Traditional Chinese medicine compound composition for treating acute radiation cystitis, preparation and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine compound composition for treating acute radiation cystitis, a preparation and a preparation method thereof, and belongs to the technical field of medicines. The traditional Chinese medicine compound composition for treating acute radiation cystitis is prepared by screening compound components on the basis of modern molecular biology means and combining the traditional Chinese medicine compound theory. The traditional Chinese medicine compound composition for treating acute radiation cystitis is prepared by extracting 2-4 parts of lysimachia christinae hance, 1-3 parts of herba epimedii, 2-4 parts of herba patriniae, 2-4 parts of rhizoma smilacis glabrae, 0.8-2.8 parts of radix sophorae flavescentis, 1-3 parts of Chinese lobelia, 1.4-3.4 parts of semen cuscutae, 1-3 parts of sea-buckthorn, 1-3 parts of erigeron breviscapus and 1-3 parts of liquorice. The traditional Chinese medicine compound can solve the problems of lack of targeted mechanism intervention, limited curative effect, large side effect, poor patient compliance and the like in the existing treatment; in addition, the invention provides key targets and effective components of drugs for acute radiation cystitis, and experiments prove that the pharmaceutical composition has an obvious treatment effect on acute radiation cystitis.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to a traditional Chinese medicine compound composition for treating acute radiation cystitis, a preparation and a preparation method thereof. BACKGROUND

[0002] Acute radiation cystitis is a common acute side injury of patients with pelvic tumor after receiving radiotherapy, which is manifested as frequent urination, urgent urination, painful urination, hematuria and the like. In severe cases, it can lead to significant decrease in bladder capacity, fibrosis of bladder wall and even urinary retention, which seriously affects the quality of life of patients. The existing bladder irrigation needs frequent and complex operation, and some patients have obvious bladder irritation symptoms during the irrigation process, so the compliance is poor. Hyperbaric oxygen therapy has a long cycle, high cost, high requirement for facilities, and is difficult to popularize, and the effect on some patients is limited. Anti-inflammatory drugs or antioxidants such as non-steroidal anti-inflammatory drugs and flavonoids have low bioavailability in local tissues of the bladder and limited efficacy. Based on the above defects, it becomes a technical problem to be solved in the prior art to provide a standard drug targeting the molecular mechanism of radiation-induced bladder injury, multiple targets, and systemically regulating local inflammation, oxidative stress and tissue damage. SUMMARY

[0003] Based on the above technical problems to be solved by the present application, the present application proposes a traditional Chinese medicine compound composition for treating acute radiation cystitis, a preparation and a preparation method thereof based on modern molecular biology means to screen compound ingredients and combined with the theory of traditional Chinese medicine compound.

[0004] One of the purposes of the present application is to provide a traditional Chinese medicine compound composition for treating acute radiation cystitis, which is prepared by extracting Lysimachia christinae Hance 2-4 parts, Epimedium 1-3 parts, Patrinia 2-4 parts, Smilax glabra 2-4 parts, Sophora flavescens 0.8-2.8 parts, Lobelia 1-3 parts, Semen Cocloris 1.4-3.4 parts, Hippophae rhamnoides 1-3 parts, Herba Erigerontis 1-3 parts and Glycyrrhiza 1-3 parts according to weight parts.

[0005] Further, the traditional Chinese medicine compound composition is prepared by extracting Lysimachia christinae Hance 2.5-3.5 parts, Epimedium 1.5-2.5 parts, Patrinia 2.5-3.5 parts, Smilax glabra 2.5-3.5 parts, Sophora flavescens 1.3-2.3 parts, Lobelia 1.5-2.5 parts, Semen Cocloris 1.9-2.9 parts, Hippophae rhamnoides 1.5-2.5 parts, Herba Erigerontis 1.5-2.5 parts and Glycyrrhiza 1.5-2.5 parts according to weight parts.

[0006] Further, the traditional Chinese medicine compound composition is prepared by extracting Lysimachia christinae Hance 2.5-3.5 parts, Epimedium 1.5-2.5 parts, Patrinia 2.5-3.5 parts, Smilax glabra 2.5-3.5 parts, Sophora flavescens 1.3-2.3 parts, Lobelia 1.5-2.5 parts, Semen Cocloris 1.9-2.9 parts, Hippophae rhamnoides 1.5-2.5 parts, Herba Erigerontis 1.5-2.5 parts and Glycyrrhiza 1.5-2.5 parts according to weight parts.

[0007] The second object of the present application is to provide a traditional Chinese medicine compound preparation for treating acute radiation cystitis.

[0008] Further, the traditional Chinese medicine compound preparation includes a mixture, a tablet and a granule.

[0009] Further, the pharmaceutical excipient is a pharmaceutically acceptable excipient.

[0010] The third object of the present application is to provide a preparation method of a traditional Chinese medicine compound preparation for treating acute radiation cystitis, comprising the following steps.

[0011] S1, weighing according to the following weight ratio: Herba Lysimachiae: Herba Epimedii: Herba Patriniae: Smilax Glabra: Sophora Flavescens: Lobelia Chinensis: Semen Lagenariae: Hippophae Rhamnoides: Herba Erigerontis: Glycyrrhiza = (2-4) : (1-3) : (2-4) : (2-4) : (0.8-2.8) : (1-3) : (1.4-3.4) : (1-3) : (1-3) : (1-3) to obtain a weighed traditional Chinese medicine compound composition.

[0012] S2, adding 8-12 times the volume of water to the weighed traditional Chinese medicine compound composition and soaking for 20-40 minutes to obtain a soaked traditional Chinese medicine compound composition. The water addition multiple and soaking time are determined by experiments. According to the influence of different water addition multiples (6 times, 8 times, 10 times, 12 times, 14 times) on the extraction rate, the results show that when the water addition multiple is less than 8 times, the drug solution concentration is too high, local decoction is uneven, and the extraction rate of some components decreases; and when the water addition multiple exceeds 12 times, the drug solution is diluted, the concentration of effective components is reduced, and the comprehensive efficacy and extraction efficiency decrease. Therefore, the water volume is determined to be 8-12 times the mass of the medicinal material. According to the influence of soaking for 10, 20, 30, 40 and 60 minutes on the content of main components (such as flavonoids and polysaccharides) in the extraction solution, the results show that soaking for 20-40 minutes can make the medicinal material fully absorb water and swell, the cell wall softens, which is beneficial to the subsequent dissolution of components, improves the yield and stability of the drug solution; about 30 minutes is the best water absorption and dissolution balance point. Therefore, the soaking time is determined to be 20-40 minutes. Using the above water addition multiple and soaking time, the extraction of effective components in the compound can be more sufficient, the drug solution concentration is stable, the batch-to-batch fluctuation is reduced, the biological activity and efficacy consistency of the compound are improved; oxidation or hydrolysis inactivation of some components caused by long-time soaking is avoided, and the preparation quality is ensured.

[0013] S3, heating and decocting the soaked traditional Chinese medicine compound composition, combining the decoction, and filtering to obtain a decocted and filtered traditional Chinese medicine compound composition extract. Insufficient decocting can cause incomplete dissolution of the effective components, and too long decocting time can cause degradation of some heat-sensitive components. The selected heating and decocting times and durations can significantly improve the extraction rate and concentration stability of the effective components of the compound, and the decoction has uniform color and is clear and transparent; meanwhile, the energy consumption and operation time are reduced, and the stability of the drug efficacy and the repeatability of the process are ensured.

[0014] S4, concentrating the decocted and filtered traditional Chinese medicine compound composition extract, and performing preparation molding, quality control, packaging and sterilization to obtain the traditional Chinese medicine compound preparation. The process can significantly improve the purity and stability of the drug powder, and the obtained preparation after freeze-drying is light yellow loose powder, which is easy to store and redissolve, has good solubility and small batch-to-batch difference. Compared with traditional atmospheric concentration or hot air drying, the retention rate of the active components is increased by about 15% to 25%, the drug efficacy retention is enhanced, and the storage period and transportation stability of the preparation are prolonged.

[0015] Further, the heating and decocting is performed 2 to 3 times, and each time is 30 to 45 min. Through comparison of different decocting times (1 to 3 times), durations (20 to 60 min) and water addition multiples (6 to 12 times), it is found that when the decocting is performed 2 to 3 times and each time is 30 to 45 min, the extraction rate of the main active components (such as flavonoids, polysaccharides and saponins) is the highest and the batch-to-batch difference is the smallest. The decocting parameters are determined by single-factor optimization experiment. When the decocting is performed less than 2 times, the effective components in the medicinal materials are not completely released; when the decocting is performed more than 3 times, the extraction rate is not significantly improved and the energy consumption is increased. When the duration is less than 30 min, the dissolution rate is insufficient, and when the duration is more than 45 min, it is detected that some flavonoids are degraded. The selected time and number of times can balance the dissolution of the effective components and the stability of the components, improve the extraction efficiency by about 15% to 25%, and ensure the consistency of the preparation quality and the reliability of the drug efficacy.

[0016] The fourth object of the present application is to provide an application of the traditional Chinese medicine compound preparation for treating acute radiation cystitis in preparing a drug for treating acute radiation cystitis.

[0017] Further, the traditional Chinese medicine compound preparation is 1 dose per day, taken orally 3 times. The administration scheme is determined according to animal experiments and clinical experience of traditional Chinese medicine. Through comparison of different administration frequencies (once a day, twice a day, and three times a day), it is found that divided administration can maintain the stability of blood drug concentration, so that the effective components in the compound can maintain a sustained effect in the body. According to the metabolism of the drug in the body and the pharmacological duration of about 6-8 hours, the selection of 1 dose per day, taken 3 times can maintain the continuity of drug efficacy, enhance the absorption utilization rate, significantly improve the treatment compliance and safety, ensure the stability of drug efficacy day and night, and avoid drug fluctuation. According to the medication principle of traditional Chinese medicine'small amount and multiple times, long-term nourishment', taking medicine in several times can help to reduce the stimulation of a large dose of administration on the gastrointestinal tract, improve the patient's compliance and absorption efficiency. Compared with single large dose administration, the administration scheme can improve the in-vivo utilization rate of effective components by about 10%-20%, while reducing the potential risk of adverse reactions, ensuring stable and repeatable efficacy.

[0018] Compared with the prior art, the present application provides a traditional Chinese medicine compound composition for treating acute radiation cystitis, a preparation and a preparation method thereof, which has the following beneficial effects: The traditional Chinese medicine compound composition for treating acute radiation cystitis provided by the present application can solve the problems of lack of targeted mechanism intervention, limited efficacy, large side effects and poor patient compliance in the prior art.

[0019] Further, the present application screens the key target points and effective components of the drug for acute radiation cystitis based on the reverse network pharmacology method, and is designed in combination with the theory of traditional Chinese medicine syndrome differentiation and treatment and the 'jun, chen, za and shi' compatibility principle, has the comprehensive effects of clearing heat and resolving toxicity, promoting dampness and removing edema, promoting blood circulation and removing blood stasis, etc., can harmonize the functions of viscera and bowels as a whole, reduce the damage of bladder tissue, promote repair, improve the bladder function index, and provides a traditional Chinese medicine compound composition and preparation for treating acute radiation cystitis, which has multiple target points, is systematic and has high safety. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 A Wayne diagram of disease target points of radiation cystitis is shown.

[0021] Figure 2 A core target point diagram of disease target points in a disease database is shown.

[0022] Figure 3 A core target point screening diagram of differential genes in single cell transcriptome data is shown.

[0023] Figure 4 A core target point screening diagram of differential genes in ordinary transcriptome data is shown.

[0024] Figure 5A "target point-compound-traditional Chinese medicine" network map of an embodiment of the present application is shown.

[0025] Figure 6 A forward network pharmacology analysis diagram of a traditional Chinese medicine compound of an embodiment of the present application is shown.

[0026] Figure 7 A verification of forward and reverse network pharmacology of an embodiment of the present application is shown in a core target intersection diagram.

[0027] Figure 8 A verification of forward and reverse network pharmacology of an embodiment of the present application is shown in a core compound intersection diagram.

[0028] Figure 9 In a network pharmacology analysis of an embodiment of the present application, a target point GO enrichment analysis diagram of a traditional Chinese medicine compound composition is shown.

[0029] Figure 10 In a network pharmacology analysis of an embodiment of the present application, a target point KEGG enrichment analysis diagram of a traditional Chinese medicine compound composition is shown.

[0030] Figure 11 A bladder tissue appearance diagram of a traditional Chinese medicine compound composition for treating acute cystitis for 14 days of an embodiment of the present application is shown.

[0031] Figure 12 A urine leakage point pressure measurement diagram of an embodiment of the present application is shown.

[0032] Figure 13 A measurement diagram of bladder capacity after 14 days of medication of an embodiment of the present application is shown.

[0033] Figure 14 A urine analysis diagram of an embodiment of the present application is shown.

[0034] Figure 15 A pathological staining analysis diagram of an embodiment of the present application is shown.

[0035] Figure 16 A transmission electron microscope analysis diagram of an embodiment of the present application is shown, in which (a) is a normal group; (b) is a model group; and (c) is a medication group.

[0036] Figure 17 A pathological staining analysis of main organs of an embodiment of the present application is shown.

[0037] Figure 18 A measurement diagram of bladder capacity after 14 days of medication is shown to observe the improvement effect of the dose in the compound medicine relative to the model group.

[0038] Figure 19 A urine analysis chart of 14 days of drug administration is shown to observe the improvement effect of the low, medium and high doses of the compound drug relative to the model group.

[0039] Figure 20 A urine analysis chart of 14 days of drug administration is shown to observe the improvement effect of the low, medium and high doses of the compound drug relative to the model group.

[0040] Figure 21 A pathological staining analysis chart of 14 days of drug administration is shown to observe the improvement effect of the low, medium and high doses of the compound drug relative to the model group.

[0041] Figure 22 A bladder capacity measurement chart of 14 days of drug administration is shown to observe the effect comparison of the low, medium and high doses of the compound drug.

[0042] Figure 23 A leakage point pressure measurement chart of 14 days of drug administration is shown to observe the effect comparison of the low, medium and high doses of the compound drug.

[0043] Figure 24 A urine analysis chart of 14 days of drug administration is shown to observe the effect comparison of the low, medium and high doses of the compound drug.

[0044] Figure 25 A pathological staining analysis chart of 14 days of drug administration is shown to observe the effect comparison of the low, medium and high doses of the compound drug.

[0045] Figure 26 A bladder capacity measurement chart of 14 days of drug administration is shown to observe the improvement effect of the medium dose of the compound drug relative to the dexamethasone treatment group.

[0046] Figure 27 A leakage point pressure measurement chart of 14 days of drug administration is shown to observe the improvement effect of the medium dose of the compound drug relative to the dexamethasone treatment group.

[0047] Figure 28 A urine analysis chart of 14 days of drug administration is shown to observe the improvement effect of the medium dose of the compound drug relative to the dexamethasone treatment group.

[0048] Figure 29 A pathological staining analysis chart of 14 days of drug administration is shown to observe the improvement effect of the medium dose of the compound drug relative to the dexamethasone treatment group.

[0049] Figure 30 A measurement chart of bladder capacity at 7 days and 14 days of medication is shown to observe the effect of the length of the treatment cycle on the recovery of bladder function.

[0050] Figure 31 A pathological staining analysis chart at 7 days and 14 days of medication is shown to observe the repair effect of the length of the treatment cycle on the bladder pathological damage.

[0051] Figure 32 A high efficiency mass spectrum analysis chart of the dry powder of the mixture traditional Chinese medicine is shown. DETAILED DESCRIPTION

[0052] Exemplary embodiments of the present application will be described herein below with reference to the accompanying drawings. While exemplary embodiments of the present application are shown in the drawings, it is understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that this application will be thoroughly and completely understood, and one skilled in the art will be able to convey the full scope of the present application to others skilled in the art.

[0053] In the following examples, if not specifically indicated, the technical means used are conventional means known to those skilled in the art, and the reagents and materials in the present application are obtained from the market or other public channels.

[0054] The experimental raw materials and equipment involved in the present application mainly include, but are not limited to: Reagents (see Table 1): Table 1 Main reagent information table Instruments (see Table 2): Table 2 Main instrument information table The technical principle of the traditional Chinese medicine compound composition, preparation and preparation method for treating acute radiation cystitis according to the present application mainly includes: The traditional Chinese medicine compound composition provided by the present application is used for treating acute radiation cystitis. The composition is developed based on the reverse network pharmacology method to screen disease-related core target points and potential active ingredients, combined with the "spleen deficiency and dampness blood stasis" syndrome type and "jun, chen, zhe and shi" compatibility theory of traditional Chinese medicine, and has the effects of clearing heat and resolving toxins, removing dampness and promoting urination, promoting blood circulation and removing blood stasis, etc. The composition is used for relieving symptoms such as frequent urination, urgent urination, painful urination, hematuria and other symptoms caused by acute radiation cystitis, regulating bladder function, protecting mucosal structure, inhibiting inflammatory response, and promoting bladder tissue repair.

[0055] The application provides a traditional Chinese medicine compound composition and preparation for treating acute radiation cystitis and a preparation method thereof. P <0.05); the contents of red blood cells, white blood cells and protein in the urine were significantly reduced, indicating that the inflammation of the bladder was reduced; HE and Masson staining showed that the epithelial structure of the bladder in the treatment group was more complete, collagen deposition was reduced, and inflammatory infiltration was significantly reduced; transmission electron microscopy observation found that the ultrastructure of the bladder epithelium in the treatment group was recovered well, the cell connection was tight, and the mitochondria were complete; transcriptome sequencing revealed that the treatment group was up-regulated in multiple signaling pathways, involving cell repair, antioxidant, immune regulation and other mechanisms. Thirdly, the safety is high, the compliance is good, and the application is suitable for promotion. The traditional Chinese medicine composition or preparation described in the application is used for acute radiation cystitis, compared with bladder irrigation or hyperbaric oxygen, the application adopts an oral administration mode, the preparation is natural in source, has small toxic and side effects, no obvious adverse reactions are observed in animal experiments, and the application has good safety and acceptability. Fourthly, the preparation is simple and can be industrially produced. The traditional Chinese medicine compound can be applied by using a traditional Chinese medicine decoction method, can be further concentrated and dried to prepare granules, tablets and other preparation forms meeting the purpose of the application.

[0056] Based on the above principle, the application provides a traditional Chinese medicine compound composition and preparation for treating acute radiation cystitis and a preparation method thereof.

[0057] The traditional Chinese medicine compound composition is prepared by extracting, according to weight parts, 2-4 parts of Lysimachia christinae, 1-3 parts of Epimedium, 2-4 parts of Patrinia, 2-4 parts of Smilax glabra, 0.8-2.8 parts of Sophora, 1-3 parts of Lobelia, 1.4-3.4 parts of Semen Taxilli, 1-3 parts of Hippophae, 1-3 parts of Herba Erigerontis and 1-3 parts of Glycyrrhiza.

[0058] Further, the traditional Chinese medicine compound composition is prepared by extraction of Herba Lysimachiae 2.5-3.5 parts, Herba Epimedii 1.5-2.5 parts, Herba Patriniae 2.5-3.5 parts, Smilax glabra 2.5-3.5 parts, Sophora flavescens 1.3-2.3 parts, Lobelia sinuata 1.5-2.5 parts, Semen Nelumbinis 1.9-2.9 parts, Hippophae rhamnoides 1.5-2.5 parts, Herba Erigerontis 1.5-2.5 parts and Radix Glycyrrhizae 1.5-2.5 parts according to weight parts.

[0059] Further, the traditional Chinese medicine compound composition is prepared by extraction of Herba Lysimachiae 2.5-3.5 parts, Herba Epimedii 1.5-2.5 parts, Herba Patriniae 2.5-3.5 parts, Smilax glabra 2.5-3.5 parts, Sophora flavescens 1.3-2.3 parts, Lobelia sinuata 1.5-2.5 parts, Semen Nelumbinis 1.9-2.9 parts, Hippophae rhamnoides 1.5-2.5 parts, Herba Erigerontis 1.5-2.5 parts and Radix Glycyrrhizae 1.5-2.5 parts according to weight parts.

[0060] The traditional Chinese medicine compound preparation for treating acute radiation cystitis according to the application includes mixture, tablet, granule and any other preparation form that can meet the purpose of the application.

[0061] The preparation method of the traditional Chinese medicine compound preparation for treating acute radiation cystitis according to the application comprises: S1, weighing according to the following weight ratio: Herba Lysimachiae: Herba Epimedii: Herba Patriniae: Smilax glabra: Sophora flavescens: Lobelia sinuata: Semen Nelumbinis: Hippophae rhamnoides: Herba Erigerontis: Radix Glycyrrhizae=(2-4):(1-3):(2-4):(2-4):(0.8-2.8):(1-3):(1.4-3.4):(1-3):(1-3):(1-3) to obtain the weighed traditional Chinese medicine compound composition.

[0062] S2, adding 8-12 times the volume of water to the weighed traditional Chinese medicine compound composition, soaking for 20-40 min to obtain the soaked traditional Chinese medicine compound composition.

[0063] S3, heating and decocting the soaked traditional Chinese medicine compound composition, combining the decoction, filtering to obtain the decoction filtrate of the decocted and filtered traditional Chinese medicine compound composition; the heating and decocting is 2-3 times, each time for 30-45 min.

[0064] S4, the decoction filtered traditional Chinese medicine compound composition extract is concentrated to obtain the traditional Chinese medicine compound preparation. The decoction filtered traditional Chinese medicine compound composition extract is concentrated under reduced pressure at 60-80 DEG C, and then is placed in a vacuum freeze dryer for freeze drying, and after the drug powder is completely freeze-dried, is stored for standby. Through process optimization test, various drying processes such as atmospheric pressure concentration, reduced pressure concentration and spray drying, vacuum freeze drying are compared, and it is determined that reduced pressure concentration combined with vacuum freeze drying can maximize the activity of heat-sensitive components (such as flavonoids, polysaccharides, volatile oils, etc.) in the traditional Chinese medicine compound. In the range of 60-80 DEG C, the water can be evaporated quickly under the condition of ensuring the stability of the main active ingredients, avoiding the oxidation or polymerization of the components under high temperature conditions; the subsequent vacuum freeze drying can sublimate and remove the remaining water in a low temperature environment, and the microstructure and pharmacological activity of the drug powder are maintained. The selection of the parameters not only optimizes the extraction liquid concentration and drying efficiency, but also ensures the integrity of the pharmacologically active substances of the compound.

[0065] The ratio range of the traditional Chinese medicine compound composition in the application is determined according to the recommended dose range of the People's Republic of China Pharmacopoeia and the equivalent conversion of animal experiments. In order to verify the rationality of the ratio, different ratio schemes are tested and compared. The comparison results of the traditional Chinese medicine compound composition based on different ratio schemes are proposed in the application, please refer to Table 3. The experimental results show that when the ratio of the main medicinal materials (Herba Lysimachiae, Herba Epimedii, Lobelia Chinensis, etc.) is low (group A), the bladder inflammation inhibition effect and tissue repair ability are insufficient; when the ratio is in the moderate interval (group B), the bladder capacity, leakage point pressure and urine inflammation index are improved most significantly; when the ratio of part of the medicinal materials is further increased (group C), the curative effect is not obviously enhanced, and some experimental animals have mild weight loss. The comprehensive analysis shows that the determined ratio range reaches an optimal balance between efficacy and safety. Further, when the ratio is lower than the lower limit (group D), the efficacy is obviously weakened. In addition, after removing Herba Patriniae and Herba Erigerontis (group E), the comprehensive score of the compound decreases by 40%, indicating that there is a significant synergistic effect among the medicinal materials in the application. In summary, the prescription ratio defined in the application not only conforms to the reasonable interval of the recommended dose of the pharmacopoeia, but also verifies the optimal efficacy and safety balance in animal experiments, proving the scientificity and creativity of the range.

[0066] Table 3 Comparison table of traditional Chinese medicine compound composition with different ratio schemes Note: The curative effect comprehensive score is evaluated according to the inflammation inhibition, tissue repair and bladder function recovery (5 points in total).

[0067] To sum up, the compound within the matching range has significant anti-inflammatory, antioxidant and tissue repair effects, especially the B group has the most significant effect, the matching outside the range has decreased efficacy or safety problems, the limited matching interval is scientific, reasonable and creative technical features, and the application has excellent efficacy and safety in the treatment of acute radiation cystitis. Further, the traditional Chinese medicine composition has good effects in improving the symptoms of radiation cystitis, restoring the function of the bladder and reducing tissue damage, and has high safety and convenience.

[0068] Example 1 The application proposes a reverse network pharmacology mining experiment for screening a traditional Chinese medicine compound for treating acute radiation cystitis. The embodiment belongs to the component screening and core target mining of the traditional Chinese medicine compound in the application, aiming to systematically identify potential pharmacological pathways related to acute radiation cystitis from the perspective of correlation, and provide a scientific basis for subsequent compound prescription and matching optimization.

[0069] Mainly includes: In order to collect potential targets related to radiation cystitis (RC), the following steps are adopted: first, by searching relevant disease information in multiple databases, all targets related to radiation cystitis are screened out in Genecards database, OMIM database, DrugBank database and Disgenet database, after removing duplicates, the intersection targets of radiation cystitis, radiation damage and cystitis are obtained; then, the collected targets are standardized by using Uniprot database to ensure the consistency and accuracy of the data; finally, the key targets representing radiation cystitis are sorted out as the basis for subsequent analysis. The intersection targets of radiation cystitis, radiation damage and cystitis are imported into the STRING website for PPI network interaction analysis, and then the data is imported into Cytoscape for core target screening.

[0070] In the application, the differential genes of the blank control group and the radiation cystitis model group in the single cell transcriptome data of rat radiation cystitis are screened, imported into the STRING website for PPI network interaction analysis, and then the data is imported into Cytoscape software for core target screening.

[0071] In the application, the differential genes of the blank control group and the radiation cystitis model group in the single cell transcriptome data of rat radiation cystitis are screened, imported into the STRING website for PPI network interaction analysis, and then the data is imported into Cytoscape software for core target screening.

[0072] Results: Please refer to Figure 1 ​, the intersection of radiation cystitis, radiation injury and cystitis target points; see Figure 2 , 41 core targets were screened out from the disease database. See Figure 3 , 24 core targets were screened out from the single-cell transcriptome data. See Figure 4 , 26 core targets were screened out from the general transcriptome data.

[0073] Example 2 The present application proposes a screening test for compounds corresponding to disease targets of radiation cystitis. This embodiment belongs to the determination of candidate compounds and core groups of traditional Chinese medicine compounds in the present application. The disease targets obtained in Example 1 are systematically matched with candidate compounds and traditional Chinese medicines by forward network pharmacology analysis to determine the drug combination highly related to the pathological process of radiation cystitis. The core nature and synergistic effect of candidate traditional Chinese medicines in the pharmacological network are verified to determine the reasonable composition of the compound. This embodiment does not involve the optimization of specific dose or ratio.

[0074] Mainly includes: In order to screen out potential effective compounds, the present application collects compound information related to radiation cystitis targets by using the traditional Chinese medicine systematic pharmacology database (TCMSP) platform. According to the pharmacokinetic parameters and Lipinski's rule, the present application preliminarily screens the compounds, and the screening standard is oral bioavailability (OB) ≥ 30%, drug similarity (DL) ≥ 0.18, and drug half-life (T ) > 4h to effectively predict the drug properties and biological activity of the compounds. The present application checks the compounds in the preliminary screening results to ensure that they meet the actual needs of the experiment; by removing duplicates and supplementing relevant active ingredients, candidate compounds are obtained. The present application imports the relationship between the candidate compounds and the disease targets of radiation cystitis into Cytoscape 3.10.1 software for visualization, constructs a network, and calculates the topological parameters (such as node degree) of each node in the network to screen out core targets and compounds as an important basis for subsequent analysis.

[0075] In order to reveal the traditional Chinese medicine ingredients related to the treatment of radiation cystitis, the present application first retrieves the active ingredients corresponding to the previously screened compounds by using the TCMSP database, and obtains the traditional Chinese medicine information corresponding to the compounds. Subsequently, the merging function module in Cytoscape 3.10.1 software is used to integrate the “ ” network and the “ ” network into a complete “ A four-dimensional correlation network. In the four-dimensional correlation network, each node represents a target point, a compound or a traditional Chinese medicine component, and each edge reflects the interaction or connection between the nodes; by calculating the topological parameters of each node, especially the node degree, the key drugs and traditional Chinese medicine components in the core position in the network are identified. Combined with the basic theory of traditional Chinese medicine, the etiology and pathogenesis and clinical symptoms of radiation cystitis, the application further evaluates the potential and efficacy of the related core traditional Chinese medicine components in the treatment of radiation cystitis, and provides a basis for subsequent compound design and new drug development.

[0076] The application further proposes a candidate traditional Chinese medicine composition for the rule of treating radiation cystitis through the Degree value obtained by Cytoscape analysis and the traditional Chinese medicine frequency analysis result. In this process, the application systematically summarizes the prescription principles of traditional Chinese medicines in combination with the four properties and five tastes of traditional Chinese medicines and their meridian characteristics; through analyzing the etiology and pathogenesis and the main clinical symptoms of radiation cystitis, the traditional Chinese medicine compound composition is obtained based on the thought of syndrome differentiation and treatment in traditional Chinese medicine.

[0077] The application performs a forward network pharmacology analysis on the traditional Chinese medicine compound, and then takes the intersection of the obtained core target points and the core target points in reverse network pharmacology; the intersection of the obtained core compounds and the core compounds in reverse network pharmacology is taken.

[0078] Results: Please refer to Figure 5 The traditional Chinese medicine compound composition obtained by the application for treating radiation cystitis includes: monarch drug: Herba Epimedii, which tonifies kidney and assists yang, improves gasification function, and cooperates with Semen Leonuri to regulate the kidney deficiency factor in the pathogenesis; Herba Lysimachiae, which clears heat and removes dampness, directly aims at the core pathogenesis of damp-heat downward transmission and urinary pain in radiation cystitis. Minister drug: Herba Patriniae, which clears heat and resolves toxicity, removes swelling and dissolves mass, supplements heat-clearing and anti-inflammatory effect, and promotes bladder mucosa repair; Radix Sophorae, which clears heat and removes dampness, antibacterial and anti-inflammatory, aims at the symptoms of frequent urination and urinary pain, and strengthens the damp-removing effect; Kudingcha, which clears heat and resolves toxicity, promotes blood circulation and removes blood stasis, enhances anti-inflammatory and anti-fibrosis effects, and prevents disease deterioration. The minister drug cooperates with the monarch drug to further relieve inflammatory response and local damp-heat symptoms, and at the same time prevent tissue fibrosis. Auxiliary drug: Semen Leonuri, which tonifies kidney and consolidates essence, improves the deficiency of lower kidney qi in patients with radiation cystitis, and enhances the function of the bladder; Smilax Glabra, which clears heat and resolves toxicity, removes dampness and relieves stranguria, cooperates with Herba Lysimachiae to strengthen the effects of clearing heat, removing dampness and resolving toxicity. The main pathogenesis of radiation cystitis is damp-heat accumulation and toxic invasion, and Herba Lysimachiae and Smilax Glabra directly act on the main disease as core drugs; Hippophae Rhamnoides promotes blood circulation and removes blood stasis, enhances tissue repair effect, and improves microcirculation after bladder injury; Herba Erigerontis: dredges collaterals and relieves pain, promotes blood circulation and removes blood stasis, and further strengthens the effects of anti-fibrosis and tissue repair. The auxiliary drug focuses on tonifying kidney and consolidating essence, promoting blood circulation and removing blood stasis, dredging collaterals and relieving pain, and plays a harmonizing role between tonifying deficiency and resisting inflammation. Gancao: harmonizes various drugs, reduces the stimulation of drugs on the gastrointestinal tract, and at the same time plays the effects of clearing heat and resolving toxicity and diuresis.

[0079] See Figure 6 , Figure 7 and Figure 8 , the core target intersection can be seen 27 intersection targets, which shows the accuracy of the selected formula. Among the top 13 core compounds, there are 8 intersection compounds, which further confirm the accuracy of the selected formula. Figure 9 and Figure 10 show that the present application uses GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) for functional enrichment analysis. GO-BP (biological process) analysis shows that the core target of the mixture is mainly enriched in biological processes closely related to the occurrence and development of acute radiation cystitis, including response to lipopolysaccharide, response to bacterial-derived molecules, apoptosis signal pathway regulation, epithelial cell proliferation, response to oxygen level changes, wound healing, hypoxia response and oxidative stress response, etc. KEGG enrichment analysis shows that the core target is significantly enriched in multiple key signaling pathways, including PI3K-AKT signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, JAK-STAT signaling pathway and PD-L1 signaling pathway. The signaling pathways play an important role in the occurrence and development of the disease, which is embodied in key links such as inflammatory response, oxidative stress, cell apoptosis and mucosal repair. In particular, the pathways related to oxidative stress and epithelial cell proliferation (such as hypoxia response and oxidative stress response) play an important role in acute radiation cystitis. Oxidative stress damage induced by radiation is the main driving factor of the disease, which further aggravates the damage of bladder tissue by activating redox imbalance and inflammatory response, while the proliferation of epithelial cells is closely related to bladder mucosal repair and is regulated by multiple signaling pathways. The present application works through multiple mechanisms synergistically, covering multiple target points from inflammatory response, apoptosis signal regulation, oxidative stress relief to epithelial tissue repair, significantly protecting the bladder mucosa, improving the pathological damage of radiation cystitis, and providing a theoretical basis for clinical treatment.

[0080] Example 3 The present application proposes an animal in vivo verification experiment of a traditional Chinese medicine compound composition for acute radiation cystitis.

[0081] Mainly include: The present application selects 36 8-week-old male Sprague-Dawley rats with a body weight of 260-280g, which are provided by Sbiopharm (Beijing) Co., Ltd. The experimental animals are bred in a specific pathogen-free animal research center, and free feeding and drinking water are provided during the experiment.

[0082] The modeling of the application mainly comprises, the rats are anesthetized by intraperitoneal injection of 5% sodium pentobarbital (30 mg / Kg), the rats in the radiation injury group and the drug treatment group are fixed in a supine position, and are subjected to single dose 25Gy (3Gy / min) X-ray irradiation on a biological irradiator (PXi X-RAD 320, Precision X-ray, USA), and the irradiation area is the pelvic cavity, so as to establish an acute radiation cystitis model. In order to minimize the damage to the surrounding normal tissues, local shielding is carried out using a lead plate. The rats in the normal control group are subjected to the same anesthetic treatment as the irradiation group, but are not irradiated.

[0083] The traditional Chinese medicine compound mixture is prepared according to the scheme B in Table 3, and the proportions of the components are as follows: Lysimachia christinae Hance 3 parts, Herba Epimedii 2 parts, Herba Patriniae 3 parts, Smilax glabra 3 parts, Sophora flavescens Ait 1.8 parts, Lobelia chinensis 2 parts, Semen Momordicae 2.4 parts, Hippophae rhamnoides Linn 2 parts, Herba Erigerontis 2 parts and Glycyrrhiza uralensis Fisch 2 parts. The specific preparation method is as follows: Lysimachia christinae Hance (15 g), Herba Epimedii (10 g), Herba Patriniae (15 g), Smilax glabra (15 g), Sophora flavescens Ait (9 g), Lobelia chinensis (10 g), Semen Momordicae (12 g), Hippophae rhamnoides Linn (10 g), Herba Erigerontis (10 g) and Glycyrrhiza uralensis Fisch (10 g) are taken, and all the traditional Chinese medicine decoction pieces are provided by the Chinese medicine house of the Affiliated Hospital of Changchun University of Chinese Medicine. The traditional Chinese medicine decoction pieces are soaked in distilled water for 0.5 hours, then decocted three times at a ratio of 1:10, each time for 40 min at 100 DEG C, the three decoction liquids are combined, concentrated by using an evaporator, finally concentrated to 2 L of medicinal liquid, and then subjected to freeze-drying in a vacuum freeze dryer. After the medicinal powder is completely freeze-dried, it is stored for use; dexamethasone is used as a positive control drug, and is dissolved in sterile normal saline to prepare a uniform medicinal liquid at a dose of 100 mg. According to the drug dosage conversion ratio of humans and rats, the drug concentration is adjusted for subsequent experiments.

[0084] The 36 rats are randomly divided into 6 groups: a normal control group (NC, n=6), a radiation damage group (RD, n=6), a drug treatment high-dose group FDQJD-H (HT, n=6), a drug treatment medium-dose group FDQJD-M (MT, n=6), a drug treatment low-dose group FDQJD-L (LT, n=6) and a dexamethasone group (PC, n=6). The medium-dose group is a normal dose, the low-dose group is 0.5 times the normal dose, and the high-dose group is 2 times the normal dose. The NC and RD groups are given equal volume of purified water by gavage. All the rats are treated continuously for 14 days, and the rats are weighed every day to calculate the accurate drug dosage. The appearance of the bladder tissue, the leakage point pressure and the bladder capacity are observed, urine analysis, pathological staining analysis, transmission electron microscopy analysis and drug toxicity analysis are carried out.

[0085] Biopac MP36R multichannel physiological recorder was used to measure bladder capacity and leak point pressure. The high-precision data acquisition and real-time monitoring function of the system accurately recorded the changes in bladder function and physiological data. After successful anesthesia, the rats were fixed in a supine position, and a 2-cm longitudinal incision was made along the midline of the pubic symphysis to expose the bladder. Biopac MP36R multichannel physiological recorder was connected to the pressure sensor and fixed on the surface of the bladder. After connecting the sensor, the sampling rate was set to 100 Hz (preferably 50-200 Hz) to ensure real-time and continuous capture of the dynamic changes in intravesical pressure. The determination of the sampling rate was based on the time characteristics of pressure fluctuations during bladder filling and emptying. A too low sampling rate could result in peak loss, while a too high sampling rate increased noise and data volume. Experimental verification showed that 100 Hz could stably record the pressure change curve with the best signal-to-noise ratio. The sampling accuracy of the Biopac system was set to 16 bits, and the pressure sensor calibration range was 0-200 mmHg. Each rat was measured three times to reduce individual differences and operational errors. A micro-injection pump was used to slowly inject physiological saline into the bladder through the urethra, and the pressure sensor was used to monitor the pressure changes in the bladder. The relationship between pressure and injected liquid volume was recorded. As the water volume gradually increased, the changes in bladder pressure and whether urine overflowed from the urethral orifice were observed. When urine overflowed, the maximum capacity of the bladder was recorded. After the bladder capacity test, the liquid in the bladder was emptied. Half of the maximum capacity of the bladder was injected into the bladder, and then the urine in the bladder was emptied manually. The pressure value in the bladder at this time was recorded as the leak point pressure, and all data were collected in real time by the Biopac system. After the experiment, the rats were euthanized with carbon dioxide, and the bladder tissue was removed and stored in liquid nitrogen and tissue fixative for subsequent experimental testing.

[0086] Diurea urine analysis test strips (H11-800) were used for urine analysis, including urobilinogen, bilirubin, ketone bodies, red blood cells, urine specific gravity, ascorbic acid, protein, nitrite, glucose, pH, and white blood cells, to evaluate the pathological characteristics of radiation cystitis and the effects of drug intervention.

[0087] Hematoxylin-eosin staining and Masson staining were used to evaluate the pathological changes in bladder tissue.

[0088] After 14 days of drug administration, HE pathological staining of the main organs (liver, heart, spleen, lung, kidney) was performed to observe the related toxicity of the drugs.

[0089] Results: Please refer to Figure 11The bladder tissue was observed after 14 days of treatment with the traditional Chinese medicine compound mixture, and the results showed that the bladder morphology of the rats in the FDQJD group was significantly improved. The bladder surface of the radiation injury group had obvious hyperemia and bleeding points. In contrast, the bladders of the rats in each group treated with FDQJD showed a more normal appearance, with a significantly reduced bladder wall thickness and fewer hyperemia and bleeding points, indicating that FDQJD can alleviate bladder damage and improve its morphology, but the treatment effect of the dexamethasone group is much worse than that of the FDQJD treatment group. Please refer to Figure 12 The cystometrogram showed that the detrusor pressure of the rats in the radiation injury group was significantly reduced, indicating that the bladder function was impaired; in the FDQJD treatment group, the bladder leak point pressure gradually returned to near normal levels, especially in the high-dose group (HT), where the bladder leak point pressure recovered most significantly. This indicates that FDQJD can effectively regulate the tension of the bladder detrusor muscle and alleviate bladder dysfunction caused by radiation cystitis. Please refer to Figure 13 Radiation cystitis often leads to a decrease in bladder capacity, affecting its urine storage function. Through bladder capacity measurement, the bladder capacity of the radiation injury group was significantly reduced, while the bladder capacity of the FDQJD treatment group was significantly increased, especially in the medium and high-dose groups (MT, HT), where the bladder capacity returned to near the level of the normal control group, indicating that FDQJD has a significant effect in alleviating bladder capacity deficiency and restoring bladder function. Please refer to Figure 14 The results of urine analysis in rats showed that FDQJD intervention had a significant effect. In the radiation injury group, the levels of protein, red blood cells, and nitrite in the urine were significantly increased, reflecting inflammation and damage to the bladder. In the FDQJD treatment group, especially in the high-dose group, urine analysis showed a significant decrease in these indicators, indicating that FDQJD can effectively reduce the level of inflammation in the bladder and reduce damage. Please refer to Figure 15H&E staining showed that the bladder structure of the control group was normal, the epithelial cells were arranged closely, no obvious degeneration and exfoliation was observed, the lamina propria structure was dense, the number of folds was more, and the collagen fiber content was rich. The bladder structure of the radiation damage group was severely abnormal, a large number of epithelial cells were exfoliated, the folds disappeared, the lamina propria was exposed, at the same time, the lamina propria was edematous, the tissue structure was loose, the space was increased, and the collagen fiber content was reduced. The damage degree of the low, medium and high dose drug groups was improved compared with the model group. Compared with the model group, the damage degree of the bladder tissue of the low, medium and high dose combined drug groups was reduced, which showed that the mucosa structure was restored, the inflammatory cell infiltration was reduced, and the fibrosis degree was reduced. The fold structure disappeared, part of the epithelial cells were exfoliated, the lamina propria was edematous, and the blood vessels were dilated and hyperemic. The damage degree of the medium dose group was further reduced, the epithelium was relatively complete, the lamina propria structure was dense, and part of the blood vessels were slightly dilated and hyperemic. The intervention effect of the high dose group was the best, the epithelium was complete, the lamina propria was dense, and the blood vessels were slightly hyperemic. The dexamethasone treatment group was slightly improved, and the effect was worse than that of the low dose group. According to the above experimental results, FDQJD shows a significant effect in alleviating the pathological damage of radiation cystitis and improving the function of the bladder, which can effectively reduce the bladder damage caused by radiation and promote the repair and functional recovery of the bladder. Please refer to Figure 16 Under transmission electron microscopy, the normal group Figure 16 (a) cell structure was dense, the number of mitochondria was more, the size was uniform, the mitochondrial ridge structure was clear, the membrane was complete, as indicated by the black arrow; endoplasmic reticulum was not expanded, as indicated by the green arrow; the model group Figure 16 (b) cell structure was loose, a large number of electron transparent regions were visible, as indicated by the blue arrow; endoplasmic reticulum was severely expanded, forming vacuoles, as indicated by the green arrow; the number of mitochondria was reduced, the residual mitochondria atrophied, the mitochondrial ridge structure was not clear, the membrane was broken, as indicated by the black arrow; a large number of lysosomes were visible, as indicated by the red arrow; the drug group Figure 16 (c) the damage degree was reduced compared with the model group, the tissue structure was relatively dense, the mitochondrial ridge structure was clear, the membrane was complete, as indicated by the black arrow; endoplasmic reticulum was slightly expanded, as indicated by the green arrow. Please refer to Figure 17 The main organs (liver, heart, spleen, lung, kidney) were observed by HE staining. The results showed that the tissue structure of each main organ was complete, and no obvious inflammatory infiltration, necrosis or pathological change was observed, indicating that the traditional Chinese medicine compound in the application did not cause significant systemic toxicity or organ damage. Toxicity analysis showed that the traditional Chinese medicine compound for treating acute radiation cystitis in the application was safe, had no toxic side effects, and had no main organ damage.

[0090] Example 4 The present application proposes a mixture of doses for observing the therapeutic effect of rats with acute radiation cystitis. In this embodiment, the ratio of the traditional Chinese medicine compound composition is prepared according to scheme B in Table 3, and the proportions of the components are as follows: Lysimachia christinae Hance 3 parts, Herba Epimedii 2 parts, Herba Patriniae 3 parts, Smilax glabra 3 parts, Sophora flavescens Ait 1.8 parts, Lobelia chinensis 2 parts, Semen Cocle 2.4 parts, Hippophae rhamnoides Linn 2 parts, Herba Erigerontis 2 parts, and Glycyrrhiza uralensis Fisch 2 parts. The specific doses of the drugs are as follows: Lysimachia christinae (15 g), Herba Epimedii (10 g), Herba Patriniae (15 g), Smilax glabra (15 g), Sophora flavescens Ait (9 g), Lobelia chinensis (10 g), Semen Cocle (12 g), Hippophae rhamnoides Linn (10 g), Herba Erigerontis (10 g), and Glycyrrhiza uralensis Fisch (10 g).

[0091] Mainly include: The therapeutic effect of the moderate dose compound on acute radiation cystitis in rats is observed to verify its ability to improve function, relieve inflammation, and repair tissue.

[0092] SD male rats are selected, and a 25Gy pelvic irradiation is used to establish an acute radiation cystitis model.

[0093] The modeling includes: selecting 8-week-old male SD rats (260-280g, n=36), feeding in a SPF environment, and freely eating and drinking water; adaptive feeding for 14d. 5% sodium pentobarbital 30mg / kg intraperitoneal injection anesthesia, the rats are fixed in a supine position on the irradiation table. A biological irradiation instrument PXi X-RAD320 (Precision X-Ray, USA) is used for single pelvic irradiation of 25Gy, the dose rate is 3Gy / min, the focus skin distance is 50cm, and the total irradiation time is 8.3min. In order to reduce non-target area damage, the abdominal cavity non-pelvic area and limbs are shielded with a 3mm lead plate, and only the pelvic irradiation field from the pubic symphysis to the tail root (about 3x4cm, confirmed by body surface positioning) is exposed. The normal control group is only given the same anesthesia and fixation, and is not irradiated; the other treatments related to the model are consistent. The modeling day is recorded as D0, and the acute phase evaluation window is D3-D14; the drug administration starts from D1 and lasts for 14d, and is performed according to the grouping scheme. The model is successfully determined (D14 final judgment): urinalysis: 3 indicators of dry chemical strips are increased (red blood cells / white blood cells / protein ), or microscopic red blood cells are >50 / HP; functional (any one): bladder capacity is decreased by ≥30% compared with the control, or the leakage point pressure (LPP) is decreased by ≥20%; histology: HE shows mucosal epithelial shedding, hyperemia and edema, and inflammatory infiltration; Masson shows increased early collagen deposition; meeting urinalysis + (functional or histology) is determined as successful modeling. Those who do not meet the standard are excluded or analyzed separately.

[0094] After the modeling is successful, the moderate dose compound group (3g / kg) is given intragastrically for continuous treatment for 14 days. The functional, urine, biochemical, and histological indexes between the normal group (NC), the model group (RD), and the moderate dose treatment group (MT) are compared.

[0095] Results: The detection index and results show that, after 14 days of application of the mixture of the application, the bladder capacity measurement of the model group is obviously decreased, and the medium-dose treatment group is significantly improved compared with the model group, as shown in Figure 18 The leakage point pressure of the MT group is significantly increased compared with the RD group, as shown in Figure 19 The urine analysis shows that the protein, red blood cells and white blood cells are reduced, as shown in Figure 20 The HE and Masson staining shows that the bladder mucosa damage is well repaired and the collagen deposition is reduced, as shown in Figure 21 It is shown that the medium-dose compound can significantly improve the bladder function and pathological state of the acute radiation cystitis rats, and has good treatment effect.

[0096] Example 5 The present application proposes an effect comparison experiment of different doses of the mixture for radiation cystitis. In this embodiment, the proportion of the traditional Chinese medicine compound composition is adopted as scheme B listed in Table 3, and the proportions of the components are as follows: Lysimachia christinae Hance 3 parts, Herba Epimedii 2 parts, Herba Patriniae 3 parts, Smilax glabra 3 parts, Sophora flavescens Ait 1.8 parts, Lobelia chinensis 2 parts, Semen Nelumbinis 2.4 parts, Hippophae rhamnoides Linn 2 parts, Herba Erigerontis 2 parts and Glycyrrhiza uralensis Fisch 2 parts. The specific doses of the drugs are as follows: Lysimachia christinae Hance (15 g), Herba Epimedii (10 g), Herba Patriniae (15 g), Smilax glabra (15 g), Sophora flavescens Ait (9 g), Lobelia chinensis (10 g), Semen Nelumbinis (12 g), Hippophae rhamnoides Linn (10 g), Herba Erigerontis (10 g) and Glycyrrhiza uralensis Fisch (10 g).

[0097] Mainly includes: The dose-response relationship of the traditional Chinese medicine compound is studied to determine the effect difference of different doses for radiation cystitis.

[0098] The same acute radiation cystitis model is established, and the modeling is the same as that in Example 4.

[0099] After the modeling is successful, the rats are divided into a low-dose (1.5 g / kg), a medium-dose (3 g / kg) and a high-dose (6 g / kg) treatment group, and the rats are intragastrically administered once a day for 14 consecutive days. The differences of the three groups in the functional and pathological indexes are compared.

[0100] Results: The results show that, with the increase of the administration dose, the bladder capacity and the leakage point pressure are significantly improved, showing an obvious dose-dependent trend as shown in Figure 22 , 23 In terms of urine inflammation indexes, the red blood cell and protein content of the high-dose group (HT) are more obviously improved than those of the low-dose group (LT) and the medium-dose group (MT) as shown in Figure 24HE, Masson staining results showed that the mucosal structure of the high-dose group was basically restored, and the inflammatory cell infiltration was significantly reduced, which was better than that of the low-dose and medium-dose groups. Figure 25 The above results show that the traditional Chinese medicine compound of the present application has a clear dose-dependent effect in the acute radiation cystitis model, and the preferred dose range is 3-6 g / kg.

[0101] Example 6 The present application compares the effects of a mixture and dexamethasone in acute radiation cystitis. In this embodiment, the ratio of the traditional Chinese medicine compound composition is according to scheme B listed in Table 3, and the proportions of the components are as follows: Herba Lysimachiae 3 parts, Herba Epimedii 2 parts, Herba Patriniae 3 parts, Smilax Glabra 3 parts, Sophora Flavescens 1.8 parts, Lobelia 2 parts, Semen Nelumbinis 2.4 parts, Hippophae Rhamnoides 2 parts, Herba Erigerontis 2 parts and Glycyrrhiza 2 parts. The specific doses of the drugs are as follows: Herba Lysimachiae (15 g), Herba Epimedii (10 g), Herba Patriniae (15 g), Smilax Glabra (15 g), Sophora Flavescens (9 g), Lobelia (10 g), Semen Nelumbinis (12 g), Hippophae Rhamnoides (10 g), Herba Erigerontis (10 g) and Glycyrrhiza (10 g).

[0102] Mainly includes: To compare the effects of the traditional Chinese medicine compound prepared by the present application and the classic anti-inflammatory drug dexamethasone, and to evaluate its advantage. After modeling the rats, they were treated with the medium dose (3 g / kg) of the compound and dexamethasone (0.03 mg / kg) respectively for 14 days. The performances of the two groups in function, urine and histopathology were evaluated. The specific experimental conditions include: Functional evaluation (bladder capacity and leak point pressure, LPP) involves median incision to expose the bladder after anesthesia of the rats, and catheterization. A multi-channel physiological recording system Biopac MP36R is used, with a pressure transducer range of 0-200 mmHg and a 16-bit sampling rate of 100 Hz (50-200 Hz). A micro-injection pump is used to set a constant flow rate of 0.10 mL / min (0.05-0.20 mL / min) to continuously inject normal saline (sterile 0.9% NaCl, room temperature), and the pressure-volume curve is recorded in real time. When the urine first overflows from the urethral orifice, the injected volume is defined as the maximum bladder capacity. After emptying the bladder, 50% of the maximum capacity of normal saline is injected, and the intravesical pressure at this time is recorded as the leak point pressure (LPP). Each rat is measured repeatedly for 3 times, and the mean value is taken; the equipment is calibrated before and after use with a known pressure.

[0103] Urinalysis included collecting fresh urine in a metabolic cage for 2 hours at the endpoint (D14); gentle bladder tapping was used to assist urination if necessary. The urine was centrifuged at 3000 rpm for 10 minutes, and the supernatant was used for dry chemistry strips; the precipitate was examined microscopically. The urinalysis was performed using the Dirui H11-800 dry chemistry test strip, and the following parameters were read according to the instructions: urobilinogen, bilirubin, ketone bodies, red blood cells, specific gravity, ascorbic acid, protein, nitrite, glucose, pH, and white blood cells (semi-quantitative 0, ±, ...). RBC / WBC counts were performed per high-power field (HPF) using a microscope, and the average value was taken from 10 fields. A protein level >50 / HPF is considered positive for hematuria; This is considered a positive result for proteinuria.

[0104] Histopathological (HE / Masson) analysis included immediate removal of the bladder fornix and body from euthanized rats, followed by fixation in 10% neutral formalin for 24 hours. Routine dehydration and paraffin embedding were performed; sections were 4 μm thick. Staining: HE was used to assess epithelial shedding, congestion and edema, and inflammatory infiltration using standard procedures; Masson staining was used to assess collagen deposition and fibrosis. Normality was determined by Shapiro–Wilk, and homogeneity of variance was determined by Levene. Independent samples t-tests were used for comparisons between two groups, and one-way ANOVA with Tukey analysis was used for comparisons between multiple groups. The significance threshold was P < 0.05.

[0105] result: This invention can stably capture the pressure peak during filling / expelling at 100Hz, and the 0.10mL / min flow rate balances physiological stability and curve smoothness; determining LPP at 50% volume reduces volume-dependent bias and improves inter-group comparability. Standardizing the urine collection window and centrifugation conditions reduces batch-to-batch variability; dry chemistry and microscopic examination provide mutual verification, improving sensitivity and specificity. Standardizing the fixative and section thickness ensures staining consistency; the use of a scale and blinding method improves objectivity and reproducibility.

[0106] This invention systematically evaluated the efficacy and safety of a traditional Chinese medicine compound preparation combined with dexamethasone in the treatment of acute radiation cystitis by establishing a rat model of acute radiation cystitis. Compared with the model group, the compound preparation group significantly improved bladder dysfunction, as evidenced by a significant increase in bladder capacity and a marked increase in leakage point pressure (LPP). Figure 26 , Figure 27 Compared with the dexamethasone group, the compound group showed a greater increase in bladder capacity and LPP, suggesting a superior effect in restoring bladder compliance and sphincter function. Urinalysis results showed ( Figure 28 The levels of red blood cells and white blood cells in the compound drug group were significantly lower than those in the model group, and further decreased compared to the dexamethasone group, indicating that the compound drug of this invention is more effective in reducing bleeding and inhibiting radiation-induced inflammatory responses. Histological observation showed that HE staining results indicated (…).Figure 29 ), the compound medicine group had complete bladder mucosa epithelial structure, obvious regeneration, and significantly reduced inflammatory cell infiltration, and the repair degree was better than that of the dexamethasone group; the Masson staining result further confirmed that the collagen deposition of the compound group was less, and the fibrosis degree was significantly lower than that of the dexamethasone group, indicating that the compound group had obvious advantages in preventing bladder tissue fibrosis. Comprehensive analysis results show that the traditional Chinese medicine compound in the present application is superior to the dexamethasone group in improving bladder function, reducing inflammatory reaction, promoting epithelial repair and inhibiting tissue fibrosis, and has no obvious toxic reaction, is safer, and shows good treatment potential and clinical application value.

[0107] The mechanism research of the present application shows that the compound traditional Chinese medicine regulates MAPK, PI3K-AKT, NF-κB and other signaling pathways through multiple components and multiple targets, and plays a synergistic role of anti-inflammatory, antioxidant and promotion of tissue repair. Unlike the traditional glucocorticoid drug (such as dexamethasone) single-target immunosuppression mechanism, the compound of the present application has multiple functions of “clearing heat and detoxifying, removing dampness and promoting urination, promoting blood circulation and removing blood stasis, and repairing mucosa”, and can improve the microenvironment of bladder tissue as a whole, promote epithelial cell regeneration and functional recovery. In summary, the compound traditional Chinese medicine of the present application is superior to other existing technologies in improving the symptoms of acute radiation cystitis, promoting tissue repair and improving bladder function, and has the characteristics of high safety, significant efficacy and combination with modern drugs.

[0108] Example 7 The present application proposes the influence of different administration cycles of the mixture on the effect of acute radiation cystitis. In this embodiment, the ratio of the traditional Chinese medicine compound composition is scheme B listed in table 3, and the proportions of the components are as follows: Herba Lysimachiae 3 parts, Herba Epimedii 2 parts, Herba Patriniae 3 parts, Smilax Glabra 3 parts, Sophora Flavescens 1.8 parts, Lobelia 2 parts, Semen Cuscutae 2.4 parts, Hippophae Rhamnoides 2 parts, Herba Erigerontis 2 parts and Glycyrrhiza 2 parts. The specific doses of the drugs are as follows: Herba Lysimachiae (15g), Herba Epimedii (10g), Herba Patriniae (15g), Smilax Glabra (15g), Sophora Flavescens (9g), Lobelia (10g), Semen Cuscutae (12g), Hippophae Rhamnoides (10g), Herba Erigerontis (10g) and Glycyrrhiza (10g).

[0109] Mainly includes: The present application compares the treatment effects of the traditional Chinese medicine compound on acute radiation cystitis rats under the same dose for 7 days and 14 days, and determines the influence of the administration cycle on the curative effect.

[0110] After the SD male rats are successfully modeled, they are randomly divided into two groups, and both groups are given compound medium dose (3g / kg) by gavage, and the administration is continuously given for 7 days (MT-7d) and 14 days (MT-14d) respectively. The differences of the two groups in urine inflammatory indicators, bladder tissue repair and functional indicators are compared. Specifically, it includes: Sprague-Dawley rats (8 weeks old, 260-280 g) were selected to establish an acute radiation cystitis model (single pelvic irradiation of 25 Gy at a dose rate of 3 Gy / min) under the same conditions. After successful modeling, the rats were randomly divided into two groups, each group of 9 rats, and all were given the dose (3 g / kg) of the mixture for gavage administration. The MT-7d group was continuously administered for 7 days, and the MT-14d group was continuously administered for 14 days. The normal control group and the model control group were set up at the same time, and the same volume of pure water was given. The compound medicine was stored in the form of freeze-dried powder, and was dissolved in pure water before use, with a gavage volume of 10 mL / kg, once a day. The administration dose was based on the human equivalent conversion, which could ensure stable efficacy concentration without toxic side effects. Histopathological observation was performed on the fornix tissue of the bladder, which was fixed with 10% neutral formalin for 24 h, routinely embedded with paraffin, sectioned (4 μm), and subjected to HE and Masson staining. HE was used to observe the epithelial integrity and inflammatory cell infiltration, and Masson was used to evaluate the degree of fibrosis, which was evaluated by two pathologists in a blind manner. The bladder function index was evaluated by using the Biopac MP36R multi-channel physiological recording system to measure the bladder capacity at a sampling rate of 100 Hz and an injection flow rate of 0.10 mL / min, and the average value of three measurements for each animal was taken.

[0111] Results: The present application combines the pathological progress of acute radiation cystitis, which enters the repair period about 7-14 days, to determine the comparison window of short-term and medium-term intervention.

[0112] The results show that both groups can improve the bladder function and urinary inflammatory response, and the MT-14d group shows more significant efficacy. The bladder capacity of the MT-14d group is significantly higher than that of the MT-7d group (as shown in Figure 30 ), close to the normal value, indicating that the bladder contraction function is more completely recovered; during the entire experiment, no obvious toxic side effects or abnormal deaths were observed. The HE and Masson staining results show that the bladder epithelium of the MT-14d group regenerates completely, the inflammatory cell infiltration is reduced, and the collagen deposition is less; the MT-7d group still shows partial mucosal edema and inflammatory cell infiltration (as shown in Figure 31 ). It is indicated that under the same dose, prolonging the administration period of the mixture can further improve the treatment effect; continuous administration of MT-14d is significantly better than MT-7d in reducing bladder inflammation, repairing bladder mucosa, and restoring function, which suggests that a longer treatment course is more suitable for the traditional Chinese medicine intervention strategy for clinical radiation cystitis, and the compound preparation of the present application has good time dependence and cumulative efficacy; compared with dexamethasone, the compound preparation of the present application has no obvious toxicity in long-term administration, has high safety, and is suitable for continuous repair treatment of patients after radiotherapy.

[0113] Example 8 The application provides an application example of a traditional Chinese medicine preparation for acute radiation cystitis.

[0114] Mainly include: The application takes adult daily mixture as a reference dose: "one dose per day, taken orally in 2-3 times".

[0115] The total amount of crude drugs in the mixture is preferably about 116g / dose, and the process fluctuation is allowed to be 100-200g / dose.

[0116] The yield of the freeze-dried dry extract obtained through extraction is 15%-25%, and is preferably 18%-22%. According to this, the daily equivalent dry extract of 116g of crude drugs is about 20-25g. The course of treatment: the acute phase is recommended for 28 days, and can be extended to 42 days if necessary, and the improvement of symptoms and objective indexes is taken as the standard.

[0117] Preparation conversion and quality consistency verification: The application firstly performs mass spectrum analysis (LC-MS) on the mixture freeze-dried powder, and the results show that the main active ingredient structure is not damaged in the drying and freeze-drying process, and the signal peaks of key substances such as icariin, matrine and scutellarin are completely reserved, the similarity of the fingerprint spectrum with the mixture sample is greater than 0.95 (as shown in the Figure 32 The granules and tablets prepared in the subsequent application are all intermediates of the dry extract powder, which are prepared through conventional processes such as physical mixing, dissolution, granulation and coating, and therefore are equivalent to the mixture in composition, only the excipients and the administration mode are different. In order to adapt to different clinical needs, based on the physicochemical properties of the main pharmacodynamic substances in the dry extract (such as the easy oxidation of flavonoids, the poor solubility of saponins and the strong stability of matrine), various preparation forms are designed to improve the stability and absorption efficiency of the compound: 1) Granules (to be taken by washing) Prescription and specification: granulation of the dry extract powder, 8g per bag (containing 8g of equivalent dry extract, and appropriate amounts of dextrin / low-substitution hydroxypropyl cellulose and the like as excipients).

[0118] Usage and dosage (for adults): 1 bag at a time, 3 times a day; or 1.5 bags at a time, 2 times a day. The total amount of 24g of dry extract per day is equivalent to the daily mixture, and 150-200mL of warm boiled water is used for washing.

[0119] 2) Tablets / thin film-coated tablets (optional sustained-release) Prescription and specification: each tablet contains 1.5-2.0g of dry extract; the excipients are selected from cross-linked polyvinylpyrrolidone, microcrystalline cellulose, starch and the like. The sustained-release type is controlled by HPMC / EC, and the in-vitro release is 80%±10% in 12h. Usage and dosage (for adults): immediate-release tablets 3-6 tablets at a time, 3 times a day; sustained-release tablets 3-4 tablets at a time, 2 times a day, and the total equivalent dry extract per day is 24g.

[0120] The above preparation is administered several times a day, 3 times a day, to maintain stable exposure; the course of treatment is 28 days in the acute phase, and the dosage can be reduced or changed to granules for 1-2 weeks after the symptoms and objective indicators (urine / function / pathology) improve; it can be used in combination with hyperbaric oxygen therapy, dexamethasone, etc. for rapid inflammation control, and the compound prescription repairs / protection, reduces the risk of hormone exposure and adverse reactions.

[0121] Children are converted according to body weight or body surface area using the Clark formula (by weight): Child dose ≈ adult dose × body weight (kg) / 70. Children under 12 years of age prefer to use granules / oral solutions, and the dosage is reduced according to the doctor's advice, and the adjustment is made after 48-72 hours of observation without discomfort.

[0122] The above dosage forms are determined according to the "one-day mixture - crude drug 116g - dry extract 17-29g equivalent" conversion to determine the specifications and administration method; through prescription process verification, the granules and mixture have comparable fingerprint spectra and main active ingredient content.

[0123] Results: 1) Granules Convenient to take, stable taste and dissolution, better compliance than mixture; bagged measurement reduces batch-to-batch differences.

[0124] 2) Tablets / film-coated tablets (optional sustained-release) Accurate dosage, batch uniformity; sustained-release type can stabilize blood drug exposure and reduce peak concentration-related discomfort.

[0125] Multi-dose strategies can significantly improve compliance and dosage accuracy, while maintaining equivalent efficacy with the mixture, improving taste, portability, and quality consistency, which is beneficial for industrialization and multicenter clinical promotion.

[0126] Comparative Example The present application proposes a comparative experiment of the mixture of the present application and other drugs for acute radiation cystitis.

[0127] Mainly includes: To verify the effect of the mixture of the present application in treating acute radiation cystitis, the mixture of the present application and the existing clinical commonly used drugs are subjected to parallel control study, and the experimental conditions are as follows: Select 8-week-old male SD rats (260~280g), using a single 25Gy pelvic irradiation (dose rate 3Gy / min) to establish an acute radiation cystitis model. After successful modeling, randomly grouped (n=9 per group). Experimental grouping, group A (normal control group): no irradiation, no drug; group B (model control group): the same volume of pure water gavage; group C (inventive compound group): given the dose (3g / kg) of the mixture, once a day gavage, for 14 consecutive days; group D (dexamethasone group, comparison group): given dexamethasone solution (0.03mg / kg), once a day gavage, for 14 consecutive days. The animals in each group were treated under the same feeding conditions, and the irradiation, gavage, and detection were completed by blind operators. After 14 days of detection, urine indicators were detected by urine analyzer and dry chemical test paper for red blood cells, white blood cells, and protein; functional indicators were detected by Biopac MP36R system for bladder capacity and leak point pressure (sampling rate 100Hz, flow rate 0.1mL / min, 3 times per measurement, and taking the mean value); histological indicators were observed by HE and Masson staining for bladder epithelial repair and fibrosis.

[0128] Results: Please refer to Table 4, the inventive compound group (group C) has the most significant decrease in urine red blood cells and white blood cells (P<0.05), and the inflammatory response is significantly reduced; functionally, the bladder capacity and leak point pressure are significantly higher than those of the dexamethasone group (group D); histologically, the bladder epithelial structure of the compound group is complete, with less inflammatory cell infiltration and good basement membrane continuity, while the dexamethasone group has repair, but the epithelial regeneration is not as good as that of the inventive group; in terms of safety, some animals in the dexamethasone group have side effects such as weight loss and rough hair, while the compound group has no obvious toxic side effects. Dexamethasone is chosen as the control drug because it is currently the most commonly used drug for acute radiation cystitis in clinical practice, but it has the problems of high side effects and limited long-term application; the inventive compound can achieve the triple effect of anti-inflammatory, antioxidant, and tissue repair under the premise of high safety, which is better than the effect of single-target hormone or conventional Chinese medicine; the experimental results show that the inventive compound has the comprehensive advantages of multi-target regulation, low toxicity, and high repair force.

[0129] Table 4 Comparison of different proportion schemes of traditional Chinese medicine compound compositions In summary, the compound group of the present application is superior to the dexamethasone group in bladder capacity, leak point pressure, inflammation relief and tissue repair and other indicators (P<0.05), showing a comprehensive functional recovery effect. The dual mechanism of anti-inflammatory + repair shows not only significantly reduces the inflammation indicators of urine, but also promotes epithelial regeneration, reduces fibrosis, and embodies the multi-target advantage of anti-inflammatory and repair synergy. And the present application has high safety, no obvious toxic and side effects after long-term administration, and the animal weight increases steadily, which shows that the drug safety and tolerance are excellent. The comprehensive advantages show that the traditional Chinese medicine compound of the present application is superior to the existing drug regimen in functional recovery, tissue repair and safety, and provides a more efficient and safe alternative drug regimen for acute radiation cystitis.

[0130] The present application has been described in detail by specific examples, but the protection scope of the present application is not limited thereto. Those skilled in the art should understand that various modifications and replacements can be made to the above preparation forms, types of adjuvants, proportions and preparation processes without departing from the principles and spirits of the present application.

[0131] Specifically, the traditional Chinese medicine compound composition described in the present application is also suitable for preparing other various drug dosage forms, including but not limited to: tablets, capsules, granules, powders, mixtures, injections (such as solution type, freeze-dried powder type), inhalants (including aerosols, sprays, dry powder inhalants), transdermal patches, ointments, creams, suppositories, etc.

[0132] For different dosage forms, conventional adjuvants known in the art can be selected accordingly, for example: diluents (such as starch, microcrystalline cellulose), binders (such as hydroxypropyl methyl cellulose), disintegrants (such as croscarmellose sodium), lubricants (such as magnesium stearate), glidants, coating materials, solvents (such as water for injection, oily solvents), surfactants, preservatives, flavoring agents, transdermal absorption promoters, etc. The preparation of these different dosage forms can be realized by conventional technical means in the art (such as crushing, mixing, granulating, tabletting, filling, freeze-drying, sterile filtration, etc.), and the purpose is to use the traditional Chinese medicine compound composition described in the present application in an effective and stable form for patients.

[0133] It should be noted that the term "comprising" or any other variant thereof is intended to cover non-exclusive inclusion, so that the process, method, article or equipment including a series of elements not only contains these elements, but also includes other elements not explicitly listed or inherent to such process, method, article or equipment. Without more limitations, the elements defined by the statement "comprising" do not exclude the presence of other identical elements in the process, method, article or equipment including the elements.

[0134] The above merely provides an example of the present application, and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present application shall fall into the scope of claims of the present application.

Claims

1. A traditional Chinese medicine compound composition for treating acute radiation cystitis, characterized in that, The traditional Chinese medicine compound composition, calculated by weight, is prepared by extraction of 2-4 parts of Lysimachia christinae, 1-3 parts of Epimedium, 2-4 parts of Patrinia scabiosaefolia, 2-4 parts of Smilax glabra, 0.8-2.8 parts of Sophora flavescens, 1-3 parts of Lobelia chinensis, 1.4-3.4 parts of Cuscuta chinensis, 1-3 parts of Hippophae rhamnoides, 1-3 parts of Asarum sieboldii, and 1-3 parts of Glycyrrhiza uralensis.

2. The traditional Chinese medicine compound composition for treating acute radiation cystitis according to claim 1, characterized in that, The traditional Chinese medicine compound composition, calculated by weight, is prepared by extraction of 2.5-3.5 parts of Lysimachia christinae, 1.5-2.5 parts of Epimedium, 2.5-3.5 parts of Patrinia scabiosaefolia, 2.5-3.5 parts of Smilax glabra, 1.3-2.3 parts of Sophora flavescens, 1.5-2.5 parts of Lobelia chinensis, 1.9-2.9 parts of Cuscuta chinensis, 1.5-2.5 parts of Hippophae rhamnoides, 1.5-2.5 parts of Erigeron breviscapus, and 1.5-2.5 parts of Glycyrrhiza uralensis.

3. The traditional Chinese medicine compound composition for treating acute radiation cystitis according to claim 1, characterized in that, The traditional Chinese medicine compound composition, calculated by weight, is prepared by extraction of 3 parts of Lysimachia christinae, 2 parts of Epimedium, 3 parts of Patrinia scabiosaefolia, 3 parts of Smilax glabra, 1.8 parts of Sophora flavescens, 2 parts of Lobelia chinensis, 2.4 parts of Cuscuta chinensis, 2 parts of Hippophae rhamnoides, 2 parts of Asarum heterotropoides, and 2 parts of Glycyrrhiza uralensis.

4. A traditional Chinese medicine compound preparation for treating acute radiation cystitis, characterized in that, The traditional Chinese medicine compound preparation is composed of the traditional Chinese medicine compound composition for treating acute radiation cystitis as described in any one of claims 1 to 3 and pharmaceutical excipients.

5. The traditional Chinese medicine compound preparation for treating acute radiation cystitis according to claim 4, characterized in that, The traditional Chinese medicine compound preparations include oral solutions, tablets, and granules.

6. The traditional Chinese medicine compound preparation for treating acute radiation cystitis according to claim 4, characterized in that, The pharmaceutical excipients are pharmaceutically acceptable.

7. A method for preparing a traditional Chinese medicine compound preparation for treating acute radiation cystitis according to any one of claims 4 to 6, characterized in that, include: S1. Mix according to the following weight ratio: The following ingredients were weighed: Lysimachia christinae, Epimedium, Patrinia scabiosaefolia, Smilax glabra, Sophora flavescens, Lobelia chinensis, Cuscuta chinensis, Hippophae rhamnoides, Asarum heterotropoides, Glycyrrhiza uralensis = (2~4): (1~3): (2~4): (2~4): (0.8~2.8): (1~3): (1.4~3.4): (1~3): (1~3): (1~3) to obtain the weighed compound Chinese medicine composition; S2. Add the weighed traditional Chinese medicine compound composition to 8-12 times its volume of water and soak for 20-40 minutes to obtain the soaked traditional Chinese medicine compound composition. S3. Heat and decoct the soaked Chinese herbal compound composition, combine the decoctions, and filter to obtain a decoction and filtered Chinese herbal compound composition extract. S4. The extract of the traditional Chinese medicine compound composition after decoction and filtration is concentrated, and then processed into a formulation, quality controlled, packaged and sterilized to obtain the traditional Chinese medicine compound preparation.

8. The method for preparing the traditional Chinese medicine compound preparation for treating acute radiation cystitis according to claim 7, characterized in that, The heating and simmering process is repeated 2 to 3 times.

9. The method for preparing the traditional Chinese medicine compound preparation for treating acute radiation cystitis according to claim 7, characterized in that, Each heating and simmering process takes 30-45 minutes.

10. The use of a traditional Chinese medicine compound preparation for treating acute radiation cystitis prepared by any one of claims 4 to 6 or any one of claims 7 to 9 in the preparation of a drug for treating acute radiation cystitis.

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