Trametes robiniophila sucrose-free granules and preparation process thereof

Abstract

The invention relates to trametes robiniophila sucrose-free granules and a preparation process thereof. The trametes robiniophila sucrose-free particles are prepared from the following components in parts by weight: 132.0 parts of trametes robiniophila clear paste (in terms of bovine serum albumin); 200 to 600 parts of maltodextrin; 0 to 10 parts of sucralose; and 50 to 200 parts of water. The auxiliary materials of the prescription are changed, the auxiliary materials such as cane sugar, dextrin and soluble starch are removed, the dosage of the auxiliary materials is reduced under the condition that the dosage of the trametes robiniophila clear paste is not changed, but the content of the medicine in each bag is not changed.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations, and particularly to Huai'er sugar-free granules and a preparation process thereof. Background Art

[0002] Huai'er granules are a new type of traditional Chinese medicine of Class 1 (original classification), and are a traditional Chinese medicine composed of Huai'er mycelium. Huai'er mycelium is safe and non-toxic, and has a strong immunomodulatory effect. It can stimulate the killing cell activities of macrophages and neutrophils, and promote the proliferation and division of T lymphocytes. The existing prescriptions of Huai'er granules all contain sucrose. The specific prescription is as follows: Huai'er extract (以牛血清白蛋白计)， 66.0 g, sucrose 253.8 g, dextrin 325.5 g, soluble starch 107.3 g, appropriate amount of flavoring agent, and made into 1000 g. The existing production process is as follows: Huai'er extract is added with sucrose, dextrin, soluble starch and flavoring agent and mixed evenly, wet granulation is carried out, drying is carried out under normal pressure, granule sizing is carried out, sieving is carried out, and packaging is carried out (each bag contains 20 g, and the patient's dosage is 20 g once and 3 times a day). The existing specification is 20 g per bag, and the validity period is 24 months.

[0003] There is a large amount of sucrose in the existing prescription of Huai'er granules. When the fine powder obtained after belt vacuum continuous drying is used for extrusion granulation, it is easy to agglomerate and difficult to extrude into granules. Moreover, since the patient's dosage per time has reached 20 g, it is difficult to solve the granulation problem by increasing the content of excipients. In addition, the existing Huai'er granules are a prescription containing sucrose and are not suitable for patients with high blood sugar or diabetes. At present, the number of patients with high blood sugar or diabetes is increasing day by day. Therefore, the demand for a sugar-free prescription is becoming stronger and stronger.

[0004] In the existing preparation process of Huai'er granules, during wet granulation, it is difficult to add all the Huai'er extract at one time. It is necessary to first add a part of the Huai'er extract to a part of the excipients, mix, granulate, dry and size the granules, and then crush them into fine powder, and then add the remaining Huai'er extract and excipients, and continuously repeat the above process to make the finished Huai'er granules. The entire production process takes a long time, consumes a large amount of energy, and has a high labor intensity. At the same time, the long-term drying of wet granules is also unfavorable to the stability of the drug. Summary of the Invention

[0005] In order to overcome the above defects, the inventors of the present application have improved both the prescription and the preparation process of Huai'er granules. For example, the excipients of the prescription are changed, and excipients such as sucrose, dextrin, and soluble starch are removed; the production process is adjusted, and belt vacuum continuous drying and dry extrusion granulation are used to replace the original wet granulation and drying under normal pressure; according to the above improvements, the drug specification is changed from 20 g per bag to 10 g per bag, and the drug content per bag remains unchanged.

[0006] Therefore, an object of the present invention is to provide a kind of Inonotus obliquus sucrose-free granule. Another object of the present invention is to provide a preparation process of the above-mentioned Inonotus obliquus sucrose-free granule. Still another object of the present invention is to provide a pharmaceutical use of the above-mentioned Inonotus obliquus sucrose-free granule.

[0007] The above objects of the present invention are achieved by the following technical solutions.

[0008] On the one hand, the present invention provides a kind of Inonotus obliquus sucrose-free granule, which is made of the following components in parts by weight:

[0009]

[0010] Preferably, the Inonotus obliquus sucrose-free granule is made of the following components in parts by weight:

[0011]

[0012] More preferably, the Inonotus obliquus sucrose-free granule is made of the following components in parts by weight:

[0013]

[0014] In a specific embodiment, the prescription of the Inonotus obliquus sucrose-free granule of the present invention is as follows:

[0015]

[0016] In another specific embodiment, the prescription of the Inonotus obliquus sucrose-free granule of the present invention is as follows:

[0017]

[0018] In this application, by adjusting the types and dosages of excipients, sucrose, dextrin, soluble starch and flavoring agents are removed, and maltodextrin (or and sucralose) is used as the excipient. Without changing the dosage of Inonotus obliquus extract, the dosage of excipients is reduced, and the filling weight per bag is reduced from 20 g to 10 g, but the drug content per bag remains unchanged.

[0019] The Inonotus obliquus sucrose-free granule of the present invention can strengthen the healthy qi and consolidate the constitution, activate blood circulation and dissipate stasis. It is suitable for the adjuvant treatment of those with weak healthy qi, blood stasis blockage, and inoperable and chemotherapy-ineligible primary liver cancer, and has the effect of improving symptoms such as liver area pain, abdominal distension, and fatigue. On the basis of standard chemical drug anti-cancer treatment, it can be used for symptoms such as fatigue, lack of qi and shortness of breath, abdominal pain or distension, poor appetite, dry or loose stools, or shortness of breath, cough, excessive phlegm, pale complexion, chest pain, blood in sputum, and discomfort in the chest and hypochondrium caused by lung cancer, gastrointestinal cancer and breast cancer, and can improve the quality of life of patients.

[0020] On the other hand, the present invention provides a preparation process for the above-mentioned Tremella aurantialba sucrose-free granules, and the process comprises the following steps:

[0021] Mix the Tremella aurantialba extract with sucralose (if any), water and an appropriate amount of maltodextrin, dry with a vacuum belt dryer, granulate by dry extrusion, sieve, mix uniformly, and package to obtain the product.

[0022] Preferably, the Tremella aurantialba extract is prepared by the following method:

[0023] (1) Take Tremella aurantialba mycelium, decoct with water three times. For the first time, add 1-15 times the amount of water, boil for 0.5-10 hours, filter, and reserve the filtrate;

[0024] (2) For the second and third times, add 1-15 times the amount of water respectively, boil for 0.5-10 hours, filter, combine the three filtrates, and concentrate under reduced pressure to a relative density of 1.35-1.40 (55 °C) to obtain the Tremella aurantialba extract.

[0025] Preferably, in step (1), add 1-10 times the amount of water for the first time, preferably 7 times the amount.

[0026] Preferably, in step (1), boil for 0.5-2 hours, preferably 1.5 hours.

[0027] Preferably, in step (2), add 3-8 times the amount of water for the second and third times respectively, preferably 5 times the amount.

[0028] Preferably, in step (2), boil for 0.5-2 hours, preferably 1 hour.

[0029] Preferably, the temperature for drying with the vacuum belt dryer is: Zone I: 30-150 °C; Zone II: 30-140 °C; Zone III: 30-130 °C, preferably Zone I: 100-120 °C; Zone II: 90-110 °C; Zone III: 70-90 °C.

[0030] Preferably, the conditions for dry extrusion granulation are: roller pressure 25-35 kg / cm 2 , the frequency of the feeding motor is 25 Hz, the frequency of the tablet pressing motor is 30 Hz, the frequency of the cutting motor is 15 Hz, and the frequency of the granule sizing motor is 12 Hz.

[0031] In a specific embodiment, the preparation process for the above-mentioned Tremella aurantialba sucrose-free granules comprises the following steps:

[0032] (1) Take Tremella aurantialba mycelium, decoct with water three times. For the first time, add 7 times the amount of water, boil for 1.5 hours, filter, and reserve the filtrate;

[0033] (2) Add 5 times the amount of water for the second and third times, boil for 1 hour, filter, combine the filtrates of the three times, and concentrate under reduced pressure to a relative density of 1.35 - 1.40 (55 °C) to obtain the Huai'er clear extract;

[0034] (3) Mix the Huai'er clear extract prepared in step (2) with sucralose (if any), an appropriate amount of water and maltodextrin, dry with a vacuum belt dryer, granulate by dry extrusion, sieve, make 1000 g of granules, and pack (10 g per bag) to obtain the product.

[0035] In step (3), the drying temperature of the vacuum belt dryer is: Zone I: 110 °C, Zone II: 100 °C, Zone III: 80 °C.

[0036] In step (3), the conditions for dry extrusion granulation are: roller pressure 25 - 35 kg / cm 2 , the frequency of the feeding motor is 25 Hz, the frequency of the tablet pressing motor is 30 Hz, the frequency of the cutting motor is 15 Hz, and the frequency of the sizing motor is 12 Hz.

[0037] The fine powder obtained by the belt vacuum continuous drying adopted in this application is not easy to adhere and is easy to be extruded into granules. After the stability test, after being placed at 40 °C and RH75% for 6 months and at 25 °C and RH60% for 24 months, various physical and chemical indexes, such as appearance, identification, moisture, particle size, content, and microbial limit, etc., have no obvious changes, and the product quality is stable and reliable.

[0038] Compared with the prior art, the sucrose-free Huai'er granules of this application and its preparation process have at least the following advantages:

[0039] In this application, the excipients are changed compared with the prior art. Sucrose, dextrin, soluble starch, and flavoring agents are replaced with maltodextrin (or and sucralose). The product has good water solubility, good taste, and is easy for patients to take; sucrose is removed in this application, and patients with high blood sugar and diabetes can also take it; the amount of excipients is reduced in this application, the drying time is shortened, the color of the granules becomes lighter, the product stability is increased, and the production cost is reduced at the same time.

[0040] Compared with the existing production process, this application adopts belt vacuum continuous drying and dry extrusion granulation. Its drying temperature is low, the time is short, the color of the granules is light, and the product stability is increased; the production process of this application is reduced, it is easy to operate and control, and the risk of particle contamination is effectively reduced; the labor intensity of workers and the production energy consumption of this application are both greatly reduced, the production cost is effectively reduced, the production cycle is shortened, and the production capacity is improved. Description of the Drawings

[0041] Figure 1 It is the process flow chart of the sucrose-free Huai'er granules of the present invention. Detailed Embodiments

[0042] The present invention will be further described in detail below in conjunction with specific embodiments.

[0043] Example 1 Huai'er Sucrose-free Granules of the present application

[0044] Prescription:

[0045]

[0046] Specification: Each bag contains 10 g. The preparation process flow chart is as Figure 1 shown. Preparation method:

[0047] Take Huai'er mycelium (obtained from Qidong Gaitianli Pharmaceutical Co., Ltd.), decoct with water three times. For the first time, add 7 times the amount of water, boil for 1.5 hours, filter, and reserve the filtrate; for the second and third times, add 5 times the amount of water respectively, boil for 1 hour, filter, combine the three filtrates, and concentrate under reduced pressure to a relative density of 1.35 - 1.40 (55 °C) to obtain Huai'er extract.

[0048] First, dissolve sucralose in water, then mix the Huai'er extract, sucralose aqueous solution and an appropriate amount of maltodextrin evenly, dry with a vacuum belt dryer, granulate by dry extrusion, sieve, make 1000 g of granules, and pack (each bag contains 10 g) to obtain the product.

[0049] Among them, the vacuum belt drying temperature: Zone I: 110 °C; Zone II: 100 °C; Zone III: 80 °C; Dry extrusion granulation conditions: roller pressure 25 - 35 kg / cm 2 , the feeding motor frequency is 25 Hz, the tablet pressing motor frequency is 30 Hz, the cutting motor frequency is 15 Hz, and the sizing motor frequency is 12 Hz.

[0050] Example 2 Huai'er Sucrose-free Granules of the present application

[0051] Prescription:

[0052]

[0053] Specification: Each bag contains 10 g

[0054] The preparation process flow chart is as Figure 1 shown. Preparation method:

[0055] Take Huai'er mycelium (obtained from Qidong Gaitianli Pharmaceutical Co., Ltd.), decoct with water three times. For the first time, add 7 times the amount of water, boil for 1.5 hours, filter, and reserve the filtrate; for the second and third times, add 5 times the amount of water respectively, boil for 1 hour, filter, combine the three filtrates, and concentrate under reduced pressure to a relative density of 1.35 - 1.40 (55 °C) to obtain Huai'er extract.

[0056] Mix the appropriate amount of Tremella fuciformis polysaccharide extract, water and maltodextrin, dry it with a vacuum belt dryer, granulate it by dry extrusion, sieve it, make 1000 g of granules, and pack them (10 g per bag) to obtain the product.

[0057] Among them, the vacuum belt drying temperature: Zone I: 110 °C; Zone II: 100 °C; Zone III: 80 °C; The conditions for dry extrusion granulation: the pressure of the rolling wheel is 25 - 35 kg / cm 2 , the frequency of the feeding motor is 25 Hz, the frequency of the tablet pressing motor is 30 Hz, the frequency of the cutting motor is 15 Hz, and the frequency of the sizing motor is 12 Hz.

[0058] Control Example 1 Tremella fuciformis sucrose-free granules

[0059] Prescription:

[0060]

[0061]

[0062] Specification: 10 g per bag

[0063] Preparation method:

[0064] Take Tremella fuciformis mycelium (obtained from Qidong Gaitianli Pharmaceutical Co., Ltd.), decoct it with water three times. For the first time, add 7 times the amount of water, boil for 1.5 hours, filter, and reserve the filtrate; for the second and third times, add 5 times the amount of water respectively, boil for 1 hour, filter, combine the three filtrates, and concentrate under reduced pressure to a relative density of 1.35 - 1.40 (55 °C) to obtain Tremella fuciformis polysaccharide extract.

[0065] First, dissolve sucralose and monosodium glutamate in water, then mix the Tremella fuciformis polysaccharide extract with the sucralose, monosodium glutamate aqueous solution, and the appropriate amount of maltodextrin and dextrin, dry it with a vacuum belt dryer, granulate it by dry extrusion, sieve it, make 1000 g of granules, and pack them (10 g per bag) to obtain the product.

[0066] Among them, the vacuum belt drying temperature: Zone I: 110 °C; Zone II: 100 °C; Zone III: 80 °C; Dry extrusion granulation: the pressure of the rolling wheel is 25 - 35 kg / cm 2 , the frequency of the feeding motor is 25 Hz, the frequency of the tablet pressing motor is 30 Hz, the frequency of the cutting motor is 15 Hz, and the frequency of the sizing motor is 12 Hz..

[0067] For this Control Example 1, the excipients selected are maltodextrin: dextrin (1:1), adding 2% monosodium glutamate and 0.25% sucralose for flavor correction. The color of the dry powder obtained by vacuum belt drying is darker, and the color of the granules further deepens after dry granulation extrusion. The taste of the obtained granules is poor.

[0068] Control Example 2 Tremella fuciformis sucrose-free granules

[0069]

[0070]

[0071] Specification: 10 g per bag

[0072] Preparation method:

[0073] As Figure 1 shown. Take Tremella fuciformis Berk. mycelium (obtained from Qidong Gaitianli Pharmaceutical Co., Ltd.), decoct with water three times. For the first time, add 7 times the amount of water, boil for 1.5 hours, filter, and reserve the filtrate; for the second and third times, add 5 times the amount of water respectively, boil for 1 hour, filter, combine the three filtrates, and concentrate under reduced pressure to a relative density of 1.35 - 1.40 (55 °C) to obtain Tremella fuciformis Berk. extract.

[0074] First, dissolve sucralose and sodium glutamate in water, then mix the Tremella fuciformis Berk. extract with the sucralose, sodium glutamate aqueous solution and an appropriate amount of maltodextrin, dry with a vacuum belt dryer, granulate by dry extrusion, sieve, make 1000 g of granules, and pack (10 g per bag) to obtain the product.

[0075] Among them, the vacuum belt drying temperature: Zone I: 110 °C; Zone II: 100 °C; Zone III: 80 °C; Dry extrusion granulation conditions: roller pressure 25 - 35 kg / cm 2 , feed motor frequency 25 Hz, tablet pressing motor frequency 30 Hz, cutting motor frequency 15 Hz, and granule finishing motor frequency 12 Hz.

[0076] In this comparative example, the excipient used is maltodextrin, adding 2% sodium glutamate and 0.25% sucralose for flavor correction. The granules obtained have good formability and a lighter color, but the taste is poor.

[0077] Experimental Example 1: Screening Test of Excipients

[0078] Using a vacuum drying oven as the drying equipment, investigate the influence of different excipients on the drying process and the dried product.

[0079] The excipients investigated: dextrin, soluble starch, microcrystalline cellulose, lactose, mannitol, sorbitol, starch hydrolyzate oligosaccharide, maltodextrin.

[0080] Research method: With a specification of 10 g per bag, mix different excipients with the Tremella fuciformis Berk. extract respectively. For the samples that can be granulated after mixing, granulate with a 14 - mesh sieve. For those that are too thin to be granulated, directly spread them in a container for drying. Compare the drying process and the ease of removing the dried product from the container.

[0081] Research equipment used: Vacuum drying oven VOS - 60A, Schottky Instrument Equipment (Shanghai) Co., Ltd.

[0082] Drying conditions: vacuum degree 0.088 MPa, temperature 110 °C

[0083] Drying time: 3 hours

[0084] The research results are shown in Table 1.

[0085] Table 1 Investigation on vacuum drying of Tremella aurantialba mycelium extract after adding different excipients

[0086]

[0087]

[0088] According to the above research, combined with the melting requirements of the granule, drying research was carried out using maltodextrin and dextrin as excipients respectively. The results showed that there was no obvious difference between the two, but the solubility of maltodextrin in water was greater than that of dextrin, and the taste was also better. The absorption of microcrystalline cellulose and mannitol by Tremella aurantialba mycelium extract was not as good as that of maltodextrin. When maltodextrin was selected as the excipient, the formed soft material was thinner, which was more conducive to uniform stirring and mixing. Therefore, maltodextrin was selected as the excipient.

[0089] Experimental Example 2: Screening Test of Drying Parameters

[0090] Using the formula and preparation method of Example 1 (the parameters different from those in Example 1 are recorded in Table 2 below), experiments were carried out under the condition of only changing the drying temperature while keeping other conditions unchanged. The inspection indexes were moisture content, protein content and the color of the dry product. The results are shown in Table 2 below:

[0091] Table 2

[0092]

[0093]

[0094] It can be seen from the above experiments that when the drying temperature in the three zones is 110 - 100 - 80 °C, the moisture content of the dry extract powder can be stably controlled below 4%, the protein content can also meet the quality requirements, and the color of the dry extract powder is lighter, being light yellowish brown.

[0095] Experimental Example 3: Influence of Different Granulation Parameters on Granulation Process and Granulation Products

[0096] Using a dry granulator as the granulation equipment, the effects of different granulation parameters on the granulation process and the granulation finished products were investigated.

[0097] Research method: The dry powder of Tremella aurantialba mycelium extract obtained by drying under the optimal conditions was granulated by dry granulation, and the friability, particle size and dissolution of the prepared granules were compared.

[0098] Research equipment: Automatic production dry granulator, model GL5 - 100, Zhangjiagang Chuangkai Machinery Manufacturing Co., Ltd.

[0099] Research Conditions and Results

[0100] The formula and preparation method used in this example are as shown in Example 1, and the parameters different from those in Example 1 are recorded in Table 3 below.

[0101] Table 3

[0102]

[0103]

[0104] The research results show that the granules made under a relatively small roller pressure (15 - 25 kg / cm 2 ) are relatively loose, have a higher particle size, poor particle formability, and it is difficult to control the quality. The granules made under a relatively large roller pressure (35 - 45 kg / cm 2 ) have a lower particle size and better particle formability, but the relatively large roller pressure causes the granules to have a darker color. Under the pressure condition of 25 - 35 kg / cm 2 , the granules have a lighter color, a lower particle size, and the formability meets the quality requirements. The feeding frequency was investigated under two conditions of 20 Hz and 25 Hz. Under the condition of 20 Hz, the feeding port was easily blocked and the output was also low, so it was adjusted to 25 Hz and the feeding was smooth.

[0105] In summary, considering factors such as the product properties color, product stability, production capacity, and economic benefits, the test parameters are determined as follows: roller pressure 25 - 35 kg / cm 2 , feeding motor frequency 25 Hz, tableting motor frequency 30 Hz, cutting motor frequency 15 Hz, and granulating motor frequency 12 Hz.

[0106] Example 4: Stability Test

[0107] Refer to the Guidelines for Stability Testing of Raw Drugs and Preparations in Part 4 of the Chinese Pharmacopoeia 2015 Edition and the Quality Standard of Trametes robiniophila Murr Granules of the National Drug Standard YBZ04202003 - 2009Z - 2012 to conduct stability investigations on the test products.

[0108] Test products:

[0109] 1. The product of Example 1;

[0110] 2. The product of Example 2;

[0111] 3. Existing sucrose-containing products: Prescription: Huai'er concentrated extract (calculated as bovine serum albumin) 66.0 g, sucrose 253.8 g, dextrin 325.5 g, soluble starch 107.3 g, appropriate flavoring agent, made into 1000 g. Production process: Add Huai'er concentrated extract, sucrose, dextrin, soluble starch and flavoring agent, mix well, granulate by wet method, dry at normal pressure, size the granules, sieve, and pack (20 g per bag, the patient's dosage is 20 g once and 3 times a day). Test method:

[0112] 1. Accelerated test: 3 batches of pilot-scale products are placed for 6 months under the conditions of temperature 40°C ± 2°C and relative humidity 75% ± 5% in the market packaging. Samples are taken once at the end of the 1st month, 2nd month, 3rd month, and 6th month during the test period, and tested according to the key items for stability test.

[0113] 2. Long-term test: 3 batches of pilot-scale products are placed for 24 months under the conditions of temperature 25°C ± 2°C and relative humidity 60% ± 5% in the market packaging. Samples are taken at 0 month, 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months respectively and tested according to the key items for stability test.

[0114] Test results: The test data of this test are presented in the form of a table to effectively evaluate the stability data of Huai'er granules.

[0115] (1) Accelerated test results:

[0116] The test results of three batches of the product in Example 1 are as described in Table 4 - 6.

[0117] Table 4

[0118]

[0119] Table 5

[0120]

[0121]

[0122] Table 6

[0123]

[0124] The accelerated test results of three batches of the product in Example 2 are as described in Tables 7 - 9.

[0125] Table 7

[0126]

[0127]

[0128] Table 8

[0129]

[0130] Table 9

[0131]

[0132] Three batches of existing sucrose-containing products were used as control examples to investigate the stability of the products under accelerated test conditions. The results are shown in Tables 10 - 12.

[0133] Table 10

[0134]

[0135] Table 11

[0136]

[0137] Table 12

[0138]

[0139] (2) Long-term test results:

[0140] The experimental results of three batches of the product of Example 1 are as described in Tables 13 - 15.

[0141] Table 13

[0142]

[0143] Table 14

[0144] Table 15

[0145]

[0146] The long-term test results of three batches of the product of Example 2 are as described in Tables 16 - 18.

[0147] Table 16

[0148]

[0149] Table 17

[0150]

[0151] Table 18

[0152]

[0153] Three batches of existing sucrose-containing products were used as control examples to investigate the stability of the products under long-term test conditions. The results are shown in Tables 19 - 21.

[0154] Table 19

[0155]

[0156]

[0157] Table 20

[0158]

[0159] Table 21

[0160]

[0161]

[0162] The results show that the fine powder obtained by belt vacuum continuous drying is not easy to agglomerate, is easy to be extruded into granules, and the quality of the finished products can meet the relevant requirements of the national drug standard YBZ04202003-2009Z-2012, the quality standard of Huai'er granules. 6 batches of pilot-scale production samples of Huai'er sucrose-free granules and 3 batches of Huai'er sucrose-containing granules were investigated by stability test. They were placed at 40 °C and RH75% for 6 months and at 25 °C and RH60% for 24 months, and various items such as appearance, identification, moisture, particle size, content and microbial limit were inspected. The experimental results show that there are no obvious changes in various physical and chemical indexes. Compared with the existing sucrose-containing products, the quality of the product of the present invention has no obvious change and is stable and reliable.

Claims

1. A Huai'er sucrose-free granule, calculated by weight parts, the Huai'er sucrose-free granule is made of the following components:

2. The tremella aurantialba sucrose-free granules according to claim 1, wherein, Calculated by weight parts, the Huai'er sucrose-free granule is made of the following components: Preferably, calculated by weight parts, the Huai'er sucrose-free granule is made of the following components:

3. A preparation process of the Huai'er sucrose-free granule according to claim 1 or 2, the process comprises the following steps: Mix the Huai'er extract paste with sucralose (if any), water and an appropriate amount of maltodextrin, dry it with a vacuum belt dryer, granulate it by dry extrusion, sieve it, mix it uniformly, and package it to obtain the product.

4. The preparation process according to claim 3, wherein, The Huai'er extract paste is prepared by the following method: (1) Take Huai'er mycelium, decoct it with water three times. For the first time, add 1 - 15 times the amount of water, boil for 0.5 - 10 hours, filter, and reserve the filtrate; (2) For the second and third times, add 1 - 15 times the amount of water respectively, boil for 0.5 - 10 hours, filter, combine the filtrates of the three times, and concentrate it under reduced pressure to a relative density of 1.35 - 1.40 (55 °C) to obtain the Huai'er extract paste.

5. The preparation process according to claim 4, wherein, In step (1), add 1 - 10 times the amount of water for the first time, preferably 7 times the amount; Preferably, in step (1), boil for 0.5 - 2 hours, preferably 1.5 hours.

6. The preparation process according to claim 4 or 5, wherein, In step (2), add 3 - 8 times the amount of water for the second and third times respectively, preferably 5 times the amount; Preferably, in step (2), boil for 0.5 - 2 hours, preferably 1 hour.

7. The preparation process according to any one of claims 3 to 6, wherein, The drying temperature of the vacuum belt dryer is: Zone I: 30 - 150 °C, Zone II: 30 - 140 °C, Zone III: 30 - 130 °C; preferably Zone I: 100 - 120 °C, Zone II: 90 - 110 °C, Zone III: 70 - 90 °C.

8. The preparation process according to any one of claims 3 to 7, wherein The conditions for dry extrusion granulation are as follows: the pressure of the rolling wheel is 25 - 35 kg / cm 2 , the frequency of the feeding motor is 25 Hz, the frequency of the tablet pressing motor is 30 Hz, the frequency of the cutting motor is 15 Hz, and the frequency of the granule finishing motor is 12 Hz.

9. The preparation process according to any one of claims 3 to 8, wherein, The preparation process of the Huai'er sucrose-free granule comprises the following steps: (1) Take Huai'er mycelium, decoct it with water three times. Add 7 times the amount of water for the first time, boil for 1.5 hours, filter, and reserve the filtrate; (2) For the second and third times, add 5 times the amount of water respectively, boil for 1 hour, filter, combine the filtrates of the three times, and concentrate it under reduced pressure to a relative density of 1.35 - 1.40 (55 °C) to obtain the Huai'er extract paste; (3) Mix the Huai'er extract paste prepared in step (2) with sucralose (if any), water and an appropriate amount of maltodextrin, dry it with a vacuum belt dryer, granulate it by dry extrusion, sieve it, make 1000 g of granules, and package it (10 g per bag) to obtain the product.

10. The preparation process according to claim 9, wherein, In step (3), the drying temperature of the vacuum belt dryer is: Zone I: 110 °C, Zone II: 100 °C, Zone III: 80 °C; Preferably, in step (3), the conditions for dry extrusion granulation are as follows: the pressure of the rolling wheel is 25-35 kg / cm 2 , the frequency of the feeding motor is 25 Hz, the frequency of the tablet pressing motor is 30 Hz, the frequency of the cutting motor is 15 Hz, and the frequency of the granule finishing motor is 12 Hz.

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