CN113425697A - Preparation and preliminary pharmaceutical evaluation method of compound qi-tonifying intestine-moistening capsule - Google Patents

Preparation and preliminary pharmaceutical evaluation method of compound qi-tonifying intestine-moistening capsule Download PDF

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CN113425697A
CN113425697A CN202110684076.0A CN202110684076A CN113425697A CN 113425697 A CN113425697 A CN 113425697A CN 202110684076 A CN202110684076 A CN 202110684076A CN 113425697 A CN113425697 A CN 113425697A
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compound
intestine
capsule
moistening
tonifying
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CN113425697B (en
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张晓平
田景振
侯林
崔清华
刘帆
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Shandong University of Traditional Chinese Medicine
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Abstract

The invention belongs to the technical field of traditional Chinese medicines and discloses a preparation method and a preliminary pharmaceutical evaluation method of a compound qi-tonifying intestine-moistening capsule. The preparation method of the compound qi-tonifying intestine-moistening capsule comprises the following steps: adding fructus Cannabis fine powder and semen Pruni fine powder into dry extract powder extracted from radix astragali, radix Codonopsis, rhizoma Polygonati Odorati and fructus Aurantii Immaturus, granulating, adding pectin, and encapsulating to obtain the compound capsule with effects of invigorating qi and moistening intestine. The pectin is added in the invention, the pectin is not absorbed basically after entering the digestive tract, and the pectin forms the peptone after absorbing water, so that the water in the intestines can be kept, and the volume of the excrement in the intestines can be increased, thereby stimulating the intestinal peristalsis to generate defecation, promoting the drug effect, tonifying qi and nourishing yin, increasing the liquid and moistening dryness, promoting qi circulation and removing stagnancy, and loosening the bowel to relieve constipation, so that the invention meets the constipation of the elderly patients caused by deficiency of qi and yin, can relieve the bowels, can improve the whole function of the patients and has the effect of treating diseases and seeking the basis.

Description

Preparation and preliminary pharmaceutical evaluation method of compound qi-tonifying intestine-moistening capsule
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a preparation method and a preliminary pharmaceutical evaluation method of a compound qi-tonifying intestine-moistening capsule.
Background
At present, constipation (constipation) is a common clinical disease, and the prevalence rate of constipation is higher and higher along with the influence of factors such as the change of modern dietary habits and the increase of social life pressure, and particularly the prevalence rate of the constipation of the old is increased year by year. Chronic constipation can lead to a variety of diseases. The chemical medicine is a common method at present for treating constipation, and long-term use of the medicine can cause the regulation disorder of flora in intestinal tracts and generate dependence aggravation of constipation. The traditional Chinese medicine has definite curative effect on the treatment of constipation diseases. However, the existing products containing traditional Chinese medicine components are mostly used for relieving the symptoms of constipation.
Through the above analysis, the problems and defects of the prior art are as follows: the existing intestine moistening preparation can take effect through the action of clearing heat and purging, is easy to damage healthy qi after long-term use, aggravates constipation and has side effect; it has poor effect on constipation due to intestinal dryness, and is not suitable for long-term administration.
Because the existing intestine moistening agent medicine mostly has the defects of stickiness, poor solubility and the like, the technology adopts natural water-soluble dietary fiber pectin as an auxiliary material on the basis of not adding other irritant components, the water absorption multiple of the natural water-soluble dietary fiber pectin is obviously higher than that of the conventional intestine moistening agent, the gastrointestinal motility is increased, and the vivotoxin can be eliminated, so that the intestine moistening agent with small dosage and high bioavailability is prepared. The preparation has improved health promoting effect, and can be taken for a long time.
The difficulty in solving the above problems and defects is:
an appropriate prescription with the functions of relaxing bowel, tonifying qi and yin and combining attack and invigoration is found, and the prescription has homology of medicine and food, can be taken for a long time and can fundamentally improve constipation.
The significance of solving the problems and the defects is as follows:
the compound Chinese patent medicine with high safety and definite curative effect is developed by combining the treatment method of loosening the bowel to relieve constipation and combining attack and supplement of the traditional Chinese medicine and applying the modern preparation process. Therefore, the development of the compound Chinese patent medicine for relaxing bowel without purgative components has higher application value.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a preparation method and a preliminary pharmaceutical evaluation method of a compound qi-tonifying intestine-moistening capsule.
The invention is realized in such a way that a preparation method of a compound capsule for tonifying qi and moistening the intestines comprises the following steps:
step one, extracting raw astragalus, codonopsis pilosula, polygonatum odoratum and immature bitter orange to obtain dry extract powder;
step two, adding the obtained dry extract powder into fructus cannabis fine powder and bunge cherry seed fine powder, taking microcrystalline cellulose as an auxiliary material and ethanol as a wetting agent, and granulating and pelletizing together;
and step three, uniformly mixing the pectin and the micro silica gel powder, mixing the mixture with the prepared particles, and filling the mixture into a capsule shell to obtain the compound qi-tonifying intestine-moistening capsule.
Further, step one, weighing the raw astragalus, the codonopsis pilosula, the polygonatum odoratum and the immature bitter orange according to the proportion of 1:1:1:1 of the prescription, adding 8 times of water, extracting at 100 ℃ for 2 times, extracting for 1 hour each time, combining the two extracting solutions, concentrating and drying to obtain dry extract powder.
Further, in the second step, the dosages of the auxiliary materials and the main materials are as follows: 1: 7.
further, the ethanol concentration was 95%.
Further, the mixing ratio of the particles, pectin and microcrystalline cellulose is as follows: 80:18:2.
Further, the preparation method of the compound qi-tonifying intestine-moistening capsule also comprises the following steps: the environmental humidity of the preparation process is below 76%.
The invention also aims to provide a compound qi-tonifying intestine-moistening capsule, which consists of fructus cannabis, bunge cherry seed, raw astragalus membranaceus, codonopsis pilosula, immature bitter orange, radix polygonati officinalis and pectin;
the fructus cannabis is prepared from the following raw materials in percentage by mass: the Chinese dwarf cherry seeds: raw astragalus root: codonopsis pilosula: immature bitter orange: 1.25:1.25:1:1:1: 1;
the pectin is used as an auxiliary material and accounts for 20% of the total mass of the fructus cannabis, the bunge cherry seed, the raw astragalus membranaceus, the codonopsis pilosula, the immature bitter orange, the radix polygonati officinalis and the pectin.
The invention also aims to provide a preliminary pharmaceutical evaluation method of the compound qi-tonifying intestine-moistening capsule, which comprises the following steps:
and (3) analyzing the pharmacology of the in-vitro bacteriostasis effect of the compound qi-tonifying intestine-moistening capsule on common intestinal bacteria by utilizing the constructed mouse animal model.
Further, the constructed mouse animal model comprises:
160 healthy male pure white mice with the weight of 20 +/-2 g and the SPF level are freely drunk and eaten, and are raised at the room temperature of 22 +/-2 ℃, the humidity: 45% -55%, and feeding normally for 1 week to make the mouse adapt to environment.
Further, the method for analyzing the pharmacology of the in-vitro bacteriostasis effect of the compound qi-tonifying intestine-moistening capsule on common intestinal bacteria comprises the following steps:
(1) in vitro bacteriostasis test;
(2) a mouse intestinal propulsion test;
(3) calculating the intestinal propulsion rate of the constipation mouse;
(4) data processing: software is adopted to carry out variance and statistical analysis, a F test method is adopted to carry out comparison among multiple groups, two-by-two comparison among groups is carried out by a t test method between independent samples, the difference significance among the samples is compared, and the result is obtained
Figure BDA0003123711020000031
The format indicates that α ═ 5 is used as a check level.
Further, the step (1) specifically includes:
(1.1) preparation method of bacteria solid culture medium, putting 6.6g of nutrient agar into a conical flask, adding 200mL of water, completely dissolving, and sterilizing in an autoclave for 15 min; taking out the solution after the solution is cooled to 50-60 ℃, pouring the solution into a sterile culture dish in a sterile environment, placing the solution in an ultra-clean workbench after solidification for ultraviolet sterilization for 15min, wrapping the solution with a preservative film, and placing the wrapped solution in a refrigerator for storage at 4 ℃;
(1.2) preparation method of bacterial liquid culture medium, putting 4.2g MH (B) meat soup powder into a conical flask, adding 200mL water, after complete dissolution, sterilizing in an autoclave for 15 min; taking out the solution after the solution is cooled to 50-60 ℃, and pouring the solution into a sterile culture dish for later use in a sterile environment;
(1.3) preparation of test bacterial suspension, the above bacteria were cultured at 37 ℃ for 24 hours, and then the concentration of the bacterial suspension was adjusted to 1X 10 by using a turbidimetric tube6CFU/mL for standby;
(1.4) an in vitro bacteriostasis test method, which is to take a 96-well plate and transfer each well into 100 mu L of bacterial liquid culture medium by adopting a microdilution method, then continuously transfer 100 mu L of liquid medicine with the concentration of 100mg/mL into the line 1 and carry out gradient dilution to the line 6; setting 7 th behavior positive control group, and adding 10 μ L gentamicin respectively; setting a 8 th behavior negative control group, and adding 100 mu L of sterile physiological saline; 10 mu L of each bacterium liquid is correspondingly added into each hole, and each bacterium is repeated three times; meanwhile, setting a corresponding dilution gradient of the drug and a blank of a culture medium as a blank control group at the rightmost side of the 96-well plate, culturing for 24 hours at 37 ℃, and detecting an OD value at 600nm of an enzyme-labeling instrument;
the step (2) specifically comprises: (2.1) dividing 48 Kunming mice with approximate body weight into 6 groups according to a random number table method, wherein the 6 groups comprise a blank control group, a positive medicine western medicine group, a positive medicine Chinese medicine group and YQRC high, medium and low dose groups; after the mice are fasted and fed with water for 20 hours, corresponding liquid medicine is given, and the dosage is 0.2mL/10 g. After 55min of administration, the carbon powder liquid is perfused according to the dose of 0.2 mL/tube; after 20min, the patient is sacrificed, and the length of the intestinal canal from the pylorus to the ileocecal part is recorded and recorded as the total length of the small intestine; the length of the intestinal canal from the pylorus to the front edge of the ink is recorded as the ink advancing length, and the intestinal advancing rate of each group of mice is calculated according to a formula;
Figure BDA0003123711020000041
(2.2) the first defecation time and the defecation weight of 6h of constipation mice are that 56 Kunming mice with similar physique and weight are divided into 7 groups according to a random digital table method, wherein the 7 groups comprise a blank control group, a model group, a positive medicine western medicine group, a positive medicine Chinese medicine group and YQRC high, medium and low dose groups; except for the blank control group, the other mice were continuously fed with loperamide hydrochloride for 7 days according to the body mass of 5.0mg/kg to manufacture the constipation model. And (5) after the molding is finished, irrigating corresponding liquid medicine into the stomach at the 8 th day, and irrigating distilled water into the stomach of the model group and the blank control group according to the ratio of 0.2mL/10 g. After timing for 55min, the carbon powder liquid is infused into the stomach according to the dosage of 0.2 mL/tube; after the intragastric administration, the mice are normally fed in a single cage, filter paper is laid at the bottom of the cage to collect excrement, a new piece of filter paper is replaced after each excrement collection, and the first black excrement discharge time and the excrement weight within 6 hours of each mouse are recorded;
the constipation mice intestinal propulsion rate of the step (3): and taking 56 Kunming mice with similar body mass, grouping and molding, continuously administering corresponding liquid medicine according to the dose of 0.2mL/10g for 7d, and administering physiological saline to the blank control group and the model group. After the 7 th day of gastric lavage, the mice are fasted and fed with water for 20h, and the intestinal propulsion rate of the mice is calculated according to the dose of the gastric lavage carbon powder liquid of 0.2 mL/mouse.
By combining all the technical schemes, the invention has the advantages and positive effects that: the invention is composed of 6 Chinese medicaments with homology of medicine and food, such as fructus cannabis, bunge cherry seed, raw astragalus root, radix codonopsitis, immature bitter orange, fragrant solomonseal rhizome and the like. The fructus cannabis in the formula is a monarch drug, is sweet, flat and moist, enters the stomach channel of foot yangming and the large intestine channel of hand yangming, and is mainly used for treating dryness-heat of intestines and stomach, constipation caused by body fluid deficiency, dryness-syndrome of stool, dryness-syndrome of moistening and intestine-lubricating. The dwarf cherry seeds are used as ministers to enhance the effect of relaxing bowel. Radix astragali and radix Codonopsis are used as adjuvant drugs to tonify qi and spleen, rhizoma Polygonati Odorati is used to nourish yin and increase fluid, and to invigorate qi to promote the conduction of large intestine, and fluid is used as 'water increasing and boat moving' method, and fructus Aurantii Immaturus is used to lower qi and eliminate food stagnation to strengthen the effect of descending qi and relaxing bowels. Furthermore, fructus Cannabis and semen Pruni can expel qi and fluid, replenish qi and nourish yin, and can make healthy without damaging healthy qi. The formula combines the intestine-moistening and qi-breaking medicines and the qi-tonifying and yin-nourishing medicines, has the effects of tonifying qi and yin, increasing fluid and moistening dryness, promoting qi circulation and removing stagnancy, and relaxing bowel, is suitable for qi and yin deficiency patients with intestine dryness and constipation, and accords with the constipation of the elderly patients caused by qi and yin deficiency. In addition, the pectin is added into the formula as an auxiliary material, so that the gel has a good water absorption and hydration effect, can absorb water in intestinal tracts, increases the volume of intestinal excreta, stimulates the intestinal tracts to generate defecation feeling, and promotes defecation. The whole prescription not only can relax the bowels, but also can improve the whole function of the patient and has the effect of treating diseases and seeking the basis.
The compound capsule for tonifying qi and lubricating intestines provided by the invention has the advantages that the contraction frequency of large and small intestines is increased, the contraction amplitude is increased, the propulsive peristalsis is obviously enhanced, the defecation time is shortened, the defecation quantity is increased, the liquid quantity in an intestinal cavity is obviously increased, the volume is increased, the congestion and reddening of intestinal mucosa are avoided, and the oily luster is obvious.
Drawings
Fig. 1 is a flow chart of a preparation method of the compound qi-tonifying intestine-moistening capsule provided by the embodiment of the invention.
Fig. 2 is a graphical representation of the percent moisture absorption curve for a dry powdered extract provided by an embodiment of the present invention.
Fig. 3 is a graphical illustration of critical rh mapping curve for a pharmaceutical powder provided in accordance with an embodiment of the present invention.
FIG. 4 is a graphical illustration of a critical RH plot for particles provided by an embodiment of the present invention.
Fig. 5 is a schematic diagram of the influence of the compound qi-tonifying intestine-moistening capsule on the intestinal propulsion of a normal mouse.
FIG. 6 is a schematic diagram showing the influence of the compound qi-tonifying intestine-moistening capsule on the first defecation time of a constipated mouse.
Fig. 7 is a schematic diagram of the influence of the compound qi-tonifying intestine-moistening capsule on the defecation weight of a constipation mouse within 6 hours.
FIG. 8 is a schematic diagram showing the effect of the compound qi-tonifying intestine-moistening capsule on the intestinal propulsion of a constipation-treated mouse.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Aiming at the problems in the prior art, the invention provides a preparation method of a compound qi-tonifying intestine-moistening capsule, which is described in detail with reference to the accompanying drawings.
The compound qi-tonifying intestine-moistening capsule provided by the embodiment of the invention consists of fructus cannabis, bunge cherry seed, raw astragalus membranaceus, codonopsis pilosula, immature bitter orange and radix polygonati officinalis.
The fructus cannabis is prepared from the following raw materials in percentage by mass: the Chinese dwarf cherry seeds: raw astragalus root: codonopsis pilosula: immature bitter orange: 1.25:1.25:1:1:1: 1;
the pectin is used as an auxiliary material and accounts for 20% of the total mass of the fructus cannabis, the bunge cherry seed, the raw astragalus membranaceus, the codonopsis pilosula, the immature bitter orange, the radix polygonati officinalis and the pectin.
The preparation method of the compound qi-tonifying intestine-moistening capsule provided by the embodiment of the invention comprises the following steps:
adding fructus Cannabis fine powder and semen Pruni fine powder into dry extract powder extracted from radix astragali, radix Codonopsis, rhizoma Polygonati Odorati and fructus Aurantii Immaturus, granulating, adding pectin, and encapsulating to obtain the compound capsule with effects of invigorating qi and moistening intestine.
As shown in fig. 1, the preparation method of the compound qi-tonifying intestine-moistening capsule provided by the embodiment of the invention comprises the following steps:
s101, extracting raw astragalus, codonopsis pilosula, radix polygonati officinalis and immature bitter orange to obtain dry extract powder;
s102, adding the obtained dry extract powder into fructus cannabis fine powder and bunge cherry seed fine powder, taking microcrystalline cellulose as an auxiliary material and 95% ethanol as a wetting agent, and granulating and pelletizing together;
s103, uniformly mixing the pectin and the micro silica gel powder, mixing the mixture with the prepared particles, and filling the mixture into a capsule shell to obtain the compound qi-tonifying intestine-moistening capsule.
The dosage of the auxiliary materials and the main materials provided by the embodiment of the invention is as follows: 1: 7.
the mixing proportion of the particles, the pectin and the microcrystalline cellulose provided by the embodiment of the invention is as follows: 80:18:2.
The preparation method of the compound qi-tonifying intestine-moistening capsule provided by the embodiment of the invention also comprises the following steps: the environmental humidity of the preparation process is below 76%.
The invention also provides a preliminary pharmaceutical evaluation method of the compound qi-tonifying intestine-moistening capsule, which comprises the following steps:
and (3) analyzing the pharmacology of the in-vitro bacteriostasis effect of the compound qi-tonifying intestine-moistening capsule on common intestinal bacteria by utilizing the constructed mouse animal model.
The constructed mouse animal model comprises the following components:
160 healthy male pure white mice with the weight of 20 +/-2 g and the SPF level are freely drunk and eaten, and are raised at the room temperature of 22 +/-2 ℃, the humidity: 45% -55%, and feeding normally for 1 week to make the mouse adapt to environment.
The method for analyzing the pharmacology of the in-vitro bacteriostatic action of the compound qi-tonifying intestine-moistening capsule on common intestinal bacteria comprises the following steps:
(1) in vitro bacteriostasis test;
(2) a mouse intestinal propulsion test;
(3) calculating the intestinal propulsion rate of the constipation mouse;
(4) data processing: software is adopted to carry out variance and statistical analysis, a F test method is adopted to carry out comparison among multiple groups, two-by-two comparison among groups is carried out by a t test method between independent samples, the difference significance among the samples is compared, and the result is obtained
Figure BDA0003123711020000071
The format indicates that α ═ 5 is used as a check level.
The technical solution of the present invention is further illustrated by the following specific examples.
Example 1:
the invention takes dry extract powder extracted from raw astragalus root, pilose asiabell root, fragrant solomonseal rhizome and immature bitter orange, adds hemp seed fine powder and bunge cherry seed fine powder for granulation, takes repose angle, bulk density and hygroscopicity as indexes, inspects the types and the dosage of auxiliary materials, and adds pectin to be filled into a No. 0 capsule shell. Lays a foundation for the subsequent test of the compound qi-tonifying intestine-moistening capsule.
1 Main instruments and materials
1.1 drugs and reagents
The required drugs and reagents are shown in table 1.
TABLE 1 Experimental drugs and reagents
Figure BDA0003123711020000081
Note: the traditional Chinese medicine decoction pieces conform to the related regulations of various medicines in the first part of the 2015 edition of Chinese pharmacopoeia.
1.2 Main instruments
The required equipment is shown in Table 2.
TABLE 2 Experimental instruments
Figure BDA0003123711020000082
Figure BDA0003123711020000091
2 test methods and results
2.1 investigation of Dry extract powder Properties
2.1.1 Dry extract powder flowability test
The flowability of the dry extract powder is measured by adopting a fixed funnel method, a funnel is fixed on a funnel frame, an outlet at the lowest end of the funnel is ground to be flat, the lowest end of the funnel is at a height of 1.20cm (H) away from horizontal coordinate paper, when the extract powder falls from the funnel, the upper end of a formed medicinal powder cone touches the lower end of the funnel, the radius (R) of the bottom surface of the medicinal powder cone is measured, the angle of repose (alpha) is calculated, 5 times of tests are repeated, the average value is obtained, and the specific data are shown in a table 3.
Calculating the formula:
Figure BDA0003123711020000101
TABLE 3 Angle of repose results for dry extract powders
Figure BDA0003123711020000102
When the angle of repose of the drug powder is 30 ° < α <40 °, it means that the powder has good flowability. As can be seen from table 3, the dry extract powder measured an average angle of repose of 51.90 °, indicating poor powder flowability, and thus increased flowability by granulation.
2.1.2 Dry extract powder hygroscopicity test
Placing the saturated NaCl solution in a dryer and standing for 24 hours at normal temperature, placing the dry extract powder in a weighing bottle which is dried to constant weight, placing the dry extract powder into a weighing bottle with the thickness of 2mm, weighing the dry extract powder and placing the dry extract powder in the dryer, sampling at regular time, weighing the dry extract powder for three times, taking an average value, and drawing a moisture absorption percentage curve of the dry extract powder according to the moisture absorption percentage of the dry extract powder, wherein the moisture absorption percentage curve is shown in table 4 and fig. 2.
Figure BDA0003123711020000103
Table 4 percent moisture absorption of dry extract powder
Figure BDA0003123711020000104
Figure BDA0003123711020000111
As can be seen from Table 4 and FIG. 2, the moisture absorption rate of the dry extract powder after being left standing in a desiccator containing a saturated NaCl solution for 12 hours was > 15%, which indicates that the dry extract powder has a strong moisture absorption property and that the moisture absorption property should be considered to be lowered by adding an auxiliary material.
2.2 granulation Process parameter investigation
2.2.1 selection of the type of adjuvant
Taking 15 parts of dry extract powder, dividing into 5 groups, respectively mixing with different excipient auxiliary materials, wherein the dosage of the excipient auxiliary materials accounts for 10 percent of the dry extract powder, spraying 95 percent ethanol, granulating by using a 20-mesh screen, drying for 1h at the temperature of 60 ℃ in an oven, grading by using a 10-mesh screen, and inspecting various indexes of granules, wherein the moisture absorption percentage test method of the granules is the same as the moisture absorption test of 2.1.2 dry extract powder. The test results are shown in Table 5.
Figure BDA0003123711020000112
The standard of qualified granules is as follows: pass through a 10 mesh screen and fail to pass through a 80 mesh screen.
TABLE 5 selection of adjuvant types
Figure BDA0003123711020000113
As can be seen from Table 5, the soft mass state obtained with dextrin, mannitol and microcrystalline cellulose was good. The mannitol and the microcrystalline cellulose are easy to form after granulation. Compared with hygroscopicity and particle yield, the microcrystalline cellulose granulation effect is more ideal, so microcrystalline cellulose is selected as an auxiliary material for granulation in the experiment.
2.2.2 testing the amount of adjuvant and the concentration of wetting agent
According to the dosage requirement of the prescription, 1.2g of dry extract powder, 1.5g of fructus cannabis powder and 1.5g of semen pruni powder (hereinafter, the mixture of the three powders is collectively called as 'medicine powder') are taken daily. Through preliminary experiments, the capsule shell 0 is used, the loading amount of each capsule shell is 0.5g, calculated by taking 12 capsules per day, the amount of all the auxiliary materials is 1.8g except the medicine powder, wherein about 20 percent of pectin is required to be added before the capsule is finished and then encapsulated, namely about 1.2 g. Therefore, the daily dose of other auxiliary materials is 0.6g at most.
In order to examine the dosage of the auxiliary material microcrystalline cellulose, a proper amount of medicine powder is mixed with the microcrystalline cellulose according to the proportion of 10:1, 8.5:1 and 7:1, ethanol with the concentration of 85 percent, 90 percent and 95 percent is respectively sprayed on 3 parts of each group, the mixture is sieved by a 20-mesh sieve for granulation, and the dosage of the auxiliary material and the concentration of the wetting agent are examined. The results are shown in Table 6.
TABLE 6 microcrystalline cellulose amounts and wetting agent concentrations
Figure BDA0003123711020000121
As can be seen from Table 6, the powder is sensitive to moisture, and when the ratio of the adjuvant to the drug is 10:1 and 8.5:1, the dosage of the adjuvant is small, and the moisture absorption percentage is large, so that the dosage of the adjuvant is 7: 1. The wetting agent concentration is 85% and 90% ethanol, the lumps are generated, the soft material is not easy to loose, 95% ethanol is selected, and the granule yield is high. Thus, finally, the microcrystalline cellulose is granulated with 95% ethanol in a dosage and concentration of the microcrystalline cellulose in a pharmaceutical adjuvant ratio of 7: 1.
2.2.3 particle drying time study
According to preliminary experiments and review of documents, the effect of setting the drying temperature to 60 ℃ is better when drying the particles with high polysaccharide content, so that the drying temperature of the particles is 60 ℃.
And (3) putting the dried particles into a dried weighing bottle, wherein the thickness of the dried particles is about 2mm, weighing the dried particles, putting the weighed particles into a 60 ℃ oven, regularly weighing the particles, and inspecting the influence of different drying times on the water content in the particles. The water content of the granules was calculated by a drying method in the method for measuring water in "Chinese pharmacopoeia" of 2015 edition. The specific results are shown in Table 7.
Figure BDA0003123711020000131
TABLE 7 moisture content in pellets at different drying times
Figure BDA0003123711020000132
The problems of moisture content and production cost in the drying process of the granules are comprehensively considered, and the drying time of the granules is finally determined to be 2 h.
2.3 examination of the Properties of the Capsule contents
Preliminary experiments show that when the pectin accounts for about 20 percent of the total content, the pectin has ideal propelling effect on the intestines of mice, so the prepared particles and the pectin are uniformly mixed according to the ratio of 8:2, the fluidity of the particles added with the pectin is measured by referring to a method of '2.1.1 dry extract powder fluidity test', and the average value of the repose angle is 40.68 degrees after 3 times of parallel tests. In order to make the capsule filling effect more ideal, the experiment considers that a proper amount of superfine silica powder is added to further improve the particle fluidity. The pectin and the micro silica gel account for 20% of the total content, and the pectin and the micro silica gel are mixed uniformly according to a certain proportion and then mixed with the prepared particles (hereinafter referred to as capsule content) to be filled into a capsule shell.
2.3.1 flowability test of Capsule Contents
Mixing the granules, pectin and silica gel micropowder at a ratio of 80:19:1, 80:18:2 and 80:17:3, and determining the flowability of the granules by referring to the flowability test method of 2.1.1 dry extract powder. The results are shown in Table 8.
TABLE 8 influence of amount of aerosil on the flowability of capsule contents
Amount of silica gel micropowder Radius R (cm) H(cm) Tanα Angle of repose alpha (°)
1％ 2.00 1.20 0.60 30.96
2％ 2.45 1.20 0.49 26.06
3％ 2.75 1.20 0.44 23.57
As can be seen from Table 8, the flowability of the contents of the capsule increased with the addition of aerosil, and the flowability was better with the addition of 2% and 3%.
2.3.2 bulk Density test of Capsule Contents
Uniformly mixing the particles, pectin and aerosil according to the proportion of 80:19:1, 80:18:2 and 80:17:3, respectively taking equal amount, respectively filling into a 10mL measuring cylinder, tossing for 50 times on a test bed, reading the volume of the capsule content in the measuring cylinder, and calculating the bulk density of each group. The results are shown in Table 9.
TABLE 9 Effect of Gum silica gel dosage on the bulk Density of Capsule Contents
Figure BDA0003123711020000141
Note: bulk density ρ (g/mL) content mass (g)/content volume (mL)
As can be seen from Table 9, the bulk density of the capsule contents increased and the loading of the capsules increased after addition of aerosil. And the difference between the addition amount of 2% and the addition amount of 3% is not large.
2.3.3 hygroscopicity test of the content of capsules
The particles, pectin and the micro silica gel are uniformly mixed according to the proportion of 80:19:1, 80:18:2 and 80:17:3, the mixture is placed at the temperature of 60 ℃ for 2 hours for drying, and the influence of different dosages of the micro silica gel on the moisture absorption of the capsule content is examined by a determination method under the item of '2.1.2 dry extract powder moisture absorption test'. The results are shown in Table 10.
TABLE 10 Effect of Gum silica gel dosage on hygroscopicity of Capsule contents
Figure BDA0003123711020000142
As can be seen from Table 10, the hygroscopicity of the capsule contents was reduced by adding aerosil, and the hygroscopicity was minimized at the use levels of 2% and 3%, and at the use level of 3%. Comparing the angle of repose, bulk density and hygroscopicity, and adopting the principle of reducing the dosage of auxiliary materials as much as possible, so that 2% of micropowder silica gel is selected as a glidant to be added into the content of the capsule.
2.3.4 examination of critical relative humidity
Precisely weighing 7 parts of each of the medicine powder and the granules, placing the medicine powder and the granules into a weighing bottle with the thickness of about 2mm, placing the bottle in a drier in 7 different humidity environments, and placing the bottle for 7 days at room temperature. The moisture absorption rates of the drug powders and granules were calculated and are shown in table 11. And drawing moisture absorption curves, specifically as shown in fig. 3 and fig. 4.
TABLE 11 hygroscopicity examination of drug powders and granules
Figure BDA0003123711020000151
As is clear from table 11 and fig. 3 and 4, the critical relative humidity of the drug powder is about 76%, the critical relative humidity of the granules is about 82%, and the hygroscopicity of the drug powder after the granulation is reduced. Therefore, in the steps of crushing, mixing and the like of the dry extract, the environmental humidity is below 76%; the ambient humidity should be below 82% during the particle production and packaging steps.
3 in the analysis of the preparation, the dry extract powder is added with the fructus cannabis fine powder and the bunge cherry seed fine powder, the microcrystalline cellulose is taken as the auxiliary material, the dosage is 7:1 (namely 10 percent of the total capsule content), and the 95 percent ethanol is taken as the wetting agent for granulation. Mixing the obtained granules with 18% pectin and 2% colloidal silica, and encapsulating. Meanwhile, the critical relative humidity test can show that the environmental humidity is below 76% in the steps of crushing and mixing the dry extract; during the production and packaging steps of the granules, the environmental humidity is controlled below 82%.
Example 2: compound qi-tonifying intestine-moistening capsule in-vitro bacteriostasis and mouse intestine propulsion experimental study
The compound qi-tonifying intestine-moistening capsule (YQRC) is researched to have the in-vitro bacteriostasis on common intestinal bacteria, defecation and intestinal propulsion on mice. Determining MIC value of the capsule to various common clinical pathogenic bacteria by adopting a microdilution method to evaluate in vitro bacteriostatic activity of the capsule; the influence of the capsule on the intestinal propulsion rate of a normally bred male Kunming SPF-level mouse at the age of 5 weeks and the effects of the capsule on the first defecation time, the defecation weight in 6 hours and the intestinal propulsion rate of a male Kunming constipation mouse at the age of 5 weeks are observed through experiments. The method is used for carrying out preliminary study on pharmacodynamic evaluation of the compound qi-tonifying intestine-moistening capsule.
1 Main instruments and materials
1.1 drugs and reagents
The required drugs and reagents are shown in Table 12.
TABLE 12 Experimental drugs and reagents
Figure BDA0003123711020000161
1.2 Main instruments
The required equipment is shown in Table 13.
TABLE 13 Experimental instruments
Figure BDA0003123711020000162
1.3 test strains and test animals
Staphylococcus aureus methicillin-resistant strain M1233, Staphylococcus aureus methicillin-resistant strain M1805, Klebsiella pneumoniae ATCC13883, Salmonella typhimurium ATCC14028, Bacillus cereus ATCC63303, enterococcus faecalis ATCC29212, Pseudomonas aeruginosa ATCC27853, Micrococcus luteus ATCC10240, all provided by the university microorganism research laboratory. 160 healthy male Kunming pure white mice with the weight of 20 +/-2 g and the SPF (laboratory animal license number: SCXK (Lu) 20140007) are freely drunk and eaten, and are raised at the room temperature of 22 +/-2 ℃, the humidity: 45% -55%, and feeding normally for 1 week to make the mouse adapt to environment.
2 test method
2.1 in vitro bacteriostasis test
2.1.1 preparation method of bacterial solid culture medium
Placing 6.6g of nutrient agar into a conical flask, adding 200mL of water, completely dissolving, and sterilizing in an autoclave for 15 min. And taking out the solution after the solution is cooled to 50-60 ℃, pouring the solution into a sterile culture dish in a sterile environment, placing the solution in an ultra-clean workbench after solidification for ultraviolet sterilization for 15min, wrapping the solution with a preservative film, and storing the wrapped solution in a refrigerator at 4 ℃.
2.1.2 preparation of bacterial liquid Medium
Putting 4.2g MH (B) bouillon powder into a conical flask, adding 200mL water, completely dissolving, and sterilizing in an autoclave for 15 min. And taking out the solution after the solution is cooled to 50-60 ℃, and pouring the solution into a sterile culture dish for later use in a sterile environment.
2.1.3 preparation of the laboratory bacterial liquid
Each of the above-mentioned bacteria was cultured at 37 ℃ for 24 hours, and then the concentration of the bacterial solution was adjusted to 1X 10 by using a turbidimetric tube6CFU/mL is ready for use.
2.1.4 in vitro bacteriostasis test method
By using the microdilution method, a 96-well plate is taken, 100 mu L of the bacterial liquid culture medium under the item of 2.1.2 is transferred into each well, then 100 mu L of the liquid medicine with the concentration of 100mg/mL is continuously transferred into the 1 st row, and the liquid medicine is subjected to gradient dilution to the 6 th row. A7 th behavior positive control group was set, and 10. mu.L of gentamicin was added to each group. The 8 th row negative control group was set and 100. mu.L of sterile physiological saline was added. 10 μ L of each bacterial suspension should be added to each well, and each bacteria is repeated three times. Meanwhile, a corresponding dilution gradient of the drug and a blank of a culture medium are arranged on the rightmost side of the 96-well plate and are used as a blank control group, the culture is carried out for 24 hours at the temperature of 37 ℃, the OD value is detected at the position of 600nm of an enzyme-labeling instrument, and the statistical result is observed by combining with naked eyes.
2.2 intestinal propulsion test in mice
2.2.1 Normal mouse intestinal Productivity
According to the random number table method, 48 Kunming mice with approximate body weight are divided into 6 groups, including blank control group (distilled water), positive western medicine group (phenolphthalein tablets 0.030g/kg), positive Chinese medicine group (Xiangdan Qing 0.243g/kg) and YQRC high, medium and low dose groups (1.820 g/kg, 0.910g/kg and 0.455g/kg respectively). After the mice are fasted and fed with water for 20 hours, corresponding liquid medicine is given, and the dosage is 0.2mL/10 g. The carbon powder liquid for stomach irrigation is administrated at a dose of 0.2 mL/tube after 55min of administration. After 20min, the patient is sacrificed, and the length of the intestinal canal from the pylorus to the ileocecal part is recorded and recorded as the total length of the small intestine; the length of the intestinal canal from the pylorus to the front edge of the ink is recorded as the ink propulsion length, and the intestinal propulsion rate of each group of mice is calculated according to a formula.
Figure BDA0003123711020000181
2.2.2 Constipation mice time to first defecation and weight of 6h defecation
According to the random digital table method, 56 Kunming mice with similar physique and weight are divided into 7 groups, including a blank control group (distilled water), a model group (loperamide hydrochloride 0.25mg/mL), a positive drug western drug group (phenolphthalein tablets 0.030g/kg), a positive drug Chinese drug group (Xiangdan Qing 0.243g/kg) and YQRC high, medium and low dose groups (1.820 g/kg, 0.910g/kg and 0.455g/kg respectively). The constipation model was made by feeding flupamide hydrochloride to the remaining mice with 5.0mg/kg body mass for 7 consecutive days except for the blank control group to which distilled water was given. And (5) after the molding is finished, irrigating corresponding liquid medicine into the stomach at the 8 th day, and irrigating distilled water into the stomach of the model group and the blank control group according to the ratio of 0.2mL/10 g. After timing for 55min, the carbon powder liquid for stomach irrigation is filled according to the dosage of 0.2 mL/tube. After the gavage, the mice are normally fed in a single cage, the filter paper is laid at the bottom of the cage to collect excrement, a new piece of filter paper is replaced after each excrement collection, and the first black excrement discharge time and the excrement weight within 6 hours of each mouse are recorded.
2.2.3 Constipation rate of intestinal motility in mice
And taking 56 Kunming mice with similar body mass, grouping and molding according to the method of step 2.2.2, continuously administering corresponding liquid medicine according to 0.2mL/10g dosage for 7d, and administering physiological saline to the blank control group and the model group. After 7 days of gavage, the mice were fasted with water for 20 hours, and the mice were gavaged with charcoal powder solution at a dose of 0.2 mL/mouse, sacrificed after 20 minutes, and the intestinal tracts were removed and the intestinal transit rate of the mice was calculated in the same manner as under "2.2.1".
2.2.4 data processing
SPSS 22.0 software and Graphpad Prism 8.0 software are adopted to carry out variance and statistical analysis, F test method is adopted to compare a plurality of groups, t test method is adopted to compare every two groups of groups
Figure BDA0003123711020000192
The format indicates that α ═ 5 is used as a check level.
3 results of the test
3.1 results of in vitro bacteriostatic test
As can be seen from the results in Table 14, the bacteria grew well in the negative control group, the positive control group did not grow significantly, and the blank group of the medium was free from contamination. The compound qi-tonifying intestine-moistening capsule has better broad-spectrum antibacterial action: the minimum inhibitory concentration MIC for Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus strain M1233 is 3.125mg/mL, the MIC for methicillin-resistant Staphylococcus aureus strain M1805, Pseudomonas aeruginosa, Bacillus cereus, enterococcus faecalis and Micrococcus luteus is 6.25mg/mL, and the MIC for Salmonella typhimurium is 25 mg/mL.
TABLE 14 external bacteriostatic results of FUFANGYIQIRUNCHANG Capsule (n ═ 3)
Figure BDA0003123711020000191
Note: +: turbid culture medium: clarification of the culture Medium
3.2 results of intestinal propulsion test in mice
3.2.1 intestinal propulsion action on Normal mice
The results in table 15 and fig. 5 show that the capsule has significant difference in intestinal propulsion rate of normal mice compared with the blank control group in the high, medium and low dose groups (P <0.05, P < 0.01). And the intestinal propulsion effect of the high-dose group is better than that of the two positive groups.
TABLE 15 influence of FUFANGYIQIRUNCHANG Capsule on intestinal propulsion of normal mice: (
Figure BDA0003123711020000201
n＝8)
Figure BDA0003123711020000202
Note: compared with the blank control group, the composition of the composition,△P<0.05，△△P<0.01
3.2.2 Effect on the first defecation time and the defecation weight of 6h of constipated mice
As can be seen from Table 16 and FIG. 7, in the first stool passage time experiment, the time taken by the constipation model group mice is significantly longer than that of the blank control group, and the stool weight of the model group mice is 6h lower than that of the blank control group (P < 0.05), indicating successful modeling. The first black excrement discharge time of the mice in the high, medium and low dose administration groups of the compound qi-tonifying intestine-moistening capsule is shorter than that of the model group (P is less than 0.05, and P is less than 0.01), the excrement weight of the mice in the high dose and medium dose YQRC groups is higher than that of the model group (P is less than 0.05, and P is less than 0.01), and the difference is significant. And the first black excrement discharge and 6h excrement discharge effects of the YQRC high-dose administration group mice are superior to those of the positive western medicine group.
TABLE 16 influence of Qi-benefiting intestine-moistening capsules on the first defecation time and weight of 6h in constipated mice: (
Figure BDA0003123711020000203
n＝8)
Figure BDA0003123711020000204
Figure BDA0003123711020000211
Note: compared with the blank control group, the composition of the composition,△P<0.05; in contrast to the set of models,*P<0.05，**P<0.01
3.2.3 intestinal propulsive action on Constipated mice
The results in Table 17 show that the average intestinal propulsion rate of the mice in the constipation model group is significantly lower than that in the blank control group (P is less than 0.05), indicating that the modeling is successful. The intestinal propulsion rate of the compound qi-tonifying intestine-moistening capsule in the high, medium and low dose administration group mice is higher than that in the constipation model group (P is less than 0.01). And the intestinal propulsion rate of the compound qi-tonifying intestine-moistening capsule to constipation mice is higher than that of the positive western medicine group.
TABLE 17 influence of Qi-benefiting and intestine-moistening capsules on intestinal propulsion of constipation mice (B)
Figure BDA0003123711020000212
n＝8)
Figure BDA0003123711020000213
Note: compared with the blank control group, the composition of the composition,△P<0.05，△△P<0.01; in contrast to the set of models,*P<0.05，**P<0.01
4 the TCM considers that constipation can be classified into excessive heat and fluid deficiency type, yin-cold stagnation type, qi-blood and fluid deficiency type, etc. The main treatment scheme for common qi deficiency type constipation of the elderly patients is to regulate qi and blood circulation, so as to achieve the effects of tonifying qi and nourishing yin, promoting qi circulation and removing food stagnation, and relaxing bowel.
The test result proves that the compound qi-tonifying intestine-moistening capsule has better broad-spectrum antibacterial effect and has the inhibiting effect on various common bacteria in intestinal tracts. The capsule has the effects of promoting the intestinal propulsion rate of mice and the defecation amount of the mice within 6h, relaxing bowel, and conforming to the treatment scheme of senile constipation caused by deficiency of qi, blood and body fluid, and has definite curative effect.
The above description is only for the purpose of illustrating the present invention and the appended claims are not to be construed as limiting the scope of the invention, which is intended to cover all modifications, equivalents and improvements that are within the spirit and scope of the invention as defined by the appended claims.

Claims (10)

1. A preparation method of a compound qi-tonifying intestine-moistening capsule is characterized by comprising the following steps:
step one, extracting raw astragalus, codonopsis pilosula, polygonatum odoratum and immature bitter orange to obtain dry extract powder;
step two, adding the obtained dry extract powder into the fructus cannabis fine powder and the bunge cherry seed fine powder according to the prescription amount, taking microcrystalline cellulose as an auxiliary material and ethanol as a wetting agent, and granulating and pelletizing together;
and step three, uniformly mixing the pectin and the micro silica gel powder, mixing the mixture with the prepared particles, and filling the mixture into a capsule shell to obtain the compound qi-tonifying intestine-moistening capsule.
2. The method for preparing the compound qi-tonifying and intestine-moistening capsule as claimed in claim 1, wherein in the first step, the raw astragalus, the codonopsis pilosula, the polygonatum odoratum and the immature bitter orange are weighed according to the proportion of 1:1:1:1, 8 times of water is added, extraction is carried out at 100 ℃ for 2 times, each time lasts for 1 hour, the two extracting solutions are combined, and the dry extract powder is obtained through concentration and drying.
3. The method for preparing the compound capsule for benefiting qi and moistening intestine according to claim 1, wherein in the second step, the dosages of the auxiliary materials and the main materials are as follows: 1: 7; the ethanol concentration is 95%.
4. The preparation method of the compound qi-tonifying intestine-moistening capsule as claimed in claim 1, wherein the mixing ratio of the granules, pectin and microcrystalline cellulose is as follows: 80:18:2.
5. The method for preparing the compound qi-tonifying and intestine-moistening capsule according to claim 1, wherein the method for preparing the compound qi-tonifying and intestine-moistening capsule further comprises: the environmental humidity of the preparation process is below 76%.
6. A compound qi-tonifying intestine-moistening capsule is characterized in that the compound qi-tonifying intestine-moistening capsule is composed of fructus cannabis, bunge cherry seed, raw radix astragali, radix codonopsitis, immature bitter orange, radix polygonati officinalis and pectin;
the fructus cannabis is prepared from the following raw materials in percentage by mass: the Chinese dwarf cherry seeds: raw astragalus root: codonopsis pilosula: immature bitter orange: 1.25:1.25:1:1:1: 1;
the pectin is used as an auxiliary material and accounts for 20% of the total mass of the fructus cannabis, the bunge cherry seed, the raw astragalus membranaceus, the codonopsis pilosula, the immature bitter orange, the radix polygonati officinalis and the pectin.
7. The preliminary pharmaceutical evaluation method of the compound qi-tonifying intestine-moistening capsule according to claim 6, wherein the preliminary pharmaceutical evaluation method of the compound qi-tonifying intestine-moistening capsule comprises:
and (3) analyzing the pharmacology of the in-vitro bacteriostasis effect of the compound qi-tonifying intestine-moistening capsule on common intestinal bacteria by utilizing the constructed mouse animal model.
8. The preliminary pharmaceutical evaluation method of FUFANGYIQIRUNCHANG Capsule as claimed in claim 7, wherein said constructed mouse animal model comprises:
160 healthy male pure white mice with the weight of 20 +/-2 g and the SPF level are freely drunk and eaten, and are raised at the room temperature of 22 +/-2 ℃, the humidity: 45% -55%, and feeding normally for 1 week to make the mouse adapt to environment.
9. The preliminary pharmacological evaluation method of the compound qi-tonifying and intestine-moistening capsule according to claim 7, wherein the method for analyzing the pharmacology of the in vitro bacteriostatic action of the compound qi-tonifying and intestine-moistening capsule on common intestinal bacteria comprises the following steps:
(1) in vitro bacteriostasis test;
(2) a mouse intestinal propulsion test;
(3) calculating the intestinal propulsion rate of the constipation mouse;
(4) data processing: software is adopted to carry out variance and statistical analysis, a F test method is adopted to carry out comparison among multiple groups, two-by-two comparison among groups is carried out by a t test method between independent samples, the difference significance among the samples is compared, and the result is obtained
Figure FDA0003123711010000021
The format indicates that α ═ 5 is used as a check level.
10. The preliminary pharmaceutical evaluation method of the compound qi-tonifying intestine-moistening capsule according to claim 9, wherein the step (1) specifically comprises:
(1.1) preparation method of bacteria solid culture medium, putting 6.6g of nutrient agar into a conical flask, adding 200mL of water, completely dissolving, and sterilizing in an autoclave for 15 min; taking out the solution after the solution is cooled to 50-60 ℃, pouring the solution into a sterile culture dish in a sterile environment, placing the solution in an ultra-clean workbench after solidification for ultraviolet sterilization for 15min, wrapping the solution with a preservative film, and placing the wrapped solution in a refrigerator for storage at 4 ℃;
(1.2) preparation method of bacterial liquid culture medium, putting 4.2g MH (B) meat soup powder into a conical flask, adding 200mL water, after complete dissolution, sterilizing in an autoclave for 15 min; taking out the solution after the solution is cooled to 50-60 ℃, and pouring the solution into a sterile culture dish for later use in a sterile environment;
(1.3) preparation of test bacterial suspension, the above bacteria were cultured at 37 ℃ for 24 hours, and then the concentration of the bacterial suspension was adjusted to 1X 10 by using a turbidimetric tube6CFU/mL for standby;
(1.4) an in vitro bacteriostasis test method, which is to take a 96-well plate and transfer each well into 100 mu L of bacterial liquid culture medium by adopting a microdilution method, then continuously transfer 100 mu L of liquid medicine with the concentration of 100mg/mL into the line 1 and carry out gradient dilution to the line 6; setting 7 th behavior positive control group, and adding 10 μ L gentamicin respectively; setting a 8 th behavior negative control group, and adding 100 mu L of sterile physiological saline; 10 mu L of each bacterium liquid is correspondingly added into each hole, and each bacterium is repeated three times; meanwhile, setting a corresponding dilution gradient of the drug and a blank of a culture medium as a blank control group at the rightmost side of the 96-well plate, culturing for 24 hours at 37 ℃, and detecting an OD value at 600nm of an enzyme-labeling instrument;
the step (2) specifically comprises: (2.1) dividing 48 Kunming mice with approximate body weight into 6 groups according to a random number table method, wherein the 6 groups comprise a blank control group, a positive medicine western medicine group, a positive medicine Chinese medicine group and YQRC high, medium and low dose groups; after the mice are fasted and fed with water for 20 hours, corresponding liquid medicine is given, and the dosage is 0.2mL/10 g. After 55min of administration, the carbon powder liquid is perfused according to the dose of 0.2 mL/tube; after 20min, the patient is sacrificed, and the length of the intestinal canal from the pylorus to the ileocecal part is recorded and recorded as the total length of the small intestine; the length of the intestinal canal from the pylorus to the front edge of the ink is recorded as the ink advancing length, and the intestinal advancing rate of each group of mice is calculated according to a formula;
Figure FDA0003123711010000031
(2.2) the first defecation time and the defecation weight of 6h of constipation mice are that 56 Kunming mice with similar physique and weight are divided into 7 groups according to a random digital table method, wherein the 7 groups comprise a blank control group, a model group, a positive medicine western medicine group, a positive medicine Chinese medicine group and YQRC high, medium and low dose groups; except for the blank control group, the other mice were continuously fed with loperamide hydrochloride for 7 days according to the body mass of 5.0mg/kg to manufacture the constipation model. And (5) after the molding is finished, irrigating corresponding liquid medicine into the stomach at the 8 th day, and irrigating distilled water into the stomach of the model group and the blank control group according to the ratio of 0.2mL/10 g. After timing for 55min, the carbon powder liquid is infused into the stomach according to the dosage of 0.2 mL/tube; after the intragastric administration, the mice are normally fed in a single cage, filter paper is laid at the bottom of the cage to collect excrement, a new piece of filter paper is replaced after each excrement collection, and the first black excrement discharge time and the excrement weight within 6 hours of each mouse are recorded;
the constipation mice intestinal propulsion rate of the step (3): taking 56 Kunming mice with similar body mass, grouping and molding, continuously administering corresponding liquid medicine according to 0.2mL/10g dosage for 7d, and administering physiological saline to a blank control group and a model group; after the 7 th day of gastric lavage, the mice are fasted and fed with water for 20h, and the intestinal propulsion rate of the mice is calculated according to the dose of the gastric lavage carbon powder liquid of 0.2 mL/mouse.
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