A Chinese medicine composition for tonifying kidney, promoting blood circulation and removing dampness, and its preparation and application

Abstract

The present invention relates to the field of traditional Chinese medicine, and in particular to a Chinese medicine composition for tonifying the kidney, activating blood circulation and removing dampness, and its preparation and application. The present invention proposes a treatment principle of tonifying the kidney, activating blood circulation and removing dampness for the pathological mechanism of knee osteoarthritis of kidney deficiency, dampness and stasis type, combined with the clinical symptoms of patients, and emphasizes the treatment method of treating dampness and stasis at the same time, so as to prepare a Chinese medicine composition for tonifying the kidney, activating blood circulation and removing dampness, which has the effects of tonifying the kidney and strengthening the spleen, activating blood circulation and removing blood stasis, and removing dampness and removing arthralgia. The present invention objectively evaluates the clinical efficacy and safety of the Chinese medicine composition of the present invention in treating knee osteoarthritis of kidney deficiency, dampness and stasis type through a clinical randomized controlled trial study. The research results show that the Chinese medicine composition can effectively improve the clinical symptoms of patients, relieve pain, and improve the quality of life of patients. It has more significant effects in relieving joint pain, fatigue, pain anxiety, etc., and has obvious efficacy, good drug safety, no obvious adverse reactions, and has important clinical application value.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness, and the preparation and application thereof. Background Art

[0002] Knee osteoarthritis is a chronic degenerative disease of the bones and joints that is common in the middle-aged and elderly. It is one of the most common causes of knee joint pain, loss of function, and even disability. Clinically, knee pain, deformity, and limited mobility are the main manifestations. Pathological changes are mainly articular cartilage damage, osteophyte formation, and damage and degeneration of tissues such as subchondral bone and meniscus. There is no name of "knee osteoarthritis" in the traditional Chinese medicine classics of the motherland. According to the pathogenesis characteristics and historical evolution of this disease, it can be classified into the categories of "arthritis" and "knee arthritis" in traditional Chinese medicine. Traditional Chinese medicine has a unique understanding of the etiology and pathogenesis of this disease. "Suwen Bi Lun" first proposed the name of "arthritis" and pointed out that the cause of arthritis is mainly caused by the invasion of wind, cold, and dampness into the human body. Doctors of all dynasties believed that the etiology and pathogenesis of knee arthritis were mainly due to liver and kidney deficiency, insufficient qi and blood, which led to the loss of nourishment of tendons and veins, and the invasion of wind, cold, dampness, heat and other evil spirits, which led to the obstruction of tendons and veins. Pain occurred when the tendons and veins were blocked, and the disease was caused. They emphasized that liver and kidney deficiency was the root cause, and the external evil spirits such as wind, cold, dampness and heat were the symptoms. Since the onset of knee arthritis was affected by a variety of pathogenic factors, doctors of all dynasties divided many different syndromes from different angles, but all believed that "liver and kidney deficiency, qi stagnation and blood stasis" was one of the main symptoms of knee arthritis. Combining the discussions of doctors of all dynasties and modern clinical research, it can be seen that the pathogenesis of kidney deficiency and blood stasis accounts for the vast majority of the incidence of knee osteoarthritis. At present, the clinical use of traditional Chinese medicine in the treatment of knee osteoarthritis mainly takes kidney tonifying and blood activating as the treatment principle, and Chinese medicine uses kidney tonifying and blood activating Chinese medicine as the treatment prescription.

[0003] From the above research, knee osteoarthritis is mostly caused by liver and spleen deficiency, long-term strain, empty pores, wind, cold and dampness, stagnation of meridians, and obstruction of qi and blood. The pathological characteristics of this disease are mixed deficiency and excess, and the underlying deficiency and superficial excess are the two major aspects of this disease. Therefore, current clinical treatment and experimental research are mostly focused on tonifying the liver and kidney and promoting blood circulation and unblocking collaterals. However, early knee osteoarthritis is mostly middle-aged people, and the main syndrome is excess syndrome; therefore, qi and blood stagnation and poor circulation are important pathological changes in OA. In the humid areas of Lingnan, dampness obstruction and phlegm and dampness stasis are more important pathological factors for this type of patients. Dampness is the main type of arthralgia, and its main pathogenesis is dampness, which causes qi and blood obstruction and meridian obstruction. This disease is mainly characterized by excess syndrome, and there are also deficiency syndromes and mixed deficiency and excess syndromes. Deficiency is mostly spleen and kidney deficiency, and the evil is mainly dampness, with different wind, cold, heat, stasis, phlegm, etc. Due to dysfunction of the spleen, kidney and other organs, and insufficient yin and yang, qi and blood, dampness is easy to occur and external dampness is easy to invade; dampness, phlegm and blood stasis block the yin and yang of the organs for a long time, and damage the qi and blood of the yin and yang of the organs, so the internal and external factors are mutually causal. Therefore, dampness is not only one of the factors that start knee arthritis, but also the root of the protracted and incurable arthritis. "Essentials of Diagnosis and Treatment" says: "Wind, cold, heat and dampness can all attack people, but dampness accumulates for a long time and stays in the joints." Therefore, the course of dampness arthritis is long and lingering, and it is difficult to cure. Doctors need to pay special attention to and strengthen the management of the disease. For patients with knee osteoarthritis with kidney deficiency, dampness and blood stasis, if the dampness is not removed, it will block the meridians and continue to affect the circulation of blood in the meridians, thereby aggravating the blockage of blood vessels. Blood stasis in the kidney collaterals can further damage the kidney qi, aggravate water and dampness, and form a vicious cycle. Therefore, only using the principle of tonifying the kidney and activating blood circulation to treat such patients will ignore the pathological conditions of dampness, and the efficacy is often lacking. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness, which can be used to treat knee osteoarthritis of kidney deficiency, dampness and stasis type.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] In a first aspect, the present invention provides a Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness, comprising the following raw materials in parts by weight: 7.5-30 parts of Polygonum cuspidatum, 7.5-30 parts of Achyranthes bidentata, 10-40 parts of Tripterygium wilfordii, 7.5-30 parts of Epimedium, 7.5-30 parts of Morus alba, 10-40 parts of Coix seeds, 5-20 parts of Eupolyphaga sinensis, 5-20 parts of Salvia miltiorrhiza, 7.5-30 parts of Paeonia lactiflora, and 15-60 parts of Astragalus.

[0007] The invention prepares a Chinese medicine composition by compounding Polygonum cuspidatum, Achyranthes bidentata, Herba Coix, Herba Epimedii, Morus alba, Semen Coix, Eupolyphaga Sinensis, Salvia miltiorrhiza, Paeonia lactiflora and Radix Astragali. Polygonum cuspidatum and Achyranthes bidentata are the main drugs, which can dispel dampness and blood stasis, strengthen tendons and bones; Herba Coix, Semen Coix, Morus alba and Radix Astragali are the assistant drugs, which can invigorate qi and invigorate spleen, dispel rheumatism and benefit joints; Eupolyphaga Sinensis, Salvia miltiorrhiza, Paeonia lactiflora and Epimedium are the adjuvant drugs, and Epimedium is used to invigorate kidney qi and strengthen tendons and bones; Eupolyphaga Sinensis, Salvia miltiorrhiza and Paeonia lactiflora can activate blood circulation, promote menstruation, dispel blood stasis and relieve pain; Achyranthes bidentata is also the guiding drug, which can lead the drugs downward to directly reach the lesion site; and the obtained Chinese medicine composition can jointly exert the effects of dispelling dampness and removing arthralgia, promoting blood circulation and removing blood stasis, invigorating kidney and invigorating spleen, and strengthening tendons and bones. The Chinese medicine composition of the present invention uses Polygonum cuspidatum, Achyranthes bidentata, Eleutherodactyla lappa, Coix seeds and Morus twigs, which has the effects of removing dampness and unblocking meridians, making up for the defect that the commonly used kidney-tonifying and blood-activating prescriptions cannot remove dampness, and is compatible with the kidney-tonifying and blood-activating Chinese medicines, so that the whole prescription has the effects of tonifying the kidney, activating blood circulation and removing dampness, which plays an important role in improving the clinical efficacy of kidney deficiency, dampness and blood stasis type knee osteoarthritis.

[0008] Preferably, the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness comprises the following raw materials in parts by weight: 15 parts of Polygonum cuspidatum, 15 parts of Achyranthes bidentata, 20 parts of Eleutherodactyla scabra, 15 parts of Epimedium, 15 parts of Morus alba, 20 parts of Coix seeds, 10 parts of Eupolyphaga sinensis, 10 parts of Salvia miltiorrhiza, 15 parts of Paeonia lactiflora and 30 parts of Astragalus.

[0009] In a second aspect, the present invention provides a method for preparing the above-mentioned Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness, comprising the following steps:

[0010] (1) weighing the raw materials according to the weight ratio, soaking them in water and then boiling them, and filtering them to obtain a filtrate and a filter residue;

[0011] (2) adding water to the filter residue obtained in step (1), boiling the mixture, and filtering the mixture twice to obtain a filtrate and a filter residue;

[0012] (3) collecting the filtrates obtained by filtering in step (1) and step (2) and mixing them to obtain the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness.

[0013] Preferably, in step (1), the weight ratio of water to the raw material is (6-10):1; in step (2), the weight ratio of water to the filter residue is (2-6):1.

[0014] More preferably, in the step (1), the weight ratio of water to the raw material is 10:1; and in the step (2), the weight ratio of water to the filter residue is 4:1.

[0015] In a third aspect, the present invention provides the use of the above-mentioned Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness in the preparation of a medicine for treating knee osteoarthritis.

[0016] Preferably, the type of knee osteoarthritis is kidney deficiency, dampness and blood stasis type knee osteoarthritis.

[0017] In a fourth aspect, the present invention provides a medicine for treating knee osteoarthritis, comprising the above-mentioned Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness.

[0018] Preferably, the drug further comprises pharmaceutically acceptable excipients.

[0019] Preferably, the dosage form of the drug is granules, tablets, pills or capsules.

[0020] The beneficial effects of the present invention are:

[0021] The invention prepares a Chinese medicine composition by compounding Polygonum cuspidatum, Achyranthes bidentata, Herba Coix, Herba Epimedii, Morus alba, Semen Coix, Eupolyphaga Sinensis, Salvia miltiorrhiza, Paeonia lactiflora and Radix Astragali. Polygonum cuspidatum and Achyranthes bidentata are the main drugs, which can dispel dampness and blood stasis, strengthen tendons and bones; Herba Coix, Semen Coix, Morus alba and Radix Astragali are the assistant drugs, which can invigorate qi and invigorate spleen, dispel rheumatism and benefit joints; Eupolyphaga Sinensis, Salvia miltiorrhiza, Paeonia lactiflora and Epimedium are the adjuvant drugs, and Epimedium is used to invigorate kidney qi and strengthen tendons and bones; Eupolyphaga Sinensis, Salvia miltiorrhiza and Paeonia lactiflora can activate blood circulation, promote menstruation, dispel blood stasis and relieve pain; Achyranthes bidentata is also the guiding drug, which can lead the drugs downward to directly reach the lesion site; and the obtained Chinese medicine composition can jointly exert the effects of dispelling dampness and removing arthralgia, promoting blood circulation and removing blood stasis, invigorating kidney and invigorating spleen, and strengthening tendons and bones. The Chinese medicine composition of the present invention uses Polygonum cuspidatum, Achyranthes bidentata, Eleutherodactyla lappa, Coix seeds and Morus twigs, which has the effects of removing dampness and unblocking meridians, making up for the defect that the commonly used kidney-tonifying and blood-activating prescriptions cannot remove dampness, and is compatible with the kidney-tonifying and blood-activating Chinese medicines, so that the whole prescription has the effects of tonifying the kidney, activating blood circulation and removing dampness, which plays an important role in improving the clinical efficacy of kidney deficiency, dampness and blood stasis type knee osteoarthritis.

[0022] The present invention objectively evaluates the clinical efficacy and safety of the Chinese medicine composition of the present invention in treating knee osteoarthritis of kidney deficiency, dampness and blood stasis type through a clinical randomized controlled trial study. The research results show that the Chinese medicine composition can effectively improve the clinical symptoms of patients, relieve pain, and improve the quality of life of patients. It is more effective in relieving joint pain, relieving fatigue, relieving pain anxiety, etc., has obvious efficacy, good drug safety, no obvious adverse reactions, and has important clinical application value. DETAILED DESCRIPTION

[0023] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0024] The polygonum cuspidatum, achyranthes bidentata, radix quinatae, epimedium, mulberry branch, coix seed, earthworm, salvia miltiorrhiza, red peony root and astragalus used in the present invention are purchased from Guangzhou Baiyunshan Chinese Medicine Piece Co., Ltd.

[0025] Embodiment 1:

[0026] An embodiment of the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness of the present invention, the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness comprises the following preparation raw materials in parts by weight: 15 parts of Polygonum cuspidatum, 15 parts of Achyranthes bidentata, 20 parts of Tripterygium wilfordii, 15 parts of Epimedium brevicornum, 15 parts of Morus alba, 20 parts of Coix seeds, 10 parts of Eupolyphaga sinensis, 10 parts of Salvia miltiorrhiza, 15 parts of Paeonia lactiflora, and 30 parts of Astragalus.

[0027] The preparation method of the Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness comprises the following steps:

[0028] (1) weighing the raw materials according to the weight ratio, adding 8 times the weight of water, soaking for 25-40 minutes, boiling for 80 minutes at a boiling temperature of 95-100° C., and filtering to obtain a filtrate and a filter residue;

[0029] (2) adding 4 times the weight of water to the filter residue obtained in step (1) and boiling for 60 minutes at a boiling temperature of 95-100° C., and filtering twice to obtain a filtrate and a filter residue;

[0030] (2) collecting the filtrates obtained by filtering in step (1) and step (2) and mixing them to obtain the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness.

[0031] Embodiment 2:

[0032] An embodiment of the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness of the present invention, the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness comprises the following preparation raw materials in parts by weight: 7.5 parts of Polygonum cuspidatum, 7.5 parts of Achyranthes bidentata, 10 parts of Eleutherodactyla scabra, 7.5 parts of Epimedium, 7.5 parts of Morus alba, 10 parts of Coix seeds, 5 parts of Eupolyphaga sinensis, 5 parts of Salvia miltiorrhiza, 7.5 parts of Paeonia lactiflora and 15 parts of Astragalus.

[0033] The preparation method of the Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness comprises the following steps:

[0034] (1) weighing the raw materials according to the weight ratio, adding 6 times the weight of water, soaking for 25-40 minutes, boiling for 80 minutes at a boiling temperature of 95-100° C., and filtering to obtain a filtrate and a filter residue;

[0035] (2) adding 2 times the weight of water to the filter residue obtained in step (1) and boiling for 60 minutes at a boiling temperature of 95-100° C., and filtering twice to obtain a filtrate and a filter residue;

[0036] (2) collecting the filtrates obtained by filtering in step (1) and step (2) and mixing them to obtain the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness.

[0037] Embodiment 3:

[0038] An embodiment of the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness of the present invention, the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness comprises the following preparation raw materials in parts by weight: 30 parts of Polygonum cuspidatum, 30 parts of Achyranthes bidentata, 40 parts of Eleutherodactyla scabra, 30 parts of Epimedium, 30 parts of Morus alba, 40 parts of Coix seeds, 20 parts of Eupolyphaga sinensis, 20 parts of Salvia miltiorrhiza, 30 parts of Paeonia lactiflora and 60 parts of Astragalus.

[0039] The preparation method of the Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness comprises the following steps:

[0040] (1) weighing the raw materials according to the weight ratio, adding 10 times the weight of water, soaking for 25-40 minutes, boiling for 80 minutes at a boiling temperature of 95-100° C., and filtering to obtain a filtrate and a residue;

[0041] (2) adding 6 times the weight of water to the filter residue obtained in step (1) and boiling for 60 minutes at a boiling temperature of 95-100° C., and filtering twice to obtain a filtrate and a filter residue;

[0042] (2) collecting the filtrates obtained by filtering in step (1) and step (2) and mixing them to obtain the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness.

[0043] Experimental Example 1: Preliminary Experimental Study on Chinese Medicine Composition

[0044] Experimental sample: the Chinese medicinal composition for tonifying the kidney, promoting blood circulation and removing dampness prepared in Examples 1-3.

[0045] 1. Research subjects: SD rats. Thirty SD rats were taken and adaptively fed for 1 week, and randomly divided into 5 groups, with 6 rats in each group. They were ① sham operation control group, ② kidney deficiency dampness and blood stasis type knee osteoarthritis model group, ③ model + Chinese medicine composition group of Example 1, ④ model + Chinese medicine composition group of Example 2, and ⑤ model + Chinese medicine composition group of Example 3. Rats were prohibited from eating 12 hours before surgery and drinking water 4 hours before surgery to prevent vomiting and aspiration caused by anesthesia and gastrointestinal paralysis and intestinal obstruction.

[0046] 2. The medial meniscus instability surgery combined with high humidity environment was used to construct a model of knee osteoarthritis of kidney deficiency, dampness and stasis type. The method is as follows:

[0047] The medial incision of the patellar ligament of the knee joint was selected, and a longitudinal incision of about 1.5 cm was made. The skin, subcutaneous tissue, and joint capsule were cut layer by layer, the joint cavity was opened, and the medial meniscus tibial collateral ligament was found and cut off. The medial meniscus was obviously loose. The sham operation group did not undergo the tibial collateral ligament of the medial meniscus cut. The joint cavity and incision were flushed with physiological saline with a syringe. A small amount of penicillin powder was added to the joint cavity to stop bleeding. The joint capsule was sutured with 5-0 absorbable sutures, and the skin was sutured with 5-0 silk thread interrupted, disinfected, and the incision was bandaged. One week after the modeling was completed, the rats were placed in a constant temperature box with a high humidity environment: an external humidity simulation environment (relative humidity (RH): (90 ± 4)%, temperature (T): (21 ± 2) ° C in an artificial climate box), and the rats were subjected to external humidity stimulation once a day, each time for 10 hours.

[0048] 3. Intervention measures

[0049] After 4 weeks in the incubator, the Chinese medicine composition was gavaged. The gavage dosage of the Chinese medicine composition was based on the formula in "Pharmacological Experimental Methodology", and the equivalent dose for rats was 6.25 times that for humans. The specific doses are as follows:

[0050] ③ Model + Chinese medicine composition of Example 1 group: The Chinese medicine composition prepared in Example 1 was concentrated to 100 mL and administered intragastrically to each mouse at 1 mL / 100 g, once a day.

[0051] ④ Model + Chinese medicine composition of Example 2 group: The Chinese medicine composition prepared in Example 2 was concentrated to 100 mL and administered intragastrically at 1 mL / 100 g per mouse, once a day.

[0052] ⑤ Model + Chinese medicine composition of Example 3 group: The Chinese medicine composition prepared in Example 3 was concentrated to 100 mL and administered intragastrically to each mouse at 1 mL / 100 g, once a day.

[0053] The swelling degree and pathological changes of the knee joint were detected 8 weeks after intragastric administration.

[0054] 4. After 8 weeks of Chinese medicine treatment, the diameter of the knee joints of rats in each group was measured. The results are shown in Table 1.

[0055] Table 1 Comparison of knee joint diameters in each group (mm, )

[0056]

[0057] The results showed that the knee joint diameter of rats in the kidney deficiency, dampness and blood stasis type knee osteoarthritis model group was significantly larger than that in the sham operation control group; while the knee joint diameter of rats after Chinese medicine treatment was significantly smaller than that in the model group, and the degree of reduction in the Chinese medicine composition group of Example 1 was the most significant.

[0058] 5. The articular cartilage of rats in each group was stained with safranin-O-fast green, and the OARSI score of articular cartilage pathology was performed. The scoring results were statistically analyzed. The results are shown in Table 2.

[0059] Table 2 Comparison of OARSI scores of knee cartilage pathology in each group

[0060]

[0061] The results showed that the OARSI score of the knee articular cartilage of rats in the kidney deficiency, dampness and stasis type knee osteoarthritis model group was significantly higher than that in the sham operation control group (the more severe the articular cartilage damage, the higher the OARSI score); while the OARSI score of the knee articular cartilage of rats after Chinese medicine treatment was significantly lower than that in the model group, and the degree of reduction in the Chinese medicine composition group in Example 1 was the most significant.

[0062] The above results show that the Chinese medicine composition of Example 1 is more effective in treating kidney deficiency, dampness and blood stasis type knee osteoarthritis, so the Chinese medicine composition of Example 1 was selected for subsequent clinical research.

[0063] Test Example 2: Verification of the therapeutic effect of the Chinese medicine composition

[0064] 1. Selection, grouping and drug intervention of research subjects

[0065] (1) Research subjects and sample size

[0066] As a clinical pre-experiment, according to my country's new drug registration management regulations, 30 subjects are included in each group of the Phase I clinical trial. Based on the expected 15% loss rate, a total of 70 subjects are required for the two groups. This experiment adopts a randomized controlled method. The 70 subjects who meet the inclusion criteria are divided into an experimental group and a control group according to the inclusion number, with 35 subjects in each group.

[0067] (2) Intervention methods

[0068] Control group: Oral administration of celecoxib 200 mg, once a day, 1 tablet each time.

[0069] Experimental group: On the basis of the control group, the Chinese medicine composition prepared in Example 1 was given, 150 mL each time, twice a day.

[0070] Both groups of patients received health education and were guided to do functional exercises while taking oral medication. These exercises included straight leg raises, wall squats, and cycling. The experiment lasted for 12 weeks, with each course of treatment lasting 2 weeks. Follow-up observation was conducted 8 weeks after the end of treatment.

[0071] (3) Observation time: before treatment, 4th week after treatment, and 12th week after treatment.

[0072] 2. General indicator observation

[0073] Observation of general indicators: The patient's personal information includes name, gender, age, course of disease, site of disease (unilateral or bilateral knee joint), height and weight, etc.

[0074] After screening, a total of 70 participants were included, and after random assignment, there were 35 subjects in both the experimental group and the control group. As shown in Table 3, in this clinical study, there was no significant difference in gender between the two groups of subjects; there was no significant difference in age group between the two groups of subjects; there was no significant difference in disease course between the two groups of subjects; there was no significant difference in BMI between the two groups of subjects; there was no significant difference in the site of disease between the two groups of subjects.

[0075] Table 3 General indicators observation

[0076]

[0077] Note: BMI: Body Mass Index.

[0078] 3. WOMAC score

[0079] The WOMAC Osteoarthritis Index score is used to assess the severity and efficacy of arthritis based on the patient's relevant symptoms and signs, including pain, stiffness, and joint function, and is used to assess the structure and function of the knee joint. This scale is designed to have a total score of 88 points, and the higher the score, the more severe the condition.

[0080] The WOMAC scores of the experimental group and the control group at each observation time point were statistically analyzed. The results are shown in Table 4.

[0081] Table 4 Median of WOMAC scores before and after treatment in the two groups of patients (P25, P75)

[0082]

[0083] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0084] 4. Visual Analog Scale (VAS) score for pain

[0085] Pain visual analogue scale (VAS): The pain severity was assessed using a 0-10 numeric pain rating scale (NRS), where 0 represented no pain, 5 represented moderate pain, and 10 represented unbearable pain.

[0086] The VAS scores of the two groups at each observation time point were statistically analyzed, and the results are shown in Table 5.

[0087] Table 5 VAS median (P25, P75) of the two groups of patients before and after treatment

[0088]

[0089] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0090] The results showed that at the three observation time points during the 12-week treatment period, the time effect of VAS scores was statistically significant, indicating that the VAS scores of both groups of patients showed a downward trend over time during the treatment period; the results of the self-comparison before and after treatment showed that the differences between the two groups before and after treatment were statistically significant, indicating that the experimental group and the control group had a definite effect in improving the VAS scores of patients. At 4 weeks and 12 weeks, the VAS scores of the experimental group were significantly lower than those of the control group, indicating that the experimental group had more advantages than the control group in improving the VAS scores of patients.

[0091] 5. SF-36 score

[0092] In assessing the quality of life, the widely used scale includes 36 questions and 8 dimensions, which are used to assess physical function, physical role, bodily pain, general health, energy, social function, emotional role, and mental health. Each dimension has a specific scoring standard and meaning.

[0093] 5.1 The scoring criteria are as follows:

[0094] (1) Overall health status: from very good (5 points) to poor (1 point).

[0095] (2) Health status compared with one year ago: much better than one year ago (1 point), better than one year ago (2 points), about the same as one year ago (3 points), worse than one year ago (4 points), much worse than one year ago (5 points). (3) Health and daily activities: including heavy physical activities, moderate activities, carrying daily necessities, climbing stairs, bending over and kneeling, etc. The degree of restriction of each activity is divided into very restricted (1 point), somewhat restricted (2 points), and no restriction (3 points).

[0096] (4) Work and daily activities: whether the time spent on work or other activities was reduced, whether the things that were intended to be done were completed, how difficult it was to complete the work, etc. The answer to each question was yes (1 point) or no (2 points).

[0097] 5.2 Evaluation significance

[0098] (1) Overall health status: reflects an individual's overall evaluation of his or her own health status.

[0099] (2) Health status compared with 1 year ago: The changing trend of health status was assessed.

[0100] (3) Health and daily activities: measured physical function, pain level, and ability to carry out daily activities.

[0101] (4) Work and daily activities: The impact of health status on work and daily life was assessed.

[0102] 5.3 Scoring range and significance

[0103] The score of each dimension ranges from 0 to 100, with 0 representing the worst and 100 representing the best. The higher the score, the better the health status and the higher the quality of life. The score of the SF-36 scale can provide a comprehensive understanding of the individual's health status and quality of life, and provide a scientific basis for medical intervention and lifestyle adjustment, thereby improving people's health level and quality of life.

[0104] (1) Physiological function score

[0105] The physiological function scores of the two groups at each observation time point were statistically analyzed, and the results are shown in Table 6.

[0106] Table 6 Median (P25, P75) of physiological function of the two groups of patients before and after treatment

[0107]

[0108] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0109] The results showed that at the three observation time points during the 12-week treatment period, the time effect of physiological function scores was statistically significant, indicating that the physiological function scores of both groups of patients showed an upward trend over time during treatment.

[0110] The results of the self-comparison before and after treatment showed that the differences between the two groups were statistically significant, indicating that the experimental group and the control group had a definite therapeutic effect in improving the physiological function scores of patients. There was no statistically significant difference in the physiological function scores between the experimental group and the control group at 4 weeks and 12 weeks, indicating that there was no significant difference between the experimental group and the control group in improving the physiological function scores.

[0111] (2) Physiological function score

[0112] The physiological function scores of the two groups at each observation time point were statistically analyzed, and the results are shown in Table 7.

[0113] Table 7 Median of physiological functions of the two groups of patients before and after treatment (P25, P75)

[0114]

[0115] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0116] The results showed that there was a statistically significant difference in the time effect of physiological function scores at the three observation points during the 12-week treatment period, indicating that the physiological function scores of both groups of patients showed an upward trend over time during treatment.

[0117] The results of the self-comparison between the two groups before and after treatment showed that the differences between the two groups before and after treatment were statistically significant, indicating that the experimental group and the control group had definite therapeutic effects in improving the physiological function scores of patients. There was no statistically significant difference in the physiological function scores between the experimental group and the control group at 4 weeks and 12 weeks, indicating that there was no significant difference between the experimental group and the control group in improving the physiological function scores of patients.

[0118] (3) Body pain score

[0119] The body pain scores of the two groups at each observation time point were statistically analyzed, and the results are shown in Table 8.

[0120] Table 8 Median of body pain in the two groups of patients before and after treatment (P25, P75)

[0121]

[0122] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0123] The results showed that there was a statistically significant difference in the time effect of body pain scores at three observation points during the 12-week treatment period, indicating that the body pain scores of both groups of patients showed an upward trend over time during the treatment period.

[0124] The results of the self-comparison between the two groups before and after treatment showed that the differences between the two groups before and after treatment were statistically significant, indicating that the experimental group and the control group had definite therapeutic effects in improving the body pain scores of patients. There was no statistically significant difference in the body pain scores between the experimental group and the control group at 4 weeks; there was a statistically significant difference in the body pain scores between the experimental group and the control group at 12 weeks, indicating that the experimental group had more advantages than the control group in improving the body pain scores of patients in the long-term efficacy.

[0125] (4) General health score

[0126] The general health scores of the two groups at each observation time point were statistically analyzed, and the results are shown in Table 9.

[0127] Table 9 Median of general health status of the two groups of patients before and after treatment (P25, P75)

[0128]

[0129] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0130] The results showed that at the three observation points during the 12-week treatment period, the time effect difference of general health scores was statistically significant, indicating that the general health scores of both groups of patients showed an upward trend over time during the treatment period.

[0131] The comparison between the two groups before and after treatment showed that the differences between the two groups before and after treatment were statistically significant, indicating that the experimental group and the control group had definite therapeutic effects in improving the general health scores of patients. At 12 weeks, the general health scores of the control group and the experimental group were compared, and the difference was statistically significant, indicating that the experimental group had more advantages than the control group in improving the general health scores of patients.

[0132] (5) Energy score

[0133] The energy scores of the two groups at each observation time point were statistically analyzed, and the results are shown in Table 10.

[0134] Table 10 Median (P25, P75) of energy in the two groups of patients before and after treatment

[0135]

[0136] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0137] The results showed that at the three observation time points during the 12-week treatment period, the time effect of energy scores was statistically significant, indicating that the energy scores of both groups of patients showed an upward trend over time during treatment.

[0138] The results of the comparison between the two groups before and after treatment showed that the differences between the two groups before and after treatment were statistically significant, indicating that the experimental group and the control group had definite therapeutic effects in improving the patients' energy scores. The energy scores of the control group and the experimental group were compared at 4 weeks and 12 weeks, and the differences were statistically significant, indicating that the experimental group had more advantages than the control group in improving the patients' energy scores.

[0139] (6) Social function score

[0140] The social function scores of the two groups at each observation point were statistically analyzed, and the results are shown in Table 11.

[0141] Table 11 Median of social function of the two groups of patients before and after treatment (P25, P75)

[0142]

[0143] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0144] The results showed that there was a statistically significant difference in the time effect of social function scores at the three observation points during the 12-week treatment period, indicating that the social function scores of both groups of patients showed an upward trend over time during treatment.

[0145] The comparison between the two groups before and after treatment showed that there were statistically significant differences between the two groups before and after treatment, indicating that the experimental group and the control group had definite therapeutic effects in improving the social function scores of patients. There was no statistically significant difference in the social function scores between the control group and the experimental group at 4 weeks and 12 weeks, indicating that there was no significant difference between the experimental group and the control group in improving the social function scores of patients.

[0146] (7) Emotional function score

[0147] The emotional function scores of the two groups at each observation point were statistically analyzed, and the results are shown in Table 12.

[0148] Table 12 Median of emotional function of the two groups of patients before and after treatment (P25, P75)

[0149]

[0150] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0151] The results showed that at the three observation points during the 12-week treatment period, the time effect of emotional function scores was statistically significant, indicating that the emotional function scores of both groups of patients showed an upward trend over time during treatment.

[0152] The comparison between the two groups before and after treatment showed that there were statistically significant differences between the two groups before and after treatment, indicating that the experimental group and the control group had definite therapeutic effects in improving the emotional function scores of patients. There was no statistically significant difference in the emotional function scores between the control group and the experimental group at 4 weeks and 12 weeks, indicating that there was no significant difference between the experimental group and the control group in improving the emotional function scores of patients.

[0153] (8) Mental health score

[0154] The mental health scores of the two groups at each observation point were statistically analyzed, and the results are shown in Table 13.

[0155] Table 13 Median of mental health of the two groups of patients before and after treatment (P25, P75)

[0156]

[0157] Note: Since the data do not follow a normal distribution, the rank sum test of multiple samples (Kruskal-Wallis H test) was used.

[0158] The results showed that there was a statistically significant difference in the time effect of mental health scores at three observation points during the 12-week treatment period, indicating that the mental health scores of both groups of patients showed an upward trend over time during treatment.

[0159] The two groups were compared before and after treatment using paired signed rank test. The differences between the two groups before and after treatment were statistically significant, indicating that the experimental group and the control group had definite efficacy in improving the mental health scores of patients. The mental health scores of the control group and the experimental group were compared at 4 weeks and 12 weeks, and the differences were statistically significant, indicating that the experimental group had more advantages than the control group in improving the mental health scores of patients.

[0160] 6. Safety evaluation index results

[0161] The main safety evaluation indicators include the determination of blood urea (Urea), blood creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the subjects before treatment and 4 weeks after treatment. The safety indicators of the two groups before and after treatment were statistically analyzed, and the results are shown in Table 14.

[0162] Table 14 Median (P25, P75) of safety indicators before and after treatment in the two groups of patients

[0163]

[0164] Note: Since the data do not follow a normal distribution, a two-sample rank sum test (Mann-Whitney U test) was used.

[0165] The results showed that there was no statistically significant difference in safety indicators between the experimental group and the control group before and after treatment, indicating that there was no significant difference in safety evaluation between the experimental group and the control group.

[0166] 7. Comparison of clinical efficacy

[0167] According to the Technical Guidelines for Clinical Research of Syndrome-Based New Chinese Medicines (2018), the efficacy is evaluated in 4 levels: clinical cure, marked effect, effective, and ineffective. The total effective rate is the sum of clinical cure, marked effect, and effective. This clinical trial uses the nimodipine scoring method to calculate the improvement rate of the WOMAC total score based on the total score of the subject's WOMAC osteoarthritis index, and the formula is: [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%.

[0168] The efficacy evaluation criteria are as follows:

[0169] (1) The improvement rate of WOMAC total score, i.e., efficacy index ≥ 75%, can be regarded as clinical recovery;

[0170] (2) The improvement rate of the WOMAC total score, i.e., the efficacy index was ≥50%, and <75% was considered as markedly effective;

[0171] (3) The improvement rate of the WOMAC total score, i.e., the efficacy index was ≥30%, and <50% was considered effective;

[0172] (4) The improvement rate of the WOMAC total score, i.e., the efficacy index, was less than 30% and was considered ineffective.

[0173] (5) Total effective rate = (number of clinically cured cases + number of markedly effective cases + number of effective cases) / total number of cases

[0174] The chi-square test was used to compare the clinical efficacy between the two groups, and the results are shown in Table 15.

[0175] Table 15 Comparison of clinical efficacy between the two groups (%)

[0176]

[0177] The results showed that the clinical efficacy of the experimental group was significantly higher than that of the control group, and there was a statistically significant difference, indicating that the efficacy of the experimental group was more advantageous than that of the control group.

[0178] 8. Adverse reactions

[0179] Observe and record the adverse reactions of patients and other adverse events during treatment, such as dizziness, headache, fatigue, stomach discomfort, nausea, vomiting or sleep disorders. During this study, 3 cases of adverse reactions occurred in the experimental group and the control group, including 2 cases in the experimental group and 1 case in the control group. All 3 cases were stomach discomfort, which was considered to be related to oral celecoxib. The stomach discomfort disappeared after oral omeprazole. No special adverse reactions were observed in the remaining cases.

[0180] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness, characterized in that: The preparation method comprises the following raw materials in parts by weight: 7.5-30 parts of polygonum cuspidatum, 7.5-30 parts of achyranthes bidentata, 10-40 parts of kelp, 7.5-30 parts of epimedium, 7.5-30 parts of mulberry branches, 10-40 parts of coix seeds, 5-20 parts of earthworm, 5-20 parts of salvia miltiorrhiza, 7.5-30 parts of red peony root and 15-60 parts of astragalus.

2. The Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness as claimed in claim 1, characterized in that: The preparation comprises the following raw materials in parts by weight: 15 parts of Polygonum cuspidatum, 15 parts of Achyranthes bidentata, 20 parts of Rhizoma Coptidis, 15 parts of Epimedium, 15 parts of Morus alba, 20 parts of Coix seeds, 10 parts of Eupolyphaga sinensis, 10 parts of Salvia miltiorrhiza, 15 parts of Paeonia lactiflora and 30 parts of Astragalus.

3. A method for preparing the Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness as claimed in any one of claims 1 to 2, characterized in that: The following steps are involved: (1) weighing the raw materials according to the weight ratio, soaking them in water and then boiling them, and filtering them to obtain a filtrate and a filter residue; (2) adding water to the filter residue obtained in step (1), boiling the mixture, and filtering the mixture twice to obtain a filtrate and a filter residue; (3) collecting the filtrates obtained by filtering in step (1) and step (2) and mixing them to obtain the Chinese medicine composition for tonifying the kidney, promoting blood circulation and removing dampness.

4. The method for preparing the Chinese medicine composition for invigorating the kidney, promoting blood circulation and removing dampness as claimed in claim 3, characterized in that: In the step (1), the weight ratio of water to the raw material is (6-10):1; in the step (2), the weight ratio of water to the filter residue is (2-6):

1.

5. Use of the Chinese medicinal composition for invigorating the kidney, promoting blood circulation and removing dampness as claimed in any one of claims 1 to 2 in the preparation of a medicament for treating knee osteoarthritis.

6. The use according to claim 5, characterized in that The type of the knee osteoarthritis is kidney deficiency, dampness and blood stasis type knee osteoarthritis.

7. A drug for treating knee osteoarthritis, characterized in that: A Chinese medicinal composition for tonifying the kidney, promoting blood circulation and removing dampness comprising any one of claims 1 to 2.

8. The drug for treating knee osteoarthritis according to claim 7, characterized in that: Also included are pharmaceutically acceptable excipients.

9. The drug for treating knee osteoarthritis according to claim 7, characterized in that: The dosage form of the medicine is granules, tablets, pills or capsules.

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