CN106822733B - Ointment for treating precancerous lesion of chronic atrophic gastritis and preparation method thereof - Google Patents

Abstract

The invention discloses an ointment for treating precancerous lesions of chronic atrophic gastritis, which is prepared from the following raw material medicines: 28-32 g of astragalus membranaceus, 16-20 g of sculellaria barbata, 28-32 g of coix seeds, 5-8 g of vinegar rhizoma sparganii, 8-10 g of angelica dahurica, 5-8 g of rhizoma kaempferiae, 5-8 g of Indian iphigenia bulb, 10-15 g of rhodiola rosea, 2-4 g of cinnamon and 2-4 g of borneol. The plaster for treating the precancerous lesion of the chronic atrophic gastritis adopts a method of acupoint application (application of Zhongwan, Zusanli, spleen acupoints and stomach acupoints) during treatment, can obviously improve the pathological changes and pathology of gastric mucosa of a patient, can effectively improve the symptoms of epigastric pain, epigastric fullness, anorexia, belching, weakness, epigastric upset and the like, is beneficial to improving the life quality of the patient, and has the treatment effect obviously superior to Qilian Shupi granules and Weifuchun, and has statistical difference (P is less than 0.05).

Description

Ointment for treating precancerous lesion of chronic atrophic gastritis and preparation method thereof

Technical Field

The invention relates to a paste for treating precancerous lesions of chronic atrophic gastritis and a preparation method thereof.

Background

Chronic Atrophic Gastritis (CAG) is a common and frequently occurring disease of the digestive system, and has a certain relationship with the occurrence of gastric cancer, WHO classified it as a precancerous disease or precancerous state of gastric cancer in 1978. Gastric cancer is the most common malignant tumor, and seriously harms human health. The gastric mucosa cancer is not changed from normal cells into cancer cells in a one-step mode, but is a multi-step canceration process, namely chronic superficial gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → gastric cancer, and the lesion appearing in the period is called precancerous lesion. Precancerous lesion refers to pathological and histological changes of gastric mucosa which are easy to become cancerous, namely dysplasia and intestinal metaplasia of gastric mucosa, which mainly accompany chronic atrophic gastritis, so that clinically, the precancerous lesion of chronic atrophic gastritis or precancerous lesion of gastric cancer is often called with the intestinal metaplasia and dysplasia, and the precancerous lesion of gastric cancer is called with the dysplasia and incomplete large intestine metaplasia which are more than moderate.

At present, in the aspect of treating the precancerous lesion of the chronic atrophic gastritis, western medicine mostly adopts a treatment method aiming at the cause of the disease, such as eradicating Helicobacter Pylori (HP) infection, improving gastric motility, protecting gastric mucosa, supplementing folic acid, B vitamins and the like, or endoscopic minimally invasive treatment, but a treatment medicament with a definite curative effect and an ideal treatment method are lacked. Although the traditional Chinese medicine has obvious curative effect, oral traditional Chinese medicines (or decoction-free granules) have the problems of inconvenience in carrying, trouble in decoction and taking, difficulty in drinking of medicines, difficulty in controlling quality, difficulty in controlling cost, poor compliance of patients and the like, and few oral Chinese patent medicines with exact curative effect are available. Therefore, it is imperative to find a treatment method with exact and simple curative effect.

Disclosure of Invention

Aiming at the prior art, the invention provides an ointment for treating precancerous lesions of chronic atrophic gastritis and a preparation method thereof.

The invention is realized by the following technical scheme:

an ointment for treating precancerous lesions of chronic atrophic gastritis is prepared from the following raw material medicines: 28-32 g of astragalus membranaceus, 16-20 g of sculellaria barbata, 28-32 g of coix seeds, 5-8 g of vinegar rhizoma sparganii, 8-10 g of angelica dahurica, 5-8 g of rhizoma kaempferiae, 5-8 g of Indian iphigenia bulb, 10-15 g of rhodiola rosea, 2-4 g of cinnamon and 2-4 g of borneol.

Preferably, the traditional Chinese medicine is prepared from the following raw material medicines: 30g of astragalus membranaceus, 18g of sculellaria barbata, 30g of semen coicis, 6g of vinegar rhizoma sparganii, 9g of radix angelicae, 6g of rhizoma kaempferiae, 6g of edible tulip, 12g of rhodiola rosea, 6g of cinnamon and 3g of borneol.

The preparation method of the ointment for treating the precancerous lesion of the chronic atrophic gastritis comprises the following steps:

(1) taking radix astragali, herba scutellariae barbatae and rhodiola rosea, adding 8 times (weight times, the same below) of 50% ethanol solution (volume percentage, the same below), heating and refluxing for 2 times, extracting for 1.5 hours each time, combining the extracting solutions, filtering, recovering ethanol from the filtrate at 50-60 ℃ under reduced pressure, and concentrating into thick paste (the water content of the thick paste is 15-20%, each 1g of the thick paste is equivalent to 2-5 g of raw medicinal materials, which is common knowledge in the field and is not described again herein);

taking coix seeds, angelica dahurica and edible tulip, adding 8 times of 80% ethanol solution, heating and refluxing for 2 times, wherein each time lasts for 1.5 hours, combining extracting solutions, filtering, recovering ethanol from filtrate at 50-60 ℃ under reduced pressure, and concentrating into thick paste;

taking vinegar rhizoma sparganii and rhizoma kaempferiae, crushing into coarse particles, adding 10 times of water, soaking for 0.5 hour, extracting and collecting volatile oil (extracting according to a volatile oil extraction method, which is a conventional method), filtering an extracting solution, concentrating to a relative density of 1.05, cooling to room temperature, adding ethanol or an ethanol solution to enable the alcohol content to reach 70%, refrigerating for 24 hours at 4 ℃, filtering, recovering ethanol from a filtrate at 50-60 ℃ under reduced pressure, concentrating into thick paste, adding the collected volatile oil, and uniformly mixing to obtain the thick paste for later use;

pulverizing cortex Cinnamomi into fine powder (120 mesh) to obtain cortex Cinnamomi powder;

adding small amount of ethanol into Borneolum, grinding and dissolving, adding cortex Cinnamomi powder, mixing, adding the above three soft extracts (containing volatile oil), and mixing to obtain medicinal extract;

(2) adding matrix into the above medicinal extract, and making into gel patch (cataplasma).

Further, the specific method of the step (2) comprises the following steps (by weight): taking 70 parts of deionized water, adding a small amount (0.001-0.003 part) of disodium ethylene diamine tetraacetate and 0.01-0.03 part of Tween-80, uniformly mixing, stirring at a low speed (60-90 revolutions per minute), adding 2 parts of carbomer-940 resin, stirring at a medium speed (200-400 revolutions per minute), adding 15 parts of carbomer-941 resin in 3-5 batches, stirring at a low speed for 2 hours until the mixture is uniform, pouring the mixture into a kneader, adjusting the temperature to 50 ℃, stirring for 2 hours, vacuumizing, uniformly stirring, and standing to obtain a blank matrix;

stirring the blank matrix at a low speed, adjusting the pH value to 5-7 (slowly adding NaOH solution with the mass fraction of 10% for adjustment), simultaneously slowly adding glycerol (the adding amount is 15% -23% of the volume of the blank matrix, and is preferably 22.67%), and uniformly mixing to obtain the blank matrix containing the glycerol;

suspending the medicinal extract in 95% ethanol solution 3 times the volume of the medicinal extract, slowly adding into the blank matrix containing glycerol under low-speed stirring (the medicinal extract accounts for 1% -5% of the total weight after adding), stirring and dispersing uniformly, coating on non-woven fabric while hot, cooling to room temperature, and cutting into blocks.

The traditional Chinese medicine considers that the precancerous lesion of the chronic atrophic gastritis is mainly caused by deficiency of spleen and stomach and deficiency of both qi and yin, and is marked by qi-blood stagnation and accumulation of damp-heat. The pathological part is in the stomach, and the pathology is centered on the deficiency of the spleen and kidney. Accordingly, the invention establishes a therapeutic method for strengthening the spleen and tonifying the kidney, promoting qi circulation and removing blood stasis, clearing heat and eliminating dampness, and resolving masses and detoxifying. The recipe selects Huang Qi, which is good at tonifying qi of spleen and stomach, promoting tissue regeneration and nourishing blood. Scutellaria barbata is good at clearing heat and removing toxicity, cooling blood and dissipating blood stasis, and can resist cancer and alleviate pain. Coix seed, semen Coicis strengthens the spleen, promotes diuresis, eliminates dampness, detoxifies and dissipates nodulation. Radix Angelicae Dahuricae has effects of dispelling pathogenic wind and dampness, promoting blood circulation, expelling pus, promoting granulation, and relieving pain. Vinegar rhizoma Sparganii has effects of promoting qi circulation, removing blood stasis, activating qi-flowing, relieving pain, and resolving food stagnation. Kaempferia galanga can promote the circulation of qi, warm the middle energizer and alleviate pain. Pseudobulbus Cremastrae Seu pleiones has effects of clearing heat and toxic substances, eliminating phlegm and resolving masses. Rhodiola rosea has the effects of tonifying qi and nourishing heart, astringing and stopping bleeding, removing blood stasis and reducing swelling, cinnamon has the effects of tonifying primordial yang, warming spleen and stomach, removing cold accumulation and promoting blood circulation. Borneol has the functions of clearing away heat and toxic material, preventing corrosion and promoting granulation. The medicines are combined to play the effects of strengthening the spleen and tonifying the kidney, tonifying qi and promoting tissue regeneration, promoting qi circulation and removing blood stasis, clearing heat and eliminating dampness, and detoxifying and dissipating stagnation.

The plaster for treating the precancerous lesion of the chronic atrophic gastritis is used for treating the precancerous lesion of the chronic atrophic gastritis, and during treatment, an acupoint application method (application of Zhongwan, Zusanli, spleen acupoints and stomach acupoints) is adopted, so that the medicine plays a role in treatment by directly and subcutaneously absorbing and indirectly stimulating the way of stimulating acupoint channel qi, can obviously improve the pathological changes and pathology of gastric mucosa of a patient, can effectively improve the symptoms of epigastric pain, epigastric fullness, anorexia, weakness, gastric upset, eructation and the like, and is beneficial to improving the life quality of the patient. The paste is superior to Qilian Shupi granules in the aspects of improving the pathological changes and the pathology of gastric mucosa of a patient, relieving epigastric pain, epigastric fullness, noisy eructation and the like, and has statistical difference (P is less than 0.05). Is superior to the stomach rejuvenation in the aspects of comprehensive curative effect, improving the pathological changes and the pathology of gastric mucosa of a patient, relieving the pain of the gastric cavity, the fullness and fullness of the gastric cavity, the gastric upset and the belching and the like, and has statistical difference (P is less than 0.05).

Detailed Description

The present invention will be further described with reference to the following examples.

Example 1 preparation of an ointment for the treatment of precancerous lesions of chronic atrophic gastritis

The formula is as follows: 30g of astragalus membranaceus, 18g of sculellaria barbata, 30g of semen coicis, 6g of vinegar rhizoma sparganii, 9g of radix angelicae, 6g of rhizoma kaempferiae, 6g of edible tulip, 12g of rhodiola rosea, 6g of cinnamon and 3g of borneol.

The method comprises the following steps:

(1) taking radix astragali, herba Scutellariae Barbatae and radix Rhodiolae, adding 8 times of 50% ethanol solution, heating and reflux-extracting for 2 times, each time for 1.5 hr, mixing extractive solutions, filtering, recovering ethanol from filtrate at 50-60 deg.C under reduced pressure, and concentrating to obtain soft extract;

taking coix seeds, angelica dahurica and edible tulip, adding 8 times of 80% ethanol solution, heating and refluxing for 2 times, wherein each time lasts for 1.5 hours, combining extracting solutions, filtering, recovering ethanol from filtrate at 50-60 ℃ under reduced pressure, and concentrating into thick paste;

crushing vinegar rhizoma sparganii and rhizoma kaempferiae into coarse particles, adding 10 times of water, soaking for 0.5 hour, extracting and collecting volatile oil, filtering an extracting solution, concentrating to a relative density of 1.05, cooling to room temperature, adding ethanol or an ethanol solution to enable the ethanol content to be 70%, refrigerating for 24 hours at 4 ℃, filtering, recovering ethanol from a filtrate at 50-60 ℃ under reduced pressure, concentrating into thick paste, adding the collected volatile oil, and mixing uniformly to obtain the thick paste for later use;

pulverizing cortex Cinnamomi into fine powder (120 mesh) to obtain cortex Cinnamomi powder;

adding small amount of ethanol into Borneolum, grinding and dissolving, adding cortex Cinnamomi powder, mixing, adding the above three soft extracts (containing volatile oil), and mixing to obtain medicinal extract;

(2) adding matrix into the above medicinal extract, and making into gel patch (cataplasma): taking 70 parts of deionized water, adding 0.002 part of disodium ethylene diamine tetraacetate and 0.002 part of Tween-800.012 part of the disodium ethylene diamine tetraacetate, uniformly mixing, stirring at a low speed (80 revolutions per minute), adding 2 parts of carbomer-940 resin, stirring at a medium speed (300 revolutions per minute), adding 15 parts of carbomer-941 resin in 4 batches, stirring at a low speed for 2 hours until the mixture is uniform, pouring the mixture into a kneader, adjusting the temperature to be 50 ℃, stirring for 2 hours, vacuumizing, uniformly stirring, and standing to obtain a blank matrix;

stirring the blank matrix at a low speed, adjusting the pH value to 6 (slowly adding NaOH solution with the mass fraction of 10 percent for adjustment), simultaneously slowly adding glycerol (the adding amount is 22.67 percent of the volume of the blank matrix), and uniformly mixing to obtain the blank matrix containing the glycerol;

suspending the medicinal extract in 3 times volume of 95% ethanol solution, slowly adding into the blank matrix containing glycerol under low speed stirring (the medicinal extract accounts for 3% of the total weight), stirring, dispersing, spreading on non-woven fabric, cooling to room temperature, and cutting into blocks.

Example 2 preparation of an ointment for the treatment of precancerous lesions of chronic atrophic gastritis

The formula is as follows: 28g of astragalus membranaceus, 20g of sculellaria barbata, 28g of coix seeds, 8g of vinegar rhizoma sparganii, 8g of angelica dahurica, 8g of rhizoma kaempferiae, 5g of edible tulip, 15g of rhodiola rosea, 2g of cinnamon and 4g of borneol.

The method comprises the following steps:

(1) taking radix astragali, herba Scutellariae Barbatae and radix Rhodiolae, adding 8 times of 50% ethanol solution, heating and reflux-extracting for 2 times, each time for 1.5 hr, mixing extractive solutions, filtering, recovering ethanol from filtrate at 50-60 deg.C under reduced pressure, and concentrating to obtain soft extract;

taking coix seeds, angelica dahurica and edible tulip, adding 8 times of 80% ethanol solution, heating and refluxing for 2 times, wherein each time lasts for 1.5 hours, combining extracting solutions, filtering, recovering ethanol from filtrate at 50-60 ℃ under reduced pressure, and concentrating into thick paste;

crushing vinegar rhizoma sparganii and rhizoma kaempferiae into coarse particles, adding 10 times of water, soaking for 0.5 hour, extracting and collecting volatile oil, filtering an extracting solution, concentrating to a relative density of 1.05, cooling to room temperature, adding ethanol or an ethanol solution to enable the ethanol content to be 70%, refrigerating for 24 hours at 4 ℃, filtering, recovering ethanol from a filtrate at 50-60 ℃ under reduced pressure, concentrating into thick paste, adding the collected volatile oil, and mixing uniformly to obtain the thick paste for later use;

pulverizing cortex Cinnamomi into fine powder (120 mesh) to obtain cortex Cinnamomi powder;

adding small amount of ethanol into Borneolum, grinding and dissolving, adding cortex Cinnamomi powder, mixing, adding the above three soft extracts (containing volatile oil), and mixing to obtain medicinal extract;

(2) adding matrix into the above medicinal extract, and making into gel patch (cataplasma): taking 70 parts of deionized water, adding 0.001 part of disodium ethylene diamine tetraacetate and 0.8978 part of Tween-800.03, uniformly mixing, stirring at a low speed (60 revolutions per minute), adding 2 parts of carbomer-940 resin, stirring at a medium speed (200 revolutions per minute), adding 15 parts of carbomer-941 resin in 5 batches, stirring at a low speed for 2 hours until the mixture is uniform, pouring the mixture into a kneader, adjusting the temperature to 50 ℃, stirring for 2 hours, vacuumizing, uniformly stirring, and standing to obtain a blank matrix;

stirring the blank matrix at a low speed, adjusting the pH value to 5 (slowly adding NaOH solution with the mass fraction of 10 percent for adjustment), simultaneously slowly adding glycerol (the adding amount is 15 percent of the volume of the blank matrix), and uniformly mixing to obtain the blank matrix containing the glycerol;

suspending the medicinal extract in 3 times volume of 95% ethanol solution, slowly adding into the blank matrix containing glycerol under low speed stirring (the medicinal extract accounts for 1% of the total weight after adding), stirring, dispersing uniformly, coating on non-woven fabric while hot, cooling to room temperature, and cutting into blocks.

Example 3 preparation of an ointment for the treatment of precancerous lesions of chronic atrophic gastritis

The formula is as follows: 32g of astragalus membranaceus, 16g of sculellaria barbata, 32g of coix seeds, 5g of vinegar rhizoma sparganii, 10g of radix angelicae, 5g of rhizoma kaempferiae, 8g of edible tulip, 10g of rhodiola rosea, 4g of cinnamon and 2g of borneol.

The method comprises the following steps:

(1) taking radix astragali, herba Scutellariae Barbatae and radix Rhodiolae, adding 8 times of 50% ethanol solution, heating and reflux-extracting for 2 times, each time for 1.5 hr, mixing extractive solutions, filtering, recovering ethanol from filtrate at 50-60 deg.C under reduced pressure, and concentrating to obtain soft extract;

taking coix seeds, angelica dahurica and edible tulip, adding 8 times of 80% ethanol solution, heating and refluxing for 2 times, wherein each time lasts for 1.5 hours, combining extracting solutions, filtering, recovering ethanol from filtrate at 50-60 ℃ under reduced pressure, and concentrating into thick paste;

crushing vinegar rhizoma sparganii and rhizoma kaempferiae into coarse particles, adding 10 times of water, soaking for 0.5 hour, extracting and collecting volatile oil, filtering an extracting solution, concentrating to a relative density of 1.05, cooling to room temperature, adding ethanol or an ethanol solution to enable the ethanol content to be 70%, refrigerating for 24 hours at 4 ℃, filtering, recovering ethanol from a filtrate at 50-60 ℃ under reduced pressure, concentrating into thick paste, adding the collected volatile oil, and mixing uniformly to obtain the thick paste for later use;

pulverizing cortex Cinnamomi into fine powder (120 mesh) to obtain cortex Cinnamomi powder;

adding small amount of ethanol into Borneolum, grinding and dissolving, adding cortex Cinnamomi powder, mixing, adding the above three soft extracts (containing volatile oil), and mixing to obtain medicinal extract;

(2) adding matrix into the above medicinal extract, and making into gel patch (cataplasma): taking 70 parts of deionized water, adding 0.003 part of disodium ethylene diamine tetraacetate and 800.01 parts of Tween, uniformly mixing, stirring at a low speed (90 revolutions per minute), adding 2 parts of carbomer-940 resin, stirring at a medium speed (400 revolutions per minute), adding 15 parts of carbomer-941 resin in 3 batches, stirring at a low speed for 2 hours until the mixture is uniform, pouring the mixture into a kneader, adjusting the temperature to 50 ℃, stirring for 2 hours, vacuumizing, uniformly stirring, and standing to obtain a blank matrix;

stirring the blank matrix at a low speed, adjusting the pH value to 7 (slowly adding NaOH solution with the mass fraction of 10 percent for adjustment), simultaneously slowly adding glycerol (the adding amount is 23 percent of the volume of the blank matrix), and uniformly mixing to obtain the blank matrix containing the glycerol;

suspending the medicinal extract in 3 times volume of 95% ethanol solution, slowly adding into the blank matrix containing glycerol under low speed stirring (the medicinal extract accounts for 5% of the total weight), stirring, dispersing, coating on non-woven fabric, cooling to room temperature, and cutting into blocks.

Clinical research data

The inventor of the invention belongs to the subject group, and the research on the mechanism of the reversing CAG precancerous lesion by the Qilian Shufu granule in the national science fund funding project of the earlier stage (NO: 30973826) and the research on the Chinese medicinal compound pharmacology and pharmacodynamics evaluation key technology (NO: 2009ZX09502-015) in the national major scientific and technical project (both of which are subject to the conclusion) shows that the formula of the invention is an effective prescription capable of blocking and reversing the CAG precancerous lesion from multiple links and multiple targets. The term "externally treating means, i.e. internally treating means", and the term "externally treating means, i.e. internally treating means". The invention researches the technology, quality, stability and the like of the 'Qilian Shupi prescription' to prepare the 'Qilian paste', takes the holistic concept of the traditional Chinese medicine, the theory of channels and collaterals and the physiological function of acupoints as theoretical basis, innovatively adopts a method of applying the acupoints, and exerts the external application method of the specific oral medicine to treat CAG precancerous lesion. The results of the clinical studies are reported below.

1 clinical data

1.1 diagnostic Standard Western medicine diagnostic Standard refer to "practical internal sciences" and "Chinese Chronic gastritis consensus opinion" in 2006.

1.2 the inclusion standard ① is in accordance with CAG diagnostic standard, ② all cases are diagnosed by electronic gastroscope and pathological examination before inclusion in the test, ③ pathological examination is accompanied by intestinal metaplasia or dysplasia, ④ is 18-65 years old, and ⑤ patients voluntarily participate in the subject and sign informed consent.

1.3 exclusion criteria ① patients with gastric and duodenal ulcers, ② patients with severe dysplasia or suspected malignant change in pathological diagnosis of gastric mucosa, ③ patients with severe primary diseases such as heart, brain, liver, kidney, lung and blood systems, ④ psychopaths, ⑤ pregnant or lactating women, ⑥ patients with allergic constitution or allergic to more than two drugs and known components in research drugs.

1.4 general data cases are 120 cases of CAG precancerous lesion patients in department of gastroenterology outpatient service of 1 month to 2016 12 months in Shandong Chinese medicine university subsidiary hospital 2014, and the patients are divided into a Qilian ointment group, a Qilian Shupi granule group and a Weifuchun group by a random digital table method, wherein each group comprises 40 cases. 23 male and 17 female in the Qiliangao group, the age is 25-64 years, the average age (51.60 +/-7.24) years, the course of disease is 6 months-17 years, and the average (4.35 +/-4.58) years. In the Qilian Shupi granule group, 22 men and 18 women have the ages of 26-65 years, the average age (49.23 +/-6.77) years, the course of disease is 5 months-15 years, and the average (4.18 +/-5.54) years. In the group of Fuchun, 21 men and 19 women had ages of 28-66 years, the mean age (50.91 + -7.98 years), the course of disease 4 months-16 years, and the mean (4.56 + -5.02) years. The difference of the patients in all groups in terms of sex, age, disease course and the like has no statistical significance (P is more than 0.05), and the patients have comparability.

2 method

2.1 methods of treatment

The astragalus and lotus paste group: the Qilian plaster (prepared in example 1 of the present invention) is applied to acupuncture points (each dose is 20g of crude drug), and the Zhongwan, Zusanli, spleen and stomach acupoints are applied. The plaster is changed 1 time every 2 days, and is applied for 6 days and stopped using for 1 day.

The Qilianshupi granule group: the Qilianshupi granules (composed of 24g of radix astragali, 12g of sculellaria barbata, 9g of fructus ligustri lucidi, 6g of rhizoma zedoariae and 24g of semen coicis) are prepared, and each bag of granules is equivalent to 10g of crude drug (produced by pharmaceutical factories of people hospitals in Weifang city). The use method comprises the following steps: 10g each time, 3 times daily, and is taken with warm water.

And (3) a stomach rejuvenation group: the compound stomach-invigorating and anti-aging tablets are orally taken, and the specification is as follows: 0.359g is multiplied by 60 tablets/bottle, Chinese medicine standard Z33020146, produced by Chongzhou Chongqing Yuntang pharmaceutical Co., Ltd, 4 tablets each time, 3 times daily.

Each group has 3 months as 1 course of treatment and 2 courses of treatment.

The pathological index graduation standard refers to the standard of Chinese Chronic gastritis consensus opinion, wherein ① inflammation is mild, inflammatory cell infiltration is located above the bottom of a stomach fovea, moderate, inflammatory cell infiltration is deep to glandular organ inherent membrane, severe, inflammatory cell infiltration is deep to mucosal muscular layer, ② atrophy is mild, inherent glandular atrophy is reduced within 1/3, moderate, inherent glandular atrophy is reduced within 1/3-2/3, inherent glandular atrophy is reduced more than 2/3, ③ intestinal metaplasia is mild, intestinal surface epithelium or/and glandular organ occupy less than 1/3 of the whole length of the mucosa, moderate, intestinal surface epithelium or/and glandular organ occupy less than 1/3-2/3 of the whole length of the mucosa, severe, intestinal surface epithelium or/and glandular organ occupy more than 2/3 of the whole length of the mucosa, ④ heterotypic rhabdoid hyperplasia is mild, nucleus, deep staining, circular, oval or columnar arrangement, gastric cell infiltration is located in the same direction as gastric cavum, gastric papillary epithelial cell infiltration, and gastric papillary cell infiltration is not dense, the abnormal cell division is not similar to the gastrointestinal mucosa is small, the gastrointestinal mucosa is not similar to the gastrointestinal mucosa is thick, the gastrointestinal mucosa is not similar to the gastrointestinal mucosa, the gastrointestinal mucosa is thick, the gastrointestinal mucosa is thick, the mucosa is thick.

2.3 the evaluation standard of the comprehensive curative effect refers to the guideline of clinical research of new drugs in traditional Chinese medicine, ① clinical recovery, clinical symptoms and physical signs disappear, gastroscope review of the chronic inflammation of the mucous membrane obviously improves the conversion to mild degree, and histopathology examination proves that the glandular atrophy, the intestinal metaplasia and the dysplasia recover to normal or disappear. ② clinical symptoms and physical signs disappear, gastroscope review of the chronic inflammation of the mucous membrane improves the conversion, and histopathology examination proves that the glandular atrophy, the intestinal metaplasia or the dysplasia recover to normal or alleviate 2 degrees. ③ is effective, clinical symptoms and physical signs are obviously alleviated, gastroscope review of the pathological change range of the gastric mucosa is reduced by more than 1/2, and histopathology examination proves that the chronic inflammation is alleviated by more than 1 degree, the glandular atrophy, the intestinal metaplasia and the dysplasia are alleviated, ④ is ineffective, and the patient does not reach the effective standard or worsen.

2.4 decision standard of gastroscope curative effect, according to the guideline of clinical research of new drugs in traditional Chinese medicine, ① is used for curing, the obvious improvement of chronic inflammation of mucous membrane is found to be mild after the gastroscope review, ② is used for showing effect, the improvement of chronic inflammation of mucous membrane is found after the gastroscope review, ③ is used for showing effect, the lesion range of the mucous membrane is reduced by 1/2 after the gastroscope review, and ④ is not used for patients who do not reach the effective standard or are deteriorated.

2.5 the index of the curative effect of the traditional Chinese medicine is judged according to the clinical research guiding principle of the new traditional Chinese medicine for treating the chronic atrophic gastritis in the 2002 clinical research guiding principle of the new traditional Chinese medicine. The main symptoms are: epigastric pain, epigastric fullness; the secondary symptoms are as follows: anorexia, asthenia, and belching. The major symptoms are respectively counted as 0, 2, 4 and 6 according to the absence, lightness, middle and weight of the disease, the minor symptoms are respectively counted as 0, 1, 2 and 3 according to the absence, lightness, middle and weight of the disease, and the integral change before and after treatment is compared.

2.6 statistical methods SPSS19.0 statistical software was used to measure data

Expression, variance analysis is adopted for counting data, rank sum test is adopted for grading data, and the difference is more than 0.05, so that the statistical significance is achieved.

3 results

3.1 comparison of the comprehensive therapeutic effects of the patients in each group

Compared with the group of the qiliangao and the group of the stomach rejuvenation, the healing, the significant effect and the effective condition have significant statistical difference (P is less than 0.01), and the total effective rate has statistical difference (P is less than 0.05). The Qilian ointment group has the advantages of recovery, obvious effect and effective patients more than the Qilian Shupi granule group, but the two groups have no statistical difference (P is more than 0.05). See table 1.

TABLE 1 comparison of the combined therapeutic effects of the groups

Note: p < 0.05, P < 0.01 compared to the stilbenic paste group.

3.2 gastroscope curative effect comparison of patients in each group

The Qiliangao group has the advantages that the curative effect, the obvious effect and the effective patients are more than the Qilian Shupi granule group (P is less than 0.05) and the WeiFuchun group (P is less than 0.01), the total effective rate of the curative effect of the Qiliangao group by the gastroscope is better than that of the other two groups, and the statistical difference (P is less than 0.05) exists. See table 2.

TABLE 2 gastroscopy efficacy comparisons

Note: p < 0.05, P < 0.01 compared to the stilbenic paste group.

3.3 comparison of pathological changes in the patients of each group

Before treatment, there were no statistical differences in pathology (P > 0.05) for each group.

The stilbene lotus paste group and the stilbene lotus Shupi granule group have obvious improvement (P is less than 0.05) on the aspects of mucosal inflammation, atrophy and intestinal epithelial metaplasia after treatment compared with the prior treatment, and the heterotypic hyperplasia is not obviously improved (P is more than 0.05); the inflammation and atrophy after the stomach rejuvenation group is treated are obviously improved (P is less than 0.05) compared with those before the stomach rejuvenation group is treated, and the intestinal metaplasia and the allotype hyperplasia are not obviously improved (P is more than 0.05).

In the aspect of inflammation, the disease improvement of the radix astragali and lotus paste group after treatment is better than that of the radix astragali and lotus comforting particle group (P is less than 0.05) and the stomach rejuvenation group (P is less than 0.01); in the aspect of atrophy, the disease improvement of the radix astragali and lotus paste group after treatment is better than that of the radix astragali and lotus Shupi granule group (P is less than 0.05) and the stomach rejuvenation group (P is less than 0.01); in the aspect of intestinal epithelization, the disease improvement of the astragalus and lotus paste group after treatment is better than that of the stomach rejuvenation group (P is less than 0.05), and compared with the astragalus and lotus disintegrating lump granule group, the astragalus and lotus disintegrating lump group has no statistical difference (P is more than 0.05); for dysplasia, there was no statistical difference in the post-treatment effect (P > 0.05) for each group, see Table 3.

TABLE 3 comparison of pathological changes in groups (examples)

3.4 comparison of symptom improvement in patients of each group

3.4.1 integral comparison of epigastric pain

After the astragalus and lotus paste composition is treated, the integral of epigastric pain is obviously reduced, and the statistical difference (P is less than 0.01) is obvious compared with that before treatment; after treatment, the epigastric pain improvement condition of the Qiliangao group is better than that of the other two groups, and the statistical difference exists (P is less than 0.05). See table 4.

TABLE 4 comparison of the epigastric pain scores for each group

Note that P is less than 0.05 and P is less than 0.01 after the treatment with the astragalus-lotus paste group, and △ P is less than 0.05 and △△ P is less than 0.01 before the treatment with the same group.

3.4.2 integral comparison of epigastric fullness

After the astragalus and lotus paste composition is used for treating, epigastric fullness is obviously improved, and the statistical difference (P is less than 0.01) is obvious compared with that before treatment. The Qilian plaster group is superior to other two groups in improving the symptoms of epigastric fullness, and has statistical difference (P is less than 0.05) compared with the Qilian Shupi granule group and has significant statistical difference (P is less than 0.01) compared with the Fufuchun group. See table 5.

TABLE 5 comparison of the epigastric fullness scores for each group

Note that P is less than 0.05 and P is less than 0.01 after the treatment with the astragalus-lotus paste group, and △ P is less than 0.05 and △△ P is less than 0.01 before the treatment with the same group.

3.4.3 integral comparison of anorexia and hypodynamia

After treatment, the anorexia and the hypodynamia of each group are obviously improved, and the statistical difference is significant compared with that before treatment (P is less than 0.01); there were no statistical differences (P > 0.05) between the groups after treatment in terms of improvement in anorexia and asthenia. See table 6.

TABLE 6 integral comparison of anorexia and hypodynamia for each group

Note that P is less than 0.05 and P is less than 0.01 after the treatment with the astragalus-lotus paste group, and △ P is less than 0.05 and △△ P is less than 0.01 before the treatment with the same group.

3.4.4 Integrated comparison of belching with noise

The gastric upset belching of each group was significantly improved after treatment, and compared with that before treatment, there was a significant statistical difference (P < 0.01). The astragalus-lotus paste group is superior to the astragalus-lotus Shupi granule group and the stomach rejuvenation group in improving the noisy eructation symptom, and has statistical difference (P is less than 0.05). See table 7.

TABLE 7 noisy belching score comparisons for each group

Note P < 0.05 and P < 0.01 after treatment with control group and △ P < 0.05 and △△ P < 0.01 before treatment with test group.

3.5 evaluation of safety

In the treatment process of each group, no obvious clinical adverse reaction occurs, and the compliance of patients is good.

Discussion 4

The formula of the astragalus and lotus paste is as follows: 30g of astragalus membranaceus, 18g of sculellaria barbata, 30g of semen coicis, 6g of vinegar rhizoma sparganii, 9g of radix angelicae, 6g of rhizoma kaempferiae, 6g of edible tulip, 12g of rhodiola rosea, 6g of cinnamon and 3g of borneol. The plaster is prepared into an acupoint application by adopting a modern process. The formula is based on the original formula of the astragalus, lotus and disintegrating tablet, the dosage of the original medicines of astragalus, barbed skullcap herb and coix seed is increased, and the effects of tonifying qi and promoting granulation, cooling blood and removing stasis, and promoting diuresis and eliminating dampness and dissipating stagnation are stronger; vinegar rhizoma sparganii replaces vinegar rhizoma zedoariae, and both the vinegar rhizoma sparganii and the vinegar rhizoma zedoariae have the effects of promoting qi circulation, removing blood stasis, promoting qi circulation, relieving pain and removing food retention, but the vinegar rhizoma sparganii has stronger effects of breaking blood and removing blood stasis, and the vinegar rhizoma zedoariae is more favorable for promoting qi circulation. The original formula of the Qilianshupi granule is changed into the formula of cinnamon, the glossy privet fruit has mild effects of tonifying liver and kidney, and the cinnamon has the effects of warming spleen and kidney, tonifying primordial yang, promoting blood circulation, and reinforcing kidney to promote blood circulation, and the medicaments such as angelica dahurica, rhizoma kaempferiae, Indian iphigenia bulb, rhodiola rosea, cinnamon, borneol and the like are added.

The traditional Chinese medicine considers that the precancerous lesion of the chronic atrophic gastritis is mainly caused by deficiency of spleen and stomach and deficiency of both qi and yin, and is marked by qi-blood stagnation and accumulation of damp-heat. The pathological part is in the stomach, and the pathology is centered on the deficiency of the spleen and kidney. Accordingly, the therapeutic method of invigorating spleen and kidney, promoting qi circulation and removing blood stasis, clearing heat and eliminating dampness, and resolving hard mass and removing toxic substance is established. The recipe selects Huang Qi, which is good at tonifying qi of spleen and stomach, promoting tissue regeneration and nourishing blood. Scutellaria barbata is good at clearing heat and removing toxicity, cooling blood and dissipating blood stasis, and can resist cancer and alleviate pain. Coix seed, semen Coicis strengthens the spleen, promotes diuresis, eliminates dampness, detoxifies and dissipates nodulation. Radix Angelicae Dahuricae has effects of dispelling pathogenic wind and dampness, promoting blood circulation, expelling pus, promoting granulation, and relieving pain. Vinegar rhizoma Sparganii has effects of promoting qi circulation, removing blood stasis, activating qi-flowing, relieving pain, and resolving food stagnation. Kaempferia galanga can promote the circulation of qi, warm the middle energizer and alleviate pain. Pseudobulbus Cremastrae Seu pleiones has effects of clearing heat and toxic substances, eliminating phlegm and resolving masses. Rhodiola rosea has the effects of tonifying qi and nourishing heart, astringing and stopping bleeding, removing blood stasis and reducing swelling, cinnamon has the effects of tonifying primordial yang, warming spleen and stomach, removing cold accumulation and promoting blood circulation. Borneol has the functions of clearing away heat and toxic material, preventing corrosion and promoting granulation. The medicines are used together to play the functions of strengthening the spleen and tonifying the kidney, tonifying qi and promoting tissue regeneration, promoting qi circulation and removing blood stasis, clearing heat and eliminating dampness, and detoxifying and dissipating stagnation.

Clinical research results show that the 'Qilian plaster' adopts a method of acupoint application to treat the precancerous lesion of the chronic atrophic gastritis, is beneficial to improving the comprehensive curative effect of a patient, improving the pathological changes and pathology of gastric mucosa of the patient, effectively improving the symptoms of epigastric pain, epigastric fullness, anorexia, fatigue, belching and the like, and is beneficial to improving the life quality of the patient. The astragalus-lotus paste is superior to astragalus-lotus disintegrating granules in the aspects of improving the pathological changes and pathology of gastric mucosa of a patient, relieving epigastric pain, epigastric fullness, epigastric belching and the like, and has statistical difference (P is less than 0.05). The Qilian plaster is superior to the group of Fuchun in the aspects of comprehensive curative effect, improvement of gastric mucosa pathological changes and pathology of patients, relief of epigastric pain, epigastric fullness, epigastric belching and the like, and has statistical difference (P is less than 0.05).

The term "externally treating means, i.e. internally treating means", and the term "externally treating means, i.e. internally treating means". The invention optimizes the clinical effect of the original Qilian Shupi granule, researches on process, quality, stability and the like, develops the Qilian ointment, takes the holistic concept of traditional Chinese medicine, the theory of channels and collaterals and the physiological function of acupoints as theoretical basis, and adopts the method of sticking and applying Zhongwan, Zusanli, spleen acupoints and stomach acupoints, so that the medicine can play a therapeutic role by directly and subcutaneously absorbing and indirectly stimulating and exciting the channels and qi of the acupoints. Not only has direct action, but also has low price, simple medicine, no wound and no pain.

The invention adopts an external treatment method of acupoint application, selects synergistic Mesona-Shu acupoint, and adopts the actions of leading yin from yang and leading yang from yin to treat precancerous lesion of gastric cancer, so that the invention has the advantages of direct action, definite curative effect, simplicity, convenience, low cost, no wound and no pain, and fully embodies the advantages of the traditional Chinese medicine external treatment method. In addition, the high-efficiency traditional Chinese medicine is carefully selected, the meticulous prescription compatibility is carried out, and a series of researches are carried out to form the modern traditional Chinese medicine externally-applied paste which has reasonable process, controllable quality, stable preparation, exact curative effect and good safety, thereby further improving the economic benefit of the medicine and providing safe and effective guarantee for the clinical popularization and application of the paste.

5 conclusion

The clinical application effect of the Qilian plaster is obviously better than that of the Qilian Shupi granule and the clinical common Chinese patent medicine of Weifuchun, the safety is good, and in addition, the Qilian plaster is simple and easy to implement in treatment and simple in price and drug, thereby providing guarantee for clinical popularization.

Claims (6)

1. A gel emplastrum for treating precancerous lesion of chronic atrophic gastritis is characterized in that: the active ingredients of the medicine are prepared from the following raw material medicines: 28-32 g of astragalus membranaceus, 16-20 g of sculellaria barbata, 28-32 g of coix seeds, 5-8 g of vinegar rhizoma sparganii, 8-10 g of angelica dahurica, 5-8 g of rhizoma kaempferiae, 5-8 g of Indian iphigenia bulb, 10-15 g of rhodiola rosea, 2-4 g of cinnamon and 2-4 g of borneol.

2. The gel patch for treating precancerous lesions of chronic atrophic gastritis as defined in claim 1, wherein: the active ingredients of the medicine are prepared from the following raw material medicines: 30g of astragalus membranaceus, 18g of sculellaria barbata, 30g of semen coicis, 6g of vinegar rhizoma sparganii, 9g of radix angelicae, 6g of rhizoma kaempferiae, 6g of edible tulip, 12g of rhodiola rosea, 6g of cinnamon and 3g of borneol.

3. The gel patch for the treatment of precancerous lesions of chronic atrophic gastritis according to claim 1 or 2, characterized in that: is prepared by the following method:

(1) taking radix astragali, herba Scutellariae Barbatae and radix Rhodiolae, adding 8 times of 50% ethanol solution, heating and reflux-extracting for 2 times, each time for 1.5 hr, mixing extractive solutions, filtering, recovering ethanol from filtrate at 50-60 deg.C under reduced pressure, and concentrating to obtain soft extract;

taking coix seeds, angelica dahurica and edible tulip, adding 8 times of 80% ethanol solution, heating and refluxing for 2 times, wherein each time lasts for 1.5 hours, combining extracting solutions, filtering, recovering ethanol from filtrate at 50-60 ℃ under reduced pressure, and concentrating into thick paste;

crushing vinegar-processed rhizoma sparganii and rhizoma kaempferiae into coarse particles, adding 10 times of water, soaking for 0.5 hour, extracting and collecting volatile oil, filtering an extracting solution, concentrating, cooling to room temperature, adding ethanol or an ethanol solution to enable the ethanol content to be 70%, refrigerating for 24 hours at 4 ℃, filtering, recovering ethanol from a filtrate at 50-60 ℃ under reduced pressure, concentrating into thick paste, adding the collected volatile oil, and uniformly mixing to obtain the thick paste for later use;

pulverizing cortex Cinnamomi into fine powder to obtain cortex Cinnamomi powder;

adding ethanol into Borneolum Syntheticum, grinding and dissolving, adding cortex Cinnamomi powder, mixing, adding the above three soft extracts, and mixing to obtain medicinal extract;

(2) adding matrix into the above medicinal extract, and making into gel patch.

4. The gel patch for treating precancerous lesions of chronic atrophic gastritis as defined in claim 3, wherein: the specific method of the step (2) is as follows: taking 70 parts of water, adding 0.001-0.003 part of disodium ethylene diamine tetraacetate and 0.01-0.03 part of Tween-800, uniformly mixing, stirring at a low speed, adding 2 parts of carbomer-940 resin, stirring at a medium speed, adding 15 parts of carbomer-941 resin in 3-5 batches, stirring at a low speed for 2 hours until the mixture is uniform, pouring the mixture into a kneader, adjusting the temperature to 50 ℃, stirring for 2 hours, vacuumizing, stirring uniformly, and standing to obtain a hollow white substrate;

stirring the blank matrix at a low speed, adjusting the pH value to 5-7, slowly adding glycerol, wherein the addition amount is 15-23% of the volume of the blank matrix, and uniformly mixing to obtain the blank matrix containing glycerol;

suspending the medicine extract in 95% ethanol solution with 3 times volume, slowly adding into the blank matrix containing glycerol under low-speed stirring, adding to the medicine extract with a weight of 1% -5% of the total weight, stirring and dispersing uniformly, coating on non-woven fabric while hot, cooling to room temperature, and cutting into blocks.

5. The method for preparing the gel emplastrum for treating the precancerous lesion of the chronic atrophic gastritis according to any one of claims 1 to 4, wherein: the method comprises the following steps:

(1) taking radix astragali, herba Scutellariae Barbatae and radix Rhodiolae, adding 8 times of 50% ethanol solution, heating and reflux-extracting for 2 times, each time for 1.5 hr, mixing extractive solutions, filtering, recovering ethanol from filtrate at 50-60 deg.C under reduced pressure, and concentrating to obtain soft extract;

taking coix seeds, angelica dahurica and edible tulip, adding 8 times of 80% ethanol solution, heating and refluxing for 2 times, wherein each time lasts for 1.5 hours, combining extracting solutions, filtering, recovering ethanol from filtrate at 50-60 ℃ under reduced pressure, and concentrating into thick paste;

crushing vinegar-processed rhizoma sparganii and rhizoma kaempferiae into coarse particles, adding 10 times of water, soaking for 0.5 hour, extracting and collecting volatile oil, filtering an extracting solution, concentrating, cooling to room temperature, adding ethanol or an ethanol solution to enable the ethanol content to be 70%, refrigerating for 24 hours at 4 ℃, filtering, recovering ethanol from a filtrate at 50-60 ℃ under reduced pressure, concentrating into thick paste, adding the collected volatile oil, and uniformly mixing to obtain the thick paste for later use;

pulverizing cortex Cinnamomi into fine powder to obtain cortex Cinnamomi powder;

adding ethanol into Borneolum Syntheticum, grinding and dissolving, adding cortex Cinnamomi powder, mixing, adding the above three soft extracts, and mixing to obtain medicinal extract;

(2) adding matrix into the above medicinal extract, and making into gel patch.

6. The method of claim 5, wherein: the specific method of the step (2) is as follows: taking 70 parts of water, adding 0.001-0.003 part of disodium ethylene diamine tetraacetate and 0.01-0.03 part of Tween-800, uniformly mixing, stirring at a low speed, adding 2 parts of carbomer-940 resin, stirring at a medium speed, adding 15 parts of carbomer-941 resin in 3-5 batches, stirring at a low speed for 2 hours until the mixture is uniform, pouring the mixture into a kneader, adjusting the temperature to 50 ℃, stirring for 2 hours, vacuumizing, stirring uniformly, and standing to obtain a hollow white substrate;

stirring the blank matrix at a low speed, adjusting the pH value to 5-7, slowly adding glycerol, wherein the addition amount is 15-23% of the volume of the blank matrix, and uniformly mixing to obtain the blank matrix containing glycerol;

suspending the medicine extract in 95% ethanol solution with 3 times volume, slowly adding into the blank matrix containing glycerol under low-speed stirring, adding to the medicine extract with a weight of 1% -5% of the total weight, stirring and dispersing uniformly, coating on non-woven fabric while hot, cooling to room temperature, and cutting into blocks.