JPH0959184A - Enteric packaging method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To seal various drugs, health foods, etc., for oral administration with an enteric package to protect the drug, etc., from the gastric juice in the stomach which is the 1st organ accepting the swallowed drug package and start the disintegration by contacting with intestinal juice in the intestine to easily release the content into the small intestine. SOLUTION: The enteric packaging of a drug or a health food is performed by applying a coating agent having the acid resistance characteristic to WAKAME seaweed (Undaria pinnatifida) as well as the water-resistance of barium and produced by using an extract (1) of the leaf of seaweed such as WAKAME seaweed as a main component and adding barium sulfate thereto. As an alternative, the enteric packaging of a drug or a health food is performed by using a capsule produced by utilizing a new material composed of a liquid mixture of gelate and an extract (2) having high acid resistance and water resistance.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention, in the case of hermetically packaging medicines, health foods, etc., which are desired to be released in the intestine and swallowing them orally, isolates and protects from stomach acid in the stomach, and then enters the intestine to contact with intestinal fluid. The present invention relates to an enteric packaging method capable of easily disintegrating the packaging portion and releasing the contents such as medicines and health foods in the intestine.

[0002]

2. Description of the Related Art Heretofore, enteric-coated packaging has been mainly used as granules, pills, tablets or capsules, for example, sucrose, starch, talc, gum, glucose, crystalline cellulose, lactose,
Calcium carbonate, gelatin, casein, alginate,
It has been practiced to form one-layer or multi-layer coatings and protective layers using one or more materials such as dilan gum.

[0003]

[Problems to be Solved by the Invention]

2. Description of the Related Art In many cases, the enteric-coated package as shown in 2. Description of the Related Art after swallowing, strong gastric acid impairs the packaging, and the effect of the contents is almost lost, or the packaging is too strong.
In the stomach as well as in the intestines, the packaging may not be collapsed and may be excreted in its original form outside the body.
It is actually recognized by the medical personnel concerned that it is not always easy to select and apply an appropriate enteric coating method because the environment of the stomach and intestines may fluctuate and not be constant.

[0004]

In the present invention, the extract extracted from the seaweed thalli (especially salted wakame seaweed) contains natural sodium alginate and short fibers as well as phosphorus, iron, calcium, potassium and other constituent structures. It is supple and durable,
It is resistant to gastric juice (mainly hydrochloric acid and salt) and does not disintegrate in the stomach, but is not resistant to intestinal juice (alkaline, mainly potassium hydrogen phosphate) and has the property of beginning to disintegrate when it comes into contact with intestinal juice in the intestine. In the viscous liquid extracted from the seaweed leaf body, the calcium component that seems to be contained in the leaf body was replaced with a part of sodium alginate sodium, which is the main constituent of the seaweed leaf body, to form water-insoluble calcium alginate. It is thought that they have changed and contributed to stabilization. Even such a strong layer easily begins to disintegrate when it comes into contact with the intestinal fluid that is weakly alkaline, and the seaweed leaf extract and short fibers in the packaging main part disintegrate, as well as an environment that promptly releases the contents into the intestine. Changes to.

[0005]

In the present invention, a medicine, health food, etc. are usually packaged at room temperature using an extract extracted from seaweed leaves, so that the contents are not damaged in the stomach during the packaging process at high temperature. It withstands gastric acid and does not disintegrate, then softens immediately upon entering the intestine. Wakame seaweed, kelp, etc. are usually used for food, and it is a known fact that they are digested in the intestine. They are easily disintegrated by the action of intestinal fluid, and their contents are almost free from changes in the gastrointestinal environment. It is possible to realize an enteric package that can be stably released in the intestine without being dominated.

[0006]

【Example】

Example 1 A blanched salted wakame seaweed was washed with water to remove salt and impurities, and a small amount of sodium hydrogencarbonate was added to water or lukewarm water to allow it to stand. After 5 to 10 minutes, the wakame absorbs water and expands to 4 to
Expand to 5 times the size. Take out the wakame seaweed, drain it, put it in a cotton cloth, (mesh cloth about the size of a washcloth), nylon cloth, wrap it, and squeeze it out in the manner of bean jam.
An extract (1) having a viscosity of 500 cps to 2000 cps is obtained. The liquid obtained by mixing the extraction liquid (1) with 6% by weight of barium sulfate gives the extraction liquid (2) having excellent acid resistance and water resistance. Barium sulfate (30% by weight) and plate gelatin or powder gelatin (1 part) were added to 9 parts of this extract (1), and the mixture was boiled in water and dispersed, and then placed on a flat stand such as polyethylene or polypropylene which has good mold release properties. When dried, a thin plate that is strong against acid and weak against weak alkali can be obtained. Using this as a raw material to make capsules and to drink medicine, it becomes a new raw material with optimal conditions for enteric coating.

Example 2 Seaweed extract (1) was mixed with barium sulfate and stirred to obtain seaweed extract (2). Seaweed extract (1) 94g Barium sulfate 6g Total 100g

Example 3 Extract (1) of Example 1 and Extract (2) of Example 2
The commercially available gelatin and capsules (# 00) were filled with 0 to 8 g of fine-grained bifidobacteria (health-prevention medicine) and sealed in two capsules. The capsules of the extract (1) are used as the sample (1) and the capsules of the extract (2) are used as the sample (2).

Example 4 Next, the results of an enteric disintegration test according to the Japanese Pharmacopoeia are shown.
The number of test sample packages is 6, respectively. 1st liquid (artificial gastric juice) 2nd liquid (artificial intestinal fluid) Specimen (1) 6 pieces All did not disintegrate in 1 hour 6 pieces Disintegrate in 5 minutes Specimen (2) 6 pieces Not disintegrate in 2 hours All 6 pieces Collapses in 5 minutes

Further, the results of the immersion test for various acidic aqueous solutions of the specimens (1) and (2) are shown in the table below. Acidic aqueous solution Specimen (1) Specimen (2) 10% hydrochloric acid 1 hour after exfoliation, no disintegration 20% Acetic acid 1 hour exfoliation, no disintegration Artificial gastric juice (Japanese Pharmacopoeia pH 1, 2) Exfoliation after 1 hour , No collapse

Next, the results obtained by immersing in artificial gastric juice (pH 1, 2) for 1 hour, taking out and immersing in various alkaline aqueous solutions are shown in the table below. Alkaline aqueous solution Specimen (1) Specimen (2) Potassium hydrogen phosphate (pH 6, 8) Peeling, whitening, and disintegration within 5 minutes Artificial intestinal fluid (JPP pH 7, 5) Peeling, whitening, and disintegration within 3 minutes

It was observed that the specimens (1) and (2) were not only dissolved in the adhesive part and collapsed in the package, but also became stronger by the immersion in the acidic aqueous solution. It is well known that seaweed is usually made of vinegar to increase its hardness. The extract (1) and the extract (2) are essentially hydrophilic and have a property of swelling in water, but after immersing the specimen (1) and the specimen (2) in artificial gastric juice (pH 1, 2) for 1 hour When the contents were opened with a scalpel and examined, the contents were observed even though the outer skin was softened and the elasticity was enhanced. No particular change was observed in the contents, and a dry drug appeared. It is considered to be able to withstand the peristalsis of the stomach.

[0013]

Since the present invention is constructed as described above, it exhibits the effects as described below.

In general, only a few drugs are expected to have a drug effect or a health food effect in the stomach, such as antacids, gastric ulcers, and drugs for throat. Internal activity is expected. However, as already mentioned, it is well known in the medical field that a proper packaging method for withstanding gastric acid and releasing the contents in the intestine is not always used satisfactorily. There is.
By the packaging method of the present invention, orally-administered powders, which are packaged and protected, granules, pills, tablets, pharmaceuticals such as capsules, and chlorella, brewer's yeast, lactic acid bacteria, in health foods such as Royal Jelly, It is completed by filling the contents with gelatin, capsules or by directly surface-treating the jelly-like pills. When taken orally, water softens immediately so that it can be swallowed easily, and even if it enters the stomach, the package will not be attacked by gastric acid regardless of the length of residence time.Next, it will come into contact with alkaline intestinal fluid and immediately. The packaging begins to disintegrate and the contents can be released in their intestine in their original condition.

For example, according to the packaging method of the present invention, essential bifidobacteria in the large intestine (a large number of infants, decrease gradually with aging, hardly grow in old age, only E. coli grows)
Without being impaired at all, it is transported and released through the stomach into the intestine, and is fermented with the elapsed time from the small intestine to the large intestine and at an appropriate abdominal temperature to maintain the intestinal condition of an infant and activate the intestinal peristalsis and vitamins. Ingestion becomes easy, and diarrhea, deodorization of gas, and habitual constipation can be improved. Further, in the future, by applying the method of the present invention, it is possible to optimize the titer of the drug for medics and reduce the phytotoxicity accompanying it, so there is much room for research, and it is widely applied to anticancer agents, antipsychotics, many antibiotics, etc. It can be applied and used.

One of the features of the present invention is that the filling of the contents, the adhesion of the opening, and the sealing process can all be carried out at around room temperature, and in the case of contents that do not want to be heated, the packaging method of the present invention is particularly preferable. Is useful.

Commercially available pills packed in jelly (commercial drug Royal Jelly), pills packed in resin (composition drug vitamins, E.C), hard punched tablets (bifidobacteria) and foreign products of pH 1 and 2 artificial gastric juice. It was tested in. All 1
Although it disintegrated in 5 to 20 minutes, all the packaged drugs treated with the extract (2) did not disintegrate for 1 hour. Furthermore, it was confirmed that the treatment with the extract (2) was tougher twice or three times than once.

Since the seaweed extract (2) contains a small amount of barium sulfate for enhancing the water resistance, the dried outer skin serves as an X-ray contrast medium. As a case experiment, three capsules were filled with live bifidobacteria, dipped in extract (2), and dried capsules were taken after oral administration. When observed for 3 minutes, 20 minutes, 30 minutes, and 60 minutes immediately after drinking, there was no change in shape or disintegration of all three grains, and after 60 to 70 minutes, some deformation occurred near the pylorus, and then collapsed and disappeared immediately. Was confirmed at the entrance of the small intestine. This is 9 of the Japanese Pharmacopoeia B-356 disintegration test method Note 13
It is suitable for 10 stations.

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[Procedure amendment]

[Submission date] January 22, 1996

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Claim 4

[Correction method] Change

[Correction contents]

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0006

[Correction method] Change

[Correction contents]

[0006]

Example 1 A blanched salted wakame seaweed is washed with water to remove salt and impurities, and a small amount of sodium hydrogencarbonate is added to water or slightly warm water for immersion and standing. After 5 to 10 hours , the seaweed absorbs water and expands to 4
Expand to ~ 5 times the size. Take out the wakame seaweed, drain it, put it in a cotton cloth, (mesh cloth about the size of a towel), wrap it, and squeeze it out in the manner of bean jam. It has a viscous strength of 1500 cps to 2000 cps. ) Get. A liquid obtained by mixing 6% by weight of barium sulfate with this extraction liquid (1) gave an extraction liquid (2) having excellent acid resistance and water resistance, and was applied to an existing gelatin capsule.
Pucelle responds to radiography in the stomach . Further , 6 to 9 parts of this extract (1) , plate gelatin, or powder
Combine 4 to 1 parts of gelatin to make a total of 10 parts
Let it mix with hot water, and then add 7% of the total weight of barium sulfate.
When melted, an extract (3) is formed. Extract (3) the <br/> releasability good Polyethylene, Polypropylene, teflon
By drying with a cold air on a mold stand such as a coat, a thin film that is strong against acid and weak against alkali can be obtained to form capsules.
In addition, extract (2) or (3) should be added to the existing gelatin capsule.
When applied to capsules and punched tablets, it becomes a new packaging material with optimal conditions for enteric coating .

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Claims (4)

[Claims] 1. An enteric packaging method for pharmaceuticals, health foods, etc., which comprises using as an encapsulating material an extract prepared from the components extracted from the leaves of seaweed as a main part. 2. An enteric packaging method for pharmaceuticals, health foods, etc., wherein the seaweed of claim 1 is seaweed or kelp. 3. Use of an extract containing various components extracted from wakame seaweed, or a mixture of barium sulfate added to the extract applied to a packaging material for pharmaceuticals, health foods, etc. which requires enteric properties. Packaging method. 4. A packaging material such as a capsule made of a mixture of barium sulfate added to an extract containing various components extracted from wakame seaweed, mixed with gelatin, boiled in water and dried to make medicines and health products. A packaging method used for enteric packaging for food and the like.