Traditional Chinese medicine preparation for treating knee osteoarthritis and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine preparation for treating knee osteoarthritis and a preparation method thereof. The medicament is prepared from 25 to 35 parts of radix cyathulae, 15 to 25 parts of cortex erythrinae, 10 to 20 parts of flos carthami, 25 to 35 parts of herba lycopodii, 25 to 35 parts of beefwood-like clubmoss herb, 15 to 25 parts of rhizoma sparganii, 15 to 25 parts of rhizoma curcumae, 10 to 20 parts of pericarpium zanthoxyli, 25 to 35 parts of radix clematidis, 15 to 25 parts of folium artemisiae argyi, 15 to 25 parts of rhizoma seu radix notopterygii, 10 to 20 parts of cassia twig, 15 to 25 parts of radix angelicae pubescentis, 5 to 15 parts of frankincense, 5 to 15 parts of myrrh, 5 to 15 parts of radix aconiti preparata, 5 to 15 parts of radix aconiti kusnezoffii preparata, 5 to 15 parts of radix saposhnikoviae, 5 to By combining the traditional Chinese medicine classical theory and the clinical practical innovative formula, the traditional Chinese medicine composition shows unique pertinence and effectiveness for treating the common disease of knee osteoarthritis, especially the cold-dampness blockage syndrome.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine preparation for treating knee osteoarthritis and a preparation method thereof. Background Art

[0002] Knee osteoarthritis (K0A) is a chronic degenerative joint disease that seriously affects the quality of life of middle-aged and elderly people, and belongs to the categories of "Bi syndrome" and "Wei syndrome" in traditional Chinese medicine. Knee osteoarthritis is mainly caused by factors such as age, gender, muscle weakness, abnormal joint alignment, and obesity. The clinical manifestations include knee joint pain, limited movement, deformity, bone friction sound, muscle atrophy, and swelling. The diagnosis mainly relies on knee joint X-ray examination. The treatment methods include basic treatment (such as changing lifestyle, weight loss, low-intensity aerobic exercise, and muscle strength training), drug treatment (such as non-steroidal anti-inflammatory drugs, analgesics, and intra-articular injection treatment), physical therapy (such as cold therapy, heat therapy, and ultrasonic therapy), and assistive treatment for movement. When conservative treatment is ineffective, surgical treatment can be considered. The preventive measures include avoiding trauma, keeping warm, performing knee joint function exercises, and maintaining good living habits.

[0003] In clinical practice, the existing traditional Chinese medicine compound for treating knee osteoarthritis has poor pertinence, specificity, and convenience in clinical application. Summary of the Invention

[0004] In view of the above problems, the present invention aims to provide a traditional Chinese medicine preparation for treating knee osteoarthritis and a preparation method thereof, so as to solve at least the problems such as poor pertinence, specificity, and convenience in clinical application of the existing traditional Chinese medicine compound for treating knee osteoarthritis.

[0005] To achieve the above object, the technical solution adopted by the present invention to solve its technical problems is as follows:

[0006] A traditional Chinese medicine preparation for treating knee osteoarthritis, comprising the following raw materials: Cyathula officinalis Kuan, Cortex Erythrinae, Flos Carthami, Herba Lycopodii, Herba Lycopodiastri, Sparganium stoloniferum Buch.-Ham., Rhizoma Curcumae, Zanthoxylum schinifolium Sieb. et Zucc., Clematis chinensis Osbeck, Folium Artemisiae Argyi, Rhizoma seu Radix Notopterygii, Ramulus Cinnamomi, Herba seu Radix Angelicae Pubescentis, Olibanum, Myrrha, Radix Aconiti Carmichaeli Praeparata, Radix Aconiti Kusnezoffii Praeparata, Radix Saposhnikoviae, Herba Asari, and Borneol.

[0007] The weight portions of different raw materials are respectively: 25-35 parts of Cyathula officinalis Kuan, 15-25 parts of Cortex Erythrinae, 10-20 parts of Flos Carthami, 25-35 parts of Herba Lycopodii, 25-35 parts of Herba Lycopodiastri, 15-25 parts of Sparganium stoloniferum Buch.-Ham., 15-25 parts of Rhizoma Curcumae, 10-20 parts of Zanthoxylum schinifolium Sieb. et Zucc., 25-35 parts of Clematis chinensis Osbeck, 15-25 parts of Folium Artemisiae Argyi, 15-25 parts of Rhizoma seu Radix Notopterygii, 10-20 parts of Ramulus Cinnamomi, 15-25 parts of Herba seu Radix Angelicae Pubescentis, 5-15 parts of Olibanum, 5-15 parts of Myrrha, 5-15 parts of Radix Aconiti Carmichaeli Praeparata, 5-15 parts of Radix Aconiti Kusnezoffii Praeparata, 5-15 parts of Radix Saposhnikoviae, 5-15 parts of Herba Asari, and 1-10 parts of Borneol.

[0008] Furthermore, the weight portions of different raw materials are as follows: Cyathula officinalis Kuan 30 portions, Erythrina arborescens Roxb. 20 portions, Carthamus tinctorius L. 15 portions, Lycopodium clavatum L. 30 portions, Lycopodiastrum casuarinoides (Spring) Holub 30 portions, Sparganium stoloniferum Buch.-Ham. 20 portions, Curcuma zedoaria (Christm.) Rosc. 20 portions, Zanthoxylum schinifolium Sieb. et Zucc. 15 portions, Clematis chinensis Osbeck 30 portions, Artemisia argyi Levl. et Van. 20 portions, Notopterygium incisum Ting ex H. T. Chang 20 portions, Cinnamomum cassia Presl 15 portions, Angelica pubescens Maxim. f. biserrata Shan et Yuan 20 portions, Olibanum 10 portions, Myrrha 10 portions, Aconitum carmichaelii Debx. prepared 10 portions, Aconitum kusnezoffii Reichb. prepared 10 portions, Saposhnikovia divaricata (Turcz.) Schischk. 10 portions, Asarum sieboldii Miq. 10 portions, Borneol 5 portions.

[0009] In the present invention, the pharmacologies of different raw materials are as follows:

[0010] King drugs: Aconitum carmichaelii Debx. prepared, Aconitum kusnezoffii Reichb. prepared, dispelling wind and removing dampness, warming the channels and stopping pain.

[0011] Minister drugs: Zanthoxylum schinifolium Sieb. et Zucc., Artemisia argyi Levl. et Van., Cinnamomum cassia Presl, Asarum sieboldii Miq., Erythrina arborescens Roxb., Clematis chinensis Osbeck, Notopterygium incisum Ting ex H. T. Chang, Angelica pubescens Maxim. f. biserrata Shan et Yuan, Saposhnikovia divaricata (Turcz.) Schischk., Cyathula officinalis Kuan;

[0012] Zanthoxylum schinifolium Sieb. et Zucc.: warming the middle-jiao to stop pain, killing insects and relieving itching; Artemisia argyi Levl. et Van.: warming the channels to stop bleeding, dispelling cold and stopping pain, removing dampness and relieving itching; Cinnamomum cassia Presl: inducing sweating to release the exterior, warming and dredging the channels, promoting yang and transforming qi, calming the adverse qi; Asarum sieboldii Miq.: warming the lungs to resolve fluid-retention, expelling wind and relieving pain, inducing sweating and releasing the exterior, opening the orifices; Erythrina arborescens Roxb.: dispelling wind and dampness, dredging collaterals and stopping pain, killing insects and relieving itching; Clematis chinensis Osbeck: dispelling wind and dampness, warming the middle-jiao and dispelling cold, purging heat and relieving constipation; Notopterygium incisum Ting ex H. T. Chang: dispersing cold and relieving the exterior, dispelling wind and dampness, relieving pain; Angelica pubescens Maxim. f. biserrata Shan et Yuan: dispelling wind and dampness, relieving pain, relieving the exterior; Saposhnikovia divaricata (Turcz.) Schischk.: inducing sweating and dispersing wind, eliminating dampness and relieving pain, stopping convulsions, stopping diarrhea; Cyathula officinalis Kuan: promoting blood circulation to dredge the channels, tonifying the liver and kidney, strengthening the bones and muscles, promoting diuresis and relieving stranguria, guiding (fire) downward.

[0013] Assistant drugs: Sparganium stoloniferum Buch.-Ham., Curcuma zedoaria (Christm.) Rosc., Lycopodium clavatum L., Lycopodiastrum casuarinoides (Spring) Holub, Olibanum, Myrrha, Carthamus tinctorius L.;

[0014] Sparganium stoloniferum Buch.-Ham., Curcuma zedoaria (Christm.) Rosc.: promoting blood circulation by breaking blood stasis, removing stasis and relieving pain; Carthamus tinctorius L.: promoting blood circulation to dredge the channels, removing stasis and relieving pain; Lycopodium clavatum L.: relaxing tendons and activating collaterals, expelling wind and cold, eliminating dampness and swelling; Lycopodiastrum casuarinoides (Spring) Holub: relaxing tendons and activating collaterals, dispelling wind and dampness, improving eyesight, detoxifying; Olibanum: promoting blood circulation and qi movement to stop pain, promoting tissue regeneration and relieving swelling; Myrrha: promoting blood circulation to stop pain, promoting tissue regeneration and relieving swelling.

[0015] Guiding drug: Borneol, enhancing the transdermal effect.

[0016] Furthermore, a preparation method of a traditional Chinese medicine preparation for treating knee osteoarthritis includes the following steps:

[0017] S1: Take Cyathula officinalis Kuan, Erythrina arborescens Roxb., Carthamus tinctorius L., Lycopodium clavatum L., Lycopodiastrum casuarinoides (Spring) Holub, Sparganium stoloniferum Buch.-Ham., Curcuma zedoaria (Christm.) Rosc., Zanthoxylum schinifolium Sieb. et Zucc., Clematis chinensis Osbeck, Artemisia argyi Levl. et Van., Notopterygium incisum Ting ex H. T. Chang, Cinnamomum cassia Presl, Angelica pubescens Maxim. f. biserrata Shan et Yuan, Olibanum, Myrrha, Aconitum carmichaelii Debx. prepared, Aconitum kusnezoffii Reichb. prepared, Saposhnikovia divaricata (Turcz.) Schischk., Asarum sieboldii Miq., Borneol and grind them into fine powder.

[0018] S2: Take the above powder and add it to a paste prepared with 80°C water and 2 g of petrolatum, and wait for the temperature to drop below the skin temperature.

[0019] The beneficial effects of the present invention are as follows: Compared with the prior art, the improvements of the present invention lie in that

[0020] 1. By combining traditional Chinese medicine theory with modern clinical practice, the present invention demonstrates its unique treatment mechanism and method, which are unique in both formulation and application method. Especially when applied to the treatment of knee osteoarthritis with cold-dampness obstruction type

[0021] it has the potential to improve the curative effect and the patient's usage experience.

[0022] 2. The innovative formulation of the present invention, which combines classic Chinese medicine theory and clinical practice, shows unique pertinence and effectiveness for the common disease of knee osteoarthritis, especially in the treatment of the "cold-dampness obstruction" syndrome type. It not only has a good curative

[0023] effect basis, but also the scientific verification of the treatment formula provides new ideas for the development of new drugs, filling the gap in this field.

[0024] 3. The present invention is applied externally in the form of powder, which is not only convenient for patients to use by themselves, but also simplifies the use process of traditional Chinese medicine, meeting the modern people's requirements for the convenience and practicality of drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is the Venn diagram of the intersection targets of XBS active ingredients and KOA proposed by the present invention;

[0026] Figure 2 It is the protein-protein interaction (PPI) network diagram proposed by the present invention;

[0027] Figure 3 It is the "traditional Chinese medicine-active ingredient-key target-disease" network diagram proposed by the present invention;

[0028] Figure 4 It is the GO enrichment analysis diagram of the key targets proposed by the present invention;

[0029] Figure 5 It is the KEGG pathway enrichment analysis diagram of the key targets proposed by the present invention;

[0030] Figure 6 It is the molecular docking diagram of quercetin and GAPDH proposed by the present invention;

[0031] Figure 7 It is the molecular docking diagram of quercetin and AKT1 proposed by the present invention;

[0032] Figure 8 It is the molecular docking diagram of quercetin and ALB proposed by the present invention;

[0033] Figure 9 The molecular docking diagram of quercetin and IL6 proposed by the present invention;

[0034] Figure 10 The molecular docking diagram of quercetin and TNF proposed by the present invention;

[0035] Figure 11 The initial diagnosis case diagram of the patient in the typical case 1 proposed by the present invention;

[0036] Figure 12 The follow-up diagnosis case diagram of the patient in the typical case 1 proposed by the present invention;

[0037] Figure 13 The initial diagnosis case diagram of the patient in the typical case 2 proposed by the present invention;

[0038] Figure 14 The follow-up diagnosis case diagram of the patient in the typical case 2 proposed by the present invention;

[0039] Figure 15 The initial diagnosis case diagram of the patient in the typical case 3 proposed by the present invention;

[0040] Figure 16 The follow-up diagnosis case diagram of the patient in the typical case 3 proposed by the present invention;

[0041] Figure 17 The initial diagnosis case diagram of the patient in the typical case 4 proposed by the present invention;

[0042] Figure 18 The follow-up diagnosis case diagram of the patient in the typical case 4 proposed by the present invention;

[0043] Figure 19 The initial diagnosis case diagram of the patient in the typical case 5 proposed by the present invention;

[0044] Figure 20 The follow-up diagnosis case diagram of the patient in the typical case 5 proposed by the present invention;

[0045] Figure 21 The initial diagnosis case diagram of the patient in the typical case 6 proposed by the present invention;

[0046] Figure 22 The follow-up diagnosis case diagram of the patient in the typical case 6 proposed by the present invention;

[0047] Figure 23 The initial diagnosis case diagram of the patient in the typical case 7 proposed by the present invention;

[0048] Figure 24 The follow-up diagnosis case diagram of the patient in the typical case 7 proposed by the present invention;

[0049] Figure 25The initial diagnosis case diagram of the patient in the typical case 8 proposed by the present invention;

[0050] Figure 26 The follow-up diagnosis case diagram of the patient in the typical case 8 proposed by the present invention;

[0051] Figure 27 The initial diagnosis case diagram of the patient in the typical case 9 proposed by the present invention;

[0052] Figure 28 The follow-up diagnosis case diagram of the patient in the typical case 9 proposed by the present invention;

[0053] Figure 29 The initial diagnosis case diagram of the patient in the typical case 10 proposed by the present invention;

[0054] Figure 30 The follow-up diagnosis case diagram of the patient in the typical case 10 proposed by the present invention; Detailed implementation manners

[0055] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0056] Embodiment 1

[0057] A traditional Chinese medicine preparation for treating knee osteoarthritis, which is made from the following raw materials: Cyathula officinalis Kuan, Pittosporum tobira, Carthamus tinctorius, Lycopodium clavatum, Lycopodium annotinum, Sparganium stoloniferum, Curcuma zedoaria, Zanthoxylum schinifolium, Clematis chinensis, Artemisia argyi, Notopterygium incisum, Cinnamomum cassia, Angelica pubescens, Olibanum, Myrrha, Radix Aconiti Lateralis Preparata, Radix Aconiti Kusnezoffii Preparata, Saposhnikovia divaricata, Asarum sieboldii, Borneol;

[0058] The weight parts of different raw materials are respectively: 30 parts of Cyathula officinalis Kuan, 20 parts of Pittosporum tobira, 15 parts of Carthamus tinctorius, 30 parts of Lycopodium clavatum, 30 parts of Lycopodium annotinum, 20 parts of Sparganium stoloniferum, 20 parts of Curcuma zedoaria, 15 parts of Zanthoxylum schinifolium, 30 parts of Clematis chinensis, 20 parts of Artemisia argyi, 20 parts of Notopterygium incisum, 15 parts of Cinnamomum cassia, 20 parts of Angelica pubescens, 10 parts of Olibanum, 10 parts of Myrrha, 10 parts of Radix Aconiti Lateralis Preparata, 10 parts of Radix Aconiti Kusnezoffii Preparata, 10 parts of Saposhnikovia divaricata, 10 parts of Asarum sieboldii, 5 parts of Borneol.

[0059] Furthermore, the important preparation provided in this application is studied based on network pharmacology and molecular docking technology;

[0060] 1. Screening of active ingredients and action targets of XBS:

[0061] Using the names of 19 traditional Chinese medicines in XBS as keywords, collect the chemical components of 15 traditional Chinese medicines such as Cyathulae Radix, Cortex Erythrinae, Flos Carthami, Herba Lycopodii, Sparganii Rhizoma, Curcumae Rhizoma, Clematidis Radix, Folium Artemisiae Argyi, Rhizoma seu Radix Notopterygii, Ramulus Cinnamomi, Radix Angelicae Pubescentis, Olibanum, Myrrha, Radix Saposhnikoviae, and Herba Asari from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). According to previous studies, set the oral bioavailability (OB) chemical components and drug-likeness (DL) components, and conduct a preliminary screening according to the standards set by previous studies to obtain active ingredients, obtain the corresponding targets of the ingredients, and query their Gene IDs in the Uniprot database. Collect the ingredient information of 4 traditional Chinese medicines, namely Radix Aconiti Lateralis Preparata, Radix Aconiti Kusnezoffii Preparata, Fructus Zanthoxyli, and Herba Lycopodii Flexuosi, in the HERB database, obtain their 3D structures from the Pubchem database, and predict their targets through the SwissTargetPrediction database;

[0062] Results: Collect 1,895 chemical components of 19 traditional Chinese medicines in the XBS compound (Cyathulae Radix, Cortex Erythrinae, Flos Carthami, Herba Lycopodii, Sparganii Rhizoma, Curcumae Rhizoma, Clematidis Radix, Folium Artemisiae Argyi, Rhizoma seu Radix Notopterygii, Ramulus Cinnamomi, Radix Angelicae Pubescentis, Olibanum, Myrrha, Radix Saposhnikoviae, Herba Asari, Radix Aconiti Lateralis Preparata, Radix Aconiti Kusnezoffii Preparata, Fructus Zanthoxyli, Herba Lycopodii Flexuosi) from the TCMSP and HERB databases. According to the oral utilization rate (OB) ≥≥ and the drug likeness (DL) ≥≥ drug property as the standard, 188 active ingredients were obtained through preliminary screening. 1,514 treatment targets corresponding to the active ingredients were obtained from the TCMSP and SwissTargetPrediction databases. After removing duplicates and unified correction by Uniprot, 761 target genes were obtained, as shown in Table 1:

[0063] Table 1 XBS, traditional Chinese medicine-active ingredient-disease target disease information

[0064]

[0065]

[0066] 2. Screening of treatment targets for KOA

[0067] Using the treatment targets corresponding to the screening components of the targets as keywords, collect disease-related targets from the GeneCards, DisGeNET, and OMIM disease databases, and remove duplicates to obtain the related targets of KOA;

[0068] Results: Obtain the disease treatment targets of KOA through the GeneCards, DisGeNET, and OMIM databases, merge and remove duplicates, and obtain 3,339 treatment targets for KOA.

[0069] 3. Screening of the intersection treatment targets of XBS and drawing of the Venn diagram

[0070] The intersection mapping of the targets of the active ingredients of the drug and the targets for disease treatment was drawn using the online platform Venny 2.1.0 to obtain the "XBS-KOA" intersection targets and the Venn diagram.

[0071] Results: Taking the intersection of the targets of the XBS active ingredients and the targets for disease treatment yielded 307 intersection targets. The Venn diagram was drawn using the online platform Venny 2.1.0, as Figure 1 shown.

[0072] 4. Construction of the protein-protein interaction (PPI) network and screening of core targets

[0073] The intersection targets were imported into the STRING database, screened with a confidence score > 0.9, and the free protein nodes in the figure were deleted to construct a protein-protein interaction (PPI) network. The species was selected as "Homo sapiens" and the threshold was set to "highest confidence". Then the result file in CSV format was downloaded, and the PPI network was visualized and analyzed for network topology using Cytoscape software (version 3.9.0). Core targets were screened according to the degree value (Degree value) of the nodes in the PPI network;

[0074] Results: The 307 intersection target genes were input into the String database to construct a protein-protein interaction (PPI) network, and the PPI network was visualized using CytoSape 3.9.0 software, as Figure 2 shown. The constructed PPI network had 306 nodes and 8992 edges. The nodes represent different gene proteins, and the edges represent the relationship of interaction between the connected proteins. The more lines, the greater the degree of association. The larger the node, the greater the drgree value, and the greater the possible role of the gene. The top 5 targets in terms of the drgree value were IL6, TNF, AKT1, GAPDH, and ALB, with degree values of 217, 214, 208, 204, and 195 respectively, suggesting that they may be the core targets for XBS to regulate KOA.

[0075] 5. Drawing of the "traditional Chinese medicine-active ingredient-key target-disease" network diagram of XBS

[0076] Using Cytoscape software (version 3.9.0) to construct the "traditional Chinese medicine-active ingredient-key target-disease" network diagram, analyze the network, and screen out the ingredients with the top-ranked Degree values as the key active ingredients of this study;

[0077] Results: For the 307 intersection target genes, corresponding to 144 active components of XBS (excluding the active components not corresponding to the intersection targets), the "traditional Chinese medicine-active component-key target-disease" network was constructed using Cytoscape 3.9.0 software, as Figure 3 shown (the triangular nodes represent traditional Chinese medicine, the circular nodes represent components, the diamond nodes represent the common components of different traditional Chinese medicines, the inverted triangular nodes represent key targets, and the regular hexagonal nodes represent the disease KOA). The constructed network has 471 nodes and 1887 edges;

[0078] The "traditional Chinese medicine-active component-key target-disease" network was analyzed. The results showed that according to the Degree value, the top 5 active components were quercetin, Karanjin, luteolin, neryl acetate, and songoramine, suggesting that these active components might be the core active components of XBS in the treatment of KOA, as shown in Table 2:

[0079] Table 2 Information of the top 5 components ranked by the Degree value of XBS

[0080]

[0081] 6. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis

[0082] The DAVID database was used to perform GO and KEGG enrichment analyses on the intersection targets. The "set analysis was selected, and the "david-gene information was selected, and the entries related to Biological Process (BP), Cellular Component (CC), and Molecular Function (MF) were selected. Filtering and enrichment analysis were performed on them with P < 0.05 to obtain the specific data of GO enrichment analysis and KEGG enrichment analysis, and bubble charts were drawn using the Weishengxin online platform respectively;

[0083] Results: GO functional enrichment analysis of the targets for treating KOA with XBS was performed using the DAVID database, and 1,428 entries were obtained, including 1,085 in BP, 116 in CC, and 227 in MF. In the GO enrichment analysis, the treatment of KOA with XBS was mainly closely related to biological processes such as inflammatory response, positive regulation of gene expression, positive regulation of cell proliferation, cellular response to lipopolysaccharide, response to lipopolysaccharide, phosphorylation, response to xenobiotic stimulus, negative regulation of apoptotic process, and protein phosphorylation, as well as molecular biological functions such as enzyme binding, protein binding, protein kinase activity, protein tyrosine kinase activity, transcriptional coactivator binding, and ATP binding. The processes involved cellular components such as plasma membrane, cytoplasm, macromolecular complex, cytosol, receptor complex, and extracellular exosome. The top 10 entries with the highest gene enrichment in biological process, molecular function, and cellular component were used to make a bubble chart, as shown in Figure 4 shown;

[0084] A total of 184 signaling pathways were obtained by KEGG enrichment analysis, including advanced glycation end product-receptor (AGE-RAGE) signaling pathway, tumor necrosis factor (TNF) signaling pathway, hypoxia-inducible factor 1 (HIF-1) signaling pathway, hepatitis C, colorectal cancer, interleukin-17 (IL-17) signaling pathway, Toll-like receptor signaling pathway, phosphatidylinositol-3-kinase-protein kinase (PI3K-Akt) signaling pathway, Th17 cell differentiation, cell senescence, etc. According to P<0.05 with significant differences, a total of 15 significantly meaningful pathways were screened out to draw a bubble chart, as shown in Figure 5 shown.

[0085] 7. Molecular docking

[0086] The top 5 active ingredients in the "active ingredient - therapeutic target" network diagram were molecularly docked with their corresponding 5 core targets (if the therapeutic targets corresponding to the active ingredients did not include the screened core targets, they were not molecularly docked with them). The lowest binding free energy was taken as the result of the molecular docking. The lower the binding energy between the small molecule ligand of the drug and the target protein receptor, the stronger the binding force between the ligand and the receptor. First, the sdf file of the core active ingredient was obtained from the PubChem database, and the compound was energy-minimized, hydrogenated, and charge-corrected using AutodockVina (version 1.1.2) software. Then, the pdb format file of the target protein was obtained from the PDB database, and the protein structure was preprocessed using AutodockVina software, including water molecules, protein inhibitors, and salt ions required for crystallization in the protein crystal structure, repairing the missing hydrogen atoms on protein residues, and optimizing the protein conformation. Finally, molecular docking was performed using AutodockVina software, with the compound as the ligand and the protein as the receptor. The all-atom docking method was selected, and the top 10 conformations ranked by docking scores were output. The docking results were visualized using Pymol (version 2.4.0) software;

[0087] Results: The core active ingredients quercetin, karanjin, luteolin, nilic acid ester, and pinostrobin were respectively docked pairwise with the core targets IL6, TNF, AKT1, GAPDH, and ALB. The stronger the affinity of the interaction between the ligand and the receptor, the less energy required, and the greater the possibility of their interaction. The more hydrogen bonds and other interactions formed between molecules indicate the stronger the binding force between the compound and the protein. Research shows that < -5.0 kcal / mol indicates good affinity. The molecular docking results showed that the main active ingredients of XBS could spontaneously bind to the core targets, and the binding energies were all lower than -5.0 kJ / mol, as shown in Table 3. This indicates that the predicted key active ingredients of XBS and the key action targets for treating KOA have good binding activity. The molecular docking of the core ingredient quercetin (quercetin) with each core target is shown in Figures 6 - 10 , and the results showed that quercetin could stably bind to 5 core target proteins.

[0088] Table 3 Binding energies of active ingredients and core targets (kcal·mol －1 )

[0089]

[0090] In this study, 5 core active components were screened and shown to interact with 5 core targets related to KOA. Among them, quercetin had the highest number of target connections, followed by karanjin, luteolin, etc. Quercetin can promote cartilage formation, reduce chondrocyte apoptosis, and inhibit endoplasmic reticulum stress and the release of inflammatory factors; modern pharmacological studies have shown that quercetin can significantly reduce the secretion of inflammatory factors such as IL-1β and TNF-α, and is a potential anti-inflammatory drug for the treatment of KOA. It was found that the gene expression profile regulated by karanjin was enriched in several signature gene sets, including early estrogen response and G2 / M checkpoint genes. The genes regulated by karanjin overlapped with those regulated by 1 nM 17β-estradiol (E2) or 1 μM tamoxifen, suggesting that karanjin has partial estrogen-like activity, and it is speculated that karanjin has a potential hormone-like protective effect on chondrocytes. Luteolin can inhibit the death, apoptosis, oxidative stress, necroptosis, and production of inflammatory mediators of H2O2-induced mouse chondrocytes. The protein-protein interaction network indicated that IL6, TNF, AKT1, GAPDH, and ALB might be the key targets for XBS in the treatment of KOA. KOA is mainly caused by chondrocyte apoptosis, inflammatory factors, and related hydrolytic proteins that damage chondrocytes, and the above-mentioned proteins have different associations with this etiology. IL-6 can induce cartilage degeneration and cause pain, and plays a protective role by increasing the expression of anti-catabolic factors. An IL-6 level exceeding 1000 pg / ml indicates the diagnosis of inflammatory arthritis. Tumor necrosis factor α can bind to two receptors, TNFR1 and TNFR2, and the two bound receptors can form a complex to activate the NF-κB and MAPK signaling pathways, promoting the production of inflammatory factors. Secondly, the MAPK pathway can cascade to activate the NF-κB signaling pathway, further exacerbating the inflammatory response. Serine / threonine protein kinase (AKT1) is a key regulator of the PI3K-AKT pathway, controlling cell growth and survival. Studies have shown that during the endochondral ossification process of bone growth and the osteophyte formation process of KOA, AKT1 controls cartilage calcification by inhibiting pyrophosphate. Pathway enrichment showed that XBS might be involved in key signaling pathways such as the IL-17 signaling pathway, PI3K / Akt pathway, Toll-like receptor signaling pathway, Th17 cell differentiation, NF-κB signaling pathway, and tumor necrosis factor signaling pathway. The pathogenesis of KOA might be positively correlated with the IL17A (rs2275913) gene. IL-17 is a homodimer composed of 155 amino acids with an N-terminal signal peptide, and can participate in the occurrence of inflammation and cause cartilage collapse and synovial infiltration in OA. The PI3K / Akt signaling pathway is an important pathway for chondrocyte metabolism. Multiple studies have shown that inhibiting the PI3K / AKT signaling pathway can reduce the expression of matrix metalloproteinase 13 and exacerbate the inflammation of osteoarthritis. Compared with normal human cartilage, the activity of the PI3K / Akt pathway in the cartilage tissue of KOA patients is reduced.The PI3K-AKT pathway plays an important role in the homeostasis of articular chondrocytes on the one hand, and on the other hand, the NF-kB pathway regulated by PI3K / AKT is also closely related to the occurrence of inflammation. Toll-like receptors are involved in the initial link of immunity and can activate related signaling pathways by recognizing pathogen-associated molecular patterns, leading to the occurrence of KOA.

[0091] In summary, based on network pharmacology and molecular docking technology, this study preliminarily explored the mechanism of action and material basis of XBS in the treatment of KOA. The results of molecular docking suggest that the main active components quercetin, karanjin, and luteolin in XBS may spontaneously bind to 5 key targets to play a potential anti-KOA role, which provides a reference basis for the clinical application of XBS in the treatment of KOA.

[0092] Example 2

[0093] Example 2 provides a preparation method of a traditional Chinese medicine preparation for treating knee osteoarthritis as described in Example 1, including the following steps:

[0094] S1: Grind Cyathula officinalis, Pittosporum tobira, safflower, Lycopodium clavatum, Lycopodiastrum casuarinoides, Sparganium stoloniferum, Curcuma zedoaria, Chinese prickly ash, Clematis chinensis, Artemisia argyi, Notopterygium incisum, Cinnamomum cassia, Angelica pubescens, frankincense, myrrh, Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Saposhnikovia divaricata, Asarum sieboldii, and borneol into fine powder;

[0095] S2: Add the above powder to a paste prepared with 80°C water and 2 g of vaseline, and wait for the temperature to drop below skin temperature.

[0096] Furthermore, 82 patients with knee osteoarthritis were randomly divided into a treatment group and a control group, with 41 cases in each group. The treatment group was given the traditional Chinese medicine preparation proposed in this application for external application, and the control group was given a placebo for external application. The treatment courses of both groups were 14 days, and the changes in the VAS score of knee pain, WOMAC score, and traditional Chinese medicine syndrome score were observed. Results: ① During the trial, 1 case dropped out in the treatment group and 1 case dropped out in the control group, and finally 80 cases completed the trial. ② Before treatment, there were no statistically significant differences in the scores of the two groups (P>0.05); after treatment, when comparing within the group, the VAS score of knee pain, WOMAC score, and traditional Chinese medicine syndrome score of both groups decreased, and the differences were statistically significant (P<0.05). However, when compared with the control group at the same time, the decrease in the VAS score, WOMAC score, and traditional Chinese medicine syndrome score of the treatment group was significantly better than that of the control group, and the differences were statistically significant (P<0.05). ③ The total effective rate of the treatment group was 95.0%, which was significantly higher than 72.5% of the control group (P<0.05).

[0097] Diagnostic criteria: Western medicine diagnostic criteria (refer to the "Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment Guidelines for Knee Osteoarthritis" formulated by the Orthopaedics and Traumatology Professional Committee of the Chinese Association of Integrated Traditional Chinese and Western Medicine in 2018): ① Repeated knee joint pain within the past 1 month; ② Age ≥ 50 years old; ③ Morning stiffness ≤ 30 minutes; ④ Presence of bone friction sound (sensation) during movement; ⑤ X-ray (standing position or weight-bearing position) shows joint space narrowing, subchondral bone sclerosis and / or cystic changes, and osteophyte formation at the joint margin; Meeting ① + (any two of ②, ③, ④, ⑤) can diagnose KOA.

[0098] The traditional Chinese medicine diagnostic criteria refer to the diagnostic criteria in the "Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Knee Osteoarthritis (2020 Edition)". The syndrome differentiation is cold-dampness obstruction syndrome: The joint pain is heavy and fixed, aggravated by cold and relieved by warmth, the joint flexion and extension are unfavorable, or accompanied by heavy pain in the waist and body, the tongue is pale, the tongue coating is white and greasy, and the pulse is slow and soggy.

[0099] Inclusion criteria: ① According to the above-mentioned traditional Chinese and Western medicine diagnostic criteria, diagnosed as primary knee osteoarthritis (KOA); ② The age range is between 45 and 80 years old, with no restrictions on weight and gender; ③ Imaging conforms to grades I - III of Kellgren & Lawrence X-ray; ④ The subjects have not received systematic treatment, including knee joint surgery or sodium hyaluronate injection; ⑤ Voluntarily sign the informed consent form to participate in the study.

[0100] Exclusion criteria: ① History of metabolic bone disease, tumor or trauma involving the knee joint; ② Complicated with other knee joint diseases (such as gouty, rheumatoid arthritis, etc.); ③ History of knee joint surgery (such as arthroscopic debridement) and less than 1 year after surgery; ④ Use of NSAIDs drugs or received intra-articular drug injection treatment within the past 1 month; ⑤ History of digestive tract bleeding; ⑥ Complicated with severe systemic diseases or mental disorders; ⑦ Pregnant, lactating and those planning pregnancy; ⑧ Long-term use of drugs that interfere with the evaluation of efficacy; ⑨ Known allergic reaction to the study drug.

[0101] Withdrawal criteria: ① Insufficient treatment compliance (failure to complete the prescribed course of treatment); ② Receiving additional intervention measures during the study period; ③ Cases of active withdrawal or loss to follow-up; ④ Missing follow-up data resulting in limited evaluation of efficacy.

[0102] Trial design: This trial uses a randomized, double-blind, placebo-controlled method for research;

[0103] 1. For random grouping, the computer software generates 40 random numbers from 1 to 80. Set as group A (control group), and the remaining 40 numbers are set as group B (treatment group). Put them in a sealed opaque envelope. The patients randomly draw lots from 1 to 80 numbers according to the order of seeing a doctor and are assigned to the treatment group (Knee Bi Powder) and the control group (placebo) in a 1:1 ratio;

[0104] 2. Blinding method This study adopted a double-blind research method for both researchers and subjects. It was required that the processes of randomization scheme formulation, blind baseline generation and retention, result recording, statistical analysis, etc. must maintain the blind state. Generally, the blinding was lifted after the study was completed and the data analysis was finished. During the trial, the pharmacy department prepared 1 box each of placebo and Xibi Powder, which were respectively labeled as A and B, and the pharmacy department was responsible for keeping the record. Emergency letters were prepared for each subject. In case of special circumstances where blinding needed to be broken during the trial, the researcher decided whether to unblind in advance. During the trial, the hospital pharmacy distributed drugs according to the trial protocol;

[0105] 3. In the placebo control treatment group and the control group, both used Xibi Powder. In the control group, a PE plastic film was used to separate the contact between the drug and the skin, and its appearance, touch and smell were the same as those of the experimental group.

[0106] Treatment method:

[0107] 1. Treatment group The traditional Chinese medicine preparation provided in this application was made into a powder and applied externally to the affected knee. The prescription was as follows: 30 g of Cyathulae Radix, 20 g of Pittospori Cortex, 15 g of Carthami Flos, 30 g of Lycopodiastri Herba, 30 g of Luffae Fructus, 20 g of Sparganii Rhizoma, 20 g of Curcumae Rhizoma, 15 g of Zanthoxyli Fructus, 30 g of Clematidis Radix, 20 g of Artemisiae Argyi Folium, 20 g of Notopterygii Rhizoma, 15 g of Cinnamomi Ramulus, 20 g of Angelicae Pubescentis Radix, 10 g of Olibanum, 10 g of Myrrha, 10 g of Aconiti Radix Praeparata, 10 g of Aconiti Kusnezoffii Radix Praeparata, and 5 g of Borneolum Syntheticum. External application method: Take 50 g of the traditional Chinese medicine powder ground into fine powder, mix it with 80°C water and 2 g of vaseline to form a paste, apply it on a medical gauze, make it as flat and uniform as possible. After the temperature drops to skin temperature, directly apply it to the affected area, with the area slightly larger than the joint part and the thickness about 3 mm. It was wrapped with a PE plastic film outside, covered with a cotton pad, fixed with a bandage, and a knee brace was worn outside to prevent it from falling off. It was applied to the affected area once a day, and each application lasted for 4 - 6 h, and the treatment continued for 2 weeks;

[0108] 2. Control group In the control group, a PE plastic film was used to separate the contact between the drug and the skin, and Xibi Powder was applied externally according to the above method. Its appearance, touch and smell were the same as those of the experimental group;

[0109] Basic treatment According to ethical requirements, all cases were provided with basic treatment measures: 1. It was required to avoid unreasonable movements (such as climbing stairs and mountains); 2. Avoid bad postures; 3. Avoid running, jumping and squatting for a long time; 4. Do appropriate activities. During the treatment process, both groups required necessary patient education and basic functional exercises; 5. Oral administration of celecoxib capsules, 100 mg, bid;

[0110] Observation items and methods:

[0111] 1. Visual Analogue Scale (VAS) score for knee pain The Visual Analogue Scale (VAS) score is marked by the patient on a scale of 0 to 10 according to their own pain level. The pain is divided into painless, mild, moderate, and severe according to the score. The scores of the two groups of patients before medication, 1 week after medication, and 2 weeks after medication are recorded respectively.

[0112] 2. Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score The WOMAC score is evaluated from three aspects: pain, stiffness, and difficulty in daily activities, covering the basic symptoms and signs of the entire osteoarthritis, and the evaluation of the two groups of patients is recorded at each time point. WOMAC osteoarthritis index: 0 points for no difficulty, 1 point for slight, 2 points for moderate, 3 points for severe, and 4 points for very severe; The scores of the two groups of patients before medication, 1 week after medication, and 2 weeks after medication are recorded respectively.

[0113] 3. Traditional Chinese Medicine (TCM) syndrome score Before and after treatment, the relevant content in the TCM syndrome grading and quantification score table (score range 0 - 24) is used to score the TCM syndrome of the subjects, and the scores of the two groups of patients before medication, 1 week after medication, and 2 weeks after medication are recorded respectively.

[0114] 4. Efficacy evaluation criteria Refer to the "Guiding Principles for Clinical Research of New Chinese Medicines" (2002 edition) to compare the TCM syndrome scores of the subjects before treatment and 2 weeks after treatment: ① Clinical control: symptoms such as pain disappear, joint movement is normal, and the syndrome score decreases by ≥ 90%; ② Marked effect: symptoms such as pain basically disappear, joint movement is basically normal, can participate in basic activities or work, and the syndrome score decreases by ≥ 60% and < 90%; ③ Effective: pain basically disappears, joint movement is slightly limited, the ability to participate in activities or work is improved, and the syndrome score decreases by ≥ 30% and < 60%; ④ Ineffective: symptoms such as pain and joint movement have no obvious improvement, and the syndrome score decreases by < 30%. Note: Calculation formula (Nimodipine method): [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × pre-treatment score;

[0115] Total effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases.

[0116] Record the adverse reaction conditions that occur during the treatment of the patients.

[0117] Statistical methods: For measurement data that meet the normal distribution, use It is indicated that the data do not conform to normality, and the median (interquartile range) [M(P25, P75)] is used to represent it. Count data are expressed as rates or constituent ratios. When measurement data conform to a normal distribution, an independent samples t-test is used for comparison between two groups, and a paired samples t-test is used for comparison before and after treatment. When the data show a skewed distribution, a non-parametric rank sum test is used. The chi-square test is used for comparison between groups of count data. The Mann-Whitney U test is used for efficacy comparison and ordinal data. The significance level α is set at 0.05, and P < 0.05 is considered statistically significant.

[0118] Results:

[0119] 1. General information: From June 2023 to May 2024, 82 patients with knee osteoarthritis admitted to the orthopedics outpatient department of Nanchuan Traditional Chinese Medicine Hospital in Chongqing all signed informed consent forms. They were randomly divided into a treatment group and a control group, with 41 cases in each group. During the trial, 1 case dropped out from the treatment group (due to mild skin itching and refusal to complete the trial), and 1 case dropped out from the control group (due to dissatisfaction with the efficacy and requiring arthroscopic debridement). Finally, 80 cases completed the trial. There were no statistically significant differences in general data such as gender, age, disease duration, BMI, imaging grading, and location between the two groups (P > 0.05), and they were comparable, as shown in Table 4.

[0120] Table 4 Comparison of clinical data between the two groups of patients

[0121]

[0122] 2. Comparison of VAS scores for knee pain: Before treatment, there were no statistically significant differences in VAS scores between the two groups (P > 0.05). Compared with before treatment in their own groups, the VAS scores of both groups decreased at 1 week and 2 weeks after treatment (P < 0.05). However, at the same time points, the decrease in the treatment group was more obvious than that in the control group (P < 0.05), and the difference was statistically significant, as shown in Table 5.

[0123] Table 5 Comparison of VAS scores between the two groups [M(P 25 , P 75 )]

[0124]

[0125] Compared with before treatment in their own groups, *P < 0.05; compared with the control group at the same treatment period, # P < 0.05.

[0126] 3. Comparison of WOMAC scores: Before treatment, there was no significant difference in WOMAC scores between the two groups (P > 0.05). Compared with before treatment in their own groups, the WOMAC scores of both groups decreased at 1 week and 2 weeks after treatment (P < 0.05). However, when compared at the same time points, the WOMAC scores of the treatment group were significantly lower than those of the control group (P < 0.05), and the difference was statistically significant, as shown in Table 6.

[0127] Table 6 Comparison of WOMAC scores between the two groups

[0128]

[0129] Compared with before treatment in their own groups, *P < 0.05; compared with the control group at the same treatment stage, # P < 0.05.

[0130] 4. Comparison of TCM syndrome scores: Before treatment, there was no significant difference in TCM syndrome scores (P > 0.05). Compared with before treatment in their own groups, the TCM syndrome scores of both groups decreased at 1 week and 2 weeks after treatment (P < 0.05). However, when compared at the same time points, the TCM syndrome scores of the treatment group were significantly lower than those of the control group (P < 0.05), and the difference was statistically significant, as shown in Table 7.

[0131] Table 7 Comparison of TCM syndrome scores between the two groups

[0132]

[0133] Compared with before treatment in their own groups, *P < 0.05; compared with the control group at the same treatment stage, # P < 0.05.

[0134] 5. Comparison of the efficacy evaluations of the two groups: After 2 weeks of treatment, the total clinical effective rate of the treatment group was 95.0%, and that of the control group was 72.5%. The difference between the two groups was statistically significant (P < 0.05), as shown in Table 8.

[0135] Table 8 Comparison of the efficacy evaluations of the two groups

[0136]

[0137] Compared with the control group, *P < 0.05.

[0138] 6. Adverse reaction situation: During the treatment period, 1 case in the treatment group had mild skin itching at the dressing site for a short time. After asking the patient about the specific situation, it was found that this patient had extended the dressing time to the next day by himself. The treatment method was to stay away from allergens. During the follow-up, the patient reported that the skin itching symptom had disappeared. In the control group, patients with allergies to non-steroidal anti-inflammatory drugs and digestive tract diseases had been excluded during the screening process, and no adverse reaction events occurred. No other adverse reactions such as drug poisoning or liver and kidney function damage occurred in both groups of patients during the treatment period.

[0139] Typical case 1

[0140] Chen **, 62 years old, diagnosed on June 13, 2023; Initial diagnosis condition: Right knee pain occurred without obvious cause 6 months ago, aggravated when going downstairs or squatting, relieved by rest, aggravated when the weather changed, and aggravated by cold, relieved by warmth; The last follow-up condition after using the traditional Chinese medicine preparation in this application for a period of time: The right knee pain was significantly reduced compared with before, the feeling of cold in the right knee was no longer obvious, and the joint movement was significantly improved compared with before. The specific case is as Figure 11 and Figure 12 shown.

[0141] Typical case 2

[0142] Wei **, 67 years old, diagnosed on June 6, 2023; Initial diagnosis condition: Left knee pain occurred without obvious cause 6 months ago, heavy, afraid of cold, aggravated by cold, relieved by warmth; The last follow-up condition after using the traditional Chinese medicine preparation in this application for a period of time: The left knee pain was significantly reduced compared with before, the feeling of cold in the left knee was no longer obvious, and the joint movement was significantly improved compared with before. There was no fear of cold or fever, normal appetite and sleep, and normal bowel and bladder movements. The specific case is as Figure 13 and Figure 14 shown.

[0143] Typical case 3

[0144] Tian *, 56 years old, diagnosed on June 18, 2023; Initial diagnosis condition: Right knee pain occurred without obvious cause 4 years ago, aggravated by cold, relieved by warmth, obvious pain was felt when sitting or just starting to walk after getting up, relieved after walking a certain distance, and the symptom aggravated after increasing the walking distance, difficult to squat; The last follow-up condition after using the traditional Chinese medicine preparation in this application for a period of time: The right knee pain was significantly reduced compared with before, the feeling of cold in the right knee was no longer obvious, and the joint movement was significantly improved compared with before. There was no fear of cold or fever, normal appetite and sleep, and normal bowel and bladder movements. The specific case is as Figure 15 and Figure 16 shown.

[0145] Typical case 4

[0146] Zhang**, 60 years old, diagnosed on July 19, 2023; Initial diagnosis condition: 10 years ago, there was left knee pain without obvious cause, the pain was aggravated by activity and relieved by rest. In the morning, the joint felt stiff and improved after moving for a few minutes. The pain was aggravated by weather changes or cold wind, and the pain was relieved by wearing a knee brace or applying heat. The last follow-up condition after using the traditional Chinese medicine preparation in this application for a period of time: The left knee pain was significantly reduced compared with before, the feeling of cold in the left knee was no longer obvious, the joint movement was significantly improved compared with before, there was no fear of cold or fever, the appetite and sleep were normal, and the bowel movements and urination were regular. Specific cases are as Figure 17 and Figure 18 shown.

[0147] Typical Case 5

[0148] Hu**, 70 years old, diagnosed on July 31, 2023; More than 20 years ago, there was bilateral knee pain without obvious cause, with the left side being more severe. The pain was aggravated when going up and down stairs and squatting, and relieved by rest. There was no migratory joint pain. The last follow-up condition after using the traditional Chinese medicine preparation in this application for a period of time: The knee pain was significantly reduced compared with before, the cold feeling in the knees was significantly relieved, the movements such as going up and down stairs and deep squatting were significantly improved compared with before, there was no fear of cold or fever, the appetite and sleep were normal, and the bowel movements and urination were regular. Specific cases are as Figure 19 and Figure 20 shown.

[0149] Typical Case 6

[0150] Zhong**, 49 years old, diagnosed on October 8, 2023; 3 years ago, there was right knee pain without obvious cause, the pain was aggravated by activity, difficult to go uphill or squat, and relieved by rest. In the morning, the joint felt stiff and improved after moving for 2 minutes. The pain was aggravated by cold weather or cold wind, and the pain was relieved by applying heat or keeping warm. The last follow-up condition after using the traditional Chinese medicine preparation in this application for a period of time: The right knee pain was significantly reduced compared with before, the feeling of cold in the right knee was no longer obvious, the movements of going uphill and squatting were significantly improved compared with before, there was no fear of cold or fever, the appetite and sleep were normal, and the bowel movements and urination were regular. Specific cases are as Figure 21 and Figure 22 shown.

[0151] Typical Case 7

[0152] He**, 59 years old, diagnosed on November 1, 2023; 7 years ago, there was left knee pain without obvious cause. The pain was obvious when sitting or just starting to walk after getting up, and was relieved after walking a certain distance. The symptoms aggravated when the walking distance increased, difficult to squat, and strenuous to go up and down stairs. The pain was aggravated by weather changes and cold wind, and relieved by getting warm. The last follow-up condition after using the traditional Chinese medicine preparation in this application for a period of time: The left knee pain was significantly reduced compared with before, the cold feeling was no longer obvious, the joint movement was significantly improved compared with before, there was no fear of cold or fever, the appetite and sleep were normal, and the bowel movements and urination were regular. Specific cases are as Figure 23 and Figure 24 shown.

[0153] Typical Case 8

[0154] Liu **, 58 years old, diagnosed on November 22, 2023. Two years ago, there was left knee pain without obvious cause, which was aggravated by activity and relieved by rest. In the morning, the joint felt stiff and improved after a few minutes of activity. It was aggravated when the weather turned cold or in winter and relieved after hot compress. The condition at the last follow-up after using the traditional Chinese medicine preparation in this application for a period of time: The left knee pain was significantly reduced compared with before, the cold intolerance symptom was not obvious, the joint activity was significantly improved compared with before, there was no morning stiffness, no fear of cold or fever, the appetite and sleep were normal, and the bowel and bladder movements were regular. The specific case is as Figure 25 and Figure 26 shown.

[0155] Typical Case 9

[0156] He *, 50 years old, diagnosed on March 5, 2024. Six months ago, there was right knee pain without obvious cause, which was aggravated by activity and relieved by rest, and was aggravated when going up and down stairs or squatting, and was aggravated when the weather turned cold or when blowing cold wind, and the pain was reduced when getting warm. The right knee cold pain recurred repeatedly and there was no morning stiffness. The condition at the last follow-up after using the traditional Chinese medicine preparation in this application for a period of time: The right knee pain was significantly reduced compared with before, the cold intolerance symptom of the right knee was not obvious, the joint activity was significantly improved compared with before, there was no fear of cold or fever, the appetite and sleep were normal, and the bowel and bladder movements were regular. The specific case is as Figure 27 and Figure 28 shown.

[0157] Typical Case 10

[0158] Zhang **, 56 years old, diagnosed on October 24, 2023. One year ago, there was pain in both knees without obvious cause, with the left side being more severe, which was aggravated by activity and relieved by rest. In the morning, the joint felt stiff and improved after a few minutes of activity. It was aggravated in a cold environment or when blowing cold wind, and had been wearing a knee brace for a long time. The condition at the last follow-up after using the traditional Chinese medicine preparation in this application for a period of time: The knee pain was significantly reduced compared with before, the cold intolerance symptom of the knees had been significantly relieved, the movements such as going up and down stairs and squatting were significantly improved compared with before, there was no fear of cold or fever, the appetite and sleep were normal, and the bowel and bladder movements were regular. The specific case is as Figure 29 and Figure 30 shown.

[0159] The above description of the embodiments is to enable those of ordinary skill in the art to understand and apply the present invention. It is obvious that those who are familiar with the technology in the art can easily make various modifications to the above embodiments and apply the general principles described herein to other embodiments without creative labor. Therefore, the present invention is not limited to the above embodiments, and the improvements and modifications made by those skilled in the art to the present invention according to the disclosure of the present invention should be within the protection scope of the present invention.

Claims

1. A Chinese medicine for treating knee osteoarthritis, characterized in that: Including the following ingredients: Sichuan Cyathula, Pittosporum bark, safflower, herba striatae, herba schizonepetae, herba schizonepetae, schizonepetae, zedoariae, Sichuan pepper, clematis, wormwood leaf, notopterygium, cassia twig, angelica pubescens, frankincense, myrrh, processed Sichuan Aconite, processed Radix Aconiti Kusnezoffii, saposhnikovia divaricata, asarum, borneol; The weight proportions of different raw materials are respectively: 25-35 parts of Cyathula officinalis, 15-25 parts of Pittosporum tobira bark, 10-20 parts of safflower, 25-35 parts of Lycopodiella cuneata, 25-35 parts of Lycopodiella spatholobi, 15-25 parts of Trillium, 15-25 parts of Curcuma zedoaria, 10-20 parts of Sichuan pepper, 25-35 parts of Clematis, 15-25 parts of Artemisia argyi, 15-25 parts of Notopterygium wilfordii, 10-20 parts of cassia twig, 15-25 parts of Angelica dahurica, 5-15 parts of frankincense, 5-15 parts of myrrh, 5-15 parts of processed Aconiti kusnezoffii, 5-15 parts of processed Aconiti kusnezoffii, 5-15 parts of Saposhnikovia divaricata, 5-15 parts of Asarum, and 1-10 parts of borneol.

2. A Chinese medicine for treating knee osteoarthritis according to claim 1, characterized in that: The weight proportions of different raw materials are respectively: 30 parts of Cyathula, 20 parts of Pittosporum tobira bark, 15 parts of safflower, 30 parts of Herba Lycopodii, 30 parts of Herba Lycopodii, 20 parts of Rhizoma Curcumae, 15 parts of Sichuan pepper, 30 parts of Radix Clematis, 20 parts of Artemisia annua, 20 parts of Notopterygium wilfordii, 15 parts of Cassia twig, 20 parts of Radix Angelicae Pubescentis, 10 parts of frankincense, 10 parts of myrrh, 10 parts of processed Aconiti Kusnezoffii, 10 parts of processed Aconiti Kusnezoffii, 10 parts of Saposhnikovia divaricata, 10 parts of Asarum, and 5 parts of Borneol.

3. The method for preparing the Chinese medicine according to claim 1 or 2, characterized in that: The following steps are involved: S1: Grind cyathula officinalis, Pittosporum tobira bark, safflower, herba striatae, herba schizonepetae, herba schizonepetae, rhizoma curcumae, Sichuan pepper, radix clematis, wormwood leaf, angelica dahuricae, cassia twig, herba angelicae pubescens, frankincense, myrrh, processed radix aconiti kusnezoffii, processed radix aconiti kusnezoffii, saposhnikovia divaricatae, asarum, and borneol into fine powder; S2: Take the above powder, add 80℃ water and 2g vaseline to make a paste, and wait for the temperature to drop below skin temperature.

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