JP4388607B2 - Casein hard capsule and method for producing the same - Google Patents

Description

BACKGROUND OF THE INVENTION
The present invention relates to a casein hard capsule comprising calcium-free casein having a calcium content of 1% or less, in which calcium ions in casein are substituted with hydrogen ions and sodium ions, and a method for producing the same. The obtained hard capsule can be used as a hard capsule for food or medicine.
[0002]
[Prior art]
Conventionally, hard capsules made of gelatin have been widely used to orally administer a certain amount of contents such as unpleasant odors and stimulating drugs. Hard capsules are an effective means for avoiding the disintegration difficulty seen in tablets, the accompanying deterioration in absorbability, and the alteration of drugs due to pressure during tableting.
Currently, only gelatin capsules are used as hard capsules. The reason for this is that gelatin hard capsules do not dissolve in cold water, but dissolve in the stomach because they dissolve in water at about body temperature and acidic gastric juice.
On the other hand, the hard capsule of the present invention is soluble in cold water but not in acidic liquid, so it passes through the acidic stomach with gastric acid while maintaining the shape of the hard capsule, and the liquid in the small intestine, which is the next digestive organ. Since it is neutral or alkaline, it has a unique property of dissolving here, and by using this property, it is possible to release the medicine in the small intestine by filling the medicine in a hard capsule. It is extremely effective against intestinal diseases.
It is also useful because it can be delivered to the target site without being killed by gastric acid, if it is taken not only in medicine but also filled with lactic acid bacteria and Bibizu bacteria that are recognized as food. is there.
[0003]
The natural protein casein has been extensively studied for its high availability and nutritional importance. As industrial applications, it is widely used for dairy foods such as cheese, binders, adhesives, water-based paints, emulsifiers, plastics, nutrients and the like.
Conventionally, the inventions related to films, sheets or fibers using casein are disclosed in JP-A-55-150839, JP-B-58-4538, JP-B-58-31182, JP-A-62-138145 and JP-A-62-138145. No. 6-197700 is described, but there is no description about the capsule.
On the other hand, regarding the encapsulation of casein, there is a description in JP-A-3-47042 that Lenette casein can be used simply as a capsule, but there is a description referring to a specific method for forming a capsule and the physical properties of the obtained capsule. Of course, there is nothing to say about hard capsules.
Microcapsules using casein as a wall membrane material are disclosed in Japanese Patent Publication No. 12-170, Japanese Patent Publication No. 25-2691, Japanese Patent Publication No. 37-12379, and Japanese Patent Publication No. 53-43567. However, depending on the type of dural treatment agent, problems in physiological metabolism remain, and it is not suitable for both food and medicine.
Furthermore, Japanese Examined Patent Publication No. 60-20059 relates to a method for producing microcapsules suitable for foods or pharmaceuticals using casein, and discloses that paracasein is immobilized by heating in the presence of calcium ion itself. ing.
[0004]
When the present invention is compared with the above prior art, what is disclosed in the prior art is generally called a microcapsule, and the microcapsule has a target active ingredient called a core component or a core component as a coating forming agent such as casein. It is a fine sphere with a surface wall formed and encapsulated, and its size is 1 to 100 μm. The core component is dispersed or dissolved in the coating component solution, and is manufactured by the complex coacervation method or the spray dry method. It is normal. On the other hand, the hard capsule of the present invention is a mere container for storing the contents by fitting the body and the cap, and the size or diameter or length of the capsule is several mm to several tens mm. Yes, the manufacturing method is also case-injection molding of casein solution, both of which are called “capsules”, but they are substantially different in shape, properties, application, and manufacturing method. It is.
In Japanese Patent Publication No. 58-33093, which discloses a casein capsule, glycerin, cellulose, and starch are mixed into an alkali or alkaline earth metal salt of a protein containing casein, and water is added to the high temperature of 110 ° C. or higher. However, the capsules are kneaded with an extruder to form capsules, but the type of capsules is not specified, and the production method is different from the capsule molding method of the present invention. There is no explanation for the content or solubility in water.
[0005]
[Problems to be solved by the invention]
It is an object of the present invention to provide a casein hard capsule that can be used for both pharmaceutical use and food use and has an excellent function of conveying contents to the small intestine, which was not obtained with a conventional hard capsule. .
[0006]
[Means for Solving the Problems]
As a result of diligent research to achieve the above-mentioned problems, the present inventors have determined that casein hardening is composed of decalcified casein having a calcium content of 1% by weight or less, in which calcium ions in the casein of the natural protein are replaced with hydrogen ions and sodium ions. The present inventors have found that the capsule is suitable as a hard capsule that can be used for both food use and pharmaceutical use, and exhibits the function of conveying contents to the small intestine, and has completed the present invention.
The decalcified casein used in the present invention is a method of neutralizing casein, a natural protein, into an aqueous solution under acidic conditions and neutralizing with sodium hydroxide or the like or an adsorption separation method using a chelate resin. It is obtained by the method of replacing with The calcium content in the decalcified casein is 1% by weight or less.
When the calcium content is more than 1% by weight, the molded capsule surface becomes uneven, partially perforated, and does not function as a capsule. This is presumed to be because the amount of casein micelles due to residual calcium is relatively increased, and the continuity of the membrane is impaired.
[0007]
In the method for producing casein hard capsules according to the present invention, decalcified casein is dissolved in distilled water or deionized water by ion exchange, an aqueous solution is prepared, and a rod-shaped mold having the shape of a capsule is immersed in the solution, and constant After pulling up at a speed and drying with hot air, the capsule is extracted from the rod-shaped mold and cut into a desired size to form a casein hard capsule.
In addition, a preservative, a colorant, a light-shielding agent, a fragrance and the like may be appropriately added to the decalcified casein as necessary.
Furthermore, in the present invention, when flexibility is required for casein hard capsules, one or more selected from glycerin, sorbitol and soybean lecithin as a plasticizer is 10 to 50% by weight, more preferably 20 to 40% by weight. % Content. If the plasticizer is less than 10% by weight, a sufficient plasticizing effect cannot be obtained. If the plasticizer is more than 50% by weight, the plasticizer becomes sticky due to bleed out, or the shape as a hard capsule is not maintained.
[0008]
In the present invention, it is effective to add a filler in order to further improve the rigidity and dimensional stability of the hard capsule. As the filler, one or more selected from rice starch, potato starch, corn starch starch particles, powdered or refined cellulose, talc and kaolin are used. The amount of filler added is 10-30% by weight per total weight. If the added amount of the filler is less than 10% by weight, the effect of improving the rigidity and dimensional stability cannot be expected. If the added amount is more than 30% by weight, the capsule becomes brittle or does not retain its shape as a hard capsule.
[0009]
The specific reaction that the hard capsule formed from the decalcified casein invented as described above disintegrates in the small intestine is currently being confirmed, but at the laboratory level that reproduces the state of the small intestine, the pH at a temperature of 36 ° C is Although there is no change in the hard capsule in the hydrochloric acid solution of 2, the hard capsule is easily dissolved in the neutral to alkaline region where the pH is 6 or higher, so that the hard capsule does not dissolve in the gastric juice and hard in the small intestine. It is considered that the contents in the capsule can be conveyed. Furthermore, the low oxygen permeability of casein film is well known, but the hard capsules obtained in this invention also have a remarkably low oxygen permeability, so the contents of drugs etc. that are adversely affected by oxygen It seems to be useful as a capsule for transporting things into the body.
[0010]
【Example】
The following examples illustrate the present invention and its effects in detail. However, the present invention is not limited to these examples.
[Example 1]
Casein containing more than 1% by weight of calcium obtained from Kishida Chemical Co., Ltd. was ion-exchanged with a sodium-type chelate resin manufactured by Mitsubishi Kasei Co., Ltd. to prepare a decalcified casein having a calcium content of 0.7% or less.
Dissolve this decalcified casein in distilled water to prepare a 20% by weight capsule forming stock solution, immerse the stainless steel capsule mold in this stock solution, slowly pull it up, and then dry it with hot air at 70 ° C for 20 minutes. Casein hard capsules of the same size as Japanese Pharmacopoeia No. 3 capsules were prepared. The capsule thickness was 100 μm over the entire area.
When this capsule was immersed in a hydrochloric acid solution having a pH of 2 at a temperature of 36 ° C., it did not dissolve at all. Next, when immersed in an acetate buffer solution having a pH of 6 at a temperature of 36 ° C., it swelled greatly and dissolved. Furthermore, when immersed in a commercial standard buffer having a pH of 9.9 at a temperature of 36 ° C., it dissolved simultaneously with the swelling.
[0011]
[Example 2]
A capsule-forming stock solution is prepared by dissolving 20 g of decalcified casein having a calcium content of 0.1 wt% or less and 4 g of edible glycerin in 96 g of distilled water obtained by the same method as the ion exchange method shown in Example 1, and preparing a capsule capsule made of stainless steel The mold was immersed in this stock solution, slowly pulled up, and then dried with hot air at 70 ° C. for 20 minutes to prepare casein hard capsules having the same size as Japanese Pharmacopoeia No. 3 capsules. Capsule thickness over the entire area
100 μm.
This capsule was more flexible than the capsule of Example 1.
When this capsule was immersed in a hydrochloric acid solution having a pH of 2 at a temperature of 36 ° C., it did not dissolve at all. Next, when immersed in an acetate buffer solution having a temperature of 36 ° C. and a pH of 6, it swelled and dissolved greatly. Furthermore, when immersed in a commercially available standard buffer having a pH of 9.9 at a temperature of 36 ° C., it dissolved simultaneously with the swelling.
[0012]
[Example 3]
A capsule forming stock solution is prepared by dissolving 20 g of decalcified casein having a calcium content of 0.1% by weight or less, 6 g of edible glycerin and 4 g of rice starch in 120 g of distilled water obtained by the same method as the ion exchange method shown in Example 1. A stainless capsule type was immersed in this undiluted solution, slowly pulled up, and then hot-air dried at 70 ° C. for 20 minutes to prepare casein hard capsules of the same size as Japanese Pharmacopoeia No. 3 capsules. The capsule thickness was 100 μm over the entire area.
This capsule was superior to the capsule of Example 1 in dimensional stability in an atmosphere of 23 ° C. and 50% RH.
The pH dependence of the solubility of the capsule was similar to that in Example 1 and Example 2.
[0013]
[Comparative Example 1]
Casein containing 5% by weight of calcium obtained from Kishida Chemical Co., Ltd. was ion-exchanged with a sodium-type chelate resin manufactured by Mitsubishi Kasei Co., Ltd. to obtain a calcium content of 2% by weight. Dissolve 20 g of the obtained casein and 4 g of edible glycerin in distilled water to prepare a capsule-forming stock solution having a solid content of 20% by weight. And dried with hot air for 20 minutes to prepare hard capsules. This hard capsule had an uneven capsule surface and a partial hole, and did not function as a capsule.
[0014]
【The invention's effect】
The casein hard capsule of the present invention is a decalcified casein hard capsule derived from a natural protein, and has no unpleasant odor or irritating odor in terms of conveying the contents to the small intestine by utilizing the pH dependence when dissolved in an aqueous solution. The capsule has excellent rigidity and dimensional stability, and is useful as a hard capsule for both food and medicine.

Claims (3)

One or more selected from glycerin, sorbitol and soybean lecithin as a plasticizer is 10 to 50% by weight per total weight, and as a filler, rice starch, potato starch, corn starch, powdered or refined cellulose, talc, It consists of decalcified casein containing 10 to 30% by weight of one or more selected from kaolin , with calcium ions in casein replaced by hydrogen ions and sodium ions, and having a calcium content of 1% by weight or less. Casein hard capsule. 1 wt. Of calcium content obtained by replacing casein, a natural protein, with aqueous solution under acidic conditions and neutralizing with sodium hydroxide or by adsorption separation using a chelate resin, replacing calcium ions in casein with hydrogen ions and sodium ions. %. A method for producing a hard capsule, comprising impregnating a capsule mold in an aqueous solution of decalcified casein in an amount of 1% or less and drying the adhered liquid film. One or more selected from glycerin, sorbitol and soy lecithin as a plasticizer and 10 to 50% by weight per total weight and / or as a filler rice starch, potato starch, corn starch, powdered or refined cellulose, talc and 3. The method for producing hard capsules according to claim 2, wherein 10 to 30% by weight of at least one selected from kaolin is added as required, based on the total weight.
[0001]