Bone arthralgia removing composition for treating knee osteoarthritis as well as preparation method and application of bone arthralgia removing composition

Abstract

The invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a bone arthralgia removing composition for treating knee osteoarthritis as well as a preparation method and application of the bone arthralgia removing composition. The traditional Chinese medicine composition is prepared from 5-15 parts of cassia twig, 5-15 parts of radix clematidis, 5-15 parts of Chinese prickly ash, 5-15 parts of radix saposhnikoviae, 5-15 parts of radix achyranthis bidentatae, 5-15 parts of lycopodium clavatum, 5-15 parts of garden balsam stem, 5-15 parts of fructus liquidambaris, 5-15 parts of cortex erythrinae, 5-15 parts of ligusticum wallichii, 5-15 parts of obscured homalomena rhizome and 5-15 parts of cowherb seed. The traditional Chinese medicine composition can improve the effect of treating knee osteoarthritis.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine compositions, and in particular relates to a Gubitong composition for treating knee osteoarthritis, a preparation method and use thereof. Background Art

[0002] Knee arthritis is a disease based on degenerative pathological changes, which mostly affects the middle-aged and elderly population. Its symptoms are mostly red, swollen and painful knees, pain when going up and down stairs, and knee pain and discomfort when sitting or standing up. Some patients may also experience swelling, snapping, and effusion. If not treated in time, it will cause joint deformity and disability. In the knee joint area, joint diseases such as knee synovitis, ligament injury, meniscus injury, loose bodies in the knee joint, popliteal cysts, patellar softening, anserine bursitis, and knee valgus / valgus are also common.

[0003] A multi-dimensional analysis of the medication and symptom patterns of knee osteoarthritis based on data mining, Huang Zhaohan, a doctoral dissertation from Beijing University of Chinese Medicine, published on 2023-05-01, discloses relevant Chinese medicines for the treatment of knee osteoarthritis. The results of external Chinese medicines in Section 4 show that ancient medicines with a high frequency of myrrh, Chuanwu, frankincense, angelica, Chinese angelica, ginger, and cinnamon appear. Modern medicines with a high frequency of Achyranthes bidentata, Chuanwu, safflower, smilax glabra, radix spatholobi, angelica, aconite, cassia twig, and asarum appear. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a Gubitong composition for treating knee osteoarthritis, a preparation method and use thereof, so as to improve the effect of treating knee osteoarthritis.

[0005] The embodiment of the present invention provides a Gubitong composition for treating knee osteoarthritis, comprising the following components in parts by weight: 5-15 parts of cinnamon twig, 5-15 parts of clematis, 5-15 parts of zanthoxylum, 5-15 parts of siler, 5-15 parts of siler, 5-15 parts of achyranthes bidentata, 5-15 parts of smilax china, 5-15 parts of radix polygoni aviculare, 5-15 parts of rhizoma smilacis Glabrae, 5-15 parts of pittosporum tobira bark, 5-15 parts of ligusticum chuanxiong, 5-15 parts of rhizoma schizonepetae, and 5-15 parts of fenugreek.

[0006] Preferably, the following components are included in parts by weight: 8-12 parts of cassia twig, 8-12 parts of clematis, 8-12 parts of zanthoxylum, 8-12 parts of siler, 8-12 parts of radix saposhnikoviae, 8-12 parts of cyathulae, 8-12 parts of herba schizonepetae, 8-12 parts of schizonepeta tenuifolia, 8-12 parts of herba schizonepetae, 8-12 parts of rhizoma schizonepetae, 8-12 parts of bark of pittosporum tobira, 8-12 parts of rhizoma ligusticum, 8-12 parts of herba schizonepetae, and 8-12 parts of fenugreek.

[0007] More preferably, it comprises the following components in parts by weight: 10 parts of cinnamon twig, 10 parts of clematis, 10 parts of zanthoxylum, 10 parts of siler, 10 parts of radix saposhnikoviae, 10 parts of cyathulae, 10 parts of herba schizonepetae, 10 parts of schizonepeta tenuifolia, 10 parts of herba schizonepetae, 10 parts of rhizoma schizonepetae, 10 parts of bark of pittosporum tobira, 10 parts of rhizoma ligustici, 10 parts of rhizoma schizonepetae, and 10 parts of fenugreek.

[0008] When used, it can be used together with oral glucosamine sulfate.

[0009] The embodiment of the present invention provides a method for preparing the Gubitong composition, which comprises mixing the components in parts by weight, boiling with water, and concentrating to obtain the Gubitong composition.

[0010] Preferably, after mixing the components by weight, they are soaked in water for at least 30 minutes before being boiled in water.

[0011] The embodiment of the present invention provides a use of the Gubitong composition in preparing a medicine for treating knee osteoarthritis.

[0012] Preferably, the dosage form of the drug is an external lotion.

[0013] The beneficial effect of the present invention is that the present invention selects cassia twig, clematis, zanthoxylum bungeanum, siler, achyranthes bidentata, herba schizonepetae, herba schizonepetae, rhizoma ... herba schizonepetae, herba schizonepetae, herba schizonepetae, herba schizonepetae, rhizoma chuanxiong, herba qiannianjian and herba schizonepetae as the traditional Chinese medicine composition for treating knee osteoarthritis. Clinical experiments have shown that the present invention has better effects in relieving pain, improving the stiffness of knee joints, improving the health of knee osteoarthritis, and alleviating the degeneration of knee joints than the combination of cassia twig, clematis, achyranthes bidentata, herba schizonepetae, herba schizonepetae and herba schizonepetae, and can effectively improve the effect of treating knee osteoarthritis. DETAILED DESCRIPTION

[0014] Example 1

[0015] A bone-binding composition for treating knee osteoarthritis comprises the following components by weight: 10g of cinnamon twig, 10g of clematis, 10g of zanthoxylum bungeanum, 10g of siler, 10g of radix siler, 10g of achyranthes bidentata, 10g of herba striatae, 10g of herba schizonepetae, 10g of rhizoma spatholobi, 10g of rhizoma schizonepetae, 10g of herba ...

[0016] The preparation method is as follows: first, soak the medicine in 5000g of water for 30min, then decoct and take 3000ml of medicine juice.

[0017] The method of use is to steam the knee joint with the medicinal juice while it is still hot, and then soak the knee joint in a bath for 10 minutes after the medicinal juice becomes warm.

[0018] Comparative Example 1

[0019] A Chinese medicine composition for treating knee osteoarthritis comprises the following components by weight: 20g of cinnamon twig, 20g of clematis root, 20g of achyranthes bidentata, 20g of smilax china, 20g of radix spatholobi, 20g of herba schizonepetae, and 20g of rhizoma ligustici. Other components are the same as those in Example 1.

[0020] Example 2

[0021] The effect of the Gubitong composition was tested, and the experimental scheme was as follows.

[0022] 1.1 Information

[0023] 1.1.1 General Information:

[0024] A total of 90 patients with cold-dampness-blocking knee osteoarthritis who visited the inpatient and outpatient departments of the Department of Orthopedics of the First Affiliated Hospital of Hunan University of Chinese Medicine from April 2023 to December 2023 were enrolled in the study. They were numbered 1-90 according to the order of visit and randomly divided into a western medicine group, a Gubitong group, and a control group 1 according to a random number table, with 30 cases in each group (each patient completed Appendix 1 and filed it). In the western medicine group, there were 12 males and 18 females; the age was 50-69 years old, with an average age of (53.66±13.01) years and an average course of disease of (4.07±2.27) years. In the Gubitong group, there were 13 males and 17 females; the age was 50-70 years old, with an average age of (53.07±12.22) years and an average course of disease of (3.78±2.14) years. In the control group 1, there were 12 males and 18 females, aged 49 to 70 years, with an average age of (53.71±11.42) years and an average disease course of (3.68±2.09) years. There were no significant differences in age, gender, body mass index (BMI), disease course, Kellgren-Lawrence grade, visual analogue scale (VAS score), Western Ontario and McMaster University osteoarthritis index score (WOMAC score), and Japanese knee osteoarthritis evaluation scale (JKOM) function scale among the three groups (P>0.05), and they were comparable (comparison of age, gender, BMI, disease course, and KL grade is shown in Table 1).

[0025] Table 1 Comparison of age, gender, BMI, disease course and KL grade among the three groups of patients before treatment

[0026]

[0027] 1.1.2 Diagnostic criteria

[0028] Western medicine diagnostic criteria: Clinical diagnostic criteria (reference standard: Guidelines for the diagnosis and treatment of knee osteoarthritis in combination with traditional Chinese and Western medicine (2023 edition)): (1) recurrent knee pain within the past month; (2) age ≥50 years; (3) morning stiffness ≤30 minutes; (4) bone friction sound (feeling) during activity; (5) X-rays (standing or weight-bearing position) showing narrowing of the joint space, subchondral bone sclerosis and (or) cystic changes, and osteophyte formation at the joint margin. The diagnosis can be made if any two of (1) and (2)(3)(4)(5) are met.

[0029] The TCM diagnostic criteria refer to the Guidelines for the Diagnosis and Treatment of Knee Osteoarthritis with Integrated Traditional Chinese and Western Medicine (2023 Edition). Cold-dampness-blocking type: (1) Main symptoms: Severe pain in the knee joint, aggravated by cold and relieved by warmth. (2) Secondary symptoms: Severe pain in the waist and body. (3) Tongue and pulse: Pale tongue with greasy white fur; soft and slow pulse.

[0030] Kellgren-Lawrence imaging grading standard: Grade 0: no change (normal); Grade I: suspected osteophytes, normal joint space; Grade II: definite osteophytes, suspected narrowing of the joint space; Grade III: moderate osteophytes, definite narrowing of the joint space, and sclerotic changes; Grade IV: large amounts of osteophytes, obvious narrowing of the joint space, severe sclerotic changes, and obvious deformities.

[0031] 1.1.3 Inclusion criteria

[0032] (1) The patients meet the above-mentioned disease and classification diagnostic criteria; KL classification standard I-III; (2) Age 50-70 years old; (3) No medication or related treatment in the past month; (4) No abnormality in rheumatoid, rheumatic, autoimmune, infection and other indicators; (5) No medical complications such as hypertension and coronary heart disease, and no arthritis in other parts of the body; (6) Normal fecal parasite detection, no history of abnormal bowel movements or gastrointestinal diseases; (7) No history of long-term antibiotic use, and the antibacterial or antibacterial drugs have been discontinued for more than 1 year before specimen collection; (8) The patient signs the informed consent form and can cooperate with subsequent treatment and follow-up.

[0033] 1.1.4 Exclusion criteria

[0034] (1) Those who do not meet the above diagnostic criteria; (2) Those aged >70 years or <50 years; (3) Those who are not within the scope of action of this drug; (4) Those who are at grade 0 and IV in the KL grading standard; (5) Those with acute synovitis and large amounts of joint effusion; (6) Those with complications that affect the joints, such as psoriasis, metabolic bone disease, acute trauma, etc.; (7) Those with allergic constitution or those who are allergic to the drug ingredients contained in this prescription; (8) Those with serious underlying medical diseases such as heart, brain, liver, kidney and respiratory system, mental disorders, hereditary diseases; patients with major systemic diseases such as tumors; (9) Women who are breastfeeding, pregnant or preparing for pregnancy; (10) Those with poor compliance and difficulty in seeing a doctor for follow-up on time.

[0035] 1.1.5 Shedding standards and treatment principles:

[0036] Dropout criteria: (1) patients who fail to receive treatment as prescribed, resulting in the inability to evaluate efficacy; (2) patients whose data are incomplete and affect the evaluation of efficacy or safety; (3) patients who are unable to continue treatment due to unexpected events during treatment; (4) patients who do not cooperate with the treatment during treatment; (5) subjects who voluntarily request to terminate the trial.

[0037] Principles of treatment: (1) Record the time and reason of subject dropout in detail, and record as many evaluable indicators as possible; (2) Contact subjects who have serious adverse reactions or who have withdrawn from the study because their condition has not improved or has worsened in a timely manner, and take relevant measures based on their individual circumstances; (3) Properly keep relevant information such as cases of subject dropouts, and do not allow additional dropout subjects to be added.

[0038] 1.2 Treatment methods

[0039] Western medicine group: oral administration of glucosamine sulfate (Isojia, Zhejiang Hisun Pharmaceutical Co., Ltd.), 2 capsules at a time, 3 times a day, for 12 consecutive weeks.

[0040] Gubitong group: In addition to oral glucosamine sulfate (Isojia, Zhejiang Hisun Pharmaceutical Co., Ltd.) (same usage as western medicine group), the Gubitong composition external wash formula of Example 1 was used to fumigate and wash the knee joint; once a day after enrollment for 12 consecutive weeks.

[0041] Usage: Soak the medicine in water for 30 minutes, decoct it in water, take 3000ml of the juice, steam the knee joint while it is hot, and soak the knee joint for 10 minutes after the juice becomes warm. The above Chinese medicines are all provided by the hospital outpatient Chinese medicine pharmacy.

[0042] Comparative Example 1: In addition to oral glucosamine sulfate (Isojia, Zhejiang Hisun Pharmaceutical Co., Ltd.) (same usage as western medicine group), the knee joints were fumigated with the Chinese medicine of Comparative Example 1; once a day after enrollment, for 12 consecutive weeks.

[0043] Usage: Soak the medicine in water for 30 minutes, decoct it in water, take 3000ml of the juice, steam the knee joint while it is hot, and soak the knee joint for 10 minutes after the juice becomes warm. The above Chinese medicines are all provided by the hospital outpatient Chinese medicine pharmacy.

[0044] During the treatment, patients were not allowed to take nonsteroidal anti-inflammatory drugs orally, avoid intra-articular injections, and temporarily not receive other external treatments of traditional Chinese medicine, acupuncture and massage. Patients were guided to perform quadriceps muscle function exercises to reduce the burden on the knee joints, such as standing for a long time, climbing stairs, and climbing mountains.

[0045] Note: If the patient experiences severe pain during treatment, nonsteroidal anti-inflammatory drugs can be taken for emergency analgesia and the pain relief should be recorded.

[0046] 1.3 Observation indicators and evaluation criteria

[0047] 1.3.1 Observation indicators

[0048] (1) Pain VAS score

[0049] The patients scored their pain sensations on the corresponding scale, with 0 indicating no pain and 10 indicating severe pain. The assessment was conducted before treatment and 12 weeks after treatment.

[0050] (2) WOMAC score for osteoarthritis

[0051] The pain, stiffness and joint function improvement of the three groups of patients were observed and recorded, and the WOMAC assessment scale was used to score, including 24 items in three aspects: joint pain degree, stiffness degree and difficulty in daily activities. Each item was divided into 0 points: normal; 1 point: mild; 2 points: moderate; 3 points: severe; 4 points: extremely severe; the total score was expressed by the total score of each component item. The higher the WOMAC score, the more severe the symptoms, and the efficacy was evaluated based on this. The evaluation was conducted before treatment and 12 weeks after treatment.

[0052] (3) Knee joint function

[0053] The Japanese knee osteoarthritis evaluation scale (JKOM) was used to evaluate knee joint function. The JKOM scale was developed based on Asian lifestyle, health status and environmental characteristics and is a patient self-rating scale. The JKOM scale includes 5 parts: knee pain, daily activities, daily activities, health status and pain and stiffness, with a total of 25 items. Each item uses a five-level scoring method of 0-4 points, with a total score of 100 points. The evaluation was conducted before treatment and 12 weeks after treatment.

[0054] (4) X-ray examination

[0055] The hospital's X-ray equipment was used to take X-rays to assess the degeneration of the knee joint. The assessment was done once before treatment and 12 weeks after treatment. The grades were determined according to the Kellgren-Lawrence imaging grading standard.

[0056] (5) Clinical efficacy evaluation

[0057] Formulated with reference to the "Guidelines for Clinical Research of New Chinese Medicines". Syndrome score reduction rate = (score before treatment - score after treatment) / score before treatment × 100%. The criteria for judging clinical efficacy are divided into the following 4 levels: Cure: symptoms and signs disappear or basically disappear, and the TCM syndrome score reduction rate ≥ 95%; Marked effect: symptoms and signs are significantly improved, and the TCM syndrome score reduction rate ≥ 70% but < 95%; Effective: symptoms and signs are improved, and the TCM syndrome score reduction rate ≥ 30% but < 70%; Ineffective: symptoms and signs are not significantly improved, or even aggravated, and the TCM syndrome score reduction is < 30%. Evaluate 12 weeks after treatment. (See Appendix 2 for the TCM syndrome and sign score scale)

[0058] (6) Safety analysis

[0059] During the treatment, each patient was followed up regularly to record whether any adverse reactions such as skin allergies, skin ulcers, and rashes occurred, and to monitor whether there were any abnormal changes in the patient's blood routine, urine routine, liver and kidney function before and after treatment.

[0060] 1.3.2 Laboratory testing indicators

[0061] Joint fluid was collected from all patients before and 12 weeks after treatment, and Elisa test-related reagents and collected serum were prepared. Blank wells, standard wells, and test sample wells were set up respectively. 100ul of the corresponding concentration gradient standard sample was added to each standard well, and 80ul of the detection buffer and 20ul of the sample were added to the sample well. Oscillating, incubating at room temperature, washing, adding diluted horseradish peroxidase-labeled streptavidin, oscillating, incubating at room temperature, washing, adding display substrate, incubating at room temperature in the dark, adding stop solution, and detecting with an enzyme marker. Detect the levels of IL-6, TNF-α, PGE2, etc.

[0062] 1.4 Statistical methods SPSS 25.0 software was used for data analysis. =Indicates; the comparison of gender and KL grade was performed by χ2 test; the comparison of different time points within the group was performed by repeated measures analysis of variance, the comparison of each time point with the pre-treatment was performed by paired sample t test, and the comparison between groups at the same time point was performed by independent sample t test. P<0.05 was considered statistically significant.

[0063] 2 Results

[0064] 2.1 Comparison of VAS scores among the three groups of patients before and after treatment

[0065] Before treatment, there was no significant difference in VAS scores among the western medicine group, Gubitong group and control group 1 (P>0.05), which was comparable; the differences in VAS scores before and after treatment within the three groups were statistically significant (P<0.001), indicating that the pain of the three groups of KOA patients improved after treatment, and the VAS scores of KOA patients in the Gubitong group decreased more than those in the other three groups (P<0.05). The results are as follows (Table 2-1).

[0066] Table 2-1 Comparison of VAS scores of the three groups of patients before and after treatment (points, Mean ± SD)

[0067]

[0068] Note: Compared with the group before treatment, *P<0.001**P<0.05; compared with the Western medicine group, ▲ P < 0.001, ▲▲ P<0.05; compared with control group 1, △ P < 0.001, △△ P<0.05.

[0069] 2.2 Comparison of WOMAC scores of osteoarthritis among the three groups of patients before and after treatment

[0070] Before treatment, there was no significant difference in WOMAC scores among the western medicine group, Gubitong group and control group 1 (P>0.05), which were comparable; the differences in WOMAC scores before and after treatment within the three groups were statistically significant (P<0.001), indicating that the three groups were improved after treatment; compared between the groups, the differences in scores among the three groups after treatment were statistically significant (P<0.05), indicating that the WOMAC scores of patients in the Gubitong group were lower than those in the other three groups. The results are as follows (Table 2-2).

[0071] Table 2-2 Comparison of WOMAC scores among the three groups of patients before and after treatment (points, Mean ± SD)

[0072]

[0073] Note: Compared with the group before treatment, *P<0.001**P<0.05; compared with the Western medicine group, ▲ P < 0.001, ▲▲ P<0.05; compared with control group 1, △ P < 0.001, △△ P<0.05.

[0074] 2.3 Comparison of knee joint function among the three groups of patients before and after treatment

[0075] Before treatment, there was no significant difference in the scores of the western medicine group, Gubitong group and control group 1 (P>0.05), which was comparable; the differences in JOA scores before and after treatment within the three groups were statistically significant (P<0.001), indicating that the three groups were improved after treatment; compared between the groups, the differences in the scores of the three groups after treatment were statistically significant (P<0.05), indicating that the JOA scores of patients in the Gubitong group were lower than those in the other two groups. The results are as follows (Table 2-3).

[0076] Table 2-3 Comparison of JOA scores of the three groups of patients before and after treatment (points, Mean±SD)

[0077]

[0078] Note: Compared with the group before treatment, *P<0.001**P<0.05; compared with the Western medicine group, ▲ P < 0.001, ▲▲ P<0.05; compared with control group 1, △ P < 0.001, △△ P<0.05.

[0079] 2.4 Comparison of clinical efficacy evaluation among the three groups of patients after treatment

[0080] The clinical efficacy of the three groups of patients after treatment was compared, the total effective rate of the Western medicine group was 83.3%, the total effective rate of the Gubitong group was 90.0%, and the total effective rate of the comparative group 1 was 80.0%, and there was no statistical difference among the three groups. The results are as follows (Table 2-4).

[0081] Table 2-4 Comparison of clinical efficacy of three groups of patients after treatment (points)

[0082]

[0083] 2.5 Comparison of PGE2, IL-6 and TNF-α in the three groups before and after treatment

[0084] There was no significant difference in the content of IL-6, TNF-α, and PGE2 before treatment in the western medicine group, Gubitong group, and control group 1 (P>0.05), and they were all comparable. After treatment, IL-6, TNF-α, and PGE2 in the three groups were significantly lower than before treatment (P<0.001); and IL-6, TNF-α, and PGE2 in the Gubitong group were significantly lower than those in the other two groups (P<0.05); the results are as follows (Table 2-5).

[0085] Table 2-5 Ratio of serum inflammatory factor levels in the three groups of patients before and after treatment (pg / mL)

[0086]

[0087] Note: Compared with the group before treatment, *P<0.001**P<0.05; compared with the Western medicine group, ▲ P < 0.001, ▲▲ P<0.05; compared with control group 1, △ P < 0.001, △△ P<0.05.

[0088] 2.6 Security Analysis

[0089] During the trial, the blood routine, urine routine and liver and kidney function test results of the three groups of patients before and after treatment were normal. One patient in the western medicine group had skin itching, which was considered to be caused by the dry skin of elderly patients. The rest of the patients did not experience any discomfort.

[0090] A person skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of protection of the present application is limited to these examples. In line with the concept of the present application, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of different aspects of one or more embodiments of the present application as described above, which are not provided in detail for the sake of simplicity.

[0091] One or more embodiments of the present application are intended to cover all such substitutions, modifications and variations that fall within the broad scope of the present application. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of one or more embodiments of the present application should be included in the protection scope of the present application.

Claims

1. A Gubitong composition for treating knee osteoarthritis, characterized in that: The invention comprises the following components in parts by weight: 5-15 parts of cassia twig, 5-15 parts of clematis, 5-15 parts of zanthoxylum bungeanum, 5-15 parts of siler, 5-15 parts of radix scutellariae, 5-15 parts of herba schizonepetae, 5-15 parts of schizonepeta tenuifoliae, 5-15 parts of rhizoma spatholobi, 5-15 parts of smilax chinae, 5-15 parts of bark of pittosporum tobira, 5-15 parts of rhizoma ligusticum, 5-15 parts of rhizoma chinensis, and 5-15 parts of fenugreek.

2. The Gubitong composition according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 8-12 parts of cassia twig, 8-12 parts of clematis, 8-12 parts of zanthoxylum bungeanum, 8-12 parts of siler, 8-12 parts of radix scutellariae, 8-12 parts of herba schizonepetae, 8-12 parts of cyperus rotundus, 8-12 parts of herba schizonepetae, 8-12 parts of rhizoma schizonepetae, 8-12 parts of herba ...

3. The Gubitong composition according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 10 parts of cassia twig, 10 parts of clematis, 10 parts of zanthoxylum bungeanum, 10 parts of siler, 10 parts of radix siler, 10 parts of herba schizonepetae, 10 parts of cyathulae, 10 parts of herba schizonepetae, 10 parts of rhizoma schizonepetae, 10 parts of herba ...

4. A method for preparing the Gubitong composition according to any one of claims 1 to 3, characterized in that: The components in parts by weight are mixed, boiled with water, and concentrated to obtain the Gubitong composition.

5. The preparation method according to claim 4, characterized in that: After mixing the components by weight, soak them in water for at least 30 minutes before adding water for boiling.

6. Use of the Gubitong composition according to any one of claims 1 to 3 in the preparation of a medicament for treating knee osteoarthritis.

7. The use according to claim 6, characterized in that: The dosage form of the medicine is an external lotion.

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