JPH0153253B2 - - 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. By the way, when a tablet is administered to a living body, it becomes medicinal only after it disintegrates and is absorbed within the body. Therefore, if a tablet does not disintegrate in the body after being administered, it will not only fail to achieve its intended medicinal effect, but may even be harmful. In order to improve this drawback, various excipients, disintegration properties, etc. have been investigated, and methods such as wet granulation and then tablet production have been used. However, these methods
I still haven't been able to get anything that satisfies me. Therefore, the present inventors have conducted various studies in order to solve this drawback and produce Chinese herbal medicine tablets that are easy to take and have good disintegration properties, and as a result, they have completed the present invention. That is, the present invention adds ultrafine silicic anhydride with a particle diameter of several 10 mμ or porous silicic anhydride with an average pore diameter of 170 Å or more to a Chinese herbal medicine extract or its concentrate.
Add 15 to 100% of the dried extract or concentrate of the herbal medicine to the dried product and spray-dry the dispersed product, either as it is or mix with appropriate excipients and lubricants. The object of the present invention is to provide a method for producing Chinese herbal medicine tablets with good disintegration properties, characterized by compression molding, and to obtain Chinese herbal medicine tablets that disintegrate and dissolve extremely quickly and are highly desirable 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 extract of the herbal medicine, the above-mentioned herbal medicine can be decocted or infused with water in a conventional manner. Silicic anhydride is added and dispersed in the extract of this herbal medicine or a concentrated solution obtained by concentrating it by an appropriate method. As the silicic anhydride, ultrafine silicic anhydride particles, for example, ultrafine silicic anhydride particles having an average particle diameter (hereinafter simply referred to as particle diameter) of 10 to several tens of microns are used. A specific example of such ultrafine particle silicic anhydride is, for example, "AEROSIL" (product manufactured by Nippon Aerosil Co., Ltd.). In addition, porous silicic anhydride with an average pore diameter (hereinafter simply referred to as pore diameter) of 50 Å or more, preferably 100 Å or more, for example, a particle size of several μ to several tens of μ
It is also possible to use porous silicic anhydride (even if it is porous silicic anhydride, the desired effect will not be achieved if the pore diameter is smaller than 50 Å). Specific examples of such porous silicic anhydride with a pore diameter of 50 Å or more include "SYLOID72", "SYLOID244",
Examples include "SYLOID404" (product manufactured by Fuji Davison Chemical Co., Ltd.). Tablets obtained by compression molding the dried product obtained by spray-drying the above-mentioned ultrafine silicic anhydride or porous silicic anhydride with a pore size of 50 Å or more and dispersing the extract or concentrate of the herbal medicine are The reason why the disintegration property becomes good is explained below using an experimental example. As described in Example 1 below, "AEROSIL200", which is ultrafine silicic anhydride, is used as silicic anhydride.
(Product manufactured by Nippon Aerosil Co., Ltd.) (Particle size 12m
Sample 1 was a tablet of Hachimijiogan manufactured using .mu.). Next, in place of "AEROSIL200" (product manufactured by Nippon Aerosil Co., Ltd.) (particle size 12 mμ) in Example 1 described later, a particle size of 3.5 μm and a pore size of 210 Å, a particle size of 10 μm and a pore size of 170 Å, and a particle size of 4 μm and a pore size of 25 Å were used. Samples 2, 3, and 4 were Hachimijiogan tablets manufactured in the same manner as described in Example 1 below, except that porous silicic anhydride was used. Note that Sample 2 is a product of Example 2 described later. Furthermore, Sample 5 was a tablet of Hachimijiogan produced in the same manner as described in Example 1 below, except that silicic anhydride was not added. The disintegration time of each sample was then measured using 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
The glass tube was covered with a 3 mm mesh, one sample tablet was placed on the mesh, and the glass tube was immersed in distilled water and raised and lowered, and the time when no residue was observed on the mesh was defined as the end of disintegration and the disintegration time. The results are shown in Table 1. Note that the first
The table shows the average disintegration time of 6 tablets each.

[Table] From the results in Table 1, it can be seen that sample 1, which contains ultrafine silicic anhydride particles, and samples 2 and 3, which contain porous silicic anhydride with large pores with a pore diameter of 50 Å or more,
It collapsed in a short time of 10 to 25 minutes, whereas the pore size
It is recognized that in Sample 4 to which porous silicic anhydride having pores smaller than 50 Å was added, it took a long time to concentrate the tablets, similar to Sample 5 to which silicic anhydride was not added. The effect of adding ultrafine silicic anhydride particles or porous silicic anhydride with a pore size of 50 Å or more as described above is due to the involvement of the silicic anhydride in the surface properties of particles produced by spray drying. Conceivable. In other words, when porous silicic anhydride having large pores with a pore diameter of 50 Å or more is added, the spray-dried particles that are formed are hollow inside and the surfaces contain components of the herbal medicine extract or its concentrate within the pores. This is because it becomes a combination of porous silicic acid anhydride in a state of being trapped. In addition, when ultrafine silicic anhydride is added, the spray-dried particles that are formed are hollow inside and their surfaces are composed of a combination of secondary particles in which a large number of ultrafine silicic anhydride aggregates. The gaps act as if they were pores, and the components of the herbal medicine extract or its concentrate can enter into these gaps. On the other hand, when adding silicic anhydride, which has a large particle size of several microns to several tens of microns and has only pores smaller than 50 Å, the spray-dried particles formed are hollow inside and the surface is the anhydrous silicic acid. Although the acid is bound, the components of the herbal medicine extract or its concentrate cannot enter the pores, and the components of the herbal medicine extract or its concentrate envelop the silicic anhydride. Become. As a result, a large amount of components of the herbal medicine extract or its concentrate are present on the surface of the spray-dried particles, resulting in a surface condition similar to that of the spray-dried particles produced without adding silicic anhydride. It is assumed that no results are obtained. Next, the amount of ultrafine silicic anhydride or porous silicic anhydride with a pore size of 50 Å or more to be added is determined by the relationship with the component amount of the herbal medicine extract or its concentrate. 15 to 100% of the dry matter of the concentrate is appropriate, preferably
20-75%, optimally 25-50%. It should be noted that if the amount of silicic anhydride added is too small, the effect will naturally not be apparent, while if it is too large, the amount to be taken will become correspondingly large, which is not preferable. Thus, it is preferable that the amount of the silicic anhydride added is kept to the minimum necessary amount, and the amount added is within the above range. Any means may be used for adding the silicic anhydride as long as the silicic anhydride can be uniformly dispersed in the extract of the Chinese herbal medicine or its concentrate,
For example, it can be carried out using a suitable stirring device. Ultrafine silicic anhydride or pore size 50Å as above
Any type of spray dryer may be used to spray dry the herbal medicine extract or its concentrate in which porous silicic anhydride is added and dispersed, and the spray drying conditions may be carried out as usual. It's fine. For example, it can be carried out at a blowing temperature of 110 to 200°C and an exhaust temperature of 90 to 160°C. In addition, in the present invention, the method of drying the extract of a Chinese herbal medicine or its concentrate to which ultrafine silicic anhydride or porous silicic acid with a pore diameter of 50 Å or more is added and dispersed as described above may be by spray drying. This is essential, and other methods such as ordinary vacuum freeze-drying and Tana type ventilation drying do 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 silicic anhydride used in the production of the sample was the same as the silicic anhydride 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 dried product was crushed to obtain a dry powder. Sample 2: When concentrating Hachimijiomaru decoction under reduced pressure, it was concentrated until it became a soft extract, and silicic anhydride was added and kneaded. Use a dryer at a blowing temperature of 50℃ and a wind speed of 1.
Tablets of Hachimijiogan produced in the same manner as described in Example 1 below, except that the dried product was dried under conditions of m/sec) and crushed to obtain a dry powder. Sample 3: Hachimijiogan tablets manufactured according to Example 1 described below. Sample 4: Hachimijiogan tablets produced in the same manner as described in Example 1 below, except that silicic anhydride was not added. The results of the experiment are shown in Table 2. Note that the disintegration time in the table indicates the average disintegration time of 6 tablets.

[Table] From the results in Table 2, it can be seen that when the drying method is vacuum freeze drying or Tana air drying in addition to 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 it is, or it may be added with suitable excipients, such as saccharides such as lactose, glucose, mannitrate, etc., starch such as corn starch, potato starch, etc. Compression molding can also be carried out after adding cellulose-based substances such as microcrystalline cellulose, cellulose-based substances such as cellulose sodium glycolate, and inorganic salts. 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), add 300 g of ultrafine silicic anhydride "AEROSIL 200" (product made by Nippon Aerosil Co., Ltd.) (particle size 12 mm), and stir and disperse with a screw motor. This liquid was spray-dried (blow temperature: 150°C, exhaust air temperature: 100°C) to obtain about 800 g of dry powder. 0.5 part of magnesium stearate was mixed with 99.5 parts of this powder, and the mixture was compressed and molded so that each tablet weighed 300 mg to obtain tablets of Hachimijiogan. The Hachimijiogan tablets produced here disintegrated in an average of 13.7 minutes in the disintegration test described above, and the ingredients were rapidly eluted. On the other hand, the disintegration time of Hachimijiogan tablets manufactured in the same manner as described above except without adding "AEROSIL200" was 69.3 as described above.
It was hot in minutes. Example 2 "SYLOID244" (product made by Fuji Davison Chemical Co., Ltd.), which is a porous silicic anhydride, was used instead of "AEROSIL200" (product made by Nippon Aerosil Co., Ltd.) (particle size 12 μm) (particle size 3.5 μ, pore size 210 Å) Tablets of Hachimijiogan were obtained in the same manner as described in Example 1, except that . In the above-mentioned disintegration test, this tablet disintegrated in an average of 11.5 minutes, and the ingredients were rapidly eluted. On the other hand, the disintegration time of the Hachimijiogan tablets produced in the same manner as described above except that the above "SYLOID244" was not added was 69.3 minutes as described above. Example 3 5kg of medicinal ginseng is decocted with 50ml of water as usual, 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 porous silicic anhydride "SYLOID404" (product manufactured by Fuji Davison Chemical Co., Ltd.) (particle size 10 μ, pore size 170 Å).
Add 150g and stir to disperse. Spray-dry this liquid (blow temperature 160℃, exhaust temperature 110℃) to approximately 600℃.
g of dry powder was obtained. This powder is compressed and molded into 1
200mg tablets were obtained. When this tablet was tested in the aforementioned concentration test, it disintegrated in an average of 19.2 minutes and the ingredients were rapidly eluted.
On the other hand, the medicinal ginseng tablets manufactured in the same manner as above except without adding "SYLOID404" were tested in the disintegration test described above and had a score of 47.3.
It took several minutes of disintegration time. Example 4 Kakkonto (consisting of 4 parts of kudzu root, 3 parts of ephedra, 3 parts of jujube, 2 parts of peony, 2 parts of peony, 2 parts of licorice, and 1 part of ginger)
Decoct 5kg of the prescribed herbal medicine with 75ml of water in the usual manner, remove the residue, and concentrate to about 1/6 at 40°C under reduced pressure. Take this liquid 5 (700 g of dry matter) and add porous silicic anhydride "SYLOID244" (product manufactured by Fuji Davison Chemical Co., Ltd.) (particle size 3.5 μ, pore size 210 Å).
Add 350g and stir to disperse. Below, Example 1
About 900 g of dry powder was obtained by spray drying as described in . 99.5 parts of this powder was mixed with 0.5 part of magnesium stearate and compressed into tablets of 300 mg each to obtain Kakkonto tablets. When the Kakkonto tablets prepared here were tested in the disintegration test described above, they disintegrated in an average of 12.4 minutes and the ingredients were rapidly eluted. On the other hand, when the Kakkonto tablets produced in the same manner as described above except for not adding the above-mentioned "SYLOID244" were tested in the above-mentioned disintegration test, they required a disintegration time of 85.6 minutes. Example 5 Tokishakuyakusan (4 parts of Paeonia, 4 parts of Sogyu, 4 parts of Sawasha,
Decoct 5kg of the prescription herbal medicine (consisting of 4 parts of Bouleo, 3 parts of Kawane, and 3 parts of Dangki) with 75% of water in the usual manner, remove the residue, and concentrate to about 1/6 at 40℃ under reduced pressure. This liquid 5
(700 g of dry matter) and 120 g of porous silicic anhydride "SYLOID244" (product manufactured by Fuji Davison Chemical Co., Ltd.) (particle size 3.5 μ, pore size 210 Å)
Add, stir, and disperse. Thereafter, spray drying was carried out in the same manner as described in Example 1 to obtain about 700 g of dry powder. 99.5 parts of this powder was mixed with 0.5 part of magnesium stearate, and the mixture was compressed and molded so that each tablet weighed 250 mg to obtain Tokishakuyakusan tablets. When the tablets of Tokishakuyakusan prepared here were tested in the disintegration test described above, they disintegrated in an average of 18 minutes and the ingredients were rapidly eluted. On the other hand, Tokishakuyakusan powder was manufactured in the same manner as described above except that the above-mentioned "SYLOID244" was not added, but each tablet was 200mg to have the same extract content as the above-mentioned tablets. Similarly compressed tablets were tested in the disintegration test described above and required a disintegration time of 42 minutes. Example 6 69.5 parts of powder obtained by spray drying in the same manner as described in Example 4 was mixed with 25.0 parts of microcrystalline cellulose and 0.5 part of magnesium stearate, and each powder was 350 mg.
The kakkonto tablets were obtained by compression molding into tablets. When the Kakkonto tablets prepared here were tested in the disintegration test described above, they disintegrated in an average of 11.6 minutes and the ingredients were rapidly eluted. In contrast, "SYLOID244"
(Product manufactured by Fuji Davison Chemical Co., Ltd.) (Particle size
Kakkonto tablets prepared in the same manner as described above except without the addition of 3.5μ, pore size 210Å) required a disintegration time of 72.9 minutes when tested in the disintegration test described above.

Claims (1)

[Claims] 1 The herbal medicine extract or its concentrate contains ultrafine silicic anhydride particles with a particle size of several tens of microns or an average pore size.
Anhydrous silicic acid with a porous diameter of 170 Å or more is added to the dried extract of the herbal medicine or its concentrate at a rate of
The dried product obtained by spray drying the 100% added and dispersed product can be used as it is, or with an appropriate excipient,
A method for producing Chinese herbal medicine tablets with good disintegration, characterized by mixing with a lubricant and compression molding.