JPH0153254B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing Chinese herbal medicine tablets with 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, and one of them is the use of tablets. However, when Chinese herbal medicines are made into tablets, the amount is large and difficult to take. Furthermore, if the extract of a Chinese herbal medicine is powdered and made into a tablet, the tablet will be in a small amount, but it will take a very long time for the tablet to disintegrate and the ingredients to dissolve. In other words, tablets made by compression molding the powdered extract of Chinese herbal medicine take a long time to disintegrate when trying to dissolve it in water. This happens when the tablet gets wet with water, forming a highly viscous film on its surface.
This is because this membrane prevents further water from entering. The present inventors have previously solved this drawback and developed a method for producing Chinese herbal medicine tablets that are easy to take and have good disintegration properties.
Ultrafine silicic anhydride particles or porous silicic anhydride with an average pore diameter of 50 Å or more are added and dispersed in the extract or concentrate of the herbal medicine at 15 to 100% of the dried extract or concentrate of the herbal medicine. He invented a method for producing Chinese herbal medicine tablets, which is characterized by compressing and molding the dried product obtained by spray-drying the dried product, either as it is or by mixing it with suitable excipients and lubricants (Patent application 1983). −54279). 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 tablets can be produced that disintegrates and dissolves extremely quickly by extracting them into a herbal medicine extract or its concentrate and spray-drying the dried product to produce tablets. I found out that it can be done. The present invention is based on this knowledge. That is, according to the present invention, ultrafine particles with a particle diameter of several 10 mμ selected from aluminum oxide, titanium oxide, synthetic aluminum silicate, and magnesium aluminate metasilicate are added to the extract of the herbal medicine or its concentrate. Add 15 to 100% of the concentrated liquid to the dried substance and spray dry the resulting dried substance, which is obtained as it is or mixed with appropriate additives such as excipients and lubricants. The object of the present invention is to provide a method for producing Chinese herbal medicine tablets with good disintegration properties, which are characterized by compression molding, and to provide a method for obtaining Chinese herbal medicine tablets that are highly desirable as pharmaceuticals and disintegrate and dissolve extremely quickly. 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, water-insoluble and non-toxic ultrafine particles other than ultrafine silicic anhydride particles are added and dispersed in the extract of this Chinese herbal medicine or a concentrated liquid obtained by concentrating it by an appropriate method. These water-insoluble, non-toxic ultrafine particles include:
It is an aggregate of ultrafine particles (preferably an aggregate of ultrafine particles with an average pore 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 agglomeration occurs. Any material may be used as long as it can incorporate the components of Chinese herbal medicine into the gaps between the fine particles of the aggregate. Specific examples include ultrafine aluminum oxide, ultrafine titanium oxide, synthetic aluminum silicate, synthetic magnesium silicate, synthetic calcium silicate, magnesium aluminate silicate, magnesium aluminate metasilicate, etc. can. The above-mentioned ultrafine particles can be used alone or in combination of two or more. When manufacturing tablets using a dried herbal medicine extract or concentrate obtained by adding the above-mentioned ultrafine particles and spray-drying, the tablet disintegrates extremely quickly. This is thought to be due to the involvement of these ultrafine particles in the surface properties of the particles. In other words, when the above-mentioned water-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 on the surface. It is made up of a combination of a large number of aggregates, and the gaps between the fine particles of these aggregates act like pores, and the components of the herbal medicine extract or its concentrate enter into these gaps. Therefore, when tablets made using these spray-dried particles get wet with water, they quickly disintegrate without forming a highly viscous film on their surface.
It is assumed that it will be dispersed. The amount of the above-mentioned ultrafine particles added is determined in relation to the component amount of the herbal medicine extract or its concentrate, and is based on the amount of the dried herbal medicine extract or its concentrate.
15-100% is suitable, preferably 20-75%, optimally 25-50%. It should be noted that if the amount of the ultrafine particles added is too small, the effect will not be exhibited, while if it is too large, the amount of tablets 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 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 be the same as usual. Just go to the street.
For example, the air temperature is 110 to 200℃, and the exhaust temperature is 90 to 160℃.
It can be done in In addition, in the present invention, the method of drying the herbal medicine extract or its concentrate to which ultrafine particles have been added and dispersed as described above must be by spray drying, and other than normal vacuum freezing. Drying or Tana type ventilation drying does not produce the desired effect at all. This point will be explained using an experimental example as follows. The disintegration time was measured for the following samples 1 to 4 using the concentration test method of the 9th revised Japanese Pharmacopoeia. In addition,
The ultrafine titanium oxide used in the production of the sample was the same as the ultrafine titanium oxide described in Example 1 below. Sample 1: Instead of spray drying, vacuum freeze-drying (after freezing to -40℃ in advance, Tana heating temperature 25℃,
Tablets of Hachimijiogan were produced in the same manner as described in Example ¹ below, except that the dry powder was obtained by crushing the dried product. Sample 2: When concentrating Hachimijiomaru decoction under reduced pressure, it was concentrated until it became a soft extract, and ultrafine titanium oxide was added to this and kneaded. Blow temperature 50 in a ventilation dryer
Tablets of Hachimijiogan were produced in the same manner as described in Example 1 below, except that the dried product was dried under the conditions of 1 m/sec at a wind speed of 1 m/sec) and pulverized to obtain a dry powder. Sample 3: Hachimijiogan tablet manufactured according to Example 1 described below. Sample 4: A tablet of Hachimijiogan produced in the same manner as described in Example 1 below, except that ultrafine titanium oxide was not added. The results of the experiment are shown in Table 1. Note that the disintegration time in the table indicates the average disintegration time of 6 tablets.

[Table] From the results in Table 1, it can be seen that when the drying method is vacuum freeze drying or TANA air drying other than spray drying, it takes a long time for the tablets to disintegrate, which is the same as Sample 4 without the addition of silicic anhydride. However, it was observed that no effect of improving disintegration property was observed. The dry powder obtained as described above may be compression molded as is, or if necessary, suitable additives such as excipients and lubricants may be added, such as lactose, grapes, mannitol, etc. After adding sugars, starches such as corn starch and potato starch, processed products thereof, cellulose substances such as microcrystalline cellulose and sodium cellulose glycolate, and inorganic salts such as calcium hydrogen phosphate and magnesium stearate, etc. It can also be compression molded. The herbal medicine tablets produced according to the present invention have better disintegration properties than conventional ones and extremely excellent dissolution and absorption properties. In addition, as a side effect, changes over time such as discoloration of the tablet surface are less likely to occur, making it extremely desirable 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 twigs, 3 parts of wild medicine, 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 3.5 (dry matter 700
g) and ultrafine particle titanium oxide [Titanium
Add 300g of "Oxide P25" manufactured by Nippon Aerosil Co., Ltd. (average particle size of ultrafine particles approximately 30mμ)],
Stir and disperse using a propeller type stirrer. This liquid was spray-dried (blow temperature: 150°C, exhaust air temperature: 100°C) to obtain about 800 g of dry powder. Mix 99.5 parts of this powder with 0.5 parts of magnesium stearate to make one tablet.
The tablets of Hachimijiogan were obtained by compression molding to 300 mg. The Hachimijiogan tablets manufactured here disintegrated extremely quickly, taking an average of 15.1 minutes in the following disintegration test.
The components were quickly eluted. On the other hand, the disintegration time of Hachimijiogan tablets produced in the same manner as described above by adding ordinary titanium oxide for pigments (average particle size 0.5μ) instead of adding the ultrafine particulate titanium oxide was 57.2 It was hot in minutes. Furthermore, the disintegration time of the Hachimijiogan tablets produced in the same manner as above except that the ultrafine particulate titanium oxide was not added was 69.3 minutes. The disintegration time was measured according to the disintegration test method of the 9th edition of the Japanese Pharmacopoeia. That is, the lower end of a glass tube with an inner diameter of 22 mm and open ends was covered with a mesh with a mesh opening of 2.0 mm, one sample tablet was placed on the mesh, and the glass tube was immersed in distilled water and moved up and down onto the mesh. The time when no residue was observed was defined as the end of the disintegration and the disintegration time. Furthermore, each disintegration time is expressed as the average time of 6 tablets. Example 2 The same procedure as described in Example 1 was used, except that ultrafine aluminum oxide ["Aluminum Oxide C", a product manufactured by Nippon Aerosil Co., Ltd. (average particle diameter of ultrafine particles, about 20 mμ)] was used instead of ultrafine titanium oxide. The procedure was carried out in the same manner as above to obtain Hachimijiogan tablets. This tablet disintegrated in an average of 14.7 minutes in the disintegration test described above, and the ingredients were rapidly eluted. On the other hand, the average disintegration time of the Hachimijiogan tablets produced in the same manner as described above, except that the ultrafine particulate aluminum oxide was not added, was 69.3 minutes as described above. Example 3 5 kg of the prescribed herbal medicine Annachusan (4 parts of pillar bark, 3 parts of oysters, 1.5 parts of oyster, 1 part of fried sand, 1 part of licorice, 0.5 parts of ginger) was mixed with 50 g of water in the usual manner. 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) and use magnesium aluminate metasilicate ["Neusilin UFL ₂ ", a product manufactured by Fuji Chemical Industry Co., Ltd. (average particle diameter of ultrafine particles, approx.
20mμ)] and stir to disperse. Spray dry this liquid (blow temperature 160℃, exhaust temperature 110℃)
About 900 g of dry powder was obtained. 0.5 parts of magnesium stearate was mixed with 99.5 parts of this powder, and 1
The tablets were compressed and molded to a size of 300 mg to obtain Annachusan tablets. The Anchusan tablets produced here disintegrated extremely quickly in the disintegration test described above, taking an average of 17.2 minutes, and the ingredients were rapidly eluted. On the other hand, the average disintegration time of Annachusan tablets produced in the same manner as described above, except that the above-mentioned magnesium aluminate metasilicate was not added, was 81.5 minutes. Example 4 A patient regularly took 5 kg of the prescribed herbal medicine Daisaikoto (6 parts Saiko, 4 parts Hanxia, 3 parts Huang, 3 parts Peony, 3 parts Daijutsu, 2 parts Junji, 1 part dried ginger, 1 part Rhubarb). Decoct with 75% water according to the method, remove the residue, and concentrate to about 1/6 at 40℃ under reduced pressure. Take this liquid 5 (800 g of dry matter), add 400 g of synthetic aluminum silicate ("synthetic aluminum silicate extra light" product manufactured by Kyowa Kakogyo Co., Ltd.), and stir and disperse. Thereafter, spray drying was carried out in the same manner as described in Example 1 to obtain about 1 kg of dry powder. 99.5 parts of this powder contains aluminum stearate
0.5 parts were mixed and compression molded so that each tablet weighed 250 mg to obtain Daisaikoto tablets. When the Daisaikoto tablets produced here were tested in the disintegration test described above, they disintegrated very quickly, taking an average of 12.4 minutes, and the ingredients were rapidly eluted. In contrast, the average disintegration time of the Daisaikoto tablets produced in the same manner as described above, except that the synthetic aluminum silicate was not added, was 65.1 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 (dry product 750%) and add aluminum metasilicate aluminate described in Example 3 to 150%
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 was compressed and molded so that each tablet weighed 200 mg to obtain medicinal ginseng tablets. When this tablet was tested in the disintegration test described above, it disintegrated in an average of 21.5 minutes, and the ingredients were rapidly eluted. On the other hand, when the medicinal ginseng tablets produced in the same manner as described above except for not adding the magnesium aluminate metasilicate were tested in the disintegration test described above, they showed an average disintegration time of 47.3 minutes. Example 6 69.5 parts of a powder obtained by spray drying in the same manner as described in Example 3 was mixed with 25.0 parts of microcrystalline cellulose and 0.5 parts of magnesium stearate, and one tablet contained 350
The tablets were compressed to give Annachusan tablets. When the Anchusan tablets produced here were tested in the disintegration test described above, they disintegrated in an average of 14.3 minutes, and the ingredients were rapidly eluted. On the other hand, magnesium aluminate metasilicate [“Neusilin UFL ₂ ”]
(A product manufactured by Fuji Chemical Industry Co., Ltd. (average particle diameter of ultrafine particles of approximately 20 mμ))] Anchusan tablets manufactured in the same manner as above were tested in the disintegration test described above, and it took 59.7 minutes. It took a long time to collapse.

Claims (1)

[Claims] 1 Add ultrafine particles with a particle diameter of several 10 mμ selected from aluminum oxide, titanium oxide, synthetic aluminum silicate, and magnesium aluminate metasilicate to the extract or concentrate of the herbal medicine. for dry matter
Disintegration characterized by compression molding the dried product obtained by spray drying a 15 to 100% added and dispersed product, either as it is or by mixing it with appropriate additives such as excipients and lubricants. A method for producing Chinese herbal medicine tablets with good properties.