Traditional Chinese medicine composition for treating refractory helicobacter pylori infection as well as preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating refractory helicobacter pylori infection and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 15-20 parts of codonopsis pilosula, 10-15 parts of roasted rhizoma atractylodis macrocephalae, 15-20 parts of oldenlandia diffusa, 6-9 parts of coptis chinensis, 6-9 parts of rhizoma pinellinae praeparata, 6-9 parts of curcuma zedoary and 6-9 parts of raw liquorice. The invention also provides a preparation method and a traditional Chinese medicine preparation of the traditional Chinese medicine composition. The traditional Chinese medicine composition and the traditional Chinese medicine preparation thereof are simple in prescription, can be used for effectively treating intractable helicobacter pylori infection, and are beneficial to relieving the medicine taking and economic burden of patients, improving the compliance and reducing the occurrence of adverse reactions.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine. More specifically, it relates to a traditional Chinese medicine composition for treating refractory Helicobacter pylori infection, a preparation method thereof, and an application thereof. Background Art

[0002] Helicobacter pylori (HP) infection is an infectious disease and is closely related to various diseases such as gastritis, peptic ulcer, gastric cancer, etc. Eradicating HP is an important measure for preventing gastric cancer. The guidelines recommend that the first choice for eradicating HP is the quadruple therapy with bismuth (Liu Wenzhong, Xie Yong, Lu Hong, etc., The Fifth National Consensus Report on the Management of Helicobacter pylori Infection [J], Chinese Journal of Gastroenterology, 2017, 22(6): 346-360). However, with the widespread use of antibiotics, the HP eradication rate has been continuously decreasing, and the treatment of HP has entered a bottleneck period. Refractory Helicobacter pylori infection (RHPI) has become a prominent problem. RHPI refers to the failure to successfully eradicate HP after two or more consecutive standard eradication treatments for HP infection. For such patients, the types of antibiotics available for selection are reduced, and the treatment is difficult.

[0003] The integrated traditional Chinese and Western medicine treatment of RHPI has advantages such as improving the HP eradication rate and reducing adverse reactions. The inventor previously proposed that the formula of invigorating the spleen, removing dampness, detoxifying, and dredging collaterals combined with the rescue quadruple therapy for treating RHPI can maintain an HP eradication rate comparable to that of the rescue quadruple therapy and can significantly improve the clinical symptoms of patients (Wang Shaoli, etc., Clinical Efficacy Observation of the Formula of Invigorating the Spleen, Removing Dampness, Detoxifying, and Dredging Collaterals Combined with the Rescue Quadruple Therapy for Treating Refractory Helicobacter pylori Infection, Chinese Journal of Integrated Traditional and Western Medicine on Digestion, 2024, 32(4): 309-314). However, at present, the traditional Chinese medicine empirical formulas for treating refractory Helicobacter pylori infection often have a large number of drug components, and at the same time, the drug doses in combination with the quadruple therapy are large, resulting in a heavy medication burden for patients, leading to a decrease in compliance and making it difficult to widely promote and apply the treatment plan.

[0004] Therefore, seeking a safe, effective, and simple-formula traditional Chinese medicine prescription for treating refractory Helicobacter pylori infection is an important problem that needs to be solved urgently. Summary of the Invention

[0005] In view of the above technical problems, the present invention simplifies the formula of invigorating the spleen, removing dampness, detoxifying, and dredging collaterals in the previous research, and provides a new traditional Chinese medicine composition that can effectively treat refractory Helicobacter pylori infection based on the clinical research foundation.

[0006] Another object of the present invention is to provide a preparation method of the above traditional Chinese medicine composition.

[0007] Another object of the present invention is to provide a traditional Chinese medicine preparation containing the above traditional Chinese medicine composition.

[0008] Another object of the present invention is to provide the use of the above traditional Chinese medicine composition and traditional Chinese medicine preparation in the preparation of a drug for treating refractory Helicobacter pylori infection.

[0009] To achieve the above object, the present invention adopts the following technical solutions:

[0010] In the first aspect, the present invention provides a traditional Chinese medicine composition for treating refractory Helicobacter pylori infection, which is made from the following raw materials in parts by weight: 15-20 parts of Codonopsis pilosula, 10-15 parts of stir-fried Atractylodes macrocephala, 15-20 parts of Hedyotis diffusa, 6-9 parts of Coptis chinensis, 6-9 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 6-9 parts of Curcuma zedoaria, and 6-9 parts of raw Glycyrrhiza uralensis.

[0011] In the present invention, Codonopsis pilosula is mild in nature and sweet in taste, entering the spleen and lung meridians. "Compendium of Materia Medica Outline" records that "Codonopsis pilosula replenishes the middle qi, is suitable for both the lung and spleen, strengthens the spleen and promotes digestion without making the middle energizer dry, nourishes the stomach yin without stagnating the chest diaphragm", and it is a good medicine for replenishing the middle qi; stir-fried Atractylodes macrocephala is sweet, bitter, and warm in nature, entering the spleen and stomach meridians. "Zhang's Medical General" records that in the Sijunzi Decoction, "Atractylodes macrocephala mainly treats spleen and stomach weakness, loose stools, or nausea and anorexia. When combined with stir-frying until charred, it has the power of strengthening transportation". In this formula, stir-fried Atractylodes macrocephala and Codonopsis pilosula are used together as the monarch drugs. On the one hand, they replenish qi and strengthen the spleen, regulating the middle energizer; on the other hand, Atractylodes macrocephala dries dampness and promotes diuresis, removing dampness and strengthening the spleen. The two drugs are used together to achieve the effects of replenishing the middle qi and strengthening the spleen and drying dampness, treating the root cause of this disease, which is spleen and stomach weakness.

[0012] Coptis chinensis is bitter and cold, capable of clearing heat and drying dampness, purging fire and detoxifying, and is good at clearing the damp-heat in the middle-jiao spleen and stomach. Modern pharmacological research has confirmed that it has obvious antibacterial effects; Pinellia ternata is pungent and warm, entering the spleen and stomach meridians, good at drying and transforming phlegm in the middle-jiao, assisting the spleen and stomach in transportation. Its pungent flavor can disperse stagnation and resolve masses, reduce phlegm and relieve fullness, and at the same time has the effect of harmonizing the stomach and descending adverse qi; when Coptis chinensis and Pinellia ternata are combined, one is bitter and descending, and the other is pungent and ascending, which can clear heat and dry dampness, regulate qi movement, so that damp-heat is transformed and the ascending and descending functions return to normal; Hedyotis diffusa is bitter and cold in taste, with the effects of clearing heat, detoxifying, and promoting diuresis. Modern pharmacological research has confirmed that it can inhibit the proliferation of gastric cancer cells and play an anti-tumor role. The above three drugs together serve as the ministerial drugs, exerting the effects of clearing heat, removing dampness, and detoxifying, treating the cause of this disease, which is the invasion of damp-heat and toxic pathogens from outside.

[0013] Curcuma zedoaria is pungent, dispersing, bitter, purging, and warm in nature, entering both the blood aspect and the qi aspect. It can break blood and promote qi movement, eliminate stasis and relieve pain. Modern pharmacological research has confirmed that Curcuma zedoaria has the effects of inhibiting the proliferation and promoting apoptosis of tumor cells. Curcuma zedoaria is the assistant drug in this formula, exerting the effects of breaking blood and removing stasis, promoting qi movement and relieving pain, treating the pathological evolution of gastric collateral stasis obstruction.

[0014] Glycyrrhiza uralensis tastes sweet and tonifies deficiency, entering the spleen and stomach meridians. It can invigorate the spleen and replenish qi, and its medicinal properties are mild and slow, capable of harmonizing various drugs. When used raw, its medicinal properties are slightly cold and can clear heat and detoxify. Modern pharmacological research has confirmed that this drug can inhibit the immune inflammatory response caused by Helicobacter pylori.

[0015] Combined use of various herbs for treating refractory Helicobacter pylori infection, with the traditional Chinese medicine syndrome type being the syndrome of intermingled deficiency and excess (weakness of the spleen and stomach, external invasion of damp-heat pathogen-toxin, stasis obstruction of the gastric collaterals).

[0016] In the present invention, by way of example, the traditional Chinese medicine composition for treating refractory Helicobacter pylori infection is prepared from the following raw materials in parts by weight: 15 parts of Codonopsis pilosula, 10 parts of stir-fried Atractylodes macrocephala, 15 parts of Hedyotis diffusa, 6 parts of Coptis chinensis, 9 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 9 parts of Curcuma zedoaria, and 6 parts of raw Glycyrrhiza uralensis.

[0017] By way of example, the traditional Chinese medicine composition for treating refractory Helicobacter pylori infection is prepared from the following raw materials in parts by weight: 20 parts of Codonopsis pilosula, 15 parts of stir-fried Atractylodes macrocephala, 15 parts of Hedyotis diffusa, 6 parts of Coptis chinensis, 9 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 6 parts of Curcuma zedoaria, and 6 parts of raw Glycyrrhiza uralensis.

[0018] By way of example, the traditional Chinese medicine composition for treating refractory Helicobacter pylori infection is prepared from the following raw materials in parts by weight: 15 parts of Codonopsis pilosula, 10 parts of stir-fried Atractylodes macrocephala, 20 parts of Hedyotis diffusa, 9 parts of Coptis chinensis, 9 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 9 parts of Curcuma zedoaria, and 9 parts of raw Glycyrrhiza uralensis.

[0019] In a second aspect, the present invention provides a preparation method of the above traditional Chinese medicine composition for treating refractory Helicobacter pylori infection. In fact, the traditional Chinese medicine composition of the present invention can be prepared according to conventional preparation methods in the art, such as decoction method, maceration method, reflux method, etc. The following preparation method is provided only for better understanding of the present invention, and those skilled in the art should understand that this preparation method should not limit the protection scope of the present invention.

[0020] The preparation method of the traditional Chinese medicine composition for treating refractory Helicobacter pylori infection of the present invention includes the following steps:

[0021] Weigh Codonopsis pilosula, stir-fried Atractylodes macrocephala, Hedyotis diffusa, Coptis chinensis, Pinellia ternata processed with Rhizoma Zingiberis Recens, Curcuma zedoaria, and raw Glycyrrhiza uralensis according to the prescription amount, add water for decoction, generally decoct at least twice, filter, and combine the filtrates to obtain the product.

[0022] Optionally, the preparation method of the present invention may further include the steps of concentrating the filtrate into a clear extract and drying.

[0023] In a third aspect, the present invention provides a traditional Chinese medicine preparation for treating refractory Helicobacter pylori infection, which includes the above traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the above preparation method.

[0024] According to actual needs, the traditional Chinese medicine preparation may further include pharmaceutically acceptable excipients. For example, solvents, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, stabilizers, flavoring agents, preservatives, suspending agents, coating materials, etc., and various preparations are made according to conventional pharmaceutical processes, such as decoctions, granules, pills, capsules, tablets, powders, oral liquids and other dosage forms.

[0025] The present invention also provides the use of the above traditional Chinese medicine composition, or the traditional Chinese medicine composition prepared by the above preparation method, or the above traditional Chinese medicine preparation in the preparation of a medicament for treating refractory Helicobacter pylori infection.

[0026] Furthermore, the medicament of the present invention can be used in combination with quadruple therapy to treat refractory Helicobacter pylori infection. The drugs used in the "quadruple therapy" are mainly proton pump inhibitors combined with bismuth agents, plus two antibiotics, and synergistic medication is required to achieve better therapeutic effects. According to the specific embodiments of the present invention, the drugs used in the quadruple therapy in the present invention can be rabeprazole sodium enteric-coated capsules, colloidal bismuth pectin capsules, amoxicillin capsules or minocycline hydrochloride capsules. The combination of the medicament of the present invention and quadruple therapy for treating refractory Helicobacter pylori infection is not limited to the quadruple drugs listed in the examples. Those skilled in the art should understand that the examples should not limit the protection scope of the present invention.

[0027] In addition, unless otherwise specified, each raw material drug of the traditional Chinese medicine composition of the present invention can be obtained through commercial purchase. Any range recorded in the present invention includes the end values and any numerical value between the end values, and the traditional Chinese medicine composition of any sub-range constituted by any numerical value between the end values or the end values can achieve the purpose of treating refractory Helicobacter pylori infection.

[0028] The beneficial effects of the present invention are as follows:

[0029] Compared with the prior art, the present invention has the following innovative features: (1) Theoretical innovation. Different from previous studies that mostly based on the theory of damp-heat in the spleen and stomach, the inventor innovatively proposed the "dual target theory of healthy qi and pathogenic factors" based on previous research. It is believed that the key pathogenesis of refractory Helicobacter pylori infection is deficiency of healthy qi and excess of pathogenic factors. Among them, weakness of the spleen and stomach is the root cause of the disease, external invasion of damp-heat pathogen is the cause of the disease, and stasis of gastric collaterals is the pathological evolution, thus forming the Chinese medicine formula of the present invention. (2) Innovation in the composition of the formula. Different from the formulas in the published studies that mostly focus on drugs for clearing heat and removing dampness, this formula uses Codonopsis pilosula and Atractylodes macrocephala for strengthening the spleen as the monarch drugs, increasing the effects of replenishing middle qi and drying dampness in the spleen to support healthy qi, and playing a role in treating weakness of the spleen and stomach caused by multiple eradication failures of refractory Helicobacter pylori infection. At the same time, it uses Rhizoma Curcumae for promoting blood circulation to remove blood stasis as the assistant drug, aiming at stasis of gastric collaterals caused by long-term onset of refractory Helicobacter pylori infection to exert the effect of promoting blood circulation and removing blood stasis and prevent the progression of the disease. (3) Simplification of the formula drugs. Different from the formulas in the published studies that mostly consist of nearly a dozen drugs, based on previous research, in view of the problems that patients reported, such as a large number of drugs and large drug doses for combined medication (generally, the antibiotic treatment course needs 14 days), the formula is simplified and only consists of 7 drugs. And the antibiotics combined with quadruple therapy only need to be taken for 10 days, which helps to reduce the medication and economic burden of patients, improve compliance, reduce the occurrence of adverse reactions, and reduce the risk of antibiotic resistance, and has better cost-effectiveness. Detailed implementation manners

[0030] To more clearly illustrate the present invention, the present invention will be further described below in conjunction with preferred embodiments. Those skilled in the art should understand that the specific content described below is illustrative rather than restrictive, and should not be used to limit the protection scope of the present invention.

[0031] Example 1 A traditional Chinese medicine composition for treating refractory Helicobacter pylori infection

[0032] Prescription of raw materials: 15 g of Codonopsis pilosula, 10 g of stir-fried Atractylodes macrocephala, 15 g of Hedyotis diffusa, 6 g of Coptis chinensis, 9 g of Pinellia ternata, 9 g of Rhizoma Curcumae, 6 g of raw Glycyrrhiza uralensis.

[0033] Preparation method: Weigh Codonopsis pilosula, stir-fried Atractylodes macrocephala, Hedyotis diffusa, Coptis chinensis, Pinellia ternata, Rhizoma Curcumae and raw Glycyrrhiza uralensis according to the prescription amount, decoct twice with water, filter, and combine the filtrates to obtain.

[0034] Example 2 A traditional Chinese medicine composition for treating refractory Helicobacter pylori infection

[0035] Prescription of raw materials: 20 g of Codonopsis pilosula, 15 g of stir-fried Atractylodes macrocephala, 15 g of Hedyotis diffusa, 6 g of Coptis chinensis, 9 g of Pinellia ternata, 6 g of Rhizoma Curcumae, 6 g of raw Glycyrrhiza uralensis.

[0036] The preparation method is the same as that of Example 1.

[0037] Example 3: A Traditional Chinese Medicine Granule for Treating Refractory Helicobacter Pylori Infection

[0038] Prescription of raw materials: 15 g of Codonopsis pilosula, 10 g of stir-fried Atractylodes macrocephala, 20 g of Hedyotis diffusa, 9 g of Coptis chinensis, 9 g of Pinellia ternata processed with Rhizoma Zingiberis Recens, 9 g of Curcuma zedoaria, 9 g of raw Glycyrrhiza uralensis

[0039] Preparation method: Weigh Codonopsis pilosula, stir-fried Atractylodes macrocephala, Hedyotis diffusa, Coptis chinensis, Pinellia ternata processed with Rhizoma Zingiberis Recens, Curcuma zedoaria and raw Glycyrrhiza uralensis according to the prescription amount, decoct twice with water, filter, and combine the filtrates; then concentrate the filtrates into clear paste, dry, and make into granules according to the conventional process of granules

[0040] Test Example 1: Clinical Research

[0041] 1.1 Case selection: Select 204 patients with refractory Helicobacter pylori infection, aged between 18 and 80 years

[0042] 1.2 Random grouping: The patients were randomly grouped according to the random seed numbers generated by the computer at a ratio of 1:1, and allocation concealment was carried out by using the sealed and light-proof envelope method. The patients were randomly assigned to the treatment group or the control group

[0043] 1.3 Diagnostic criteria

[0044] Western medicine diagnostic criteria: ① Stop using drugs that may affect the test results, such as antibiotics, bismuth agents or traditional Chinese medicines with antibacterial effects for 4 weeks, and proton pump inhibitors for 2 weeks, then conduct HP detection. The results show that the DOB value of the 13C-urea breath test is ≥4, the DPM value of the 14C-urea breath test is ≥100, or the urease test of gastric mucosa biopsy under gastroscopy is positive. ② Have failed standardized eradication treatment ≥2 times in the past, and the drug withdrawal time is at least 3 months away from the last eradication treatment

[0045] Traditional Chinese medicine diagnostic criteria: If the patient meets 1-2 items of the following deficiency syndrome and 1-2 items of the excess syndrome, and refers to the tongue and pulse conditions, the diagnosis can be made. Excess syndrome: ① Epigastric fullness or pain with resistance to pressure, relatively severe; ② Dry mouth, bitter taste in the mouth, bad breath; ③ Acid reflux and heartburn; ④ Constipation or unsmooth defecation; ⑤ Nausea or vomiting; ⑥ Yellow urine. Red tongue, thick and greasy yellow coating. Slippery and rapid pulse. Deficiency syndrome: ① Epigastric fullness or dull pain, relatively mild; ② Preferring warmth and pressure; ③ Fatigue and weakness; ④ Weak defecation or loose stools; ⑤ Vomiting clear water; ⑥ Loss of appetite; ⑦ Cold hands and feet. Pale and plump tongue or with tooth marks on the sides, white coating. Deep, slow and weak pulse or thready and weak pulse

[0046] 1.4 Treatment plan

[0047] (1) Control group: Given the standard rescue quadruple therapy for 14 days: Rabeprazole Sodium Enteric Capsules (National Medicine Approval No. H20050228, produced by Zhuhai Runde Pharmaceutical Co., Ltd., 10mg×7 capsules / box, 20mg / time, 2 times / day, 30 minutes before breakfast and dinner) + Colloidal Bismuth Pectin Capsules (National Medicine Approval No. H20063479, produced by North China Pharmaceutical Co., Ltd., 50mg×24 capsules / box, 150mg / time, 3 times / day, 60 minutes before breakfast, lunch and dinner) + Amoxicillin Capsules (National Medicine Approval No. H33021381, produced by Zhejiang Jinhua Conba Biopharmaceutical Co., Ltd., 0.25g×24 capsules / box, 1000mg / time, 2 times / day, orally after breakfast and dinner) + Minocycline Hydrochloride Capsules (National Medicine Approval No. H20174081, produced by Hanyu Pharmaceutical Co., Ltd., 50mg×20 capsules / box, 100mg / time, 2 times / day, orally after breakfast and dinner). The course of treatment was 14 days.

[0048] (2) Treatment group: The standard rescue quadruple therapy for 10 days (the same as the control group) + the traditional Chinese medicine of the present invention for 14 days (the specific medicine is made from the following raw materials: Codonopsis pilosula 15g, stir-fried Atractylodes macrocephala 10g, Hedyotis diffusa 15g, Coptis chinensis 6g, Pinellia ternata 9g, Curcuma zedoaria 9g, raw Glycyrrhiza uralensis 6g). One dose per day, taken separately after breakfast and dinner. The course of the standard rescue quadruple therapy was 10 days (taken on the 1st - 10th day after inclusion), and the course of the traditional Chinese medicine was 14 days (taken on the 11th - 24th day after inclusion).

[0049] 1.5 Efficacy evaluation indicators

[0050] HP eradication rate: In both the treatment group and the control group, the HP infection status of the patients after treatment was detected by 13C / 14C-urea breath test 8 weeks after drug withdrawal. Negative indicates successful HP eradication, and positive indicates failed HP eradication. Calculate the HP eradication rate of each group of patients. The calculation formula: HP eradication rate = number of HP-negative subjects / total number of subjects in each group × 100%.

[0051] Traditional Chinese Medicine symptom scores: Symptoms such as epigastric fullness, epigastric pain, belching, acid reflux and heartburn, dry mouth / bitter taste, loss of appetite, nausea / vomiting, short and yellow urine, dry stools, unsmooth stools, loose stools, stomach discomfort, and fatigue are divided into 4 levels of none, mild, moderate, and severe according to the severity and frequency of occurrence, and are scored as 0, 2, 4, and 6 points. Based on the baseline, the difference in the total score of the above-mentioned Traditional Chinese Medicine symptoms after treatment in each group compared with the baseline was compared, and the efficacy grade index was used for evaluation. Efficacy grade index = [(score before treatment - score after treatment)] / score before treatment × 100%. The specific classification criteria are as follows: Clinical cure: Symptoms basically disappear, and the efficacy grade index decreases by ≥ 95% compared with the enrollment, which can be considered basically cured; Marked effect: Symptoms are significantly improved, and the efficacy grade index decreases by 70% - 95% compared with the enrollment, which can be considered a marked effect; Effective: Symptoms are significantly improved, and the efficacy grade index decreases by 30% - 70% compared with the enrollment, which can be considered effective; Ineffective: Symptoms are not significantly improved, and even worsen. The efficacy grade index decreases by less than 30% compared with the enrollment, which can be considered ineffective. Total effective rate = (clinical cure + marked effect + effective) / total number of cases × 100%.

[0052] Quality of life scale score: The European Five-Dimensional Health Scale [EuroQol (Quality of life)-5 Dimensions-3-level, EQ-5D-3L] was used to evaluate the quality of life of patients. Based on the baseline, the scores before and after treatment within each group and between groups were compared respectively. At the same time, the difference in the scores after treatment in the two groups compared with the baseline was compared to evaluate the statistical significance and clinical significance.

[0053] 1.6 Research results

[0054] (1) Completion of the trial: During the research process, 19 cases dropped out, and the dropout rate was 9.31%; 10 cases dropped out in the control group, and the dropout rate was 9.80%. 3 cases dropped out due to adverse reactions, and 7 cases dropped out due to loss to follow-up. Finally, 92 patients were included; 9 cases dropped out in the treatment group, and the dropout rate was 8.82%. 3 cases dropped out due to adverse reactions, and 6 cases dropped out due to loss to follow-up. Finally, 93 patients were included.

[0055] (2) HP eradication rate: HP reexamination was not conducted for the dropout cases in both groups. In the full analysis set (FAS), the eradication failure was counted. Among the control group, 73 patients had successful eradication, and among the treatment group, 83 patients had successful eradication. FAS analysis showed that the HP eradication rates of the control group and the treatment group were 71.57% (73 / 102) and 81.37% (83 / 102) respectively (P = 0.099). See Table 1 for details. The risk difference (RD) of the H. pylori eradication rate was calculated using the VassarStats tool (http: / / vassarstats.net / index.html), indicating that the eradication effect of the treatment group was not inferior to that of the control group (RD = 9.8%, 95% CI = [-0.0187, 0.2117] > -0.15). Per protocol set (PPS) analysis showed that the HP eradication rates of the control group and the treatment group were 79.35% (73 / 92) and 89.25% (83 / 93) respectively (P = 0.064). See Table 2 for details. The eradication effect of the treatment group was not inferior to that of the control group (RD = 9.9%, 95% CI = [-0.0068, 0.2043] > -0.15). The results of FAS analysis were consistent with those of PPS analysis. The HP eradication rate of the treatment group was higher than that of the control group, but the difference in HP eradication rates between the two groups was not statistically significant (P > 0.05 for both).

[0056] Table 1 FAS analysis of HP eradication rates in two groups of patients [n (%)]

[0057]

[0058] Table 2 PPS analysis of HP eradication rates in two groups of patients [n (%)]

[0059]

[0060] (3) The TCM symptom curative effects of the 185 patients included in this study were analyzed. Compared with before treatment, the total effective rates of the control group and the treatment group after treatment were 84.78% and 93.55% respectively. The total effective rate of the treatment group was higher than that of the control group, and the difference between the two groups was statistically significant (P < 0.05). See Table 3 for details.

[0061] Table 3 TCM symptom curative effects after treatment in two groups of patients [n (%)]

[0062]

[0063] (4) The total TCM symptom scores of 185 patients included in this study were analyzed. After treatment, the total TCM symptom scores of both groups of patients decreased compared with those before treatment, and there were significant differences compared with before treatment (both P < 0.05). Comparison between groups after treatment showed that the differences between the two groups were statistically significant (both P < 0.05), as shown in Table 4 for details.

[0064] Table 4 Total TCM symptom scores of two groups of patients [score, M(Q1,Q3)]

[0065]

[0066] (5) The scores of individual TCM symptoms of 185 patients included in this study were analyzed. After treatment, the symptom scores of epigastric fullness, epigastric pain, belching, acid reflux and heartburn, dry mouth and bitter taste, short and yellow urine, dry stools, unsmooth stools, stomach discomfort, and fatigue and weakness in both groups of patients decreased compared with those before treatment. The score of loose stools in the treatment group of patients decreased compared with that before treatment (both P < 0.05). Comparison between groups showed that after treatment, there were significant differences between the treatment group and the control group in terms of epigastric fullness, epigastric pain, dry mouth and bitter taste, short and yellow urine, dry stools, and stomach discomfort (both P < 0.05), as shown in Table 5 for details.

[0067] Table 5 Scores of individual TCM symptoms of two groups of patients [score, M(Q1,Q3)]

[0068]

[0069]

[0070] 1) indicates that P < 0.05 compared with before treatment. 2) indicates that P < 0.05 compared with the control group.

[0071] (6) Quality of life score:

[0072] ① The EQ-5D was used to analyze the EQ-5D scores of patients, as shown in Table 6 for details. There was no significant difference in the EQ-5D scores of patients between the two groups before treatment (P > 0.05). Compared with before treatment, the EQ-5D scores of both groups increased after treatment, and the differences were statistically significant (both P < 0.05). Comparison between groups showed that there was no significant difference in the EQ-5D scores of patients between the two groups after treatment (P > 0.05).

[0073] ② The EQ-VAS was used to analyze the EQ-VAS scores of patients, as shown in Table 7 for details. There was no significant difference in the EQ-VAS scores of patients between the two groups before treatment (P > 0.05). Compared with before treatment, the EQ-VAS scores of both groups increased after treatment, and the differences were statistically significant (both P < 0.05). Comparison between groups showed that the differences in the EQ-VAS scores of patients between the two groups after treatment were significant (both P < 0.05).

[0074] Table 6 EQ-5D scores of two groups of patients [points, M(Q1,Q3)]

[0075]

[0076] Note: Normality tests were performed on the EQ-5D scores and their differences before and after treatment in the two groups, and P<0.05 in both cases

[0077] Table 7 Total EQ-VAS scores of two groups of patients [points, M(Q1,Q3)]

[0078]

[0079]

[0080] Note: Normality tests were performed on the EQ-VAS scores and their differences before and after treatment in the two groups, and P<0.05 in both cases

[0081] (5) Incidence of adverse reactions

[0082] No abnormal liver or kidney function was observed in either group of patients. The adverse reactions in the patients were all mild and returned to normal after drug withdrawal. Seven cases in the treatment group had adverse reactions, with an incidence of adverse reactions of 7.53%. Thirteen cases in the control group had adverse reactions, with an incidence of adverse reactions of 14.13%. The difference in the incidence of adverse reactions between the two groups was not statistically significant (P>0.05), as shown in Table 8. The results suggest that the combined traditional Chinese and Western medicine treatment can reduce the tendency of adverse reactions to occur

[0083] Table 8 Incidence of adverse reactions in two groups of patients [cases(%)]

[0084]

[0085] Compared with the clinical efficacy of the Jianpi Qushi Jiedu Tongluo formula combined with rescue quadruple therapy for the treatment of refractory Helicobacter pylori infection in the previous research of the inventor team (Wang Shaoli et al., Observation on the clinical efficacy of the Jianpi Qushi Jiedu Tongluo formula combined with rescue quadruple therapy for the treatment of refractory Helicobacter pylori infection, Chinese Journal of Integrated Traditional and Western Medicine on Digestion, 2024, 32(4): 309-314):

[0086] ① FAS analysis: The HP eradication rate of the Jianpi Qushi Jiedu Tongluo formula was 84.00% (21 / 25), and the FAS analysis of the traditional Chinese medicine of the present invention was 81.37% (83 / 102), P = 0.76, with no significant difference

[0087] ② PPS analysis: The HP eradication rate of the Jianpi Qushi Jiedu Tongluo formula was 91.30% (21 / 23), and the PPS analysis of the traditional Chinese medicine of the present invention was 89.25% (83 / 93), P = 1.00, with no significant difference

[0088] The results showed that the optimized pharmaceutical composition of the present invention could maintain an HP eradication rate comparable to that of the traditional Chinese medicine formula for strengthening the spleen, removing dampness, detoxifying and dredging collaterals in the previous research. At the same time, compared with other traditional Chinese medicine compositions for treating Helicobacter pylori infection recorded in the prior art (most of them have nearly 15 ingredients), the formula of the present invention is more concise, reducing the drug components, which is more conducive to improving the compliance of patients and reducing the medication burden and economic pressure of patients.

[0089] Conclusion: The traditional Chinese medicine composition of the present invention combined with the rescue quadruple therapy for treating refractory Helicobacter pylori infection has a tendency to increase the HP eradication rate while reducing the dosage of antibiotics (the antibiotic course of treatment in the treatment group is only 10 days, and the general antibiotic course is 14 days). Moreover, it can improve the curative effect of traditional Chinese medicine symptoms and the quality of life of patients, and has a tendency to reduce the occurrence of adverse reactions.

[0090] Typical cases

[0091] Case 1: Wang, male, 57 years old, with Helicobacter pylori infection. He had been treated with the standard quadruple therapy for eradication 2 times before, and the medications included amoxicillin, clarithromycin, metronidazole, levofloxacin, etc. In this eradication treatment, after 10 days of the quadruple therapy, he took the traditional Chinese medicine composition of the present invention for 14 days (15 g of Codonopsis pilosula, 10 g of stir-fried Atractylodes macrocephala, 15 g of Hedyotis diffusa, 6 g of Coptis chinensis, 9 g of Pinellia ternata, 9 g of Curcuma zedoaria, 6 g of raw Glycyrrhiza uralensis, made into granules), taken orally with boiling water 2 times a day, after meals. The reexamination result 4 weeks after drug withdrawal showed that Helicobacter pylori was negative. The blowing test results at 6 months and 1 year after drug withdrawal both showed that Helicobacter pylori was negative.

[0092] Case 2: Shi, female, 59 years old, with Helicobacter pylori infection. She had been treated with the standard quadruple therapy for eradication 2 times before, and the medications included amoxicillin, clarithromycin, etc. In this eradication treatment, after 10 days of the quadruple therapy, she took the traditional Chinese medicine composition of the present invention for 14 days (20 g of Codonopsis pilosula, 15 g of stir-fried Atractylodes macrocephala, 15 g of Hedyotis diffusa, 6 g of Coptis chinensis, 9 g of Pinellia ternata, 6 g of Curcuma zedoaria, 6 g of raw Glycyrrhiza uralensis, made into granules), taken orally with boiling water 2 times a day, after meals. The reexamination result 8 weeks after drug withdrawal showed that Helicobacter pylori was negative. The gastroscopy result at 6 months after drug withdrawal showed that Helicobacter pylori was negative.

[0093] Case 3: Yang, female, 54 years old, with Helicobacter pylori infection. She had been treated with the standard quadruple therapy for eradication 2 times before, and the medications included levofloxacin, amoxicillin, etc. In this eradication treatment, after 10 days of the quadruple therapy, she took the traditional Chinese medicine composition of the present invention for 14 days (15 g of Codonopsis pilosula, 10 g of stir-fried Atractylodes macrocephala, 20 g of Hedyotis diffusa, 9 g of Coptis chinensis, 9 g of Pinellia ternata, 9 g of Curcuma zedoaria, 9 g of raw Glycyrrhiza uralensis, made into granules), taken orally with boiling water 2 times a day, after meals. The reexamination result 8 weeks after drug withdrawal showed that Helicobacter pylori was negative. The blowing test result nearly 1 year after drug withdrawal showed that Helicobacter pylori was negative.

[0094] Case 4: Meng, female, 35 years old, Helicobacter pylori infection, previously received quadruple therapy for eradication twice, including metronidazole, clarithromycin, amoxicillin, etc. This eradication treatment was 10 days after the quadruple therapy, and took Jianpi Qushi Jiedu Tongluo prescription for 14 days (20g of Codonopsis pilosula, 15g of stir-fried Atractylodes macrocephala, 15g of Hedyotis diffusa, 6g of Coptis chinensis, 9g of Pinellia ternata, 6g of Curcuma zedoaria, 6g of raw licorice, made into granules), taken with boiled water, twice a day, after meals. The results of the reexamination after stopping the drug for 8 weeks showed that Helicobacter pylori was negative. The results of the reexamination after stopping the drug for 1 and a half years showed that Helicobacter pylori was negative.

[0095] Case 5: Xu, male, 35 years old, Helicobacter pylori infection, previously treated with triple / quadruple therapy for 2 times, including levofloxacin, clarithromycin, amoxicillin, etc., this eradication treatment was 10 days after the quadruple therapy, and the Chinese medicine composition of the present invention was taken for 14 days (15g of Codonopsis pilosula, 10g of stir-fried Atractylodes macrocephala, 20g of Hedyotis diffusa, 9g of Coptis chinensis, 9g of Pinellia ternata, 9g of Curcuma zedoaria, 9g of raw Licorice root, made into granules), taken with boiled water, twice a day, after meals. The results of the reexamination after 8 weeks of drug withdrawal showed negative for Helicobacter pylori. The results of the reexamination after 1 year of drug withdrawal showed negative for Helicobacter pylori.

[0096] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating refractory Helicobacter pylori infection, characterized in that: The invention is prepared from the following raw materials in parts by weight: 15-20 parts of Codonopsis pilosula, 10-15 parts of stir-fried Atractylodes macrocephala, 15-20 parts of Hedyotis diffusa, 6-9 parts of Coptis chinensis, 6-9 parts of Pinellia ternata, 6-9 parts of Curcuma zedoaria and 6-9 parts of raw liquorice.

2. The Chinese medicine composition according to claim 1, characterized in that: The drug is prepared from the following raw materials in parts by weight: 15 parts of Codonopsis pilosula, 10 parts of stir-fried Atractylodes macrocephala, 15 parts of Hedyotis diffusa, 6 parts of Coptis chinensis, 9 parts of Pinellia ternata, 9 parts of Curcuma zedoaria, and 6 parts of raw liquorice.

3. The Chinese medicine composition according to claim 1, characterized in that The drug is prepared from the following raw materials in parts by weight: 20 parts of Codonopsis pilosula, 15 parts of stir-fried Atractylodes macrocephala, 15 parts of Hedyotis diffusa, 6 parts of Coptis chinensis, 9 parts of Pinellia ternata, 6 parts of Curcuma zedoaria, and 6 parts of raw liquorice.

4. The Chinese medicine composition according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 15 parts of Codonopsis pilosula, 10 parts of stir-fried Atractylodes macrocephala, 20 parts of Hedyotis diffusa, 9 parts of Coptis chinensis, 9 parts of Pinellia ternata, 9 parts of Curcuma zedoaria, and 9 parts of raw liquorice.

5. The method for preparing the Chinese medicine composition for treating refractory Helicobacter pylori infection according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: Weigh codonopsis pilosula, stir-fried atractylodes macrocephala, oldenlandia diffusa, coptis chinensis, pinellia ternata, zedoaria and raw licorice according to the prescription amount, add water to boil, filter, and combine the filtrates to obtain the product.

6. The preparation method according to claim 5, characterized in that: The preparation method also includes the steps of concentrating the filtrate into a clear paste and drying.

7. A Chinese medicine preparation for treating refractory Helicobacter pylori infection, characterized in that: The invention relates to a Chinese medicine composition comprising the Chinese medicine composition according to any one of claims 1 to 4 or a Chinese medicine composition prepared by the preparation method according to any one of claims 5 to 6.

8. The Chinese medicine preparation according to claim 7, characterized in that: The traditional Chinese medicine preparation also includes pharmaceutically acceptable excipients.

9. The Chinese medicine preparation according to claim 7 or 8, characterized in that: The dosage form of the Chinese medicine preparation is decoction, granules, pills, capsules, tablets, powders or oral liquid.

10. Use of the Chinese medicine composition according to any one of claims 1 to 4, or the Chinese medicine preparation according to any one of claims 7 to 9 in the preparation of a medicament for treating refractory Helicobacter pylori infection.

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