Use of corydaline in preparing medicine for treating rheumatoid arthritis

Abstract

The present invention belongs to the field of medical technology, and specifically relates to the use of corydaline or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating rheumatoid arthritis. Experimental results show that corydaline can effectively alleviate the level of paw swelling in CIA rats, reduce arthritis scores, and inhibit the progression of rheumatoid arthritis. Routine blood analysis shows that administration of corydaline reduces the number of immune cells in the blood and weakens the body's immune level. In addition, experimental results also show that corydaline can inhibit synovial hyperplasia and alleviate joint damage. Therefore, corydaline has the prospect of being developed into an oral medication for treating rheumatoid arthritis, providing more treatment options for the clinical treatment of rheumatoid arthritis, and has important social benefits and economic value.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and particularly relates to use of corydaline or a pharmaceutically acceptable salt thereof in preparing a medicine for treating rheumatoid arthritis. Background Art

[0002] Rheumatoid arthritis (RA) is a common inflammatory autoimmune disease. Epidemiological studies show that the incidence of RA is 0.5% to 1%, and the incidence in women is approximately three times that of men. RA is characterized by persistent synovitis, systemic inflammation, and the continuous production of autoantibodies. It is a chronic autoimmune disease with a protracted course of illness. Most patients experience recurrent symmetrical pain, swelling, and dysfunction in the small joints of the hands and feet, accompanied by morning stiffness. Its pathological features are primarily inflammatory cell infiltration and synovial cell proliferation, affecting multiple joints throughout the body, impacting patients' normal lives and, in severe cases, leading to joint deformities and disability.

[0003] The treatment goal for RA patients is to control inflammation while preserving joint structure and function, preventing structural damage, and restoring normal body function to maximize quality of life. Currently, glucocorticoids, anti-inflammatory drugs, and disease-modifying antirheumatic drugs (DMARDs) are the main treatments for RA. Furthermore, in the context of precision medicine, biologics and targeted drugs will also be the future direction of RA treatment. However, RA is a chronic disease that requires long-term medication to control the condition. Long-term, high-dose administration can lead to gastrointestinal reactions and damage to the liver, kidneys, and blood systems. Therefore, finding new drugs for the treatment of RA with higher efficacy and lower toxicity remains the future direction of RA prevention and treatment.

[0004] Natural product monomer compounds are monomer components extracted and separated from natural products. They may have multiple pharmacological activities, such as antioxidant, anti-tumor, antibacterial, and anti-inflammatory. They have a single component and few side effects, making them valuable resources for new drug research and development. Corlumidin is an isoquinoline alkaloid derived from traditional Chinese medicines such as Xiatianwu. The molecular formula of this compound is C 20 H 19 NO6, its chemical structure is as follows:

[0005]

[0006] Currently, there are relatively few studies on the pharmacological activity of corydaline, and there are no reports on the treatment of rheumatoid arthritis with corydaline. Summary of the Invention

[0007] The purpose of the present invention is to solve the problem of insufficient clinically available oral medications of natural origin for the treatment of rheumatoid arthritis that are highly effective, safe and inexpensive, to achieve in-depth development and utilization of natural products using modern pharmaceutical research methods, and to provide the use of corydaline in the preparation of medications for the treatment of rheumatoid arthritis in combination with a large number of pharmacodynamic experimental studies.

[0008] Specifically, the present invention is achieved through the following technical solutions:

[0009] The present invention provides use of corydaline or a pharmaceutically acceptable salt thereof in preparing a medicine for treating rheumatoid arthritis.

[0010] Preferably, the pharmaceutically acceptable salt is selected from hydrochloride.

[0011] As an optional mode, in the above use, the corydaline inhibits the progression of rheumatoid arthritis, reduces the number of immune cells in the blood, weakens the body's immune level, inhibits synovial hyperplasia, and relieves joint damage.

[0012] As an optional mode, in the above use, the drug comprises a therapeutically effective amount of corydaline and a pharmaceutically acceptable carrier.

[0013] As an optional mode, in the above use, the medicine further comprises other natural products commonly used in clinical treatment of rheumatoid arthritis.

[0014] As an optional mode, in the above use, the active ingredients in the medicine are composed of corydaline and other natural products.

[0015] As an optional mode, in the above use, the other natural products are selected from one or more of the following: oridonin, triptolide, resveratrol, sclareol, curcumin, decarinine, punicalagin, gentisic acid or naringin.

[0016] Preferably, the other natural products are selected from decaline.

[0017] As an optional mode, in the above use, the weight ratio of the corydaline to the other natural products is 1:10 to 10:1.

[0018] As an optional mode, in the above use, the weight ratio of the corydaline to the other natural products is 1:5 to 5:1.

[0019] Preferably, the weight ratio of the corydaline to the other natural products is 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10.

[0020] As an optional mode, in the above-mentioned use, when corydaline is used in combination with other natural products, the dosage forms of the former and the latter can be the same or different, and the former and the latter can be administered simultaneously or separately.

[0021] As an optional mode, in the above use, the drug is in oral dosage form.

[0022] As an optional mode, in the above use, the oral dosage form is selected from oral liquid, tablet, powder, capsule or granule.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) The present invention combines my country's advantages in natural product research and discovers for the first time a new use of the natural product corydaline in the treatment of rheumatoid arthritis.

[0025] (2) Experimental results showed that corydaline can effectively alleviate the level of paw swelling in CIA rats, reduce arthritis scores, and inhibit the progression of rheumatoid arthritis. Blood routine analysis showed that the administration of corydaline reduced the number of immune cells in the blood and weakened the body's immune level. In addition, experimental results also showed that corydaline can inhibit synovial hyperplasia and alleviate joint damage.

[0026] (3) Corydaline has the prospect of being developed into an oral drug for the treatment of rheumatoid arthritis, which provides more treatment options for the clinical treatment of rheumatoid arthritis and has important social benefits and economic value.

[0027] (4) In addition, the present invention also found that the combination of corydaline and certain natural products (especially decarinine) can produce significant synergistic effects in the treatment of rheumatoid arthritis. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0029] Figure 1: Changes in hind paw volume of rats during drug administration. **, p < 0.01, compared with the CIA group.

[0030] Figure 2 : Changes in the thickness of the rat hind paws during the drug administration period. **, p < 0.01, compared with the CIA group.

[0031] Figure 3 : Changes in arthritis scores of rats during drug administration. **, p < 0.01, compared with the CIA group.

[0032] Figure 4 : Micro-CT analysis of the ankle joints of rats after administration (bone damage evaluation).

[0033] Figure 5 : HE staining analysis of the ankle joints of rats after administration (evaluation of synovial hyperplasia).

[0034] Figure 6 : Safranin fast green staining analysis of the ankle joints of rats after administration (evaluation of cartilage destruction).

[0035] Figure 7 : Immunohistochemical analysis of S100A4 (analysis of synovial fibroblast markers) in the ankle joints of rats after administration.

[0036] Figure 8 : Immunohistochemical analysis of vimentin (synoviocyte marker analysis) in the ankle joints of rats after administration.

[0037] Figure 9 : Corydaline inhibits the migration of synovial fibroblasts.

[0038] Figure 10 : Statistical graph of the inhibition of synovial fibroblast migration by corydaline. **, p < 0.01, compared with the 0-dose group.

[0039] Figure 11 : MTT analysis of the inhibition of synovial fibroblast proliferation by corydaline. **, p < 0.01, compared with the 0-dose group.

[0040] Figure 12 : Analysis of edu staining on the inhibition of synovial fibroblast proliferation by corydaline.

[0041] Figure 13 : Statistical analysis of the inhibition of synovial fibroblast proliferation by corydaline using edu staining. *, p < 0.5; **, p < 0.01, compared with the 0-dose group. DETAILED DESCRIPTION

[0042] The present inventors have used modern pharmaceutical research methods to conduct in-depth development and utilization of natural products. Through extensive screening, they have discovered for the first time that oral administration of corydaline can effectively treat rheumatoid arthritis. Based on this, the present invention was completed.

[0043] The dosage form of the drug of the present invention is preferably an oral dosage form.

[0044] The oral dosage form is a capsule, tablet, granule or oral solution, preferably a tablet or capsule.

[0045] The pharmaceutically acceptable carrier refers to a conventional pharmaceutical carrier in the field of pharmaceutical preparations, and is selected from one or more of fillers, binders, disintegrants, lubricants, suspending agents, wetting agents, pigments, flavoring agents, solvents, and surfactants.

[0046] The fillers of the present invention include but are not limited to starch, microcrystalline cellulose, sucrose, dextrin, lactose, powdered sugar, glucose, etc.; the lubricants include but are not limited to magnesium stearate, stearic acid, sodium chloride, sodium oleate, sodium lauryl sulfate, poloxamer, etc.; the binders include but are not limited to water, ethanol, starch slurry, syrup, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, sodium alginate, polyvinyl pyrrolidone, etc.; the disintegrants include but are not limited to starch effervescent mixtures, i.e., sodium bicarbonate and citric acid, tartaric acid, low-substituted hydroxypropyl cellulose, etc.; the suspending agents include but are not limited to polysaccharides such as acacia gum, agar, alginic acid, cellulose ether, and carboxymethyl chitosan, etc.; the solvents include but are not limited to water, balanced salt solutions, etc.

[0047] The drug can be prepared into various solid oral preparations, liquid oral preparations, etc. Pharmaceutically acceptable oral solid preparations include: ordinary tablets, dispersible tablets, enteric-coated tablets, granules, capsules, dripping pills, powders, etc., and oral liquid preparations include oral liquids, emulsions, etc.

[0048] The above-mentioned various dosage forms can be prepared according to conventional processes in the field of pharmaceutical preparations.

[0049] "Corymidine" can be extracted and separated from plants such as summer jasmine containing the active ingredient using conventional natural product extraction methods in the art, or can be purchased from commercial products.

[0050] In the medical use described herein, the administration time, number of administrations, and frequency of administration of corydaline need to be determined according to the specific diagnosis results of the disease, which is within the technical scope mastered by those skilled in the art.

[0051] The treatment regimen for rats can be applied to humans, and the effective doses of all drugs for humans can be converted by the effective doses of the drugs for rats, which is also easy to achieve for ordinary technicians in this field.

[0052] In order to better understand the essence of the present invention, the following specific embodiments section uses pharmacodynamic experiments and their results to further illustrate the new use of corydaline in the pharmaceutical field for treating rheumatoid arthritis.

[0053] The present invention will be further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0054] If no specific techniques or conditions are specified in the examples, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product instructions. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0055] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0056] In the following examples, for cost-saving considerations, this application and another patent application for tetrahydrojatrorrhizine filed by the inventor on the same day share a normal control group, a model group, a positive drug control group, and a group of natural product monomers for combined use.

[0057] Example 1: In vivo efficacy study of corydaline in a collagen-induced rheumatoid arthritis animal model

[0058] 1.1 Experimental methods:

[0059] Rheumatoid arthritis is an autoimmune disease characterized by synovitis. Pathological manifestations include immune enhancement, synovial hyperplasia, and bone destruction. The collagen-induced arthritis model (CIA model) in rats can be used to simulate rheumatoid arthritis.

[0060] SD rats (180-200 g) were obtained from the Department of Laboratory Animal Science, Peking University Health Science Center. A total of 75 rats were 8 weeks old, male, SPF grade, and divided into 5 groups.

[0061] Animal groups: normal control group, 15 animals / group; CIA model group, 15 animals / group; positive drug group (methotrexate, 1 mg / kg / 2d), 15 animals / group; drug-treated group (corydaline, 5 mg / kg / d, 20 mg / kg / d), divided into 2 groups, 15 animals / group in each.

[0062] Administration: Oral administration.

[0063] Procedure: The animals were first divided into 7 groups according to the grouping scheme and subjected to adaptive feeding for 6 days to acclimate to the environment. The animal room maintained a 12-hour light and 12-hour dark cycle. During this period, the animals were free to eat and drink. The experiment used bovine type II collagen injection at the base of the tail to establish the model. The specific method is as follows: (1) Bovine type II collagen solution: bovine type II collagen was dissolved in an acetic acid aqueous solution with a pH of 3 to a concentration of 2 mg / mL and mixed on a shaker at 4°C for 2 hours. (2) Emulsion I: 2 mg / mL bovine type II collagen solution was mixed with complete Freund's adjuvant in a 1:1 ratio of equal volumes and vortexed. (3) Emulsion II: 2 mg / mL bovine type II collagen solution was mixed with incomplete Freund's adjuvant in a 1:1 ratio of equal volumes and vortexed. After SD rats were anesthetized with an anesthesia machine, 0.1 mL of emulsion I was subcutaneously injected at the base of the tail of rats in the model group and the treatment group. After 7 days, the rats' survival status was observed. If normal, the rats were anesthetized using an anesthesia machine. 0.1 mL of Emulsion II was injected subcutaneously at the base of the tail in both the model and treatment groups. Seven days later, a successful arthritis model was established (signs of successful arthritis model establishment included significant swelling of the rat's hind leg toes, inability to bend the hind leg joints, and creeping gait), and dosing began in the designated groups.

[0064] Animals in the treatment group were gavage-administered, while the control and model groups received only an equal volume of 0.5% CMC-Na solution. Paw swelling, paw thickness, and arthritis scores were monitored during the treatment period. Four weeks after treatment, the animals were anesthetized, micro-CT scans of the hind limbs were performed, and orbital blood was collected before euthanasia.

[0065] Animal Handling and Subsequent Analysis: After anesthesia, orbital blood was collected, serum was separated, and the animals were euthanized. The spleen, thymus, hind limbs, and other organs were harvested. Three animals were randomly selected from each group for paraffin embedding. The ankle joints were then stained with hematoxylin and eosin, safranin fast green, and immunohistochemically analyzed for S100A4 and vimentin.

[0066] Experimental data presentation method: Foot swelling level (foot volume), sole thickness and arthritis score are recorded in Figures 1 to 3 Data at each time point are presented as mean ± standard deviation. Anticoagulation was tested using a routine blood analyzer, and the results are reported in Table 1. Statistical analysis of experimental data was performed using GraphPad-Prism 6.0 software using one-way analysis of variance (ANOVA) to compare the mean values ​​of each column for significant differences. A significant difference was considered to be present at p < 0.05.

[0067] 1.2 Experimental results:

[0068] The results showed that (see Figures 1 to 3), paw volume, paw thickness, and arthritis scores in CIA rats were significantly higher than those in the normal group and did not decrease during treatment. Corydaline (CM) effectively alleviated paw swelling and reduced arthritis scores in CIA rats, inhibiting the progression of rheumatoid arthritis.

[0069] Routine blood analysis showed that the administration of corydaline reduced the number of immune cells (neutrophils, lymphocytes) in the blood (see Table 1), and weakened the body's immune level.

[0070] Table 1: Blood routine analysis results of various experimental animals after administration of corydaline

[0071]

[0072] CT analysis showed a decrease in bone damage (see Figure 4 ), HE staining showed that synovial proliferation was inhibited (see Figure 5 ), Safranin fast green staining showed that it alleviated the cartilage destruction in CIA rats (see Figure 6 ), S100A4 and vimentin immunohistochemistry showed that the proliferation of synovial fibroblasts was inhibited (see Figures 7 and 8 ).

[0073] Example 2: In vitro efficacy study of corydaline on primary synovial fibroblasts 2.1 Experimental methods:

[0074] The cells were obtained from primary synovial fibroblasts of rats with rheumatoid arthritis.

[0075] Primary rat synovial fibroblast culture: The synovial tissue of the rat hindfoot joint was digested with 1 mg / mL type II collagenase at 37°C for 2 h. The supernatant was filtered through a strainer and centrifuged at 1000×g for 2 min to collect the synovial fibroblasts. The cells were cultured in DMEM complete medium (DMEM high glucose medium supplemented with a mixed solution of 10% fetal bovine serum and 1% penicillin-streptomycin) at 37°C, 5% CO2, and 95% humidity.

[0076] (1) MTT assay

[0077] Synovial fibroblasts were seeded in 48-well plates at a density of 2 × 10 4 / well, after growing in the incubator for 12 hours, a control group and a drug-treated group were randomly set up, and 4 wells were repeated. The control group was not treated, and the drug-treated group was treated with corydaline, and the concentrations of corydaline were set at 1.5, 3, and 6 μM. After 24 hours of corydaline treatment, the original culture medium in the 48-well plate was carefully aspirated, and DMEM high-glucose medium containing 50 μg / mL MTT was added. The cells were incubated in the dark for 4 hours at 37°C, 5% CO2, and 95% humidity. The culture medium in the 48-well plate was carefully aspirated, and 350 μL DMSO was added to dissolve the purple crystals. The sample absorbance was detected using a multi-function microplate reader with the detection wavelength set at 570 nm. Cell viability = (absorbance of the drug-treated group - blank) / (absorbance of the control group - blank) * 100%.

[0078] (2) Wound healing experiment

[0079] Synovial fibroblasts were seeded in 12-well plates at a density of 5 × 10 5 After cells were fully grown, uniform wounds were created using a sterile 200 μL pipette tip. After washing twice with PBS, the cells were randomly assigned to a control group and a treatment group. The control group received no treatment, while the treatment group received corydaline at concentrations of 1.5, 3, and 6 μM. After 24 hours of corydaline treatment, the culture medium in the 12-well plate was discarded, and the cells were fixed with 4% paraformaldehyde for 30 minutes. Images were captured using a Zeiss microscope, and relative mobility was analyzed using Image J software. Relative mobility = (initial wound area - healed wound area) / initial wound area * 100%.

[0080] (3)Edu experiment

[0081] Synovial fibroblasts were seeded in 24-well plates at a density of 4 × 10 4After 12 hours of growth in an incubator, cells were randomly assigned to control and treatment groups, with triplicate wells. The control group received no treatment, while the treatment group received corydaline at concentrations of 1.5, 3, and 6 μM. After 4 hours of culture, EdU solution preheated to 37°C was added to a final concentration of 10 μM. After 20 hours of incubation, the culture medium in the 24-well plate was carefully aspirated, and the cells were fixed with 4% paraformaldehyde solution at room temperature for 40 minutes. After washing the cells twice with PBS, the wells were perforated with 0.5% Triton X-100 in PBS at room temperature for 40 minutes. After washing the cells twice with PBS, 400 μL / well of Click reaction solution (a mixture of 430 μL Click Reaction Buffer, 20 μL CuSO4, 1 μL AlexaFluor 488, and 50 μL Click Additive Solution) was added in the dark and allowed to react at room temperature for 30 minutes in the dark. The click reaction solution was discarded, and the wells were washed three times with pre-chilled PBS. 400 μL of Hoechst 33342 diluted 1:1000 in PBS was added to each well. The wells were incubated at room temperature in the dark for 10 minutes and washed thoroughly with PBS. Images were captured using a Zeiss fluorescence microscope, and the number of EDU-positive cells was analyzed using Image J software. The excitation / emission wavelengths for Alexa Fluor 488 were 495 nm / 520 nm, and the excitation / emission wavelengths for Hoechst 33342 were 360 ​​nm / 450 nm. The EDU-positive cell percentage = number of 488-positive cells / number of cell nuclei * 100%. Statistical analysis of data was performed using GraphPad-Prism 6.0 software. The mean values ​​of each column were compared using a t-test under one-way analysis of variance (ANOVA). Significant differences were considered to be present at p < 0.05.

[0082] 2.2 Experimental results:

[0083] Wound healing experiments showed that Figures 9 and 10 ), the wound healing degree of the drug-treated group was lower than that of the non-drug-treated group, indicating that CM inhibited the migration of synovial fibroblasts. Figure 11 ), edu proliferation assay (see Figures 12 to 13 ), the number of edu-positive cells in the CM-treated group was significantly lower than that in the non-CM-treated group, indicating that CM inhibits the proliferation of synovial fibroblasts. CM may alleviate rheumatoid arthritis by inhibiting the proliferation of synovial fibroblasts.

[0084] Example 3: In vitro efficacy study of corydaline combined with other natural products on primary synovial fibroblasts

[0085] In this example, the inventors also preliminarily investigated the effect of using corydaline in combination with a variety of other natural product monomers that may have therapeutic effects on rheumatoid arthritis (oridonin, triptolide, resveratrol, sclareol, curcumin, decarinine, scutellaria baicalensis alkaloids, punicalagin, gentisic acid, and naringin).

[0086] 3.1 Experimental methods:

[0087] The cells were obtained from primary synovial fibroblasts of rats with rheumatoid arthritis.

[0088] Primary rat synovial fibroblast culture: The synovial tissue of the rat hindfoot joint was digested with 1 mg / mL type II collagenase at 37°C for 2 h. The supernatant was filtered through a strainer and centrifuged at 1000×g for 2 min to collect the synovial fibroblasts. The cells were cultured in DMEM complete medium (DMEM high glucose medium supplemented with a mixed solution of 10% fetal bovine serum and 1% penicillin-streptomycin) at 37°C, 5% CO2, and 95% humidity.

[0089] MTT assay

[0090] Synovial fibroblasts were seeded in 48-well plates at a density of 2 × 10 4 / well, after growing in the incubator for 12 hours, a control group and a drug-treated group were randomly set up, and 4 wells were repeated. The control group was not treated, and the drug-treated group was treated with the above-mentioned various natural product monomers to be tested, and the concentration was set to 3μM. After 24 hours of treatment with the drug to be tested, the original culture medium in the 48-well plate was carefully aspirated, and DMEM high-glucose medium containing 50μg / mL MTT was added. The reaction was incubated in the dark for 4 hours at 37°C, 5% CO2 and 95% humidity. The culture medium in the 48-well plate was carefully aspirated, and 350μL DMSO was added to dissolve the purple crystals. The sample absorbance was detected using a multi-function microplate reader, and the detection wavelength was set to 570nm. Cell viability = (absorbance of the drug-treated group - blank) / (absorbance of the control group - blank) * 100%.

[0091] The experimental data were statistically analyzed using GraphPad-Prism 6.0 software. The method was to compare whether there was a significant difference in the mean values ​​of each column using the t-test under one-way analysis of variance (ANOVA). A significant difference was considered when p < 0.05.

[0092] The synergy index is determined using the Kim Jung-gwan q-value method, and the q-value is calculated using the following formula:

[0093] q=P A+B / (P A +P B -P A ×P B). Where P A 、P B and P A+B These are the treatment improvement rates for drug A, drug B, and the combination of the two drugs. q < 1 indicates an antagonistic effect between the two drugs; q > 1 indicates a synergistic effect; and q = 1 indicates an additive effect.

[0094] 3.2 Experimental results:

[0095] The experimental results are shown in Table 2 below.

[0096] Table 2 Survival rate of synovial fibroblasts in each drug group (%)

[0097]

[0098] The experimental results show that although natural product monomer compounds such as oridonin and triptolide may have different degrees of inhibitory effects on the proliferation of rat synovial fibroblasts when used alone, these natural product monomer compounds may exhibit three types of results when used in combination with corydaline: antagonism, additive effect and synergistic effect. It can be seen that the effect of corydaline combined with other natural products on rat synovial fibroblasts is difficult to predict.

[0099] As shown in the results in Table 2 , the combination of corydaline and decaline may have a synergistic effect in the treatment of rheumatoid arthritis.

[0100] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. Use of corydaline or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating rheumatoid arthritis.

2. The use according to claim 1, characterized in that: The corydaline inhibits the progression of rheumatoid arthritis, reduces the number of immune cells in the blood, weakens the body's immune level, inhibits synovial hyperplasia, and alleviates joint damage.

3. The use according to claim 1, characterized in that: The medicine comprises a therapeutically effective amount of corydaline and a pharmaceutically acceptable carrier.

4. The use according to claim 3, characterized in that: The medicine also contains other natural products commonly used in clinical treatment of rheumatoid arthritis.

5. The use according to claim 4, characterized in that: The active ingredients in the medicine are composed of corydaline and other natural products.

6. The use according to claim 5, characterized in that: The other natural products are selected from one or more of the following: oridonin, triptolide, resveratrol, sclareol, curcumin, decarinine, borfenobine, punicalagin, gentisic acid or naringin.

7. The use according to claim 6, characterized in that: The weight ratio of the corydaline to the other natural products is 1:10 to 10:

1.

8. The use according to claim 7, characterized in that: The weight ratio of the corydaline to the other natural products is 1:5 to 5:

1.

9. The use according to claim 1, characterized in that: The drug is in oral dosage form.

10. The use according to claim 9, characterized in that: The oral dosage form is selected from oral liquid, tablet, powder, capsule or granule.

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