JPS62230714A - Enteric capsule - Google Patents

Abstract

PURPOSE:To provide an enteric capsule composed of a core part obtained by dissolving or dispersing an enteric active component in a liquid substance and a wall membrane composed of a hardened oil having a melting point higher than body temperature, resistant to disintegration in mouth and stomach and easily disintegrating first in the intestine. CONSTITUTION:An enteric active component such as bifidus bacteria or a drug absorbable through intestinal wall is dissolved or dispersed in a liquid substance such as water, liquid oil or fat, alcohol or their emulsion, etc., and the solution or dispersion is used as a core-forming substance. The core-forming substance is encapsulated with a wall-membrane-forming substance composed of a hardened oil having a melting point higher than body temperature. The obtained capsule is resistant to disintegration in mouth or stomach in the case of oral administration and the lowering of the activity of the active component by the action of gastric juice or an enzyme of gastric juice can be prevented. It is easily disintegrated first in the intestine to enable effective utilization of the active component in the intestine. The encapsulation can be easily carried out by conventional method.

Description

[Detailed Description of the Invention] The Retired Emperor Hada Tomomitsu! The present invention provides enteric-coated capsules, more specifically, when ingested orally, the wall membrane of the capsule, which protects the internal organs (core) consisting of intestinal active substances, disintegrates only after reaching the intestine. Accordingly, the present invention relates to a capsule in which substances effective in the intestines can be effectively utilized in the intestines without their activity being impaired by the action of gastric juice or enzymes in the gastric juice.

Conventional technology Conventionally, bifidobacteria were protected from environmental conditions such as oxygen by coating intestinal active substances such as bifidobacteria with fats and oils that melt at body temperature (Japanese Patent Laid-Open No. 57-335
No. 43), a mixture of viable bifidobacterium cells and their protective film forming solution is injected into a coagulating salt solution to coagulate, the coagulated product is dried, and if necessary, an oil or fat having a melting point above body temperature is added. A method for obtaining bacterial cell granules that can be stored for a long period of time by coating with the following methods has been proposed (Japanese Unexamined Patent Publication No. 141281/1981).

However, as disclosed in JP-A No. 57-33543,
Since oils and fats that are fluid at temperatures above 35°C are used, when bifidobacteria coated with such oils are ingested, the oil coating disintegrates in the mouth or stomach, and as a result, the bifidobacteria enter the intestines. There is a problem that most of the bacteria are killed by gastric juices before they reach the target temperature, and in addition, since the bifidobacteria are directly coated with molten oil, heat has an adverse effect on the bacteria.

Furthermore, the method disclosed in JP-A-60-141281 requires a complicated process of solidifying the bacterial fluid and then drying it, and the bacteria may die due to freezing damage during freeze-drying. Furthermore, the bacterial cells are coated on the protective film with an oil or fat that has a melting point above body temperature, such as hydrogenated oil, but at that time, the protective film of the bacterial cell granules obtained by coagulation and drying is thin, There is a possibility that the bacteria may come into contact with the hot hydrogenated oil that melts during coating and die.

Mf, -1 The bacterial granules obtained by the above method are coated with a hydrogenated oil coating on top of the protective film as described above, so they are further protected in the intestine after the hydrogenated oil coating collapses. There is also the problem that it cannot be used effectively in the intestines unless the membrane collapses.

On the other hand, enteric-coated microcapsules include those in which an enteric substance is contained as a core material in a wall made of ethyl cellulose (Japanese Patent Application Laid-open No. 58-67616), and furthermore, enteric-coated microcapsules contain polystyrene, polybutadiene, styrene-methacrylate in the wall material. It is composed of a membrane made of a polymer material such as a methyl acrylate copolymer, and a complex coacervate membrane made of gelatin and an enteric polymer electrolyte (e.g. methyl acrylate-methacrylic acid copolymer) thereon. (Japanese Unexamined Patent Publication No. 105615/1983) has been proposed.

However, there have been no reports yet on enteric-coated capsules using a hydrogenated oil having a melting point above body temperature as a wall membrane.

6. Problems to be Solved by Meiji The present invention deals with beneficial intestinal microorganisms (e.g. bifidobacteria), medicinal substances that are absorbed in the intestine, and medicinal substances that are active in the intestine without being absorbed in the intestine. When a substance is encapsulated and ingested orally, the capsule wall does not disintegrate in the mouth or stomach, and the enteric coating only disintegrates once it reaches the intestines, and can be easily encapsulated by conventional methods. The challenge is to provide capsules.

The present inventor has solved the above-mentioned problem when encapsulating an intestinal effective substance dissolved or dispersed in a liquid substance as a core-forming substance and using a hardened oil with a melting point higher than body temperature as a wall-forming substance. The present invention was achieved based on the knowledge that it is possible to provide an enteric-coated capsule that can achieve the following.

The present invention will be explained in detail below.

I related to the present invention! A-soluble capsules are characterized by being composed of a core made of a substance effective in the intestines dissolved or dispersed in a liquid substance, and a wall made of a hydrogenated oil having a melting point above body temperature.

The term "intestinal effective substances" as used herein refers to various pharmaceutical substances that are active after being absorbed through the intestinal wall, various pharmaceutical substances that are active without being absorbed through the intestinal wall, and bifidobacteria that are active in the intestine. Intestinal effective microorganisms, etc.

The present invention has a core that is made by dissolving or dispersing intestinal effective substances in a liquid substance, and the liquid substance used here may be any substance that is liquid at room temperature. There are no restrictions, and examples include water, liquid fats and oils, alcohol, and emulsions thereof, and the choice may actually be made depending on the type of enteric active substance to be dissolved or dispersed therein. For example, in the case of bifidobacteria, substances inert to bifidobacteria such as glycerin, medium chain triglyceride (MCT), and corn oil are selected and used.

In addition, enteric substances that are dissolved or dispersed in a liquid substance and used as the core material of capsules include: (1) Pharmaceutical substances whose physiological activity may be reduced by gastric juice or enzymes in the gastric juice, such as vancreatin. Enzymes, antibiotics such as erythromycin, hormones, ■Substances that stimulate the stomach or inhibit its digestive function, such as ethionamide, ateprin, salicylic acid, tannic acid, ■Active in a concentrated manner in the intestines Examples include medicinal substances such as anthelmintic agents, intestinal preservatives, etc., and (2) effective intestinal microorganisms that are easily killed by gastric acid, such as Bifidobacterium.

The proportion (concentration) at which these enteric substances are dissolved or dispersed in the liquid substance is not particularly limited, as long as the liquid form can be maintained.

The present invention is capable of producing enteric-coated capsules by encapsulating a substance that is effective in the intestines in a liquid form as a core material and using a hardened oil having a melting point higher than body temperature as a wall material. get.

Here, the hardened oil as the wall material can be used without any restrictions as long as it has a melting point above body temperature, and if necessary, an emulsifier can be added to impart hydrophilicity to the surface of the capsule. You can also do it.

Next, as a method for preparing enteric-coated capsules according to the present invention,
Examples include encapsulation using a submerged drying method, a spray drying method, a spray cooling method, etc., but it is preferable to prepare by encapsulating using a spray cooling method using a three-dimensional nozzle system. This encapsulation method using the Miura body nozzle method is a newly developed method (Japanese Patent Application No. 61-42276), and its outline is as follows: Encapsulation is carried out by spraying a liquid substance as a jet stream into a cooling gas, a molten substance of hardened oil as a wall material from a medium-walled cylindrical tube, and pressurized air from an outer cylindrical tube, respectively. This method has advantages such as being able to easily control the particle size of the capsules and not requiring a step of drying the capsules.

The capsule according to the present invention has a particle size of 10 to 2000 μm,
Preferably it is in the range of 100 to 1000 μm, and
The thickness of the wall membrane is set at a total of 20 to 20% relative to the particle size in order to prevent capsule destruction due to previous expansion and contraction when ingested orally.
80%, preferably in the range of 50-70%.

As described above, the enteric-coated capsule according to the present invention is encapsulated using an enteric active substance dissolved or dispersed in a liquid substance as a core material and a hardened oil having a melting point higher than body temperature as a wall material. Because it is a product obtained from a gastrointestinal tract, when it is ingested orally, the active substance forming the core of the capsule is protected by a wall made of solidified hydrogenated oil and is protected against the action of gastric juices and enzymes in the gastric juices. It is not until it reaches the intestine that the intestinal fluid is exposed due to the collapse of the above-mentioned wall membrane mainly due to the action of pancreatic lipase in the intestinal fluid, and becomes effectively utilized within the intestine.

In addition, the enteric-coated capsule of the present invention is prepared by simply dissolving or dispersing the enteric substance as a core substance in a liquid substance, and is hardly affected by heat, enzymes, moisture, etc. during its preparation. Therefore, if encapsulation using the above-mentioned hydrogenated oil as a wall material is carried out by the spray cooling method using the Miura body nozzle method as described above, it will have an adverse effect on the intestinal effective substances, which are the core substances. It becomes possible to encapsulate without

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

1 Cliff ± and l Practical Example l Bifidobacterium longum (Bifidbacterium longum)
terium longum) ATCC-15707
A 10% corn salad oil dispersion of the above-mentioned bacteria dispersed in corn salad oil at a ratio of about 100 g per 1) was used as the core material, while hydrogenated palm oil having an edge point of 58°C was used as the wall material. encapsulation was carried out according to the spray cooling method using the Miura nozzle described above. The average particle size of the obtained capsules was 150 μm, and the film thickness was 40 μm.
It was μm.

The above capsules were mixed with artificially prepared gastric juice (pepsin 0.
Br1gg5 Liver Broth containing 32% was adjusted to al13.0 with hydrochloric acid) and reacted with the above gastric juice while stirring in a constant temperature bath at 37°C for 3 hours. After the reaction, the filtered capsules were thoroughly washed with water, and the number of viable bifidus bacteria was measured by a conventional method.

As a result, the number of viable bacteria in 1 g of capsules at the start of the reaction was 4 x 10@, but after the reaction the number of viable bacteria was 3 x 10'.
Therefore, there was virtually no effect of gastric juice. On the other hand, as a control, when the above-mentioned Bifidobacterium powder was dispersed in peptone water and the same reaction was carried out by adding it to the above-mentioned gastric juice, the number of viable bacteria in 1 g of bacterial powder at the start of the reaction was 1X10''. After the reaction, the temperature dropped to less than 10 liters and almost died.

Example 2 15g of aspirin was mixed with medium chain triglyceride (MCT)
The 100 g of the dispersion was encapsulated in the same manner as in Example 1. The average particle size of the obtained capsules is 500
μm, and the film thickness was 150Ij1).

The above capsules were added to the same artificial gastric juice as used in Example 1 and reacted at 37°C for 3 hours, and then the capsules were filtered. The amount of aspirin in the obtained filtrate was measured, but it was not detected.

Next, when lipase was applied to the filtered capsules, all the capsules disintegrated within 15 minutes and almost 100% of aspirin was recovered.

Claims (3)

[Claims] (1) An enteric-coated capsule characterized by comprising a core made of a substance effective in the intestines dissolved or dispersed in a liquid substance, and a wall made of a hydrogenated oil having a melting point above body temperature. (2) The enteric-coated capsule according to claim (1), wherein the enteric active substance is Bifidobacterium. (3) The enteric-coated capsule according to claim (1), wherein the enterically effective substance is a medicinal substance that is absorbed through the intestinal wall.