Traditional Chinese medicine compound composition with functions of consolidating urinary tract infection, treating and preventing recurrence as well as preparation method and application of traditional Chinese medicine compound composition

Abstract

The invention discloses a traditional Chinese medicine compound composition for consolidating urinary tract infection treatment and preventing relapse and a preparation method thereof. The traditional Chinese medicine compound composition is prepared from 15-45 parts of astragalus membranaceus, 15-45 parts of pyrrosia lingua, 15-45 parts of radix salviae miltiorrhizae, 15-45 parts of perilla stem and 4-12 parts of liquorice. According to clinical experience for many years, in combination with urinary tract infection pathogenesis, a formula is screened, and astragalus membranaceus, pyrrosia lingua, radix salviae miltiorrhizae, perilla stem and liquorice are used to jointly achieve the effects of tonifying spleen and kidney, eliminating dampness and heat, promoting qi to activate blood and relieving pain. All the medicines in the formula are blended, and the traditional Chinese medicine composition becomes a common formula for consolidating treatment and preventing relapse after urinary tract infection is relieved clinically by tonifying spleen qi, tonifying kidney essence, activating qi and blood and clearing damp-heat. Clinical research results show that the traditional Chinese medicine compound (Qiwei anti-compound granules) has a great effect on consolidating treatment and reducing recurrence of urinary tract infection.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine composition, and particularly to a traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence and its preparation method, belonging to the technical field of traditional Chinese medicine. Background Art

[0002] Urinary tract infection is a common clinical disease with a high incidence rate, easy recurrence, protracted course, and can cause renal function damage over time. The western medicine treatment of this disease mainly focuses on sterilization, and sensitive antibiotics are the main means for treating urinary tract infection at present. However, due to the repeated occurrence of the disease, highly susceptible patients mostly use low-dose antibiotics for preventive treatment, but this will lead to the continuous increase of the patient's antibiotic resistance, the continuous change of pathogenic bacteria, and the increasingly complex treatment plan. At the same time, the recurrence rate of urinary tract infection has not decreased significantly, but shows an upward trend, which greatly increases the economic burden and psychological pressure of patients. At present, most of the existing traditional Chinese medicine preparations for treating urinary tract infection are aimed at the acute attack period of infection, and there is no corresponding effective traditional Chinese medicine for the conditioning treatment and prevention of the remission period of patients with repeated attacks.

[0003] In traditional Chinese medicine theory, urinary tract infection belongs to the categories of "stranguria syndrome", "hematuria", etc. The key to its onset is kidney deficiency, damp-heat, and blood stasis. The pathogenesis characteristics are mostly deficiency in origin and excess in superficiality, with both deficiency and excess syndromes. Kidney deficiency is the root cause of the onset of stranguria syndrome. The kidney is in charge of water and controls opening and closing. Generally, the diseases of the bladder and small urine should be attributed to the kidney. Kidney deficiency is also an important cause for the repeated occurrence of urinary tract infection. Therefore, for patients with the remission of acute symptoms of urinary tract infection, it is mainly to replenish the kidney and strengthen the root, supplemented by clearing and promoting diuresis, and long-term consolidation, so as to effectively reduce the recurrence of urinary tract infection.

[0004] Traditional Chinese medicine has unique advantages in consolidating the treatment of urinary tract infection, reducing recurrence, and alleviating symptoms during attacks. Therefore, under the guidance of traditional Chinese medicine theory and combined with clinical practice, the present invention optimizes a traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence. Summary of the Invention

[0005] Object of the Invention: The object of the present invention is to solve the deficiencies of the prior art. According to traditional Chinese medicine theory, syndrome differentiation and treatment are carried out, and traditional Chinese medicines are preferably selected to tonify the spleen qi, replenish kidney essence, activate qi and blood, and clear damp-heat, so as to optimize a traditional Chinese medicine compound composition that can effectively consolidate the treatment of urinary tract infection and prevent recurrence. Another object of the present invention is to provide a preparation method and application of the traditional Chinese medicine compound composition.

[0006] Technical Solution: In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] A traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence is made from the following raw materials: Astragalus membranaceus, Pyrrosia lingua, Salvia miltiorrhiza, Perilla stem, and Licorice root.

[0008] As a preferred embodiment, the traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence is made from the following raw materials in parts by weight:

[0009] Prepared from 15 - 45 parts of Astragalus membranaceus, 15 - 45 parts of Pyrrosia lingua, 15 - 45 parts of Salvia miltiorrhiza, 15 - 45 parts of Perilla frutescens stem, and 4 - 12 parts of Glycyrrhiza uralensis.

[0010] As a further preferred embodiment, the traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence is made from the following raw materials in parts by weight:

[0011] Prepared from 15 - 30 parts of Astragalus membranaceus, 15 - 30 parts of Pyrrosia lingua, 15 - 30 parts of Salvia miltiorrhiza, 15 - 30 parts of Perilla frutescens stem, and 4 - 8 parts of Glycyrrhiza uralensis.

[0012] As a more preferred embodiment, the traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence is made from the following raw materials in parts by weight:

[0013] Prepared from 15 parts of Astragalus membranaceus, 15 parts of Pyrrosia lingua, 15 parts of Salvia miltiorrhiza, 15 parts of Perilla frutescens stem, and 4 parts of Glycyrrhiza uralensis.

[0014] The preparation method of the traditional Chinese medicine compound composition described in the present invention includes the following steps:

[0015] Take Astragalus membranaceus, Pyrrosia lingua, Salvia miltiorrhiza, Perilla frutescens stem, and Glycyrrhiza uralensis, immerse the medicinal materials with water or alcohol, soak first, then extract, filter, combine the filtrates, rotary evaporate and concentrate, and dry to obtain.

[0016] As a preferred embodiment, the preparation method of the traditional Chinese medicine compound composition includes the following steps:

[0017] Take Astragalus membranaceus, Pyrrosia lingua, Salvia miltiorrhiza, Perilla frutescens stem, and Glycyrrhiza uralensis, immerse the medicinal materials with 5 - 15 times the volume of water based on the weight of the medicinal materials, soak for 30 - 40 min, decoct and extract for 30 - 60 min, filter, collect the decoction, take the medicinal residues and decoct again with 5 - 15 times the volume of water for 30 - 60 min, filter, collect the decoction, filter, rotary evaporate and concentrate the filtrate, and freeze - dry to obtain the freeze - dried powder.

[0018] A traditional Chinese medicine compound composition is prepared with a pharmaceutically acceptable carrier into dosage forms such as granules, tablets, capsules, pills, oral liquids, powders, mixtures, ointments, etc.

[0019] When the present invention is made into tablets, the extract of the traditional Chinese medicine compound composition is added with the carrier lactose or corn starch, and magnesium stearate as a lubricant is added if necessary, mixed evenly, and then compressed into tablets.

[0020] When the present invention is made into capsules, the extract of the traditional Chinese medicine compound composition is uniformly mixed with dextrin or starch, granulated, and then filled into capsules to make capsules.

[0021] When the present invention is made into granules, the extract of the traditional Chinese medicine compound composition is uniformly mixed with dextrin, etc., granulated, and dried to make granules.

[0022] When the present invention is made into mixture, the traditional Chinese medicine extract is dissolved in purified water to make mixture.

[0023] When the present invention is made into oral liquid, the traditional Chinese medicine extract is dissolved in purified water, steviol glycoside or aspartame is added, and the pH is adjusted to make oral liquid.

[0024] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0025] (1) Through years of clinical experience and in combination with the pathogenesis of urinary tract infection, the present invention screens and formulates a prescription, and selects astragalus membranaceus, pyrrosia lingua, purple salvia miltiorrhiza, perilla stem, and licorice. Among them, astragalus membranaceus is sweet and warm, and belongs to the lung and spleen meridians, tonifying the lung and spleen, nourishing the kidney and replenishing qi; pyrrosia lingua is sweet, bitter, and slightly cold, and belongs to the lung and bladder meridians, having the functions of clearing heat and promoting diuresis, expelling stones and stopping bleeding; astragalus membranaceus and pyrrosia lingua together play the role of tonifying the spleen and kidney, clearing and removing damp-heat, and are the monarch drugs. Salvia miltiorrhiza is bitter and slightly cold, and belongs to the heart and liver meridians, having the functions of clearing away vexation, promoting blood circulation and relieving pain; perilla stem is pungent and warm, and belongs to the lung and spleen meridians, with the efficacy of promoting qi circulation to relieve pain and inducing sweating and dispersing lung qi; the two together are the ministerial drugs. Raw licorice has a sweet and flat nature and belongs to the heart, lung, spleen and stomach meridians, having the functions of invigorating the spleen and replenishing qi, clearing heat and detoxifying, relieving spasm and pain, and coordinating the properties of various drugs, and is the adjuvant and guiding drug. The whole prescription has the functions of tonifying the kidney and strengthening the spleen, clearing and removing damp-heat, promoting qi circulation, activating blood circulation and relieving pain, and is especially suitable for the remission period of acute and chronic urinary tract infections, consolidating the curative effect and preventing recurrence. Clinically, the symptoms such as frequent urination, urgency of urination, and pain during urination are reduced or disappeared, but there are still symptoms such as soreness and weakness of the waist, distension and fullness in the lower abdomen, aversion to cold and cold limbs, spontaneous sweating, weakness in urination, incomplete urination, clear and long urine, and frequent nocturia. Taking this product can achieve the effects of thoroughly treating the uncomfortable symptoms of urinary tract infection, improving immunity, and preventing the recurrence of urinary tract infection. The results of network pharmacology research show that the traditional Chinese medicine compound of the present invention has a great effect on consolidating the treatment of urinary tract infection and preventing recurrence.

[0026] (2) The traditional Chinese medicine compound composition provided by the present invention, which can consolidate the treatment of urinary tract infection and prevent recurrence, can be conveniently prepared into various dosage forms with pharmaceutical carriers, is convenient to take clinically, and the experimental results show that the composition provided by the present invention has reliable curative effect, is safe to use, and has no toxic and side effects after long-term use. Description of the Drawings

[0027] Figure 1 For the statistical results of the recurrence rates of the study group and the control group.

[0028] Figure 2 For the "traditional Chinese medicine - ingredient - target" interaction network diagram.

[0029] Figure 3 It is a PPI network topology analysis diagram. Specific implementation manners

[0030] According to the following embodiments, the present invention can be better understood. However, those skilled in the art can easily understand that the specific material ratios, process conditions and their results described in the embodiments are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0031] Example 1

[0032] 1. A traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence, which is made from raw materials of the following weights:

[0033] Astragalus membranaceus 15 g, Pyrrosia lingua 15 g, Salvia miltiorrhiza 15 g, Perilla frutescens stem 15 g, Licorice 4 g.

[0034] 2. The preparation method of the traditional Chinese medicine compound composition includes the following steps:

[0035] Take Astragalus membranaceus 15 g, Pyrrosia lingua 15 g, Salvia miltiorrhiza 15 g, Perilla frutescens stem 15 g, Licorice 4 g, add water to submerge the medicinal materials and soak for 30 min, make up to 5 L of pure water, bring to a boil over high heat and then decoct over low heat for 30 min, filter, collect the decoction, add 5 L of pure water again and decoct for 30 min, filter, obtain the decoction liquid, collect the decoction liquids of the two times, and concentrate by rotary evaporation to 400 mL.

[0036] Load into 50 mL EP tubes (15 - 20 mL per tube), pre-freeze at -80 °C for 24 h and then treat with a vacuum freeze dryer for 72 h to obtain freeze-dried powder.

[0037] When in use, take the compound freeze-dried powder, add an appropriate amount of ultrapure water, and add 0.5% sodium carboxymethylcellulose and stir evenly for immediate use.

[0038] Example 2

[0039] 1. A traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence, which is made from raw materials of the following weight portions:

[0040] Astragalus membranaceus 30 g, Pyrrosia lingua 30 g, Salvia miltiorrhiza 30 g, Perilla frutescens stem 30 g, Licorice 8 g.

[0041] 2. The extract of the traditional Chinese medicine compound is prepared by the following method:

[0042] Take 30 g of Astragalus membranaceus, 30 g of Pyrrosia lingua, 30 g of Salvia miltiorrhiza, 30 g of Perilla frutescens stem, and 8 g of Glycyrrhiza uralensis. Add water to submerge the medicinal materials and soak for 30 min, then make up to 5 L of pure water. Bring to a boil over high heat and then simmer for 30 min. Filter and collect the decoction. Add another 5 L of pure water and simmer for 30 min; collect the decoction from the two simmerings and filter. Concentrate by rotary evaporation to about 400 mL, then dispense into 50 mL EP tubes (15 - 20 mL per tube). Pre-freeze at -80 °C for 24 h and then treat with a vacuum freeze dryer for 72 h to obtain freeze-dried powder.

[0043] When in use, take the compound freeze-dried powder, add an appropriate amount of ultrapure water, and add 0.5% sodium carboxymethylcellulose and stir evenly. Prepare and use immediately.

[0044] Example 3

[0045] 1. A traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence, which is made from the following raw materials in parts by weight:

[0046] 45 g of Astragalus membranaceus, 45 g of Pyrrosia lingua, 45 g of Salvia miltiorrhiza, 45 g of Perilla frutescens stem, and 12 g of Glycyrrhiza uralensis.

[0047] 2. The extract of the traditional Chinese medicine compound is prepared by the following method:

[0048] Take 45 g of Astragalus membranaceus, 45 g of Pyrrosia lingua, 45 g of Salvia miltiorrhiza, 45 g of Perilla frutescens stem, and 12 g of Glycyrrhiza uralensis. Add water to submerge the medicinal materials and soak for 30 min, then make up to 5 L of pure water. Bring to a boil over high heat and then simmer for 30 min. Filter and collect the decoction. Add another 5 L of pure water to the medicinal residues and simmer for 30 min; filter and collect the decoction. Add another 5 L of pure water to the medicinal residues and simmer for 30 min; collect the decoction from the three simmerings and filter. Concentrate by rotary evaporation to about 400 mL, then dispense into 50 mL EP tubes (15 - 20 mL per tube). Pre-freeze at -80 °C for 24 h and then treat with a vacuum freeze dryer for 72 h to obtain freeze-dried powder.

[0049] When in use, take the compound freeze-dried powder, add an appropriate amount of ultrapure water, and add 0.5% sodium carboxymethylcellulose and stir evenly. Prepare and use immediately.

[0050] Example 4 Clinical Efficacy Observation of a Traditional Chinese Medicine Compound Composition for Consolidating the Treatment of Urinary Tract Infection and Preventing Recurrence 1. Research Objects

[0051] Patients in the consolidation stage of recurrent urinary tract infection who visited the outpatient department of Nephrology in Jiangsu Provincial Hospital of Traditional Chinese Medicine from January 1, 2024, to December 30, 2024.

[0052] 1.2 Diagnostic Criteria

[0053] 1.2.1 Western Medicine Diagnostic Criteria

[0054] Refer to "Chinese Nephrology" in 2008 (edited by Li Leishi and Liu Zhihong, People's Military Medical Press), "Internal Medicine" in 2018 (edited by Ge Junbo, Xu Yongjian, and Wang Chen, 9th edition, People's Medical Publishing House), and "Chinese Expert Consensus on the Diagnosis and Treatment of Urinary Tract Infections (2015 Edition)". As the gold standard for the diagnosis of urinary tract infections, urine bacterial culture can effectively judge the patient's condition. However, bacterial culture takes a long time, and clinically, patients use antibiotics frequently, resulting in about 70% of the bacterial culture results in the submitted specimens being negative, wasting time and energy and delaying diagnosis and treatment. Urinalysis is a commonly used method in the diagnosis and treatment effect evaluation of urinary tract infections, with advantages such as being fast, convenient, and inexpensive. Therefore, the following criteria are formulated:

[0055] The urinary tract infection recurs more than once within half a year, or more than twice within one year;

[0056] Clinical manifestations: Dysuria, frequent urination, urgency, dysuria, with or without hematuria, and some patients have systemic symptoms such as low back pain and fever;

[0057] Laboratory examination: Urinalysis shows positive urine white blood cells and elevated urine white blood cell count, etc.

[0058] 1.2.2 Traditional Chinese Medicine Diagnostic Criteria

[0059] Urinary tract infection belongs to the category of "stranguria" in Traditional Chinese Medicine. Refer to the relevant content of "stranguria" in the national-level planning textbook of general higher education "Internal Medicine of Traditional Chinese Medicine" (edited by Zhang Boli and Wu Mianhua, China Press of Traditional Chinese Medicine, 2017.2). Frequent urination, dripping pain, the feeling of incomplete urination, urgency in the lower abdomen, or pain radiating to the lower back and abdomen are the main symptoms of various stranguria syndromes and the main basis for diagnosing stranguria.

[0060] 1.2.3 Traditional Chinese Medicine Syndrome Differentiation Criteria: Formulated by referring to the relevant content of relevant chapters such as "Diagnosis and Treatment Plan for Dominant Diseases of Traditional Chinese Medicine in Jiangsu Province (Trial)":

[0061] Consolidation period (prevention of recurrence period): Main symptoms of the syndrome of qi deficiency of the spleen and kidney: ① Frequent urination or no urination, ② Easy fatigue, ③ Discomfort in the urethra after fatigue, ④ A feeling of heaviness in the lower abdomen, ⑤ Lassitude of the limbs, ⑥ History of urinary tract infection

[0062] Sub-symptoms: ① Soreness and weakness of the waist and knees, ② Poor mental state, ③ Prone to catching cold, ④ Dry mouth

[0063] Tongue and pulse: The tongue is pale red, the coating is thin white or greasy, and the pulse is thin and stringy.

[0064] Syndrome diagnosis: Meeting 1 main symptom, or 2 or more sub-symptoms, and referring to the tongue and pulse, the diagnosis can be made.

[0065] 1.3 Inclusion Criteria

[0066] (1) Meeting the Western medicine and Traditional Chinese Medicine consolidation period diagnostic criteria for recurrent urinary tract infections;

[0067] (2) The age should be above 18 years old, both male and female are eligible.

[0068] (3) Have not taken or injected drugs that seriously affect the functions of organs such as the liver and kidneys in the past 3 months.

[0069] (4) Sign the informed consent form.

[0070] 1.4 Exclusion Criteria

[0071] (1) Patients with complex urinary tract infections diagnosed with urinary tract anatomical structure and functional abnormalities.

[0072] (2) Those with other serious diseases.

[0073] (3) Patients with allergic constitution and allergic to the drugs used in this research.

[0074] (4) Females during pregnancy, childbirth, puerperium and lactation.

[0075] 1.5 Grouping and Treatment Methods

[0076] 1.5.1 General treatment: Instruct the patients to have appropriate rest and, if necessary, stay in bed; ensure sufficient water intake to facilitate frequent urination; eat less greasy food and appropriately more vegetables, etc.

[0077] 1.5.2 Control group: Use Zishen Tongguan Capsules (a hospital preparation of Jiangsu Provincial Hospital of Traditional Chinese Medicine), 6 capsules each time, three times a day. 1.5.3 Research group: Administer the extract prepared by the method of Example 1, 200 mL each time, three times a day. The course of treatment is 12 weeks, and follow-up is for 6 months.

[0078] 1.6 Observation Indicators

[0079] 1.6.1 General Indicators

[0080] General items: Patient's name, contact information;

[0081] Biological indicators (demographic characteristics): Gender, age, height, weight;

[0082] 1.6.2 Efficacy Indicators

[0083] (1) Main efficacy indicators: Number of clinical relapses / average relapse frequency during the follow-up period, number of positive urine white blood cell relapses / average relapse frequency during the follow-up period;

[0084] (2) Secondary efficacy indicators: TCM syndrome integral (as shown in Table 4);

[0085] 1.7 Efficacy Judgment

[0086] 1.7.1 Treatment Effective Rate

[0087] Evaluation of the curative effect of traditional Chinese medicine syndromes: The curative effect evaluation criteria were formulated with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial)".

[0088]

[0089] Note: Calculation formula (Nimodipine method): [(Integral before treatment - Integral after treatment) ÷ Integral before treatment] × 100%. Total effective rate = (Number of cured cases + Number of markedly effective cases + Number of effective cases) / Total number of cases × 100%

[0090] 1.7.2 Clinical recurrence rate

[0091] For the follow-up patients from the 5th week to the 6th month, the recurrence was defined as the reappearance of symptoms and signs related to urinary tract infection, positive urine white blood cells, and a significant increase in the urine white blood cell count.

[0092] Recurrence rate = Number of recurrence cases / Total number of observed cases × 100%.

[0093] 1.8 Research results

[0094] From January 2023 to December 2023, a total of 120 patients entered the study cohort in this trial (60 cases in the control group and 60 cases in the study group).

[0095] 1.8.1 Description of the statistical results of the recurrence rate: As Figure 1 and Table 1, the statistical analysis results showed that the recurrence rate of urinary tract infection in the study group of the present invention was 15%, while that in the control group was 31.67%. There was a statistically significant difference in the recurrence rate between the two groups (P < 0.05).

[0096] Table 1 Comparison of recurrence situations between the two groups

[0097]

[0098] 1.8.2 Description of the results of traditional Chinese medicine syndrome scores:

[0099] As shown in Table 2, the statistical analysis results showed that there were statistically significant differences in the traditional Chinese medicine syndrome scores of the two groups of patients after treatment compared with before treatment (P < 0.001 in the study group, P < 0.05 in the control group).

[0100] As shown in Table 3, when comparing the study group with the control group, there was a statistically significant difference in the improvement of the traditional Chinese medicine syndrome scores of the patients after treatment (P < 0.05).

[0101] Table 2 Improvement of traditional Chinese medicine syndrome scores of the two groups of patients before and after treatment

[0102]

[0103] Note: Compared with before treatment in this group, *P < 0.05, #P < 0.001.

[0104] Comparison of the improvement of traditional Chinese medicine syndrome scores in two groups of patients before and after treatment

[0105] Frequent urination Urethral burning sensation Discomfort with a feeling of fullness and distension in the lower abdomen Soreness in the lower back Significance (P) 0.018 0.037 0.111 0.034

[0106] Table 4 Traditional Chinese medicine syndrome scoring scale

[0107]

[0108]

[0109] Pharmacodynamic experiment of Example 5 for consolidating the treatment of urinary tract infection and preventing recurrence

[0110] 1 Materials and methods

[0111] 1.1 Obtaining the effective chemical components and their targets of the traditional Chinese medicine compound composition

[0112] The chemical components of the traditional Chinese medicine raw materials (Astragalus membranaceus, Pyrrosia lingua, Perilla frutescens, Salvia miltiorrhiza, Glycyrrhiza uralensis) of the traditional Chinese medicine compound composition (Qiwei Fangfu Granules) were retrieved and obtained using the TCMSP database (https: / / old.tcmsp-e.com / cvdsp.php / ). After summarization, they were preliminarily screened with the simultaneous satisfaction of the oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18 in the TCMSP database. The screening results were further screened with the secondary screening criteria of High for GI absorption and ≥ 2 Yes for Druglikeness in the SwissADME platform (http: / / www.swissadme.ch / ) to obtain the effective components of Qiwei Fangfu Granules. The Canonical SMILES and 2D Structure of the known chemical components were obtained using the Pubchem database (https: / / pubchem.ncbi.nlm.nih.gov / ) and the Novopro online tool (https: / / www.novopro.cn / tools / mol2smiles.html), and were respectively imported into SwissTargetPrediction (http: / / www.swisstargetprediction.ch / ) to predict the targets of the effective components, and an active ingredient library and target library of "Qiwei Fangfu Granules" were established.

[0113] 1.2 Obtaining disease targets and intersection targets

[0114] Search in the GeneCards and OMIM databases using "recurrent urinary tract infection" as the keyword. In the GeneCards database, screen with a Score value ≥ 24.77. After removing duplicates of the obtained genes, establish a target library for recurrent urinary tract infection diseases.

[0115] Use the online platform of Microbioinformatics (https: / / www.bioinformatics.com.cn / ) to take the intersection between the potential action targets of Qiwei Fangfu Granules and the gene targets related to recurrent urinary tract infection screened above, and obtain the intersection targets of the active ingredients of Qiwei Fangfu Granules - recurrent urinary tract infection.

[0116] 1.3 Construct the network relationships of traditional Chinese medicine - ingredient - target and traditional Chinese medicine - ingredient - target - disease for Qiwei Fangfu Granules

[0117] Import the drug composition, active ingredients, intersection targets, etc. of Qiwei Fangfu Granules into Cytoscape 3.10.2 software to construct the relationships of "traditional Chinese medicine - ingredient - target" and "traditional Chinese medicine - ingredient - target - disease" respectively.

[0118] 1.4 Construct protein - protein interaction (PPI) networks and obtain core targets

[0119] Input the obtained intersection target set into the STRING 12.0 platform (https: / / cn.string - db.org / ), select the "multiple proteins" analysis mode, limit the species to "Homo sapiens", export the results as a.tsv file and set parameters using the centiscape 2.2 plugin in Cytoscape 3.10.2 software. Retain the intersection targets that are simultaneously greater than the median of the three values of degree, betweeness centrality, and closeness centrality to construct the PPI network.

[0120] 1.5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis

[0121] KEGG enrichment analysis was performed on the intersection targets through the DAVID platform (https: / / david.ncifcrf.gov / ), and the data was imported into the Microbial Information online platform to achieve data visualization, analyze the biological functions of the targets of Qiwei Fangfu Granules in the treatment of recurrent urinary tract infection, and explore its potential signaling pathways.

[0122] 1.6 Molecular Docking

[0123] The structures of the selected target proteins and ligands were obtained through the RCSBPDB platform and the Pubchem database respectively. The water in the target proteins and the ligand small molecules were removed using PyMol 2.5.5, and then imported into AutoDockVina for docking. The LocalSearch 4.2 algorithm was used in the calculation process, and finally the results were imported into PyMol 2.5.5 for visualization processing.

[0124] 2 Results

[0125] 2.1 Obtaining the potential active ingredients and targets of Qiwei Fangfu Granules

[0126] After preliminary extraction using the TCMSP database and the TCMIPv2.0 platform, and unified ADME screening with the ingredients obtained from literature retrieval, the following traditional Chinese medicine active ingredients were obtained: 17 for Astragalus membranaceus; 5 for Pyrrosia lingua; 52 for Salvia miltiorrhiza; 10 for Perilla frutescens; 84 for Glycyrrhiza uralensis. After merging and removing duplicates, a total of 185 active compounds were obtained. Further collecting their related action targets, a total of 948 potential targets were obtained after merging and removing duplicates.

[0127] 2.2 Obtaining the disease action targets and intersection targets

[0128] 1288 disease targets were collected from the GeneCards database and 119 from the OMIM database. Combining the above collection results and removing duplicate genes, a total of 1384 intervention targets for recurrent urinary tract infection were obtained. Using the Microbial Information online cloud platform, 244 intersection targets were obtained, as shown in Figure 2 .

[0129] 2.3 Traditional Chinese medicine - ingredient - target and network of Qiwei Fangfu Granules

[0130] First, the drug composition, active ingredients, intersection targets, etc. of Qiwei Fangfu Granules were imported into the Cytoscape 3.10.2 software to obtain an interaction network relationship of "traditional Chinese medicine - ingredient - target" containing 1101 nodes and 9242 edges. Analyzing the above network using the plug-in centiscape 2.2 and arranging according to degree from high to low, the top 5 active ingredients in the network were all kaempferol, quercetin, flavanol, isorhamnetin, luteolin, etc., which may play a greater role in the treatment of recurrent urinary tract infection by Qiwei Fangfu Granules.

[0131] 2.4 PPI Network Topology Analysis

[0132] The 244 intersecting targets obtained were input into the STRING 12.0 platform (https: / / cn.string-db.org / ) to obtain the PPI network diagram as Figure 3 shown. The plugin Centiscape 2.2 in the Cytoscape 3.10.2 software was used for visualization and analysis of the core targets, including 243 nodes and 5,730 edges. The larger the node in the network, the higher the degree of freedom value and the greater the role in the network. Taking the median of the degree of freedom value, betweenness centrality, and closeness centrality of the nodes as the threshold, a PPI network with 52 nodes and 1,014 edges was obtained. Finally, the first 30 nodes were retained to obtain a core cluster with 30 nodes and 414 edges. As Figure 3 shown, in the protein-protein interaction network, AKT1, IL6, NFkB1, JUN, and EGFR are in the central positions. The above targets may play an important role in the prevention and treatment of recurrent urinary tract infections by Qiwei Fangfu Granules.

Claims

1. A traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infections and preventing recurrence, characterized in that, It includes the following raw materials: Astragalus membranaceus, Pyrrosia lingua, Salvia miltiorrhiza, Perilla stem and Glycyrrhiza uralensis Fisch.

2. The traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence according to claim 1, wherein It is made from the following raw materials in parts by weight: Made from 15 - 45 parts of Astragalus membranaceus, 15 - 45 parts of Pyrrosia lingua, 15 - 45 parts of Salvia miltiorrhiza, 15 - 45 parts of Perilla stem and 4 - 12 parts of Glycyrrhiza uralensis Fisch.

3. The traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence according to claim 2, wherein, It is made from the following raw materials in parts by weight: Made from 15 - 30 parts of Astragalus membranaceus, 15 - 30 parts of Pyrrosia lingua, 15 - 30 parts of Salvia miltiorrhiza, 15 - 30 parts of Perilla stem and 4 - 8 parts of Glycyrrhiza uralensis Fisch.

4. The traditional Chinese medicine compound composition for consolidating the treatment of urinary tract infection and preventing recurrence according to claim 3, characterized in that, It is made from the following raw materials in parts by weight: Made from 15 parts of Astragalus membranaceus, 15 parts of Pyrrosia lingua, 15 parts of Salvia miltiorrhiza, 15 parts of Perilla stem and 4 parts of Glycyrrhiza uralensis Fisch.

5. The preparation method of the traditional Chinese medicine compound composition according to any one of claims 1 to 4, characterized in that, It includes the following steps: Take Astragalus membranaceus, Pyrrosia lingua, Salvia miltiorrhiza, Perilla stem and Glycyrrhiza uralensis Fisch., immerse the medicinal materials with water or alcohol, soak first, then extract, filter, combine the filtrates, concentrate by rotary evaporation, and dry to obtain.

6. The preparation method of the traditional Chinese medicine compound composition according to claim 5, characterized in that, It includes the following steps: Take Astragalus membranaceus, Pyrrosia lingua, Salvia miltiorrhiza, Perilla stem and Glycyrrhiza uralensis Fisch., immerse the medicinal materials with 5 - 15 times the volume of water based on the weight of the medicinal materials, soak for 30 - 40 min, decoct and extract for 30 - 60 min, filter, collect the decoction liquid, take the medicinal residues and decoct again with 5 - 15 times the volume of water for 30 - 60 min, filter, collect the decoction liquids of the two times, filter, concentrate the filtrate by rotary evaporation, and freeze - dry to obtain the freeze - dried powder.

7. A traditional Chinese medicine preparation for consolidating the treatment of urinary tract infection and preventing recurrence, characterized in that, Prepare the extract of the traditional Chinese medicine compound composition into granules, tablets, capsules, pills, oral liquids, powders, mixtures or ointments with pharmaceutically acceptable carriers.

8. Use of the traditional Chinese medicine compound composition according to any one of claims 1 - 4 in the preparation of a drug for consolidating the treatment of urinary tract infection and preventing recurrence.

9. Use of the traditional Chinese medicine compound composition according to any one of claims 1 - 3 in the preparation of a drug for treating recurrent urinary tract infection.

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