JPH07309769A - Moistureproof herb granule preparation - Google Patents

Abstract

PURPOSE: To prepare the subject preparation having improved moisture resistance of a granular preparation of an extract of a Chinese medicine and further improved condensing magnification of the extract of the Chinese medicine by coating a granule comprising the condensed extract of the Chinese medicine, and corn starch with a composition for coating comprising water-soluble polysaccharides. CONSTITUTION: The objective moisture proof granular preparation of Chinese medicine having improved moisture resistance and heightened condensing magnification is obtained by dipping simotuto, etc., comprising Ligusticum acutilobum, Rehmannia glutinosa, Paeonia lactiflora and Cnidium officinale in water for 2 hr, heating the dipping liquid to boil for 1 hr to extract, filtering and gathering the resultant liquid and carrying out condensation of the filtrate to provide a condensed extract of the Chinese medicine, mixing the resultant condensed extract with corn starch, spraying and granulating the obtained mixture by a fluidized bed type granulator to provide granules, charging the obtained granules to the fluidized bed type granulator, sending a hot wind of about 70 deg.C from the lower part of the fluidized bed while spraying 1% aqueous solution of water-soluble polysaccharides (e.g. guar gum) under 2-3 kg/cm<2> nozzle pressure at 100 ml/hr spraying rate to coat the granules with a coating composition comprising the water-soluble polysaccharides.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a concentrated Chinese herbal medicine extract granule preparation, and more particularly to a moisture-proof granule preparation in which granules are coated with a water-soluble polysaccharide.

[0002]

2. Description of the Related Art Conventionally, concentrated Chinese herbal medicines have a high hygroscopic property, and therefore, in general, several times as much excipient is needed as the concentrated Chinese herbal medicines in order to produce a granular preparation. there were. Therefore, it is difficult to increase the concentration factor of the Chinese herbal medicine, and sometimes the therapeutic effect can be obtained only when the patient takes the concentrated Chinese herbal medicine to which a large amount of excipient is added. Further, due to its hygroscopicity, the stability of the granular preparation was poor and it was difficult to store it.

[0003]

The present invention relates to a moisture-proof Chinese herb granule preparation comprising granules of concentrated Chinese herb extract and corn starch coated with a water-soluble polysaccharide coating composition.

[0004]

In order to solve the above-mentioned problems, the present invention utilizes a fluidized bed granulation method which has a simple process and is efficient, and is highly safe and has a moisture-proof coating. A method for producing a granular preparation by coating the extract is used. The whole process is also simple and convenient, and since water-soluble polysaccharides such as Harieng gum and / or guar gum are used as the coating agent, a production method which does not require any organic solvent can be used. By using the moisture-proof Chinese herb granule preparation of the present invention, the concentration factor can be improved (up to about 1.5 times), so that the dose of the patient can be reduced. Furthermore, since the granular preparation of the present invention has the effect of preventing moisture and masking the unpleasant taste of the drug, it is easy to take and the stability is improved in long-term storage.

[0005]

[Examples] In this specification, readings such as names of Kampo medicines are shown in parentheses, and technical terms of Kampo therapy are explained by Mr. Jiro Kobayashi of Acupuncture and Fudoin ("Latest Chinese Information Dictionary", p. 6). 6 lines from the bottom, see Shogakukan, 1985 first edition).

The present invention is a granule preparation produced by mixing a concentrated Chinese herbal medicine extract and an excipient into granules, and then coating the granules with a water-soluble polysaccharide.

In the present invention, the concentrated herbal medicine extract is
Any one can be used as long as the exudate of the Chinese medicine is concentrated according to the description of the Chinese medicine prescription in the general Chinese medicine prescription guide. Specific examples of such concentrated herbal medicine extracts include, for example, Shimonoto (Shimotsuto) extract, Kihito (Kihito) extract, Shikunshito (Bikmondito) extract, Bakumondoto (Bakumondoto) extract or Hochuchuki. Examples include hot water extract.

Shimonotsuto is a toki,
It is used for the symptoms such as menstrual irregularity, menopause, uterine bleeding, dizziness or palpitations of an anemia-like woman, which is a decoction of four kinds of kawakyu (senkyu), white peony (junior radix japonica) and jukujio (jukujiou). It also improves blood circulation and is used for high blood pressure and heart disease.

Kihito is a carrot,
Radix Astragalus (Ougi), Toki (Touki), Longan Meat (Ryuganiku), Satsumune (Sansonin) and Enshi (Onji)
It is mixed and used for the symptoms such as menorrhagia, physical deficiency, insomnia or amnesia of delicate women.

Shikunshito is a mixture of 6 kinds of carrot, carrot, white juniper, bukuryo, ginger, ginseng, licorice and licorice. It is used for symptoms such as gastrointestinal weakness, mental fatigue, loss of appetite or loose stool.

Bakumondoto (Bakumondoto) is a mixture of six types of bakumondoto (bakumondou), half-summer (hange), non-glutinous rice, large jujube, carrot and licorice. Decoction is used for mucosal anti-inflammatory, nutritional tonic, antitussive, expectorant, enhancement of lung function, stomach or intestinal regulation. It has a diuretic effect on people with hot flashes.

Hochuekkito is a Chinese cabbage (carrot), carrot (carrot), licorice (kanzo), white syrup (junior beetle), toki (toki), soma (shouma), and saiko (saiko). It is a mixture of 10 kinds of psyche, chinpi, red citrus and ginger, and is a decoction that is commonly used for anal prolapse or uterine dip.

The excipient used in the present invention means corn starch, but other starch may be used.

Corn starch is suitable for use in moisture-proof granule formulations because it absorbs less moisture than commonly used sucrose.

In the present invention, the method for producing the granules by mixing the concentrated Chinese herbal medicine extract and corn starch and granulating the mixture may be any conventional granule production method other than the wet extrusion granulation method. Specific examples of the production method include a fluidized bed granulation method and a spray granulation method. FIG. 1 is a reference block diagram for explaining a method for producing a granular preparation of the present invention.

The weight ratio of the concentrated Chinese herbal medicine extract and corn starch is preferably concentrated Chinese herbal medicine extract: corn starch = 1: 0.5 to 2.0, and more preferably 1: 1 to 1.
1.5 is preferable, and 1: 1 is particularly preferable.

The coating composition used in the present invention may be any composition containing a water-soluble polysaccharide as a main component, and specific examples of the preferable water-soluble polysaccharide include guar gum or harrienju. Examples include gum (Locust bean gum).
Select one or more of these water-soluble polysaccharides,
It may be used as a mixture with other coating agents such as gum arabic, agar or sodium alginate. The water-soluble polysaccharide is prepared so as to be contained in an amount of 0.2 to 3%, preferably 0.5 to 1% based on the total weight of the coating composition.

The coating composition is prepared so as to account for 1 to 10%, preferably 1.2 to 5%, of the product weight of the obtained granular preparation.

The coating method of the granules in the present invention is
Conventional coating methods such as fluidized bed coating or pan coating are used. In the present invention, the water-soluble polysaccharide is coated on the extract granules in the form of an aqueous solution, but since it is dried with hot air, it does not adversely affect the quality of the extract granules.

The granular preparation of the present invention is a single prescription (a prescription for combining one or two kinds of Kampo medicines to treat a single symptom or a multiple prescription (for combining two or more kinds of Kampo medicines to treat a plurality of symptoms). It can be applied to any of the prescriptions.

The granule preparation of the present invention is superior in moisture resistance to conventional Kampo granule preparations.

In addition, Harieng gum and guar
Due to the use of water-soluble polysaccharides such as gums it is not necessary to use the organic solvents normally used to dissolve coatings. Therefore, it has an advantage that further safety in taking can be obtained as compared with the conventional granular preparation.

Hereinafter, the granular preparation of the present invention will be described with reference to Examples, but the present invention is not limited to these Examples.

Example 1 (a) Production of Shimonoto (Shimotsuto) Extract Granules 50 kg of Shimonoto (Shimotsuto) (Toki 15)
kg, Jukujio 15kg, White peony 12.5kg, and River cucumber
(7.5 kg) is soaked in 400 liters of water for 2 hours, then heated and boiled for 1 hour, then 147μ
The decoction was filtered and collected using a standard m (100 mesh) sieve. After adding 350 liters of water as the second decoction and boiling for 30 minutes, the decocted liquid was collected by filtration using the standard sieve, and the obtained two decoctions were combined and concentrated under reduced pressure to obtain Shimonotsuto (Shimotsuto). ) Extract solution 86
kg (water content rate 82.93%) was obtained. This extract solution and 16.95 kg of corn starch (water content 13.38%) were mixed with a fluid bed granulator (Fluidco).
spray granulation with (ater), Shimonoto (Shimotsou) (extract solid: corn starch = 1: 1 (weight ratio))
The granules of

(B) Coating of Shimotsubo extract granules with a moisture-proof coating composition 0.4 kg of Shimotto extract granules prepared in (a) above were placed in a fluidized bed granulator. 200 ml of 1% guar gum aqueous solution, nozzle pressure 2-3 kg / cm ² ,
While spraying at a spray rate of 100 ml / hour, hot air of about 70 ° C. was blown from below the fluidized bed to coat the granules with a coating film of guar gum. The whole process is completed in about 2 hours, and about 0.37 kg of Shimotsuto granules with a particle size of 420-88 μm (40-170 mesh)
I got it.

Examples 2 to 10 The procedure of Example 1 was repeated, except that the coating composition and the production conditions were as shown in Table 1. Table 1 shows the yield of each of the obtained Shimonotsuto granules.

[0027]

[Table 1]

Example 11 (a) Production of Bakumondoto (Bakumondoto) Extract Granules 115 kg of Bakumondoto (Bakumondoto) (45 kg of Bakumondou), 30 kg of half-summer (hange),
Non-glutinous rice 12.5kg, Tasumugi 12.5k
g, ginseng (7.5 g of carrot) and licorice (7.5 g of licorice) was soaked in 805 liters of water for 2 hours, then heated and boiled and then decocted for 1 hour, as in Example 1. The decoction was collected by filtration. After adding 575 liters of water as the second decoction and decocting for 1 hour, collect the decoction by filtering in the same manner as above and concentrate the two types of decoction under reduced pressure. 20 kg (moisture) extract solution (water content 60.88%) was obtained.

10 kg of a 60.88% bakumondoto extract solution and 4.44 kg of corn starch (water content 12%) were uniformly mixed and placed in a dryer to 60 to 70 ° C. Was dried with hot air, and the dried product was taken out and pulverized and sieved to obtain granules of Bakumondoto (extract solid matter: corn starch = 1: 1 (weight ratio)).

Bakumondo is a dried and decocted root enlargement of the lily family Jardinium mustache, which is used as a mucosal anti-inflammatory, nutritional tonic, antitussive, and expectorant. It has a diuretic effect on people with hot flashes.

In the mid-summer (Hange), the tuber of Corydalis sinensis of the Araceae family is removed and dried. It is used as a vomiting suppressant, sedative or expectorant, and causes nausea, vomiting, cough, and palpitations resulting from gastric suspension. Also effective for insomnia.

Taiso is a dried fruit of jujube, a member of the buckthorn family, which is used as a relaxing, tonic or diuretic agent to relieve muscle tension, hyperesthesia, cough, irritability, pain or Also used for symptoms such as abdominal pain.

Licorice (liquorice) is a root and rhizome of peanut licorice and larvae of the leguminous family, and is used as a relieving, antitussive, analgesic or expectorant drug, and it effectively relieves and eliminates urgent symptoms such as pain due to sudden muscle tension. Therefore, it is also used for stomach cramps and gastric ulcers.

(B) Coating of Bakumondoto Extract Granules with a Composition for Moisture-Proof Coating 0.4 kg of Bakumondoto Granules produced in (a) above is fluidized Put in a granulator and add 1000 ml of 1% Harienju gum aqueous solution, nozzle pressure 2-3 kg
/ Cm ² , while spraying at a spray rate of 200 ml / hour,
Hot granules of about 80 to 90 ° C. were blown from the bottom of the fluidized bed to coat the granules with a coating film of Harieng Gum. The whole process is completed in about 5 hours and the particle size is 420-88.
About 0.37 kg of a bakumondoto powder granule preparation having a size of 40 μm (40 to 170 mesh) was obtained.

Examples 12 to 19 The procedure of Example 11 was repeated, except that the coating composition and the production conditions were as shown in Table 2. The yield of each of the obtained Bakumondo-to granule preparations is shown in Table 2.

[0036]

[Table 2]

Example 20 (a) Production of Kihito (Kihito) Extract Granules 30 kg of Kihito (Kihito) (Ougi 3.4)
5kg, carrot 2.07kg, white juniper 3.45kg, bukuryu 3.45k
g, sour juniper (sansounin) 3.45 kg, longan meat (ryuganik) 3.45 kg, toki (touki) 2.07
kg, Onji 2.07 kg, Licorice
1.4kg, Mokkou 1.4kg, Ginger 2.07kg and Taju 1.6
(7 kg) was soaked in 300 liters of water for 2 hours, then heated, boiled and decocted for 1 hour, and the decocted solution was collected in the same manner as in Example 1. After adding 250 liters of water as the second decoction and boiling for 30 minutes, the decoction was collected by filtration in the same manner as above. The two types of decoctions are combined and concentrated under reduced pressure, and 33 kg of Kihito extract solution
(Moisture content rate 75.2%) was obtained. This extract solution and 9 kg of corn starch (water content 9.1
%) By spray granulation using a fluidized bed granulator and Kihito (Kihito)
(Extract solids: corn starch = 1: 1 (weight ratio)) granules were obtained.

(B) Coating of Kihito (Kihito) extract granules with the composition for moisture-proof coating 0.4 g of Kihito (Kihito) granules produced in (a) above
g in a fluidized bed granulator, while spraying 1000 ml of a 1% aqueous Hariengju gum solution at a nozzle pressure of ² to 3 kg / cm ² and a spraying rate of 200 ml / hour, about 80 to 90 from the bottom of the fluidized bed. C. Hot air was sent to coat the granules with a coating film of Harienju gum. The whole process is completed in about 5 hours and the particle size is 420-88 μm.
About 0.37 kg of (40-170 mesh) Kihito-to (kihito) granule preparation was obtained.

Examples 21 to 22 The procedure of Example 20 was repeated, except that the coating composition and the production conditions were as shown in Table 3. Table 3 shows the yield of each of the obtained Kihito-to (kihito) granule preparations.

[0040]

[Table 3]

Example 23 (a) Production of Shikunshito Extract Granules 40 kg of Shikunshito (carrot) 10.3 kg of white ginseng (Bijakujutsu) 7.77 k
g, bukuryo 6.4kg, licorice
5.2 kg, 5.2 kg of ginger (ginger) and 5.2 kg of taiso (mixed with taiso) were soaked in 400 liters of water for 2 hours, then heated and boiled and then decocted for 1 hour. The liquid decocted as in 1 was collected by filtration. As the second decoction, 350 liters of water was added and boiled for 30 minutes, then the decoctions were collected by filtration in the same manner as above, and the two types of decoctions obtained were combined and concentrated under reduced pressure to obtain a Shikunshito extract solution. 25 kg (water content 58.7
4%). This extract solution and 11 kg of corn starch (water content 6.2%) were spray-granulated by a fluidized bed granulator and then Shikunshito (solid extract: corn starch = 1: 1 (weight ratio)). The granules of

(B) Coating of Sikkunshito extract granules with a composition for moisture-proof coating 0.4 kg of Sikkunshito granules prepared in (a) above was put into a fluidized bed granulator and 1% While spraying 1000 ml of the Hariengju gum aqueous solution of No. ^{3 at} a nozzle pressure of ² to 3 kg / cm ² and a spraying speed of 200 ml / hour, hot air of about 80 to 90 ° C. is sent from the lower part of the fluidized bed, and the granules are removed from the Hariengju gum. Was coated with The whole process is completed in about 5 hours and the particle size is 420-8.
About 0.385 kg of a granule preparation of Sikkunshito having a size of 8 μm (40 to 170 mesh) was obtained.

Examples 24 to 25 The same procedure as in Example 23 was carried out except that the coating film composition and the production conditions were changed to those shown in Table 4. Table 4 shows the yield of each of the obtained granule preparations of Shikunshito.

[0044]

[Table 4]

Comparative Example 1 Preparation of Extract Granules of Shimonotsuto (Shimotsuto) 50 kg of Shimonoto (Shimotsuto) was soaked in 400 liters of water for 2 hours, heated and boiled and then decocted for 1 hour. The decoction as in Example 1 was collected by filtration. As the second decoction, add 350 liters of water and boil for 30 minutes, then filter and collect the decoction in the same manner as above, combine the two decoctions, and then concentrate under reduced pressure to obtain an extract solution of Shimotsuto. 86 kg (water content 82.93%)
I got it.

This extract solution and 16.95 kg of corn starch (water content 13.38%) were mixed and granulated with a fluid bed granulator to give a particle size of 420 μm to 88 μm.
(40-170 mesh) Shimotsuto granules.

Comparative Example 2 Production of Bakumondoto (Bakumondoto) Extract Granules Bakumondoto (Bakumondoto) (45 kg of Bakumondoto), 30 kg of half-summer (hange), 1 of non-glutinous rice
2.5 kg, taiso (12.5 kg), ginseng (carrot) 7.5 kg, and licorice (liquorice) 7.5 kg
Was blended in 805 liters of water for 2 hours, then heated and boiled and then brewed for 1 hour. The brewed solution was collected by filtering with a filter in the same manner as in Example 1. After adding 575 liters of water as the second decoction and decocting for 1 hour, the decoction was collected by filtration in the same manner as above, and these two types of decoction were combined and concentrated under reduced pressure to obtain Bakumondoto. An extract solution (water content 50 to 60%) was obtained.

4.44 kg of corn starch (water content 12%) and 10 kg of bakumondoto extract solution (water content 60.88%) were uniformly mixed and placed in a drier. And dried with hot air at 60 to 70 ° C., and the dried product was taken out, crushed and sieved. Bakumondoto powder granules having a particle size of 420 μ to 88 μ (40 to 170 mesh) were prepared.

Test Example Product Test 1. Disintegration dispersibility test (1) Model: CT-1 single tank type disintegration disperser (manufactured by Shinko Seiki Co., Ltd.) (2) Operation method: 1) Add appropriate amount of water to the water tank and 1 liter beaker, and place the beaker. It was placed in an aquarium and the lid of the aquarium was closed. 2) Turn on the power switch and then set the temperature dial to 37
The temperature was set to ° C, and the heating switch was turned on to heat. 3) Samples of 1 gram each were placed in an auxiliary sieving bucket and placed in a tube in the dispersibility test bucket. 4) After waiting for the water inside the beaker to reach 37 ° C, the dispersibility test bucket was fixed to the lifting column, and then the lifting switch was turned on to vibrate vertically. 5) The disintegration dispersion time of the granules in each auxiliary bucket was observed and recorded.

(3) Notes: 1) Disintegration time of granules is 3
Must be within 0 minutes. 2) The cycle of vertical vibration is 28 to 32 times / minute. 3) The lifting width is 5 to 6 cm. 4) Set the beaker temperature to 37 ± 2 ° C.

The results are shown in Table 5 below. In the table, "pass" indicates that the granules collapsed within 30 minutes.

[0052]

[Table 5]

2. Moisture determination method A minute amount of moisture was quantified using a Karl-Fischer humidity titrator to determine the moisture content. The model is Kyoto Electronics Industry Co., Ltd.
tronics Manufacturing C
o. , Ltd. ) Made by Karl-Fisher Moisture Analyzer MKC
It was -210. The results are shown in Table 6 below. In the table, a moisture content of 10% or less is shown as “pass”.

[0054]

[Table 6]

3. Indicator components Ferulic acid and Paeoniflorin were used as two indicator components, and the Shimonotsuto component of Examples 1 to 6 and the Shimonoto salt of Comparative Example 1 were analyzed by HPLC (high performance liquid chromatography). The (Shimotsou) component was measured. As a result, it was confirmed that each of the four ingredients contained the above-mentioned two components. As a result of comparison with Comparative Example 1, there was no significant difference between the two kinds of indicator components of Examples 1 to 6 and Comparative Example 1.

4. Moisture absorption test An accelerated test (30 ° C, 98RH; RH = relative humidity) and a normal temperature (15 ° C to 25 ° C) moisture absorption test were performed. The results for Shimonoto (Shimotsuto) are shown in Table 7, and the results for Bakumondoto (Bakumondoto) are shown in Table 8.
In Table 7, "good" indicates that fluidity was recognized and did not aggregate, and "poor" indicates that fluidity was poor and moisture was absorbed to aggregate. The angle of repose (an in Tables 7 and 8)
Gleof response is a unit showing the fluidity of the granules, and the smaller the value, the greater the fluidity. “Commercial products” in Tables 7 and 8 are commercially available Shimonotsuto granules and Bakumondoto granules, respectively. In addition, since the fluidity of Comparative Example 2 and the commercially available granules was not good, the angle of repose could not be measured.

[0057]

[Table 7]

[0058]

[Table 8]

From the above test examples, it can be seen that the physical or chemical properties of the granular preparation of the present invention are lower in hygroscopicity and less likely to aggregate as compared with the conventional granular preparation.

[0060]

EFFECTS OF THE INVENTION The moisture-proof Chinese herb granule preparation of the present invention can not only improve the concentration multiple, but also reduce the dose of the concentrated Chinese herb, and have the effect of preventing moisture and masking the unpleasant taste of the medicine. Therefore, indirectly improve the convenience and stability when using Chinese herbs.

[Brief description of drawings]

FIG. 1 is a reference diagram illustrating a processing method of the present invention in blocks.

Claims (5)

[Claims] 1. A moisture-proof Chinese herb granule preparation comprising granules comprising concentrated Chinese herb extract and corn starch coated with a water-soluble polysaccharide coating composition. 2. The coating composition comprises Harienju.
The moisture-proof Chinese herb granule preparation according to claim 1, which comprises a gum. 3. The moisture-proof Chinese herb granule preparation according to claim 1, wherein the coating composition comprises guar gum. 4. The coating composition comprises Harienju.
The moisture-proof Chinese herb granule preparation according to claim 1, which comprises gum and guar gum. 5. The moisture-proof Chinese herb granule preparation according to claim 1, wherein the weight of the coating composition is 1 to 10% of the weight of the granule preparation.