JPH0322370B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing Chinese herbal medicine hard capsules whose contents have good disintegration properties.

In recent years, Chinese herbal medicine has been reconsidered, and demand for it is rapidly increasing. However, herbal medicines tend to be avoided due to their medicinal odor and taste. Various efforts have been made to compensate for this drawback, one of which is the use of hard capsules. However, if Chinese herbal medicines are packaged directly into hard capsules, the amount would be large, making it difficult to take. Furthermore, if the extract of a Chinese herbal medicine is powdered and packed, a small amount can be obtained, but the hard capsule requires a very long time for the contents to disintegrate and elute, making it extremely undesirable as a pharmaceutical product. In other words, when hard capsules are made by filling powdered Chinese herbal medicine extracts into hard capsules, when trying to dissolve them in water, the powdered Chinese herbal medicine extracts contained in the capsules clump together and take a long time to disintegrate. It takes. This is because the entire contents consisting of the Chinese herbal medicine extract powder get wet with water and form a highly viscous film on its surface, which prevents further water from penetrating.

The present inventors previously solved this drawback by adding ultrafine silicic anhydride or average Pore diameter is 50
Porous silicic acid anhydride with a size of 5 to 100% based on the dried extract of the herbal medicine or its concentrate.
A process for producing hard capsules of Chinese herbal medicine, characterized in that the dried product obtained by spray-drying the added and dispersed product is compressed as it is or after compression molding, and then crushed and packed into hard capsules as granules or powder. (Japanese Patent Application Laid-Open No. 56-30914).

After that, the present inventors continued research on this manufacturing method, and found that not only the above-mentioned ultrafine silicic anhydride but also generally water-insoluble and non-toxic additives can be added to extracts or concentrates of Chinese herbal medicines. Ultrafine particles are sufficient, and by manufacturing hard capsules using the dried product obtained by adding it to the extract or concentrate of the Chinese herbal medicine and spray drying it, the disintegration and elution of the contents can be minimized. We have discovered that it is possible to quickly produce hard capsules of Chinese herbal medicine. The present invention is based on this knowledge.

That is, the present invention adds at least one type of ultrafine particulate material selected from ultrafine particulate aluminum oxide, ultrafine particulate titanium oxide, synthetic aluminum silicate, and magnesium aluminate metasilicate to an extract of a Chinese herbal medicine or a concentrate thereof. The dried product obtained by spray-drying 5 to 100% addition and dispersion of the extract or concentrate of the Chinese herbal medicine to the dried product can be made into granules either directly or after compression molding. Or, a method for producing a Chinese herbal medicine hard capsule with good disintegration of the contents, characterized in that it is packed in a hard capsule as a powder, the disintegration of the contents, the disintegration of the contents,
The object of the present invention is to provide a method for obtaining hard capsules of Chinese herbal medicines, which are extremely fast in dissolution and are always preferred as pharmaceuticals.

The present invention will be explained in detail below.

The herbal medicine used in the present invention includes not only herbal medicines referred to in Chinese medicine, but also so-called herbal medicines or herbal medicine preparations consisting of one or a mixture of two or more kinds of herbal medicines.

As the herbal medicine extract, not only those obtained by decocting or infusing the above-mentioned herbal medicines with water in a conventional manner, but also those extracted using alcohol or other organic solvents can be used.

In the present invention, at least one member selected from ultrafine particulate aluminum oxide, ultrafine particulate titanium oxide, synthetic aluminum silicate, and magnesium aluminate metasilicate is added to the extract of this herbal medicine or a concentrate obtained by concentrating it by an appropriate method. Add and disperse ultrafine particles with an average particle size of several tens of microns.

These water-insoluble, non-toxic ultrafine particles include:
It is an aggregate of ultrafine particles (preferably an aggregate of ultrafine particles with an average particle diameter of several tens of microns or less), and when it is added to a Chinese herbal medicine extract or its concentrate and spray-dried, the Any material may be used as long as it can incorporate the components of the herbal medicine into the gaps between the fine particles of the aggregate. Specific examples include ultrafine aluminum oxide, ultrafine titanium oxide, synthetic aluminum silicate, magnesium aluminate metasilicate, and the like.

The above-mentioned ultrafine particles can be used alone or in combination of two or more.

When hard capsules are manufactured using dried Chinese herbal medicine extracts or concentrates obtained by adding the above-mentioned ultrafine particles and spray-drying, the contents of the capsules disintegrate extremely quickly. This is thought to be due to the involvement of these ultrafine particles in the surface properties of particles produced by spray drying. In other words,
When the above-mentioned insoluble, non-toxic ultrafine particles are added to a Chinese herbal medicine extract or its concentrate and spray-dried, the spray-dried particles that are formed are hollow inside and have ultrafine particles, that is, aggregated ultrafine particles, on the surface. It consists of a combination of aggregates, and the gaps between the fine particles of these aggregates act as if they were pores, and the components of the herbal medicine extract or its concentrate enter into these gaps. It is presumed that when hard capsules manufactured using spray-dried particles get wet with water, the contents will quickly disintegrate and disperse without forming a highly viscous film.

The amount of the ultrafine particles added is determined in relation to the component amount of the herbal medicine extract or its concentrate, and is suitably 5 to 100%, preferably 10% to the dry matter of the herbal medicine extract or its concentrate. ~50%, optimally 15-30%. It should be noted that if the amount of the ultrafine particles added is too small, the effect will not be apparent, while if it is too large, the amount of capsules to be taken will increase accordingly, which is not preferable. Thus, it is preferable to keep the amount added to the minimum necessary amount, and an amount within the above range is appropriate.

Any means may be used for adding and dispersing the ultrafine particles as long as the ultrafine particles can be uniformly dispersed in the extract of the Chinese herbal medicine or its concentrate. For example, an appropriate stirring device may be used. can.

Spray-drying the herbal medicine extract or its concentrate to which the ultrafine particles have been added and dispersed as described above may be carried out using any type of spray dryer, and the spray-drying conditions may also be constant. Just follow the law. For example, the air temperature is 110~200℃, the exhaust temperature is 90~
It can be done at around 160℃.

The dry powder obtained as described above may be directly packed into hard capsules, such as gelatin capsules, or it may be compression-molded using an appropriate device and then crushed to form granules or powder before being hardened. It can also be packed in capsules. Furthermore, when filling hard capsules, suitable additives such as excipients such as lactose, microcrystalline cellulose, magnesium stearate, etc. can be added before filling.

The Chinese herbal medicine hard capsule prepared according to the present invention is
The contents have good disintegration properties and extremely excellent dissolution and absorption properties. In addition, as a side effect, changes over time such as discoloration and solidification of the filler are less likely to occur, making it extremely preferable as a pharmaceutical product.

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 Hachimijiogan (6 parts of Jianjiang, 3 parts of Sawatan, 3 parts of Bulyo,
2.5 parts of peony bark, 1 part of katsura, 3 parts of wild herbs, 3 parts of wild mushrooms,
Decoct 5 kg of prescribed herbal medicine (consisting of 0.5 parts of processed bush) with 50 kg of water in the usual manner, remove the residue, and boil under reduced pressure for 40 kg.
Concentrate to approximately 1/5 at °C. This liquid 4 (dry matter 800
g) and ultrafine particle titanium oxide [Titanium
OxideP25” (product manufactured by Nippon Aerosil Co., Ltd.)
(average particle size of ultrafine particles of approximately 30 mμ)] was added and stirred and dispersed using a propeller type stirrer. Spray dry this liquid (blow temperature 150℃, exhaust temperature 100℃)
About 900 g of dry powder was obtained. Fill this powder directly into No. 1 gelatin capsules (in 1 capsule
(480mg filling) to obtain hard capsules of Hachimijiogan.

The hard capsules of Hachimijiogan manufactured here are
In the disintegration test described below, it disintegrated very quickly, taking an average of 4.6 minutes, and the components were quickly eluted. In contrast, instead of adding the ultrafine particulate titanium oxide, the hard capsules of Hachimijiogan, which were produced in the same manner as above by adding ordinary titanium oxide for pigments (average particle size 0.5μ), collapsed. The time was 11.6 minutes. Further, the disintegration time of hard capsules of Hachimijiogan produced in the same manner as described above except that the ultrafine particulate titanium oxide was not added was 13.5 minutes on average.

The disintegration time was measured according to the disintegration test method of the 9th edition of the Japanese Pharmacopoeia. In other words, the lower end of a glass tube with an inner diameter of 22 mm and open ends is
Place one capsule of the sample on the net, and add 1000 ml of the test solution (2.0 g of sodium chloride, 24.0 ml of diluted hydrochloric acid, and water) to the glass tube.
It was immersed in a liquid with a pH of approximately 1.2) and raised and lowered, and the time when no residue was observed on the screen was defined as the end of the collapse and the collapse time. Furthermore, each disintegration time is expressed as the average disintegration time of 6 capsules.

Example 2 The same as in Example 1 except that ultrafine aluminum oxide [Aluminum Oxide C (product manufactured by Nippon Aerosil Co., Ltd.) (average particle diameter of ultrafine particles approximately 20 mμ)] was used instead of ultrafine titanium oxide. Hard capsules of Hachimijiogan were obtained in the same manner as above.

This hard capsule has an average
It disintegrated in 4.0 minutes and the components were rapidly eluted. On the other hand, the disintegration time of hard capsules of Hachimijiogan produced in the same manner as above except that the ultrafine particulate aluminum oxide was not added was 13.5 minutes on average, as described above.

Example 3 5 kg of the prescription crude drug Annachusan (4 parts Katsura, 3 parts Enkosao, 3 parts Oyster, 1.5 parts Boka, 1 part Chisago, 1 part Licorice, 0.5 parts Ryojyo) was mixed with 50 kg of water as usual. After decoction and removing the residue, concentrate to about 1/5 at 40℃ under reduced pressure. Take this liquid 5 (750 g of dry matter), add 250 g of magnesium aluminate metasilicate ["Neusilin UFL ₂ " (product manufactured by Fuji Chemical Industry Co., Ltd.) (average particle diameter of ultrafine particles about 20 mμ)], and stir and disperse. . Spray dry this liquid (blow temperature 160℃, exhaust temperature 110℃)
℃) to obtain about 900 g of dry powder. This powder was directly filled into No. 1 gelatin capsules (430 mg in each capsule) to obtain hard capsules of Annachusan.

The hard capsules of Annachusan produced here disintegrated very quickly in the disintegration test described above, taking an average of 3.2 minutes, and the ingredients were rapidly eluted. On the other hand, the average disintegration time of hard capsules of Anchu-san produced in the same manner as described above except that the magnesium aluminate metasilicate was not added was 17.8 minutes.

Example 4 Prescription of Daisaikoto (6 parts of Saiko, 4 parts of Hanxia, 3 parts of Ojutsu, 3 parts of Paeonia, 3 parts of Daio, 2 parts of Japanese betel, 1 part of dried ginger, 1 part of Rhubarb) 5Kg of conventional herbal medicines Stew in water 75%,
After removing the residue, concentrate to about 1/6 at 40°C under reduced pressure.
Take this liquid 5 (800 g of dry matter) and add synthetic aluminum silicate ["synthetic aluminum silicate special light"]
(Product manufactured by Kyowa Chemical Industry Co., Ltd.) (Average particle diameter of ultrafine particles approximately 20 mμ)] Add 300 g and stir and disperse. The following was spray-dried in the same manner as described in Example 1, and filled into No. 1 gelatin capsules (each capsule contained
(420mg filling) to obtain hard capsules of Daisaikoto.

When the hard capsules of Daisaikoto produced here were tested in the disintegration test described above, they disintegrated very quickly, taking an average of 4.3 minutes, and the ingredients were rapidly eluted. In contrast, the average disintegration time of the hard capsules of Daisaikoto produced in the same manner as described above except that the synthetic aluminum silicate was not added was 21.6 minutes.

Example 5 5kg of medicinal ginseng is decocted with 50% of water in a conventional manner, and after removing the residue, it is concentrated to about 1/4 at 40°C under reduced pressure. Take this liquid 4 (750 g of dry matter) and add 150 g of magnesium aluminate metasilicate described in Example 3.
g and stir to disperse. This liquid was spray-dried (blow temperature: 160°C, exhaust temperature: 105°C) to obtain about 800 g of dry powder. This powder is compressed and molded using a dry granulator (bulk compactor), then crushed to form a powder. 20% microcrystalline cellulose is added to this powder and packed into No. 1 gelatin capsules (440 mg in each capsule). Then, hard capsules of medicinal ginseng were obtained.

When this hard capsule was tested in the disintegration test described above, it disintegrated in an average of 3.0 minutes, and the ingredients were rapidly eluted. On the other hand, hard capsules of medicinal ginseng produced in the same manner as described above except that the magnesium aluminate metasilicate was not added required a disintegration time of 18.5 minutes when tested in the disintegration test described above.

Claims (1)

[Claims] 1 At least one ultrafine particle with an average particle diameter of several tens of mμ selected from ultrafine aluminum oxide, ultrafine titanium oxide, synthetic aluminum silicate, and magnesium aluminate metasilicate is added to the extract of Chinese herbal medicine or its concentrate. 5 for the dried extract of the Chinese herbal medicine or its concentrate.
The disintegration of the contents is characterized by spray-drying a 100% added and dispersed product, either as it is, or after compression molding, crushing it and filling it into hard capsules as granules or powder. A method for manufacturing Chinese herbal medicine hard capsules with good properties.