A preparation method and application of Jiao Sanxian formula granules

Abstract

The present invention belongs to the technical field of Chinese medicine formula granules, and specifically relates to a preparation method and application of Jiao Sanxian formula granules. The scorched hawthorn, scorched malt, and scorched Shenqu pieces are mixed in a mass ratio of 1:1:1, and after the mixture is soaked, decocted and filtered, the filtrate is treated to obtain a thick extract, which is dried under reduced pressure and crushed to form a dry extract powder; the obtained dry extract powder is wet granulated. The present invention adopts reduced pressure drying and wet granulation processes, strictly controls the process step parameters, improves the extract yield and chlorogenic acid content of Jiao Sanxian pieces, and the prepared formula granules have a high content of effective ingredients and a small dosage. The finished granules are of excellent quality, and the product quality meets the requirements of the "Chinese Pharmacopoeia", which is specifically manifested in: uniform particle size, high content of alcohol-soluble extracts, impurities and fungi meet the requirements of the pharmacopoeia, and the finished product has high stability and is easy to preserve. Pharmacodynamic experiments were designed to investigate its effects.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine formula granules, and particularly relates to a preparation method and application of Jiao Sanxian formula granules. Background Art

[0002] In the "Ten Lectures on the Use of Medicines", there is a record that "Scorched Shenqu, scorched malt, and scorched hawthorn are collectively called: Scorched Three Immortals, which can enhance each other's ability to digest food and relieve stagnation". Hawthorn, malt, and Liushenqu complement each other and are the best combination of Chinese medicines for digestion and stagnation. According to traditional Chinese medicine experience, the digestion and stagnation effects of these three herbs are enhanced after they are scorched. In order to describe the efficacy of the scorched products of these three herbs, they are called "Scorched Three Immortals".

[0003] The "Jiao Sanxian Concentrated Granules" and "Da Shanzhao Pills" products currently on the market are prone to drug resistance in the body. In the clinical use of traditional Chinese medicine, Jiao Sanxian is often used in combination with other traditional Chinese medicines as an auxiliary medicine. There is no research on the best extraction method, effective substance evaluation and quality standard for this classic formula used alone.

[0004] As a dietary supplement, prebiotics have a beneficial effect on the host by selectively stimulating the growth and activity of one or a few bacterial colonies, thereby improving the host's health. The intake of functional oligosaccharides by the human body leads to an increase in the number of bifidobacteria. Bifidobacteria in the intestine ferment oligosaccharides to produce a large amount of short-chain fatty acids such as acetic acid and lactic acid, which can promote intestinal peristalsis, increase fecal moisture, and maintain a certain osmotic pressure, so it can improve and prevent constipation.

[0005] Most Chinese herbal medicines are usually taken orally and eventually reach the gastrointestinal tract. Most of the active ingredients of Chinese herbal medicines contain water-soluble sugars in the form of glucosides. These compounds are difficult to absorb in the intestines, have low bioavailability, and stay in the intestines for a long time, making them susceptible to the effects of intestinal flora. If the intestinal flora is imbalanced, the beneficial enzymes secreted by bacteria will decrease or their activity will decrease, affecting the metabolic rate and efficiency of the drug, indirectly affecting the concentration of herbal medicines in the blood and affecting the efficacy.

[0006] At this stage, the need for drugs to cooperate with each other to achieve the maximum efficacy is an urgent goal that needs to be studied. Summary of the invention

[0007] The present invention aims to provide a method for preparing Jiao San Xian formula granules.

[0008] To achieve the above purpose, the present invention adopts the following technical solution:

[0009] A method for preparing Jiao Sanxian formula granules comprises the following steps: mixing scorched hawthorn, scorched malt and scorched Shenqu pieces in a mass ratio of 1:1:1, soaking, decocting and filtering the mixture, treating the filtrate to obtain a thick extract, drying under reduced pressure and then crushing to form a dry extract powder; and wet granulating the obtained dry extract powder.

[0010] The mixed pieces are soaked in water for 2-3 hours, decocted for 2-4 times, filtered after decocting, and the filtrate is concentrated to a relative density between 1.10 and 1.25, concentrated under reduced pressure, dried under reduced pressure, and then crushed to form a dry extract powder; wherein, the pressure in the reduced pressure concentration is 0.09MPa and the temperature is 40-60°C; the vacuum degree in the reduced pressure drying is 0.09MPa and the temperature is 40-60°C.

[0011] The mass ratio of the mixed slices to water is 1:10-15.

[0012] The dry extract powder and the auxiliary material are mixed in a mass ratio of 1:0.5-2.5, and then wet granulated. After granulation, the Jiao Sanxian formula granules are obtained by drying at 60°C; wherein the auxiliary material is a wetting agent.

[0013] The wetting agent is 60-100% ethanol or water.

[0014] An application of a method for preparing Jiao Sanxian formula granules, wherein the Jiao Sanxian formula granules prepared by the method are compounded to obtain Jiao Sanxian formula granules containing prebiotics.

[0015] A prebiotic Jiao San Xian formula granule is prepared by mixing the dry extract powder with the prebiotic and auxiliary materials, and then wet granulating the mixture to obtain the prebiotic Jiao San Xian formula granule, wherein the Jiao San Xian content in each 1 g of granule is 0.55-0.75 g / g.

[0016] The prebiotics are one or more of fructooligosaccharides, galacto-oligosaccharides, xylooligosaccharides, isomaltooligosaccharides, soybean oligosaccharides, and inulin;

[0017] The auxiliary material is one or more pharmaceutically acceptable fillers.

[0018] The filler is maltodextrin, sucrose, lactose, mannitol or xylitol.

[0019] The beneficial effects of the present invention are:

[0020] The present invention prepares the existing "Jiao Sanxian" in a specific way, and then adds probiotics, so that after the drug enters the body, it will colonize in the intestine, multiply in large quantities, form a dominant flora, and produce a large amount of enzymes, so as to facilitate the body's absorption of the drug and exert its efficacy; specifically:

[0021] 1. The "Jiao Sanxian" prepared by the present invention is prepared in a specific manner, namely, reduced pressure drying and concentration, wet granulation process, strict control of process step parameters, and use of two index components, namely, paste yield and chlorogenic acid content, to control the extraction conditions of the effective ingredients of Jiao Sanxian, thereby increasing the content of the effective ingredients of Jiao Sanxian and reducing the dosage.

[0022] 2. The present invention adds prebiotics to promote the decomposition of the glycoside components of traditional Chinese medicine in the intestine into aglycones that can be absorbed by the human body, regulate the balance of intestinal microecological flora, promote better absorption and exertion of the effective substances of Jiao Sanxian, and effectively alleviate the drug resistance caused by the lack of flora in the intestine that can decompose the effective ingredients of traditional Chinese medicine.

[0023] 3. The Jiao Sanxian prebiotic formula granules obtained by the method of the present invention have excellent quality, and the product quality meets the requirements of the "Chinese Pharmacopoeia", which is specifically manifested in: uniform particle size, high content of alcohol-soluble extract, impurities and fungi (total aerobic bacteria, total number of molds and yeasts, Escherichia coli, etc.) meet the requirements of the Pharmacopoeia, and the finished product has high stability and is easy to preserve.

[0024] 4. The process of the method of the present invention is simple and reasonable, with low cost, and is suitable for promotion to large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a flow chart of the preparation process of the Jiao Sanxian prebiotic formula granules provided in an embodiment of the present invention.

[0026] Figure 2 This is a diagram showing the water absorption effect of Jiao Sanxian provided in an embodiment of the present invention.

[0027] Figure 3 This is a diagram of the extraction temperature effect provided by an embodiment of the present invention.

[0028] Figure 4 This is a diagram showing the effect of dosing water provided by an embodiment of the present invention.

[0029] Figure 5 This is a rendering of the types of auxiliary materials provided in an embodiment of the present invention.

[0030] Figure 6 This is a diagram showing the effect of auxiliary material dosage provided in an embodiment of the present invention.

[0031] Figure 7 This is a diagram showing the effect of wetting agent concentration provided by an embodiment of the present invention.

[0032] Figure 8 This is a drying temperature effect diagram provided by an embodiment of the present invention.

[0033] Fig. 9 This is a diagram showing the effect of mouse feed dosage provided by an embodiment of the present invention.

[0034] Fig.10 This is a diagram showing the effect of mouse weight changes provided in an embodiment of the present invention. Specific implementation methods

[0035] The present invention is further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the protection scope of the present invention. After reading the contents disclosed in the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the protection scope defined by the present invention.

[0036] Unless otherwise stated, the raw materials, substrates or reagents in the following examples are all commercially available products. If appropriate, they can also be prepared by methods known in the art.

[0037] Instrument information:

[0038] DZ-A / BCIV series vacuum drying oven (Tianjin Test Instrument Co., Ltd.);

[0039] ZXZ rotary vane vacuum pump (Beijing Zhongxing Weiye Century Instrument Co., Ltd.);

[0040] DZKW-4 electronic constant temperature water bath (Beijing Zhongxing Weiye Instrument Co., Ltd.);

[0041] B220 constant temperature water bath (Shanghai Yarong Biochemical Instrument Factory);

[0042] Rotary evaporator RE52CS (Shanghai Yarong Biochemical Instrument Factory);

[0043] SHZ-DⅢ Yuhua brand circulating water vacuum pump (Gongyi Yuhua Instrument Co., Ltd.);

[0044] L-7000 high performance liquid chromatograph (Hitachi, Japan).

[0045] Example 1

[0046] Weigh Jiao Sanxian (by mass ratio, Jiao Shan Hawthorn: Jiao Malt: Jiao Shenqu = 1:1:1), heat and reflux extraction according to the best process optimized by orthogonal test (soak the medicinal materials for 2 hours, add 12 times the amount of water, extract three times at 70℃, each time for 2 hours), concentrate to 100mL under reduced pressure at 60℃, and dry under vacuum conditions at 60℃ for 2 hours to obtain dry extract powder. According to the mass ratio, dry extract powder: maltodextrin = 1:0.5, dry extract powder: oligofructose = 1:0.25, add maltodextrin and oligofructose, add 80% ethanol, granulate through 80 mesh sieve, dry the granules under vacuum conditions at 60℃, granulate, and bag.

[0047] Single factor study on extraction of effective components from Jiao Sanxian

[0048] Soaking time study

[0049] Since the medicinal materials themselves will absorb a certain amount of solvent during the extraction process, the water absorption rate of the medicinal materials should be measured first, and the water absorption should be supplemented during the first extraction to avoid reducing the actual amount of solvent added and affecting the accuracy of the examination.

[0050] Test method: Take 30g of Jiao Sanxian medicinal material (according to the mass ratio, Jiao Hawthorn: Jiao Malt: Jiao Shenqu = 1:1:1), weigh 5 parallel portions in a beaker, add 10 times the mass of the medicinal material water to immerse the medicinal material and soak it, filter out the excess water, weigh it, and calculate the water absorption rate. The results are shown in Figure 2 The experiment showed that the water absorption rate of Jiao Sanxian changed little at 120 minutes. Considering the time saving cost, the optimal soaking time of the medicinal material was determined to be 2 hours.

[0051] Extraction temperature investigation

[0052] Take 30g of Jiao Sanxian medicinal materials (according to the mass ratio, Jiao Hawthorn: Jiao Malt: Jiao Shenqu = 1:1:1), and divide into 5 parallel portions, add 10 times the mass of the medicinal materials with water, control the water temperature at 60, 70, 80, 90, and 100℃ respectively, heat and reflux to extract for 2h, filter, fix the volume, and observe the paste yield. Figure 3 The experiment shows that the paste yield is the highest at 90℃ and decreases at 100℃. Considering energy saving and the possible deterioration of the effective ingredients in Jiao Sanxian at high temperatures, the orthogonal test is conducted under three conditions of 70, 80 and 90℃ as a group of parallel.

[0053] Water dosing test

[0054] Take 30g of Jiao Sanxian medicinal materials (according to the mass ratio, Jiao Hawthorn: Jiao Malt: Jiao Shenqu = 1:1:1), design five parallel experiments, add 8, 10, 12, 14, and 16 times the mass of the medicinal materials, heat and reflux at 80℃ for 1h, filter, fix the volume, and observe the paste yield. Figure 4 The experiment shows that the maximum paste yield is achieved when 10 times the amount of water is added. Considering energy saving and paste yield, 8, 10, and 12 times the amount of water are selected for subsequent orthogonal tests.

[0055] Orthogonal test of extraction of effective components of Jiao Sanxian: four factors and three levels

[0056] Orthogonal test was used to optimize the extraction process conditions of Jiao Sanxian formula granules. According to the experimental results of single factor test, extraction temperature (A), extraction time (B), water addition (C), and extraction times (D) were selected as the factors for investigation, and the comprehensive score of the paste yield and chlorogenic acid content was used as the investigation index. Since the content of effective ingredients in Chinese medicine granules is an important factor in evaluating the quality of Chinese medicine granules, the orthogonal test results were evaluated with chlorogenic acid content accounting for 70% and paste yield accounting for 30%. The experiment was arranged according to the orthogonal test factor levels shown in Table 1. According to the single factor experimental results and literature research, the selected factor levels and orthogonal test schemes are shown in Table 2 below.

[0057] Table 1. Table of factors and levels of orthogonal test for extraction process

[0058]

[0059] According to the design and arrangement of Table 1, 30g of Jiao Sanxian medicinal materials (by mass ratio, Jiao Hawthorn: Jiao Malt: Jiao Shenqu = 1:1:1) were weighed, extracted, filtered, combined, and fixed to volume under corresponding conditions, and the chlorogenic acid content and the yield of the paste were determined respectively. The data of each index were analyzed visually and by variance, and the results are shown in Table 2.

[0060] Table 2 Results of orthogonal test of extraction process

[0061]

[0062]

[0063] Comprehensive score = (cream yield / cream yield max)*0.3+(chlorogenic acid content / chlorogenic acid content max)*0.7

[0064] From Table 2, we can see that the influence of each factor on the comprehensive score is as follows: extraction times > water addition times > extraction time > extraction temperature. In summary, A1B3C3D3 is the best condition, that is, soaking for 2h, adding 12 times of water, extracting at 70℃ for 2h, and extracting three times.

[0065] Granulation single factor test

[0066] Diluent selection

[0067] In order to solve the moisture absorption problem of the formula granules, four common excipients were selected: corn starch, maltodextrin, sucrose, and lactose. Since the amount of excipients and the concentration of wetting agents have not been investigated, the mass ratio of excipients: extract powder = 1:1 is used for wet granulation. The wetting agent is 85% ethanol. The standard is "kneaded into a ball by hand, and scattered when pressed lightly", and the material properties, particle qualification rate, drying condition and solubility are used as evaluation indicators. The results are shown in Figure 5 .

[0068] Conclusion: According to the above results, the solubility and particle forming rate of maltodextrin, sucrose and lactose are all good, but from the perspective of texture, the particles of maltodextrin as an auxiliary material are fuller. At the same time, considering the need to save costs in industrial production, soluble starch was selected as the auxiliary material of Jiao Sanxian formula granules.

[0069] Amount of auxiliary materials

[0070] Using maltodextrin as auxiliary material and 85% ethanol as wetting agent for wet granulation, the dosage range of maltodextrin was investigated with three mass ratios of maltodextrin: extract powder 1:0.5, 1:1, and 1:1.5. The material properties, particle qualification rate, drying condition and solubility were used as evaluation indicators. The results are shown in Figure 6 .

[0071] Conclusion: From the experimental results in the table, it can be seen that when the ratio of extract powder to maltodextrin is 1:1.5, the viscosity and hardness of the prepared material are the best, and the particle forming property, drying condition and solubility are the best. When the ratio is greater than this, the results of various inspection indicators decrease. Considering energy saving, three ratios of extract powder to maltodextrin = 1:0.5, 1:1, and 1:1.5 are selected for subsequent orthogonal tests.

[0072] Alcohol concentration

[0073] Based on the above experiments, the concentration range of the wetting agent was investigated. Different concentrations of ethanol were slowly sprayed for granulation, and the standard for soft material production was "kneaded into a ball by hand, and scattered when pressed lightly". The material properties, particle formation rate, drying conditions, and solubility were used as indicators. The results are shown in Figure 7 .

[0074] Conclusion: According to the results in the table above, when the ethanol concentration is 80%, 85%, and 90%, the viscosity and hardness of the obtained material are better, the particle formation rate is higher, and the drying condition and solubility are better. Therefore, these three concentrations of wetting agents are selected for orthogonal experiments.

[0075] Drying temperature

[0076] Since baking temperature will affect the Jiao Sanxian formula granules, the mass ratio of extract powder: maltodextrin = 1:1.5, 85% ethanol as diluent, was temporarily used to investigate the forming rate, material viscosity, hardness, and solubility of the Jiao Sanxian formula granules at different temperatures. The results are shown in Figure 8 .

[0077] Conclusion: According to the above table, when the drying temperature is 60℃, the particle qualification rate is the best, and the particle viscosity and hardness are good. Considering the energy saving reasons, 50, 55 and 60℃ are selected as the next orthogonal test conditions.

[0078] Orthogonal experiment for pellet making: three factors and three levels

[0079] Orthogonal test was used to optimize the process conditions of Jiao Sanxian formula granules. According to the experimental results of single factor test, diluent dosage (A), alcohol concentration (B), and drying temperature (C) were selected as the factors to be investigated, and the particle qualification rate and comprehensive score of solubility were selected as the indicators to be investigated.

[0080] The experiment was arranged according to the orthogonal test factor levels shown in Table 3. According to the single factor experiment results and literature research, the selected factor levels and orthogonal test scheme are shown in the table below.

[0081] Table 3. Table of factors level of orthogonal test for granulation process

[0082]

[0083] Table 4 Granulation process orthogonal test results

[0084]

[0085]

[0086] According to the test results in Table 4, it was found that A1B1C3 was the best result, that is, dry extract powder: maltodextrin = 1:0.5, alcohol concentration 80%, and drying temperature 60°C. The particles were the best, with the best particle forming rate and full appearance.

[0087] Example 2

[0088] Preparation and determination of Jiao Sanxian standard decoction

[0089] (1) Preparation of Jiao San Xian standard decoction: Weigh 10 g each of three batches of Jiao Shan Xia, Jiao Maiya and Jiao Shen Qu Chinese medicine slices and mix them (respectively marked with batch numbers 1, 2 and 3), add 12 times the weight of the mixture of water to soak for 2 hours, replenish the water absorption capacity, heat to boiling, decoct at 70°C for 2 hours, filter while hot (100 mesh sieve), add 12 times the weight of the morning water to the residue, boil, decoct at 70°C for 2 hours, filter while hot (100 mesh sieve), add 12 times the weight of the morning water to the residue, boil, decoct at 70°C for 2 hours, filter while hot (100 mesh sieve), add Boil 12 times its mass of water, then cook at 70℃ for 2 hours, filter while hot (100 mesh sieve), combine the three filtrates (measure the filtrate paste yield and chlorogenic acid content), and concentrate the obtained filtrate at low temperature and reduced pressure to a thick extract with a relative density of 1.20-1.25 (measured at 60℃), and then dry it under reduced pressure (60℃; vacuum degree 0.09MPa), grind it after drying, and obtain dry extract powder as standard decoction samples (batch numbers 1, 2, 3) for later use.

[0090] (2) Determination of chlorogenic acid content in standard decoction:

[0091] 1) First, determine the chlorogenic acid standard curve, and use the chlorogenic acid standard to accurately prepare the reference solution with concentrations of 10, 20, 30, 40, 50, 60, 70, 80, and 90 μg / mL. Chromatographic column: KromasiL C18 (4.6mm×250mm), mobile phase: acetonitrile: 0.2% acetic acid water = 16:84, column temperature: 25℃, injection volume 20μL, detection wavelength 327nm, flow rate 1.0mL / min. Record the chromatogram, use the peak area (A) as the ordinate and the mass concentration (C) as the abscissa for linear regression. The linear equation is: y=73875x–251553(r=0.9993). The above results show that the mass concentration of chlorogenic acid has a good linear relationship with the peak area within 10-90μg / mL. And the methodological verification was carried out, that is, the precision, stability, repeatability, and sample recovery rate were investigated, and the RSD was less than 2%.

[0092] 2) Determination of chlorogenic acid content in standard decoction: Take the standard decoction samples of each batch number mentioned above, inject them according to the method described in step 1), obtain the peak area value, and substitute it into the linear regression equation to calculate the chlorogenic acid content (see Table 5).

[0093] (3) Determination of the comprehensive score of the standard decoction: Weigh 20 mL of each of the above standard decoction samples accurately, put them into an evaporating dish after constant weight, evaporate them in a water bath, dry them in an oven at 105°C for 2 hours, cool them in a desiccator for 30 minutes, weigh them accurately, calculate the paste rate and chlorogenic acid content, and determine the comprehensive score range of the Jiao Sanxian standard decoction with 70% to 130% of the average comprehensive score. The test results are shown in Table 5.

[0094] Paste yield (%) = (m1-m2) / 20×V / 30×100%·········(1)In formula (1), V (mL) is the volume after constant volume, m2 (g) is the weight of the evaporating dish at constant weight, and m1 (g) is the weight of the evaporating dish after the extract is dried.

[0095] Since the content of effective ingredients in Chinese herbal granules is an important factor in evaluating the quality of Chinese herbal granules, the orthogonal test results were evaluated with chlorogenic acid content accounting for 70% and paste yield accounting for 30%.

[0096] Comprehensive score = (cream yield / cream yield max)*0.3+(chlorogenic acid content / chlorogenic acid content max)*0.7

[0097] Table 5. Determination results of comprehensive scores of Jiao Sanxian standard decoction

[0098]

[0099] Example 3

[0100] Jiao Sanxian Granules containing prebiotics:

[0101] The dry extract powder obtained above is mixed with oligofructose and maltodextrin, and after mixing, wet granulation is performed according to the conventional method (80% ethanol as a wetting agent, drying at 60°C for 15 minutes), sieved through an 80-mesh sieve, and granulated into 240g of granules (batch numbers 1#, 2#, and 3#), and packaged to obtain the finished product. The mass ratio of the dry extract powder obtained above to oligofructose is 1:0.25, and the mass ratio of the dry extract powder obtained above to maltodextrin is 1:0.5.

[0102] Example 4

[0103] (1) Weigh three batches of Jiao Sanxian Chinese medicinal slices, 300 g each, with the mass ratio of Jiao Hawthorn, Jiao Malt and Jiao Shenqu in each batch being 1:1:1, and then add 12 times the mass of water of the Chinese medicinal slices to soak for 2 hours, replenish the water absorption capacity and heat to boiling, boil at 70°C for 2 hours, filter while hot (100 mesh sieve), add 12 times the mass of water to the residue, boil and boil at 70°C for 2 hours, filter while hot (100 mesh sieve), and boil again according to the steps, combine the three filtrates (determine the paste yield and chlorogenic acid content), and concentrate the obtained filtrate at low temperature and reduced pressure to a thick extract with a relative density of 1.20-1.25 (measured at 60°C), and then reduce the pressure to concentrate the obtained thick extract (60°C; vacuum degree 0.09 MPa), and then reduce the pressure to dry (60°C; vacuum degree 0.09 MPa), and then grind after drying to obtain a dry extract powder (alcohol-soluble extract content 48%).

[0104] Alcohol-soluble extract detection method:

[0105] Weigh 3g of the sample into a 250mL conical flask, add 100mL of 80% ethanol, seal it, weigh 245.32g, let it stand for 1h, connect a reflux condenser, heat to boiling, and keep it boiling for 1h. After cooling, remove the conical flask, seal it, weigh it again, make up the lost weight with 80% ethanol, shake it well, filter it with a 0.45 micron drying filter, accurately measure 25mL of the filtrate, place it in an evaporating dish that has been dried to constant weight (R1=158.08g), evaporate it in a water bath, dry it at 105℃ for 3 hours, cool it in a desiccator for 30min, and quickly and accurately weigh it (R2=158.44g). Unless otherwise specified, the content of alcohol-soluble extracts in the sample is calculated based on the dry product (H=48%).

[0106] H=100%*(R2-R1)*4 / 3

[0107] According to the mass ratio of dry extract powder to oligofructose of 1:0.25, 35g of oligofructose was added, and according to the mass ratio of dry extract powder to maltodextrin of 1:0.5, 70g of maltodextrin was added, mixed evenly, wet granulated (80% ethanol as a wetting agent, dried at 60°C for 15 minutes), passed through an 80-mesh sieve, and granulated 240g (batch numbers 1#, 2#, and 3#) was obtained, and packaged to obtain the finished product.

[0108] (2) Properties of the finished Jiao San Xian prebiotic formula granules: dark brown granules; slight odor, light taste, slightly sour.

[0109] (3) Product specifications of Jiao Sanxian prebiotic formula granules: Each 1g of formula granules is equivalent to 1.24g of medicinal pieces.

[0110] (4) Determination of the comprehensive score of Jiao San Xian prebiotic formula granules: Referring to the operation of Preparation Example 1, the comprehensive score of Jiao San Xian prebiotic formula granules was determined and calculated. The results are shown in Table 6.

[0111] Table 6 Determination results of the paste yield and chlorogenic acid content of Jiao Sanxian prebiotic formula granules

[0112]

[0113] Detection of the Jiao San Xian Granules and the Jiao San Xian Granules containing prebiotics obtained above:

[0114] (1) According to the provisions of the 2020 edition of the Chinese Pharmacopoeia, Part IV, General Rules, Item 0104, Granules, the appearance, particle size, moisture, solubility, and filling amount of the Jiao Sanxian Granules obtained in step 1) of Example 2 and the finished Jiao Sanxian Granules containing prebiotics obtained in Example 4 were tested.

[0115] Appearance of the two granules: The finished product is dry, uniform in size and shape, consistent in color, no moisture absorption, no softening, no caking and deliquescence. Particle size: The sum of the mass percentages that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is between 3.2 and 5.5wt%; the moisture content is between 4.87 and 5.41wt%; Solubility: Take 1 bag of the test sample, add 200mL of hot water, stir for 5 minutes, and observe immediately, all melted or slightly turbid; Take 10 bags of the test sample, remove the packaging, accurately weigh the weight of each bag, and record the weight of each bag and the average filling amount. No bag exceeds 1 times the filling amount difference limit, and the filling amount difference is within ±10%.

[0116] This shows that the obtained granules all meet the requirements of the pharmacopoeia.

[0117] (2) According to the lead, cadmium, arsenic, mercury and copper determination method (0406 atomic absorption spectrophotometry or 0412 inductively coupled agent plasma mass spectrometry in the general rules of Part IV of the 2020 edition of the Chinese Pharmacopoeia), the heavy metals and harmful elements (including lead, cadmium, arsenic, mercury and copper) in the Jiao Sanxian granules obtained in step 1) of Example 2 and the Jiao Sanxian granules containing prebiotics prepared in Example 4 were determined.

[0118] Test results:

[0119] The finished product of Jiao Sanxian granules does not contain lead, cadmium, arsenic, mercury, and copper.

[0120] In the finished product of Jiao Sanxian prebiotic formula granules, the lead content is less than 3 mg / Kg, the cadmium content is less than 0.1 mg / Kg, the arsenic content is less than 1 mg / Kg, the mercury content is less than 0.1 mg / Kg, and the copper content is less than 10 mg / Kg.

[0121] This shows that the obtained granules all meet the requirements of the pharmacopoeia.

[0122] (3) According to the microbial limit test method (General Rules 1105, 1106, and 1107 of Part IV of the 2020 edition of the Chinese Pharmacopoeia), the total number of aerobic bacteria, the total number of molds and yeasts, and the number of Escherichia coli in the Jiao Sanxian granules obtained in step 1) of Example 1 and the finished Jiao Sanxian granules containing prebiotics prepared in Example 4 were determined.

[0123] Test results:

[0124] Jiao Sanxian granules and the finished products of Jiao Sanxian granules containing prebiotics are free of Escherichia coli, aerobic bacteria, molds and yeasts.

[0125] It can be seen that the obtained granules meet the requirements of total aerobic bacteria ≤ 500 cfu / g, total mold and yeast count ≤ 50 cfu / g, and no Escherichia coli was detected.

[0126] (4) According to the repose angle test specified in the 2020 edition of the Chinese Pharmacopoeia, the Jiao Sanxian granules obtained in step 1 of Example 2 and the Jiao Sanxian granules containing prebiotics obtained in Example 4 were tested.

[0127] Test results:

[0128] The angle of repose of three batches of granules was tested, and the results were similar, namely 26.6°, 28.7° and 27.1°, which are within the range of 25-30° specified in the pharmacopoeia, so the prepared granules have excellent fluidity.

[0129] (5) According to the extract determination method specified in Item 2201 of the General Rules of Part IV of the 2020 edition of the Chinese Pharmacopoeia, the Jiao Sanxian Granules obtained in Step 1 of Example 1 and the Jiao Sanxian Granules containing prebiotics obtained in Example 2 were prepared.

[0130] Test results:

[0131] The extract contents of the three batches of Jiao Sanxian granules were 48.2%, 49.1% and 48.5% respectively.

[0132] There are no clear indicators for Chinese medicine extracts in the pharmacopoeia. Based on the extract data of this preparation method, it is set that the extract content of Jiao Sanxian prebiotic formula granules shall not be lower than 70% of the average of this experimental data, that is, 34%.

[0133] In summary, the indicators of the granules and prebiotic-containing granules prepared by the present invention meet the requirements of the 2020 edition of the Chinese Pharmacopoeia under the general rules of Part IV, item 0104, for granules.

[0134] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

[0135] Example 5

[0136] Fifty Kunming mice, half male and half female, weighing 12-15 g / mouse, were randomly divided into 5 groups, 10 mice in each group (n=10), including a blank control group, a model group, a positive control group, i.e., a Da Shanzhao Wan group, a Jiao Sanxian granule group (any batch prepared in Example 2), and a Jiao Sanxian granule group containing prebiotics (any batch prepared in Example 3).

[0137] The experiment lasted for 11 days, during which the blank group consumed ordinary feed, and the other groups consumed high-fat feed. Drug treatment began on the second day of the experiment. The positive control group was gavaged with Da Shanzhao pills, and the drug concentration of the positive control group, Jiao Sanxian granule group, and Jiao Sanxian granule group containing prebiotics was 5g / kg. The gavage volume of the five groups was 20mL / kg, and the blank control group and model group were gavaged with distilled water. The drug was administered continuously for 10 days, once a day. During the modeling and treatment period, each group was free to eat and drink water.

[0138] The mental state, food intake, and body weight of the mice were recorded. The mice in the model group were listless, less active, huddled together, had dull yellow fur, swollen abdomen, yellow urine, and sticky, soft, brown-yellow feces. Fig. 9 The figure shows the record of the mouse feed consumption. From the 3rd to the 11th day of the experiment, the blank control group had a significantly reduced food intake compared with the model group. The model group's food intake was less than 30% of the blank control group, and the model was judged to be successful. The food intake of the Jiao San Xian formula granule group containing prebiotics was significantly better than that of the positive control group and the Jiao San Xian group. Fig.10 Shown is the record of weight changes in mice. Comparing the 5 groups, the weight change of the Jiao Sanxian formula granules group containing prebiotics was significantly better than that of the positive control group and the Jiao Sanxian group.

[0139] One hour after the last administration, mice were gavaged with nutritious semisolid paste (40 mL / kg). After 20 minutes, blood was collected from the eye sockets. After the blood was drained out, the mice were killed by cervical dislocation. The abdomen was opened, the cardia and pylorus were ligated, the stomach was taken, and the total weight was weighed after absorbing the water with filter paper. The stomach contents were washed with saline and then dried with filter paper, and the net weight was weighed to calculate the residual rate in the stomach. The small intestine was taken and laid flat on white paper. The total length of the small intestine (cm) and the distance from the pylorus to the front of the charcoal powder (cm) were measured to calculate the small intestine propulsion rate. Calculate according to the following formula:

[0140] Gastric residual rate (%) = (total stomach weight - net stomach weight) / semi-solid paste weight × 100%

[0141] Small intestinal propulsion rate (%) = distance from pylorus to the front of carbon end / total length of small intestine × 100%

[0142] The results are as follows:

[0143] Table 7 Residual rate of gastric contents and small intestinal propulsion rate in mice

[0144]

[0145] Note: n=10, p<0.05, different letters indicate significant differences.

[0146] The larger the value of the small intestinal propulsion rate, the better. After drug treatment, the small intestinal propulsion rate of groups 2C, 3C and 4C was significantly increased compared with the model group, among which the result of group 2C was significantly higher than that of groups 3C and 4C, and there was no significant difference with the blank control. The smaller the value of the gastric residual rate, the better. After drug treatment, the gastric residual rate of groups 2C, 3C and 4C was significantly reduced compared with the model group, among which the result of group 2C was significantly lower than that of groups 3C and 4C. The above data show that after drug treatment, the small intestinal propulsion rate and gastric residual rate of mice with food accumulation model were restored, among which the Jiao Sanxian granules group containing prebiotics had the best treatment effect, and the small intestinal propulsion rate could be restored to normal levels.

[0147] The above results show that treatment with Jiao Sanxian probiotic granules can effectively improve the food intake, body weight, mental state, hair condition, small intestinal propulsion rate and gastric residual rate of mice with food accumulation, and the effect is better than that of the Jiao Sanxian granule group.

Claims

1. A prebiotic-containing Jiao San Xian formula granule for improving food stagnation, characterized in that: The preparation method of the Jiao San Xian formula granules containing prebiotics is as follows: dry extract powder is mixed with prebiotics and auxiliary materials, and the mixture is wet granulated after mixing to obtain the Jiao San Xian formula granules containing prebiotics, wherein the content of Jiao San Xian in each 1 g of granules is 0.55-0.75 g / g; The preparation method of dry extract powder is as follows: scorched hawthorn, scorched malt and scorched Shenqu slices are mixed in a mass ratio of 1:1:1, the mixed slices are soaked in water for 2 hours, 12 times the amount of water is added, and the mixture is extracted at 70°C for 2 hours, and the extraction is performed three times, and the filtrate is concentrated to a relative density between 1.10 and 1.25, and after concentration, the filtrate is concentrated under reduced pressure, dried under reduced pressure, and then crushed to form dry extract powder; wherein, the pressure in the reduced pressure concentration is 0.09MPa and the temperature is 60°C; the vacuum degree in the reduced pressure drying is 0.09MPa and the temperature is 60°C.

2. The Jiao San Xian formula granules containing prebiotics for improving food stagnation according to claim 1, characterized in that: The prebiotics are one or more of fructooligosaccharides, galacto-oligosaccharides, xylooligosaccharides, isomaltooligosaccharides, soybean oligosaccharides and inulin; and the auxiliary materials are one or more pharmaceutically acceptable fillers.

3. The Jiao San Xian formula granules containing prebiotics for improving food stagnation according to claim 2, characterized in that: The filler is maltodextrin, sucrose, lactose, mannitol or xylitol.

4. A method for preparing the Jiao San Xian formula granules containing prebiotics for improving food stagnation according to claim 1, characterized in that: The dry extract powder is mixed with the prebiotics and the auxiliary materials, and after mixing, the mixture is wet granulated to obtain the prebiotic-containing Jiao San Xian formula granules, wherein the content of Jiao San Xian in each 1 g of the granules is 0.55-0.75 g / g; The preparation method of dry extract powder is as follows: scorched hawthorn, scorched malt and scorched Shenqu slices are mixed in a mass ratio of 1:1:1, the mixed slices are soaked in water for 2 hours, 12 times the amount of water is added, and the mixture is extracted at 70°C for 2 hours, and the extraction is performed three times, and the filtrate is concentrated to a relative density between 1.10 and 1.25, and after concentration, the filtrate is concentrated under reduced pressure, dried under reduced pressure, and then crushed to form dry extract powder; wherein, the pressure in the reduced pressure concentration is 0.09MPa and the temperature is 60°C; the vacuum degree in the reduced pressure drying is 0.09MPa and the temperature is 60°C.

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