TW201436818A - Astragalus membranaceus (Fisch.) Bge. wall-breaking dosage form - Google Patents

Abstract

The present invention relates to a Chinese medicine dosage form and relates specifically to an Astragalus membranaceus (Fisch.) Bge. wall-breaking dosage form. The present invention pulverizes Astragalus membranaceus (Fisch.) Bge. into ultrafine powder, which is subjected to an alcohol-water wetting process to be granulated, extrusion formed under a predetermined rotational speed and then dried. The Astragalus membranaceus (Fisch.) Bge. wall-breaking dosage form so manufactured has an increased bioavailability and the dosage form has improved stability and good disintegrability. The Astragalus membranaceus (Fisch.) Bge. wall-breaking dosage form is characterized in that Astragalus membranaceus (Fisch.) Bge. is subjected to wall-breaking pulverization to obtain ultrafine powder that is added with alcohol-water solution to form a soft material and is subjected to extrusion to form wet granules, which are then dried to form the Astragalus membranaceus (Fisch.) Bge. dosage form. The particle sizes of 90% or more of the ultrafine powder are less than or equal to 45 <mu>m.

Description

Astragalus breaking preparation

The invention relates to the field of traditional Chinese medicine, and more particularly to a yellow sputum breaking preparation.

Superfine pulverization technology is a new technology that has developed rapidly in recent years. Most of the active ingredients in Chinese herbal medicines are distributed in the cells. When the conventional decoction pieces are boiled, only some of the active ingredients can be released, and the effective ingredient utilization rate is 10-30%; and the broken wall crushing technology, such as the Chinese medicine decoction pieces, is crushed to 300 mesh. Left and right, the cell wall breaking rate will reach 86.7%, which improves the dissolution of the active ingredients in the medicinal materials, greatly enhances its efficacy, and the utilization rate of the active ingredients is above 90%, thereby reducing the amount of medicinal materials used and protecting the medicinal materials, and also improving the medicines. The quality of the product increases the efficacy. However, the current main ultrafine powder technology still stays at the stage of pulverizing Chinese herbal medicines to ultrafine preparations. Due to the increased cell wall breaking rate of the ultrafine preparation, the surface area of the broken wall preparation is increased, the shape is irregular, the fluidity, the dispersibility is poor, the moisture absorption is easy, and the stability is poor, and the granulation is performed to improve the stability of the product. The preparation prepared by the invention solves the above problems well and maximizes the utilization and use of the medicine.

At present, the following technical problems exist in the broken wall preparation and its granulation process: (1) The current broken wall preparation is easy to be oxidized due to high utilization rate of traditional Chinese medicine ingredients, and the stability is not high, and the efficacy is low. It is easy to lose; (2) It is difficult to ensure the yield, disintegration and stability of the traditional Chinese medicine varieties obtained by soft material granulation; (3) Some Chinese medicine varieties are not suitable for using broken wall powder-soft The granulation method is prepared into a preparation, such as scorpion, achyranthes and the like; and the invention screens out the traditional Chinese medicine varieties suitable for the broken wall powder-soft material granulation method through a large number of experimental groping, and explores each The conditions of the steps.

Astragalus is the dried root of the leguminous Astragalus membranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. It mainly contains triterpenoid saponins: astragaloside I, II, III, IV (xanthine), soy saponin I, capsular baicalin I, II, etc.; flavonoids: formononetin, flavonoids, glucose Glycosides and the like; also contains polysaccharides, amino acids and the like. The traditional decoction method is easy to destroy the heat-sensitive component, and on the other hand, the active ingredient is not fully boiled, resulting in the loss of the active ingredient. The preparation of astragalus ultrafine powder is beneficial to increase the utilization rate of the active ingredient, but at the same time, due to the increase of the specific surface area of the powder, it has the disadvantages of easy moisture absorption, oxidation, deterioration and the like. Therefore, on the basis of preparation of ultrafine powder, it is necessary to further process and modify it to effectively overcome these unfavorable factors and maximize the therapeutic effect of the drug.

The technical problem to be solved by the present invention is to provide a yellow scorpion broken wall preparation in order to overcome the above-mentioned deficiencies of the scutellaria broken powder.

The above technical problem to be solved by the present invention is achieved by the following technical solution: the invention provides a yellow scorpion broken wall preparation, which adopts the following technical scheme: the scutellaria is subjected to wall pulverization to obtain an ultrafine powder, and the ethanol-water solution is added and thoroughly mixed. The soft material is obtained, further extruded to obtain wet granules, and dried to obtain a scutellaria broken-wall preparation; 90% or more of the ultrafine powder has a particle diameter of 45 μm or less.

The yellow scorpion broken wall preparation prepared by the invention can make the consumption of the active ingredient maximized by the consumer without decocting by washing with warm water.

The scutellaria can be first pulverized to 100 mesh and further subjected to ultrafine pulverization so that 90% or more of the ultrafine powder (for example, 90%, 91%, 92%, 93%, 94% or 95%) may be granulated. The particle size is less than or equal to 45 μm. The ultrafine powder used in the present invention, 90% of the particle size is nearly 45μm powder, more than 35~45μm (such as 35, 36, 37, 38, 39, 40, 41, 41, 42, 43, 44 or 45μm), but as long as the particle size is less than or equal to 45μm The present invention has been achieved.

Preferably, the ultrafine powder has a wall breaking rate of 80 to 95%.

The present invention employs an ethanol-water solution for wet granulation, which has the outstanding advantage that the ultrafine powder of the present invention can be subjected to subsequent granulation and drying to form scutellaria preparation granules without any other additives. However, in the process, what concentration of ethanol-water solution should be used, and the ratio between the solution and the ultrafine powder are parameters that need to be strictly controlled to make the moisture, solid content, viscosity, etc. of the soft material. It can be applied to the characteristics of the scutellariae breaking preparation, so that the preparation can be effectively bonded; further, through the setting of specific extrusion parameters, the soft material is extruded into a suitable density and size of the scutellaria granule preparation to make the density/fluffiness appropriate. Therefore, after drying into a finished product, even if it is placed in air at room temperature, the oxidation of air can be prevented. Moreover, when the finished product obtained is washed with warm water, the ultrafine preparation can be dispersed relatively quickly, so that the active ingredient dissolves and diffuses rapidly and fully, and the utilization ratio of the active ingredient is improved.

The invention has repeatedly selected the following schemes: in the wet granulation, the ethanol component in the ethanol-water solution has a quality fraction of 20% to 80%; preferably, the ethanol quality fraction is 30% to 70%. More preferably, it is 45% to 65%. When the ethanol quality fraction is 20% to 29%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~0.65, preferably 1:0.6; when the ethanol quality fraction is 30%~39%, super The ratio of the fine powder to the ethanol-water solution is 1:0.6 to 0.9, preferably 1:0.6 to 0.65; when the ethanol quality fraction is 40% to 49%, the ratio of the ultrafine powder to the ethanol-water solution is by weight. It is 1:0.6~1.0, preferably 1:0.6~0.7; when the ethanol quality fraction is 50%~59%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~1.1 by weight, preferably 1: 0.6~0.8; when the ethanol quality fraction is 60%~69%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~1.2, preferably 1:0.8~1.0 by weight, when the ethanol quality score is When it is 70% to 80%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.6 to 1.3 by weight, preferably 1:0.8 to 1.1.

When the soft material is extruded into wet granules, it is preferably controlled under the following conditions: a pre-packed 10 mesh to 30 mesh screen, a pressing force of 0.05 MPa to 1 MPa, a rotational speed of 50 r/min to 100 r/min; preferably, extrusion The strength is 0.7Mpa~0.8Mpa, and the speed is 55r/min~65r/min.

The wet particle size obtained by extrusion is 14 mesh to 30 mesh, the drying temperature during drying is 45 ° C to 85 ° C, and the drying time is 0.5 h to 4.0 h.

The bulk density of the obtained scutellariae breaking preparation was 0.30 g/ml to 0.65 g/ml.

Compared with the prior art, the present invention has the following beneficial effects: (1) The xanthine preparation obtained by the method of the invention has greatly improved utilization rate of active ingredients, and the utilization rate is close to 100%; it is confirmed by bioequivalence test that 1 is adopted. /4 parts of the Astragalus membranaceus breaking preparation can be equivalent to the efficacy of 1 part of traditional scutellaria; (2) The invention obtains a suitable wet granulation process by groping, so that the granulation process is not introduced except for the addition of ethanol-water. With any other additives, a soft material with a solid content and a moderate viscosity can be obtained to smoothly carry out the extrusion granulation process, and the formed Chinese medicinal particles have high stability and are not easily collapsed during storage and transportation; (3) The invention Extrusion conditions explored the appropriate rotation speed and extrusion force, thereby preparing a viscous, moderate-density scutellaria granule preparation, which is easy to disintegrate and disperse during the taking process, and is easy to warm water. Crushed.

In order to more clearly understand the technical content of the present invention, the following embodiments are specifically described, but the embodiments of the present invention are not limited thereto.

Example 1

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, then ultrafinely pulverize into 90% of the ultrafine powder with a particle size of 45 μm or less, and add an ethanol-water solution (the ethanol quality fraction is 20%). Wet method soft material, the ratio of solution to ultrafine powder is 0.6:1 (by weight), after mixing, pre-loaded with 10 mesh sieve, select extrusion speed 50r/min, extrusion strength 1MPa to make wet particles The wet granules are transferred into a hot air loop oven, and the drying temperature is set at 85 ° C, dried for 2.5 h to dryness, and the whole granules are sieved to obtain a scutellaria scutellariae preparation.

Example 2

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, then ultrafinely pulverize into 90% of the ultrafine powder with a particle size of 45 μm or less, and add an ethanol-water solution (the ethanol quality fraction is 40%). Wet method soft material, the ratio of solution to ultrafine powder is 0.9:1 (by weight), after mixing, pre-loaded with 10 mesh sieve, using extrusion speed 70r/min, pressing force 0.9MPa The granules and wet granules were transferred into a vacuum microwave drying oven, and the drying temperature was set at 45 ° C, dried for 0.75 h to dryness, and the whole granules were sieved to obtain a scutellaria scutellariae preparation.

Example 3

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, then ultrafinely pulverize into 90% of the ultrafine powder with a particle size of 45 μm or less, and add an ethanol-water solution (the ethanol quality fraction is 60%). Wet method soft material, the ratio of solution to ultrafine powder is 1.0:1 (by weight), after mixing, pre-loaded with 30 mesh sieve, using extrusion speed 80r/min, pressing force 0.3MPa Granule, wet The granules are placed in a hot air loop oven, set to a drying temperature of 85 ° C, dried for 2.5 h to dryness, and the whole granules are sieved to obtain a scutellaria scutellariae preparation.

Example 4

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh. After ultrafine pulverization into 90% of the ultrafine powder, the powder with a particle size of 45 μm or less is added to the ethanol-water solution (the ethanol quality fraction is 80%). Wet method soft material, the ratio of solution to ultrafine powder is 1.1:1 (by weight), after mixing, pre-loaded with 30 mesh sieve, using extrusion speed of 60r/min, extrusion force of 0.6MPa The granules and the wet granules were transferred into a vacuum microwave drying oven, and the drying temperature was set at 50 ° C, dried for 0.5 h to dryness, and the whole granules were sieved to obtain a scutellariae broken wall preparation.

Example 5

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to about 100 mesh coarse powder, then pulverize it into ultrafine powder to 90% of the powder with particle size less than or equal to 45μm, and add ethanol-water solution (B quality score is 70) %) Wet method soft material, the ratio of solution to ultrafine powder is 0.8:1 (by weight), after mixing, pre-installed 20 mesh sieve, select extrusion speed 100r/min, extrusion force 0.05MPa The wet granules and the wet granules are transferred into the hot air circulation bellows, and the drying temperature is set to 70 ° C, dried for 2.0 h to dryness, and the whole granules are sieved to obtain the jaundice broken wall preparation.

Example 6

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 45 μm or less. The mass fraction of the ethanol-water solution added is 40%. The solution is made of wet method, the ratio of solution to ultrafine powder is 1.1:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 80r/min, and the extrusion force is 0.2MPa. The wet granules are boiled and dried, set to dry air temperature of 85 ° C, dried for 1.0 h to dry, and the whole granules are sieved to obtain jaundice broken wall preparation.

Example 7

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, then ultrafinely pulverize into 90% of the ultrafine powder with a particle size of 45 μm or less, and add an ethanol-water solution (the ethanol quality fraction is 20%). Wet method for soft material, the ratio of solution to ultrafine powder is 0.7:1 (by weight). After mixing, pre-loaded with 10 mesh sieve, select extrusion speed 50r/min, extrusion strength 1MPa to make wet particles. The wet granules are transferred into a hot air loop oven, and the drying temperature is set at 85 ° C, dried for 2.5 h to dryness, and the whole granules are sieved to obtain a scutellaria scutellariae preparation.

Example 8

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 45 μm or less. The mass fraction of the ethanol-water solution added is 30%. The solution is made of wet method, and the ratio of solution to ultrafine powder is 0.65:1 (by weight). After uniformization, pre-installed 20 mesh sieve, select the extrusion speed 65r/min, the extrusion strength 0.7MPa wet particles, use boiling drying, set the dry inlet air temperature 85 ° C, dry 1.0h to dry, after the whole sieve That is, the yellow sputum broken wall preparation.

Example 9

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 45 μm or less. The mass fraction of the ethanol-water solution added is 50%. The solution is made of wet method, and the ratio of solution to ultrafine powder is 0.8:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 85r/min, and the extrusion force is 0.5MPa. The wet granules are boiled and dried, set to dry air temperature of 85 ° C, dried for 1.0 h to dry, and the whole granules are sieved to obtain jaundice broken wall preparation.

Example 10

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh. After ultrafine pulverization into 90% of the ultrafine powder, the powder with a particle size of 45 μm or less is added to the ethanol-water solution (the ethanol quality fraction is 80%). Wet method soft material, the ratio of solution to ultrafine powder is 1.3:1 (by weight), after mixing, pre-loaded with 30 mesh sieve, select extrusion speed 50r/min, extrusion force 0.8MPa to make wet The granules and the wet granules were transferred into a vacuum microwave drying oven, and the drying temperature was set at 50 ° C, dried for 0.5 h to dryness, and the whole granules were sieved to obtain a scutellariae broken wall preparation.

Remarks: The full score is 10.

Example 11

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh. After ultrafine pulverization into 90% of the ultrafine powder, the powder with a particle size of 45 μm or less is added to the ethanol-water solution (the ethanol quality fraction is 80%). Wet method for making soft materials, the ratio of solution to ultrafine powder is 1.3:1 (by weight), after mixing, pre-loaded with 30 mesh sieve, using extrusion speed of 70r/min, extrusion force of 1.0MPa The granules and the wet granules were transferred into a vacuum microwave drying oven, and the drying temperature was set at 50 ° C, dried for 0.5 h to dryness, and the whole granules were sieved to obtain a scutellariae broken wall preparation.

Example 12

Take the Astragalus membranaceus medicinal material and coarsely pulverize it to a coarse powder of about 100 mesh, and then pulverize it into ultrafine powder to 90% of the powder with a particle size of 45 μm or less. The mass fraction of the ethanol-water solution added is 25%. The solution is made of wet method, and the ratio of solution to ultrafine powder is 0.65:1 (by weight). After mixing, pre-loaded with 20 mesh sieve, the extrusion speed is 100r/min, and the extrusion force is 0.03MPa. The wet granules are boiled and dried, set to dry air temperature of 85 ° C, dried for 1.0 h to dry, and the whole granules are sieved to obtain jaundice broken wall preparation.

Example 13

The finished products of Examples 1~5 and 8~9 were tested according to the finished product quality standards, and the results were all in accordance with the requirements of the relevant Chinese Pharmacopoeia related dosage forms. The results are shown in Table 1.

Further, the scutellaria scutellariae preparations of Example 1~5, 8~9, and the traditional scutellariae of Astragalus membranaceus and Astragalus membranaceus were used as indicators for evaluation of traits, water and active ingredient Astragaloside IV, all of which were sealed in sealed plastic bags. Thereafter, the stability of each preparation was evaluated after being placed at a temperature of 40 ° C ± 2 ° C and a relative humidity of 75% ± 5% for 30 days, 60 days, and 90 days. The results are as follows:

It can be seen from the above table that the moisture content of the Huangqi broken wall preparation prepared by the invention is very stable in different periods, and the moisture content in the ultrafine powder of Astragalus membranaceus varies greatly in different periods, indicating that the yellow peony ultrafine powder absorbs moisture. Stronger. Because the ultrafine powder of Astragalus membranaceus is easy to absorb moisture, it is easy to breed bacteria in the ultrafine powder, which will lead to accelerated decomposition of the active ingredient. The decrease of the content of astragaloside IV in the above table also proves that the active ingredient of the astragalus ultrafine powder is easily decomposed. When the method of the present invention is used to prepare the scutellariae breaking preparation, the moisture content thereof is very stable, and it is not easy to absorb moisture, and the stability is greatly improved compared with the scutellaria ultrafine powder.

Example 14

In the following step, the advanced nature of the present invention is demonstrated by an acute toxicity and efficacy comparison experiment, and the astragalus preparation prepared in Example 3 is compared with a conventional decoction piece.

First, acute toxicity test

KM mice, 60 male and female, were randomly divided into control group, Huangqi conventional decoction group (32g/kg body weight) and Huangqi broken wall preparation group (32g/kg body weight).

The results in Tables 1 and 2 indicate that the maximum daily dose of Huangqi Traditional Decoction Pieces and Astragalus membranaceus Broken Preparations on mice was 32g/kg body weight, which is equivalent to 64 times of clinical dose, and no obvious acute toxicity was produced.

The results in Table 1 showed that there was no significant difference in weight gain between the Astragalus membranaceus group and the Astragalus membranaceus group (P>0.05).

The results in Table 2 showed that there was no significant difference in the index of the animals in the Astragalus membranaceus group and the Astragalus membranaceus group compared with the control group (P>0.05).

Second, pharmacodynamic comparison

SPF-class KM mice, male and female, weighing 18-22g, were randomly divided into normal control group, model control group, Shengmai capsule group, Huangqi traditional decoction group (traditional decoction method, gavage), and jaundice broken wall. The preparations were 0.25g/kg group, Huangqi broken wall preparation 0.5g/kg group, Huangqi broken wall preparation 1.0g/kg group, and Huangqi broken wall preparation 2.0g/kg group, 10 groups in each group. In the broken wall preparation group, after the preparation prepared in Example 3 was allowed to stand for 90 days, it was prepared by applying warm water of about 60°, and the supernatant was administered by intragastric administration.

The results in Tables 3 and 4 indicate that the pharmacodynamic effect of Astragalus membranaceus breaks is better than that of Astragalus membranaceus, which is equivalent to 1/8.

Claims (9)

A yellow scorpion broken wall preparation characterized in that the scutellaria is subjected to wall pulverization to obtain an ultrafine powder, and an ethanol-water solution is added to prepare a soft material, and further extruded to obtain wet granules, and dried to obtain a scutellaria broken preparation; the ultrafine powder 90% or more of the particles in the body have a particle diameter of 45 μm or less. The jaundice breaking preparation according to claim 1, wherein the ethanol-water solution has a quality fraction of ethanol of 20% to 80%. The jaundice breaking preparation according to claim 1, characterized in that the quality ratio of the ultrafine powder to the ethanol-water solution is 1:0.6 to 1.3. The jaundice breaking preparation according to claim 1, characterized in that, when the ethanol quality fraction is 20% to 29%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.6 to 0.65 by weight; When the fraction is 30%~39%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~0.9; when the ethanol quality fraction is 40%~49%, the ratio of ultrafine powder to ethanol-water solution is compared. The weight is 1:0.6~1.0; when the ethanol quality fraction is 50%~59%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~1.1 by weight; when the ethanol quality score is 60%~69% When the ratio of the ultrafine powder to the ethanol-water solution is 1:0.6 to 1.2 by weight; when the ethanol quality fraction is 70% to 80%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.6 by weight. 1.3. The scutellaria breaking preparation according to claim 4, wherein when the ethanol quality fraction is 20% to 29%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.6 by weight; when the ethanol quality fraction is When 30%~39%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~0.65; when the ethanol quality fraction is 40%~49%, the ratio of ultrafine powder to ethanol-water solution is by weight. 1:0.6~0.7; when the ethanol quality fraction is 50%~59%, the ratio of ultrafine powder to ethanol-water solution is 1:0.6~0.8 by weight; when the ethanol quality score is 60%~69%, The ratio of ultrafine powder to ethanol-water solution is 1:0.8~1.0 by weight. When the ethanol quality fraction is 70% to 80%, the ratio of the ultrafine powder to the ethanol-water solution is 1:0.8 to 1.1 by weight. The jaundice breaking preparation according to claim 1, wherein the scutellaria breaking preparation has a bulk density of 0.30 g/ml to 0.65 g/ml. The scutellaria breaking preparation according to claim 1, characterized in that the extrusion condition is: wet granulation: the number of pre-loaded sieve meshes is 10 mesh to 30 mesh, the pressing force is 0.05 Mpa to 1 Mpa, and the rotational speed is 50 r. /min~100r/min. The jaundice broken wall preparation according to claim 7, wherein the extrusion condition is: wet granulation: a pressing force of 0.7 Mpa to 0.8 MPa, and a rotation speed of 55 r/min to 65 r/min. The scutellaria breaking preparation according to claim 1, characterized in that the wet particle size obtained by extrusion is 14 mesh to 30 mesh, the drying temperature during drying is 45 ° C to 85 ° C, and the drying time is 0.5 h to 4.0 h. .