of 65%. The number of viable bacteria was checked every month. The number of viable bacteria was measured by culturing the sample using a commercially available BL agar medium supplemented with 0.05% cysteine hydrochloride. As a control standard in this case, the raw material powder used in this example was diluted five times with dry starch.

Table 1 shows the number of viable bacteria per unit weight when the sample was cultured on the above BL agar medium.

Table 1 Unit: pieces/g [Example 2] FIG. 2 is a schematic cross-sectional view showing a capsule containing bacteria useful for the intestines, which is Example 2 of the present invention.

The capsule of Example 2 is a seamless capsule with a two-layer structure. That is, the first layer 1 at the center is made of solid fat (non-flowable hydrophobic substance), and the outer layer 213 is made of gelatin gel (capsule coating). , Bifido
A carrier powder 2 made of skim milk powder carrying bacteria (bacterium iongum) is uniformly dispersed.

The intestinal useful bacteria-containing capsule of Example 2 was prepared using the method described above (
3). That is, from the first nozzle of a double nozzle (not shown), 16 mols of oil and fat containing 200 g of Vifidus bacteria-supported powder with a viable cell number density of 1.2 x 10''/g are injected.
From the second nozzle, the dispersion liquid uniformly dispersed in 00g is
A 0% aqueous gelatin solution was simultaneously ejected, and droplets with a two-layer structure formed in the same manner as in Example 1 were dropped into a hardening bath, thereby obtaining capsules with a diameter of about 41 cm.

The oil is a mixture of 90 parts of hardened rapeseed oil and 10 parts of rapeseed oil, and is heated to about 50° C. together with the gelatin aqueous solution at the time of ejection to maintain a liquid state. Also,
In Example 2, the curing bath is composed of Miglyol (trade name: Dynamit Nobel, medium chain fatty acid triglyceride) at 20°C.

In the capsule of Example 2, since the oil constituting the first layer is solid at room temperature, the supported powder 2 carrying Bifidus bacteria is fixed in the oil and most of it is isolated from the capsule coating. There is.

Comparison (1) In the capsule of Comparative Example 2, the solid oil constituting the first layer in the capsule of Example 2 was replaced with miglyol, which is a liquid oil even at room temperature. Its manufacture can also be carried out in accordance with Example 2 above.

(Storage Test) A storage test was conducted on the capsule of Example 2 and the capsule of Comparative Example 2 based on the same method as in Example 1. The results are shown in Table 2 below.

Table 2 Unit: pieces/g Although the present invention has been described above based on Examples, it goes without saying that the present invention is not limited to the Examples.

For example, the first N of a three-layer capsule is glycerin,
Although the second layer is made of oil and fat and the third layer is made of gelatin gel, the constituent materials of each layer are not limited to the above materials, and can be changed in various ways. Specifically, the first
Capsules in which the layer is made of a solid material obtained by compression molding a powder carrying lactic acid bacteria, etc. can also be produced by the above method (4).Also, by method (1), instead of glycerin, an oil that is liquid at room temperature is used as the first layer. It may also form a layer.

In the case of a capsule with a two-layer structure, various modifications can be made as in the case of a three-layer structure.

Moreover, although only an example in which intestinal useful bacteria are supported in powder is shown, it goes without saying that the bacteria may be directly dispersed.

Furthermore, although the fats and oils have been described as being solid at room temperature, they do not necessarily need to be solidified, and even if they are in a liquid state, they may be fats and oils that have almost no fluidity at room temperature.

In addition, although the capsule shape is spherical in the above example, it goes without saying that the capsule shape is not limited to this. In particular, when manufacturing by the method (4) above, it is difficult to compress the capsule. It is possible to change the shape in various ways. Therefore, in this case, it is possible to easily produce a capsule containing bacteria useful for the intestines and having a shape suitable for tableting, which constitutes the first layer.

〔Effect of the invention〕

By isolating the encapsulated intestinal beneficial bacteria from the capsule coating via non-fluid oils and fats at room temperature, it is possible to prevent the intestinal beneficial bacteria from coming into direct contact with the capsule coating, and to prevent the intestinal beneficial bacteria from coming into direct contact with the capsule coating. Since moisture and the like can be prevented from penetrating into the interior, moisture and the like in the air can be prevented from having an adverse effect on the useful bacteria. Therefore,
The storage stability of beneficial intestinal bacteria encapsulated in capsules can be greatly improved.

[Brief explanation of drawings]

FIG. 1 is a schematic cross-sectional view showing a capsule containing bacteria useful for the intestines, which is an embodiment of the present invention, and FIG. 2 is a schematic cross-sectional view showing a capsule containing bacteria useful for the intestines, which is Example 2 of the present invention. l...First layer, 2...Supported powder, 3...Second layer, 4...Third layer.

Claims (2)

[Claims] (1) A capsule containing beneficial intestinal bacteria, in which the bacteria useful for the intestinal tract are isolated from the capsule coating via a hydrophobic substance that is non-flowing at room temperature. (2) The capsule containing bacteria useful for the intestines according to claim 1, wherein the bacteria useful for the intestines are carried in powder.