Sugar-free traditional Chinese medicine granules with functions of tonifying spleen, nourishing stomach and improving immunity and preparation method of sugar-free traditional Chinese medicine granules

Abstract

The invention relates to sugar-free traditional Chinese medicine granules capable of tonifying spleen, nourishing stomach and improving immunity and a preparation method of the sugar-free traditional Chinese medicine granules, and belongs to the technical field of medicines. The invention provides a preparation method of sugar-free traditional Chinese medicine granules, which comprises the following steps: weighing traditional Chinese medicine components, crushing half of Chinese yam and hawthorn as flavoring agents, extracting volatile oil of pericarpium citri reticulatae, clathrating the volatile oil with beta-cyclodextrin, mixing and decocting the remaining medicines for three times, merging decoction liquids, concentrating, drying and crushing to obtain extract powder, and packaging the extract powder to obtain the sugar-free traditional Chinese medicine granules. And finally, mixing and granulating the obtained components to obtain the sugar-free traditional Chinese medicine granules. According to the sugar-free traditional Chinese medicine granules, astragalus membranaceus is used as a monarch drug; chinese yam, codonopsis pilosula, malt and dendrobe are used as ministerial drugs; hawthorn, pericarpium citri reticulatae, poria cocos, pawpaw and rhizoma atractylodis macrocephalae are used as adjuvant drugs; the preparation process is combined, so that the content of effective components of the traditional Chinese medicine components is increased, and the effects of strengthening the spleen, nourishing the stomach and improving the immunity of the sugar-free traditional Chinese medicine granules are remarkably improved.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technologies, and in particular to a sugar-free traditional Chinese medicine granule with the functions of strengthening the spleen and stomach and enhancing immunity, and a preparation method thereof. Background Art

[0002] Anorexia and repeated colds (recurrent respiratory tract infections, low immune function) are common diseases in children, which directly affect the healthy development of children. The main reasons for these diseases in children are insufficient endowment, deficiency of the lungs, spleen, and stomach. When the lung qi is weak, the exterior defense is not firm; when the spleen and stomach are weak, the source of qi transformation is insufficient, and all five zang-organs are weak, so children are vulnerable to pathogenic attacks. Qihu Zhacha Granule has the functions of strengthening the spleen and stomach and enhancing immune function, and can treat common anorexia and repeated cold symptoms in children. However, with the continuous improvement of living standards, people's material life is becoming more and more abundant. Due to the lack of exercise in children, their physical fitness shows a downward trend, and the effects of Qihu Zhacha Granule in enhancing children's immunity and strengthening the spleen and stomach also need to be improved.

[0003] Based on this, the present invention is proposed. Summary of the Invention

[0004] The purpose of the present invention is to provide a sugar-free traditional Chinese medicine granule with the functions of strengthening the spleen and stomach and enhancing immunity, and a preparation method thereof, so as to solve the problems of the decline in children's physical fitness and low immunity in the prior art.

[0005] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0006] The present invention provides a preparation method of a sugar-free traditional Chinese medicine granule, which includes the following steps:

[0007] (1) Weigh the following parts by mass of traditional Chinese medicine components:

[0008] Astragalus membranaceus 28 - 32 parts, Dioscorea opposita 18 - 22 parts, Radix Glycyrrhizae Praeparata 4 - 8 parts, Poria cocos 13 - 17 parts, Dendrobium officinale 8 - 12 parts, Germinated Barley 10 - 14 parts, Hawthorn Fruit 10 - 14 parts, Steamed Chaenomeles sinensis 6 - 10 parts, Codonopsis pilosula 18 - 22 parts, Pericarpium Citri Reticulatae 7 - 11 parts, Atractylodes macrocephala 13 - 17 parts;

[0009] (2) Mix and pulverize half of the parts by mass of Dioscorea opposita and Hawthorn Fruit, and sterilize to obtain a mixed powder;

[0010] (3) Mix Pericarpium Citri Reticulatae with water, soak, and perform steam distillation for 1 - 2 h to obtain Pericarpium Citri Reticulatae volatile oil and an aqueous solution of Pericarpium Citri Reticulatae residue;

[0011] (4) Mix Pericarpium Citri Reticulatae volatile oil with β - cyclodextrin to obtain an inclusion compound;

[0012] (5) Mix half of the mass portion of Chinese yam and hawthorn with the aqueous solution of astragalus root, roasted licorice root, poria cocos, dendrobium officinale, stir-fried malt, steamed papaya, codonopsis pilosula, atractylodes macrocephala, and dried tangerine peel residue to obtain mixture 2;

[0013] (6) Mix mixture 2 and water, ultrasonicate and then decoct for 1.5 - 2.5 h, filter, the filtrate is decoction 1, and the filter residue is decoction residue 1;

[0014] (7) Mix decoction residue 1 and water, decoct for 1 - 2 h, filter, the filtrate is decoction 2, and the filter residue is decoction residue 2;

[0015] (8) Mix decoction residue 2 and water, decoct for 1 - 2 h, filter and take the filtrate as decoction 3;

[0016] (9) Mix decoction 1, decoction 2, and decoction 3, filter to obtain the filtrate, concentrate the filtrate to a relative density of 1.15 - 1.20 to obtain the extract, dry and pulverize to obtain the extract powder;

[0017] (10) Mix the mixed powder obtained in step (2), the clathrate obtained in step (4), the extract powder obtained in step (9), and hydroxypropyl cellulose, granulate to obtain the sugar-free traditional Chinese medicine granules.

[0018] Preferably, the particle size of the pulverization in step (2) is 180 - 220 mesh;

[0019] The temperature of the sterilization is 110 - 120 °C, and the time is 25 - 35 min.

[0020] Preferably, the mass ratio of dried tangerine peel and water in step (3) is 1:2 - 4.

[0021] Preferably, the mass ratio of dried tangerine peel volatile oil and β-cyclodextrin in step (4) is 1:6 - 10.

[0022] Preferably, the mass ratio of mixture 2 and water in step (6) is 1:8 - 12;

[0023] The power of the ultrasonic wave is 6 - 10 kW, and the time is 10 - 20 min.

[0024] Preferably, the mass ratio of decoction residue 1 and water in step (7) is 1:6 - 10.

[0025] Preferably, the mass ratio of decoction residue 2 and water in step (8) is 1:6 - 10.

[0026] Preferably, the pore size of the filtration in step (9) is 280 - 320 mesh;

[0027] The temperature of the concentration is 60 - 85 °C;

[0028] The drying is spray drying, the inlet air temperature of the spray drying is 110-130°C, and the outlet air temperature is 65-105°C.

[0029] Preferably, the granulation in step (10) is dry granulation, the pressure of the dry granulation is 3-5 MPa, and the rotation speed is 20-25 rpm.

[0030] The present invention provides a sugar-free traditional Chinese medicine granule prepared by the described preparation method, and the sugar-free traditional Chinese medicine granule has the effects of strengthening the spleen and stomach and enhancing immunity.

[0031] The present invention has the following technical effects and advantages:

[0032] The present invention provides a preparation method of a sugar-free traditional Chinese medicine granule, which includes the following steps: weighing traditional Chinese medicine components, crushing half of the Chinese yam and hawthorn as flavoring agents, extracting the volatile oil of tangerine peel and encapsulating it with β-cyclodextrin, mixing the remaining all drugs and decocting three times, combining the decoction liquids, then concentrating, drying, and pulverizing to obtain an extract powder, and finally mixing the obtained components to granulate to obtain the sugar-free traditional Chinese medicine granule. The traditional Chinese medicine granule of the present invention has been deeply studied for many years, and its safety and effectiveness have been verified through experiments. The formula has been improved for many generations, and the ratio has been optimized to ensure the synergistic effect of each component, improve the bioavailability. The preparation method adopts modern extraction technology, retains the activity of the active ingredients, and reduces the toxic and side effects at the same time.

[0033] In the sugar-free traditional Chinese medicine granule of the present invention, astragalus membranaceus is the monarch drug, which belongs to the liver, spleen, lung, and kidney meridians, and has the functions of replenishing qi and consolidating the exterior, arresting sweating and relieving collapse, etc.; Chinese yam replenishes qi and nourishes yin, tonifies the spleen, lung, and kidney; codonopsis pilosula replenishes qi and strengthens the spleen; malt promotes digestion and regulates the middle energizer; dendrobium officinale strengthens the spleen and replenishes qi and promotes fluid production; these four are the ministerial drugs. Hawthorn, tangerine peel, poria cocos, chaenomeles speciosa, and atractylodes macrocephala each have the functions of promoting digestion, regulating qi, removing dampness, and assisting digestion and transportation as the adjuvant drugs. Prepared licorice root strengthens the spleen and stomach and harmonizes various drugs as the guiding drug. Combining with the preparation process further improves the content of the active ingredients of the traditional Chinese medicine components, and significantly improves the effects of the sugar-free traditional Chinese medicine granule in strengthening the spleen and stomach and enhancing immunity. Description of the Drawings

[0034] Figure 1 is the AMS standard curve of normal rat serum;

[0035] Figure 2 is the HE staining diagram of the gastric antrum of normal group mice;

[0036] Figure 3 is the HE staining diagram of the gastric antrum of blank control group mice;

[0037] Figure 4 is the HE staining diagram of the gastric antrum of positive control group mice;

[0038] Figure 5 is the HE staining diagram of the gastric antrum of high-dose group mice of the traditional Chinese medicine granule;

[0039] Figure 6 It is the HE staining diagram of the gastric antrum of mice in the medium-dose group of traditional Chinese medicine granules;

[0040] Figure 7 It is the HE staining diagram of the gastric antrum of mice in the low-dose group of traditional Chinese medicine granules;

[0041] Figure 8 It is the HE staining diagram of the jejunum tissue of mice in the normal group;

[0042] Figure 9 It is the HE staining diagram of the jejunum tissue of mice in the blank control group;

[0043] Figure 10 It is the HE staining diagram of the jejunum tissue of mice in the positive control group;

[0044] Figure 11 It is the HE staining diagram of the jejunum tissue of mice in the high-dose group of medicine granules;

[0045] Figure 12 It is the HE staining diagram of the jejunum tissue of mice in the medium-dose group of medicine granules;

[0046] Figure 13 It is the HE staining diagram of the jejunum tissue of mice in the low-dose group of medicine granules. Specific implementation manner

[0047] The present invention provides a preparation method of sugar-free traditional Chinese medicine granules, which includes the following steps:

[0048] (1) Weigh the following parts by mass of traditional Chinese medicine components:

[0049] Astragalus membranaceus 28 - 32 parts, preferably 30 parts; Chinese yam 18 - 22 parts, preferably 20 parts; Honey-fried licorice root 4 - 8 parts, preferably 6 parts; Poria cocos 13 - 17 parts, preferably 15 parts; Dendrobium officinale 8 - 12 parts, preferably 10 parts; Stir-fried germinated barley 10 - 14 parts, preferably 12 parts; Hawthorn 10 - 14 parts, preferably 12 parts; Steamed papaya 6 - 10 parts, preferably 8 parts; Codonopsis pilosula 18 - 22 parts, preferably 20 parts; Tangerine peel 7 - 11 parts, preferably 9 parts; Atractylodes macrocephala 13 - 17 parts, preferably 15 parts;

[0050] (2) Mix and pulverize half of the parts by mass of Chinese yam and hawthorn, and sterilize to obtain a mixed powder;

[0051] (3) Mix tangerine peel and water, soak, and perform steam distillation for 1 - 2 h to obtain tangerine peel volatile oil and tangerine peel residue aqueous solution;

[0052] The soaking time is 0.5 - 1.5 h, preferably 1 h; The distillation time is preferably 1.5 h;

[0053] (4) Mix the volatile oil of tangerine peel and β-cyclodextrin to obtain an inclusion complex;

[0054] (5) Mix half of the mass portion of Chinese yam, hawthorn, astragalus root, roasted licorice root, poria cocos, dendrobium, stir-fried malt, steamed papaya, codonopsis pilosula, atractylodes macrocephala, and the aqueous solution of tangerine peel residue to obtain mixture 2;

[0055] (6) Mix mixture 2 and water, ultrasonicate and then decoct for 1.5 - 2.5 h, filter, the filtrate is decoction 1, and the filter residue is decoction residue 1;

[0056] The preferred decocting time is 2 h;

[0057] (7) Mix decoction residue 1 and water, decoct for 1 - 2 h, filter, the filtrate is decoction 2, and the filter residue is decoction residue 2;

[0058] The preferred decocting time is 1.5 h;

[0059] (8) Mix decoction residue 2 and water, decoct for 1 - 2 h, filter and take the filtrate as decoction 3;

[0060] The preferred decocting time is 1.5 h;

[0061] (9) Mix decoction 1, decoction 2, and decoction 3, filter to obtain a filtrate, concentrate the filtrate to a relative density of 1.15 - 1.20 to obtain an extract, dry and pulverize to obtain an extract powder;

[0062] The preferred relative density for concentration is 1.18;

[0063] (10) Mix the mixed powder obtained in step (2), the inclusion complex obtained in step (4), the extract powder obtained in step (9), and hydroxypropyl cellulose, granulate to obtain sugar-free traditional Chinese medicine granules.

[0064] In the present invention, the particle size of the pulverization in step (2) is 180 - 220 mesh, preferably 200 mesh;

[0065] The temperature for sterilization is 110 - 120 °C, preferably 115 °C, and the time is 25 - 35 min, preferably 30 min.

[0066] In the present invention, the mass ratio of the tangerine peel and water in step (3) is 1:2 - 4, preferably 1:3.

[0067] In the present invention, the mass ratio of the volatile oil of tangerine peel and β-cyclodextrin in step (4) is 1:6 - 10, preferably 1:8.

[0068] In the present invention, the mass ratio of mixture 2 and water in step (6) is 1:8 - 12, preferably 1:10;

[0069] The power of the ultrasonic wave is 6 - 10 kW, preferably 8 kW, and the time is 10 - 20 min, preferably 15 min.

[0070] In the present invention, the mass ratio of the decoction residue 1 and water in step (7) is 1:6 - 10, preferably 1:8.

[0071] In the present invention, the mass ratio of the decoction residue 2 and water in step (8) is 1:6 - 10, preferably 1:8.

[0072] In the present invention, the filtration in step (9) is cartridge filtration, and the pore size of the filtration is 280 - 320 mesh, preferably 300 mesh;

[0073] The temperature of the concentration is 60 - 85 °C, preferably 75 °C;

[0074] The drying is spray drying. The inlet air temperature of the spray drying is 110 - 130 °C, preferably 120 °C, and the outlet air temperature is 65 - 105 °C, preferably 85 °C.

[0075] In the present invention, the granulation in step (10) is dry granulation. The pressure of the dry granulation is 3 - 5 MPa, preferably 4 MPa, and the rotation speed is 20 - 25 rpm, preferably 23 rpm.

[0076] The present invention provides sugar-free traditional Chinese medicine granules prepared by the preparation method described above. The sugar-free traditional Chinese medicine granules have the effects of strengthening the spleen and nourishing the stomach and enhancing immunity.

[0077] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0078] Example 1

[0079] Preparation of sugar-free traditional Chinese medicine granules:

[0080] (1) Weigh 300 g of astragalus membranaceus, 200 g of Chinese yam, 60 g of roasted licorice root, 150 g of poria cocos, 100 g of dendrobium officinale, 120 g of stir-fried malt, 120 g of hawthorn, 80 g of steamed papaya, 200 g of codonopsis pilosula, 90 g of tangerine peel and 150 g of atractylodes macrocephala;

[0081] (2) Mix 100 g of Chinese yam and 60 g of hawthorn, crush and pass through a 200-mesh sieve, and sterilize at 115 °C for 30 min to obtain a mixed powder;

[0082] (3) Mix 90 g of tangerine peel with 270 g of water, soak for 1 h, and perform steam distillation for 1.5 h to obtain 1.1 g of tangerine peel volatile oil and an aqueous solution of tangerine peel residue;

[0083] (4) 1.1 g of volatile oil from dried tangerine peel was included with 8.8 g of β-cyclodextrin to obtain an inclusion compound;

[0084] (5) 100 g of Chinese yam, 60 g of hawthorn, 300 g of astragalus membranaceus, 60 g of honey-fried licorice root, 150 g of poria cocos, 100 g of dendrobium officinale, 120 g of stir-fried germinated barley, 80 g of steamed papaya, 200 g of codonopsis pilosula, 150 g of atractylodes macrocephala and the aqueous solution of the residue of dried tangerine peel were mixed to obtain mixture 2;

[0085] (6) 10 times the mass of water was added to mixture 2, and it was ultrasonically treated for 15 min at a power of 8 kW, then decocted for 2 h, filtered, the filtrate was decoction liquid 1, and the filter residue was decoction residue 1;

[0086] (7) 8 times the mass of water was added to decoction residue 1, decocted for 1.5 h, filtered, the filtrate was decoction liquid 2, and the filter residue was decoction residue 2;

[0087] (8) 8 times the mass of water was added to decoction residue 2, decocted for 1.5 h, and the filtrate was taken by filtration as decoction liquid 3;

[0088] (9) Decoction liquid 1, decoction liquid 2 and decoction liquid 3 were combined, filtered by a cylindrical filter, the filtrate was obtained by filtration under 300 meshes, concentrated at 75 °C to obtain an extract with a relative density of 1.18, and the extract was spray-dried under the conditions of an inlet air temperature of 120 °C and an outlet air temperature of 85 °C, and pulverized to obtain an extract powder.

[0089] (10) The mixed powder obtained in step (2), the inclusion compound obtained in step (4), the extract powder obtained in step (9) and hydroxypropyl cellulose were mixed, and dry granulation was carried out under the conditions of a pressure of 4 MPa and a rotation speed of 23 rpm to obtain sugar-free traditional Chinese medicine granules.

[0090] Example 2

[0091] Preparation of sugar-free traditional Chinese medicine granules:

[0092] (1) Weigh 290 g of astragalus membranaceus, 200 g of Chinese yam, 55 g of honey-fried licorice root, 140 g of poria cocos, 110 g of dendrobium officinale, 130 g of stir-fried germinated barley, 120 g of hawthorn, 90 g of steamed papaya, 180 g of codonopsis pilosula, 90 g of dried tangerine peel and 170 g of atractylodes macrocephala;

[0093] (2) 100 g of Chinese yam and 60 g of hawthorn were mixed and pulverized through a 200-mesh sieve, and sterilized at 115 °C for 30 min to obtain a mixed powder;

[0094] (3) 90 g of dried tangerine peel was mixed with 270 g of water, soaked for 1 h, and steam-distilled for 1.3 h to obtain 1 g of volatile oil from dried tangerine peel and the aqueous solution of the residue of dried tangerine peel;

[0095] (4) 1 g of volatile oil from dried tangerine peel was included with 8 g of β-cyclodextrin to obtain an inclusion compound;

[0096] (5) 100 g of Chinese yam, 60 g of hawthorn, 290 g of astragalus membranaceus, 55 g of roasted licorice root, 140 g of poria cocos, 110 g of dendrobium officinale, 130 g of stir-fried germinated barley, 90 g of steamed papaya, 180 g of codonopsis pilosula, 170 g of atractylodes macrocephala and the aqueous solution of dried tangerine peel residue were mixed to obtain mixture 2;

[0097] (6) 9 times the mass of water was added to mixture 2, and it was ultrasonically treated for 15 min at a power of 8 kW, then decocted for 2 h, filtered, the filtrate was decoction liquid 1, and the filter residue was decoction residue 1;

[0098] (7) 9 times the mass of water was added to decoction residue 1, decocted for 1.5 h, filtered, the filtrate was decoction liquid 2, and the filter residue was decoction residue 2;

[0099] (8) 9 times the mass of water was added to decoction residue 2, decocted for 1.5 h, and the filtrate was taken by filtration as decoction liquid 3;

[0100] (9) Decoction liquid 1, decoction liquid 2 and decoction liquid 3 were combined, filtered by a cylinder filter, the filtrate was obtained by filtration at 290 mesh, the filtrate was concentrated at 80 °C to obtain an extract with a relative density of 1.15, and the extract was spray-dried under the conditions of an inlet air temperature of 115 °C and an outlet air temperature of 80 °C, and pulverized to obtain an extract powder.

[0101] (10) The mixed powder obtained in step (2), the inclusion compound obtained in step (4), the extract powder obtained in step (9) and hydroxypropyl cellulose were mixed, and dry granulation was carried out under the conditions of a pressure of 5 MPa and a rotation speed of 22 rpm to obtain sugar-free traditional Chinese medicine granules.

[0102] Example 3

[0103] Preparation of sugar-free traditional Chinese medicine granules:

[0104] (1) Weigh 320 g of astragalus membranaceus, 180 g of Chinese yam, 80 g of roasted licorice root, 140 g of poria cocos, 100 g of dendrobium officinale, 120 g of stir-fried germinated barley, 100 g of hawthorn, 80 g of steamed papaya, 200 g of codonopsis pilosula, 80 g of dried tangerine peel and 150 g of atractylodes macrocephala;

[0105] (2) 90 g of Chinese yam and 50 g of hawthorn were mixed and pulverized through a 200-mesh sieve, and sterilized at 115 °C for 30 min to obtain a mixed powder;

[0106] (3) 80 g of dried tangerine peel was mixed with 240 g of water, soaked for 1 h, and steam-distilled for 1.5 h to obtain 0.95 g of volatile oil from dried tangerine peel and an aqueous solution of dried tangerine peel residue;

[0107] (4) 0.95 g of volatile oil from dried tangerine peel was included with 7.6 g of β-cyclodextrin to obtain an inclusion complex;

[0108] (5) 90 g of Chinese yam, 50 g of hawthorn, 320 g of astragalus membranaceus, 80 g of roasted licorice root, 140 g of poria cocos, 100 g of dendrobium officinale, 120 g of stir-fried malt, 80 g of steamed papaya, 200 g of codonopsis pilosula, 150 g of atractylodes macrocephala, and the aqueous solution of dried tangerine peel residue were mixed to obtain mixture 2;

[0109] (6) 12 times the mass of water was added to mixture 2, and it was ultrasonicated for 15 min at a power of 8 kW, then decocted for 2 h, filtered, the filtrate was decoction liquid 1, and the filter residue was decoction residue 1;

[0110] (7) 7 times the mass of water was added to decoction residue 1, decocted for 1.5 h, filtered, the filtrate was decoction liquid 2, and the filter residue was decoction residue 2;

[0111] (8) 8 times the mass of water was added to decoction residue 2, decocted for 1.5 h, and the filtrate was taken by filtration as decoction liquid 3;

[0112] (9) Decoction liquid 1, decoction liquid 2, and decoction liquid 3 were combined, filtered using a cartridge filter, the filtrate was obtained by filtration at 300 mesh, concentrated at 70 °C to obtain an extract with a relative density of 1.18, and the extract was spray-dried at an inlet air temperature of 125 °C and an outlet air temperature of 85 °C, and pulverized to obtain an extract powder.

[0113] (10) The mixed powder obtained in step (2), the inclusion complex obtained in step (4), the extract powder obtained in step (9), and hydroxypropyl cellulose were mixed, and dry granulation was carried out under the conditions of a pressure of 4 MPa and a rotation speed of 23 rpm to obtain sugar-free traditional Chinese medicine granules.

[0114] Experimental Example 1: Effect of traditional Chinese medicine granules on the gastric emptying experiment in mice

[0115] 1. Experimental materials

[0116] 1.1 Experimental reagents and drugs

[0117] Experimental drug: Traditional Chinese medicine granules prepared in Example 1

[0118] Blank control: Blank granules (dry granulated with hydroxypropyl cellulose as the component)

[0119] Positive drug: Jianweixiaoshi tablets, produced by Jiangzhong Pharmaceutical Co., Ltd., batch number: 21061002.

[0120] 1.2 Experimental animals

[0121] 50 ICR mice (SPF grade), weighing 20 ± 2 g, with an equal number of males and females. They were provided by Beijing Vital River Laboratory Animal Technology Co., Ltd., with the certificate numbers: male 20211019Abzz0619000707, female 20211019Abzz0619000738.

[0122] 1.3 Experimental conditions

[0123] The experiment was conducted in a barrier environment laboratory (SPF grade). ICR experimental mice were selected, with free access to water and sufficient food. Room temperature: 22 °C, humidity: 40%, air change rate: 15 times / h, and alternating light and dark lighting with fluorescent lamps.

[0124] 2. Experimental methods

[0125] 2.1 Dose design

[0126] In the experimental drug settings, high, medium, and low doses were set. The medium dose was 5.4 g / kg, the high dose was 10.8 g / kg, and the low dose was 2.7 g / kg; when used, it was prepared into the required concentration with distilled water;

[0127] The blank control was set at a dose of 5.4 g / kg and prepared into the required concentration with distilled water when used;

[0128] The positive drug was set at a dose of 0.94 g / kg and prepared into the required concentration with distilled water when used.

[0129] 2.2 Animal grouping

[0130] Fifty ICR mice, weighing 18 - 22 g, with an equal number of males and females, were randomly divided into 5 groups: blank control group (blank granule group), positive control group (Jianweixiaoshi tablets), high, medium, and low dose groups of traditional Chinese medicine granules. Once a day for 7 consecutive days, after the last administration, the animals were fasted for 24 hours, and then administered again 2 hours before the experiment. Then, each mouse was gavaged with 0.2 mL of 0.04% phenol red aqueous solution. Twenty minutes later, the animals were sacrificed, the stomachs were removed, placed in a beaker, and 10 mL of 0.5 mol / L NaOH aqueous solution was added. The stomach was cut along the greater curvature, and the contents were thoroughly washed into the 0.5 mol / L NaOH aqueous solution. The supernatant was obtained by centrifugation. Using a UV-visible spectrophotometer (wavelength 560 nm), the absorbance measured by mixing 0.2 mL of 0.04% phenol red aqueous solution with 10 mL of distilled water and shaking well was used as the reference value to compare the phenol red absorption in the stomachs of mice in each group. The gastric emptying rate of each group of mice was calculated according to the following formula.

[0131] Gastric emptying rate (%) = (Absorbance reference value of phenol red - Absorbance of phenol red in gastric juice) / Absorbance reference value of phenol red × 100%

[0132] The results of the gastric emptying rate of mice in different treatment groups are shown in Table 1. In the table, "#" indicates P < 0.05 compared with the blank control group, and "##" indicates P < 0.01 compared with the blank control group.

[0133] Table 1 Gastric emptying rate of mice in different treatment groups

[0134] Group Dosage (g / kg) Gastric emptying rate (%) Blank control group 5.4 40.64±11.60 Positive control group 0.94 <![CDATA[63.88±13.97 ## > High-dose traditional Chinese medicine granule group 10.8 <![CDATA[65.53±15.27 ## > Medium-dose traditional Chinese medicine granule group 5.4 <![CDATA[60.17±13.54 ## > Low-dose traditional Chinese medicine granule group 2.7 <![CDATA[52.64±12.98 # >

[0135] As can be seen from Table 1, the traditional Chinese medicine granules prepared by the scheme of this application have an obvious promoting effect on the gastric emptying of mice.

[0136] Experimental Example 2: Effect of traditional Chinese medicine granules on spleen qi deficiency syndrome

[0137] 1 Experimental materials

[0138] 1.1 Experimental reagents and drugs

[0139] Experimental drug: Traditional Chinese medicine granules prepared in Example 1;

[0140] Blank control: Blank granules (prepared by dry granulation with hydroxypropyl cellulose as the component);

[0141] Positive drug: Sliced astragalus membranaceus;

[0142] AMS and CK ELISA kits were provided by Wuhan Elitre Biotech Co., Ltd., batch number: 20211217.

[0143] 1.2 Experimental animals

[0144] SD rats (SPF grade), weighing 200 ± 20 g, half male and half female, animal certificate number 20211109Aazz0619000383, provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0145] 1.3 Experimental conditions

[0146] Carried out in a barrier environment laboratory (SPF grade), SD experimental rats were selected, with free access to water and sufficient food, room temperature: 22 °C, humidity: 40%, air change rate: 15 times / h, and alternating lighting of fluorescent lamps.

[0147] 1.4 Experimental instruments

[0148] MODEL 550 microplate reader, produced by BIO-RAD Company, Japan. AL-104 electronic precision balance, produced by Mettler Toledo Co., Ltd. (Shanghai), with a precision of one ten-thousandth.

[0149] 2. Experimental methods

[0150] 2.1 Dose design

[0151] In the experimental drug settings, high and low doses were set. The medium dose was 5.4 g / kg, the high dose was 10.8 g / kg, and the low dose was 2.7 g / kg. When used, it was prepared into the required concentration with distilled water.

[0152] In the blank control settings, the dose was 5.4 g / kg, and when used, it was prepared into the required concentration with distilled water.

[0153] In the positive drug settings, the dose was 1.35 g / kg, and when used, it was prepared into the required concentration with distilled water.

[0154] 2.2 Animal grouping

[0155] After adaptively feeding SD rats for 7 days, 60 rats were randomly divided into a normal group of 10 rats and a model preparation group of 50 rats by the random number table method. After the model was successfully prepared, the model preparation group was randomly divided into 5 groups, namely the blank control group, the positive control group (astragalus slices), and the high, medium, and low dose groups of traditional Chinese medicine granules, with 10 rats in each group.

[0156] 2.3 Model preparation

[0157] A rat model of spleen qi deficiency was established by the multi-factor method of "controlling diet with five flavors, partial eating, and swimming to exhaustion". The method is as follows:

[0158] ① On the first day of model preparation, 50° white wine was intragastrically administered to rats at a dose of 1 mL / 100 g of rat body weight.

[0159] ② After the second day of model preparation: at 9:00 am, 4℃ vinegar was intragastrically administered to rats at a dose of 1 mL / 100 g of rat body weight, and at the same time, mixed feed was fed at 8% of the body weight for 14 consecutive days. At 3:00 pm, rats were weighted at the tail (10% of the body weight of heavy objects), placed in a water tank with a water depth and water temperature of 20℃, and swam until the endurance limit (the nose tip was submerged under the water for 3 seconds) for 14 consecutive days.

[0160] 2.4 Evaluation criteria for animal models of spleen qi deficiency

[0161] ① Visible diarrhea, and rectal prolapse in severe cases; ② Poor appetite; ③ Emaciation, weight loss; ④ Listlessness, limp limbs, dull hair; ⑤ Preferring to be quiet and curled up; ⑥ Easy fatigue. The first and second items are the main symptoms, and the third and sixth items are the concurrent symptoms.

[0162] When two main symptoms and two concurrent symptoms are simultaneously present, it can be considered that the animal model of spleen qi deficiency is successfully replicated.

[0163] 2.5 Symptom quantification score table for animal models of spleen qi deficiency

[0164] According to the above evaluation criteria for the animal model of spleen qi deficiency syndrome, observe the relevant symptoms of the animals. Record the body weight, food intake and other indicators of the rats before the start of the experiment and on the 15th day respectively, and score according to the following symptom quantification score table for the animal model of spleen qi deficiency syndrome. Exclude the animals that do not meet the criteria. Among them, no symptoms are recorded as 0 points, mild as 1 point, moderate as 2 points, and severe as 3 points.

[0165] 2.6 Dosage and administration method

[0166] After successful modeling, each group of rats was given intragastric administration respectively, once a day for 14 consecutive days. The animals in the normal group and the blank control group were given blank granules dissolved in an equal amount of distilled water. After the administration was completed, the animals were anesthetized and sacrificed, and the serum, spleen and thymus tissues were taken.

[0167] 2.7 Detection indexes

[0168] (1) General condition observation

[0169] During the modeling period, observe and record the changes in the body weight, diet, stools, mental state, behavior changes, etc. of the rats every day. After modeling, measure the body weight once a week and conduct physical signs scoring.

[0170] (2) Determination of serum amylase (AMS) activity.

[0171] After thawing the serum of normal rats at room temperature, it was measured according to the instructions of the amylase (AMS) kit. The serum was diluted with physiological saline into 2-fold, 4-fold, 8-fold, 16-fold, 32-fold, 64-fold, 128-fold, and 256-fold dilution solutions. 0.1 mL of the sample was taken for testing, and a standard curve was drawn to determine the optimal sampling concentration. The samples were diluted and reserved for use as the test samples. Take 2 test tubes and a blank tube, add 0.5 mL of substrate buffer to each, and incubate in a water bath at 37 °C for 5 min; add 0.1 mL of the test sample to the test tube, mix well and incubate in a water bath at 37 °C for 7.5 min; add 0.5 mL of iodine application solution to each tube; add 3.0 mL of double-distilled water to the blank tube, and add 3 mL of double-distilled water to the test tube, mix well, at a wavelength of 660 nm, 1 cm light path, zero with double-distilled water, and measure the absorbance of each tube respectively.

[0172] AMS activity calculation formula:

[0173] Serum AMS activity (U / dL) = (blank OD value - measured OD value) / blank OD value × 80 × dilution factor before sample measurement

[0174] (3) Detection of glucose kinase (CK) content in liver tissue (ELISA method)

[0175] Before the experiment, the reagents and the samples to be tested were placed at room temperature until equilibrium. The absorbance of the blank microplate was read using a microplate reader at the wavelength. In the microwells, the standards and the samples to be tested were added sequentially to each well, and corresponding marks were made. Then, the enzyme-labeled substances were added in sequence and mixed well. The coated microplate was covered with a film and placed at 37 °C. After incubation, the liquid in the wells was completely discarded and the remaining residual liquid in the wells was removed. The wells were rinsed repeatedly with the pre-diluted washing solution for [X] times. Substrate was added to each well in sequence, and the substrate was mixed well. The reaction was carried out in the dark at room temperature. The stop solution was added to each well in sequence and mixed thoroughly to terminate the reaction. The corresponding absorbance values were read using a microplate reader at [wavelength]. The protein content was determined by the Coomassie brilliant blue method. A standard curve was plotted, and the corresponding concentrations of each sample were calculated based on the absorbance values of each sample to be tested.

[0176] (4) Calculate the spleen and thymus coefficients.

[0177] 3. Experimental results

[0178] 3.1 General conditions and body weight

[0179] The results showed that the animals in the normal group had shiny hair, normal activities, good spirits, and normal diet and defecation. Compared with the normal group, after 3 - 4 days of animal modeling, the hair gloss became worse and the activities decreased. After 7 - 8 days, the activities decreased, the spirits were listless, the diet decreased, the animals curled up, the fur became withered and yellow, the stools were unformed and the fecal volume increased, and the body weight gain slowed down. After 2 weeks, symptoms such as diarrhea, reduced diet, poor spirits, and emaciation were visible, and the animals had reduced activities, withered and yellow hair, and abdominal distension. According to the symptom scoring standard for the animal model of spleen qi deficiency, each modeled rat had varying degrees of spleen deficiency symptoms. The successfully modeled rats were randomly divided into 5 groups according to the experimental method and given corresponding drugs.

[0180] Compared with before drug administration, after 1 week of drug administration, the symptoms of spleen qi deficiency in the animals in the blank control group did not change significantly, and the symptoms of some individual animals even worsened. Compared with the blank control group, the positive control group and the high-dose group of traditional Chinese medicine granules had obvious improvement effects on the above-mentioned symptoms of spleen qi deficiency. After 2 weeks of drug administration, the symptoms of the animals in the model group were slightly alleviated but not significantly, and 3 animals died; compared with the blank control group, the positive control group and the high- and medium-dose groups of traditional Chinese medicine granules could significantly alleviate the above-mentioned symptoms of spleen qi deficiency. One rat died in each of the positive control group and the high-dose group of traditional Chinese medicine granules, no rats died in the medium-dose group of traditional Chinese medicine granules, and 2 rats died in the low-dose group of traditional Chinese medicine granules.

[0181] The body weights of rats in different treatment groups before drug administration and 1 week and 2 weeks after drug administration were measured, and the results are shown in Table 2.

[0182] Table 2 Body weights of rats in different treatment groups before drug administration and 1 week and 2 weeks after drug administration

[0183]

[0184] As can be seen from Table 2, compared with the normal group, before drug administration (after modeling), the body weights of animals in each group showed an obvious decreasing trend, but the difference was not significant; there was no obvious difference in the body weights of animals among the drug administration groups. After 1 week of drug administration, compared with the normal group, the body weight of animals in the blank control group showed an obvious decreasing trend, but the difference was not significant. Compared with the blank control group, the body weights of animals in the positive control group and the high-dose traditional Chinese medicine granule group showed an obvious increasing trend, but the difference was not significant. The medium- and low-dose traditional Chinese medicine granules had no obvious improvement effect on the body weight of animals. After 2 weeks of drug administration, the results were similar to those after 1 week of drug administration.

[0185] 3.2 Effects of Traditional Chinese Medicine Granules on the Quantitative Score of Spleen Qi Deficiency in Rats

[0186] The results of the quantitative score of spleen qi deficiency in rats in different treatment groups are shown in Table 3. In the table, "**" indicates P < 0.01 compared with the normal group, "#" indicates P < 0.05 compared with the blank control group, and "##" indicates P < 0.01 compared with the blank control group.

[0187] Table 3 Quantitative Score of Spleen Qi Deficiency in Rats in Different Treatment Groups

[0188]

[0189]

[0190] As can be seen from Table 3, no obvious symptoms of spleen qi deficiency were found in the animals of the normal group, and the score was 0. After modeling, compared with the normal group, the quantitative scores of spleen qi deficiency in animals in each group increased significantly, and the difference was significant. After 1 week of drug administration, the score value of the animals in the model group was still very high. Compared with the normal group, the difference was significant; compared with the model group, the score value of the animals in the positive group decreased significantly, and the difference was significant. The score value of the high-dose group showed an obvious decreasing trend, but the difference was not significant. After 2 weeks of drug administration, compared with the normal group, the score value of the model group showed a certain decreasing trend, but still remained at a relatively high level. Compared with the model group, the positive group and the high-, medium-dose traditional Chinese medicine granule groups could significantly reduce the quantitative score value of spleen qi deficiency, and the difference was significant.

[0191] 3.3 Effects of Different Treatment Groups on the Activity of Serum Amylase (AMS)

[0192] The standard curve of AMS in rat serum is as Figure 1 shown. The activities of serum amylase in rats in different treatment groups are shown in Table 4. In the table, "**" indicates P < 0.01 compared with the normal group, "#" indicates P < 0.05 compared with the blank control group, and "##" indicates P < 0.01 compared with the blank control group.

[0193] Table 4 Activities of Serum Amylase in Rats in Different Treatment Groups

[0194] Group Dosage (g / kg) n Amylase activity (U) Normal group / 10 45.28±5.46 Blank control group 5.4 7 <![CDATA[27.27±4.75 ** > Positive control group 1.35 9 <![CDATA[40.28±6.21 ## > High-dose traditional Chinese medicine granule group 10.8 9 <![CDATA[42.85±7.50 ## > Medium-dose traditional Chinese medicine granule group 5.4 10 <![CDATA[40.78±7.42 ## > Low-dose traditional Chinese medicine granule group 2.7 8 32.37±6.58

[0195] According to Figure 1 and Table 4, it can be seen that compared with the normal group, the AMS activity of the rats in the blank control group was significantly decreased, and the difference was significant. Compared with the blank control group, the positive control group, the high, medium and low dose groups of traditional Chinese medicine granules could significantly increase the serum AMS of rats, and the difference was significant.

[0196] 3.4 Content of Glucokinase (CK) in Liver Tissue of Rats in Different Treatment Groups

[0197] The results of the content of glucokinase (CK) in tissues of rats in different treatment groups are shown in Table 5. In the table, "**" indicates P < 0.01 compared with the normal group, "#" indicates P < 0.05 compared with the blank control group, and "##" indicates P < 0.01 compared with the blank control group.

[0198] Table 5 Content of Glucokinase (CK) in Tissues of Rats in Different Treatment Groups

[0199] Group Dosage (g / kg) n CK (mmol / L) Normal group / 10 1.08±0.20 Blank control group 5.4 7 <![CDATA[2.13±0.27 ** > Positive control group 1.35 9 <![CDATA[1.34±0.24 ## > High-dose traditional Chinese medicine granule group 10.8 9 <![CDATA[1.30±0.22 ## <!-- 10 -->]]> Medium-dose traditional Chinese medicine granule group 5.4 10 <![CDATA[1.35±0.24 ## > Low-dose traditional Chinese medicine granule group 2.7 8 <![CDATA[1.73±0.29 # >

[0200] According to Table 5, it can be seen that compared with the normal group, the CK content in the blank control group was significantly increased, and the difference was significant. Compared with the blank control group, the positive control group, the high, medium and low dose groups of traditional Chinese medicine granules could significantly decrease the CK content in the liver of rats, and the difference was significant.

[0201] 3.5 Spleen and Thymus Indexes of Rats in Different Treatment Groups

[0202] The results of the spleen and thymus indexes of rats in different treatment groups are shown in Table 6. In the table, "**" indicates P < 0.01 compared with the normal group, "#" indicates P < 0.05 compared with the blank control group, and "##" indicates P < 0.01 compared with the blank control group.

[0203] Table 6 Spleen and Thymus Indexes of Rats in Different Treatment Groups

[0204]

[0205] According to Table 6, it can be seen that compared with the normal group, the thymus and spleen indexes in the blank control group were significantly decreased, and the difference was significant. Compared with the blank control group, the positive control group and the high dose group of traditional Chinese medicine granules could significantly increase the thymus index, and the difference was significant; the positive group and the high, medium dose groups of traditional Chinese medicine granules could significantly increase the spleen index, and the difference was significant.

[0206] To sum up, traditional Chinese medicine granules have an obvious improving effect on spleen qi deficiency in rats.

[0207] Experimental Example 3: Therapeutic Effect of Traditional Chinese Medicine Granules on Model Rats with Infantile Anorexia

[0208] 1. Experimental Materials

[0209] 1.1 Experimental Reagents and Drugs

[0210] Experimental drug: Chinese medicine granules prepared in Example 1;

[0211] Blank control: Blank granules (prepared by dry granulation with hydroxypropyl cellulose as a component);

[0212] Positive drug: Xiao'er Qixingcha Granules, produced by Guangzhou Wanglaoji Pharmaceutical Co., Ltd., batch number: 2008017.

[0213] 1.2 Experimental animals

[0214] 70 SPF-grade SD rats, 1-week-old after weaning, weighing 60 ± 10 g, with half males and half females. Certificate number: male, 20220218Aazz0619000355, female, 20220218Aazz0619000347, provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0215] 1.3 Experimental conditions

[0216] Barrier environment laboratory, carried out at SPF level, using SD experimental rats, with free access to water and sufficient food, room temperature: 22 °C, humidity: 40%, air change rate: 15 times / h, and alternating lighting with fluorescent lamps.

[0217] 2. Experimental methods

[0218] 2.1 Dosage design

[0219] High, medium, and low doses were set for the experimental drug. The medium dose was 5.4 g / kg, the high dose was 10.8 g / kg, and the low dose was 2.7 g / kg; it was formulated into the required concentration with distilled water when used;

[0220] A dose of 5.4 g / kg was set for the blank control, and it was formulated into the required concentration with distilled water when used;

[0221] A dose of 1.35 g / kg was set for the positive drug, and it was formulated into the required concentration with distilled water when used.

[0222] 2.2 Animal grouping

[0223] After 7 days of adaptive feeding of SD rats, 60 rats were randomly divided into a blank control group of 10 rats and a model preparation group of 50 rats by the random number table method; after the model was successfully prepared, the model preparation group was randomly divided into 5 groups, namely the blank control group (blank granules), the positive control group (Xiao'er Qixingcha Granules), and the high, medium, and low dose groups of Chinese medicine granules, with 10 rats in each group.

[0224] 2.3 Model preparation

[0225] The model was established by the etiological simulation method. The special modeling feed was composed of high-fat, high-protein and high-sugar components such as fish floss, corn flour, milk powder, soybean powder, white sugar, fresh eggs and fresh fat. The blank control group was fed with conventional feed, and the modeling group was fed with special feed. They were allowed to eat ad libitum and drink freely. The feeding period was 28 days. The food intake and body weight changes of the rats were monitored every day. The criteria for successful model preparation were as follows: the food intake of the rats in the modeling group was reduced by 40-60% on average compared with that of the blank group, and / or the body weight was 10-15% lower than that of the blank group.

[0226] 2.4 Dosage and administration method

[0227] Seven days after successful modeling, the rats in each group were fed with conventional feed. At the same time, according to the designed dose, each group was given intragastric administration once a day for 42 consecutive days. The normal group and the blank control group were given an equal amount of distilled water. After the administration was completed, the animals were anesthetized and sacrificed, and samples were collected. The antrum and jejunum tissues were taken, part of which was fixed with formaldehyde and part was stored at -80 °C for later measurement.

[0228] 3 Detection indexes

[0229] 3.1 Food intake monitoring

[0230] From the start of modeling to the end of administration, the feed intakes of the rats in the blank group and the model group were measured and recorded twice a week, and the changes in the food intakes of the rats in each group were recorded.

[0231] 3.2 Body weight monitoring

[0232] From the start of modeling to the end of administration, the body weights of the rats in the blank group and the model group were measured and recorded twice, and the changes in the body weights of the rats in each group were recorded.

[0233] 3.3 Observation and scoring of HE-stained pathological sections of antrum and jejunum tissues

[0234] The antrum and jejunum tissues were fixed with conventional paraformaldehyde and paraffin sections were made. HE staining was used to observe the pathological damage changes of the antrum and jejunum tissues of the rats in each group, and scoring was performed according to the corresponding pathological change degree.

[0235] Scoring criteria for antrum inflammation degree:

[0236] It was graded according to the density and infiltration depth of chronic inflammatory cells in the mucosal layer.

[0237] 0: There were no more than 5 cells (including lymphocytes, plasma cells, etc. that could not be distinguished under light microscopy) in each high-power field of view. If the number was slightly more than normal, the pathology could be diagnosed as basically normal;

[0238] +: There were fewer chronic inflammatory cells and they were limited to the superficial layer of the mucosa, not exceeding 1 / 3 of the mucosal layer;

[0239] ++: The chronic inflammatory cells are relatively dense, not exceeding 2 / 3 of the mucosal layer;

[0240] +++: The chronic inflammatory cells are dense, occupying the entire mucosal layer.

[0241] 0: No inflammation; +: 1 point; ++: 2 - 3 points; +++: 4 points

[0242] Cavity tissue: The villus length, villus width, and crypt depth were measured under a microscope.

[0243] 4. Experimental results

[0244] 4.1 Model evaluation

[0245] 4.1.1 General situation

[0246] During model establishment and drug administration, the animals in the blank group were active normally, with shiny hair, no abnormalities in diet, defecation, and urination, and in good spirits. During model establishment, after one week of feeding with the special feed, the animals began to lose weight, their hair was less shiny, their activities were basically normal, and their stools became loose. After 3 weeks of model establishment, the above situation improved, which may be related to the animals' adaptation to the special feed.

[0247] 4.1.2 Animal food intake

[0248] Ten animals were selected from the blank group, with 5 males and 5 females, separated into two cages for feeding, 5 animals in each cage. In the model group, 60 animals were actually selected, with 30 males and 30 females, separated into 12 cages for feeding, 5 animals in each cage. The food intake results of the animals in the blank group and the model group during model establishment are shown in Table 7. In the table, "**" indicates P < 0.01 compared with the blank group.

[0249] Table 7 Food intake of animals in the blank group and the model group

[0250]

[0251] According to Table 7, compared with the blank group, after one week of model establishment, the food intake of the animals decreased significantly and continued until 4 weeks after model establishment. The food intake decreased by 47.5%. According to the standard, it indicates that the model establishment was successful.

[0252] 4.1.3 Animal body weight

[0253] The body weight results of the animals in the blank group and the model group during model establishment are shown in Table 8. In the table, "*" indicates P < 0.05 compared with the blank group, and "**" indicates P < 0.01 compared with the blank group.

[0254] Table 8 Body weight of animals in the blank group and the model group

[0255]

[0256] According to Figure 8It can be seen that compared with the blank group, after 1 week of modeling, the body weight of the animals decreased significantly, with a significant difference, which continued until 3 weeks after modeling; in the 4th week of modeling, the body weight of the animals decreased, with a weight reduction of 8.6%, but compared with the blank group, there was no significant difference, which may be related to the animals' adaptation to the special feed and the increase in food intake.

[0257] 4.2 Effects of different treatment groups on the food intake of animals

[0258] Ten normal animals were selected as the normal group, and then 50 animals after modeling were randomly selected and divided into 5 groups: blank control group, positive control group, high, medium, and low dose groups of traditional Chinese medicine granules, with 10 animals in each group, half male and half female. Each group was divided into 2 cages for feeding, and the food intake was calculated. The results are shown in Table 9.

[0259] Table 9 Food intake of animals in different treatment groups

[0260]

[0261]

[0262] According to Table 9, compared with the normal group before administration, the food intake of the animals in the blank control group decreased significantly (decreased by 32.46%). By the end of administration, the food intake recovered somewhat, but still decreased by 32.46% compared with the normal group. Compared with the blank control group, the food intake of the animals in the high and medium dose groups of traditional Chinese medicine granules began to increase significantly 3 weeks after administration. By the end of administration, they increased by 43.58% and 39.10% respectively compared with the blank control group. The effect of the low dose group was relatively weak, and the food intake increased by 19.23% compared with the blank control group. The food intake of the positive control increased by 41.67% compared with the blank control group.

[0263] 4.3 Effects of different treatment groups on the body weight of animals

[0264] The body weight results of animals in different treatment groups are shown in Table 10.

[0265] Table 10 Body weight of animals in different treatment groups

[0266]

[0267]

[0268] According to Table 10, compared with the normal group, the body weight of the animals in the blank control group increased relatively slowly. By the end of administration, the body weight decreased by 11.83%. Compared with the blank control group, the high and medium dose groups of traditional Chinese medicine granules could significantly promote the growth of the animals' body weight. By the end of administration, the body weights increased by 13.42% and 11.14% respectively. The effect of the low dose group was relatively weak, and the body weight increased by 4.82%.

[0269] 4.4 Effects of Different Treatment Groups on Gastric Antrum Pathology of Mice

[0270] 4.4.1 Observation under Light Microscope

[0271] The gastric antrums of mice in different treatment groups were fixed with paraformaldehyde and paraffin sections were made. HE staining was used to observe the pathological damage changes of the gastric antrums of rats in each group. The results are as Figures 2 - 7 shown Figure 2 Figure Figure 3 shows the HE staining map of the gastric antrum of mice in the normal group Figure 4 Figure Figure 5 shows the HE staining map of the gastric antrum of mice in the high-dose traditional Chinese medicine granule group Figure 6 Figure Figure 7 shows the HE staining map of the gastric antrum of mice in the medium-dose traditional Chinese medicine granule group

[0272] According to Figures 2 - 7 it can be seen that the gastric mucosal cells of mice in the normal group are evenly distributed, with normal morphology, and the smooth muscle cells are arranged normally. Compared with the normal group, a large number of inflammations appear in the mucosal layer of the blank control group, the mucosal layer is severely damaged, there are a large number of inflammatory cell infiltrations, and the smooth muscle cells are disordered. Compared with the blank control group, the number of inflammatory cells in the positive control group and the high, medium, and low-dose traditional Chinese medicine granule groups is significantly reduced, and the mucosal structure gradually tends to be complete. Among them, the therapeutic effects of the high and medium-dose traditional Chinese medicine granule groups and the positive control group are the most obvious, approaching the normal group

[0273] 4.4.2 Gastric Antrum Inflammation Degree Scoring

[0274] The results of the gastric antrum inflammation degree scoring of rats in different treatment groups are shown in Table 11. In the table, "**" indicates P < 0.01 compared with the normal group, "#" indicates P < 0.05 compared with the blank control group, and "##" indicates P < 0.01 compared with the blank control group

[0275] Table 11 Gastric Antrum Inflammation Degree Scoring of Rats in Different Treatment Groups

[0276]

[0277]

[0278] According to Table 11, it can be seen that compared with the normal group, the scores of the density and infiltration depth of inflammatory cells in the blank control group are significantly increased, with significant differences. Compared with the blank control group, the high, medium, and low-dose traditional Chinese medicine granule groups and the positive control group can significantly reduce the inflammation degree score value, with significant differences. The high and medium doses have more obvious effects, and the low dose has relatively weak effects

[0279] 4.5 Effects of Different Treatment Groups on Jejunum Tissue Pathology

[0280] 4.5.1 Observation under light microscope

[0281] The jejunum tissues of mice in different treatment groups were fixed with paraformaldehyde and paraffin sections were made. HE staining was used to observe the pathological damage changes of the jejunum tissues of rats in each group. The results are as Figures 8 - 13 shown Figure 8 represents the HE staining diagram of the jejunum tissue of normal group mice Figure 9 represents the HE staining diagram of the jejunum tissue of blank control group mice Figure 10 represents the HE staining diagram of the jejunum tissue of positive control group mice Figure 11 represents the HE staining diagram of the jejunum tissue of high-dose traditional Chinese medicine granule group mice Figure 12 represents the HE staining diagram of the jejunum tissue of medium-dose traditional Chinese medicine granule group mice Figure 13 represents the HE staining diagram of the jejunum tissue of low-dose traditional Chinese medicine granule group mice

[0282] According to Figures 8 - 13 it can be seen that in the jejunum tissue of normal group mice, the intestinal villi are dense, arranged regularly and evenly, there are a few lymphocytes distributed in the villi, the mucosal muscular layer and the submucosa are clearly demarcated, the basic structure is complete, and the cell staining is uniform. Compared with the normal group, the villi in the blank control group are shorter and wider, sparser, with obvious inflammatory cell infiltration, a large number of inflammatory cells in the mucosal muscular layer, and the muscular layer structure is relatively complete with a clear demarcation line. Compared with the blank control group, the intestinal villi in the positive control group and the high, medium-dose traditional Chinese medicine granule groups are significantly longer and the inflammatory cells are significantly reduced; the intestinal villi in the low-dose traditional Chinese medicine granule group are slightly longer and the inflammatory cells are somewhat reduced

[0283] 4.5.2 Effects of different treatment groups on jejunal villi of rats

[0284] The length, width and crypt depth of jejunal villi of rats in different treatment groups were measured. The results are shown in Table 12. In the table, "**" indicates P < 0.01 compared with the normal group, "#" indicates P < 0.05 compared with the blank control group, and "##" indicates P < 0.01 compared with the blank control group

[0285] Table 12 Jejunal villi of rats in different treatment groups

[0286]

[0287] According to Table 12, it can be seen that compared with the normal group, the length of jejunal villi in the blank control group of rats is significantly shortened and thickened, and the crypt depth becomes shallower, with significant differences. Compared with the blank control group, the high, medium and low-dose traditional Chinese medicine granule groups and the positive control group can significantly increase the villus length, with significant differences. The high and medium-dose groups can significantly reduce the villus length and width and increase the crypt depth, with very significant differences

[0288] In summary, the traditional Chinese medicine granules have an obvious improvement effect on the gastrointestinal pathological changes of young rats with anorexia.

[0289] As can be seen from the above embodiments, the present invention provides a preparation method of sugar-free traditional Chinese medicine granules, which includes the following steps: weighing traditional Chinese medicine components, crushing half of the yam and hawthorn as flavoring agents, extracting the volatile oil of tangerine peel and encapsulating it with β-cyclodextrin, mixing and decocting the remaining all drugs three times, combining the decoction liquid, then concentrating, drying, and crushing to obtain an extract powder, and finally mixing the obtained components to granulate to obtain sugar-free traditional Chinese medicine granules. In the sugar-free traditional Chinese medicine granules of the present invention, astragalus membranaceus is the monarch drug, belonging to the liver, spleen, lung, and kidney meridians, with the effects of replenishing qi and consolidating the exterior, astringing sweating and arresting prolapse, etc.; yam replenishes qi and nourishes yin, tonifies the spleen, lung, and kidney; codonopsis pilosula replenishes qi and strengthens the spleen; malt promotes digestion and regulates the middle energizer; dendrobium officinale strengthens the spleen, replenishes qi, and promotes fluid production; these four are the ministerial drugs. Hawthorn, tangerine peel, poria cocos, papaya, and atractylodes macrocephala each have the functions of promoting digestion, regulating qi, removing dampness, and assisting digestion and transportation as the adjuvant drugs. Prepared licorice root strengthens the spleen and stomach and harmonizes various drugs as the envoy drug. Combining with the preparation process further improves the content of active ingredients of the components, and significantly improves the functions of the sugar-free traditional Chinese medicine granules in strengthening the spleen and stomach and enhancing immunity.

[0290] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art of this technology, without departing from the principle of the present invention, several improvements and refinements can still be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing sugar-free Chinese medicine granules, characterized in that: The steps include: (1) Weigh the following parts by mass of the Chinese medicinal components: 28-32 parts of Astragalus, 18-22 parts of Chinese Yam, 4-8 parts of Roasted Licorice, 13-17 parts of Poria, 8-12 parts of Dendrobium, 10-14 parts of Roasted Malt, 10-14 parts of Hawthorn, 6-10 parts of Steamed Papaya, 18-22 parts of Codonopsis, 7-11 parts of Tangerine Peel, 13-17 parts of Atractylodes; (2) mixing and crushing half the mass fraction of Chinese yam and hawthorn, and sterilizing to obtain a mixed powder; (3) mixing tangerine peel and water, soaking, and steam distilling for 1 to 2 hours to obtain tangerine peel volatile oil and tangerine peel residue aqueous solution; (4) mixing tangerine peel volatile oil and β-cyclodextrin to obtain an inclusion compound; (5) mixing half the mass fraction of Chinese yam and hawthorn with an aqueous solution of astragalus, roasted licorice, Poria, dendrobium, roasted malt, steamed papaya, Codonopsis pilosula, Atractylodes macrocephala, and tangerine peel residue to obtain a mixture 2; (6) Mixing mixture 2 and water, decocting for 1.5 to 2.5 h after ultrasonication, filtering, the filtrate is the decoction liquid 1, and the filter residue is the decoction residue 1; (7) Mix the decoction residue 1 and water, decoct for 1 to 2 hours, filter, and the filtrate is the decoction liquid 2, and the filter residue is the decoction residue 2; (8) Mix the decoction residue 2 and water, decoct for 1 to 2 hours, and filter the filtrate to obtain the decoction solution 3; (9) mixing decoction 1, decoction 2 and decoction 3, filtering to obtain a filtrate, concentrating the filtrate to a relative density of 1.15 to 1.20 to obtain an extract, drying, and crushing to obtain an extract powder; (10) The mixed powder obtained in step (2), the inclusion compound obtained in step (4), the extract powder obtained in step (9) and hydroxypropyl cellulose are mixed and granulated to obtain sugar-free Chinese medicine granules.

2. The preparation method according to claim 1, characterized in that: The particle size of the crushed product in step (2) is 180-220 mesh; The sterilization temperature is 110-120° C. and the sterilization time is 25-35 minutes.

3. The preparation method according to claim 1, characterized in that: The mass ratio of the tangerine peel and water mixed in step (3) is 1:2-4.

4. The preparation method according to claim 1, characterized in that: The mass ratio of the tangerine peel volatile oil and beta-cyclodextrin mixed in step (4) is 1:6-10.

5. The preparation method according to claim 1, characterized in that: The mass ratio of the mixture 2 and water in step (6) is 1:8-12; The power of the ultrasound is 6-10 kW, and the time is 10-20 min.

6. The preparation method according to claim 1, characterized in that: The mass ratio of the mixture of the decoction residue 1 and water in step (7) is 1:6-10.

7. The preparation method according to claim 1, characterized in that: The mass ratio of the mixture of the decoction residue 2 and water in step (8) is 1:6-10.

8. The preparation method according to claim 1, characterized in that: The pore size of the filtration in step (9) is 280-320 mesh; The concentration temperature is 60-85°C; The drying is spray drying, the air inlet temperature of the spray drying is 110-130°C, and the air outlet temperature is 65-105°C.

9. The preparation method according to claim 1, characterized in that: The granulation in step (10) is dry granulation, and the pressure of dry granulation is 3-5 MPa and the rotation speed is 20-25 rpm.

10. The sugar-free Chinese medicine granules prepared by the preparation method according to any one of claims 1 to 9, characterized in that: The sugar-free Chinese medicine granules have the effects of strengthening the spleen and stomach and improving immunity.

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