Pharmaceutical composition for treating helicobacter pylori infectious gastropathy

Abstract

A pharmaceutical composition for treating helicobacter pylori infectious stomach disease belongs to the technical field of medicine, and comprises the following raw materials by weight: 5-30 g of adenophora stricta, 10-30 g of hairyvein agrimony, 10-30 g of fried coix seed, 5-20 g of lily, 10-20 g of oldenlandia diffusa, 5-30 g of pericarpium citri reticulatae, 5-20 g of bighead atractylodes rhizome, 5-30 g of dandelion, 10-30 g of sculellaria barbata, and 5-30 g of scutellaria baicalensis. By soothing liver and regulating qi, clearing heat and harmonizing stomach, strengthening spleen and calming middle-jiao and taking both symptoms and root causes into consideration, the medicine makes up the deficiency of western medicines, and pays attention to enhancing the defense function of the body, protecting the gastric mucosal barrier and correcting the gastrointestinal tract function while eliminating helicobacter pylori infection, thereby achieving the purposes of strengthening body resistance and expelling evil. The spleen-tonifying and detoxifying decoction is combined with western medicines to remarkably improve the eradication rate of helicobacter pylori, improve symptoms and relieve the side effects of the western medicines, and has the advantages of quick response, high effective rate, definite curative effect, short treatment course, no toxic or side effect, low price and the like.

Description

Technical Field

[0001] The invention relates to a pharmaceutical composition for treating Helicobacter pylori infectious gastropathy and a preparation method thereof, belonging to the technical field of medicine. Background Art

[0002] Helicobacter pylori (Hp) infection is a major public health issue and is relatively common worldwide, with an overall infection rate of approximately 50%, and can be as high as 80% in some parts of developing countries.

[0003] Hp is mainly transmitted through oral-oral route, but can also be transmitted through fecal-oral route. It is closely related to a variety of stomach diseases, is the main cause of chronic gastritis, and is also an important pathogenic factor for gastric ulcers and duodenal ulcers. It is also closely related to the occurrence and development of gastric cancer.

[0004] After HP reaches the stomach through the mouth, it colonizes on the gastric mucosal cells and causes infection. It then destroys the structure of the gastric mucosal layer by producing a variety of enzymes, secreting cytotoxins, inducing gastric epithelial cells to release interleukin-8, etc., causing active inflammation of the gastric mucosa. The TCM symptoms of Helicobacter pylori infection generally include liver-stomach disharmony, spleen-stomach damp-heat syndrome, stomach yin deficiency, spleen-stomach weakness syndrome, etc. Patients often have symptoms such as bad breath, dry mouth and bitter mouth. Modern medicine treats Hp infection with the goal of eradicating Hp. Currently, bismuth-containing quadruple therapy is mainly recommended. Due to the influence of Hp resistance and special constitution, some patients may face failure of Hp eradication. Therefore, developing traditional medicine and using TCM to treat Hp infection has become a valuable research direction.

[0005] Not only that, Chinese medicine is more effective in improving Hp-related gastritis symptoms such as abdominal pain, bloating, and indigestion, and can serve as an effective supplement to eradication programs. Summary of the invention

[0006] The purpose of the present invention is to provide a pharmaceutical composition for treating Helicobacter pylori-infected gastric disease. The pharmaceutical composition can inhibit the activity of Helicobacter pylori, hinder its reproduction and growth, improve the acid-base environment and flora balance of the stomach, repair the gastric mucosal damage caused by Helicobacter pylori, and has a satisfactory effect on drug-resistant Helicobacter pylori-infected chronic gastritis. The drug has also been subjected to in vitro antibacterial tests to further clarify the main active ingredients and antibacterial effects of the prescription.

[0007] The technical solution for achieving the above purpose is: a pharmaceutical composition for treating Helicobacter pylori infectious gastropathy, comprising the following raw materials in parts by weight: 5-30 parts of Adenophora Root, 10-30 parts of Herba Agrimoniae, 10-30 parts of stir-fried Coix Seeds, 5-20 parts of Lilium, 10-20 parts of Hedyotis Diffusa, 5-30 parts of Tangerine Peel, 5-20 parts of Atractylodes Macrocephala, 5-30 parts of Taraxacum Herba, 10-30 parts of Scutellaria Barbatae, and 5-30 parts of Scutellaria Baicalensis.

[0008] The efficacy of each raw material is as follows:

[0009] Adenophora has the effects of nourishing the stomach and promoting fluid production, nourishing yin and detoxifying. It is used for symptoms such as insufficient stomach yin, loss of appetite and vomiting, insufficient qi and yin, irritability, heat and dry mouth.

[0010] Scutellaria barbata has the effects of clearing away heat and detoxifying, removing blood stasis and promoting diuresis. It is used to remove damp-heat poison in the stomach, reduce swelling and relieve pain, and improve stomach pain and bloating caused by stagnation of qi and blood in the stomach.

[0011] Atractylodes macrocephala has the effects of strengthening the spleen and stomach, drying dampness and promoting diuresis. It is used for poor appetite, abdominal distension, diarrhea caused by spleen and stomach qi deficiency and inability to transport and transform, to remove dampness and improve the spleen and stomach environment.

[0012] Scutellaria baicalensis has the effects of clearing away heat and dampness, purging fire and detoxifying, and anti-inflammatory and antibacterial. It is used for damp-heat, chest tightness and nausea, damp-heat fullness, diarrhea, jaundice and sticky stool, regulating the transportation and transformation environment of the spleen and stomach; treating stomach pain and heartburn caused by hyperactivity of stomach fire; it can inhibit harmful bacteria such as Helicobacter pylori and help prevent and treat gastritis and other stomach diseases.

[0013] Dandelion is used to treat carbuncles, boils and to relieve burning pain in the stomach. It has anti-inflammatory and antibacterial properties, inhibits harmful bacteria such as Helicobacter pylori, and helps relieve stomach inflammation. It is a stomachic and bile-boosting herb, and can improve symptoms such as indigestion and bloating.

[0014] Oldenlandia diffusa has antibacterial, anti-inflammatory and antioxidant effects. It can inhibit a variety of pathogens and reduce oxidative stress damage. It can enhance the activity of immune cells, improve the body's immunity, remove free radicals, and reduce cell damage. It can increase the eradication rate of Helicobacter pylori, improve stomach discomfort, and promote gastric mucosal repair.

[0015] Agrimony has the effects of detoxification, insecticide, astringency, hemostasis, dysentery and tonification. It has an inhibitory or killing effect on bacteria, fungi and trichomonas, can destroy the cell membrane and protein structure of pathogens, affect their metabolism and reproduction, and can also regulate the immune and endocrine systems and improve fatigue and weakness.

[0016] Lily has the effects of nourishing stomach yin, clearing stomach heat, moistening the lungs and relieving cough, clearing the heart and calming the mind. It helps to regulate stomach yin deficiency, stomach heat and stomach pain, increase appetite and promote digestion.

[0017] Tangerine peel has the effects of regulating qi and strengthening the spleen, soothing the liver and promoting bile secretion, and stopping vomiting. It can relieve qi stagnation in the stomach and spleen, eliminate fullness, relieve wrist and abdominal pain, belching, nausea and vomiting, enhance gastrointestinal digestion function, and improve loss of appetite.

[0018] Fried coix seeds have the effects of strengthening the spleen and stomach, promoting water and dampness, removing numbness and relieving pain. It can regulate gastrointestinal function, promote the secretion of digestive juice, enhance gastrointestinal motility, increase water metabolism, eliminate edema, and can resist inflammation and relieve pain, and help enhance the body's immune function.

[0019] Beneficial effects of the present invention: It is found through experiments that the clearance rate of Helicobacter pylori infection by the Chinese medicine composition + quadruple therapy of the present invention can reach more than 95%. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is the extracted ion chromatogram of quercetin in drug-containing serum samples;

[0021] Figure 2 This is the extracted ion chromatogram of isorhamnetin in drug-containing serum samples;

[0022] Figure 3 This is the extracted ion chromatogram of baicalin in drug-containing serum samples. DETAILED DESCRIPTION

[0023] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0024] The invention discloses a pharmaceutical composition for treating gastric disease caused by Helicobacter pylori infection. The pharmaceutical composition can inhibit the activity of Helicobacter pylori, hinder its reproduction and growth, improve the acid-base environment and flora balance of the stomach, and repair the gastric mucosal damage caused by Helicobacter pylori. Specifically, the pharmaceutical composition is prepared from the following raw materials in parts by weight: 5-30 parts of Adenophora radix, 10-30 parts of Herba Agrimoniae, 10-30 parts of stir-fried Coix seeds, 5-20 parts of Lilium, 10-20 parts of Hedyotis diffusa, 5-30 parts of Citrus reticulatae, 5-20 parts of Atractylodes macrocephalae, 5-30 parts of Taraxacum officinale, 10-30 parts of Scutellaria barbata, and 5-30 parts of Scutellaria baicalensis.

[0025] 1. Analysis of active ingredients of drugs

[0026] The components of the medicinal composition include: 15 grams of Adenophora Root, 15 grams of Herba Agrimoniae, 20 grams of stir-fried Coix Seed, 10 grams of Lilium, 15 grams of Hedyotis Diffusa, 15 grams of Tangerine Peel, 15 grams of Atractylodes Macrocephala, 15 grams of Taraxacum Herba, 20 grams of Scutellaria Barbata, and 15 grams of Scutellaria Baicalensis.

[0027] Preparation method: Mix the above raw materials evenly, mix and soak in 1000mL of water for 30min, then boil over high heat for 15min, simmer over low heat for 20min, filter the extract and concentrate it by thermal evaporation to prepare the extract with a final concentration of 2.4g / mL and store it at 4°C.

[0028] Preparation of rat drug serum:

[0029] The extract prepared above was gavaged to 6-8 week old rats for 4 consecutive days, and blood was collected from the inferior vena cava. The blood was placed in a 37°C water bath for 2 hours and centrifuged at 2500 rpm for 10 minutes to collect the drug-containing serum, which was then stored in a -80°C refrigerator.

[0030] Drug serum sample preparation:

[0031] The drug-containing serum (1 mL) was added to acetonitrile (2 mL), vortexed for 1 min, and centrifuged at 4000 r / min for 15 min. The supernatant (1.5 mL) was taken and concentrated by centrifugation at 12000 rpm for 4 h, leaving only the solute, and then 200 μL of acetonitrile was added to redissolve it, shaken well, and ultrasonicated for 5 min to obtain the serum sample.

[0032] Chromatography and mass spectrometry:

[0033] Conditions: HPLC: chromatographic column: Agilent C18 (2.1 mm × 150 mm, 5 μm); mobile phase A is acetonitrile, mobile phase B is H2O (0.1% formic acid (FA)); flow rate: 0.3 mL / min; column temperature: 35°C; gradient elution; injection volume: 5 μL. The ion source of the mass spectrometer is ESI, and the acquisition mode is MRM mode.

[0034] The experiment used high performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) to determine the content of the main active ingredients in the prepared extract, and selected the main active ingredients with relatively high content to observe their in vitro antibacterial effects. Subsequently, the drug-containing serum was subjected to an in vitro antibacterial test to further clarify the main active ingredients and antibacterial effects of the prescription.

[0035] Analysis of drug serum components: The main active ingredients found in relatively high levels in the drug serum of this prescription are quercetin, isorhamnetin, and baicalin. Figure 1-3 .

[0036] Determination of minimum inhibitory concentration (MIC): The antibacterial activity MIC of the main active ingredients in the extract was detected by micro-broth dilution. The prepared extract solutions of different concentrations (800μg / mL, 400μg / mL, 200μg / mL, 100μg / mL, 10μg / mL, 1μg / mL, 0.1μg / mL, 0.01μg / mL) were added to the sterilized 96-well polystyrene plate, and the drug solution was added from the 1st to the 8th well, 100μL per well, and the 9th well was not added with drug as a growth control (solvent control group was also set up); Staphylococcus aureus, Staphylococcus albus, Escherichia coli, Salmonella, and Proteus in LB were shaken in a shaking incubator (RPM: 200, T: 37°C) for 16-18h, and the bacterial solution was diluted to 5×10 6CFU / mL. Helicobacter pylori LB is also used for the recovery and dilution of Helicobacter pylori. Add 100 μL of bacterial suspension to each well, seal it and place it in a 37°C incubator, incubate for 18-20 hours and judge the result. The lowest drug concentration that completely inhibits bacterial growth in the well is the MIC. According to the micro-measurement of the main active ingredients in the drug-containing serum and the in vitro antibacterial experiment, the MIC concentration of quercetin to inhibit bacteria (Staphylococcus aureus, Staphylococcus albus, Escherichia coli, Salmonella, Proteus, Helicobacter pylori) is 200μg / mL, while the MIC of isorhamnetin to inhibit Helicobacter pylori is 400μg / mL, and the MIC for other bacteria is 200ug / mL, and the MIC of baicalin to inhibit Helicobacter pylori is 400μg / mL, and the MIC for other bacteria is 200μg / mL; the MIC of drug-containing serum according to the volume ratio is 1:4 (Staphylococcus aureus, Escherichia coli and Proteus), 1:1 (Salmonella and Helicobacter pylori); succinic acid does not inhibit the growth of these bacteria. The results are as follows:

[0037] Minimum inhibitory concentrations of quercetin, isorhamnetin, baicalin and drug-containing serum (μg / mL)

[0038]

[0039]

[0040] Note: “—” indicates drug resistance

[0041] The main active ingredients in the drug-containing serum, quercetin, isorhamnetin and baicalin, have the effect of inhibiting Helicobacter pylori and other bacteria. This result explains the main reason why the drug of the present invention directly inhibits bacteria and inflammation, and also lays the foundation for further clinical application. 2. Specific embodiments

[0043] Example 1

[0044] The invention discloses a pharmaceutical composition for treating gastric disease caused by Helicobacter pylori infection, and is the most preferred embodiment of the invention, comprising 15 grams of Adenophora radix, 15 grams of Herba Agrimoniae, 20 grams of stir-fried Coix seeds, 10 grams of Lilium, 15 grams of Hedyotis diffusa, 15 grams of Citrus reticulatae, 15 grams of Atractylodes macrocephalae, 15 grams of Taraxacum officinale, 20 grams of Scutellaria barbata, and 15 grams of Scutellaria baicalensis.

[0045] Preparation method: mix the above ingredients evenly, add about 10000 ml of pure water, boil over high heat for 50 minutes, simmer over low heat for 40 minutes, filter the extract to obtain the Helicobacter pylori treatment drug (Spleen-strengthening and Detoxification Decoction) of the present invention.

[0046] Example 2

[0047] The invention discloses a pharmaceutical composition for treating gastric disease caused by Helicobacter pylori infection, comprising 5 grams of Adenophora radix, 30 grams of Herba Agrimoniae, 10 grams of stir-fried Coix seeds, 20 grams of Lilium bulbs, 20 grams of Hedyotis diffusa, 30 grams of Citrus reticulatae, 5 grams of Atractylodes macrocephalae, 5 grams of Taraxacum officinale, 30 grams of Scutellaria barbata and 30 grams of Scutellaria baicalensis.

[0048] The preparation method is the same as that of Example 1

[0049] Example 3

[0050] The invention discloses a pharmaceutical composition for treating gastric disease caused by Helicobacter pylori infection, comprising 30 grams of Adenophora radix, 10 grams of Herba Agrimoniae, 30 grams of stir-fried Coix seeds, 5 grams of Lilium, 10 grams of Hedyotis diffusa, 5 grams of Citrus reticulatae, 20 grams of Atractylodes macrocephalae, 20 grams of Taraxacum officinale, 20 grams of Scutellaria barbata and 5 grams of Scutellaria baicalensis.

[0051] The preparation method is the same as that of Example 1

[0052] Example 4

[0053] The invention discloses a pharmaceutical composition for treating gastric disease caused by Helicobacter pylori infection, comprising 30 grams of Adenophora radix, 10 grams of Herba Agrimoniae, 30 grams of stir-fried Coix seeds, 5 grams of Lilium, 10 grams of Hedyotis diffusa, 15 grams of Citrus reticulatae, 10 grams of Atractylodes macrocephalae, 30 grams of Taraxacum officinale, 10 grams of Scutellaria barbata and 30 grams of Scutellaria baicalensis.

[0054] The preparation method is the same as that of Example 1

[0055] 3. Experiment 1

[0056] 1. A total of 106 patients from outpatient clinics of the system hospitals and local tertiary hospitals were selected, including 56 males and 50 females with an average age of 34.3±3.6 years. All patients underwent electronic gastroscopy and 13 C breath test. Diagnostic criteria: ① Gastroscopy reveals congestion, edema, bleeding spots and erosion spots in the gastric mucosa. ② 13 C. HP test is positive in breath test. ③. Halitosis, epigastric distension and pain, burning sensation, repeated acid vomiting, hiccups and other upper gastrointestinal symptoms.

[0057] 2. Treatment Methods The patients were divided into two groups, the quadruple therapy group and the quadruple therapy + Jianpi Jiedu Decoction group, with 53 people in each group. There was no statistical difference in gender, age, and course of disease between the two groups. Quadruple therapy group: The specific application method is: esomeprazole 30mg, one capsule in the morning and evening, colloidal pectin 100mg, one bag in the morning and evening, take before meals, and take the two medicines half an hour apart; amoxicillin clavulanate potassium 0.5g, clarithromycin each 0.5g, both are taken after meals, one capsule in the morning and evening, 14 days as a course of treatment.

[0058] Four-combination therapy + Jianpi Jiedu Decoction group: Specific method: On the basis of the four-combination therapy, take the Jianpi Jiedu Decoction prepared in Example 1 170ml / time, twice a day, half an hour before meals, 14 days as a course of treatment. After one course of treatment, stop taking the medicine for one month and reexamine the above two groups. 13 C breath test. The treatment status of the two groups of patients is as follows:

[0059] Comparison of the two groups after HP treatment

[0060] Group Number of cases Significant effect efficient invalid Total Effectiveness Quadruple therapy group 53 33 12 8 84.91％ Quadruple therapy + Jianpi Jiedu decoction group 53 44 7 2 96.22％

[0061] Comparison of Helicobacter pylori infection clearance rate: quadruple therapy group + Jianpi Jiedu Decoction group > quadruple therapy group, the difference was statistically significant (P < 0.05).

[0062] The TCM syndrome scores of the two groups were compared. The TCM syndrome scores included epigastric fullness, epigastric distension and pain, epigastric noise, poor appetite and less food intake. Each item was scored using 0, 2, 4, or 6. The higher the score, the more severe the symptom. The syndrome scores showed that the combination of this prescription and the quadruple drug was significantly better than the quadruple drug alone, and the related symptoms were significantly improved.

[0063] TCM Syndrome Scoring Table

[0064]

[0065] Comparison of TCM syndrome scores: quadruple therapy group > quadruple therapy group + Jianpi Jiedu decoction group, the difference between the two groups was significant (P < 0.05)

[0066] IV. Test 2

[0067] Twelve patients who failed the quadruple therapy for HP in the system hospitals and the outpatient clinics of the local tertiary hospitals were selected (esomeprazole 30 mg, one tablet in the morning and evening, colloidal pectin 100 mg, one bag in the morning and evening, taken before meals, with a half-hour interval between the two drugs; amoxicillin clavulanate potassium 0.5 g, clarithromycin 0.5 g each, both taken after meals, one tablet in the morning and evening, 14 days as a course of treatment), including 6 males and 6 females with an average age of 32.5±2.4 years.

[0068] Treatment Methods The patients were evenly divided into 2 groups, the quadruple therapy group and the Jianpi Jiedu Decoction group, with 6 people in each group. There was no statistical difference in gender, age, and course of disease between the two groups. For the quadruple therapy group, the specific method of taking was: 30 mg of esomeprazole, one tablet in the morning and evening, 100 mg of colloidal pectin, one bag in the morning and evening, taken before meals, with a half-hour interval between the two drugs; 100 mg of furazolidone tablets and 500 mg of clarithromycin, both taken after meals, once in the morning and evening, 14 days as a course of treatment.

[0069] The specific method of the Jianpi Jiedu Decoction group is as follows: take 170 ml of the Jianpi Jiedu Decoction prepared by any one of the above examples 1-4, twice a day, half an hour before meals, and 14 days as a course of treatment. After one course of treatment, the above two groups will stop taking the medicine for one month and then reexamine. 13 C breath test.

[0070] Treatment status of group II drug-resistant patients

[0071] Group Number of cases Significant effect efficient invalid Total Effectiveness Quadruple therapy group 6 3 1 2 66.67％ Jianpi Jiedu Decoction Group 6 4 1 1 83.33％

[0072] Comparison of Helicobacter pylori infection clearance rate: Jianpi Jiedu Decoction group > quadruple therapy group, the difference was statistically significant (P < 0.05).

[0073] The present invention is further described in detail below in conjunction with clinical trials:

[0074] Typical case 1:

[0075] Liu, male, 31 years old, had upper abdominal discomfort and dull pain for half a year, with occasional symptoms of acid reflux, belching, nausea and vomiting. 13 HP was positive in breath test, DOB value: 26.35, gastroscopy diagnosis: gastric angle ulcer, chronic non-atrophic gastritis. Pathology report: gastric angle is consistent with gastric ulcer, chronic inflammation of mucosa, no intestinal metaplasia and dysplasia. Diagnosis: Helicobacter pylori infection gastritis, Jianpi Jiedu decoction and four drugs were used for a course of 14 days, and the patient's symptoms were significantly relieved. One month later, 13 C's HP test turned negative, and he continued to take this prescription for two courses. All symptoms disappeared and there was no recurrence during the one-year follow-up.

[0076] Typical case 2:

[0077] Miao, male, 40 years old, had been suffering from stomach distension, belching, and poor appetite for more than 5 months. 13 The DOB value of C breath test was 19.87. The diagnosis of gastroscopy was: chronic non-atrophic gastritis with antral erosion. After a course of treatment with adequate dose and duration of quadruple drug therapy, the patient's symptoms did not improve significantly. The patient was reexamined one month later. 13 C, DOB value 19.12, anti-HP treatment failed. Then Jianpi Jiedu Decoction was used for a course of 14 days. The patient's stomach distension and discomfort were relieved, appetite increased, and there was no acid reflux. The patient was reexamined on the 45th day. 13 C. HP turned negative, and one more course of treatment was taken to consolidate the therapeutic effect. All symptoms disappeared, and the gastroscopy was normal and HP was negative.

Claims

1. A pharmaceutical composition for treating Helicobacter pylori-induced gastropathy, characterized in that : It comprises the following raw materials in parts by weight: 5-30 parts of Adenophora Root, 10-30 parts of Agrimoniae Herba, 10-30 parts of stir-fried Coix Seeds, 5-20 parts of Lilium Bulbs, 10-20 parts of Hedyotis Diffusa Grass, 5-30 parts of Tangerine Peel, 5-20 parts of Atractylodes Macrocephala, 5-30 parts of Taraxacum Herba, 10-30 parts of Scutellaria Barbatae, and 5-30 parts of Scutellaria Baicalensis.

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