METHOD FOR THE PRODUCTION OF ADDITIVE-FREE CHINESE HERBAL MEDICINAL POWDER GRANULES WITH BROKEN CELL WALL

Description

TECHNICAL FIELD

[0001] The present invention relates to a method for preparing a cell-wall-broken powder of a Chinese medicinal material.BACKGROUND

[0002] Superfine grinding technology is a new technology that has developed rapidly in recent years. Using a cell-wall-broken grinding technology to grind a Chinese Medicine decoction piece to around 48 µm (300 mesh), a cell-wall-broken rate can reach 86.7%, which improves a dissolution of an active ingredient in medicinal materials and greatly enhances a pharmacodynamic effect thereof, with a utilization rate of the active ingredient of more than 90%, achieving a reduction of a usage amount of the medicinal materials and a protection of resources of the medicinal materials, and improving a quality of medicines and increasing a pharmacodynamic effect at the same time.

[0003] However, as most Chinese medicinal materials are natural animals and plants, with complex components, including a variety of small molecule chemical ingredients, macromolecule organic matters (proteins, nucleic acids, lipids and carbohydrates), inorganic matters (such as water, salts and minerals) and cell ergastic substances (metabolites, storage substances, etc.). As the active ingredient that exerts the pharmacodynamic effect at the same time, it is generally a cell ergastic substance with a relatively low content. Moreover, a distribution of a variety of active ingredients in different parts of the medicinal materials or in cells with different constituents in the same part is inconsistent. Medicinal parts of the Chinese medicinal materials are complex, including various medicinal parts such as a flower, a leaf, a root, a stem and the whole plant. Properties of various different medicinal parts differ greatly, from a cell level, various constituent tissues thereof from outside to inside, such as a phellem layer, a cortex, a phloem, a cambium, and a xylem are composed of different types of cells, physical and chemical properties such as a density and a cell-wall-breaking stress of the constituent cells thereof, such as a parenchyma cell, a stone cell, a vessel, a wood fiber, a cork cell and other cells, are different, and thus a cell-wall-breaking property thereof differs greatly. Only through a simple process of cell-wall-breaking and grinding, it is easy to cause that a cell-wall-broken powder obtained in a certain section of a cell-wall-broken material is an ingredient which is easy to be cell-wall-broken with a small particle size, while a certain part is an ingredient hard to be cell-wall-broken with a relatively large particle size, and the distribution of ingredients in the entire cell-wall-broken powder is uneven, which is impossible to obtain an uniform cell-wall-broken powder product with an evenly distributed particle size and active ingredient content, so as to affect the effect and safety of clinical medication.

[0004] At the same time, as the cell-wall-broken rate of a superfine preparation increases, there are inherent problems such as an increased surface area of the cell-wall-broken preparation, an irregular shape, a poor fluidity and dispersion, a high hygroscopicity, and a poor stability. A current treatment method is to perform pelletization on the superfine cell-wall-broken powder, to increase the stability of the product. A patent application with an application No. 201610596213.4 discloses an ultrasonic cell-wall-breaking method of the Chinese Medicine decoction piece and a device thereof, which solves a problem of a high manufacturing cost of the Chinese Medicine decoction piece. However, there are still problems of a low utilization efficiency of raw materials of the Chinese Medicine decoction piece, a poor cell-wall-breaking uniformity of the raw materials of the Chinese Medicine decoction piece, and a poor stability and a slow dissolution and diffusion rate of the Chinese Medicine decoction piece.

[0005] CN-A-101147746 describes a processing method to prepare cell-wall-broken powder for a Chinese medicinal material wherein crude drugs undergo a first pulverization step to obtain a 60 mesh coarse powder; a pulverization and cell-wall-breaking step to obtain a more than 300 mesh powder; two granulate steps wherein water or ethanol is used, and a dispense and pack step. Parameters such as temperature and humidity during the cell-wall-breaking step are discussed.

[0006] CN-A-104055832 discloses a process to prepare cell-wall-broken powder from Radix Astragali comprising at least two steps of grinding to obtain a powder with at least 90% of the grain having a diameter less than or equal to 45 µm (that is about 325 mesh); and a granulation step wherein an ethanol-water solution is used. A discussion of the effect of the mass concentration of ethanol is provided.

[0007] The Article WANG YAN-PING et Al "Influence of particle sizes and content of effective compositions of Panax notoginseng powders crashing by superfine somminution technique", CHINA JOURNAL OF CHINESE MATERIA MEDICA, vol. 39, n. 8, p. 1430-1434 describes a method for preparing a powder with a particle size distribution having a single peak. Such result is obtained by providing a superfine comminution technique and to use it for two hours. It is also observed that the total content of active compound (saponin) has been improved.

[0008] CN-A-106423490 describes a method of ultrasonication of prepared slices of Chinese crude drugs that provides three cell-wall-breaking steps. The first step allows to obtain a mean particle diameter of 10-100 µm (about 150-1250 mesh), the second step lasts for 30-90 minutes and the third step lasts for about 20 minutes. Such successive cell-wall-breaking steps lead to a micropowder with a particle diameter that is not more than 5 µm (estimated about 2500 mesh).

[0009] None of these documents discloses a step of screening between a first cell-wall-breaking step and a second cell-wall-breaking step, a second cell-wall-breaking step wherein only part of the powder is newly processed, or a step of pelleting wherein two water-ethanol solutions with different concentrations of ethanol are alternately used.SUMMARY OF THE INVENTION

[0010] A purpose of the present invention, which is identified in the appended set of claims, is to overcome shortcomings of the prior art, and to provide a method for preparing a cell-wall-broken granule, which has a good cell-wall-breaking uniformity, a high stability and a rapid dissolution and diffusion rate.

[0011] A technical solution adopted by the present invention to solve the technical problem thereof is a method for preparing an additive-free cell-wall-broken granule of a medicinal material of plant origin including the following steps: (1) medicinal material of plant origin concocting: picking, washing, slicing and drying the medicinal material of plant origin to obtain a clean medicinal material; (2) medicinal material of plant origin grinding: taking and grinding the the clean medicinal material of plant origin with a mill to obtain a 120-180 µm (80-120 mesh) medicinal coarse powder; (3) first wall-breaking and grinding: performing cell-wall-breaking and grinding on the obtained medicinal coarse powder to obtain a 13-74 µm (200-1000 mesh) cell-wall-broken powder; (4) particle size screening: screening the cell-wall-broken powder to separate a 13-48 µm (300-1000 mesh) cell-wall-broken powder; (5) second cell-wall-breaking and grinding: returning the screened powder with at least 48 µm (a mesh below 300) to a cell-wall-breaking and grinding cavity for re-grinding to a 25-48 µm (300-500 mesh) cell-wall-broken powder; (6) mixing: mixing different materials obtained from two times of the cell-wall-breaking and grinding to obtain a uniform cell-wall-broken powder with different partical sizes and different cell ingredients which are evenly distributed; (7) pelletizing: placing the cell-wall-broken powder recovered in the step (6) into a mixing agitator, adding a high-concentration ethanol-water solution and a low-concentration ethanol-water solution alternately to make a soft material, extruding with a granulator with a 420-2000 µm (10-40 mesh) sieve to make a wet granule, and drying the made wet granule; wherein a volume fraction of ethanol in the high-concentration ethanol-water solution is 50%-95%, and a volume fraction of ethanol in the low-concentration ethanol-water solution is 10-30%; and (8) granulating and sieving: granulating and sieving the granule in the step (7) to make a 250-850 µm (20-60 mesh) granule.

[0012] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material of plant origin as mentioned above, after the first cell-wall breaking and grinding, it is screened to make a powder particle size distribution concentrated in 23-28 µm (500-600 mesh), and this part of the cell-wall-broken powder is mainly composed of cell-wall-broken parenchyma cells; while the screened powder with at least 48 µm (a mesh below 300) is performed the second cell-wall-breaking and grinding, making the powder particle size distribution concentrated in 28-38 µm (400-500 mesh), and this part of the cell-wall-broken powder is mainly composed of cells with a relatively large grinding stress such as a vessel, a wood fiber and a cork cell. By the operation of performing two times of the cell-wall-breaking and grinding on the medicinal material, the effective grinding of different tissues of the medicinal materials is realized, and the obtained cell-wall-broken powder has a good uniformity, which effectively utilizes resources of Chinese medicines and improves a quality of the medicines.

[0013] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, a weight ratio of the ethanol-water solution used in the step (7) to a superfine powder is (0.1-0.99):1.

[0014] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, the weight ratio of the ethanol-water solution used in the step (7) to the superfine powder is (0.3-0.8): 1.

[0015] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, the weight ratio of the ethanol-water solution used in the step (7) to the superfine powder is (0.5-0.7):1.

[0016] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, in the step (7), when extruding to make the wet granule, a force of the extruding is 0.05-1 MPa and a rotation speed is 0,667-1,667 r / s (40-100 r / min).

[0017] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, the force of the extruding is 0.25-0.45 MPa and the rotation speed is 1,25-1,417 r / s (75-85 r / min).

[0018] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, a step of the grinding in the step (3) and the step (5) is performed in a jet mill, a temperature of a grinding space is 18-26°C, a relative humidity is ≤ 55%, a inlet working pressure is ≥ 0.7 MPa, and a rotation speed of a grader is 30-35 r / s.

[0019] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, the volume fraction of the ethanol in the high-concentration ethanol-water solution in the step (7) is 60%-90%, and the volume fraction of the ethanol in the low-concentration ethanol-water solution is 10%-20%.

[0020] In the method for preparing the additive-free cell-wall-broken granule of the Chinese medicinal material as mentioned above, the volume fraction of the ethanol in the high-concentration ethanol-water solution in the step (7) is 70%-80%, and the volume fraction of the ethanol in the low-concentration ethanol-water solution is 15%-20%.

[0021] The beneficial effects of the present invention are as follows: (1) the Chinese medicinal material is cell-wall-broken and ground to 48 µm or less (above 300 mesh), with the cell-wall-broken rate above 99%, so that the active ingredient of the medicine can be fully dissolved, saving resources of Chinese medicinal materials; (2) the Chinese medicinal material is cell-wall-broken and ground twice through the jet mill, and the cell-wall-broken powder has the uniform particle size, the even distribution of various ingredients and the good uniformity; and (3) during the pelletizing process, different concentrations of ethanol-water solutions are added alternately to make the granule, so that the made granule has a good dissolution and diffusion and a rapid disintegration, overcoming problems of a difficulty of dissolution and diffusion and a poor stability of the cell-wall-broken granules in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG. 1 is a particle size distribution graph of a mixed powder from two times of the cell-wall-breaking of Astragalus membranaceus in Embodiment 1. FIG. 2 is a particle size distribution graph of a mixed powder from two times of the cell-wall-breaking of Salvia miltiorrhiza in Embodiment 2. FIG. 3 is a particle size distribution graph of a mixed powder from two times of the cell-wall-breaking of Radix scrophulariae in Embodiment 3. FIG. 4 is a particle size distribution graph of a cell-wall-broken powder of Astragalus membranaceus in Comparative example 1. FIG. 5 is a particle size distribution graph of a cell-wall-broken powder of Astragalus membranaceus in Comparative example 2. DETAILED DESCRIPTION

[0023] The present invention will be further described in detail below with reference to specific embodiments. Unless otherwise specified, reagents, equipment and methods used in the present invention are conventionally commercially available reagents and equipment and conventionally used methods in the art.Embodiment 1:

[0024] (1) medicinal material concocting: Astragalus membranaceus was picked, washed, sliced and dried to obtain clean Astragalus membranaceus; (2) medicinal material grinding: the clean Astragalus membranaceus was taken and ground with a mill with a 150 µm (100 mesh) sieve to obtain an 125-180 µm (80-120 mesh) Astragalus membranaceus coarse powder; (3) first cell-wall-breaking and grinding: cell-wall-breaking and grinding was performed on the obtained Astragalus membranaceus coarse powder to obtain a 13-74 µm (200-1000 mesh) cell-wall-broken powder; (4) particle size screening: the cell-wall-broken powder was screened to separate a 13-48 µm (300-1000 mesh) cell-wall-broken powder, and a powder particle size distribution was concentrated in 23-28 µm (500-600 mesh); (5) second cell-wall-breaking and grinding: the screened powder with a dimension of at least 48 µm (a mesh below 300) was returned to a cell-wall-breaking and grinding cavity for re-grinding to be cell-wall-broken and ground into a 28-48 µm (300-500 mesh) cell-wall-broken powder, with the powder particle size distribution concentrated in 28-38 µm (400-500 mesh); (6) mixing: different materials obtained from two times of the cell-wall-breaking and grinding were mixed through a material transfer mixing system; (7) pelletizing: the cell-wall-broken powder recovered in the step (6) was placed into a mixing agitator, a 90% ethanol-water solution and a 20% ethanol-water solution were added alternately to make a soft material, a total added amount of the ethanol-water solution was 0.5 of a weight of the cell-wall-broken powder, a wet granule was made through extrusion with a granulator with a 600 µm (30 mesh) sieve, and the made wet granule was dried; and (8) granulating and sieving: the granule obtained in the step (7) was granulated and sieved to make a 250-850 µm (20-60 mesh) granule. Embodiment 2:

[0025] According to the preparation method of Embodiment 1, Salvia miltiorrhiza was processed to obtain a corresponding Salvia miltiorrhiza granule. Differences were that in the step (7), the volume fractions of the high concentration ethanol-water solution and the low concentration ethanol-water solution were 75% and 30%, respectively, and the total added amount of the ethanol-water solution was 0.3 of the weight of the cell-wall-broken powder, and a 425 µm (40 mesh) sieve was selected for the pelletizing through the extrusion.Embodiment 3:

[0026] According to the preparation method of Embodiment 1, Radix scrophulariae was processed to obtain a corresponding Radix scrophulariae granule. Differences were that in the step (7), the volume fractions of the high concentration ethanol-water solution and the low concentration ethanol-water solution were 60% and 10%, respectively, and the total added amount of the ethanol-water solution was 0.8 of the weight of the cell-wall-broken powder, and a 850 µm (20 mesh) sieve was selected for the pelletizing through the extrusion.Comparative Example 1:

[0027] (1) medicinal material concocting: Astragalus membranaceus was picked, washed, sliced and dried to obtain clean Astragalus membranaceus; (2) medicinal material grinding: the clean Astragalus membranaceus was taken and grindd with a mill with a 150 µm (100 mesh) sieve to obtain an 125-180 µm (80-120 mesh) Astragalus membranaceus coarse powder; (3) first cell-wall-breaking and grinding: ultrasonic cell-wall-breaking and grinding was performed on the obtained Astragalus membranaceus coarse powder to obtain a 50-80 µm cell-wall-broken powder; (4) second cell-wall-breaking and grinding: the cell-wall-broken powder obtained in the step (3) was superfinely ground to be cell-wall-broken and ground into a 23-28 µm (500-600 mesh) wall-broken powder; (5) mixing: different materials obtained from two times of the cell-wall-breaking and grinding were mixed; (6) pelletizing: the cell-wall-broken powder recovered in the step (5) was placed into a mixing agitator, a 90% ethanol-water solution and a 20% ethanol-water solution were added alternately to make a soft material, a total added amount of the ethanol-water solution was 0.5 of a weight of the cell-wall-broken powder, a wet granule was made through extrusion with a granulator with a 600 µm (30 mesh) sieve, and the made wet granule was dried; and (7) granulating and sieving: the granule in the step (6) was granulated and sieved to make a 250-850 µm (20-60 mesh) granule. Comparative Example 2:

[0028] (1) medicinal material concocting: Astragalus membranaceus was picked, washed, sliced and dried to obatin clean Astragalus membranaceus; (2) medicinal material grinding: the clean Astragalus membranaceus was taken and ground with a mill with a 150 µm (100 mesh) sieve to obtain an 125-180 µm (80-120 mesh) Astragalus membranaceus coarse powder; (3) cell-wall-breaking and grinding: cell-wall-breaking and grinding was performed on the obtained Astragalus membranaceus coarse powder to obtain a cell-wall-broken powder with a dimension of 48 µm or less (a mesh above 300); (4) preparation of a soft material of the cell-wall-broken powder: the obtained cell-wall-broken powder was placed into a trough-type mixer, a suitable amount of 80-99% ethanol was added to make a soft material; (5) granule preparation: a small amount of the Astragalus membranaceus cell-wall-broken powder obtained in the step (3) was placed into a swing-type pelletor first, a 600 µm (30-mesh) sieve was used to pelletize a granule, in the granule preparation, as the cell-wall-broken powder soft material made in the step (4) was added, the Astragalus membranaceus cell-wall-broken powder obtained in the step (3) was added, and a ratio of the soft material to the dry powder was 6:0.5; and (6) a qualified cell-wall-broken decoction piece granule was put into an oven at 50°C-60°C for drying, after drying, an oscillating granulator with a 850 µm (20 mesh) sieve in an upper layer and a 250 µm (60 mesh) sieve in a bottom layer was used to granulate and sieve for three times, after subpackaging, a Astragalus membranaceus cell-wall-broken granule was obtained. Particle size uniformity detection test

[0029] The mixed powders obtained from two times of the cell-wall-breaking in Embodiment 1 to Embodiment 3 and the cell-wall-broken powders obtained in Comparative Example 1 and Comparative Example 2 were taken to measure sizes of the cell-wall-broken powder particles by a laser particle size analyzer. Results are shown in Table 1. Table 1 Detection results of sizes of cell-wall-broken powder particlesCharacteristic particle size (µm)D10D25D50D75D90D95D99Embodiment 12.8154.6348.15013.82421.02435.48341.670Embodiment 23.8166.49811.12418.19627.44835.55637.489Embodiment 33.9666.34910.26715.99323.06128.25139.277Comparative Example 13.8997.02813.24324.71745.090109.157154.485Comparative Example 25.37911.54024.72349.950109.687143.506175.672

[0030] It can be seen from data in Table 1 that the cell-wall-broken powder obtained by the grinding method provided by the present invention has an even particle size and a better uniformity.

[0031] Through statistics of the particle size distribution of Embodiment 1 to Embodiment 3, results are shown in FIGs. 1-3. The particle size of the cell-wall-broken powder is in a normal distribution and the particle size is even with a good uniformity.Ingredient uniformity detection test

[0032] Three parts of the Radix scrophulariae cell-wall-broken granule in Embodiment 3 were randomly selected, and active ingredients in the powder, harpagide and harpagoside, were measured by High Performance Liquid Chromatography (General Principle 0512), with octadecylsilane chemically bonded silica as a filler; acetonitrile was used as a mobile phase A, and a 0.03% phosphoric acid solution as a mobile phase B, to perform a gradient elution as specified in the following table; and a detection wavelength was 210 nm. A number of theoretical plates should not be less than 5000 according to peaks of harpagoside and harpagide. Time (min)Mobile phase A (%)Mobile phase B (%)0 to 103→1097→9010 to 2010→3390→6720 to 2533→5067→5025 to 3050→8050→2030 to 35802035 to 3780→320→97

[0033] Preparation of a reference substance solution was that an appropriate amount of a harpagide reference substance and an appropriate amount of a harpagoside reference substance were taken and accurately weighed, with 30% methanol added to prepare a mixed solution containing 60 µg harpagide and 20 µg harpagoside per 1 ml, and the reference substance solution was obtained.

[0034] Preparation of a test substance solution was that the three parts of the Radix scrophulariae cell-wall-broken powder in Embodiment 3 (through a No. 3 sieve), 0.5 g × 3, were randomly selected, accurately weighed, and placed in a conical flask with a stopper, with 50 ml of 50% ethanol accurately added, closely stoppered, weighed, soaked for 1 hour, with a ultrasonic treatment (power of 500 W, frequency of 40 kHz) for 45 minutes, cooled and weighed again, with 50% ethanol to make up for a lost weight, well shook, and filtered to take a subsequent filtrate, and the test substance solution was obtained.

[0035] According to a determination method, 10 µl of the reference substance solution and 10 µl of the test substance solution were accurately taken and injected into a liquid chromatographer for measurement.

[0036] A total amount of harpagide (C 15 H 24 O 10 ) and harpagoside (C 24 H 30 O 11 ) contained in this product shall not be less than 0.45%, calculated on the anhydrous substance.

[0037] The total amounts of harpagide (C 15 H 24 O 10 ) and harpagoside (C 24 H 30 O 11 ) in the three samples were determined to be 0.65%, 0.63%, and 0.63%, respectively, with a RSD of 1.81%.

[0038] It can be seen that contents of the active ingredients in the three samples randomly weighed are similar, so the mixed cell-wall-broken powder obtained from two times of the cell-wall-breaking has good particle uniformity, which ensures a stability of a medicine quality.Dissolution and diffusion time detection test

[0039] Test method: 2 g of each of the dry granules obtained in Embodiment 1 to Embodiment 3 and Comparative Examples were accurately weighed, placed in a 300 ml transparent cup, with 100 ml of water at 90°C to 95°C added (without heating during shaking), a dissolution and diffusion status of the granules in the cup was checked after shaking clockwise at a speed of 1 circle per second for 1 minute, 2 minutes, 3 minutes, 5 minutes, 10 minutes; and another 0.5 ml of liquid in the cup was taken to detect a shading rate with a laser particle size analyzer. Test results are shown in Table 2 below. Table 2 Dissolution and diffusion test results of the cell-wall-broken granules Shading rate (%)Embodiment 1Embodiment 2Embodiment 3Comparative Example 1Comparative Example 21 min1.761.351.470.981.352 min4.724.334.513.273.573 min6.385.946.235.085.745 min8.969.439.626.987.6510 min12.5712.0612.2310.9611.39

[0040] The data in Table 2 show that the method for preparing cell-wall-broken granules provided by the present invention has better effects and a more rapid dissolution and diffusion rate.

Claims

1. A method for preparing a granule of a medicinal material of plant origin comprising the following steps: (1) medicinal material of plant origin concocting: picking, washing, slicing and drying the medicinal material of plant origin to obtain a clean medicinal material; (2) medicinal material of plant origin grinding: taking and grinding the clean medicinal material of plant origin with a mill to obtain a 120-180 µm (80-120 mesh) medicinal coarse powder; (3) first cell-wall-breaking and grinding: performing cell-wall-breaking and grinding on the obtained medicinal coarse powder to obtain a 13-74 µm (200-1000 mesh) cell-wall-broken powder; (4) particle size screening: screening the cell-wall-broken powder to separate a 13-48 µm (300-1000 mesh) cell-wall-broken powder; (5) second cell-wall-breaking and grinding: returning the screened powder with at least 48 µm (a mesh below 300) to a cell-wall-breaking and grinding cavity for re-grinding to be cell-wall-broken and ground into a 25-48 µm (300-500 mesh) cell-wall-broken powder; (6) mixing: mixing different materials obtained from two times of the cell-wall-breaking and grinding to obtain a uniform cell-wall-broken powder with different particle sizes and different cell ingredients which are evenly distributed; (7) pelleting: placing the cell-wall-broken powder recovered in the step (6) into a mixing agitator, adding a high-concentration ethanol-water solution and a low-concentration ethanol-water solution alternately to make a soft material, extruding with a granulator with a 420-2000 µm (10-40 mesh) sieve to make a wet granule, and drying the made wet granule; wherein a volume fraction of ethanol in the high-concentration ethanol-water solution is 50%-95%, and a volume fraction of ethanol in the low-concentration ethanol-water solution is 10-30%; and (8) granulating and sieving: granulating and sieving the granule in the step (7) to make a 250-850 µm (20-60 mesh) granule.

2. The method for preparing the granule of the medicinal material according to claim 1, wherein in the step (4), the screening is performed on the cell-wall-broken powder in a force field to separate the 13-48 µm (300-1000 mesh) cell-wall-broken powder.

3. The method for preparing the granule of the medicinal material according to claim 1, wherein a weight ratio of the ethanol-water solution used in the step (7) to a superfine powder is (0.1-0.99):1.

4. The method for preparing the granule of the medicinal material according to any one of claims 1 and 2, wherein in the step (7), when extruding to make the wet granule, a force of the extruding is 0.05-1 MPa and a rotation speed is 0,667-1,667 r / s (40-100 r / min).

5. The method for preparing the granule of the medicinal material according to claim 4, wherein the force of the extruding is 0.25-0.45 MPa and the rotation speed is 1,25-1,417 r / s (75-85 r / min).

6. The method for preparing the granule of the medicinal material according to claim 1, wherein a step of the grinding in the step (3) and the step (5) is performed in a jet mill, a temperature of a grinding space is 18-26°C, a relative humidity is ≤ 55%, an inlet working pressure is ≥ 0.7 MPa, and a rotation speed of a grader is 30-35 r / s.

7. The method for preparing the granule of the medicinal material according to claim 1, wherein the volume fraction of the ethanol in the high-concentration ethanol-water solution in the step (7) is 60%-90%, and the volume fraction of the ethanol in the low-concentration ethanol-water solution is 10%-20%.

8. The method for preparing the granule of the medicinal material according to claim 7, wherein the volume fraction of the ethanol in the high-concentration ethanol-water solution in the step (7) is 70%-80%, and the volume fraction of the ethanol in the low-concentration ethanol-water solution is 15%-20%.