Application of mirabilitum praeparatum and periplaneta americana composition in preparation of medicine for treating gastric ulcer caused by helicobacter pylori

Abstract

The invention belongs to the field of traditional Chinese medicines, and provides application of a watermelon frost and periplaneta americana composition in preparation of a medicine for treating gastric ulcer caused by helicobacter pylori. The invention provides an application of a mirabilitum praeparatum and periplaneta americana composition in treatment of gastric ulcer, the composition has an effect of inhibiting and killing helicobacter pylori in vitro, and has a good synergistic effect in a specific proportion; the composition can reduce the ulcer index of a gastric ulcer model rat, and has good effects of protecting gastric mucosa and improving gastric ulcer; compared with a control Chinese patent medicine, the medicament prepared from the composition can improve the effective rate of helicobacter pylori induced gastric ulcer and the HP eradication rate. The invention provides a novel pharmaceutical composition for helicobacter pylori induced gastric ulcer, and the pharmaceutical composition is high in safety and few in side effect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a composition of watermelon frost and American cockroach for treating gastric ulcers caused by Helicobacter pylori. Background Technology

[0002] The information disclosed in this background section is intended to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Gastric ulcer (GU) is a common digestive disorder characterized by ulceration of the stomach lining. The primary causes are long-term Helicobacter pylori infection and / or overuse of nonsteroidal anti-inflammatory drugs (NSAIDs), leading to damage to the gastric mucosa. Typical symptoms include stomach pain, decreased appetite, and weight loss; in severe cases, gastric perforation or bleeding may occur. GU is a common digestive disease, affecting approximately 10% of the global population at some point in their lives. Treatment for GU is primarily drug-based, using chemical medications including proton pump inhibitors and antibiotics.

[0004] Modern medicine has found that approximately 70% of gastric ulcer patients are caused by Helicobacter pylori (H. pylori). Helicobacter pylori Helicobacter pylori (H. pylori) infection is the primary cause of gastric ulcers. Modern medicine primarily treats them with antibiotics and proton pump inhibitors (PPIs) to kill H. pylori and reduce the irritation of the ulcer by stomach acid. While this treatment method is effective in targeting the underlying cause and alleviating stomach pain, it is prone to causing numerous adverse reactions. For example, long-term suppression of stomach acid can lead to gastric mucosal atrophy, chronic atrophic gastritis, and impaired gastrointestinal function; reduced stomach acid secretion can cause an increase in gastric pH, promoting small intestinal bacterial overgrowth and increasing the risk of intestinal infection. In some cases, it can also cause abnormalities in liver and kidney function. Therefore, although the cause of gastric ulcers caused by H. pylori is clear and the treatment is relatively targeted, the treatment effect remains unsatisfactory.

[0005] Traditional Chinese medicine (TCM) has unique advantages in treating gastric ulcers. TCM believes that the occurrence of gastric ulcers is closely related to factors such as external pathogens invading the stomach, dietary damage to the stomach, emotional distress, blood stasis obstructing the meridians, and prolonged illness leading to physical weakness. Based on different etiologies and symptoms, gastric ulcers are classified into four types: liver-stomach qi stagnation, liver-stomach heat stagnation, spleen-stomach deficiency-cold, and stomach yin deficiency, with prescriptions tailored to each type. Long-term medical practice has shown that the combination of watermelon frost and American cockroach (Periplaneta americana) has significant efficacy and good safety in treating gastric ulcers caused by Helicobacter pylori. This combination can serve as a basic prescription for clinical diagnosis and treatment, and it can also be developed into an innovative TCM drug for treating gastric ulcers caused by Helicobacter pylori.

[0006] Watermelon Frost is a plant of the Cucurbitaceae family, specifically watermelon.Citrullus lanatus The mature fresh fruit of Periplaneta americana of the family Blattidae is processed with skin nitre. It is salty and cold, and is attributed to the lung, stomach and large intestine meridians. It has the functions of clearing heat and purging fire, and reducing swelling and relieving pain. It is mainly used for treating sore throat, laryngeal obstruction, and aphtha. Periplaneta americana The dried body of Periplaneta americana of the family Blattidae is salty and flat, and is attributed to the liver, kidney and spleen meridians. It has the functions of activating blood and resolving stasis, clearing heat and resolving toxin, reducing swelling and promoting tissue regeneration, and eliminating accumulation. It can be used for treating accumulation of masses, infantile malnutrition, sore throat, sore and swollen throat, sore and swollen throat, hemorrhoids, oral ulcer, gastric and duodenal ulcer. SUMMARY

[0007] In view of the poor effect of current drugs on Helicobacter pylori induced gastric ulcer, the application of a composition of watermelon cream and Periplaneta americana in treating Helicobacter pylori induced gastric ulcer is provided. The composition has a synergistic bacteriostatic effect on Helicobacter pylori and a good protective effect on gastric ulcer.

[0008] To achieve the above-mentioned purpose, the technical scheme is adopted as follows.

[0009] The application of a composition in the preparation of a gastric ulcer drug, wherein the composition is prepared from watermelon cream and Periplaneta americana in a mass ratio of 1:8-1:1.

[0010] Preferably, the gastric ulcer is caused by Helicobacter pylori.

[0011] Preferably, in the composition, the mass ratio of watermelon cream to Periplaneta americana is 1:4-1:2.

[0012] The Periplaneta americana is Periplaneta americana or an extract of Periplaneta americana; the extraction solvent of the extract is water or an alcohol solution; and the concentration of the alcohol solution is preferably 20wt%-95wt%, more preferably 50wt%-70wt%.

[0013] Preferably, the preparation method of the water extract of Periplaneta americana comprises the following steps: decocting and extracting Periplaneta americana with water, concentrating the decocting liquid, and drying to obtain.

[0014] The preparation method of the alcohol extract of Periplaneta americana comprises the following steps: taking Periplaneta americana and extracting with 20wt%-95wt% ethanol, recovering ethanol from the extract, and concentrating and drying to obtain.

[0015] In order to improve the extraction efficiency of effective components in Periplaneta americana, the extraction method can adopt heating reflux method, immersion method or percolation method.

[0016] The present application has the following advantages: The application provides application of a composition of watermelon frost and Periplaneta americana in treatment of gastric ulcer, the composition has effects of inhibiting and killing Helicobacter pylori in vitro, and has good synergistic effect under a specific ratio; the composition can reduce ulcer index of a gastric ulcer model rat, has good effects of protecting gastric mucosa and improving gastric ulcer; compared with a control Chinese medicine, a medicament prepared from the composition can improve effective rate and HP eradication rate on gastric ulcer caused by Helicobacter pylori. The application provides a new medicament combination for gastric ulcer caused by Helicobacter pylori, and has high safety and few side effects. DETAILED DESCRIPTION

[0017] The application will be further described below in combination with examples, but the application is not limited by the following examples.

[0018] Example 1 Preparation of a composition of watermelon frost and Periplaneta americana and bacteriostatic effect 1. Preparation of the composition The Periplaneta americana is extracted twice by heating reflux with 70% ethanol, 8 times the amount is added in the first time, and 6 times the amount is added in the second time, each time is refluxed for 2 hours, and then filtered, the ethanol in the filtrate is recovered, and the filtrate is concentrated under reduced pressure to a clear paste with a relative density of 1.30-1.34 (65 DEG C), the clear paste is dried under reduced pressure, and is crushed into fine powder to obtain the Periplaneta americana ethanol extract.

[0019] The Periplaneta americana ethanol extract is divided into four equal parts, and watermelon frost fine powder is weighed according to 0.125, 0.25, 0.5 and 1 times the mass of Periplaneta americana (the amount of the extract is converted into the original Periplaneta americana medicinal material), and then the watermelon frost fine powder is mixed with the Periplaneta americana ethanol extract to obtain compositions 1-4, and the ratio of watermelon frost to Periplaneta americana is 1:8, 1:4, 1:2 and 1:1 respectively.

[0020] 2. In vitro bacteriostatic effect on HP The compositions 1-4, watermelon frost and Periplaneta americana 70% ethanol extract are respectively prepared into mother liquor by adding water, and then gradient-diluted drug solution is obtained by dilution according to the ratio. The HP bacteria in the logarithmic growth phase are adjusted to 1x10 6 CFU / mL, and then the MIC and MBC are detected according to the micro-liquid dilution method.

[0021] MIC determination: 50 μL of various drugs in gradient dilution is taken by a sterile micro-sampler in a sterile 96-well microplate, and then an equal amount of bacterial solution is added, mixed, placed in an anaerobic condition for incubation, and the result is observed after 16 hours. The lowest drug concentration without bacterial growth observed by naked eye is MIC.

[0022] MBC determination: the culture in the microplate without bacterial growth observed by naked eye is picked by a sterile inoculation loop, and is streaked and inoculated on a culture medium flat plate. After 24 hours of culture under anaerobic conditions, the lowest drug concentration without bacterial colony growth is observed.

[0023] In the above detection, the positive control is without the liquid medicine, only with the bacterial liquid and the same amount of liquid medium; the negative control is without the bacterial liquid, only with the same amount of liquid medium of various liquid medicines.

[0024] Table 1 Comparison of the bacteriostatic effects of different treatments As shown in Table 1, the four compositions all have good inhibitory and killing effects on Helicobacter pylori. Watermelon cream and Periplaneta americana 70% ethanol extract also have inhibitory and killing effects on Helicobacter pylori, but the inhibitory and killing effects of the combination of the two are significantly more obvious than the effects of each of them alone, so the combination of the two is reasonable.

[0025] As can be seen from the experimental results, the addition of watermelon cream can improve the bacteriostatic and bactericidal effects of Periplaneta americana. When the ratio of the two is 1:2-1:8, the bacteriostatic and bactericidal effects of Periplaneta americana are significantly improved, and there is a synergistic effect. When the mass ratio of watermelon cream to Periplaneta americana is 1:2-1:4, the bacteriostatic and bactericidal effects are better.

[0026] Example 2 Preparation of watermelon cream and Periplaneta americana composition and bacteriostatic effect 1. Preparation of composition The Periplaneta americana was divided into five parts, and then water, 25% ethanol, 50% ethanol, 70% ethanol and 95% ethanol were added respectively for heating and reflux extraction twice. The first time was with 8 times the amount, and the second time was with 6 times the amount. Each time was refluxed for 2 hours. The filtrate was concentrated or the ethanol was recovered. The filtrate was concentrated under reduced pressure to a clear paste with a relative density of 1.30-1.34 (65°C). The clear paste was dried under reduced pressure, and then pulverized into fine powder to obtain Periplaneta americana ethanol extract.

[0027] Watermelon cream (watermelon cream: Periplaneta americana medicinal material mass ratio 1:4) with a mass of 0.25 times that of Periplaneta americana was pulverized into fine powder and mixed with the above-mentioned Periplaneta americana ethanol extract to obtain compositions 5-9.

[0028] 2. In vitro bacteriostatic effect on HP The inhibitory and killing effects of compositions 5-9 on Helicobacter pylori were tested according to the method in Example 1.

[0029] Table 2 Comparison of the bacteriostatic effects of different treatments As shown in Table 2, the compositions (1:4) prepared by watermelon cream and different concentrations of ethanol extracts of Periplaneta americana all have good inhibitory effects on Helicobacter pylori, and the effects are better than those of watermelon cream and Periplaneta americana extract alone. Among them, the composition of watermelon cream and 50% ethanol extract and 70% ethanol extract has the best inhibitory effect on Helicobacter pylori.

[0030] Example 3 Preparation of watermelon frost and Periplaneta americana composition and medicine prepared therefrom The fine powder of watermelon frost and Periplaneta americana was mixed in a mass ratio of 1:4, and an appropriate amount of excipients (dextrin, mannitol, magnesium stearate, and microcrystalline cellulose) was added to compress tablets, obtaining tablets, each tablet equivalent to 1 g of the original medicinal material.

[0031] Example 4 Preparation of watermelon frost and Periplaneta americana composition and medicine prepared therefrom Periplaneta americana was decocted twice with water, 8 times the amount of water was added in the first decoction, and 6 times the amount of water was added in the second decoction, each decoction for 2 hours, filtered, and the filtrate was concentrated under reduced pressure to a clear concentrate with a relative density of 1.30-1.34 (65°C), dried under reduced pressure, and the dry extract was pulverized into fine powder to obtain the water extract of Periplaneta americana.

[0032] Watermelon frost in an amount of 0.25 times the mass of Periplaneta americana was pulverized into fine powder, mixed with the water extract of Periplaneta americana described above, and an appropriate amount of excipients (dextrin) was added to mix uniformly, and then filled into capsules, with each capsule equivalent to 1 g of the original medicinal material.

[0033] Example 5 Preparation of watermelon frost and Periplaneta americana composition and medicine prepared therefrom Periplaneta americana was extracted twice by heating reflux with 70% ethanol, 8 times the amount of ethanol was added in the first extraction, and 6 times the amount of ethanol was added in the second extraction, each extraction for 2 hours, filtered, and the filtrate was concentrated or ethanol was recovered, and the filtrate was concentrated under reduced pressure to a clear concentrate with a relative density of 1.30-1.34 (65°C), and the concentrate was dried under reduced pressure, and pulverized into fine powder to obtain the ethanol extract of Periplaneta americana.

[0034] Watermelon frost in an amount of 0.25 times the mass of Periplaneta americana was pulverized into fine powder, mixed with the ethanol extract of Periplaneta americana described above, and obtained as a powder, and packaged into bags, with each bag equivalent to 1 g of the original medicinal material.

[0035] Example 6 Protective effect of watermelon frost and Periplaneta americana composition on gastric ulcer The protective effect of watermelon frost and Periplaneta americana composition on gastric ulcer was verified in a rat model of gastric ulcer induced by acetic acid.

[0036] 1. Experimental grouping SPF male Wistar rats with a body weight of (200±20) g were adaptively fed for 1 week, and then taken out one by one, and randomly divided into 9 groups, each group with 5 rats, namely, a control group, a gastric ulcer model group, a watermelon frost group, a Periplaneta americana powder group, a water extract of Periplaneta americana group, a 70% ethanol extract of Periplaneta americana group, an example 3 group, an example 4 group, and an example 5 group.

[0037] 2. Modeling After 24 h of fasting without water, the rats were anesthetized by intraperitoneal injection of 40% chloral hydrate (300 mg / kg), the abdominal wall was shaved and disinfected, and the stomach was pulled out after the abdominal wall was incised. 0.03 mL of glacial acetic acid was injected into the submucosa of the antrum of the stomach near the muscle layer using a microsyringe. After a semi-transparent white spot with a diameter of about 3 mm appeared, the stomach was returned to the abdominal cavity, and the abdominal wall was sutured in layers. The control group was subjected to the same operation, but normal saline was injected instead of glacial acetic acid. After the operation, the rats in each group were individually caged and given free access to food the next day.

[0038] 3. Experimental treatment One day after modeling, the rats in each group were given the corresponding drugs by gavage: the control group and the model group were given normal saline 10 mL / (kg·d) by gavage; the tablets in Example 3 were crushed, and the contents in Examples 4 and 5 were given by gavage; all the drug treatment groups were given the original medicinal material at a dose of 0.2 g / (kg·d) for watermelon cream and 0.8 g / (kg·d) for Periplaneta americana; the watermelon cream group, the Periplaneta americana powder group, the Periplaneta americana water extract group, and the Periplaneta americana 70% ethanol extract group were given the original medicinal material at a dose of 1 g / (kg·d); the administration lasted for 2 weeks.

[0039] 4. Evaluation of protective effect One day after the last administration, the rats were sacrificed, the stomach was removed, and the contents were washed out with normal saline. The degree of gastric mucosal damage, congestion, and ulceration were observed under a dissecting microscope. The number, size, and distribution of the ulceration and hemorrhage were observed, and the length of each ulceration was measured. Each 1 mm was scored as 1 point, and if the width exceeded 1 mm, the score was doubled. The total score was taken as the ulcer index.

[0040] Ulcer inhibition rate = (ulcer index of the model group - ulcer index of the administration group) / ulcer index of the model control group × 100%.

[0041] Table 3 Comparison of the protective effect of three preparations and watermelon cream and Periplaneta americana on acetic acid-induced gastric ulceration in rats Note: compared with the model group, p <0.05, # p <0.01.

[0042] As can be seen from the test results, the compositions have good protective and improving effects on gastric ulceration. Compared with the model group, the watermelon cream group and the Periplaneta americana group also have good improving effects on gastric ulceration, and there are significant differences compared with the model group. As can also be seen from the test results, the improving effect of Examples 3-5 on gastric ulceration is significantly better than that of the watermelon cream group and the Periplaneta americana group and their extracts, indicating that the composition of the two has a synergistic effect on protecting the gastric mucosa and improving gastric ulceration.

[0043] Example 7 Treatment effect of watermelon frost and Periplaneta americana composition medicament on gastric ulcer caused by Helicobacter pylori 1. Diagnostic criteria a. Chinese diagnostic criteria Main symptoms: Stomach pain (distending pain, stabbing pain, dull pain, severe pain, and pressing pain), abdominal distension, belching, acid regurgitation, frequent sighing, frequent belching, poor appetite, dry mouth, dry stool.

[0044] Secondary symptoms: Irritability, chills, dizziness, vomiting, diarrhea, constipation, cold drinks, insomnia, hot palms, yellow urine.

[0045] Diagnosis can be made if 2 main symptoms and 1 secondary symptom are present, or 1 main symptom and 2 secondary symptoms are present.

[0046] b. Western diagnostic criteria Diagnosis requires that the patient meet (1), (2), (5), or (3) or (4).

[0047] (1) Chronic course, periodic onset, and rhythmic epigastric pain with acid reflux.

[0048] (2) With upper gastrointestinal bleeding, perforation history or present symptoms.

[0049] (3) Gastric ulcer confirmed by gastroscope.

[0050] (4) X-ray barium meal examination confirmed as peptic ulcer.

[0051] (5) Helicobacter pylori test (breath method).

[0052] 2. Inclusion and exclusion criteria Patients who meet the above diagnostic criteria are included, and the following patients are excluded: (1) Patients with a history of allergy to watermelon frost and Periplaneta americana; (2) Patients with liver, heart, kidney and other organ dysfunction; (3) Patients with gastric cancer, gastric perforation, etc.; (4) Patients with infectious diseases or mental disorders; (5) Pregnant or lactating women, and patients who have taken antibiotics, proton pump inhibitors and other drugs in the past two weeks.

[0053] 3. Treatment method The included patients are divided into 4 groups, taking Example 1, Example 2 capsule group 4 capsules each time, 3 times a day; Example 3 powder group 4g each time, 3 times a day, and positive control drug Weikangling capsule 4 capsules each time, 3 times a day. Each group takes for 4 weeks.

[0054] Example 3 group: 21 males, 17 females, 25 patients aged 20-60 years old, 13 patients over 60 years old, a total of 38 patients, with an average age of 42.1 years.

[0055] Example 4 group: 22 males, 18 females, 25 patients aged 20-60 years old, 15 patients over 60 years old, a total of 40 patients, with an average age of 43.1 years.

[0056] Example 5 group: 20 males, 20 females, 24 patients aged 20-60 years old, 1 patient over 60 years old, a total of 40 patients, with an average age of 42.8 years.

[0057] Weikangling capsule group: 20 males, 16 females, 21 patients aged 20-60 years old, 15 patients over 60 years old, a total of 36 patients, with an average age of 42.4 years.

[0058] 4. Effect evaluation (1) Helicobacter pylori (Hp) eradication rate Breath test (UBT) review, if the result shows negative, it indicates that Hp eradication is successful, and positive indicates that Hp eradication fails.

[0059] (2) Clinical efficacy Marked effect: abdominal discomfort symptoms disappear or significantly relieve, and ulcers disappear; effective: abdominal discomfort symptoms are relieved, and ulcers are reduced by ≥50%; ineffective: symptoms are not improved or further aggravated.

[0060] The effective rate is calculated according to the following formula: Effective rate = × 100%.

[0061] Table 4 Comparison of clinical efficacy of different drugs in treating gastric ulcer caused by Helicobacter pylori Note: Compared with the Weikangling capsule group, there is a significant difference (P<0.05). p <0.05).

[0062] As can be seen from the data in Table 4, the eradication rate of the traditional Chinese medicine composition capsules prepared by different processes for Helicobacter pylori is significantly better than that of the control drugs. From the clinical effect, it can be seen that the traditional Chinese medicine composition capsules prepared by different processes have a significantly better clinical effect on gastric ulcers caused by Helicobacter pylori than the control group.

[0063] The above only describes the embodiments of the present application and is not intended to limit the present application. Those skilled in the art can make various modifications and changes to the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the scope of the claims of the present application.

Claims

1. Use of a composition for the manufacture of a medicament for gastric ulcer, characterized in that, The composition is made of watermelon frost and Periplaneta americana in a mass ratio of 1:8-1:

1.

2. Use according to claim 1, characterized in that, The gastric ulcer is caused by Helicobacter pylori.

3. Use according to claim 1, characterized in that, The mass ratio of watermelon frost and Periplaneta americana is 1:4-1:

2.

4. Use according to claim 1, characterized in that, The Periplaneta americana is Periplaneta americana or an extract of Periplaneta americana; the extraction solvent of the extract is water or an alcohol solution.

5. Use according to claim 4, characterized in that, The concentration of the alcohol solution is 20wt%-95wt% or 50wt%-70wt%.

6. Use according to claim 4, characterized in that, The preparation method of the water extract of Periplaneta americana comprises the following steps: decocting and extracting Periplaneta americana with water, concentrating the decocting liquid, and drying to obtain; The preparation method of the alcohol extract of Periplaneta americana comprises the following steps: extracting Periplaneta americana with 20wt%-95wt% ethanol, recovering ethanol from the extract, and concentrating and drying to obtain.

7. Use according to claim 6, characterized in that, The extraction method can adopt heating reflux method, immersion method or percolation method.

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