CN111228406A

CN111228406A - Medicine for treating chronic atrophic gastritis and preparation method thereof

Info

Publication number: CN111228406A
Application number: CN201811442182.2A
Authority: CN
Inventors: 范玉; 杜杉; 夏传涛; 刘桂端; 徐军
Original assignee: Shaanxi Dongke Pharmaceutical Co ltd
Current assignee: Shaanxi Dongke Pharmaceutical Co ltd
Priority date: 2018-11-29
Filing date: 2018-11-29
Publication date: 2020-06-05

Abstract

The invention discloses a medicine for treating chronic atrophic gastritis and a preparation method thereof, belonging to the technical field of traditional Chinese medicines. The related medicine is prepared from fourteen medicinal materials of dendrobium, rhizoma anemarrhenae, coptis chinensis, radix sophorae flavescentis, poria cocos, bighead atractylodes rhizome, astragalus mongholicus, rhizoma bletillae, purslane, fructus aurantii, radix clematidis, garden burnet, blackberry lily and fructus forsythiae, volatile oil is extracted from the bighead atractylodes rhizome, the fructus aurantii and the fructus forsythiae, dregs of a decoction and the rest eleven medicinal materials of the poria cocos and the like are extracted by water, the filtrate and the distilled water solution are mixed and concentrated, then a proper amount of auxiliary materials. Can be used for treating chronic atrophic gastritis with syndrome of stagnated heat in stomach and impairment of qi and yin. Pharmacodynamics and clinical evaluation prove that the medicine prepared by the method is safe and has definite curative effect on the chronic atrophic gastritis. And the preparation method of the traditional Chinese medicine compound is simple and is easy for large-scale production.

Description

Medicine for treating chronic atrophic gastritis and preparation method thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, and relates to a medicine which is prepared by taking traditional Chinese medicinal materials as main raw materials and adopting modern extraction and preparation technologies and can be used for treating chronic atrophic gastritis.

Background

Chronic Atrophic Gastritis (CAG) is a common chronic digestive system disease characterized by atrophy of gastric mucosal epithelium and glands, thinning of mucosa, thickening of mucosal muscularis, and atypical hyperplasia accompanied by metaplasia of intestinal epithelium, which is considered to be a typical sign of atrophy and a precursor of carcinogenesis. The incidence rate of CAG is on the rise in the current society, the development mode is chronic gastritis → gastric mucosa atrophy → intestinal metaplasia → dysplasia → gastric cancer, and the research shows that the detection rate of CAG in gastric mucosa biopsy is in positive correlation with the death rate of gastric cancer.

The chronic atrophic gastritis has no specific expression clinically. General symptoms comprise epigastric discomfort, stomach pain, fullness, inappetence, eructation, nausea, emaciation and the like, and some patients are accompanied with psychoneurosis symptoms such as insomnia, anxiety and the like. The diagnosis of atrophic gastritis relies mainly on gastroscopy and pathology. Under the primary gastroscope of the chronic atrophic gastritis, the gastric mucosa is pale gray and has uneven color tone, a large number of pale areas, the gastric mucosa becomes thin, glands are reduced, and blood vessels are hidden; in the middle and later stage of chronic atrophic gastritis, the stomach mucous membrane is congested and edematous when the stomach gland obviously shrinks and disappears, and the stomach mucous membrane is complicated with the proliferation of stomach fovea epithelial cells on the atrophic mucous membrane, so that the local mucous membrane layer becomes thick and is in granular or nodular bulge. In 2006, the two national chronic gastritis diagnosis and treatment consensus conference held in Shanghai in 9 months passes the conference consensus opinion: the mucosal changes seen by naked eyes under the endoscope of endoscopic diagnosis of chronic gastritis need to be combined with the pathological examination result for judgment. The diagnosis of CAG still relies primarily on pathological examination, i.e., a reduction in the indigenous glands of the stomach.

In traditional Chinese medicine, the disease belongs to the categories of epigastric pain, fullness in the stomach, epigastric fullness and epigastric upset, the disease is localized in the stomach, and the etiology is manifested by eating disorder, seven emotions disharmony, overstrain, congenital deficiency, invasion of exogenous pathogenic factors to the stomach and the like. CAG is a precancerous state, and has great significance for dry period diagnosis and dry period treatment of gastric cancer. Because the pathogenesis of the gastric precancerous condition is not completely clear, the modern medicine has no satisfactory treatment means for the gastric precancerous condition, and the traditional Chinese medicine in the past accumulates abundant experience in the treatment of the gastric precancerous condition and shows unique advantages.

The yin-nourishing and stomach-clearing granules are prepared from fourteen medicinal materials such as dendrobium, rhizoma anemarrhenae and the like, the dendrobium, the rhizoma anemarrhenae are used for tonifying stomach and promoting fluid production, the yin-nourishing and heat-clearing granules are used for simultaneously removing deficiency and excess heat in stomach and tonifying stomach fluid, the coptis chinensis and the radix sophorae flavescentis are used for clearing heat and drying dampness and regulating stomach and intestine to remove pathogenic heat accumulated in intestines and stomach, and the four medicinal materials are used as monarch medicaments together. The sophora flavescens, the bighead atractylodes rhizome and the astragalus root have the effects of tonifying spleen, replenishing qi, regulating the middle warmer, dispelling warm evil, giving evil, assisting monarch drugs, having mild action without damaging yin liquid and being used as ministerial drugs. Clematis root is used for dredging the channels and collaterals, removing food retention and stagnation, fructus aurantii is used for regulating qi and relieving epigastric distention, relieving distension and fullness, enjoying the ground, and rhizoma bletillae is used for clearing heat and activating blood, and relieving swelling and pain; the purslane, the blackberrykiky rhizome and the weeping forsythia have the effects of clearing away heat and toxic materials, relieving pain and dissipating stagnation, removing accumulated stagnation and pathogenic heat of stomach and hollow organs, and combining the functions of accepting and transporting the spleen and stomach, and serving as an assistant and guide medicament to assist the monarch and minister medicaments, and the combination of the medicaments can play the effects of nourishing yin, clearing the stomach, strengthening the spleen and regulating the middle warmer. It has good therapeutic effects on chronic atrophic gastritis with syndrome of stagnation of heat, and impairment of qi and yin, manifested by symptoms of gastric distention and fullness, burning pain, anorexia, emaciation, dry lip, and halitosis.

Disclosure of Invention

The invention provides a Chinese medicinal preparation for treating chronic atrophic gastritis; it is still another object of the present invention to provide a scientific and reasonable process for preparation, thereby ensuring the therapeutic effect of the drug and being embodied in production.

The invention is realized by adopting the following technical scheme on the basis of long-term and repeated experimental research:

the medicine of the invention contains the following traditional Chinese medicine raw materials in parts by weight: 170 parts of dendrobium officinale, 225 parts of rhizoma anemarrhenae, 100 parts of coptis chinensis, 120 parts of radix sophorae flavescentis, 150 parts of poria cocos, 170 parts of rhizoma atractylodis macrocephalae, 150 parts of astragalus membranaceus, 225 parts of rhizoma bletillae, 100 parts of purslane, 170 parts of fructus aurantii, 225 parts of radix clematidis, 150 parts of sanguisorba officinalis, 170 parts of rhizoma belamcandae and 150 parts of fructus forsythiae.

The medicine of the invention comprises the following traditional Chinese medicine raw materials in the optimal weight proportion: 160 parts of dendrobium, 214 parts of rhizoma anemarrhenae, 107 parts of coptis, 107 parts of radix sophorae flavescentis, 160 parts of poria cocos, 160 parts of bighead atractylodes rhizome, 160 parts of astragalus membranaceus, 214 parts of rhizoma bletillae, 107 parts of purslane, 160 parts of fructus aurantii, 214 parts of radix clematidis, 160 parts of garden burnet root, 160 parts of blackberry lily and 160 parts of fructus forsythiae.

The medicine of the invention adopts a water decoction mode to extract the traditional Chinese medicine raw materials, and extracts the volatile oil from the largehead atractylodes rhizome, the bitter orange and the weeping forsythia; decocting the residue and the rest eleven materials such as tuckahoe and the like in water twice, wherein 8-12 times of water is added in the first time, and the decoction is carried out for 2-4 hours; adding 6-10 times of water for the second time, and decocting for 2-4 hr; mixing the decoctions, filtering, and concentrating the filtrate to obtain fluid extract with a relative density of 1.34-1.36 (60 ℃); mixing the fluid extract 1 part, sucrose 0.8 part, and dextrin 1 part, granulating with appropriate amount of ethanol, drying, adding the volatile oil such as Atractylodis rhizoma, and mixing.

Compared with the prior art, the invention has the following beneficial technical effects:

research results show that the medicine has better treatment effect on chronic gastritis and is superior to a vitamin tablet; the medicine of the invention has obvious prevention and treatment effects on rat acute gastritis models caused by aspirin hydrochloride, and the action strength of the medicine is the same as that of a vitamin tablet. The results of the clinical tests on 400 patients with chronic atrophic gastritis who have stagnated heat accumulated in the stomach and hurt qi and yin indicate that: the cure rate of the treatment group is 16.67%, the significant efficiency is 49%, the effective rate is 25.67%, the ineffective rate is 8.67%, and the total effective rate is 91.34%. The cure rate of the control group is 5%, the significant efficiency is 20%, the effective rate is 48%, the ineffective rate is 27%, and the total effective rate is 73%. Through statistical treatment, the comparison and difference of the total curative effects of the two groups have significance, and the curative effect of the granules for nourishing yin and clearing stomach is obviously superior to that of the vitamin tablets. The yin-nourishing and stomach-clearing granules have the effects of nourishing yin, clearing stomach, invigorating spleen and regulating stomach, and have definite curative effects on improving symptoms and mucosa under gastroscope and mucosa pathological biopsy. Especially has remarkable curative effect on improving heartburn, dry lips, nausea, vomiting, bad breath, dry stool, tongue coating, pulse condition and the like.

Drawings

FIG. 1 is a process flow diagram of the present invention.

Detailed Description

The present invention will now be described in further detail with reference to the attached drawings, which are illustrative, but not limiting, of the present invention.

According to the literature, the effective components of the traditional Chinese medicinal materials in the formula of the medicine are mostly water-soluble components, and the bighead atractylodes rhizome, the fructus aurantii and the fructus forsythiae contain more volatile oil, so that the bighead atractylodes rhizome, the fructus aurantii and the fructus forsythiae are decocted in water, after the volatile oil is extracted, the decoction dregs and the rest eleven materials such as poria cocos are extracted again by water, and the main components of the traditional Chinese medicinal materials in the formula are fully extracted as far.

The invention discloses a preparation method of granules for nourishing yin and clearing stomach, which specifically comprises the following steps:

1) the formula is as follows: 160g of dendrobium, 214g of rhizoma anemarrhenae, 107g of coptis, 107g of radix sophorae flavescentis, 160g of poria cocos, 160g of bighead atractylodes rhizome, 160g of astragalus membranaceus, 214g of rhizoma bletillae, 107g of purslane, 160g of fructus aurantii, 214g of radix clematidis, 160g of sanguisorba officinalis, 160g of blackberry lily and 160g of fructus forsythiae;

2) cleaning the fourteen medicinal materials of dendrobium, common anemarrhena rhizome and the like in the formula, and dividing the medicinal materials into two groups.

① extracting volatile oil from rhizoma Atractylodis Macrocephalae, fructus Aurantii, and fructus forsythiae, sealing the volatile oil, and filtering the water extract;

② adding ① medicinal residues into the rest eleven materials such as Poria cocos, decocting with water twice, 10 times of water for 2.5 hours for the first time, 8 times of water for 2 hours for the second time, mixing decoctions, filtering, mixing the filtrate with ① filtrate, and concentrating to obtain fluid extract with relative density of 1.34-1.36 (60 deg.C);

3) mixing the fluid extract 1 part, sucrose 0.8 part, and dextrin 1 part, granulating with appropriate amount of ethanol, drying, adding the volatile oil such as Atractylodis rhizoma, and mixing.

Extracting according to the property of the effective components of the medicine in the prescription of the yin-nourishing stomach-clearing granules, establishing a medicine quality standard to test samples and ensuring the controllable product quality. Meanwhile, pharmacodynamic tests and clinical tests are developed to evaluate the safety and effectiveness of the medicine.

First, the research of the particle technique for nourishing yin and clearing stomach

1. Pharmaceutical composition

Dendrobe: mainly contains alkaloid, flavonoid, polysaccharide, terpenes, phenolic compounds and the like. The alkaloid includes dendrobine, dendrobiicin, 8-hydroxy dendrobiicin, 6-hydroxy dendrobiicin, dendrobine, etc.

Rhizoma anemarrhenae: the chemical components mainly comprise steroid saponin and bisphenone, and contain flavonoid, lignin, polysaccharides, organic acids, trace elements, etc.

Coptis chinensis: the effective components are berberine and berberine, and the main pharmacological actions of the berberine hydrochloride are anti-pathogen, antibacterial, anti-diarrhea, anti-inflammatory, antipyretic, sedative and hypnotic, hypoglycemic, anti-ulcer, anti-tumor, anti-cerebral ischemia, anti-platelet aggregation and the influence on the cardiovascular system.

Flavescent sophora root: mainly contains amino acids, saccharides, fatty acids, triterpenoid saponins, sterols, alkaloids, flavonoids, dialkyl chromone, quinones, coumarins, etc.

Tuckahoe, poria cocos: the effective components are pachyman and triterpenes, and pachyman has effects of enhancing immunity, preventing gland atrophy, reducing spleen enlargement possibility, and inhibiting tumor growth. Pachyman and triterpenes have anti-tumor effect.

White atractylodes rhizome: the effective components are volatile oil, atractylenolide, atractylenovata polysaccharide, etc. The volatile oil of Atractylodis rhizoma has complex components, mainly contains atractylone, atractylol, etc., and has effects of inhibiting various tumors and promoting gastrointestinal motility.

Astragalus root: contains multiple active ingredients including astragalus polysaccharides, astragalus saponin, astragalus flavonoids, etc.

And (3) common bletilla pseudobulb: the main chemical components are bibenzyl, phenanthrene and derivatives thereof, and in addition, a small amount of volatile oil, mucilage, bletilla mannan, starch, glucose and the like are also contained.

Purslane: mainly contains organic acid, flavonoid, terpenes, steroids, alkaloid, coumarin, protein, amino acid and the like.

Fructus aurantii: contains flavone, alkaloid and volatile oil, and the flavone components include naringin, neohesperidin, and small amount of hesperidin, nobiletin, tangeretin, etc. The alkaloid components include synephrine, tyramine, N-methyltyramine, and quinoline.

Clematis root: mainly contains saponins, glycosides, polysaccharides, flavonoids, coumarins, lignans, volatile components, alkaloids, etc.

Garden burnet root: mainly contains tannin, phenolic acid, saponin, flavone and polysaccharide.

Shooting: the chemical components mainly comprise flavones, isoflavones and derivatives thereof, and comprise tectorigenin, wild tectorigenin, sub-wild tectorigenin, tectoridin, Belamcandin, irigenin, irisolidone, tectorigenin, etc.

Fructus forsythiae: mainly contains phenylethanoid glycosides, lignans, volatile oil, terpenes, flavonoids, alkaloids, organic acids, sterols and the like.

2. Research on the Process

Because the effective components of the traditional Chinese medicinal materials in the prescription of the medicine are mostly water-soluble components, and the bighead atractylodes rhizome, the fructus aurantii and the fructus forsythiae contain more volatile oil, the bighead atractylodes rhizome, the fructus aurantii and the fructus forsythiae are decocted in water, after the volatile oil is extracted, the decoction dregs and the rest eleven materials such as tuckahoe are extracted again by water, so that the main components of the traditional Chinese medicinal materials in the prescription are fully extracted as far as possible.

2.1 study of extraction Process

The experiment takes the paste yield and the berberine hydrochloride content as investigation indexes to carry out investigation and verification research on the process so as to obtain the optimal process parameters. Weighing the medicinal materials according to the prescription of 1/10, totally 9 groups, wherein each group is parallel to 3 parts, decocting the largehead atractylodes rhizome, the bitter orange and the weeping forsythia in water, extracting volatile oil, and extracting decoction dregs and eleven types of tuckahoe and the like in water by adopting an orthogonal experimental design. An orthogonal table L9(34) is selected to arrange experiments, and factor and level tables, verification result analysis tables and variance analysis tables 1-3 are selected.

TABLE 1 factor level table

TABLE 2 first extraction orthogonal experimental design and results analysis

The paste yield and the berberine hydrochloride content are taken as investigation indexes to carry out visual analysis, so that the influence of the water addition amount on the paste yield is not obvious, and the influence of the decoction time is large. Combining the experimental results with the actual production, the final preferred process is A4B4, i.e. adding 10 times of water for the first time and decocting for 2.5 hours.

TABLE 3 second extraction orthogonal Experimental design and results analysis

The paste yield and the berberine hydrochloride content are taken as investigation indexes to carry out visual analysis, so that the influence of the water addition amount on the paste yield is not obvious, and the influence of the decoction time is large. Combining the experimental results with the actual production, the final preferred process is A4B4, i.e. 8 times of water is added for the second time, and the decoction is carried out for 2 hours.

The extraction mode of the process is determined by integrating the secondary extraction conditions: decocting with 10 times of water for 2.5 hr; adding 8 times of water for the second time, and decocting for 2 hr.

2.2 study of Molding Process

Through detailed experimental research and investigation on the extraction process of medicinal materials, the optimal extraction conditions are determined, and in order to ensure the quality of finished products, experimental research needs to be carried out on the preparation forming process of the finished products. Because the medicine extract of the invention has larger viscosity, ethanol with different concentrations is adopted for granulation. Repeated tests prove that the 95% ethanol granulation is better, and the prepared granules meet the standard of granules.

2.3 Process verification experiment

The pilot plant test was carried out in the plant under the above preferred process conditions. Weighing the medicinal materials according to the prescription amount of 450 times, paralleling the medicinal materials by 3 parts, randomly compiling the medicinal materials into 1-3 experiment numbers, carrying out experiments according to an optimal process, and determining. The results are shown in Table 4.

TABLE 4 statistical table of experimental results of pilot plant test process verification

The experimental results show that: the preparation process is stable, simple and convenient to operate, and stable and controllable in quality.

Second, research on efficacy test of yin-nourishing stomach-clearing granule

Prevention effect of yin-nourishing stomach-clearing granules on aspirin model

1. Materials and instruments

Experimental animals: wistar male rats with the weight of 150-200 g are provided by the medical experimental animal center of the Siann university of transportation.

The test drugs are: the yin-nourishing stomach-clearing granules are provided by Shanxi Dongke pharmaceutical Limited liability company.

Positive control drug: the vitamin tablets are produced by Xian northern pharmaceutical Co.

2. Test method

Wistar male rats meeting the test requirements are selected and randomly divided into four groups, two groups are administrated, a positive control drug vitamin tablet group and a blank control group. Before molding, the components are respectively infused into the stomach for administration, wherein the volume of the granules for nourishing yin and clearing stomach is 1.3g/kg, 2.3g/kg, the volume of the vitamin tablets is 0.14g/kg, and the distilled water is the same, and the administration is once per day and is continuously carried out for 8 days. Immediately fasting without water after the last administration, feeding a mixed solution of aspirin and hydrochloric acid to each group after 24 hours, killing the head after 4 hours, dissecting and ligating pylorus, injecting 10ml of 2% formalin into the stomach from esophagus, then ligating cardia, removing the stomach, soaking in 2% formalin for 16 minutes, taking out and cutting along the greater curvature of the stomach, and measuring the average value of the sum (namely injury index) of lengths (mm) of glandular and gastric mucosal hemorrhage, ulcer and erosive lesion of each group as an index. Comparing the glandular stomach injury indexes of each group, conventionally fixing the specimen, taking materials, dehydrating, waxing, embedding, slicing, performing histological examination, and evaluating the degree among the groups by taking inflammatory cell infiltration of each animal slice as an index: microscopic examination of the entire visual field grading standard for each section: mild: 1/4 the following inflammatory cells, moderate: 1/4-2/4 inflammatory cells, severe: 1/2 above.

3. Test results

(1) The oral administration of the yin-nourishing and stomach-clearing granules has obvious prevention effect on aspirin gastritis model rats (Table 5).

TABLE 5 preventive effects of Yin-nourishing and stomach-clearing granules on aspirin model

(2) The oral prophylactic administration of the yin-nourishing and stomach-clearing granules has obvious effect of reducing the infiltration of inflammatory cells of gastric tissues on an aspirin gastritis model (Table 6).

TABLE 6 antagonism of inflammatory cell infiltration of gastric tissue by aspirin gastritis model by prophylactic administration of Yin-nourishing stomach-clearing granules

According to the result of non-parameter Ridit analysis, the inflammatory cell infiltration degree of the group with the dosage of 2.3g/kg of the yin-nourishing and stomach-clearing granules and the blank control group is obviously different; and no significant difference with the vitamin tablet group.

Therapeutic action of yin-nourishing stomach-clearing granules on aspirin gastritis model

1. Test materials: same as before

2. The test method comprises the following steps: wistar male rats meeting the test requirements are selected and randomly divided into four groups, two groups of administration groups, a vitamin tablet group and a blank control group are provided, the rats are fasted for 24 hours before the test, water is not forbidden, then 2% aspirin and 0.6N.HC1 liquid lml are administered to each rat through intragastric administration, the treatment is carried out through intragastric administration after 4 hours, administration is carried out once every four hours for four times, and the dosages are 1.3g/kg, 2.3g/kg and 0.14g/kg of a vitamin tablet respectively. At 24 hours after the start of molding, the rats are killed according to the method, the stomach is taken out, and the glandular stomach injury index is observed and counted after the fixed 15 minutes by 2 percent formalin; and (5) evaluating the inflammatory cell infiltration degree of the specimen by conventional specimen preparation and microscopic examination.

3. Test results

(1) The oral administration of the yin-nourishing and stomach-clearing granules has obvious therapeutic effect on aspirin gastritis model rats (Table 7)

TABLE 7 therapeutic effect of Yin-nourishing and stomach-clearing granules on aspirin gastritis model

(2) The oral treatment administration of the yin-nourishing and stomach-clearing granules has obvious effect of relieving the infiltration of inflammatory cells of stomach tissues on an aspirin gastritis model. (Table 8)

TABLE 8 antagonism of inflammatory cell infiltration by aspirin gastritis model with administration of yin-nourishing stomach-clearing granule therapy

(III) therapeutic action of Yin-nourishing stomach-clearing granules on mouse chronic gastritis model

1. Test materials

Reagent: deoxysodium cholate, produced by Shanghai chemical pilot plant.

Experimental animals: the weight of the white mouse is 18-22 g, and the white mouse is male and is provided by the medical experimental animal center of the Sigan university of transportation.

2. Test method

(1) Model building and validation

Taking about 400 male mice, feeding the male mice with normal feed, changing drinking water into 0.1% deoxysodium cholate suspension, controlling each mouse to be about 25mlI every day, continuously feeding the mice for four months, normally feeding a blank control group at the same time, changing the nest for 1-2 times every week in the feeding period, observing drinking water and diet conditions, taking part of the mice to die after four months, taking stomach to carry out conventional fixation and flaking, checking tissue sections of the mice by a light mirror, recording intestinal epithelial metaplasia, inflammatory cell infiltration and reduction or disorder degree of indigenous glands, comparing the tissue sections with the blank control group to confirm whether a chronic gastritis model is formed or not, and using the mice for test after confirming that the model is formed. The results of the various indexes of the model are shown in Table 9.

TABLE 9 comparison of the percentage of the indices of the chronic gastritis model present with the control blank

The three indexes, the model group is heavier than the blank control group, which shows that the indexes can be used as specific indexes of the chronic gastritis animal model for comparing the index change degree after drug treatment. In order to compare the comprehensive change degrees of the three indexes, the three indexes are processed by a grading method, namely:

1) all three indexes are absent, namely-;

2) only one of the three indexes is +;

3) two of the three indicators are + +;

4) the three indicators are all shown as +++;

the above-mentioned grades are classified, statistical treatment is carried out by Ri di t analysis method of nonparametric index grade test, and the results are shown in Table 10.

TABLE 10 Ridit analysis of the composite indices of the model of chronic gastritis

After the treatment of the comprehensive indexes, the R of the model group is 0.99, the 95% confidence limit of the R is 0.86-1.12, the R of the blank control group is 0.50, the confidence limit of the R is 0.38-0.62, and the difference between the R and the blank control group is significant (P is less than 0.05), which indicates that the model is established.

(2) Group test

Mice formed by the confirmed model are divided into five groups, wherein 1.57g/kg (equivalent to 1/2 equivalent dose) of the yin-nourishing and stomach-clearing granules are administered to one group of the mice by intragastric administration, 3.148 g/kg (equivalent to equivalent dose) of the yin-nourishing and stomach-clearing granules are administered to two groups of the mice by intragastric administration, 0.6g/kg (equivalent to four times of equivalent dose) of the vitamin tablets are administered to three groups of the mice by intragastric administration, 20ml/kg of physiological saline is administered to four groups of the mice by intragastric administration, and normal mice are used as a blank control group. After each group is continuously administrated by gastric lavage for one month, the group is respectively killed, the stomach is taken, the conventional fixing and the section making are carried out, the change degree of the three indexes is examined by optical microscope, the difference degree among the occurrence percentage is compared by a t inspection method, and the difference degree among the groups is compared by a nonparametric grading Ridit analysis method according to the comprehensive indexes.

3. Test results

(1) The effect of yin-nourishing and stomach-clearing granules on the degree of intestinal metaplasia in mice model of chronic gastritis is shown in table 11.

TABLE 11 influence of Yin-nourishing and stomach-clearing granules on the degree of intestinal metaplasia in mice

As seen from the results in table 11: the degree of intestinal epithelization of the normal saline group is obviously reduced (P <0.01) compared with that of a model group, but compared with a blank control group, the intestinal epithelization degree of the normal saline group is still kept at 29.4 percent, the intestinal epithelization degree is very obviously different (P <0.01) from that of the yin-nourishing and stomach-clearing granules, the vitamin tablets and the groups, the dosage of the vitamin tablets is 4 times of the equivalent dose seen from the dosage of experimental design, the percentage of intestinal epithelization occurrence is equivalent to that of the equivalent dose of the yin-nourishing and stomach-clearing granules, and the effect of the yin-nourishing and stomach-clearing granules is better than that of the vitamin tablets. It also shows that the model remains relatively stable for one month despite its natural recovery.

(2) The effect of the yin-nourishing and stomach-clearing granules on the degree of inflammatory cell infiltration caused by the mouse chronic gastritis model is shown in table 12.

TABLE 12 Effect of Yin-nourishing and stomach-clearing granules on the degree of infiltration of inflammatory cells in mice

The percentage of inflammatory cell infiltration, and the insignificant difference between the model and saline groups (P >0.05) shown in table 12 indicate that the degree of inflammatory cell infiltration is stable in this model. The other groups had very significant differences (P <0.01) compared to the saline group. Thus, each group showed significant therapeutic effects on inflammatory cell infiltration. And the curative effect of the yin nourishing and stomach clearing granules is superior to that of the vitamin tablets.

(3) The effect of yin-nourishing and stomach-clearing granules on the degree of reduction of the intrinsic glands caused by the mouse model of chronic gastritis is shown in Table 13.

TABLE 13 influence of Yin-nourishing and stomach-clearing granules on reduction of stomach-inherent glands in mice

As seen from the results in table 13: the comparison between the normal saline group and the control group (P <0.01) shows that the percent reduction of the inherent gland of the normal saline control group is reduced and the natural recovery tendency is existed, but the difference (P <0.01) is still very significant compared with the blank control group, and the difference between other administration groups and the normal saline control group is very significant, which shows that the normal saline control group has a certain treatment effect on the reduction of the inherent gland.

(4) The comprehensive effects of the yin-nourishing and stomach-clearing granules on three indexes of the mouse chronic gastritis model are shown in Table 14.

TABLE 14 comprehensive influence of Yin-nourishing and stomach-clearing granules on three indexes of mouse chronic gastritis model

Table 14 the results show that: the model group and the normal saline control group R have obvious difference, which shows that the comprehensive evaluation model group of the three indexes has the influence of natural recovery, but has obvious difference (P <0.05) compared with the blank control group. It is also stated that a relatively stable model of the three markers should be ensured in the case of a month of administration. Therefore, the R of each dosage group has a significant difference (P <0.05) compared with the normal saline control group, the treatment effect of each administration group is reflected, and the two dosage groups of the granules for nourishing yin and clearing stomach are the same as the treatment effect of the vitamin tablet group (P >0.05) from the credible limit range of R. However, the dosage of the vitamin tablet (calculated by equivalent amount) is 4 times (high dosage) and 8 times (low dosage) of the yin-nourishing and stomach-clearing granules, which shows that the drug effect of the yin-nourishing and stomach-clearing granules is better than that of the vitamin tablet.

The result shows that ① model group and normal saline control group have obvious difference (P <0.05), which indicates that each index has different degree of natural recovery after the model is formed without adding medicine but does not recover to the level of blank control group, ② model group index and blank control group have obvious difference (P <0.05), which indicates that chronic gastritis model is established, ③ each administration group has obvious difference (P <0.05) compared with normal saline control group, but the comparison difference between each administration group is not obvious (P >0.05), which indicates that each administration group has the function of treating chronic gastritis, and the effect of the granules for nourishing yin and clearing stomach is better than the effect of the vitamin tablet.

(IV) conclusion and discussion

1. The sodium deoxycholate suspension is continuously drunk by male mice for 4 months to form a mouse chronic gastritis animal model, and the indexes of the mouse chronic gastritis animal model are judged to be feasible by three indexes of inflammatory cell infiltration, intestinal metaplasia and reduction of the inherent gland in gastric histological examination, and are consistent with main indexes selected by clinical cases.

2. In the established chronic gastritis animal model, within one month after drinking of the sodium deoxycholate suspension is stopped, all indexes of the model are naturally recovered to different degrees, but the indexes are still obviously different from those of a blank control mouse. Under the condition that the treatment period does not exceed one month, the model index can still be kept stable, and the comparison with a treatment medicament is convenient.

3. 1.57g/kg of the yin-nourishing and stomach-clearing granules, and the difference of the dosage of 3.14g/kg of the yin-nourishing and stomach-clearing granules and a normal saline control group is obvious, and the granules show the treatment effect on the chronic gastritis. The dosage of the yin nourishing and stomach clearing granules is only 1/4 and 1/8 (in equal amount) of the dosage of the vitamin tablet, the same effect as the therapeutic effect of the vitamin tablet is obtained, and the therapeutic effect of the stomach nourishing and stomach clearing granules on chronic gastritis is better than that of western vitamin tablet.

4. The yin-nourishing stomach-clearing granules have obvious prevention and treatment effects on a rat acute gastritis model caused by aspirin hydrochloric acid. The action intensity is the same as that of the vitamin tablets.

Clinical research of yin-nourishing stomach-clearing granules

The granule has been tested by Dongdong hospital of Beijing university of traditional Chinese medicine, and has been tested by phase II clinical tests with Liaoning institute of traditional Chinese medicine, Dalian institute of traditional Chinese medicine, Benxi institute of traditional Chinese medicine, and Liaoning national hospital. In total, 400 patients with chronic atrophic gastritis were observed, 300 patients in the treatment group and 100 patients in the control group. And (3) test results: the total effective rate of the treatment group is 91.37 percent, the total effective rate of the control group is 73 percent, and the difference of the two groups of curative effects is high through statistical treatment

The degree of significance (p < <0.005) is obviously superior to that of the control group in the treatment group. In the clinical trial process, a few patients have stomach discomfort, nausea and abdominal distension after taking the medicine, and besides, the medicine has no toxic or side effect.

Method of treatment

In the contrast test stage of the clinical test, the clinical test adopts a single blind method to randomly group, and the clinical test is divided into a treatment group and a contrast group, wherein the ratio of the treatment group to the contrast group is 3:1, 30 treatment groups of Beijing university of traditional Chinese medicine and 30 contrast groups; 80 cases of the treatment group of Liaoning institute of traditional Chinese medicine and 30 cases of the control group; 40 treatment groups of TCM of Dalian City and 40 control groups of TCM.

The open control treatment trial phase of this clinical trial was observed for a total of 150 patients in the treatment group. 60 cases of Liaoning province people hospitals; 90 cases of Hospital of materia Medica in Benxi. The clinical curative effect and the toxic and side effects are observed.

135 inpatients and 265 outpatients.

1. Treatment groups: in 300 cases, the medicine is orally taken 15g (1 bag) once, 2 times a day with boiled water half an hour before meal.

2. Control group: in 100 cases, the oral administration of vitamin tablets is 1.2g (6 tablets) once, and one day

2 times, half an hour before meals.

3. The course of treatment is as follows: the treatment group and the control group are two and a half months. Gastroscopy pathology was reviewed within one month after treatment was completed.

(II) detecting the index

1. Safety index

① general physical examination

② examination of liver and kidney function (1/3 more cases)

③ electrocardiographic examination (hospitalized person)

④ routine examination of blood, urine and feces.

2. Observation of efficacy

① related symptoms, signs

② gastroscopy and embolotherapy

③ pathological examination.

(III) therapeutic efficacy determination criteria

The medicine is divided into four grades of clinical cure, obvious effect, effectiveness and ineffectiveness.

Clinical cure: the main symptoms and physical signs completely disappear, the secondary symptoms disappear or basically disappear, chronic inflammation of gastric mucosa is obviously improved after repeated examination by a gastroscope, and gland atrophy, intestinal metaplasia and dysplasia are recovered to be normal or disappear after the pathological examination. The total integral is reduced by more than 90%.

The effect is shown: the principal symptoms and physical signs basically disappear or are obviously improved, the secondary symptoms are improved, the chronic inflammation of the mucosa is rechecked by a gastroscope to improve, the gland atrophy, the intestinal metaplasia and the dysplasia are rechecked or reduced by 2 degrees by pathological examination, and the total integral is reduced by more than 70 percent.

The method has the following advantages: the major symptoms, the minor symptoms and the physical signs are all improved, the gastric mucosa atrophy is improved after the gastroscope review, the chronic inflammation is reduced by 1 degree as proved by pathological examination, and the total integral is reduced by 30-60%.

And (4) invalidation: symptoms and signs were unchanged, there was no improvement on gastroscopy, and the total score dropped by < 30% or was exacerbated.

(IV) therapeutic results

1. Overall therapeutic effect

The clinical test result shows that the total efficiency of 300 patients in the treatment group is 91.3 percent, the total effective rate of the control group is 73 percent, and the difference of the total effects of the two groups has high significance, which is shown in table 15.

TABLE 15 comparison of Total therapeutic effects

2. The curative effects of the major and minor symptoms are compared

TABLE 16-1 comparison of therapeutic effects of the major symptoms

The results show that: the difference after the treatment of the main symptoms of the two groups is highly significant, and P is less than 0.01. The treatment group was significantly better than the control group.

TABLE 16-2 comparison of the curative effects of two groups of secondary symptoms

The results show that: the difference of the curative effect of the secondary symptoms of the two groups of patients is highly significant, and P is less than 0.005. The curative effect of the treatment group for secondary symptoms is obviously better than that of the control group.

(V) adverse reactions

In the process of taking the yin-nourishing and stomach-clearing granules, 2 patients (male 1 and female 1) in the treatment group have stomach discomfort of different degrees; nausea occurred in 4 cases (male 2, female 2); abdominal distension occurred in 2 cases (male 1 female 1). The medicine taking is not affected, and the treatment is not carried out. As treatment continues, symptoms gradually disappear.

(sixth) discussion

1. The results of the clinical tests on 400 patients with chronic atrophic gastritis who have stagnated heat accumulated in the stomach and hurt qi and yin indicate that: the cure rate of the treatment group is 16.67%, the significant efficiency is 49%, the effective rate is 25.67%, the ineffective rate is 8.67%, and the total effective rate is 91.34%. The cure rate of the control group is 5%, the significant efficiency is 20%, the effective rate is 48%, the ineffective rate is 27%, and the total effective rate is 73%. Through statistical treatment, the comparison difference of the total curative effects of the two groups has high significance (P <0.005), and the curative effect of the yin-nourishing and stomach-clearing granules is obviously superior to that of a vitamin tablet.

2. Chronic atrophic gastritis is a common disease, and moderate and severe precancerous lesions. The course of disease is longer and the disease is lingering. At present, western medicines are not products with definite curative effects. The dialectical treatment of the traditional Chinese medicine has great advantages in the aspects of improving symptoms, improving mucosa image under gastroscope and pathological biopsy image of mucosa and the like, and has obvious curative effect.

The main pathogenesis of chronic atrophic gastritis is that food, smoke, wine, emotion and other factors damage stomach qi, resulting in disorder of qi movement, stomach disorder, dampness and heat accumulation, and qi and yin impairment due to stagnated heat. The main clinical manifestations are epigastric fullness, pain, anorexia, secondary manifestations are heartburn, dry lips, halitosis, sticky mouth, nausea, vomiting, fullness and stuffiness in chest and diaphragm, dry stool. Red or tender red tongue with yellow or greasy coating, thick greasy coating, deep and thready and slippery, wiry and slippery pulse. Herbs for nourishing yin and clearing heat are required to nourish body fluid and clear heat.

The embodiments given above are preferable examples for implementing the present invention, and the present invention is not limited to the above-described embodiments. Any non-essential addition and replacement made by the technical characteristics of the technical scheme of the invention by a person skilled in the art belong to the protection scope of the invention.

Claims

1. The traditional Chinese medicine preparation for treating chronic atrophic gastritis is characterized by being prepared from the following raw material medicines in parts by weight: 170 parts of dendrobium officinale, 225 parts of rhizoma anemarrhenae, 100 parts of coptis chinensis, 120 parts of radix sophorae flavescentis, 150 parts of poria cocos, 170 parts of rhizoma atractylodis macrocephalae, 150 parts of astragalus membranaceus, 225 parts of rhizoma bletillae, 100 parts of purslane, 170 parts of fructus aurantii, 225 parts of radix clematidis, 150 parts of sanguisorba officinalis, 170 parts of rhizoma belamcandae and 150 parts of fructus forsythiae.

2. The traditional Chinese medicine preparation for treating chronic atrophic gastritis as defined in claim 1, which is prepared from the following raw material medicines in parts by weight: 160 parts of dendrobium, 214 parts of rhizoma anemarrhenae, 107 parts of coptis, 107 parts of radix sophorae flavescentis, 160 parts of poria cocos, 160 parts of bighead atractylodes rhizome, 160 parts of astragalus membranaceus, 214 parts of rhizoma bletillae, 107 parts of purslane, 160 parts of fructus aurantii, 214 parts of radix clematidis, 160 parts of garden burnet root, 160 parts of blackberry lily and 160 parts of fructus forsythiae.

3. The method for preparing a Chinese medicinal preparation for treating chronic atrophic gastritis of claim 1 or 2, which comprises the following steps:

step one, extracting volatile oil from bighead atractylodes rhizome, fructus aurantii and fructus forsythiae, sealing the volatile oil for later use, and filtering and collecting aqueous extract for later use;

step two, decocting the dregs and the rest eleven materials such as the tuckahoe in water twice, adding 8-12 times of water in the first time, and decocting for 2-3 hours; adding 6-10 times of water for the second time, and decocting for 1.5-2.5 hr; mixing the decoctions, filtering, and concentrating the filtrate to obtain fluid extract with a relative density of 1.34-1.36 (60 ℃);

and step three, mixing the clear paste 1 part, the sucrose 0.8 part and the dextrin 1 part, granulating with a proper amount of ethanol, drying, adding the volatile oil of the bighead atractylodes rhizome and the like, and uniformly mixing to obtain the traditional Chinese medicine.

4. The preparation method of the traditional Chinese medicine preparation for treating chronic atrophic gastritis as defined in claim 3, which is characterized by comprising the following steps: and in the second step, the extraction process of the white atractylodes rhizome, the bitter orange and the forsythia dregs and the rest medicinal materials comprises the steps of reflux extraction twice, wherein the ratio of the first material to the liquid is 1:10, the decoction is carried out for 2.5 hours, and the ratio of the second material to the liquid is 1:8, and the decoction is carried out for 2 hours.