JPH0595988A - Herb extract granule and preparation of solid drug containing herb extract - Google Patents

Abstract

PURPOSE:To make it possible to perform easily and efficiently granulation by spraying water while water content of a mixture in a granulator is kept in a specified range when granulation is performed by spraying water to a mixture consisting of a herb extract powder and a shaping agent. CONSTITUTION:When a mixture consisting of 100 pts.wt. herb extract powder and 2-20 pts.wt. excipient is floatingly and revolutionally fluidized in a floatingly and revolutionally fluidized layer granulator and granulation is performed by spraying water or a binder water soln. to the mixture under this fluidized condition, the water or the binder water soln. is sprayed while the water content y or the mixture is controlled in a range of an equation of 0.9X-9.8<=Y<=1.1X-6.8, wherein X is the limit of the compsn. of the mixture and is set in a range of 14<=X<=40. As the excipient, for example, silicic anhydride, hydrated silicon dioxide, synthetic aluminum silicate, etc., are used and as the binder water soln., a diluted water soln. of a water-soluble polymer such as hydroxypropyl cellulose is used.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a granulated Chinese herb extract and a method for producing a solid preparation containing the Chinese herb extract. More specifically, a method for industrially advantageously producing a granulated product having a higher Kampo extract content than a Kampo extract powder and an excipient by a fluidized bed granulation method, and a Kampo medicine using the granulated product obtained by the method The present invention relates to a method for producing an extract-containing solid preparation.

[0002]

2. Description of the Related Art Dry granulation, wet extrusion granulation, fluidized bed granulation and the like are known as granulation methods for pharmaceutical products. Among them, the fluidized bed granulation method has been adopted widely in the pharmaceutical industry because it has a simpler process than other methods and can produce granules efficiently.

A fluidized bed granulation method is also adopted for the production of granules containing Chinese herb extract, but this method is limited to the production of granules having a low extract content. that is,
When an attempt was made to produce a granulated product with a high Kampo extract content by the fluidized bed granulation method, the flow stopped due to the high hygroscopicity of the Kampo extract powder, making it impossible to granulate efficiently. is there.

Therefore, the production of granules having a high content of Kampo extract must rely on the wet extrusion granulation method or the dry crushing granulation method, which has lower production efficiency than the fluidized bed granulation method. is there. Even in this case, since the Kampo extract powder has high hygroscopicity, it is necessary to devise it for smooth granulation. For example, in the wet extrusion granulation method, it is inevitable to use an organic solvent such as ethanol for the kneading liquid.

[0005]

[Problems to be Solved by the Invention] Producing granules having a high content of Chinese herb extract is an important issue for downsizing and easy administration of solid formulations containing Chinese herb extract, and efficient granulation. Establishing a method is desired. The present inventors conducted various studies on a fluidized bed granulation method of Kampo extract powder in order to efficiently obtain granules having a high Kampo extract content.

An object of the present invention is to use a fluidized bed granulator to efficiently produce granules having a high Kampo extract content,
Another object of the present invention is to provide a method for producing a solid preparation containing a Chinese herb extract, which uses the granules obtained by the method.

[0007]

As a result of the investigation, the present inventors have found that when a mixture of Kampo extract powder and an excipient is sprayed with water or a binder aqueous solution by a fluidized bed granulation method, the mixture is granulated. When the water content or the binder aqueous solution is sprayed while maintaining the water content of the mixture in the floating whirled fluidized bed granulator in a specific range determined for the plastic limit of the mixture, the content of the Chinese herb extract powder is increased. The present invention has been completed by finding that even a high mixture can be easily and efficiently granulated. That is, a mixture of Chinese herb extract powder and an excipient is floated and swirled, and the water content Y of the mixture during flowing is expressed by the following formula (I): 0.9X-9.8 ≦ Y ≦ 1.1X-6. ........ (I) (wherein X represents the plastic limit of the mixture of Kampo extract powder and excipient, where 14 ≦ X ≦ 40) while controlling within the range When the mixture is sprayed with water or a binder aqueous solution, the ratio of Kampo extract powder in the mixture is 80%.
It was found that the mixture can be efficiently granulated without causing blocking even when the content exceeds the weight percentage, and the present invention was completed based on this finding.

The plastic limit is a value defined as the water content of the wet powder when the cohesive force shows the maximum resistance to the flow deformation of the wet powder (Handbook of Powder Engineering, February 28, 1986).
Nikkan, Nikkan Kogyo Shimbun, page 600), plasticity limit measuring method (see JIS A1206), stirring torque test (see Journal of Powder Engineering, Volume 21, No. 6, page 327, 1984) or containment hardness test (Powder and Industry, Volume 8, 5
No., p. 49, 1976).

Further, the water content (Y) of the mixture of the Kampo extract powder and the excipient in the flowing state is, for example, an infrared moisture meter (a name of Moiswatch from Okawara Seisakusho Co., Ltd. and a name of Weteye from Fuji Paudal Co., Ltd.). It is commercially available in Japan).

In the present specification, the water content of a mixture of Kampo extract powder and an excipient is represented by the following formula (II). (Where A is the dry Kampo extract powder weight, B is the dry excipient weight, and C is the weight of the water contained in the mixture of Kampo extract powder and excipient). .. Therefore, X and Y in the formula (I) are also numerical values expressed based on this notation.

[0011] The Kampo extract powder in the present invention means a decoction brewed from a usual Kampo formula described in a general Kampo formula guide (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, published by Yakugyo Jikhosha, 1975). Kampo extract powder obtained by concentrating and drying according to the method, for example, Keishikashakuyakuto extract powder, Kamikihito extract powder, Kakkonto extract powder, Shoseiryuto extract powder, Saiko Keishito extract powder, Gakkutoto Extract powder, Dokatsu Kakkonto extract powder, Daisaikoto extract powder, Shosaikoto extract powder, Fufutsu Seisan powder extract powder, Keishibukuryo pill extract powder, Hochuekkito extract powder, Ninjinyoeito extract Powder, Sairei-to extract powder, Hachimi-jio-gan extract powder and Toki-shakuyaku powder extract powder, etc. are brewed from one or more other herbal medicines, and the brewed liquid is concentrated and dried by a conventional method. Various crude drugs obtained from Scan powder also encompasses.

The average particle size of the extract powder used is usually 50 to 100 μm.

Excipients include, for example, silicic acid anhydride, hydrous silicon dioxide, water-insoluble inorganic compounds such as synthetic aluminum silicate, magnesium aluminate silicate or magnesium aluminate metasilicate, and cellulose such as cellulose such as carboxymethyl cellulose calcium. Derivatives, for example, one or more selected from starch derivatives such as dextrin and hydroxypropyl starch, and starch may be used. The average particle size of the excipient used is usually 0.01 to 100 μm.

The mixing ratio of the Chinese herb extract powder and the excipient is
In order to produce a granulated product having a high extract content, the amount of the excipient is 2 to 20 parts by weight based on 100 parts by weight of the Kampo extract powder.

The binder aqueous solution contains a binder usually used in the manufacture of pharmaceuticals, such as hydroxypropyl cellulose,
A dilute aqueous solution of a water-soluble polymer such as hydroxypropylmethylcellulose, polyvinylpyrrolidone or methylcellulose (usually 0.1 to 10% aqueous solution) is used.

In the method for producing the granulated product of the present invention, a mixture consisting of 100 parts by weight of Kampo extract powder and 2 to 20 parts by weight of an excipient is placed in a fluidized bed granulator, and the mixture is subjected to floating whirl flow,
While measuring the water content Y of the mixture, the value Y is expressed by the following formula (I) 0.9X-9.8 ≦ Y ≦ 1.1X-6.8 (I) (wherein X Indicates the plastic limit of a mixture of Kampo extract powder and excipients, provided that the mixture is sprayed with water or an aqueous binder solution while being controlled within the range of 14 ≦ X ≦ 40).

In the above formula (I), the lower limit of Y (Y =
0.9X-9.8) is a mixture of Kampo extract powder and excipients showing various plastic limits (X), sprayed with water or an aqueous binder solution, and the mixture is granulated in a granulator. It is a regression line obtained by measuring the minimum water content (YL) to start and by the least square method (see Example 1 below).

On the other hand, the upper limit of Y (Y = 1.1X-6.8)
Is a mixture of Kampo extract powder and excipients showing various plastic limits (X), sprayed with water or an aqueous binder solution,
Maximum water content (YH) at which the mixture can flow in the granulator
[Meaning water content (YH) at which the mixture starts to stop flowing] is a regression line obtained by the least square method (see Example 1 below).

That is, even if water or a binder aqueous solution is sprayed, the water content of the mixture of Kampo extract powder and excipient in the fluidized bed should be less than the value indicated by Y = 0.9X-9.8. If so, the mixture is not granulated. Conversely, Y = 1.1X-6.
Spraying more than 8 water or aqueous binder solution stops the flow of the mixture, making granulation impossible.

Therefore, in granulating, the X value of the mixture of the Chinese herb extract powder and the excipient was measured in advance, and this X value was measured.
The range of the Y value with respect to the value is obtained from the formula (I), and water or a binder aqueous solution is sprayed within this range while controlling the water content of the mixture.

The floating swirling flow of a mixture of Kampo extract powder and excipients is described, for example, in Japanese Patent Publication No. 46-10878.
JP-A-63-205136 or JP-A-64-67
No. 249, etc., and hot air is aerated from below while stirring horizontally on the fluidized bed.

The hot air temperature is preferably 70 to 100 ° C.

The water or the binder aqueous solution is sprayed continuously or intermittently from the upper part of the mixture while measuring the water content Y of the mixture of the Kampo extract powder and the excipient which are floating and swirling. To do. In particular, it is preferable to spray water or an aqueous binder solution continuously from the top of the mixture because the operation is easy.

The water content Y is measured by, for example, an infrared moisture meter as described above.

The spraying speed varies depending on the water content Y regulated by the formula (I), but is usually 20 to 100 ml / min. Although the spraying time cannot be generally specified depending on the target particle size of the granulated product, it is usually 1 minute to 3 hours, whereby fine granules and / or granular granules are obtained.

The granules obtained by the method of the present invention can be used as fine granules or granules as they are, but the granules can be formulated by a usual method to easily produce a solid preparation containing Kampo extract. Can be done. That is, after sieving, if necessary, it is divided into capsules by filling Kampo extract fine granules or Kampo extract granules into capsules, or tableting to produce Kampo extract-containing solid preparations such as tablets. You can

When a granular granulated product is used in the production of tablets, uneven color spots may occur on the tablet surface,
It is preferable to use a finely granulated material.

For the production of these solid preparations, pharmaceutical additives such as magnesium stearate, calcium carboxymethyl cellulose, lactose, cellulose, synthetic magnesium silicate, starch and the like can be appropriately added.

[0029]

INDUSTRIAL APPLICABILITY By the method of the present invention, Chinese herb extract granules having a high extract content can be efficiently produced. Moreover, since the method for producing a granulated product of the present invention does not use an organic solvent, it is safe in production, and there is no fear of residual solvent in the granulated product.

The solid preparations containing Kampo extract such as fine granules, granules, capsules and tablets obtained from the granules obtained in the present invention have a high content of Kampo extract and also have high dissolution and disintegration properties. Excellent formulation characteristics.

The formulation characteristics of the tablets produced by the method of the present invention will be described below with reference to test examples. Test example Disintegration test 1. Samples Tablets of Examples 54 to 68 and tablets of Comparative Examples 1 to 12 corresponding thereto.

The tablets of Examples 54 to 68 correspond to the tablets of Comparative Examples 1 to 12 as follows.

Tablet of Example 54 ... Tablet of Comparative Example 1 Tablet of Example 55 ... Tablet of Comparative Example 2 Tablet of Example 56 ... Tablet of Comparative Example 3 Tablet of Example 57 ... Tablet of Comparative Example 4 Tablet of Example 58 ... Tablet of Comparative Example 5 Tablet of Example 59 ... Tablet of Comparative Example 6 Tablet of Example 60 ... Tablet of Comparative Example 7 Tablet of Example 61. ..Tablet of Comparative Example 8 Tablet of Example 62 ... Tablet of Comparative Example 9 Tablet of Example 63 ... Tablet of Comparative Example 10 Tablet of Example 64 ... Tablet of Comparative Example 8 Tablet of Example 65 Tablet: Tablet of Comparative Example 8 Tablet of Example 66: Tablet of Comparative Example 8 Tablet of Example 67: Tablet of Comparative Example 11 Tablet of Example 68: Tablet of Comparative Example 12 Test method Disintegration test method described in the 12th Revised Japanese Pharmacopoeia (Twelfth Revised Japanese Pharmacopoeia, Supervised by the Japanese Official Book Association, Daiichi Law Publishing Co., Ltd., April 20, 1991, 63- (See page 66).

That is, 30 round trips per minute and an amplitude of 55 mm
The tablets were placed one by one in a glass tube of a tester which was adjusted to smoothly move up and down, and were moved up and down.
Water at 37 ° C. was used as the test solution. The state of the tablets was observed and the time until the tablets disintegrate (disintegration time) was measured. The disintegration time of 6 tablets was measured for each sample and the average value was calculated. 3. Test results The test results are shown in Table 1.

[0035]

[Table 1] As shown in Table 1, each of the tablets of the present invention has a shorter disintegration time as compared with the tablets of the corresponding comparative examples, and has excellent formulation characteristics.

[0036]

EXAMPLES The present invention will be described below with reference to examples.

The fluidized bed granulator used in the examples is a fluidized bed granulator with a stirrer on the fluidized bed, Spiral Flow SFC-5 type manufactured by Freund Sangyo Co., Ltd.

The Kampo extract powder used in the examples was obtained from the Kampo extract by a conventional method. In all, 90% or more of the total amount was a powder having a particle diameter of 150 μm or less, and the average particle diameter was 150 μm or less. Is about 70 μm.

Unless otherwise specified, the particle diameters of the excipients used in the examples are synthetic aluminum silicate (synthetic aluminum silicate special light, manufactured by Kyowa Chemical Industry Co., Ltd.): average particle diameter 13 μm, light anhydrous. Silicic acid (AER
OSIL ^™ 200, manufactured by Nippon Aerosil Co., Ltd.): average particle size 0.012 μm, hydrous silicon dioxide (Carplex ^™ # 80, manufactured by Shionogi & Co., Ltd.): average particle size 0.03 μm, crystalline cellulose (Avicel ^™ PH1)
01, manufactured by Asahi Kasei Co., Ltd.): average particle diameter 40 μm,
Corn starch: 17 μm, carboxymethyl cellulose calcium (ECG ^TM 505, manufactured by Gotoku Yakuhin Co., Ltd.): 95% or more of the total amount is 75 μm or less, magnesium aluminometasilicate (Neucillin ^TM FH)
1, manufactured by Fuji Chemical Industry Co., Ltd.): average particle diameter 0.1 μ
m.

In the examples, the plastic limit of the mixture comprising the Chinese herb extract powder and the excipient is represented by X, and the water content of the mixture in the fluid bed granulator is represented by Y. The X value uses a universal mixing stirrer 5DMr type manufactured by DALTON, and a stirring torque test (Journal of Powder Engineering, Volume 21, No. 6,
327, 1984). The Y value was measured using an infrared moisture meter Moiswatch (manufactured by Okawara Seisakusho Co., Ltd.).

Example 1 Determination of Correlation between Y Value and X Value for Granulation The X value of a mixture of Kampo extract powders of the following a to v and an excipient was measured, and these mixtures were placed on a fluidized bed. It was placed in a fluid bed granulator equipped with a stirrer. Hot air of about 80 ° C. was sent from the lower part of the fluidized bed to spray the water from the upper part while floating and swirling the mixture, to continuously measure the water content (Y) of the mixture and to measure the flow of the mixture in the fluidized bed. The water content when the mixture started to be granulated (YL) and the water content when the flow of the mixture started to stop (YH) were determined by visual observation.

Mixtures tested : Mixture a: 2.0 kg of Shoseiryuto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 21.6) Mixture b: 2.0 kg of Shoseiryuto extract powder. Mixture with 0.4 kg of synthetic aluminum silicate (X value: 29.7) Mixture c: Mixture of 2.0 kg of Shoseiryuto extract powder and 0.2 kg of light anhydrous silicic acid (X value: 33.3) Mixture d: a mixture of 2.0 kg of Shoseiryuto extract powder and 0.4 kg of light anhydrous silicic acid (X value: 39.6) mixture e: 2.0 kg of Shoseiryuto extract powder and 0.2 kg of hydrous silicon dioxide Mixture (X value: 32.5) Mixture f: A mixture of 2.0 kg of Keishikashakuyakuto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 16.
0) Mixture g: a mixture of 2.0 kg of Kamikihito extract powder and 0.2 kg of synthetic aluminum silicate (X value: 14.
1) Mixture h: a mixture of 2.0 kg of Gekfu-dokuto extract powder and 0.2 kg of hydrous silicic acid dioxide (X value: 21.6) Mixture i: 2.0 kg of Geki-dengto extract powder and light anhydrous silicic acid Mixture with 0.2 kg (X value: 24.6) Mixture j: Kakkonto extract powder 2.0 kg and synthetic aluminum silicate 0.2 kg (X value: 17.7) Mixture k: Kakkonto extract powder Mixture of 2.0 kg and light anhydrous silicic acid 0.2 kg (X value: 27.0) Mixture 1: Mixture of 2.0 kg of Saiko-keishito extract powder and 0.2 kg of light anhydrous silicic acid (X value: 29. 3) Mixture m: a mixture of 2.0 kg of Dokkkakakkonto extract powder and 0.2 kg of light anhydrous silicic acid (X value: 28.0) Mixture n: 2.0 kg of Hochuekkito extract powder and synthetic aluminum silicate Mixture with 0.2 kg (X value: 16.
9) Mixture 0: Mixture of 2.0 kg of windproof Tsusho powder extract powder and 0.2 kg of light anhydrous silicic acid (X value: 25.7) Mixture p: 2.0 kg of windbreak Tsusho powder extract and synthetic silica Mixture with 0.2 kg of aluminum acid salt (X value: 18.
3) Mixture q: a mixture of 2.0 kg of Shosaikoto extract powder and 0.2 kg of light anhydrous silicic acid (X value: 29.1) Mixture r: 2.0 kg of Shosaikoto extract powder and synthetic aluminum silicate Mixture with 2 kg (X value: 21.8) Mixture s: Mixture of 2.0 kg of Saireito extract powder and 0.2 kg of light anhydrous silicic acid (X value: 28.6) Mixture t: Ninjinyoeito extract Mixture of 2.0 kg of powder and 0.2 kg of light anhydrous silicic acid (X value: 24.1) Mixture u: Mixture of 2.0 kg of powder of Keishibukuryo pill extract and 0.2 kg of light anhydrous silicic acid (X value : 30.4) Mixture v: A mixture of 2.0 kg of Daisaikoto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 22.4) Water spraying rate (ml / min), X value of mixture, Moisture content (YL) and mixing when the mixture begins to granulate Table 2 shows the water content (YH) when the flow of the compound started to stop.

[0043]

[Table 2] Relational expression between Y and X when granulation starts by the method of least squares from the values of X and YL of the mixture (Y = 0.9X-9.8)
I asked. On the other hand, the relational expression (Y = 1.1) between Y and X when the flow starts to stop from the values of X and YH by the method of least squares.
X-6.8) was calculated. And from the relational expression of these two,
The following formula (I) showing the range of Y when granulation operation is possible 0.9X-9.8 ≦ Y ≦ 1.1X-6.8 (I) (wherein, X is The plastic limit of a mixture of Kampo extract powder and excipient is shown, provided that 14 ≦ X ≦ 40).

Example 2 Granulation of Shoseiryuto Extract Powder 2.0 kg of Shoseiryuto extract powder and 0.2% of light anhydrous silicic acid
The mixture with kg (X value: 33.3) was placed in a fluid bed granulator equipped with a stirrer on the fluidized bed. Hot air of about 80 ° C. is sent from below the fluidized bed to swirl the mixture in a floating manner, and the moisture content of the mixture is monitored by an infrared moisture meter.
While controlling to control, water was sprayed intermittently for 20 minutes at a spraying rate of 40 ml / min from the upper part (that is, the spraying was stopped when the Y value reached 25, and the spraying was started when the Y value dropped to 22). The operation of doing was repeated for 20 minutes). Thereafter, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below, and sieved with a No. 12 sieve (nominal size 1400 μm) and then a No. 83 sieve (nominal size 180 μm) to obtain an average particle diameter of 360 μm. Granules of 1.88 kg (yield 85.5
%) Was obtained.

Example 3 Granulation of Shoseiryuto Extract Powder 2.0 kg of Shoseiryuto extract powder and 0.4 g of light anhydrous silicic acid
A mixture with kg (X value: 39.6) was granulated and sieved in the same manner as in Example 2. Water was sprayed intermittently for 60 minutes while controlling the Y value to 26 to 31 (spraying speed 60
ml / min). Granules with an average particle diameter of 360 μm 1.99k
g (yield 82.9%) was obtained.

Example 4 Granulation of Shoseiryuto Extract Powder 2.0 kg of Shoseiryuto extract powder and 0.1% light anhydrous silicic acid
A mixture with kg (X value: 25.8) was granulated and sieved in the same manner as in Example 2. Water was sprayed intermittently for 75 minutes while controlling the Y value to 14 to 15 (spraying speed 40
ml / min). Granules with average particle diameter of 420 μm 1.75k
g (yield 83.3%) was obtained.

Example 5 Granulation of Shoseiryuto Extract Powder 2.0 kg of Shoseiryuto extract powder and hydrous silicon dioxide
A mixture with 2 kg (X value: 32.5) was granulated and sieved in the same process as in Example 2. Water was continuously sprayed for 10 minutes in the Y value range of 20 to 21 (spraying speed 40 ml /
Minutes). 1.68 kg (yield 76.4%) of granules having an average particle diameter of 480 μm were obtained.

Example 6 Granulation of Shoseiryuto Extract Powder 2.0 kg of Shoseiryuto extract powder and 0.2 of crystalline cellulose
A mixture with kg (X value: 17.1) was granulated and sieved in the same manner as in Example 2. Water was sprayed intermittently for 125 minutes while controlling the Y value to 6 to 7 (spraying speed 40 ml
/ Min). 1.61 kg of granules with an average particle diameter of 260 μm
(Yield 73.2%) was obtained.

Example 7 Granulation of Shoseiryuto Extract Powder A mixture of 2.0 kg of Shoseiryuto extract powder and 0.2 kg of corn starch (X value: 17.1) was prepared as in Example 2.
Granulation and sieving were carried out in the same process as above. Water is sprayed intermittently for 60 minutes while controlling the Y value to 6 to 8 (spraying speed 40 ml
/ Minute). Granules with an average particle size of 250 μm 1.60 k
g (yield 72.7%) was obtained.

Example 8 Granulation of Shoseiryuto Extract Powder A mixture of 2.0 kg of Shoseiryuto extract powder and 0.2 kg of carboxymethylcellulose calcium (X value: 16.
9) was granulated and sieved in the same manner as in Example 2. Water was sprayed intermittently (spraying speed 40 ml / min) for 120 minutes while controlling the Y value to 6-9. Average particle size 320μm
The obtained granules of 1.78 kg (yield 80.9%) were obtained.

Example 9 Granulation of Shoseiryuto Extract Powder A mixture of 2.0 kg of Shoseiryuto extract powder and 0.2 kg of magnesium aluminometasilicate (X value: 20.1)
Was granulated and sieved in the same manner as in Example 2. Water is Y
It sprayed intermittently (spraying rate 40 ml / min) for 55 minutes, controlling the value to 9-12. 1.61 kg (yield 73.2%) of a granulated product having an average particle diameter of 260 μm was obtained.

Example 10 Granulation of Shoseiryuto Extract Powder A mixture of 2.0 kg of Shoseiryuto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 21.6) was used as in Example 2. Was granulated and sieved in the step of. Water has a Y value of 10
It was sprayed intermittently (spraying rate 25 ml / min) for 120 minutes while controlling to 17. 1.69 kg (yield 76.8%) of a granulated product having an average particle diameter of 390 μm was obtained. Example 11 Granulation of Shoseiryuto Extract Powder A mixture of 2.0 kg of Shoseiryuto extract powder and 0.4 kg of synthetic aluminum silicate (X value: 29.7) was processed in the same manner as in Example 2. Granulated and sieved. Water has a Y value of 18-2
5 continuous spraying for 15 minutes (spraying speed 40 ml /
Minutes) 2.06 kg of granules with an average particle diameter of 510 μm
(Yield 85.8%) was obtained.

Example 12 Granulation of Shoseiryuto Extract Powder A mixture of 2.0 kg of Shoseiryuto extract powder and 0.1 kg of synthetic aluminum silicate (X value: 19.2) was used as in Example 2. Was granulated and sieved in the step of. Water has a Y value of 8 to 1
While controlling to 1 for 65 minutes, spraying intermittently (spraying speed 40
ml / min). Granulated product 1.6 having an average particle diameter of 380 μm
8 kg (yield 80.0%) was obtained.

Example 13 Granulation of Shoseiryuto Extract Powder While controlling the Y value to 10 to 15, instead of water, a 5% aqueous solution of hydroxypropylmethylcellulose was intermittently sprayed for 55 minutes (spraying rate 40 ml / minute). The same as in Example 10 except that the above), a granulated product having an average particle diameter of 380 μm and consisting of Shoseiryuto extract and synthetic aluminum silicate.
81 kg (yield 82.3%) was obtained.

Example 14 Granulation of Shoseiryuto Extract Powder While controlling the Y value to 10 to 16, instead of water, a 5% aqueous solution of polyvinylpyrrolidone K-30 was intermittently sprayed for 70 minutes (spraying speed 40 ml). 1.62 kg of granules having an average particle diameter of 300 μm and consisting of Shoseiryuto extract and synthetic aluminum silicate in the same manner as in Example 10 except that
(Yield 73.6%) was obtained.

Example 15 Granulation of Keishika-Shakuyakuyu Extract Powder A mixture of 2.0 kg of Keishika-Shakeyakuto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 16.0) was placed on a fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. Hot air of about 80 ° C was sent from below the fluidized bed to swirl the mixture in a floating manner, and the water content of the mixture was monitored by an infrared moisture meter. When the Y value was in the range of 6 to 10, water was continuously supplied from the upper portion for 20 minutes. It was sprayed (spray rate, 30 ml / min). After that, the spraying of water was stopped, the generated granules were dried by sending hot air from below, and sieved through No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) to obtain an average particle diameter. 370
1.65 kg (yield 75.0%) of a granulated product having a size of μm was obtained.

Example 16 Granulation of Keishika-Shakakuyaku-to extract powder A mixture (X value: 24.6) of 2.0 kg of Keishi-Kakeshaku-yu extract powder and 0.2 kg of light anhydrous silicic acid was used in Example 1.
Granulation and sieving were carried out in the same process as 5. Y value of water is 13 ~
Continuous spraying for 10 minutes in the range of 18 (spraying speed 40 ml
/ Minute). Granules with average particle diameter of 340 μm 1.95k
g (yield 88.6%) was obtained.

Example 17 Granulation of Keishika-Shakuyaku-to extract powder A mixture of 2.0 kg of Keishi-Kakeshaku-yu extract powder and 0.04 kg of light anhydrous silicic acid (X value: 14.7) was prepared as in Example 15. Granulation and sieving were carried out in the same process as above. Water has a Y value of 4 to
While controlling to 7, spray intermittently for 35 minutes (spraying speed 40
ml / min). Granulated product with an average particle diameter of 310 μm 1.4
8 kg (yield 72.5%) was obtained.

Example 18 Granulation of Kamikihito Extract Powder A mixture of 2.0 kg of Kamikito extract powder and 0.2 kg of synthetic aluminum silicate (X value: 14.1) was stirred on a fluidized bed. It was put in a fluidized bed granulator equipped with. Hot air of about 80 ° C was sent from below the fluidized bed to swirl the mixture in a floating manner, and the moisture content of the mixture was monitored by an infrared moisture meter. When the Y value was in the range of 4 to 8, water was continuously supplied from the top for 10 minutes. It was sprayed (spray rate, 30 ml / min). Then, the spraying of water is stopped, and the produced granulated product is dried by sending hot air from below to
The mixture was sieved through a No. 2 sieve (nominal size 1400 μm) and then a No. 83 sieve (nominal size 180 μm) to obtain 1.61 kg (yield 73.2%) of a granulated product having an average particle diameter of 360 μm.

Example 19 Granulation of Kamikihito Extract Powder 2.0 kg of Kamikihito extract powder and light anhydrous silicic acid
A mixture with 2 kg (X value: 22.8) was granulated and sieved in the same manner as in Example 18. Water has a Y value of 11-15
For 10 minutes continuously (spraying speed 40 ml /
Minutes) 1.93 kg of granulated material having an average particle diameter of 460 μm
(Yield 87.7%) was obtained.

Example 20 Granulation of Gekifu-dokuto extract powder A mixture of 2.0 kg of Gak-dokuto extract powder and 0.2 kg of hydrous silicon dioxide (X value: 21.6) was placed on a fluidized bed in a stirrer. It was put in the fluidized bed granulator. Hot air of about 80 ° C was sent from below the fluidized bed to swirl and flow the mixture, and the moisture content of the mixture was monitored by an infrared moisture meter.
Water was sprayed continuously from the top for 15 minutes in the range of 0 to 15 (spray rate, 40 ml / min). After that, the spraying of water was stopped, the generated granules were dried by sending hot air from below, and sieved through No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) to obtain an average particle diameter. 370
1.59 kg (yield 72.3%) of a granule having a size of μm was obtained.

Example 21 Granulation of Gekifu-doku-to extract powder A mixture of 2.0 kg of Geki-doku-to extract powder and 0.1 kg of hydrous silicon dioxide (X value: 17.2) was used in Example 2.
Granulation and sieving were carried out in the same process as 0. Water has a Y value of 6 to 1
20 minutes intermittently while controlling to 0 (spraying speed 40
ml / min). Granulated material 1.6 with an average particle diameter of 230 μm
1 kg (yield 76.7%) was obtained.

Example 22 Granulation of Gekifu-dokuto extract powder A mixture of 2.0 kg of Gekidou-dokuto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 17.1) was used in the same manner as in Example 20. Was granulated and sieved in the step of. Water has a Y value of 6
It sprayed intermittently (spraying speed 40 ml / min) for 35 minutes, controlling at -10. 1.57 kg (yield 71.4%) of a granulated product having an average particle diameter of 270 μm was obtained. Example 23 Granulation of Gekifu-gedokuto extract powder 2.0 kg of Gekifu-dokuto extract powder and light anhydrous silicic acid
A mixture with 1 kg (X value: 19.1) was granulated and sieved in the same process as in Example 20. Water is sprayed intermittently for 30 minutes while controlling the Y value to 8 to 10 (spraying speed 40 ml
/ Minute). Granules with average particle diameter of 380 μm 1.64k
g (yield 78.1%) was obtained.

Example 24 Granulation of Gekifu-gedokuto extract powder 2.0 kg of Gekifu-gedokuto extract powder and light anhydrous silicic acid
A mixture with 2 kg (X value: 24.6) was granulated and sieved in the same manner as in Example 20. Water has a Y value of 15-19
For 10 minutes continuously (spraying speed 40 ml /
Minutes) 1.78 kg of granulated material having an average particle diameter of 400 μm
(Yield 80.9%) was obtained.

Example 25 Granulation of Daisaikoto Extract Powder A mixture of 2.0 kg of Daisaikoto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 22.4) was placed on a fluidized bed with a stirrer. Placed in a fluid bed granulator. A hot air of about 80 ° C. is sent from the bottom of the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter.
Water was sprayed intermittently (spraying rate, 30 ml / min) from the upper part for 50 minutes while controlling to 2 to 13. After that, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below, and sieved through a No. 12 sieve (nominal size 1400 μm) and then a No. 83 sieve (nominal size 180 μm) to obtain an average particle diameter of 300.
1.66 kg (yield 75.5%) of a granulated product of μm was obtained.

Example 26 Granulation of Daisaikoto extract powder 2.0 kg of Daisaikoto extract powder and 0.2 light anhydrous silicic acid
A mixture with kg (X value: 33.8) was granulated and sieved in the same manner as in Example 25. Water is sprayed continuously for 10 minutes in the Y value range of 21 to 25 (spraying speed 40 ml / min)
did. 1.80 kg (yield 81.8%) of a granulated product having an average particle diameter of 380 μm was obtained.

Example 27 Granulation of Kakkonto Extract Powder 2.0 kg of Kakkonto extract powder and 0.2 k of light anhydrous silicic acid
The mixture with g (X value: 27.0) was placed in a fluid bed granulator with a stirrer on the fluid bed. About 8 from the bottom of the fluidized bed
The mixture is floated and swirled by sending hot air of 0 ° C., the water content of the mixture is monitored by an infrared moisture meter, and water is continuously sprayed for 10 minutes from the upper part in the Y value range of 15 to 21 (spraying speed,
40 ml / min). After that, the spraying of water was stopped, the generated granules were dried by sending hot air from below, and sieved through No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) to obtain an average particle diameter. 1.76 kg (yield 80.0%) of 340 μm granulated product was obtained.

Example 28 Granulation of Kakkonto Extract Powder A mixture of Kakkonto extract powder (2.0 kg) and synthetic aluminum silicate (0.2 kg) (X value: 17.7) was used in Example 2.
Granulation and sieving were carried out in the same process as in 7. Water has a Y value of 6 to 1
For 55 minutes while controlling to 0, spraying intermittently (spraying speed 30
ml / min). 1.7 granules with an average particle size of 330 μm
1 kg (yield 77.7%) was obtained.

Example 29 Granulation of Saiko-keishi-to extract powder 2.0 kg of saiko-keishi-to extract powder and light anhydrous silicic acid
The mixture with 2 kg (X value: 29.3) was placed in a fluid bed granulator with a stirrer on the fluid bed. Hot air of about 80 ° C. is sent from below the fluidized bed to make the mixture float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter.
In the range of 2, water was sprayed continuously from the top for 10 minutes (spray rate, 40 ml / min). Then stop spraying water,
The produced granules were dried by sending hot air from below, and sieved through No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) to obtain 1.95 kg of granules having an average particle diameter of 490 μm ( Rate 88.6%).

Example 30 Granulation of Dokkkaito Kakkonto extract powder 2.0 kg of Dokkkakakkonto extract powder and light anhydrous silicic acid
The mixture with 2 kg (X value: 28.0) was placed in a fluid bed granulator equipped with a stirrer on the fluid bed. Hot air of about 80 ° C. is sent from below the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter.
In the range of 0, water was continuously sprayed from the top for 10 minutes (spray rate, 40 ml / min). Then stop spraying water,
The produced granules were dried by sending hot air from below, and sieved through No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) to obtain 1.70 kg of granules having an average particle diameter of 260 μm (collection Rate 77.3%).

Example 31 Granulation of Hochuekkito extract powder A mixture of 2.0 kg of Hochuekkito extract powder and 0.2 kg of synthetic aluminum silicate (X value: 16.9) was placed on the fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. Hot air of about 80 ° C was sent from below the fluidized bed to swirl the mixture in a floating manner, and the moisture content of the mixture was monitored by an infrared moisture meter, while controlling the Y value to 6-9, water was intermittently supplied from the upper portion for 50 minutes. Spraying (spray rate, 40 ml / min). After that, the spraying of water was stopped, the generated granules were dried by sending hot air from below, and sieved with No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) to obtain an average particle diameter of 230 μm.
1.64 kg (yield 74.5%) of a granulated product of m was obtained.

Example 32 Granulation of wind-proof Tsusho powder extract powder A mixture of 2.0 kg of wind-proof Seisho powder extract and 0.2 kg of light anhydrous silicic acid (X value: 25.7) was placed on a fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. Hot air of about 80 ° C was sent from below the fluidized bed to swirl and flow the mixture, and the moisture content of the mixture was monitored by an infrared moisture meter.
Water was sprayed continuously from the top for 15 minutes in the range of 6 to 21 (spray rate, 40 ml / min). After that, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below, and sieved with a No. 12 sieve (nominal size 1400 μm) and then a No. 83 sieve (nominal size 180 μm) to obtain an average particle diameter of 380 μm.
1.78 kg (yield 80.9%) of a granulated product of m was obtained.

Example 33 Granulation of Windproof Tsusho Powder Extract Powder A mixture of 2.0 kg of windproof Seisho powder extract and 0.2 kg of synthetic aluminum silicate (X value: 18.3) was prepared in Example 32. Granulation and sieving were carried out in the same process as above. Water was intermittently sprayed (spray rate 30 ml / min) for 60 minutes while controlling the Y value to 8 to 13. 1.84 kg (yield 83.7%) of a granulated product having an average particle diameter of 410 μm was obtained.

Example 34 Granulation of Shosaikoto Extract Powder 2.0 kg of Shosaikoto extract powder and 0.2 light anhydrous silicic acid
The mixture with kg (X value: 29.1) was placed in a fluid bed granulator equipped with a stirrer on the fluid bed. A hot air of about 80 ° C. is sent from the bottom of the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter.
Water was continuously sprayed for 10 minutes (spray rate, 40 ml / min) from the top in the range of. Then stop spraying water,
The produced granules were dried by sending hot air from below, and sieved through No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) to obtain 1.82 kg of granules having an average particle diameter of 460 μm ( Rate 82.7%).

Example 35 Granulation of Shosaikoto Extract Powder A mixture of 2.0 kg of Shosaikoto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 21.8) was treated in the same manner as in Example 34. Granulated and sieved. Water has a Y value of 10
It was sprayed intermittently (spraying rate 40 ml / min) for 50 minutes while controlling to -14. 1.61 kg (yield 73.2%) of granules having an average particle diameter of 360 μm were obtained. Example 36 Granulation of Sairei-to extract powder 2.0 kg of Sairei-to extract powder and 0.2 k of light anhydrous silicic acid
The mixture with g (X value: 28.6) was placed in a fluid bed granulator with a stirrer on the fluid bed. About 8 from the bottom of the fluidized bed
The mixture is floated and swirled by sending hot air of 0 ° C., the moisture content of the mixture is monitored by an infrared moisture meter, and water is continuously sprayed for 10 minutes from the upper part in the Y value range of 16 to 23 (spraying speed,
40 ml / min). Then, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below, and the No. 12 sieve (nominal size 1400 μm) and then the No. 83 sieve (nominal size 1
80 μm) to obtain 1.99 kg (yield 90.5%) of a granulated product having an average particle diameter of 380 μm.

Example 37 Granulation of Ninjin-yoei-to extract powder 2.0 kg of ginseng-yoei-to extract powder and light anhydrous silicic acid
The mixture with 2 kg (X value: 24.1) was placed in a fluid bed granulator with a stirrer on the fluid bed. A hot air of about 80 ° C. is sent from below the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter, and the Y value is 12 to 1
In the range of 5, water was sprayed continuously from the top for 10 minutes (spraying rate 40 ml / min). Then, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below, and the No. 12 sieve (nominal size 1400 μm) and then the No. 83 sieve (nominal size 1
80 μm), and 1.84 kg (yield 83.6%) of a granulated product having an average particle diameter of 340 μm was obtained.

Example 38 Granulation of Keishibukuryo banyan extract powder A mixture of 2.0 kg of keishibukuryo banyan extract powder and 0.2 kg of light anhydrous silicic acid (X value: 30.4) was placed on a fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. Hot air of about 80 ° C was sent from below the fluidized bed to swirl and flow the mixture, and the moisture content of the mixture was monitored by an infrared moisture meter.
In the range of 8 to 21, water was continuously sprayed from the top for 10 minutes (spraying rate 40 ml / min). After that, the spraying of water was stopped, and the generated granules were dried by sending hot air from below,
No. 12 sieve (nominal size 1400 μm) and then No. 83 sieve (nominal size 180 μm) were passed through to obtain 1.73 kg (yield 78.6%) of granules having an average particle diameter of 300 μm.

Example 39 Granulation of Shosaikoto Extract Powder 2.0 kg of Shosaikoto extract powder and 0.2 light anhydrous silicic acid
The mixture with kg (X value: 29.1) was placed in a fluid bed granulator equipped with a stirrer on the fluidized bed. A hot air of about 80 ° C. is sent from the bottom of the fluidized bed to make the mixture flow in a floating orbit, and the moisture content of the mixture is monitored by an infrared moisture meter.
The water was continuously sprayed from the top for 5 minutes (spraying rate 60 ml / min) while controlling the above. Thereafter, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to give 2.12 kg of a granulated product having an average particle diameter of 100 μm (yield 96.4%).
Got

Example 40 Granulation of Windproof Tsusho Powder Extract Powder A mixture of 2.0 kg of windproof Seisho powder extract and 0.2 kg of light anhydrous silicic acid (X value: 25.7) was placed on a fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. A hot air of about 80 ° C. is sent from the bottom of the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter.
Water was continuously sprayed from the upper portion for 5 minutes while controlling the rate at 3 to 20 (spraying rate 43 ml / min). After that, the spraying of water was stopped, and the generated granules were dried by sending hot air from below,
Granules with an average particle diameter of 120 μm 2.00 kg (yield 9
0.9%) was obtained.

Example 41 Granulation of Hachimi Yellow Pill Extract Powder A mixture of 2.0 kg of Hachimiji yellow pill extract powder and 0.2 kg of light anhydrous silicic acid (X value: 31.8) was placed on a fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. A hot air of about 70 ° C. is sent from the bottom of the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter, and the Y value is set to 1
Water was continuously sprayed from the upper portion for 3 minutes (spraying rate 67 ml / min) while being controlled at 9 to 23. After that, the spraying of water was stopped, and the generated granules were dried by sending hot air from below,
1.98 kg of granules having an average particle diameter of 160 μm (yield 9
0.0%) was obtained.

Example 42 Granulation of Daisaikoto extract powder 2.0 kg of Daisaikoto extract powder and 0.2 light anhydrous silicic acid
The mixture with kg (X value: 33.8) was put in a fluid bed granulator equipped with a stirrer on the fluidized bed. Hot air of about 70 ° C is sent from below the fluidized bed to swirl the mixture in a floating manner, and the moisture content of the mixture is monitored by an infrared moisture meter. While controlling the Y value to about 21, water is continuously fed from the top for 1 minute. Spraying (spraying speed 7
0 ml / min). After that, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain an average particle size of 1
2.12 kg of a 10 μm granulated product (yield 96.4%) was obtained.

Example 43 Granulation of Shoseiryuto Extract Powder 2.0 kg of Shoseiryuto extract powder and light anhydrous silicic acid 0.2
The mixture with kg (X value: 33.3) was placed in a fluid bed granulator equipped with a stirrer on the fluidized bed. A hot air of about 70 ° C. is sent from the bottom of the fluidized bed to cause the mixture to float and swirl, the moisture content of the mixture is monitored by an infrared moisture meter, and the Y value is 20 to 21.
Water was continuously sprayed from the top for 1 minute (spraying rate 67 ml / minute) while controlling the above. Thereafter, spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain 2.04 kg (yield 92.7%) of a granulated product having an average particle diameter of 90 μm.

Example 44 Granulation of Keishibukuryo banyan extract powder A mixture (X value: 30.4) of 2.0 kg of kyushibukuryo banyan extract powder and 0.2 kg of light anhydrous silicic acid was placed on a fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. A hot air of about 70 ° C. is sent from the bottom of the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter, and the Y value is set to 1
Water was continuously sprayed from the top for 2 minutes while controlling the rate at 8 to 20 (spraying rate 63 ml / min). After that, the spraying of water was stopped, and the generated granules were dried by sending hot air from below,
1.94 kg of granules having an average particle diameter of 80 μm (yield 88.
2%) was obtained.

Example 45 Granulation of Hochuekkito extract powder 2.0 kg of Hochuekkito extract powder and light anhydrous silicic acid
The mixture with 2 kg (X value: 26.1) was placed in a fluid bed granulator equipped with a stirrer on the fluidized bed. A hot air of about 70 ° C. is sent from below the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter, and the Y value is 14 to 1
While controlling to 9, water was continuously sprayed from the top for 4 minutes (spraying rate 67 ml / min). Then stop spraying water,
The produced granulated product was dried by sending hot air from below to obtain 2.02 kg of a granulated product having an average particle diameter of 90 μm (yield 91.8).
%) Was obtained.

Example 46 Granulation of Kakkonto Extract Powder 2.0 kg of Kakkonto extract powder and 0.2 k of light anhydrous silicic acid
The mixture with g (X value: 27.0) was placed in a fluid bed granulator equipped with a stirrer on the fluidized bed. About 7 from the bottom of the fluidized bed
Hot air of 0 ° C. is sent to make the mixture float and swirl, the moisture content of the mixture is monitored by an infrared moisture meter, and water is continuously sprayed for 4 minutes from the top while controlling the Y value to 15 to 18 (spraying speed 61 ml. / Minute). Thereafter, spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain 1.98 kg (yield 90.0%) of a granulated product having an average particle diameter of 160 μm.

Example 47 Granulation of Kakkonto Extract Powder 2.0 kg of Kakkonto extract powder and 0.1 k of light anhydrous silicic acid
The mixture with g (X value: 19.3) was placed in a fluid bed granulator equipped with a stirrer on the fluid bed. About 7 from the bottom of the fluidized bed
Hot air of 0 ° C. is sent to float and swirl the mixture, and the moisture content of the mixture is monitored by an infrared moisture meter. While controlling the Y value to 8 to 9, water is continuously sprayed from the top for 4 minutes (spraying speed 48
ml / min). Thereafter, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain an average particle size of 12
2.02 kg of 0 μm granules (yield 96.2%) were obtained.

Example 48 Granulation of Kakkonto Extract Powder 2.0 kg of Kakkonto extract powder and 0.4 k of light anhydrous silicic acid
The mixture with g (X value: 36.9) was placed in a fluid bed granulator equipped with a stirrer on the fluid bed. About 7 from the bottom of the fluidized bed
The mixture is floated and swirled by sending hot air of 0 ° C., the water content of the mixture is monitored by an infrared moisture meter, and the Y value is controlled to about 23 while continuously spraying water from the top for 1 minute (spraying speed 59
ml / min). Thereafter, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain an average particle size of 11
2.00 kg (yield 83.3%) of 0 μm granules were obtained.

Example 49 Granulation of Kakkonto Extract Powder A mixture of 2.0 kg of Kakkonto extract powder and 0.2 kg of synthetic aluminum silicate (X value: 17.7) was placed on a fluidized bed in a fluidized bed with a stirrer. I put it in the granulator. Hot air of about 70 ° C is sent from below the fluidized bed to swirl the mixture in a floating manner, and the moisture content of the mixture is monitored by an infrared moisture meter. While controlling the Y value to about 6, water is continuously fed from the top for 1 minute. It was sprayed (spray rate 49 ml / min). Then stop spraying water,
The produced granulated product was dried by sending hot air from below, and 1.82 kg of a granulated product having an average particle diameter of 370 μm (yield 83.0
%) Was obtained.

Example 50 Granulation of Kakkon-to extract powder 2.0 kg of Kakkon-to extract powder and 0.2 of hydrous silicon dioxide
The mixture with kg (X value: 21.1) was placed in a fluid bed granulator with a stirrer on the fluid bed. Hot air of about 70 ° C. is sent from below the fluidized bed to make the mixture float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter, while controlling the Y value to 9 to 14, water is continuously supplied from the top. It was sprayed for a minute (spray rate 53 ml / min). Thereafter, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain 1.92 kg (yield 87.3%) of a granulated product having an average particle diameter of 80 μm.

Example 51 Granulation of Kakkonto Extract Powder A mixture of 2.0 kg of Kakkonto extract powder and 0.2 kg of magnesium aluminometasilicate (X value: 29.2).
Was placed in a fluid bed granulator with a stirrer on the fluid bed.
Hot air of about 70 ° C. is sent from below the fluidized bed to swirl the mixture in a floating manner, and the moisture content of the mixture is monitored with an infrared moisture meter, while controlling the Y value to 16 to 17, water is continuously added from the top to 1 It was sprayed for a minute (spraying rate 48 ml / min). afterwards,
The spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain 2.02 kg of a granulated product having an average particle diameter of 80 μm.
(Yield 91.8%) was obtained.

Example 52 Granulation of Tokishakuyaku powder extract powder A mixture (X value: 30.0) of 2.0 kg of Tokishakuyaku powder extract powder and 0.2 kg of light anhydrous silicic acid was placed on a fluidized bed. It was put in a fluidized bed granulator equipped with a stirrer. A hot air of about 70 ° C. is sent from the bottom of the fluidized bed to cause the mixture to float and swirl, and the moisture content of the mixture is monitored by an infrared moisture meter, and the Y value is set to 1
Water was continuously sprayed from the upper part for 20 minutes while controlling at 7 to 30 (spraying speed 40 ml / min). Thereafter, spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain 2.08 kg (yield 94.5%) of a granulated product having an average particle diameter of 330 μm.

Example 53 Granulation of Dokatsu-kakkonto extract powder 3.0 kg of Dokkak-kakkon-to extract powder and light anhydrous silicic acid
The mixture with 3 kg (X value: 28.0) was put in a fluid bed granulator equipped with a stirrer on the fluidized bed. Hot air of about 60 ° C is sent from below the fluidized bed to swirl the mixture in a floating manner, and the moisture content of the mixture is monitored by an infrared moisture meter. While controlling the Y value to about 15, water is continuously fed from the top for 1 minute. It was sprayed (spraying rate 40 ml / min). Thereafter, the spraying of water was stopped, and the produced granulated product was dried by sending hot air from below to obtain 3.10 kg (yield 93.9%) of a granulated product having an average particle diameter of 100 μm.

Example 54 Manufacture of Tablets Containing Shosaikoto Extract (Formulation) Component Weight Part Granule of Example 39 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Magnesium Stearate 1 (Operation) Mix each of the above components thoroughly, and mix the mixture to 300 m.
Each g was compressed with a tableting pressure of 0.6 tons / punch and a diameter of 9 mm,
A tablet containing Shosaikoto extract having a hardness of 6 kg was obtained.

Example 55 Production of Tablets Containing Windproofing Seisho Powder Extract (Formulation) Components by Weight Granules of Example 40 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Stearic Acid Magnesium 1 (Operation) Mix the above components thoroughly and mix the mixture to 300 m.
Each g was compressed with a tableting pressure of 1.1 tons / punch and a diameter of 9 mm,
A windproof Tsusho powder extract-containing tablet having a hardness of 6 kg was obtained.

Example 56 Production of tablets containing Hachimijiogan pill extract (formulation) Component parts by weight Granules of Example 41 77 Synthetic aluminum silicate 5 Carboxymethylcellulose calcium 15 Crystalline cellulose 2 Stearic acid Magnesium 1 (Operation) Mix the above components thoroughly and mix the mixture to 300 m.
Each g was compressed with a tableting pressure of 0.7 tons / punch and a diameter of 9 mm,
A tablet containing Hachimijiogan pill extract having a hardness of 6 kg was obtained.

Example 57 Production of Daisaikoto extract-containing tablet (formulation) Ingredient Weight part Granule of Example 42 77 Synthetic aluminum silicate 5 Carboxymethylcellulose calcium 15 Crystalline cellulose 2 Magnesium stearate 1 (Operation) Mix each of the above components thoroughly, and mix the mixture to 300 m.
Each g was compressed with a tableting pressure of 0.4 tons / punch and a diameter of 9 mm,
A tablet containing Daisaikoto extract having a hardness of 6 kg was obtained.

Example 58 Production of Tablets Containing Shoseiryuto Extract (Formulation) Component Weight Part Granule of Example 43 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Magnesium Stearate 1 (Operation) Mix the above components thoroughly and mix 300m.
Each g was compressed with a tableting pressure of 0.6 tons / punch and a diameter of 9 mm,
A tablet containing Shoseiryuto extract having a hardness of 6 kg was obtained.

Example 59 Production of Tablet Containing Keishi Fukuryo Pill Extract (Prescription) Component Weight Part Granules of Example 44 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Stearic Acid Magnesium 1 (Operation) Mix the above components thoroughly and mix the mixture to 300 m.
Each g was compressed with a tableting pressure of 0.7 tons / punch and a diameter of 9 mm,
A tablet containing the Keishibukuryo rye extract having a hardness of 6 kg was obtained.

Example 60 Production of tablets containing Hochuekkito extract (formulation) Component parts by weight Granules of Example 45 77 Synthetic aluminum silicate 5 Carboxymethylcellulose calcium 15 Crystalline cellulose 2 Stearic acid Magnesium 1 (Operation) Mix the above components thoroughly and mix the mixture to 300 m.
Each g was compressed with a tableting pressure of 0.5 tons / punch and a diameter of 9 mm,
A tablet containing Hochuekkito extract having a hardness of 6 kg was obtained.

Example 61 Production of Kakkonto Extract-Containing Tablet (Formulation) Component Weight Part Granules of Example 46 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Magnesium Stearate 1 ( Operation) Mixing the above components thoroughly, the mixture 300m
Each g was compressed with a tableting pressure of 0.6 tons / punch and a diameter of 9 mm,
A Kakkonto extract-containing tablet having a hardness of 6 kg was obtained.

Example 62 Production of Kakkonto Extract-Containing Tablets (Formulation) Component Weight Part Granules of Example 47 73.5 Synthetic aluminum silicate 5 Carboxymethylcellulose calcium 15 Crystalline cellulose 5.5 Stearin Magnesium acid 1 (operation) Mixing the above components thoroughly, the mixture 300m
Each g was compressed with a tableting pressure of 0.5 tons / punch and a diameter of 9 mm,
A Kakkonto extract-containing tablet having a hardness of 6 kg was obtained.

Example 63 Production of Kakkonto Extract-Containing Tablet (Formulation) Ingredients Weight Parts Granules of Example 48 84 Carboxymethylcellulose calcium 15 Magnesium stearate 1 (Operation) The above components were thoroughly mixed, The mixture 300m
Tablets each with a tableting pressure of 0.8 ton / punch and a diameter of 9 mm,
A Kakkonto extract-containing tablet having a hardness of 6 kg was obtained.

Example 64 Production of Kakkonto Extract-Containing Tablet (Formulation) Component Weight Part Granule of Example 49 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Magnesium Stearate 1 ( Operation) Mixing the above components thoroughly, the mixture 300m
Tablets are compressed with a tableting pressure of 0.75 tons / punch each 9g, diameter 9m
A Kakkonto extract-containing tablet having m and a hardness of 6 kg was obtained.

Example 65 Production of Tablets Containing Kakkonto Extract (Formulation) Ingredients Parts by Weight Granules of Example 50 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Magnesium Stearate 1 ( Operation) Mixing the above components thoroughly, the mixture 300m
Each g was compressed with a tableting pressure of 0.4 tons / punch and a diameter of 9 mm,
A Kakkonto extract-containing tablet having a hardness of 6 kg was obtained.

Example 66 Production of Kakkonto Extract-Containing Tablet (Formulation) Component Weight Part Granule of Example 51 77 Synthetic Aluminum Silicate 5 Carboxymethyl Cellulose Calcium 15 Crystalline Cellulose 2 Magnesium Stearate 1 ( Operation) Mixing the above components thoroughly, the mixture 300m
Each g was compressed with a tableting pressure of 0.4 tons / punch and a diameter of 9 mm,
A Kakkonto extract-containing tablet having a hardness of 6 kg was obtained.

Example 67 Production of tablets containing Tokishakuyakuyaku powder extract (formulation) Component parts by weight Granules of Example 52 76 Synthetic aluminum silicate 3 Carboxymethylcellulose calcium 18 Crystalline cellulose 2 Stearic acid Magnesium 1 (Operation) Mix the above components thoroughly and mix the mixture to 300 m.
Each g was compressed with a tableting pressure of 1.0 ton / punch and a diameter of 9 mm,
Tokishakushakuyaku powder extract-containing tablets having a hardness of 6 kg were obtained.

Example 68 Production of tablets containing Dokatsukakkonto extract (formulation) Component parts by weight Granules of Example 53 64 Synthetic aluminum silicate 9 Carboxymethylcellulose calcium 19 Crystalline cellulose 7 Magnesium stearate 1 (Operation) Mix the above components thoroughly, and mix the mixture to 400 m.
Tablets with a tableting pressure of 1.25 tons / punch each with a diameter of 10 m
m and hardness of 10 kg were obtained.

Example 69 Production of tablets containing Dokatsukakkonto extract (formulation) Component parts by weight Granules of Example 30 3080 Synthetic aluminum silicate 200 Carboxymethyl cellulose calcium 900 Crystalline cellulose 572 Magnesium stearate 48 (Operation) Each of the above Mix the ingredients well and mix 400m
Tablets with a tableting pressure of 1.25 tons / punch each with a diameter of 10 m
m and hardness of 10 kg were obtained.

Tablets of Comparative Example Instead of the extract granulation product, a mixture of the extract powder and crystalline cellulose (the mixing ratio is the same as the mixing ratio of the extract powder and the excipient used for the production of the extract granulation product). Tablets of comparative examples corresponding to the tablets of Examples 54 to 68 were produced in the same manner as in Examples 54 to 68 except that they were used. In each comparative example, the reason for using the mixture of the extract powder and the crystalline cellulose is that the extract powder and the excipient used for the granulation (eg, light anhydrous silicic acid, hydrous silicon dioxide).
This is because tableting was difficult when using a mixture with.

The formulations of the tablets of each comparative example are shown below.

Comparative Example 1 Formulation of Tablets Containing Shosaikoto Extract (Comparison with Example 54) 77 parts by weight of a mixture of Shosaikoto extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic aluminum silicate 5
Parts by weight, carboxymethyl cellulose calcium 15 parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 2 Formulation of Tablets Containing Windproofing Seisho Powder Extract (Comparison with Example 55) 77 parts by weight of a mixture of windproofing Seisho powder extract and crystalline cellulose (mixing weight ratio 10: 1), synthetic silicic acid Aluminum 5 parts by weight, carboxymethyl cellulose calcium 15
Parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 3 Formulation of Tablets Containing Hachimi Yellow Pill Extract (Comparison with Example 56) 77 parts by weight of a mixture of Hachimijio pill extract and crystalline cellulose (mixing weight ratio 10: 1), synthetic silicic acid Aluminum 5 parts by weight, carboxymethyl cellulose calcium 15
Parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 4 Formulation of Daisaikoto Extract-Containing Tablets (Comparison with Example 57) 77 parts by weight of a mixture of Daisaikoto extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic aluminum silicate 5 parts by weight Part, carboxymethyl cellulose calcium 15
Parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 5 Formulation of Tablets Containing Shoseiryuto Extract (Comparison with Example 58) 77 parts by weight of a mixture of Shoseiryuto extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic aluminum silicate 5 parts by weight, carboxymethyl cellulose calcium 15
Parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 6 Formulation of tablets containing Keishibukuryo pill extract (comparison with Example 59) 77 parts by weight of a mixture of Keishibukuryo pill extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic silica Aluminum oxide 5 parts by weight, carboxymethyl cellulose calcium 15 parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 7 Formulation of Hochuekkito Extract-Containing Tablets (Comparison with Example 60) 77 parts by weight of a mixture of Hochuekkito extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic silica Aluminum oxide 5 parts by weight, carboxymethyl cellulose calcium 1
5 parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 8 Formulation of Kakkonto Extract-Containing Tablets (Comparison of Examples 61, 64, 65 and 66) 77 parts by weight of a mixture of Kakkonto extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic silica Aluminum acid 5
Parts by weight, carboxymethyl cellulose calcium 15 parts by weight, crystalline cellulose 2 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 9 Preparation of Tablets Containing Kakkonto Extract (Comparison with Example 62) 73.5 parts by weight of a mixture of Kakkonto extract powder and crystalline cellulose (mixing weight ratio 20: 1), 5 parts by weight of synthetic aluminum silicate Part, carboxymethyl cellulose calcium 1
5 parts by weight, crystalline cellulose 5.5 parts by weight, magnesium stearate 1 part by weight.

Comparative Example 10 Formulation of Kakkonto Extract-Containing Tablets (Comparison with Example 63) 84 parts by weight of a mixture of Kakkonto extract powder and crystalline cellulose (mixing weight ratio 5: 1), carboxymethylcellulose calcium 15 parts by weight Parts, 1 part by weight of magnesium stearate.

Comparative Example 11 Formulation of Tablets Containing Tokishakuyaku Powder Extract (Comparison with Example 67) 76 parts by weight of a mixture of Tokishakuyaku powder extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic silica 3 parts by weight of aluminum acid salt, 18 parts by weight of carboxymethyl cellulose calcium, 2 parts by weight of crystalline cellulose, 1 part by weight of magnesium stearate.

Comparative Example 12 Formulation of tablets containing Dokkkakakkonto extract (comparison with Example 68) 64 parts by weight of a mixture of Dokkkakakkonto extract powder and crystalline cellulose (mixing weight ratio 10: 1), synthetic aluminum silicate 9 parts by weight Part, carboxymethyl cellulose calcium 1
9 parts by weight, crystalline cellulose 7 parts by weight, magnesium stearate 1 part by weight.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Akira Suzuki 747 Kada, Oita, Tomitabayashi-shi, Osaka

Claims (2)

[Claims] 1. 100 parts by weight of Kampo extract powder and excipient 2
A mixture of about 20 parts by weight is floated and swirled, and the water content Y of the mixture is expressed by the following formula (I) 0.9X-9.8 ≦ Y ≦ 1.1X-6.8. I) (In the formula, X represents the plastic limit of a mixture of Kampo extract powder and excipients, provided that 14 ≦ X ≦ 40) while controlling the mixture to contain water or a binder aqueous solution. A method for producing a granulated product comprising a Chinese herb extract and an excipient, which comprises spraying. 2. A method for producing a solid preparation containing Chinese herb extract, which comprises formulating the granulated product obtained by the method according to claim 1.