Traditional Chinese medicine composition for treating chronic refractory gout and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating chronic refractory gout. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 10-15 parts of astragalus membranaceus, 15-20 parts of rhizoma smilacis glabrae, 6-10 parts of earthworm, 6-10 parts of radix angelicae pubescentis, 10-15 parts of radix clematidis, 3-6 parts of honey-fried licorice root, 6-10 parts of angelica sinensis, 10-15 parts of white hyacinth bean, 6-10 parts of curcuma zedoary, 10-15 parts of white paeony root and 10-15 parts of roasted malt. The traditional Chinese medicine composition can significantly reduce the blood uric acid level, improve the symptoms of traditional Chinese medicine and reduce the recurrence frequency of gout, has a potential protection effect on renal functions, and provides a safe and effective new scheme for treatment of chronic refractory gout.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for treating chronic refractory gout and an application thereof. Background Art

[0002] Chronic refractory gout is a chronic metabolic disease caused by purine metabolism disorders and uric acid excretion disorders. It is more common in middle-aged and elderly people and has shown a trend of becoming younger in recent years. Its clinical characteristics are blood uric acid levels that are continuously higher than the normal range (males>420μmol / L, females>360μmol / L), repeated deposition of urate crystals in the joints to form tophi, and accompanied by intermittent recurrent acute arthritis, joint deformities, renal damage and other serious complications; according to epidemiological data, the prevalence of gout in my country has reached 1.1%-1.4%, of which chronic refractory gout accounts for about 30%, and due to the lack of effective treatment, the five-year disability rate of patients is as high as 25%, seriously affecting the quality of life and increasing the social medical burden.

[0003] At present, Western medicine's treatment of the intermittent period of chronic refractory gout focuses on lowering uric acid. Commonly used drugs include xanthine oxidase inhibitors (such as febuxostat) and uricosuric drugs. Although these drugs can effectively lower blood uric acid levels, clinical practice has shown that Western medicine treatment alone has significant limitations: First, it cannot fundamentally improve the core pathogenesis of traditional Chinese medicine of "Qi deficiency as the root and dampness turbidity and blood stasis as the symptoms", resulting in patients with joint pain, fatigue, skin and nail discoloration, abdominal distension and other symptoms of Qi deficiency, dampness turbidity and blood stasis that are difficult to eliminate; second, long-term use of Western medicine may cause adverse reactions such as abnormal liver function and gastrointestinal reactions, and the blood uric acid rebound rate after discontinuation of the drug is as high as 40%-60%, and the risk of recurrence is significant; third, there is a lack of targeted intervention measures for the already formed tophi and joint structure damage, making it difficult to reverse the progression of the disease.

[0004] According to Traditional Chinese Medicine theory, chronic refractory gout falls into the category of "bi syndrome", "lijie" and "gout", and its onset is closely related to congenital deficiency, acquired dietary irregularities, and improper work and rest. The key to the pathogenesis lies in the deficiency of vital energy (especially qi deficiency), which leads to the endogenous generation of dampness and turbidity, blood stasis, and obstruction of meridians and joints. The Yellow Emperor's Classic of Internal Medicine states: "When vital energy is stored within, evil cannot invade; where evil gathers, the qi must be weak", which clearly points out that qi deficiency is the internal basis of the disease, and dampness and stasis are the pathological products. The two are intertwined, forming a syndrome of deficiency in the root and excess in the superficial. Existing traditional Chinese medicine treatment plans mostly focus on clearing heat and dampness or promoting blood circulation and unblocking the meridians, but the comprehensive conditioning plan for the "qi deficiency-dampness-blood stasis" ternary pathogenesis is still imperfect, and there is a lack of traditional Chinese medicine compound prescriptions based on high-level evidence-based medicine. In addition, modern medical research shows that patients with chronic refractory gout generally have pathological mechanisms such as immune-inflammatory imbalance, vascular endothelial function damage and renal tubular uric acid excretion disorders, and the multi-component and multi-target characteristics of traditional Chinese medicine may play a unique advantage in regulating metabolism, anti-inflammatory and analgesic, and protecting target organs. Therefore, the present invention provides a traditional Chinese medicine composition for the treatment of chronic refractory gout and its application, which can not only make up for the shortcomings of simple Western medicine treatment, but also improve the patient's symptoms through overall conditioning and reduce the recurrence rate. Summary of the Invention

[0005] In view of the above problems in the treatment of the intermittent period of chronic refractory gout, the present invention is proposed.

[0006] Therefore, the object of the present invention is to provide a Chinese medicine composition for treating chronic refractory gout and its application, which solves the above-mentioned technical problems.

[0007] In order to achieve the above object, the present invention provides the following technical solutions: A traditional Chinese medicine composition for treating chronic refractory gout, comprising the following raw materials in parts by weight: 10-15 parts of Astragalus, 15-20 parts of Smilax glabra, 6-10 parts of Earthworm, 6-10 parts of Angelica dahurica, 10-15 parts of Clematidis, 3-6 parts of Radix Glycyrrhizae, 6-10 parts of Angelica sinensis, 10-15 parts of Lablab dal, 6-10 parts of Curcuma, 10-15 parts of White Peony Root, and 10-15 parts of roasted malt.

[0008] Furthermore, the weight of the raw material is: 12 parts of Astragalus, 18 parts of Rhizoma Smilacis Glabrae, 8 parts of Earthworms, 8 parts of Radix Angelicae Pubescentis, 12 parts of Radix Clematidis, 5 parts of Radix Glycyrrhizae Preparata, 8 parts of Radix Angelicae Sinensis, 12 parts of Lablab dahuricae, 8 parts of Rhizoma Curcumae, 12 parts of Radix Paeoniae Alba, and 12 parts of roasted malt.

[0009] Furthermore, when the composition is prepared into granules, the preparation method includes the following steps: a) Grinding each API into coarse powder; b) adding water to the mixture and decocting twice, first adding 8-10 times the amount of water and decocting for 1.5-2 hours, and second adding 6-8 times the amount of water and decocting for 1-1.5 hours; c) Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of 1.10-1.20 (60°C); d) adding dextrin and lactose, drying and forming granules.

[0010] Furthermore, when the composition is prepared into a decoction, the preparation method is: After mixing all the raw materials, add 8-10 times the amount of water and boil for 1.5-2 hours, then filter and take the juice.

[0011] Use of a traditional Chinese medicine composition for treating chronic refractory gout in the preparation of a drug for lowering blood uric acid levels.

[0012] The invention relates to the use of a traditional Chinese medicine composition for treating chronic refractory gout in the preparation of a medicine for improving the traditional Chinese medicine symptoms of chronic refractory gout, wherein the traditional Chinese medicine symptoms include joint pain, redness and swelling, fatigue, weakness, and soreness of the waist and knees.

[0013] Use of a traditional Chinese medicine composition for treating chronic refractory gout in preparing a drug for reducing the frequency of gout recurrences.

[0014] Application of a traditional Chinese medicine composition for treating chronic refractory gout in preparing a medicine for reducing the volume of tophi.

[0015] A pharmaceutical preparation for treating chronic refractory gout, a traditional Chinese medicine composition for treating chronic refractory gout, and pharmaceutically acceptable excipients.

[0016] In the above technical solution, the technical effects and advantages provided by the present invention are: The present invention provides a traditional Chinese medicine composition composed of astragalus, smilax glabra, earthworm, angelica dahurica, clematis root, roasted licorice root, angelica sinensis, white hyacinth bean, zedoaria, white peony root, and stir-fried malt. The composition can significantly lower blood uric acid levels, improve traditional Chinese medicine symptoms, reduce the number of gout recurrences, and has a potential protective effect on renal function, providing a safe and effective new solution for the treatment of chronic refractory gout. DETAILED DESCRIPTION

[0017] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below.

[0018] Example 1 A traditional Chinese medicine composition for treating chronic refractory gout, comprising the following raw materials in parts by weight: 10-15 parts of Astragalus, 15-20 parts of Smilax glabra, 6-10 parts of Earthworm, 6-10 parts of Angelica dahurica, 10-15 parts of Clematidis, 3-6 parts of Radix Glycyrrhizae, 6-10 parts of Angelica sinensis, 10-15 parts of Lablab dal, 6-10 parts of Curcuma, 10-15 parts of White Peony Root, and 10-15 parts of roasted malt.

[0019] Furthermore, the weight of the raw material is: 12 parts of Astragalus, 18 parts of Rhizoma Smilacis Glabrae, 8 parts of Earthworms, 8 parts of Radix Angelicae Pubescentis, 12 parts of Radix Clematidis, 5 parts of Radix Glycyrrhizae Preparata, 8 parts of Radix Angelicae Sinensis, 12 parts of Lablab dahuricae, 8 parts of Rhizoma Curcumae, 12 parts of Radix Paeoniae Alba, and 12 parts of roasted malt.

[0020] Furthermore, when the composition is prepared into granules, the preparation method includes the following steps: a) Grinding each API into coarse powder; b) adding water to the mixture and decocting twice, first adding 8-10 times the amount of water and decocting for 1.5-2 hours, and second adding 6-8 times the amount of water and decocting for 1-1.5 hours; c) Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of 1.10-1.20 (60°C); d) adding dextrin and lactose, drying and forming granules.

[0021] Furthermore, when the composition is prepared into a decoction, the preparation method is: After mixing all the raw materials, add 8-10 times the amount of water and boil for 1.5-2 hours, then filter and take the juice.

[0022] Use of a traditional Chinese medicine composition for treating chronic refractory gout in the preparation of a drug for lowering blood uric acid levels.

[0023] The invention relates to the use of a traditional Chinese medicine composition for treating chronic refractory gout in the preparation of a medicine for improving the traditional Chinese medicine symptoms of chronic refractory gout, wherein the traditional Chinese medicine symptoms include joint pain, redness and swelling, fatigue, weakness, and soreness of the waist and knees.

[0024] Use of a traditional Chinese medicine composition for treating chronic refractory gout in preparing a drug for reducing the frequency of gout recurrences.

[0025] Application of a traditional Chinese medicine composition for treating chronic refractory gout in preparing a medicine for reducing the volume of tophi.

[0026] A pharmaceutical preparation for treating chronic refractory gout, a traditional Chinese medicine composition for treating chronic refractory gout, and pharmaceutically acceptable excipients.

[0027] Example 2 1 Study Design 1.1 Research Methods Prospective, randomized, double-blind, controlled study: Patients with chronic refractory gout (acute phase) who met the inclusion criteria were randomly divided into a trial group (Yiqi Xiaozhuo Zhuyu prescription treatment group) and a control group (placebo group). The results of the two groups were prospectively observed and compared. 1.11 Grouping: A randomized design with block randomization was used, using SAS 9.2 statistical software. A random seed generator was used to generate random seeds, resulting in a table of random numbers for the treatments (experimental drug and control drug) received by 44 subjects. The selected block length and random initial seed parameters were sealed in a blinded container as confidential data. The randomization table and emergency envelopes were sealed in opaque envelopes. The researchers entered the randomization numbers on the medical record form in the order in which the subjects were selected, and notified the subjects to distribute the experimental drug with the same randomization number.

[0028] 1.12 Blind Method: Double-blind: Prepare a simulant that is essentially identical to the Yiqi Xiaozhuo Zhuyu Chinese medicine granules in color, size, odor, and weight, making it difficult for clinical trial subjects to distinguish and facilitate double-blind testing. Drug coding is performed by personnel unrelated to clinical observation, monitoring, and statistical analysis. The intervention and control drugs are numbered according to the established random sequence. The corresponding drug number is affixed to a conspicuous location on the outer packaging of the drug. The entire process is recorded as required.

[0029] Unblinding Method: After the clinical trial is completed, the applicant, investigator, and third-party supervisor jointly unblind the trial and control groups, dividing them into Groups A and B. Statistical analysis and processing of the data are then performed. After statistical analysis is complete, the blind is unblinded again to announce whether Groups A and B represent the trial drug or the control drug, respectively.

[0030] Emergency unblinding: Emergency unblinding should not be performed unless the subject must know the group assignment information for medical treatment. If a subject experiences a medical emergency, the trial medication the subject is taking should be immediately clarified. The sponsor and principal investigator should be notified as much as possible before unblinding, and emergency unblinding should be performed to obtain the subject's group assignment information. If the sponsor's relevant personnel cannot be contacted before breaking the blind, the sponsor must be contacted within 24 hours after the emergency unblinding. The investigator should record the time, location, and reason for the emergency unblinding.

[0031] 1.2 Research subjects 1.21 Inclusion criteria: (1) Age 18-60 years old; (2) Patients with acute attacks of chronic refractory gout who meet the Western medical diagnosis; (3) Meet the diagnostic criteria for Qi deficiency, dampness turbidity and blood stasis syndrome; (4) The subjects gave their informed consent and signed the informed consent form.

[0032] 1.22 Exclusion criteria: (1) Arthritis caused by secondary gout or other diseases (such as rheumatoid arthritis, pyogenic arthritis, traumatic arthritis, traumatic arthritis, senile osteoarthritis, pseudogout, chemotherapy, radiotherapy, chronic lead poisoning and acute obstructive nephropathy); (2) Patients taking drugs that affect blood UA metabolism, such as hydrochlorothiazide, furosemide, low-dose aspirin, and drugs containing the above ingredients, such as compound risperidone and hydrochlorothiazide; or patients who stopped taking glucocorticoids less than 1 month before registration; or patients who used nonsteroidal anti-inflammatory drugs or other analgesics or external ointments 24 hours before baseline assessment; (3) Severe chronic diseases (heart failure, liver or kidney dysfunction, systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg, fasting blood glucose >12.9 mmol / L or postprandial blood glucose >16.9 mmol / L, combined with severe diabetic complications) or major mental or neurological diseases; (4) history of cancer; (5) Those aged ≥60 or younger than 18 years old; (6) Cognitive dysfunction, unable to accurately complete the scale score; (7) Allergic constitution, known or suspected to be allergic to the test drug and its excipients; (8) Pregnant women, breastfeeding women or women who are planning to become pregnant in the near future.

[0033] 1.3 Intervention measures 1.31 Medication Usage: The experimental group took the Yiqi Xiaozhuo Zhuyu Formula Chinese Medicine Granules prepared from the Chinese medicine composition. Yiqi Xiaozhuo Zhuyu Formula Chinese Medicine Granules, 1 packet each time, orally twice daily for 4 consecutive weeks, taken with boiled water. 1.32 Basic treatment plan: The uric acid-lowering drug of choice is febuxostat 40 mg once daily, which should be taken continuously during the trial and follow-up period; the analgesic drug is diclofenac sodium extended-release tablets 75 mg twice daily for 7 days; and targeted dietary guidance is provided.

[0034] 1.4 Data Collection 1.41 Collecting Metrics Background Information (1) Demographic data: age, gender, height, weight, ethnicity, occupation, and marital and reproductive history.

[0035] (2) General clinical data: course of disease, treatment history, comorbidities and medication, etc.

[0036] Safety indicators (1) Vital signs: body temperature, respiration, heart rate, heart rhythm, blood pressure after 10 minutes of rest, etc.

[0037] (2) Laboratory examination: routine blood test, routine urine test, routine stool test, liver and kidney function test.

[0038] (3) Any adverse reactions that may occur.

[0039] Efficacy indicators Main efficacy outcome measure: VAS score (0 = no pain, 10 = unbearable pain). VAS scores were assessed three times daily, consistent with the patient's pain perception, and the average of the scores was used as the daily VAS score. Pre- and post-treatment VAS scores and time to pain improvement (VAS < 3 was defined as pain improvement) were compared.

[0040] TCM symptom efficacy: Determination of TCM symptom efficacy: Determine the TCM symptom efficacy based on the integral method.

[0041] Efficacy index (n) = (pre-treatment score - post-treatment score) × 100% / pre-treatment score Clinical control: Clinical symptoms disappear or basically disappear, and the total symptom score decreases by ≥95% compared with before treatment.

[0042] Markedly effective: Clinical symptoms improved significantly, with the total symptom score reduced by ≥70% compared with before treatment.

[0043] Effective: Clinical symptoms are alleviated, and the total symptom score is reduced by ≥30% compared with before treatment.

[0044] Ineffective: clinical symptoms have no significant improvement or worsening, and the total symptom score is reduced by <30% compared with before treatment.

[0045] Traditional Chinese Medicine (TCM) symptom scoring method (referring to the TCM Symptom Diagnosis and Treatment Criteria and the 2021 Guidelines for the Combined Diagnosis and Treatment of Gout and Hyperuricemia) Traditional Chinese Medicine Symptom Scoring Standard Secondary indicators: Blood uric acid: Compare the difference in blood uric acid before and after treatment; Joint function classification: compare the differences before and after treatment; Number of relapses: the total number of relapses during medication and follow-up after medication discontinuation.

[0046] 1.42 Observation and follow-up plan: (1) Symptoms, signs, tongue and pulse were observed and recorded before and after treatment, every 2 weeks and at the end of the trial.

[0047] (2) VAS score and joint function grade were calculated once before treatment (week 0) and once every day after treatment. The pain relief time of each group was calculated after VAS < 3, and then calculated once every week after treatment (week 1 and week 4). Serum uric acid was tested once before treatment (week 0), every week after treatment (week 1), and every week after treatment (week 4).

[0048] (3) Liver and kidney function, blood, urine and stool routine tests were performed once before treatment and once every 4 weeks after treatment.

[0049] (4) During the treatment and follow-up period, the number of recurrences in each group was recorded.

[0050] (5) For those who experience adverse events during the trial, follow-up should be carried out until the symptoms or signs and corresponding physical and chemical examinations return to normal, or a positive medical conclusion is reached.

[0051] 1.5 Data Analysis Methods This study used SPSS 26.0 statistical software for data analysis; (1) Descriptive analysis: Qualitative indicators are described using frequency tables, percentages or composition ratios; quantitative indicators are described using mean, standard deviation, minimum and maximum values.

[0052] (2) Enumeration data were expressed as frequencies and tested using the chi-square test; a two-sided P < 0.05 was considered statistically significant. Measurement data were expressed as mean ± standard deviation (x ± s) when normally distributed and as median ± interquartile range (M ± Q) when non-normally distributed. If the data conformed to a normal distribution and had homogeneous variances, independent sample t-tests were used for comparisons between two groups; one-way analysis of variance was used for comparisons between multiple groups; if the data did not conform to a normal distribution, nonparametric tests were used, including the Mann-Whitney U test for pairwise comparisons and the Kruskal-Wallis H test for comparisons between multiple groups.

[0053] Through reasonable data analysis methods, we can accurately compare the differences in various observation indicators between the Yiqi Xiaozhuo Zhuyu prescription treatment group and the control group, thereby scientifically evaluating the efficacy and safety of Yiqi Xiaozhuo Zhuyu prescription in the treatment of chronic refractory gout.

[0054] 2. Research Results 1. Comparison of patient baseline information A total of 44 patients with chronic refractory gout who met the criteria were enrolled in this study and randomly divided into an experimental group and a control group, with 22 patients in each group. During the trial, 2 patients dropped out of the experimental group and 3 patients dropped out of the control group, resulting in a final total of 20 patients in the experimental group and 19 in the control group, including 37 males and 2 females. The age ranged from 60 to 22 years, with an average of (38.82±8.88) years. The duration of gout ranged from 3 years to 29 years, with an average of (8.18±4.82) years. There were no statistically significant differences between the two groups in age, gender, disease duration, VAS score, and baseline serum uric acid (P>0.05), indicating comparability (see Table 1). This indicates that the baseline conditions of the two groups were similar at the start of the study, providing a reliable basis for subsequent comparison of the efficacy of the Yiqi Xiaozhuo Zhuyu prescription with conventional Western medicine.

[0055] Table 1 Comparison of basic information of patients in the two groups (x±s) (2) Evaluation of treatment efficacy 1. Results of the main efficacy indicators VAS level: Joint pain severity was assessed using the visual analogue scale (VAS). Before treatment, the VAS score in the experimental group was (6.10±1.37) points, while that in the control group was (5.42±1.98). There was no statistically significant difference between the two groups (P>0.05). After one week of treatment, the VAS score in the experimental group decreased to (2.50±0.69) points, while that in the control group decreased to (3.26±1.10). Within-group differences were statistically significant (P<0.05). The VAS score in the experimental group was lower than that in the control group, and the inter-group difference was statistically significant (P<0.05). After four weeks of treatment, the VAS score in the experimental group further decreased to (1.85±0.81) points, while that in the control group decreased to (2.89±1.60) points. The differences between the two groups remained statistically significant (P<0.05). See Table 2 for details.

[0056] VAS Relief Time: Comparison of VAS relief time between the two groups after treatment showed that the experimental group had a shorter VAS relief time, with a statistically significant difference (P < 0.05). See Table 3 for details. This indicates that the Yiqi Xiaozhuo Zhuyu recipe is significantly effective in relieving joint pain and can better alleviate patients' suffering.

[0057] Table 2 Comparison of VAS levels between the two groups before and after treatment (x±s) Note: Compared with before treatment, *P<0.05; compared with the control group, # P<0.05.

[0058] Table 3 Comparison of VAS relief time between the two groups of patients after treatment (x±s) Note: Compared with the control group, *P<0.05.

[0059] TCM symptom scores: The effective rate in the experimental group reached 90%, significantly higher than that in the control group. Both groups showed significant improvement in TCM symptom scores before and after treatment (P < 0.05), with the improvement in the experimental group being more pronounced than in the control group (P < 0.05). See Tables 4 and 5 for details.

[0060] Table 4 Analysis of clinical efficacy of the experimental group Table 5 Comparison of TCM symptom scores between the two groups of patients before and after treatment (x±s) Note: Compared with before treatment, *P<0.05; compared with the control group, # P<0.05, compared with the control group, ## P>0.05.

[0061] 2. Secondary efficacy index results Serum uric acid: Before treatment, the serum uric acid level in the experimental group was (546.50±127.88) μmol / L, and in the control group was (603.21±158.94) μmol / L. There was no statistically significant difference between the two groups (P>0.05). After one week of treatment, the serum uric acid level in the experimental group decreased to (505.22±96.15) μmol / L, and in the control group to (571.67±79.97) μmol / L. However, there was no statistically significant difference between the two groups before and after treatment (P>0.05). However, the serum uric acid level in the experimental group was significantly lower than that in the control group, and the difference between the two groups was statistically significant (P<0.05). After four weeks of treatment, the serum uric acid level in the experimental group decreased to (439.25±114.78) μmol / L, and in the control group to (529.32±105.61) μmol / L. There were statistically significant differences both within and between the two groups (P<0.05). See Table 6 for details. This indicates that the Yiqi Xiaozhuo Zhuyu formula has a significant effect in lowering blood uric acid levels and is superior to the placebo group.

[0062] Relapses: During treatment, the experimental group experienced fewer relapses, a statistically significant difference compared to the control group (P < 0.05). During 12 weeks of follow-up after treatment, the total number of relapses in the experimental group was significantly lower than in the control group (P < 0.05). See Table 7 for details. This suggests that the Yiqi Xiaozhuo Zhuyu formula helps reduce the risk of acute gout relapse in patients.

[0063] Table 6 Comparison of blood uric acid in the two groups before and after treatment (x±s) Note: Compared with before treatment, *P<0.05; compared with the control group, # P<0.05.

[0064] Table 7 Comparison of the number of recurrences between the two groups of patients during treatment and follow-up period (x±s) Note: Compared with the control group, *P<0.05.

[0065] 3. Security Analysis During treatment, both groups were closely monitored for adverse reactions. No serious adverse reactions occurred in either group. There were no significant differences in liver and kidney function between the two groups (P>0.05), and no significant differences in liver and kidney function before and after treatment between the two groups (P>0.05). See Table 8 for details. This demonstrates that the Yiqi Xiaozhuo Zhuyu formula has a good safety profile for the treatment of chronic refractory gout, comparable to that of the placebo regimen.

[0066] Table 8 Comparison of safety indicators before and after treatment between the two groups of patients Note: Compared with the control group before treatment, a P>0.05; compared with the control group after treatment, b P>0.05; compared with the group before treatment, c P>0.05.

[0067] Example 3 1 Study Design 1.1 Research Methods Prospective randomized double-blind controlled study: Patients with chronic refractory gout (intermittent period) who met the inclusion criteria were randomly divided into a trial group (Yiqi Xiaozhuo Zhuyu prescription treatment group) and a control group (placebo group). The results of the two groups were prospectively observed and compared; 1.12 Grouping method: Random number table method was used to ensure randomness and concealment of grouping, and to avoid the influence of subjective factors of researchers and patients on grouping; 1.13 Blinding Method: A double-blind method was used to prepare a simulant that was essentially identical to the Yiqi Xiaozhuo Zhuyu Granules in color, particle size, odor, and weight, making it difficult for clinical trial subjects to distinguish between them. Drug coding was performed by a dedicated individual, and the entire process was recorded as required. Unblinding was conducted twice: the first unblinding was conducted after the clinical trial was completed, and the second unblinding was conducted after the statistics were completed. Emergency unblinding was conducted only in the event of a medical emergency, and relevant information was recorded.

[0068] 1.2 Research subjects 1.21 Inclusion criteria: Age 18-80 years; Patients in the intermittent period of chronic refractory gout diagnosed by Western medicine; Patients meeting the diagnostic criteria for Qi deficiency, dampness turbidity, and blood stasis syndrome; Subjects provided informed consent and signed an informed consent form; 1.22 Exclusion criteria: patients with secondary gout or arthritis caused by other diseases; patients taking drugs that affect blood UA metabolism; patients with serious chronic diseases or major mental or neurological diseases; patients with a history of cancer; patients aged 80 or younger than 18 years; patients with cognitive impairment and inability to accurately complete the scale score; patients with allergic constitution, known or suspected allergy to the trial drug and its excipients; pregnant women, breastfeeding women, or women planning to become pregnant in the near future.

[0069] 1.3 Intervention measures 1.31 Medication Usage: The experimental group took the Yiqi Xiaozhuo Zhuyu Formula Chinese Medicine Granules prepared from the Chinese medicine composition, one bag each time, twice a day, washed down with boiled water; the control group took the placebo, one bag each time, twice a day, washed down with boiled water; 1.32 Basic treatment plan: Both groups of patients were given the uric acid-lowering drug febuxostat 20 mg once daily and provided with targeted dietary guidance.

[0070] 1.4 Data Collection 1.41 Collecting Metrics Background Information (1) Demographic data: age, gender, height, weight, ethnicity, occupation, and marital and reproductive history.

[0071] (2) General clinical data: course of disease, treatment history, comorbidities and medication, etc.

[0072] Safety indicators (1) Vital signs: body temperature, respiration, heart rate, heart rhythm, blood pressure after 10 minutes of rest, etc.

[0073] (2) Laboratory examination: routine blood test, routine urine test, routine stool test, liver and kidney function test.

[0074] (3) Any adverse reactions that may occur.

[0075] Efficacy indicators (1) Main efficacy indicator: blood uric acid Secondary indicators: TCM symptom efficacy: Determination of TCM symptom efficacy: Determine the TCM symptom efficacy based on the integral method.

[0076] Efficacy index (n) = (pre-treatment score - post-treatment score) × 100% / pre-treatment score Clinical control: Clinical symptoms disappear or basically disappear, and the total symptom score decreases by ≥95% compared with before treatment.

[0077] Markedly effective: Clinical symptoms improved significantly, with the total symptom score reduced by ≥70% compared with before treatment.

[0078] Effective: Clinical symptoms are alleviated, and the total symptom score is reduced by ≥30% compared with before treatment.

[0079] Ineffective: clinical symptoms have no significant improvement or worsening, and the total symptom score is reduced by <30% compared with before treatment.

[0080] Traditional Chinese Medicine (TCM) symptom scoring method (referring to the TCM Symptom Diagnosis and Treatment Criteria and the 2021 Guidelines for the Combined Diagnosis and Treatment of Gout and Hyperuricemia) Traditional Chinese Medicine Symptom Scoring Standard Synovial thickness and tophi diameter under musculoskeletal ultrasound: Comparison of volume and anteroposterior diameter of tophi under musculoskeletal ultrasound; Joint function classification: compare the differences before and after treatment; Number of relapses: the total number of relapses during medication and follow-up after medication discontinuation.

[0081] 1.42 Observation and follow-up plan: Symptoms, signs, tongue and pulse were observed and recorded once before treatment and at the end of the trial.

[0082] Joint function grade was assessed once at week 0 before treatment and once at week 4 after treatment; serum uric acid was measured once at week 0 before treatment and once at week 4 after treatment; synovial thickness and tophi diameter were measured at week 0 before treatment and once at week 4 after treatment by joint ultrasound.

[0083] Liver and kidney function, blood and urine routine tests were performed once before treatment and once every 4 weeks after treatment.

[0084] During the treatment and follow-up period, the number of recurrences in each group was recorded.

[0085] For those who experience adverse events during the trial, follow-up should be carried out until the symptoms or signs and corresponding physical and chemical examinations return to normal, or a positive medical conclusion is reached.

[0086] 1.5 Data Analysis Methods This study used SPSS 26.0 statistical software for data analysis; (1) Descriptive analysis: Qualitative indicators are described using frequency tables, percentages or composition ratios; quantitative indicators are described using mean, standard deviation, minimum and maximum values.

[0087] (2) Enumeration data were expressed as frequencies and tested using the chi-square test; a two-sided P < 0.05 was considered statistically significant. Measurement data were expressed as mean ± standard deviation (x ± s) when normally distributed and as median ± interquartile range (M ± Q) when non-normally distributed. If the data conformed to a normal distribution and had homogeneous variances, independent sample t-tests were used for comparisons between two groups; one-way analysis of variance was used for comparisons between multiple groups; if the data did not conform to a normal distribution, nonparametric tests were used, including the Mann-Whitney U test for pairwise comparisons and the Kruskal-Wallis H test for comparisons between multiple groups.

[0088] 2 Research results 2.1 Comparison of patients’ basic information A total of 58 patients with chronic refractory gout who met the criteria were enrolled in this study and randomly divided into an experimental group and a control group, with 29 cases in each group. Finally, 29 cases were included in the experimental group and the control group, including 56 males and 2 females. The oldest age was 60 years old and the youngest was 24 years old, with an average of (38.96±8.96) years. The shortest gout course was 3 years and the longest was 27 years, with an average of (8.17±4.76) years. There was no statistically significant difference in basic information such as age, gender, course of disease, height, weight, number of affected joints, and joint grade between the two groups of patients (P>0.05), and they were comparable, as shown in Tables 1 and 2 for details. This shows that at the beginning of the study, the basic conditions of the two groups of patients were similar, which provides a reliable prerequisite for the subsequent comparison of the efficacy of the Yiqi Xiaozhuo Zhuyu prescription and conventional Western medicine treatment options.

[0089] Table 1 Comparison of general conditions of patients in the two groups (x±s) 2.2 Treatment efficacy evaluation 2.21 Results of the main efficacy indicators Serum uric acid: Before treatment, the serum uric acid level in the experimental group was (581.25±125.03) μmol / L, and that in the control group was (552.43±168.95) μmol / L. There was no statistically significant difference between the two groups (P>0.05). After 4 weeks of treatment, the serum uric acid level in the experimental group further decreased to (447.20±118.16) μmol / L, and that in the control group to (520.95±108.47) μmol / L. The difference between the two groups was statistically significant (P < 0.05), the difference within the experimental group was statistically significant (P < 0.001), and the difference within the treatment group was not statistically significant (P > 0.05). See Table 2 for details. This indicates that the Yiqi Xiaozhuo Zhuyu recipe has a significant effect in lowering serum uric acid levels and is superior to the placebo group.

[0090] Table 2 Comparison of blood uric acid levels before and after treatment in the two groups (x±s) Note: Compared with before treatment, *P<0.001; compared with before treatment, **P>0.05; compared with the control group, # P<0.05, compared with the control group, ## P>0.05.

[0091] 2.22 Secondary Efficacy Index Results TCM symptom scores: The total effective rate in the experimental group was 93.1%, significantly higher than that in the control group (see Table 3 for details). Before treatment, there was no statistically significant difference in TCM symptom scores between the two groups (P>0.05). After four weeks of treatment, the scores in the experimental group further decreased to (9.41±3.96) and in the control group to (15.00±6.26), with statistically significant differences both within and between the two groups (P<0.05). (See Table 4 for details.) This demonstrates that the Yiqi Xiaozhuo Zhuyu formula, in addition to traditional treatment, effectively improves the symptoms of patients with refractory gout (intermittent period).

[0092] Table 3 Analysis of the effectiveness of TCM symptom scores in the experimental group Table 4 Comparison of TCM symptom score levels before and after treatment in the two groups of patients (x±s) Note: Compared with before treatment, *P<0.05; Compared with before treatment, **P>0.05; Compared with the control group, # P<0.05, compared with the control group, ## P>0.05.

[0093] Joint-related indicators: After treatment, the joint function grade of both groups of patients improved, and the joint function grade of the experimental group improved more significantly than that of the control group, and the difference was statistically significant (P < 0.05). After treatment, the proportion of patients with improved tophi volume in the experimental group was higher, and the difference was statistically significant (P < 0.05). See Table 5 for details. This shows that the Yiqi Xiaozhuo Zhuyu recipe can help further improve the joint function of patients with refractory gout (intermittent period) and reduce the volume of tophi on the basis of traditional treatment.

[0094] Table 5 Comparison of joint-related indicators between the two groups of patients before and after treatment Note: Compared with the control group before treatment, a P>0.05; compared with the control group after treatment, b P<0.05; compared with the group before treatment, c P<0.05.

[0095] Relapse frequency: 4 weeks after treatment and 16 weeks after treatment and follow-up, the relapse frequency of patients in the experimental group was significantly reduced compared with that in the control group, as shown in Table 6. This shows that the Yiqi Xiaozhuo Zhuyu prescription can further reduce the relapse frequency of acute gout in patients with refractory gout (intermittent period) on the basis of traditional treatment.

[0096] Table 6 Comparison of the number of relapses between the two groups during treatment and follow-up (x±s) Note: Compared with the control group, *P<0.05.

[0097] 3 Security Analysis During the treatment, the two groups of patients were closely observed for adverse reactions; no adverse reactions occurred in either group; the comparison results of safety indicators such as liver and kidney function between the two groups before and after treatment showed no significant differences (P>0.05), there was no significant difference in liver and kidney function before and after treatment in the control group, and there was no significant difference in liver function before and after treatment in the experimental group, but the blood creatinine was significantly lower than before treatment, see Table 7 for details; this shows that the Yiqi Xiaozhuo Zhuyu prescription has good safety in the treatment of chronic refractory gout, which is comparable to the safety of the placebo regimen, but may have a potential improvement in renal function.

[0098] Table 7 Comparison of safety indicators before and after treatment between the two groups of patients Note: Compared with the control group before treatment, a P>0.05; compared with the control group after treatment, b P>0.05; compared with the group before treatment, c P>0.05; compared with the group before treatment, d P<0.05.

[0099] It should be understood that the embodiments of the present application are not limited to the precise structure described above, and various modifications and changes can be made without departing from the scope thereof. The scope of the embodiments of the present application is limited only by the appended claims.

[0100] The above-described embodiments merely represent several implementation methods of the embodiments of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention. It should be noted that a person skilled in the art may make various modifications and improvements without departing from the concept of the embodiments of the present application, and these modifications and improvements fall within the scope of protection of the embodiments of the present application.

Claims

1. A Chinese medicine composition for treating chronic refractory gout, characterized in that: Made from the following raw materials in parts by weight: 10-15 parts of Astragalus, 15-20 parts of Smilax glabra, 6-10 parts of Earthworm, 6-10 parts of Angelica dahurica, 10-15 parts of Clematidis, 3-6 parts of Radix Glycyrrhizae, 6-10 parts of Angelica sinensis, 10-15 parts of Lablab dal, 6-10 parts of Curcuma, 10-15 parts of White Peony Root, and 10-15 parts of roasted malt.

2. A Chinese medicine composition for treating chronic refractory gout according to claim 1, characterized in that: The weight parts of the raw material medicine are: 12 parts of Astragalus, 18 parts of Rhizoma Smilacis Glabrae, 8 parts of Earthworms, 8 parts of Radix Angelicae Pubescentis, 12 parts of Radix Clematidis, 5 parts of Radix Glycyrrhizae Preparata, 8 parts of Radix Angelicae Sinensis, 12 parts of Lablab dahuricae, 8 parts of Rhizoma Curcumae, 12 parts of Radix Paeoniae Alba, and 12 parts of roasted malt.

3. A Chinese medicine composition for treating chronic refractory gout according to claim 1, characterized in that: When the composition is prepared into granules, the preparation method comprises the following steps: a) Grinding each API into coarse powder; b) adding water to the mixture and decocting twice, first adding 8-10 times the amount of water and decocting for 1.5-2 hours, and second adding 6-8 times the amount of water and decocting for 1-1.5 hours; c) Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of 1.10-1.20 (60°C); d) adding dextrin and lactose, drying and forming granules.

4. A Chinese medicine composition for treating chronic refractory gout according to claim 1, characterized in that, When the composition is prepared into a decoction, the preparation method is as follows: After mixing all the raw materials, add 8-10 times the amount of water and boil for 1.5-2 hours, then filter and take the juice.

5. Use of the Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for lowering blood uric acid levels.

6. Use of the Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for improving the TCM symptoms of chronic refractory gout, wherein the TCM symptoms include joint pain, redness and swelling, fatigue, and soreness of the waist and knees.

7. Use of the Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for reducing the frequency of gout recurrences.

8. Use of the Chinese medicine composition according to any one of claims 1 to 4 in preparing a medicament for reducing the volume of tophi.

9. A pharmaceutical preparation for treating chronic refractory gout, characterized in that: The invention relates to a Chinese medicine composition comprising the Chinese medicine composition according to any one of claims 1 to 4, and pharmaceutically acceptable excipients.

Images