JPS603046B2 - improved gelatin capsules - Google Patents

Description

[Detailed description of the invention] The present invention relates to improved gelatin capsules.

More specifically, the present invention relates to gelatin capsules whose disintegrability is particularly enhanced by coating the gelatin capsules with a coating material containing proteolytic enzymes. Gelatin capsules are known as hard capsules and soft capsules, and these are widely used to encapsulate various forms of pharmaceuticals and foods, from solids such as powders and parent granules to oily liquids and creams. .

However, the gelatin membrane used has various advantages as well as disadvantages. Although research has been conducted to improve these drawbacks, it is still not sufficient. For example, when a hydrophilic base material such as polyethylene glycol is added to a gelatin coating, the disintegration properties of the gelatin coating in the gastrointestinal tract are improved, but this has the disadvantage of poor moisture resistance. Furthermore, addition of cellulose acetate phthalate, acylation of the gelatin coating with acid anhydrides or acid chlorides such as succinic acid, maleic acid, and phthalic acid, and acylation of the gelatin coating with N-acetylhomocystine thiolactone, etc. Although thiolation of groups improves the heat resistance and moisture resistance of gelatin coatings, it has the disadvantage of poor disintegration in the gastrointestinal tract. Furthermore, the surface of the gelatin coating is often treated with formalin, but the gelatin coating becomes enteric and is significantly stabilized, but the disintegrability of the gelatin capsule is reduced. Furthermore, if gelatin capsules are left at high temperatures for a long period of time, the film will gradually become insolubilized, leading to a window of disintegration within the gastrointestinal tract, and the disintegration properties will also be reduced by ultraviolet irradiation. As described above, since the constituent components of the gelatin coating are protein molecules, it is inevitable that the gelatin coating will gradually become unbreakable and its disintegration properties will decrease due to the addition of drugs, heat, light, etc.

Therefore, although gelatin capsules are one of the important dosage forms for pharmaceuticals, they have major problems such as hygroscopicity and poor disintegration due to progressive insolubilization over time due to the reasons mentioned above. There is.

Based on the knowledge of gelatin capsules, the present inventors conducted intensive research to improve the drawbacks of gelatin capsules, especially improving the disintegration properties. According to the method of coating the capsules, gelatin capsules can not only be significantly improved in competitiveness, but also have excellent moisture resistance, heat resistance, etc., and can be provided in an industrially extremely advantageous method. This is what led us to arrive at the present invention.

That is, the present invention is an improved gelatin capsule characterized by coating the gelatin capsule with a coating material containing a proteolytic enzyme.

According to the research conducted by the present inventors, the reasons why the disintegration properties of gelatin capsules are significantly improved by the present invention are as follows.

In other words, gelatin consists of a unique polypeptide molecule in which glycine, proline, and hydroxyproline are regularly arranged in a ratio of about 3:1:1, and when these molecules are folded together, it has a Q-keutine type structure. . When these gelatin coatings are left at high temperatures for long periods of time, or when they coexist with certain drugs, the hydrogen bonds or hydrophobic bonds in the gelatin protein molecules are broken, and the polybetide chains of the protein molecules are elongated. He changes into a Keuchin type and becomes immortal. If this insolubilized gelatin capsule is coated with a coating material containing a proteolytic enzyme, when the gelatin capsule is administered into the gastrointestinal tract or rectum, the enzyme will be eluted from the coating material by body temperature or body secretions. It acts on the insolubilized gelatin capsule, decomposes the polypeptide chains (8-Ketin type) that have been elongated due to gelatin denaturation, and promptly disintegrates the gelatin capsule. Coaching is a method commonly applied to tablets, capsules, etc. for the purpose of removing the main drug from outside air (light, humidity, air, etc.) to prevent its effects or to increase its commercial value. There is no need for the process to become complicated in order to carry out the invention. Next, aspects of the present invention will be described in detail.

Add the proteolytic enzyme to the preheated and dissolved coaching solution and mix uniformly. At this time, a surfactant or a solubilizing agent may be used if necessary in order to uniformly mix the enzyme into the coating material. The coating material containing the enzyme uniformly dispersed in this way is then placed in a coaching pan while blowing hot air at 50-60 pm into gelatin capsules (hard capsules, European capsules) produced by a conventional method. Coach and manufacture.
The enzymes used at this time may be any proteolytic enzymes that are harmless from a sanitary point of view.
Enzymes with wide substrate specificity such as enzyme, papain, trypsin, and chymotrypsin may also be used. Moreover, the enzyme used is not limited to one type, and several types of composite enzymes may be used. The larger the amount of enzyme used, the more remarkable the effect will be, but if too much enzyme is present in the coating, uneven coating may occur when coating gelatin capsules, or coloring may occur due to the color of the enzyme itself. The appearance may be damaged. Therefore, the amount is the amount of enzyme and the amount of coating material (
W/W) is most preferably 2/10 to 1/10. The amount of coating on the capsule varies depending on the type of capsule, etc., but is preferably 10-30 females/cap. The coachsog material used may be either oil-based or hydrophilic, but it is preferably solid at room temperature, moisture resistant, and quickly dissolved by body temperature or body fluids.

If the coating material is solid at room temperature, the enzyme dissolved in the coating material will be prevented from transferring to the gelatin film, and since it will contain a small amount of moisture, the enzyme itself will not change its structure and will not be affected. This is because no decrease in value was observed. Therefore, although there are various types of such coating materials, it is preferable to use a mixture of several types of macrogol oils and fats. As described above, according to the present invention, it is possible to produce gelatin capsules that are particularly fast-acting by coating gelatin capsules with a coating material containing a proteolytic enzyme, which is an extremely industrially advantageous method. Its uses are wide-ranging, and it is expected that it will make great progress.

Such an effect can only be achieved by coating a proteolytic enzyme together with a coating material. The present invention will be explained in detail with reference to Examples below.

Example 1 Proteolytic enzyme Pronase-P (manufactured by Kaken Chemical Co., Ltd.) was added to 50 t of a coating material prepared by heating and dissolving and mixing 9 parts by weight of Macrogol 4000 (hereinafter simply referred to as "parts") with 1 part by weight of Wichipsol E-75. 5000 guys at 60℃
An enzyme-containing coating material was produced by melting and uniformly dispersing the enzyme while blowing hot air into it.

2,000 soft gelatin suppositories prepared in advance were added to this, and the mixture was coated in a coaching pan while blowing hot air at 60°C, and then the coaching was completed while gradually blowing cold air. The enzyme-coated gelatin suppositories obtained in this way were placed in a cellulose tube, both ends of which were closed, and the tube was placed in a disintegration container.Table 1 shows the results of examining the disintegration time. Shown below.

Table 1 Disintegration tester: manufactured by Tomiyama Sangyo Disintegration time: time until the capsule first forms a hole Example 2 Soft gelatin capsules made insolubilized by heat using an enzyme coating material obtained by the same method as in Example 1 coated with agent.

The disintegrability of this material was shown in Taiichi 2. Table 2 Regarding the stability of the enzyme in this enzyme coating material, the potency hardly decreased even after an abuse test at 40°C for about 5 months.

Example 3 The same mirror orientation as in Example 1 was obtained as a result of coating in the same manner as in Example 1 using hard capsules instead of soft gelatin capsules.

Example 4 Enzyme coating was performed using the same method as in Example 1 except that papain was used as the enzyme. As a result, the same trends as in Example 1 were obtained.

Example 5 Coating agent used: 97 parts of Wichitupsol E-85,
Enzyme coating was carried out in the same manner as in Example 1, except that a coating agent consisting of 3 parts of the surfactant ARACEL 169 was used, and the same trends as in Example 1 were obtained.

Example 6 Enzyme coating was carried out in the same manner as in Example 1, except that a gelatin paste consisting of an acid-treated gelatin film was used. As a result, the same face size as in Example 1 was obtained.

Claims (1)

[Claims] 1. An improved gelatin capsule characterized by coating the gelatin capsule with a coating material containing a proteolytic enzyme.