JPH0482827A - Entero-soluble capsule - Google Patents

Abstract

PURPOSE:To obtain an entero-soluble capsule capable of attaining to inside of an intestine and readily dissolving having resistance to an acid without feeling of a foreign matter in adding to other food by dispersing powder of an enteral effective substance or a heat-sensitive substance into hardened oils and fats having melting point exceeding body temperature and making a capsule. CONSTITUTION:Powder of an enteral effective substance or a heat-sensitive substance (e.g. dried lactic acid bacterium containing one, two or more of powdered skim milk, dextrin, cellulose and starch as dispersion medium) is dispersed into hardened oil (e.g. hardened soybean oil, hardened rape oil, hardened coconut oil or palm kernel oil) having melting temperature (preferably 40-60 deg.C) exceeding body temperature and made to a capsule. The capsule body by said method is obtained in simple processes and has a simple structure without changing its effect.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to enteric-coated capsules that are effectively dissolved in the intestines. More specifically, enteric-coated capsules are enteric-coated capsules that disintegrate only after the enteric active substance or heat-sensitive substance reaches the intestine when taken orally, and whose activity is not impaired even when subjected to the action of gastric juice or enzymes in the gastric juice. Regarding.

(Prior art) In the past, effective intestinal substances such as bifidobacteria were coated with fats and oils that melt at body temperature (Japanese Patent Application Laid-Open No. 57-33543) or raw in order to protect them from surrounding conditions such as oxygen. A mixture of bacterial cells and their protective film-forming solution is injected into a coagulating salt solution to solidify, and after drying, if necessary, coated with an oil or fat having a melting point above body temperature to form bacterial cells suitable for long-term storage. Method for obtaining granules (JP-A-60-141281)
is proposed.

However, in the former method, oils and fats that exhibit fluidity at 35°C or higher are used, so when bifidobacteria coated with such oils are ingested orally, the oils and fats disintegrate in the mouth or stomach, resulting in bifidobacterium There is a problem that most of the bacteria are killed by gastric juices before they reach the intestines, and the coating is simply a mixture of bifidobacteria and oil, so this mixed cream can only be ingested in a limited way. Ta.

In addition, the latter method involves encapsulating bacterial cells and a substance that has a humidity control function and a dehydration shock prevention function in a calcium alginate film and then coating them with oil, which results in a complicated process and high costs. there were.

On the other hand, enteric-coated capsules include those in which an enteric substance is contained as a core material in a wall made of ethylcellulose (Japanese Patent Application Laid-open No. 58-67616); Japanese Patent Laid-Open No. 1986-55, in which a polymer membrane such as a methyl conjugate is coated with a complex coacervate membrane made of gelatin and an enteric polymer electrolyte to form a double structure.
405615) etc. have been proposed.

(Problems to be Solved by the Invention) However, all of these methods are complicated and time-consuming, and a simple and concise method has not yet been reported.

That is, although there is a technique for coating bifidobacterium cells or gel with oil or fat in order to improve the storage stability of bifidobacteria, a polynuclear capsule in which bifidobacterium powder is uniformly dispersed in oil or fat as in the present invention has not been obtained.

The present invention provides effective intestinal substances, such as bifidobacteria, and pharmaceutical substances that are absorbed in the intestines or are active without being absorbed in the intestines, by encapsulating them in a powder form. An object of the present invention is to provide an enteric-coated capsule that does not disintegrate at a temperature of 100 mL and is easily melted after reaching the intestine.

(Means for Solving the Problems) The present invention is an enteric-coated capsule in which a powder of an intestinally effective substance or a heat-sensitive substance is dispersed in a hydrogenated fat or oil having a melting point above body temperature, and the dispersed powder is encapsulated.

Substances that are effective in the intestine include: ■Medicinal substances whose physiologically active functions may be reduced by gastric juice or enzymes in the gastric juice, such as enzymes such as pancreatin, enzymes or hormones such as erythromycin, and ■Medicinal substances that may irritate the stomach. Substances that give the effect of dissolving or inhibiting the digestive function, such as ethionamide, athepurin salicylic acid, tannic acid, ■Medicinal substances that act intensively in the intestine, such as anthelmintics, intestinal preservatives, and (2) active substances in the intestines that are easily killed by gastric acid, such as bifidobacteria.

In addition, heat-sensitive substances are substances that, when left in a temperature range from above human body temperature to the boiling point of water for a certain period of time, change their structure or color or lose their activity due to the influence of heat. etc. refers to substances whose original properties change. Specific examples of heat-sensitive substances include vitamin C1, various enzymes, and useful bacteria.

When using bifidobacteria for encapsulation, the concentration of bifidobacteria in the resulting product should be 10 7 to 10 8 bacteria/g, considering the daily intake requirement, so a highly concentrated cultured bacteria powder is preferred. The degree of concentration is 109-1011
pieces/g. This highly concentrated cultured bacteria powder is mixed with about 10 times the weight of hydrogenated oil and fat to obtain a hydrogenated oil and fat capsule having 10B to 10IO bacteria/g. When Bifidobacterium is in powder form, it is not affected even if it is immersed in oil or fat at 40 to 60°C for a short period of time, for example, within 30 minutes, and the number of viable bacteria remains unchanged.

Examples of methods for preparing intestinal capsules include encapsulation methods such as submerged drying method, spray drying method, and spray cooling method.
Among these, the spray cooling method is preferred from the viewpoints of (1) high encapsulation rate and (2) small particle size.

For example, after a hydrogenated fat with a melting point of 45° C. is dissolved in a jacketed tank, dry powder of Bifidobacterium is quickly dispersed in the oil. While stirring the dispersion liquid uniformly, a pump (snake pump, gear pump, plunger pump) supplies a constant flow rate to the nozzle, and cold air is sprayed into the chamber in parallel flow. At this time, the cold air should not be flowed in parallel (or counterflow may be used. Cool the hardened oil at a sufficient cooling temperature and solidification time necessary to solidify it. The temperature of the cold air for cooling is -80 to 20 degrees Celsius. Under these conditions, a capsule body with a diameter of 30 to 2000 units can be obtained.

Considering the solubility in the intestines, the diameter is 50~1ooo/
7m is preferred. The obtained capsule is a polynuclear capsule in which the substance to be encapsulated is uniformly dispersed in the oil and fat.

Intestinal active substances or heat-sensitive substances are encapsulated in a powdered state, but at that time, one or more powders such as skim milk powder, dextrose, cellulose, starch, etc. may be added as a dispersion medium. is preferred. By adding these dispersion media, the water activity of the enterically active substance or heat-sensitive substance is reduced, and as a result, the shelf life of the encapsulated product is increased. Further, the addition of the dispersion medium is preferably 5 to 50% by weight. If it is less than 5%, there is no effect on storage stability, and if it exceeds 50% by weight, the shape of the capsule becomes irregular, which is not preferable.

The type of hydrogenated fat may be any oil that does not melt at body temperature (approximately 38°C), such as hydrogenated soybean oil, hydrogenated rapeseed oil, hydrogenated coconut oil, palm kernel oil, and hydrogenated corn oil. These are used by adjusting the melting point to an appropriate value depending on the degree of hydrogenation. Hardened beef tallow has a melting point of 53°C, so it can be used as is. The melting point of the hardened oil is preferably 40 to 60°C. If it is lower than 40°C, the fluidity at room temperature will decrease, and if it exceeds 60°C, the influence of heating on the encapsulated material will be increased, which is not preferable.

The enteric-coated capsules of the present invention can be hardened into capsules by dispersing a powder of enterically effective substances or heat-sensitive substances in hardened fats and oils that do not melt at body temperature, and then spraying them into cooled air using a simple nozzle. .

Therefore, even if it is ingested orally, it does not dissolve at body temperature and reaches the intestines without being broken down by gastric juice or enzymes in the gastric juice. Internally active substances or heat-sensitive substances will be exposed in the intestines.

The present invention and its effects will be explained below with reference to Examples.

(Example) Example 1 Cured beef tallow stored at 60°C (m, p, 53°C) 55
450 g of a dry bacterial strain containing 5 x 10'' bifidobacteria per 1 g was dispersed in 0 g, and fed to the nozzle with a high-pressure pump while stirring.The bifidobacterium dispersion was sprayed from a mono nozzle at an atmospheric temperature of 5°C in the chamber. , particle size 4
Capsule bodies ranging from 0 to 600 tm were obtained.

The content of Bifidobacteria was 3.5 x lO''/g.

This capsule body was prepared in artificial gastric fluid (pH 3,0) at 37°C.
3.5 XIO” pieces/g even after 3 hours, 3
．． The number of viable bacteria was 5 x 1010 cells/g.

Example 2 Bifidobacterium longum (Bifidobacterium longum)
terium ton un) in salad oil.
A liquid dispersed at 0 W/W% was used as the core material, and hydrogenated rapeseed oil with a melting point of 53° C. was used as the wall material, and the core material was encapsulated by spray cooling using a mono nozzle.

The average particle size of the obtained microcapsules was 200 ttt.
It was h.

The same good results as in Example 1 were obtained in the acid resistance test.

Example 3 Bifidobacterium longum (Bifidobacterium longum)
The core material was prepared by dispersing live bacterial cells of C. cterium jon um at a concentration of 10 w/w% in hydrogenated oil with a melting point of 37° C. kept at 40° C., and sprayed and cooled using a two-liquid nozzle. encapsulated. The average particle size of the resulting microcapsules was 100 tm, and the number of viable bacteria in the capsules was 5 x 10''/g.

The same good results as in Example 1 were obtained in the acid resistance test.

Example 4 Bifidobacterium longum (Bifidob
A dispersion of viable bacterial cells of A. The mixture was added dropwise to an organic liquid (8% ethanol aqueous solution). The average particle size of the obtained microcapsules was 1.5 ml, and the film thickness was 400 mm.

The same good results as in Example 1 were obtained in the acid resistance test.

Example 5 Cured beef tallow (300g of vitamin C powder kept at 60°C)
m, p, 53° C.) and spray-cooled. The resulting microcapsules have a particle size of approximately 500 u.
It was a stable polynuclear dispersion capsule of vitamin C of rn.

The same good results as in Example 1 were obtained in the acid resistance test.

Example 6 Cured beef tallow heated to 60°C (m, p, 53°C) 80
100 g of bifidobacteria dry powder and 100 g of cornstarch were dispersed in 0 g of the mixture, and the mixture was sprayed and cooled in the same manner as in Example 1. The particle size of the obtained capsules was approximately 300 capsules, and the number of bacteria in the capsules was 5 xlo''/g.

The same good results as in Example 1 were obtained in the acid resistance test.

Example 7 Hydrogenated rapeseed oil heated to 58°C (n+, p, 53°C)
150 g of bifidobacteria dry powder and 100 g of skim milk powder were dispersed in 750 g, and the mixture was spray-cooled by the method of Example 1. The particle size of the obtained capsules was about 100 to 450, and the number of bacteria in the capsules was 7.2 x lO''/g.

The same good results as in Example 1 were obtained in the acid resistance test.

(Effects of the Invention) The capsule body according to the present invention is: - Because it is a fine spherical body, it does not feel like a foreign body even when added to other foods. - Because it has four acidic properties,
Even when added to acidic drinks or yogurt, it does not change due to the acid in the stomach; it dissolves only when it reaches the intestines and has an effective effect on the intestines.

Moreover, (1) the process is much simpler than the conventional encapsulation method, and the structure of the capsule itself is simple. Moreover, the effect is no different from the conventional one.

Handbook continuation supplementary book

Claims (5)

[Claims] (1) Enteric-coated capsules obtained by dispersing a powder of an intestinally effective substance or a heat-sensitive substance in hydrogenated oil and fat having a melting point above body temperature, and encapsulating the resultant. (2) The intestine according to claim 1, wherein the powder of the enteric effective substance or the heat-sensitive substance is dried lactic acid bacteria containing one or more of the group consisting of skim milk powder, dextrin, cellulose, and starch as a dispersion medium. Soluble capsule. (3) The enteric-coated capsule according to claim 1, wherein the enteric effective substance or heat-sensitive substance is a medicinal substance that is absorbed through the intestinal wall. (4) Claim 1, wherein the hydrogenated fat has a melting point of 37 to 60°C;
Enteric-coated capsule according to 2 or 3. (5) The enteric-coated capsule according to any one of claims 1 to 4, wherein the enteric-coated capsule has a diameter of 30 to 1000 mm.