CN114191476B - Traditional Chinese medicine composition for dredging collaterals and eliminating hemorrhoids and preparation method thereof - Google Patents

Abstract

The invention discloses a traditional Chinese medicine composition for promoting digestion and eliminating hemorrhoids and a preparation method thereof, belongs to the technical field of traditional Chinese medicine compositions, and particularly discloses the following raw materials in parts by weight: 7-12 parts of rose mallow, 4-9 parts of common achyranthes herb, 1-6 parts of humifuse euphorbia herb and 1-6 parts of garden burnet root. Meanwhile, the preparation method comprises the following steps: weighing the raw materials, soaking in water, decocting and extracting for 2 times, then combining the filtrates, concentrating to thick paste with the relative density of 1.24-1.26 at 60 ℃, then adding auxiliary materials, uniformly mixing, granulating, drying and subpackaging to obtain the traditional Chinese medicine composition for activating qi and removing the hemorrhoids. The traditional Chinese medicine composition provided by the invention has the functions of resisting bacteria, diminishing inflammation, relieving pain, stopping bleeding and improving small intestine movement, and can effectively treat swelling pain and bleeding of hemorrhoids. Meanwhile, the product is prepared into the granules for removing hemorrhoids, so that the technical effects of safe and efficient medicine, controllable quality, convenient clinical medication, convenient carrying and storage and the like are achieved.

Description

Traditional Chinese medicine composition for dredging collaterals and eliminating hemorrhoids and preparation method thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine composition for removing blood stasis and treating hemorrhoids and a preparation method thereof.

Background

Hemorrhoids are common diseases located at the anus part and can be caused at any age, but the incidence rate is higher and higher along with the increase of the age, and the incidence rate of the hemorrhoids is very high in the common saying that 'nine hemorrhoids for ten people'. The hemorrhoids can be divided into internal hemorrhoids, external hemorrhoids and mixed hemorrhoids according to the difference of the occurrence parts. The main manifestations of the disease are swelling and pain, hematochezia, which can be classified into painless, intermittent and hematochezia after defecation, blood dripping during defecation or bloody strips on toilet paper, constipation, alcohol drinking or irritating food eating can aggravate the symptoms of hemorrhoids.

Therefore, how to provide a hemorrhoid-eliminating product is a problem which needs to be solved by the technical personnel in the field.

Disclosure of Invention

In view of the above, the invention provides a traditional Chinese medicine composition for promoting digestion and eliminating hemorrhoids and a preparation method thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

a traditional Chinese medicine composition for removing blood stasis and hemorrhoids comprises the following raw materials in parts by weight:

7-12 parts of rose mallow, 4-9 parts of common achyranthes herb, 1-6 parts of humifuse euphorbia herb and 1-6 parts of garden burnet root.

Preferably, the feed comprises the following raw materials in parts by weight:

9 parts of rose mallow, 6 parts of common achyranthes herb, 3 parts of humifuse euphorbia herb and 3 parts of garden burnet root.

Has the advantages that: the flos Urenae Lobatae is root or whole plant of flos Urenae Lobatae or coarse leaf flos Urenae Lobatae of Malvaceae. Sweet, pungent and cool in nature. It enters spleen and lung meridians. The chemical components mainly comprise kaempferol (1), rutin (2), quercetin (3), afzerin (4), astragalin (5), tiliroside (6), camptothecine (kaempferol-3-O-B-D-vicinal glucopyranosyl-7-0-a-L-rhamnoside, 7), kaempferol-7-O-alpha-L-rhamnoside (8), kaempferol-7-O-alpha-L-rhamnose-4-O-beta-D-rebuke glucopyranoside (9) and rhodioside (10). Has the effects of dispelling wind, promoting diuresis, promoting blood circulation, relieving swelling, and clearing away heat and toxic materials. Can be used for treating common cold, rheumatalgia, dysentery, diarrhea, stranguria syndrome, leukorrhagia, menoxenia, traumatic injury with swelling and pain, sore and furuncle, sore and wound due to venomous snake.

The herba Polygoni Cymosi is whole plant of radix Achyranthis bidentatae of Amaranthaceae. Bitter and sour in taste, slightly cold in nature. It enters liver, lung and bladder meridians. The main ingredients are ecdysterone (ecdysterone), echinacoside (achyranophylla saponin) A and echinacoside B. And alkaloids, triacontanol (tritriacontanol), and the like. Has the effects of promoting blood circulation, removing blood stasis, inducing diuresis, treating stranguria, clearing away heat and relieving exterior syndrome. It is commonly used for amenorrhea, dysmenorrhea, menoxenia, traumatic injury, rheumatic arthralgia, gonorrhea, edema, leukorrhagia due to damp-heat, fever due to exogenous pathogenic factor, malaria, pharyngalgia, furuncle, carbuncle, and carbuncle.

The herba Euphorbiae Humifusae is dry whole plant of Euphorbia humifusa or Euphorbia maculata of Euphorbiaceae, and has a nature and taste of Xin Ping, and enters liver and large intestine meridians. Sanguisorba contains various flavonoids such as kaempferol, quercetin and glucoside, and also contains polyphenol acid components such as gallic acid and ellagic acid. Has the effects of clearing away heat and toxic materials, cooling blood, stopping bleeding, promoting diuresis and eliminating jaundice. Can be used for treating dysentery, diarrhea, hemoptysis, hematuria, hematochezia, metrorrhagia, furuncle, carbuncle, swelling, and jaundice due to damp-heat pathogen.

Sanguisorba officinalis, name of traditional Chinese medicine. Is dried root of sanguisorba officinalis or sanguisorba longifolia belonging to Rosaceae. Bitter, sour, astringent and slightly cold in nature. It enters liver and large intestine meridians. The sanguisorba contains more medicinal chemical components, mainly comprising gallic acid, saponin, polysaccharide, flavonoid and catechin; 4-O- β -D-rebuke glucopyranos-1-yl-5-kish-3-methoxybenzoic acid methyl ester; 4-trimethyl arachidic acid; (40-8) -fisetinol catechin and the like. Has effects of cooling blood, stopping bleeding, removing toxic substance and healing sore. Can be used for treating hematochezia, hemorrhoidal bleeding, bloody dysentery, metrorrhagia, scald due to hot water and fire, carbuncle, swelling, and sore.

The composition for removing the hemorrhoids through the ventilation and the elimination of the tiny hemorrhoids does not contain medicinal materials which are marked with toxicity in legal standards and proved to be toxic by modern toxicology, does not contain eighteen antagonisms and nineteen incompatibilities, and the dosage of each medicinal material does not exceed the standard specification. The prescription is designed for treating hemorrhoids with syndromes of downward flow of damp-heat and qi stagnation and blood stasis, and is prepared by taking the effects of clearing away heat and toxic materials, promoting blood circulation to remove swelling, dredging the meridian, relieving pain and relaxing bowel. Can be used for treating anal swelling and pain, pruritus, numbness, hematochezia, and prolapse of hemorrhoid. It is suitable for patients with first, second, third and fourth stage internal hemorrhoid, inflammatory external hemorrhoid, and thrombosed external hemorrhoid in modern medicine.

A preparation method of a traditional Chinese medicine composition for removing blood stasis and hemorrhoids comprises the following steps:

weighing the raw materials, adding water, decocting and extracting for 2 times, combining the filtrates, concentrating to obtain thick paste with the relative density of 1.24-1.26 at the temperature of 60 ℃, adding auxiliary materials, uniformly mixing, granulating, drying and subpackaging to obtain the traditional Chinese medicine composition for activating qi and eliminating hemorrhoids.

Preferably, the mass ratio of the water to the raw material is 6:1.

Preferably, the soaking temperature is normal temperature, and the soaking time is 30min.

Preferably, the decoction time is 1h.

Preferably, the auxiliary materials comprise dextrin and sodium carboxymethyl starch, and the mass ratio of the dextrin to the sodium carboxymethyl starch is 9:1.

Preferably, the mass ratio of the thick paste to the auxiliary materials is 1.

Preferably, the drying comprises the steps of:

drying the granulated material at 70-75 deg.C for 2 hr, sieving with 14 mesh sieve, grading, and drying at 70-75 deg.C until the water content is below 6%.

Has the advantages that: the invention adopts water decoction for extraction, does not influence the curative effect of the original decoction, ensures and shortens the production period, reduces the cost of energy consumption and the like, and is more suitable for industrial production.

According to the technical scheme, compared with the prior art, the traditional Chinese medicine composition for removing hemorrhoids through dredging and removing blood stasis and the preparation method thereof are provided, and the traditional Chinese medicine composition provided by the invention has the functions of resisting bacteria, diminishing inflammation, relieving pain, stopping bleeding and improving small intestine movement, and can effectively treat hemorrhoidal bleeding. In order to ensure the clinical curative effect and overcome the inconvenience of decoction and carrying, the invention develops preparation research on the proved prescription of the medicine and prepares the medicine into the particles for removing hemorrhoids by dredging micro, thereby achieving the technical effects of safe and high-efficiency medicine, controllable quality, convenient clinical medication, convenient carrying, storage and the like.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 is a diagram of thin-layer chromatography identification of quercetin, wherein A is sample A, B is sample B, C is sample C, D is quercetin control, and E is negative control of herba Euphorbiae Humifusae and flos Urenae Lobatae;

FIG. 2 is a gallic acid thin layer chromatography identification chart, wherein A is sample A, B is sample B, C is sample C, D is gallic acid control, and E is negative control of herba Euphorbiae Humifusae and flos Urenae Lobatae;

FIG. 3 is a drawing showing the morphologic effect of colorectal tissues of rats in each group, wherein A is a blank control group, a model B control group, a fructus Sophorae pill group C, a hemorrhoid treating group D, a hemorrhoid treating group E and a hemorrhoid treating group F;

FIG. 4 is a photograph of a rat taken with a light microscope showing a cardiac stained section, wherein part a is a blank control group taken out of dose for 24 hours, part b is a blank control group taken out of dose for 14 days, part c is a high dose group taken out of dose for 24 hours, and part d is a high dose group taken out of dose for 14 days;

FIG. 5 is a photograph of a rat taken with a light microscope showing a liver stained section, wherein part a is a blank control group which is stopped taking the drug for 24 hours, part b is a blank control group which is stopped taking the drug for 14 days, part c is a high dose group which is stopped taking the drug for 24 hours, and part d is a high dose group which is stopped taking the drug for 14 days;

FIG. 6 is a photograph taken with a light microscope of a stained section of rat spleen, wherein part a is a blank control group and is stopped taking the drug for 24 hours, part b is a blank control group and is stopped taking the drug for 14 days, part c is a high dose group and is stopped taking the drug for 24 hours, and part d is a high dose group and is stopped taking the drug for 14 days;

FIG. 7 is a photograph of a lung stained section of a rat taken with a light microscope, wherein part a is a blank control group and is stopped taking the drug for 24 hours, part b is a blank control group and is stopped taking the drug for 14 days, part c is a high dose group and is stopped taking the drug for 24 hours, and part d is a high dose group and is stopped taking the drug for 14 days;

FIG. 8 is a photograph taken with a light microscope of a rat trachea-stained section, wherein part a shows that the drug is stopped for 24 hours in the blank control group, part b shows that the drug is stopped for 14 days in the blank control group, part c shows that the drug is stopped for 24 hours in the high dose group, and part d shows that the drug is stopped for 14 days;

FIG. 9 is a photograph of a rat taken with a light microscope showing a stained section of the kidney, wherein part a is the control blank taken for 24 hours, part b is the control blank taken for 14 days, part c is the high dose taken for 24 hours, and part d is the high dose taken for 14 days;

FIG. 10 is a photograph of a rat taken from a gastric staining section taken with a light microscope, wherein part a is a blank control group and is stopped taking the drug for 24 hours, part b is a blank control group and is stopped taking the drug for 14 days, part c is a high dose group and is stopped taking the drug for 24 hours, and part d is a high dose group and is stopped taking the drug for 14 days;

FIG. 11 is a photograph taken with a light microscope of a stained section of rat's esophagus, in which part a is a blank control group and is stopped taking the drug for 24 hours, part b is a blank control group and is stopped taking the drug for 14 days, part c is a high dose group and is stopped taking the drug for 24 hours, and part d is a high dose group and is stopped taking the drug for 14 days;

FIG. 12 is a photograph of a rat taken with a light microscope showing a small intestine stained section, wherein part a is a blank control group and is stopped taking the drug for 24 hours, part b is a blank control group and is stopped taking the drug for 14 days, part c is a high dose group and is stopped taking the drug for 24 hours, and part d is a high dose group and is stopped taking the drug for 14 days;

FIG. 13 is a photomicrograph of a stained colon section of a rat, where part a is a control blank taken for 24 hours, part b is a control blank taken for 14 days, part c is a high dose taken for 24 hours, and part d is a drug taken for 14 days;

FIG. 14 is a photograph taken with a light microscope of a stained section of the thymus of a rat, wherein part a is the drug withdrawal of the blank control group for 24 hours, part b is the drug withdrawal of the blank control group for 14 days, part c is the drug withdrawal of the high dose group for 24 hours, and part d is the drug withdrawal for 14 days;

FIG. 15 is a photomicrograph of an ovarian stained section of a rat, wherein part a is a placebo run out for 24 hours, part b is a placebo run out for 14 days, part c is a high dose run out for 24 hours, and part d is a high dose run out for 14 days;

FIG. 16 is a photomicrograph of a stained section of the uterus of a rat, where part a is the placebo group stopped taking the drug for 24 hours, part b is the placebo group stopped taking the drug for 14 days, part c is the high dose group stopped taking the drug for 24 hours, and part d is the high dose group stopped taking the drug for 14 days;

FIG. 17 is a photograph of a stained testis section taken with a microscope, wherein part a is a control blank taken for 24 hours, part b is a control blank taken for 14 days, part c is a high dose taken for 24 hours, and part d is a control high dose taken for 14 days;

FIG. 18 is a photograph of epididymal staining section of rat with a microscope, in which part a is a blank control group and stops drug administration for 24 hours, part b is a blank control group and stops drug administration for 14 days, part c is a high dose group and stops drug administration for 24 hours, and part d is a high dose group and stops drug administration for 14 days;

FIG. 19 is a photomicrograph of an adrenal stained section of a rat in which portion a is a blank control group at 24 hours off, portion b is a blank control group at 14 days off, portion c is a high dose group at 24 hours off, and portion d is a high dose group at 14 days off;

FIG. 20 is a photograph of a rat taken from a stained section of the submaxillary gland under a microscope, in which part a is a blank control group and is stopped taking the drug for 24 hours, part b is a blank control group and is stopped taking the drug for 14 days, part c is a high dose group and is stopped taking the drug for 24 hours, and part d is a high dose group and is stopped taking the drug for 14 days;

FIG. 21 is a photograph of a rat taken with a light microscope showing a stained section of arterial blood vessel, wherein part a is a blank control group and is stopped for 24 hours, part b is a blank control group and is stopped for 14 days, part c is a high dose group and is stopped for 24 hours, and part d is a high dose group and is stopped for 14 days.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

The preparation method of the traditional Chinese medicine composition for removing the hemorrhoids by dredging the micron comprises the following raw materials in parts by weight:

900g of rose mallow, 600g of common achyranthes herb, 300g of humifuse euphorbia herb, 300g of garden burnet root

A preparation method of a traditional Chinese medicine composition for removing blood stasis and hemorrhoids comprises the following steps:

extracting with water for 2 times, soaking in 6 times of water for 0.5 hr, decocting for 1 hr, and filtering to obtain filtrate; adding 6 times of water for 2 times, decocting for 1 hour, filtering, combining the filtrates, concentrating into thick paste with the relative density of 1.24-1.26 (60 ℃), adding a proper amount of dextrin and carboxymethyl starch sodium, uniformly mixing, granulating, drying, and subpackaging to obtain the traditional Chinese medicine composition.

Example 2

A traditional Chinese medicine composition for removing blood stasis and hemorrhoids comprises the following raw materials in parts by weight:

54Kg of rose mallow, 36Kg of common achyranthes herb, 18Kg of humifuse euphorbia herb and 18Kg of garden burnet root.

A preparation method of a traditional Chinese medicine composition for removing hemorrhoids through removing blood stasis comprises the following steps:

placing the above medicinal materials in a multifunctional TQ3000 extraction tank, adding 6 times of water, soaking for 30min, decocting and extracting for 2 times, each time for 1 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.24-1.26 (60 deg.C), adding dextrin 37.8kg and carboxymethyl starch sodium 4.2kg, mixing in CHE-400 trough mixer, making into soft material, granulating with YK160EC swing granulator, wet granulating, drying at 70-75 deg.C for 2 hr with reciprocating granule automatic drying line, sieving with 14 mesh sieve, drying to water content below 6%, granulating with EYH-2000 mixer, packaging with DX DK40VI automatic granule packaging machine, and packaging.

Three batches of A, B, C are continuously produced according to the preparation process, the yield is 96.8-97.7%, and therefore, the preparation process provided by the invention is reasonable and feasible in conditions and is suitable for large-scale production.

The technical effects are as follows:

1. quercetin detection

Taking 10g of the product obtained in the example 2, grinding, adding 50ml of 70% ethanol, carrying out ultrasonic treatment for 30 minutes, filtering, evaporating the filtrate to be nearly dry, adding 15ml of water into the residue to dissolve the residue, adding 20ml of diethyl ether to carry out shaking extraction, discarding the ethyl ether solution, adding 5ml of hydrochloric acid into the aqueous solution, placing the aqueous solution in a water bath to carry out hydrolysis for 1 hour, taking out the solution, rapidly cooling, carrying out shaking extraction for 2 times by using diethyl ether, 20ml of each time, combining the diethyl ether extract, washing by using 20ml of water, discarding the aqueous solution, evaporating the ethyl ether solution to dryness, and adding 1ml of methanol into the residue to dissolve the residue to obtain a sample solution.

And preparing negative control solution by the same method by taking 10g of negative control samples of humifuse euphorbia herb and prunus persica flower. Adding methanol into quercetin control solution to obtain 1mg solution per 1ml solution as control solution.

Performing thin layer chromatography (2020 edition of Chinese pharmacopoeia, general rules of the four parts 0502), sucking 10 μ l of test solution and 2 μ l of control solution, respectively spotting on the same silica gel G thin layer plate, spreading with toluene-ethyl acetate-formic acid (4.5). As a result, as shown in FIG. 1, the degree of separation and the reproducibility were good.

2. Gallic acid detection

Taking the test solution. And preparing negative control solution by the same method by taking 10g of negative control samples lacking the garden burnet and the humifuse euphorbia herb. Adding methanol to obtain gallic acid control solution containing 1mg per 1ml, and making into control solution.

The test was performed by thin layer chromatography (0502, national pharmacopoeia 2020 edition, four general guidelines), in which 10. Mu.l of the test solution and 5. Mu.l of the control solution were spotted on the same silica gel G thin layer plate, developed with toluene-ethyl acetate-formic acid (6. Spots of the same color appear in the chromatogram of the test solution at positions corresponding to those in the chromatogram of the control solution. As shown in FIG. 2, the results showed that the separation degree and reproducibility were good, and the negative control did not interfere.

3. Stability test

The test method comprises the following steps: (1) Long-term stability test: the A, B, C samples obtained in example 2 are stored at room temperature under the condition of clinical medicine package, and are examined once in month of January, march and June except for one examination in month of the same month (0 month), and the characters, components and microbial limits of the traditional Chinese medicine composition for removing naughts and eliminating naughts are examined according to the quality standard (draft) of the particles for removing naughts and the microbial limit examination method of the first part of the Chinese pharmacopoeia 2020 edition. The results are shown in tables 1, 2 and 3.

Table 1 date of sample a experiment: 2021.06-2021.12 temperature: normal temperature relative humidity: 45 to 90 percent of

Table 2 date of sample B experiment: 2021.06-2021.12 temperature: normal temperature relative humidity: 45 to 90 percent of

Table 3 date of sample C experiment: 2021.06-2021.12 temperature: normal temperature relative humidity: 45 to 90 percent of

(2) Accelerated stability testing: under the condition of packaging clinical medicines, the A, B, C samples obtained in example 2 are placed in a stability test box, the temperature of the constant temperature box is adjusted, so that the samples are examined once in the month of January, march and June except for one examination in the month of the same month (0 month) under the conditions of 40 +/-2 ℃ and 75% +/-5% relative humidity, and the examination is carried out according to the microbial limit examination method of Tong Xiaozhi granule quality standard (draft) and the 2020 edition of Chinese pharmacopoeia. The results are shown in tables 4, 5 and 6.

Table 4 date of experiment for sample a: 2021.06-2021.12 temperature: normal temperature relative humidity: 45 to 90 percent of

Table 5 date of sample B experiment: 2021.06-2021.12 temperature: relative humidity of 40 ± 2 ℃:75 +/-5 percent

Table 6 date of sample C experiment: 2021.06-2021.12 temperature: relative humidity of 40 ± 2 ℃:75 +/-5 percent

And (4) conclusion:

the long-term stability test and the accelerated stability of the hemorrhoid-eliminating granules obtained in example 1 are continuously examined for 6 months, the influence of a packaging material directly contacted with a medicine on the stability of the medicine is observed, the properties, the identification, the examination and the content measurement of three batches of samples all accord with the regulations, and the microorganism limit examination accords with the regulations, namely the test result accords with the regulations. The long-term stability test and the accelerated stability test of the product under the condition of clinical medicine packaging indicate that the product is stable within two years.

4. Study of pharmacodynamics

1 materials and methods

1.1 experimental animal KM mouse, weight 18-22g, SD rat (6-7 weeks old), SPF grade, license number: SCXK Gui 2014-0002, provided by the medical laboratory animal center of Guangxi medical university. Mice and rats were bred by sex, laboratory temperature: 23 +/-3 ℃; relative humidity: 40 to 70 percent; feeding standard granulated feed and freely drinking water.

1.2 test strains: staphylococcus aureus [ CMCC (B) 26003], escherichia coli [ CMCC (B) 44102], pseudomonas aeruginosa [ CMCC (B) 10104], bacillus subtilis [ CMCC (B) 63501], candida albicans [ CMCC (F) 98001], and the test strains were purchased from Guangxi Nanning Biochemical apparatus.

1.3 drugs and reagents

The composition for treating hemorrhoids obtained in example 1;

aspirin enteric-coated tablets, german bayer product, production lot number: BJ50920;

fructus sophorae pills, a product of li shizhen pharmaceutical group ltd, production lot number: 201812002;

zhisuning tablets, jiangxi Yatong and pharmaceutical Co Ltd, production lot number: 210403;

the new compound aloe capsule, hebei Mo Bang, comes back to the products of pharmaceutical industry Co., ltd, and the production batch number: 1808107;

evans blue, shanghai chemical reagent procurement and supply station split charging plant, production lot number: 20111006;

glacial acetic acid, product of Xilong chemical Co., ltd, production lot number: 190921;

activated carbon, product of Guangdong Guanghua science and technology, production lot number: 20161115;

compound diphenoxylate tablets, a product of Changzhou Kangpu pharmaceutical Co., ltd, production batch number: 202005;

rat IL-6ELISA kit, shanghai pan Ke industry Co., ltd, production batch number: F3066-A;

rat TNF ELISA kit, shanghai pan Koko industry Co., ltd product, production batch number: F3056-A;

h & E dye liquor, product of Beijing Lei Gen Biotechnology Limited, lot number: 0603A20.

1.4 Main instruments: thermo Multiskan go multifunctional microplate reader, american type siamese product; EG 1150H paraffin embedding machine, RM2255 slicer and DM2500 microscope are all products of German come card company; RB-200 intelligent hot plate instrument, product of union science and technology Limited, chengdu Tai; model BS224S electronic analytical balance, product of beijing sidoris instruments systems limited.

1.5 statistical method, the obtained experimental data are expressed by mean plus or minus standard deviation, and Excel2007 software is used for t test to compare the significance of the difference between groups.

2 method

2.1 antibacterial experiment: minimum Inhibitory Concentration (MIC) assay: the solution of the Tongxift hemorrhoid-eliminating granule obtained in example 1 of 1:2 was diluted in duplicate by in vitro dilution method using tryptone Soytone liquid Medium (TSB) containing Tween and Twain Sa's medium to make 1: 4. 1: 8. 1: 16. 1: 32. 1:64 …, the 9 th tube was used as TSB control, and the 10 th tube was used as test sample control. Respectively adding 0.1ml of prepared staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, bacillus subtilis and candida albicans (glucose solution) bacteria liquid into the 1 st tube to the 9 th tube, shaking up, culturing at 33 ℃ for 24h, checking the candida albicans, culturing at 28 ℃ to 30 ℃ for 24h to 48h to observe the growth condition of the bacteria, and taking the mass concentration without turbidity as the Minimum Inhibitory Concentration (MIC) of a tested sample.

The results of the in vitro antibacterial action of the Tongxiao hemorrhoid-eliminating granules on 5 strains are shown in Table 7, and the results show that the Tongxiao hemorrhoid-eliminating granules provided by the invention have the in vitro antibacterial action and the best antibacterial effect on Candida albicans.

TABLE 7 in vitro antibacterial test results of 5 kinds of bacteria for the hemorrhoid treating granule obtained in example 1

2.2 Effect of Tongxiao Xiaozhi granules on mouse auricle swelling caused by croton oil

Taking 50 KM mice, half each male and female, randomly dividing into model control group, aspirin (0.2g^-1) Group, high, medium and low dosage (7.0, 3.5, 1.75 g.kg) of micro-dredging hemorrhoid-eliminating granules^-1) Groups of 10 pieces each. The dosage group mice are 20 mL/kg per day^-1The volume is gavaged 1 time, and the blank control group is given equal volume of distilled water for 5 days continuously. After the last administration for 1h, 30ul 2% croton oil was applied to the right ear of the mouse with a micro-syringe, and the mouse was sacrificed after 4 h. Immediately, a punch with a bore of 8mm was used to punch a sample along the same portion of the left and right auricles of the mouse, and then weighed, respectively, and the difference in weight (mg) between the two auricles was used as an index of the degree of swelling, and the swelling inhibition (%) was calculated. Swelling inhibition (%) = (degree of swelling in ear of blank control group-degree of swelling in ear of administration group)/degree of swelling in ear of control group × 100%.

The experimental results show that: compared with the blank control group, the aspirin and the hemorrhoid-eliminating granules obtained in example 1 have high and medium dosage (7.00, 3.50 g.kg)^-1) Can reduce swelling degree of mouse auricle caused by croton oil, and the difference has statistical significance (P)<0.05). The results are shown in Table 8.

TABLE 8 Effect of the Tongxiao Xiaozhi granules on swelling of auricle of mice caused by croton oil: (

n＝10)

Comparison with model control group: * P <0.05

2.3 Effect of Tongxiao Xiaozhi granules obtained in example 1 on toe swelling of rats caused by egg white SD rats 50 rats, each half of male and female, were randomly divided into a model control group and a hemorrhoid-treating tablet group (0.30 g kg)^-1) Group, the fine hemorrhoid eliminating granules obtained in example 1 have high, medium and low dosages (4.00, 2.00, 1.00 g.kg)^-1) Groups of 10 pieces each. The dosage of the rats is 10mL/kg per day^-1The volume was gavaged 1 time, and the model control group was given an equal volume of distilled water for 5 consecutive days. After 1h of the last administration, each rat was injected subcutaneously into the right hind toe of a 10% fresh egg white solution at a rate of 0.1 ml/paw to cause inflammation, resulting in an acute toe swelling model. Measuring the circumferences of the toes of the rats with inflammation before inflammation and after inflammation for 0.5h, 1h, 2 h, 3h, 4h and 5h by using a flexible ruler, and calculating the swelling degree and swelling inhibition rate of the toes. Swelling degree (mm) = postinflammatory toe circumference (mm) -postinflammatory toe circumference (mm); swelling inhibition (%) = (degree of swelling in model control group-degree of swelling in administered group)/degree of swelling in model control group × 100%.

The experimental results show that: compared with model control group, high dosage of ZHI SU NING PIAN and TONG WEI XIAO ZHI KE LI (7.00 g kg)^-1) Can inhibit toe swelling of rats at 3h after inflammation, and the difference has statistical significance (P)<0.01). The results are shown in Table 9.

TABLE 9 Effect of the hemorrhoid-eliminating Tong granule obtained in example 1 on the swelling of toes of rats caused by egg white (± s, n = 10)

Comparison with model control group: * P <0.01

2.4 Hot plate test

Taking 60 KM mice, female, placing the mice on a hot plate at (55 +/-1) DEG C, and recording the time(s) from the placement of the mice on the hot plate to the licking of the mice as a pain threshold valueSelecting mice with pain threshold of 5-30s as qualified mice, and eliminating allergy<5 s) or sluggish reaction(s)>30 s). Selecting qualified 50 mice 24h later, randomly dividing into model control group, zhisuning tablet (0.62 g kg)^-1) Group, the micro hemorrhoid dredging granule obtained in example 1 has high, medium and low dosage (7.00, 3.50, 1.75 g.kg)^-1) Groups of 10 pieces each. Mice in the administration group were each at 20mL/day^-1The administration is carried out for 1 time by volume intragastric administration, the equivalent volume of distilled water is given to a model control group, the pain threshold value of each mouse is measured as the pain response index respectively 30min, 60min, 120min and 180min after the administration before and at the last time, and the pain threshold value is counted as 60s when exceeding 60 s.

The experimental results show that: compared with the model control group, the hemorrhoid treating tablet and the hemorrhoid treating granule prepared in example 1 have high, medium and low dosage (7.00, 3.50, 1.75 g/kg)^-1) Can inhibit pain threshold of mice at last administration time of 90min, and has statistical significance (P)<0.05 ); the middle and low dose of the hemorrhoid eliminating granule obtained in example 1 (3.50, 1.75 g/kg) were compared with the model control group^-1) Can inhibit pain threshold of mice at last 120min, and has statistical significance (P)<0.01). The results are shown in Table 4.

TABLE 4 Effect of the hemorrhoid treatment granules obtained in example 1 on the pain threshold of mice on hotplate response (. + -. S, n = 10)

Comparison with model control group: * P <0.05, P <0.01

2.5 twist test

Taking 50 KM mice, half each male and female, randomly dividing into model control group, aspirin (0.2 g kg. Kg)^-1) Group, high, middle and low dosage of the TONGWEIXIAOZHI granule obtained in example 1 (7.00, 3.50, 1.75 g.kg)^-1) Groups of 10 pieces each. Mice in the administration group were administered at 20mL.kg daily^-1The volume was gavaged 1 time, and the model control group was given an equal volume of distilled water for 2 consecutive days. After the last administration for 1h, each mouse was intraperitoneally injected with 10ml/kg of 0.6% acetic acid solution according to body weight^-1Immediately observe and recordThe number of writhing times of the mice in 20 minutes was used as an index of pain response.

The experimental results show that: compared with the model control group, the aspirin and the hemorrhoid-eliminating granule for treating hemorrhoid obtained in example 1 have high and medium dosage (7.00, 3.50 g.kg)^-1) All can reduce the mouse writhing frequency caused by acetic acid, and the difference has statistical significance (P)<0.05，P<0.01). The results are shown in Table 10.

TABLE 10 influence of the hemorrhoid-eliminating granule on the body writhing frequency of mice induced by acetic acid: (

n＝10)

Comparison with model control group: * P <0.05; * P <0.01

2.6 Effect of the granule for removing hemorrhoid and promoting digestion on the Small intestine movement function of mice

Collecting 60 KM mice, male and female half, randomly dividing into blank control group, model control group, and positive control drug compound Aloe capsule (0.20 g.kg)^-1) Group, the micro hemorrhoid dredging granule obtained in example 1 has high, medium and low dosage (7.00, 3.50, 1.75 g.kg)^-1) Groups of 10 pieces each. The dosage group mice are 20 mL/kg per day^-1The volume was gavaged 1 time, and the blank group was given an equal volume of distilled water for 2 consecutive days. After the last dose, mice in each group were fasted for 16 hours without water deprivation. 5 mg/kg compound diphenoxylate for intragastric administration of model control group and administration groups^-1The blank control group was given an equal volume of distilled water. After 0.5h of administration of the compound diphenoxylate, the Chinese ink was administered to each group. After 25 minutes, the cervical vertebrae are taken off immediately to kill the mouse, the abdominal cavity is opened to separate mesentery, the intestinal canal with the upper end from the pylorus, the lower end to the ileocecal part is cut and placed on a tray, the small intestine is slightly pulled into a straight line, the length of the intestinal canal is measured as the total length of the small intestine, and the length of the intestinal canal from the pylorus to the front edge of ink is measured as the advancing length of the ink. The ink propulsion rate was calculated according to the following formula. Ink propulsion rate (%) = ink propulsion length (cm)/total small intestine length (cm) × 100%.

The experimental results show that: compared with a blank control group, the ink propulsion rate of the model control group is obviously reduced, the difference has statistical significance (P is less than 0.01), and the success of preparing the small intestine peristalsis inhibition model is proved; compared with the model control group, the new compound aloe capsule and the hemorrhoid-eliminating granule obtained in example 1 have high dosage (7.00 g.kg)^-1) The ink propulsion rate can be obviously improved, the difference has statistical significance (P is less than 0.01), and the results are shown in a table 11.

TABLE 11 Effect of XIAO WEI XIAO ZHI KE LI on small intestine motility function of mice: (

n＝10)

P <0.01; comparison with model group: * P <0.01

2.7 Effect of the hemorrhoid-eliminating granule obtained in example 1 on the clotting time of mice

Taking 50 KM mice, male and female half, randomly dividing into blank control group and positive control medicine fructus Sophorae pill (2.00 g kg^-1) Group, the micro hemorrhoid dredging granule obtained in example 1 has high, medium and low dosage (7.00, 3.50, 1.75 g.kg)^-1) Groups of 10 pieces each. The dosage group mice are 20 mL/kg per day^-1The volume is gavaged 1 time, and the normal control group is given equal volume of distilled water for 3 days continuously. After 1h from the last administration, the clotting time was determined by the slide method: blood was collected from the mouse orbit, the 1 st drop of blood was removed by rubbing with a cotton ball, and then 1 drop of blood was added to each end of the slide glass, and a stopwatch was immediately used to time. Gently flick every 30s with a clean needle from the edge of the drop inward and observe the presence or absence of the pick-up of the blood filaments. The time from the beginning of blood collection to the beginning of blood drawing to the end of blood drawing is the blood coagulation time.

The experimental results show that: the amount of fructus Sophorae pills and the hemorrhoid-eliminating granule obtained in example 1 was high (7.00 g/kg) compared with the blank control group^-1) Can obviously shorten the blood coagulation time of mice, and the difference has statistical significance (P is less than 0.05), and the results are shown in table 12.

TABLE 12 Effect of the hemorrhoid smoothing granules obtained in example 1 on bleeding time of mice: (

n＝10)

Comparison with blank control: * P <0.05

2.8 Effect of the hemorrhoid-eliminating granule obtained in example 1 on bleeding time of mice

Taking 50 KM mice, male and female half, randomly dividing into blank control group and positive control medicine fructus Sophorae pill (2.00 g kg^-1) Group, the micro hemorrhoid dredging granule obtained in example 1 has high, medium and low dosage (7.00, 3.50, 1.75 g.kg)^-1) Groups of 10 pieces each. The dosage group mice are 20 mL/kg per day^-1The administration is performed by volume intragastric administration for 1 time, and the normal control group is administered with distilled water of the same volume for 3 days continuously. After 1h of the last administration, bleeding time was measured by tail-off method: the tail of the mouse was fixed and the tip of the tail was cut off by about 1cm with scissors to allow blood to spill out by itself. And (4) lightly sucking the blood drops by using filter paper every 30s, wherein the bleeding time is the time from the wound surface blood to the bleeding stop through the automatic overflow of the wound surface blood.

The experimental results show that: fructus Sophorae pill and the above-mentioned hemorrhoid eliminating granule prepared in example 1 have high, middle and low dosage (7.00, 3.50, 1.75 g/kg) compared with blank control group^-1) The bleeding time of the mice can be obviously shortened, the difference has statistical significance (P is less than 0.01), and the results are shown in a table 13.

TABLE 13 influence of hemorrhoid eliminating granule on bleeding time of mice

Note: p <0.01 in comparison to placebo

2.9 Effect on croton oil-induced anal swelling in rats

60 SD rats with male and female halves were prepared, and a model of rat anal swelling was prepared using croton oil mixture (prepared from croton oil mixture: 1 part distilled water, 4 parts pyridine, 5 parts diethyl ether and 10 parts 6% croton oil diethyl ether). The model was prepared by inserting a cotton ball soaked with 16uL of croton oil mixture into the anus of a rat under light anesthesia with ether for 10s. The rats successfully molded were randomly divided into a blank control group, a model control group and a positive drug Zhisuning tablet (0.31 g.kg)^-1) Group, the fine hemorrhoid eliminating granules obtained in example 1 have high, medium and low dosages (4.00, 2.00, 1.00 g.kg)^-1) Groups of 10 per group. Each group of rats was treated at a daily dose of 10ml/kg^-1Gavage was given 1 time, and a normal control group was given an equal volume of distilled water for 5 consecutive days. After 1h of the last administration, rats were anesthetized and bled to determine serum inflammatory factors; weighing tissue about 2cm from the anus to the rectum by wet weight, and calculating organ coefficients; stripping rat colorectal, washing intestinal contents with running water, fixing with Foel Ma Linye, paraffin embedding, section HE staining, and performing optical examination.

The experimental results show that: compared with a blank control group, the anus swelling degree of the rat in the model control group, the IL-6 and TNF levels of inflammatory factors are obviously increased, and the difference has statistical significance (P is less than 0.01), so that the preparation success of the anus swelling model of the rat is proved; compared with the model control group, the Zhisuning tablet and the Zhisuning granule for removing hemorrhoid obtained in example 1 have high and medium dosage (4.00, 2.00 g.kg)^-1) Can obviously reduce the anus swelling degree of rats (P is less than 0.05 and P is less than 0.01), and the high dosage (4.00 g.kg) of the embodiment 1^-1) Can obviously reduce the levels of IL-6 and TNF of inflammatory factors, and the difference has statistical significance (P is less than 0.01), and the results are shown in a table 14.

The colorectal histomorphometry results HE (100 fold) for each group of rats are shown in FIG. 3. As can be seen from fig. 3, the rat colorectal region of the blank control group has a normal structure, epithelial cells and endocrine cells in the rectal region of the anal canal are distributed and arranged regularly, and the blood vessels in the submucosa do not cause hyperemia; the mucous membrane of the colorectal area of the rat in the model group is thickened, squamous epithelialization is generated, and peripheral tissues are subjected to visible hemorrhage; the thickening phenomenon of the mucous membrane in the colorectal area of the rat in the positive control group is relieved, and the micro blood vessels in the submucosa are not hyperemic; the rat colon-rectum area of the micro-dredging hemorrhoid-eliminating high-dose group is normal in structure, epithelial cells and endocrine cells in the anal canal-rectum area are distributed and arranged regularly, and micro blood vessels in the submucosa are not hyperemic; micro-dredging and hemorrhoid eliminating middle and low dose groups of rats have thickened mucous membrane in colorectal area, squamous epithelialization and congestion of submucosal microvascular. The granules for removing the hemorrhoids through promoting digestion provided by the invention have good treatment effect on rat hemorrhoid models.

TABLE 14 Effect on anal swelling and inflammatory factors in rats: (

n＝10)

Group of	Dosage (g.kg)-1)	Swelling degree (mg)	IL-6(pg·ml-1)	TNF(ng·ml-1)
					Blank control group	-	0.13±0.03	273.26±16.4	600.63±24.62
Model control group	-	0.44±0.12*	302.19±19.80*	646.59±26.23*
					Zhisuning tablet for curing hemorrhoid	0.31	0.33±0.07**	274.85±21.75**	595.65±28.52**
Example 1	4.00	0.32±0.08**	279.32±21.11**	619.97±30.88**
					Example 1	2.00	0.27±0.05***	296.55±14.34	649.40±51.44
Example 1	1.00	0.36±0.18	309.55±24.96	683.88±68.36

Comparison with blank control: * P <0.01; comparison with model groups: * P <0.05, P <0.01

3 conclusion

The data show that the traditional Chinese medicine composition for promoting circulation of qi and removing hemorrhoids provided by the invention has the effects of resisting bacteria, diminishing inflammation, relieving pain, stopping bleeding and improving small intestine motion functions, and has a good treatment effect on a rat hemorrhoid model. Provides a theoretical basis for the clinical treatment of hemorrhoids.

5. Repeated administration toxicity test

The purpose of the test is as follows: the toxic reaction and the reversibility of the reaction of the micro hemorrhoid dredging granule obtained in the long-term example 1 on SD rats are observed, and a basis is provided for clinical safe medication.

The tested drugs are: the granules for removing the micro-hemorrhoid and eliminating the hemorrhoid obtained in the example 1 and 3.89 medicinal materials per gram of concentrated solution are prepared into required concentration by distilled water during the test.

Animal and feeding conditions: SD rats (6-7 weeks old), 80, male and female (male and female), SPF grade, changsha tianqin biotechnology limited, license number: SCXK (Xiang) 2019-0014. The laboratory temperature is 23 +/-3 ℃, the relative humidity is 40-70%, and clean tap water is provided for rats to freely drink. The cage is cleaned and the padding is replaced for 1 time every 3 to 4 days. Animals were acclimatized for one week before dosing was initiated.

The administration method comprises the following steps: according to the guiding principle of repeated drug administration toxicity research technology^[3]The related requirements adopt the gastric lavage administration route, which is consistent with the clinical administration route. The administration was carried out in a volume of 10ml/kg, 1 time per day for 30 consecutive days. And setting blank control group.

The test method comprises the following steps: the SD rats are randomly divided into 4 groups, and each group comprises 20 male and female. The first group of rats was a blank control group (gavage for equal volume of water), the second group of rats was a hemorrhoid dredging granule high dose group (42.0 g/kg) obtained in example 1, the third group of rats was a hemorrhoid dredging granule medium dose group (21.0 g/kg) obtained in example 1, and the fourth group of rats was a hemorrhoid dredging granule low dose group (10.5 g/kg) obtained in example 1. Once daily for 1 month, food intake was recorded daily and body weight was weighed 1 time per week. During the test, the rats were observed for general conditions including physical signs, behavioral activities, food intake, defecation, death, and the like. The administration is carried out for 1 month, 10 rats (female and male) are taken from each group 24 hours after the last administration, 10% chloral hydrate (0.3 mL/100 g) is injected into the abdominal cavity for anesthesia, blood sampling is carried out on abdominal aorta for hematology examination and blood biochemistry examination, comprehensive autopsy is carried out on main organs, brain, heart, liver, spleen, lung, kidney, adrenal gland, thymus, uterus, ovary, testis, epididymis and other organs are taken for weighing, organ coefficients (g/100 g weight) are calculated, and histology examination is carried out on the organs, stomach, intestine, bone and the like. The rest rats are stopped taking the medicine and observed for 14 days, and the indexes are detected by the same method.

The statistical method comprises the following steps: test results were compared for significance of differences between groups using Excel2007 software for t-test.

And (3) test results:

1. general conditions are as follows: no death of rats in each administration group is observed in the test period, the behavioral activities, breathing, defecation and the like of animals in each group are not abnormal in the administration period and after the administration is stopped, and the weight of the group with the injection of the micro-hemorrhoid removal granules obtained in the example 1 is increased, and has no significant difference compared with a blank control group. The results are shown in Table 1. EXAMPLE 1 the second high dose of the hemorrhoid eliminating granule obtained in example 1

III

All around

Second after administration of the Medium group

Three weeks

Low dose group two

The food intake of the third (female) week is obviously different from that of the blank control group. The results are shown in Table 15.

Table 15: after gavage, the average food intake scale per week in rats: (

g)

t-test, P <0.05, P <0.01, P <0.001, compared to the blank control group

2. Examination of hematological indices: measurement of leukocyte count WBC, neutrophil count Neu, lymphocyte count Lym, intermediate cell count Mon,

3. Eosin count Eos, basophil count Bas, neutrophil ratio Neu%, lymphocyte ratio Lym%, intermediate cell ratio Mon%, eosinophil ratio Eos%, basophil ratio Bas%, red blood cell count RBC, hemoglobin HGB, red blood cell specific volume HCT%, mean red blood cell volume MCV, mean RBC hemoglobin content MCH, mean RBC hemoglobin concentration MCHC hc, red blood cell distribution width RDW-CV, red blood cell distribution width variation coefficient RDW-SD, platelet count PLT, mean platelet volume MPV, platelet volume distribution width PDW, platelet hematocrit PCT, prothrombin time, activated partial thromboplastin time APTT25 hematologic indices. After 24 hours of drug withdrawal, the group with high dose had a significant difference in MCH and Eos% compared to the group with no control (P < 0.05). 14 days after withdrawal, the high-dose group RBC, HGB, PLT, PCT, the medium-dose group Neu, eos, neu%, PCT, APTT, and the low-dose group Neu%, lym%, MCHC, APTT were significantly different (P <0.05, P < -0.01) compared to the blank control group. The above measured values were all within the normal range, and the results are shown in Table 16.

TABLE 16 Effect of Long-term toxicity test on hematological indices by discontinuation of drug for 24 hours and 14 days: (

n＝10)

t-test, P <0.05, P <0.01, compared to placebo

3. Biochemical index of blood: detecting alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), alkaline phosphatase (ALP), UREA (UREA), creatinine (CREA), total Protein (TP), albumin (ALB), blood glucose (Glu), total bilirubin (T-BIL), total Cholesterol (TC), triglyceride (TG), and potassium (K)⁺) Sodium, sodium (Na)⁺) Chlorine (Cl)^-) 14 biochemical indexes of blood. After stopping the drug for 24 hours, TG of the high dose group and T-BIL of the low dose group are significantly different (P) compared with the blank control group<0.05). After 14 days of withdrawal, the AST, CREA, cl of the medium group were compared with those of the blank group^-Cl of lower dose group^-With a significant difference (P)<0.01、P<0.05). The above measured values were within the normal range except for TG in the high dose group. The results are shown in Table 17.

TABLE 17 influence of long-term toxicity test on biochemical indices by 24 hours and 14 days after drug withdrawal: (

n＝10)

t-test, P <0.05, P <0.01 compared to the blank control group.

4. Examination of major organ coefficients: the organ coefficients (g/100 g body weight) of the brain, heart, liver, spleen, lung, kidney, adrenal gland, thymus, uterus, ovary, testis, epididymis and the like of rats in each dose group were weighed and calculated. After stopping the drug for 24 hours, compared with a blank control group, the ovary and the epididymis of a high-dose group and the epididymis of a medium-dose group are significantly different (P <0.05, P is formed by the cloth of 0.01), and the coefficients of other organs of the high-dose, medium-dose and low-dose groups are not significantly different (P > 0.05). After stopping taking the drug for 14 days, compared with a blank control group, the organ coefficients of the high, medium and low dose groups have no significant difference (P is more than 0.05). The results are shown in Table 18.

TABLE 18 Effect of 24 hours and 14 days of drug withdrawal on the coefficients of major organs: (

g/100g body weight, n = 10)

t-test, P <0.05, P <0.01, compared to placebo

5. Gross necropsy and histological examination: the heart, liver, spleen, lung, kidney, stomach, small intestine, large intestine, adrenal gland, thymus, esophagus, aorta, uterus, ovary, testis, epididymis and the like of 20 rats (10 rats after stopping medicine for 24 hours, 10 rats after stopping medicine for 14 days, half of males and females) respectively in the group of micro hemorrhoid removal granule high dose (42.0 g/kg) and the blank control group are taken, general examination is carried out, and then conventional fixing and HE staining are carried out, and then, the examination is carried out by a light microscope.

As can be seen from figures 4-21, after stopping administration for 24 hours, all animals had no abnormal appearance of heart, no other substances appeared in pericardium, endocardium and stroma, the cardiac muscle cell nucleus was oval, the cytoplasm was fine and smooth, the stroma was clear, the cardiac muscle fiber bundle was branched and arranged, and there was no abnormal morphology. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the medicine for 24 hours, the appearance of the liver of all animals is not abnormal, the cells are polygonal, the nucleus is large, nucleolus, hepatic cords and hepatic sinuses are radially arranged, stellate cells are distributed in a scattered manner, and the structures of all levels of blood vessels and bile ducts in central veins and a manifold area are normal, and other substances are not shown. After the medicine is stopped for 14 days, the appearance of the liver of all animals is not abnormal, the cells are polygonal, the nucleus is large, nucleolus, hepatic cords and hepatic sinuses are seen to be arranged radially, stellate cells are distributed in a scattered manner, and the structures of all levels of blood vessels and bile ducts in central veins and a manifold area are normal, and other substances are not seen.

After stopping taking the medicine for 24 hours, all animals have no abnormal spleen envelopes, red marrow to white marrow ratio, lymph follicles, various lymphocytes in germinal centers, spleen sinuses and the like, and no other substances appear. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, the appearance of the lung of all animals is grey white, the bronchial mucosa epithelium at all levels does not denaturize and fall off, no other substances appear in the lumen, the alveolar epithelium is flat and is not changed, and the interstitium is not abnormal. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, all animals have complete tracheal mucosa and have no abnormalities in ciliated epithelium, submucosa, cartilage morphology and structure. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping taking the medicine for 24 hours, the shape, the color and the section of all the kidneys of all the animals are normal, the renal envelopes are smooth, the renal glomeruli, the renal bursa, the renal tubules at all levels, the renal pelvis, the interstitial cells and the epithelial cells are not abnormal in shape, and other substances are not deposited in the lumens. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the medicine for 24 hours, the gastric mucosa of all animals is intact, the epithelial cell morphology is normal, the mucus cell, the main cell and the parietal cell morphology are not abnormal, the muscle layer and the capsule are intact, and no other substances are deposited in the stroma. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, all the esophageal mucosa of all the animals are intact, and the morphologies and structures of the stratified squamous epithelial cells, the inherent membrane and the muscular layer are not abnormal. After 14 days of withdrawal, all animals had no abnormalities.

After stopping taking the medicine for 24 hours, all animals have intact small intestinal mucosa epithelium, intestinal gland cells and various epithelial cell forms are not changed, and other substances do not appear in mesenchyme, muscular layer and serosa. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, all animals had intact colonic mucosal epithelium and no abnormalities were observed in epithelial cells, submucosa and interstitium. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, all the thymuses of all the animals are normal in size and shape, the density, arrangement and shape of lymphocytes are not abnormal, and other substances do not appear in interstitial substances. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, all animals have no abnormal appearance of ovaries, and various follicles, corpus luteum, corpus albilineans and interstitium have no obvious change. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, all animals have normal uterus morphology, and the mucosa, the muscle layer, the serosa and the interstitium of the uterus are not changed. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping taking the medicine for 24 hours, the whole testis of all animals is moderate in size, the shapes and the proportions of spermatogonium, spermatocyte, secondary spermatocyte and spermatid are not abnormal, and the stroma is not obviously changed. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping taking the medicine for 24 hours, the epididymal epithelium, smooth muscle, intraluminal sperm and interstitium of all animals are not abnormal. After 14 days of withdrawal, all animals had no abnormalities. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, the appearance of all adrenal glands of all animals is not abnormal, and the stroma of the corticosphere zone, the fasciculate zone, the reticular zone and the medulla part of the caseophile cells is not obviously changed. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, all the submandibular gland mucous acinar epithelia and ducts of all the animals have no abnormality. All animals had no abnormality even after the drug was stopped for 14 days.

After stopping the drug for 24 hours, the intima of all arteries of all animals is smooth, endothelial cells, elastic membranes and smooth muscles of all layers are not abnormal, and other substances are not deposited under the mucosa. All animals had no abnormality even after the drug was stopped for 14 days.

In conclusion, after the medicine is stopped for 24 hours and 14 days, the heart, the liver, the spleen, the lung, the kidney, the adrenal gland, the thymus, the ovary, the stomach, the intestine and other organs of the rat are subjected to comprehensive naked eye autopsy, and the administration group and the blank control group have no abnormal expressions such as congestion, swelling, necrosis and the like; the gastric mucosa and the intestinal mucosa are not found to be red, swollen or ulcerated. The pathological examination result does not find the pathological morphological change of the main organs caused by drug toxicity.

6. Conclusion

From the above tests, it can be seen that the micro hemorrhoid dredging granule provided by the invention is used for gavage administration (42.0 g, 21.0g and 10.5g/kg of medicinal materials) for 1 time every day (equivalent to 60, 30 and 15 times of clinical medication), the blank control group is used for gavage administration for equal volume of water (10 ml/kg), continuous 1 month, no death occurs in rats of each administration group during the test period, the general performances of behavior activity, breathing, defecation and the like of animals of each group during the administration period are not abnormal, the weight of the rats of the micro hemorrhoid dredging granule high, medium and low dosage administration group obtained in example 1 is increased well, and compared with the blank control group, the micro hemorrhoid dredging granule has no significant difference. The weekly intake of each group was affected to various degrees at 2, 3 and 4 weeks after administration, but did not substantially affect the weight gain of the rats. The food intake recovers to normal after the medicine is stopped. The hematological indexes, blood biochemical indexes and main organ coefficients which are taken 24 hours after the medicine withdrawal are checked, except TG, ovary and epididymis of a high-dose group and epididymis of a medium-dose group, most of detection items of an administration group have no significant difference compared with a blank control group, other individual detection items have significant difference, but the measured values are all in a normal range, so the difference has no practical significance; 14 days after stopping the drug administration, the hematological indexes, blood biochemical indexes and main organ coefficients are checked, most of detection items of each administration group have no significant difference compared with a blank control group, and the measurement values of the individual detection items are in a normal range although the significant difference exists, so that the difference has no practical significance; no obvious pathological histological change damage related to the drug is found in histological examination of each administration group after the drug is stopped for 24 hours and 14 days. Therefore, it is considered that the hemorrhoid eliminating granule obtained in example 1 should be used safely in the prescribed dosage, application and treatment course.

The embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other. The device disclosed by the embodiment corresponds to the method disclosed by the embodiment, so that the description is simple, and the relevant points can be referred to the method part for description.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (9)

1. The traditional Chinese medicine composition for eliminating hemorrhoids is characterized by being prepared from the following raw materials in parts by weight:

7-12 parts of rose mallow, 4-9 parts of common achyranthes herb, 1-6 parts of humifuse euphorbia herb and 1-6 parts of garden burnet root.

2. The hemorrhoid-eliminating traditional Chinese medicine composition according to claim 1, which is prepared from the following raw materials in parts by weight:

9 parts of rose mallow, 6 parts of common achyranthes herb, 3 parts of humifuse euphorbia herb and 3 parts of garden burnet root.

3. The preparation method of the hemorrhoid-eliminating traditional Chinese medicine composition according to any one of claims 1-2, which is characterized by comprising the following steps:

weighing raw materials, soaking in water, decocting and extracting for 2 times, then combining filtrates, concentrating to obtain thick paste with the relative density of 1.24-1.26 at 60 ℃, then adding auxiliary materials, uniformly mixing, granulating, drying and subpackaging to obtain the traditional Chinese medicine.

4. The preparation method of the hemorrhoid-eliminating traditional Chinese medicine composition according to claim 3, wherein the mass ratio of the water to the raw materials is 6:1.

5. The preparation method of the hemorrhoid-eliminating traditional Chinese medicine composition according to claim 3, wherein the soaking temperature is normal temperature, and the soaking time is 30min.

6. The preparation method of the hemorrhoid-eliminating traditional Chinese medicine composition according to claim 3, wherein the decoction time is 1h.

7. The preparation method of the hemorrhoid-eliminating traditional Chinese medicine composition according to claim 3, wherein the auxiliary materials comprise dextrin and carboxymethyl starch sodium, and the mass ratio of the dextrin to the carboxymethyl starch sodium is 9:1.

8. The preparation method of the hemorrhoid-eliminating traditional Chinese medicine composition according to claim 7, wherein the mass ratio of the thick paste to the auxiliary materials is 1.

9. The preparation method of the hemorrhoid-eliminating traditional Chinese medicine composition according to claim 3, wherein the drying comprises the following steps:

drying the granulated material at 70-75 deg.C for 2 hr, sieving with 14 mesh sieve, grading, and drying at 70-75 deg.C until the water content is below 6%.

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