A composition for rheumatoid arthritis and its preparation method and application

Abstract

The application discloses a composition for rheumatoid arthritis and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine. The technical problem to be solved is how to provide a composition for rheumatoid arthritis which is simple in medicinal ingredient composition, small in dosage and good in effect, and a preparation method and application thereof. The technical solution is as follows: a composition for rheumatoid arthritis is prepared from the following raw materials in parts by weight: Sargentodoxa 10-15 parts, Artemisia ann L. 8-12 parts, Atractylodes lancea 3-8 parts, Phellodendron amurense 6-12 parts, Coix lachryma-jobi 10-15 parts, Gentiana 6-12 parts, Lonicera japonica 12-18 parts, Dipsacus asper 8-12 parts and Taxillus 10-15 parts.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a composition for rheumatoid arthritis, its preparation method, and its application. Background Technology

[0002] Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease primarily affecting the joints. Its main clinical manifestations include joint swelling and pain caused by synovial membrane damage in small joints, followed by cartilage destruction, narrowing of the joint space, and in later stages, severe bone destruction and resorption leading to joint stiffness, deformity, and functional impairment. Currently, commonly used drugs for treating RA include methotrexate, sulfasalazine, leflunomide, and TNFα antagonists. However, many patients do not achieve satisfactory therapeutic effects with these drugs in clinical practice, or cannot adhere to long-term medication due to side effects. Therefore, people are now turning to traditional Chinese medicine.

[0003] There are various traditional Chinese medicine formulas for treating rheumatoid arthritis in the prior art. For example, Chinese invention patent application CN106177642A discloses an oral medication for treating rheumatoid arthritis, in which the components and their mass proportions are as follows: 10-15 parts of Sangjisheng (Taxillus chinensis), 2-11 parts of Zhigancao (Glycyrrhiza uralensis), 4-8 parts of Jiujiechangpu (Acorus tatarinowii), 15-25 parts of Dangshen (Codonopsis pilosula), 10-32 parts of Shudihuang (Rehmannia glutinosa), 15-26 parts of Duzhong (Eucommia ulmoides) (salt-processed), 10-23 parts of Baishao (Paeonia lactiflora), 5-10 parts of Fangfeng (Saposhnikovia divaricata), 8-16 parts of Danggui (Angelica sinensis), 5-16 parts of Niuxi (Achyranthes bidentata), 5-12 parts of Qinjiu (Gentiana macrophylla), 15-26 parts of Fuling (Poria cocos), 5-16 parts of Duhuo (Angelica pubescens), 2-8 parts of Guizhi (Cinnamomum cassia), and chuanxiong (Ligusticum chuanxiong). The patent application lists 5-10 parts of raw herbs, 10-16 parts of kudzu root, 15-45 parts of coix seed, 6-10 parts of alisma rhizome, 6-9 parts of clematis root, 6-12 parts of red peony root, 5-10 parts of fangji root, 8-16 parts of papaya, 2-10 parts of ephedra, 3-10 parts of stir-fried atractylodes rhizome, and 5-16 parts of loofah sponge. However, the patent application contains a large number of 25 herbs and requires a large daily dosage. Each mL of the oral liquid contains 1 part of raw herbs, and patients need to take it three times a day, morning, noon, and evening, at a dosage of 120 ml / time. The daily dosage is 360 mL, which is equivalent to taking 360 parts of raw herbs. Therefore, the patent application has the technical problem of having many herbs and a large dosage. Chinese invention patent application CN109512961A discloses a traditional Chinese medicine composition for treating rheumatoid arthritis, comprising the following raw materials in parts by weight: 20-25 parts of mulberry twig, 20-25 parts of coix seed, 10-15 parts of saposhnikovia root, 10-15 parts of gentian root, 10-15 parts of eleutherococcus root bark, 10-15 parts of astragalus root, 10-15 parts of notopterygium root, 6-9 parts of angelica root, 6-9 parts of cinnamon twig, 6-9 parts of atractylodes rhizome, 6-9 parts of angelica root, and 6-9 parts of licorice root. This composition can promote blood circulation, remove blood stasis, dispel wind and dampness, relieve pain, nourish yin and tonify the kidneys, soften bone spurs, and inhibit hyperplasia. It has a good therapeutic or symptom-relieving effect on pain and swelling caused by rheumatoid arthritis and various types of arthritis. However, the dosage is not disclosed, and the therapeutic effect needs further improvement.

[0004] Therefore, there is an urgent need to provide a composition for rheumatoid arthritis that has a simple medicinal composition, small dosage, and good effect, as well as its preparation method and application. Summary of the Invention

[0005] The present invention aims to overcome the above-mentioned deficiencies of the prior art and provide a composition for rheumatoid arthritis, a method for preparing the composition, and an application thereof.

[0006] Terminology Explanation:

[0007] Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter pertains. Unless otherwise stated, all patents, patent inventions, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0008] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0009] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0010] The terms “optional / arbitrary” or “optionally / arbitrarily” mean that the event or situation described below may or may not occur, including both the occurrence and non-occurrence of the event or situation.

[0011] In a first aspect, the present invention provides a composition for rheumatoid arthritis, said composition being prepared from the following raw materials in parts by weight: 10-15 parts of *Sinomenium acutum*, 8-12 parts of *Artemisia annua*, 3-8 parts of *Atractylodes lancea*, 6-12 parts of *Phellodendron chinense*, 10-15 parts of *Coix lacryma-jobi*, 6-12 parts of *Gentiana macrophylla*, 12-18 parts of *Lonicera japonica*, 8-12 parts of *Dipsacus asper*, and 10-15 parts of *Taxillus chinensis*.

[0012] In one embodiment of the present invention, the composition is prepared from the following raw materials in parts by weight: 10-12 parts of *Sinomenium acutum*, 8-10 parts of *Artemisia annua*, 3-6 parts of *Atractylodes lancea*, 8-12 parts of *Phellodendron chinense*, 10-12 parts of *Coix lacryma-jobi*, 6-9 parts of *Gentiana macrophylla*, 15-18 parts of *Lonicera japonica*, 8-10 parts of *Dipsacus asper*, and 12-15 parts of *Taxillus chinensis*.

[0013] In one embodiment of the present invention, the composition is prepared from the following raw materials in parts by weight: 12 parts of *Sinomenium acutum*, 10 parts of *Artemisia annua*, 6 parts of *Atractylodes lancea*, 10 parts of *Phellodendron chinense*, 12 parts of *Coix lacryma-jobi*, 9 parts of *Gentiana macrophylla*, 15 parts of *Lonicera japonica*, 10 parts of *Dipsacus asper*, and 12 parts of *Taxillus chinensis*.

[0014] The second aspect of the present invention relates to a method for preparing the above-mentioned composition for rheumatoid arthritis, wherein the preparation method is as follows: decocting *Sinomenium acutum* for 30-40 minutes, then adding *Atractylodes lancea*, *Phellodendron chinense*, *Coix lacryma-jobi*, *Gentiana macrophylla*, *Lonicera japonica*, *Dipsacus asper*, and *Taxillus chinensis*, and continuing to decoct; adding *Artemisia annua* 5-10 minutes before the end of decoction, and continuing to decoct until the first decoction is finished, filtering, and obtaining the final product.

[0015] In one embodiment of the present invention, the total time for the first decoction is 50-60 minutes.

[0016] In one embodiment of the present invention, after the first decoction, the decoction is repeated 1-2 times, with each decoction lasting 15-30 minutes.

[0017] As one embodiment of the present invention, the preparation method includes the following steps: (1) Pretreatment: Pick out Qingfengteng and Qinghao separately for later use, and mix the remaining medicinal materials, Atractylodes lancea, Phellodendron chinense, Coix lacryma-jobi, Gentiana macrophylla, Lonicera japonica, Dipsacus asper, and Taxillus chinensis for later use; (2) Soaking: Soak the mixed medicinal materials and the separately picked Qingfengteng in cold water; (3) First decoction: Add the soaked Qingfengteng along with the soaking water to the decoction container, add water and decoct first; (4) Combined decoction: Add the mixed medicinal materials soaked in step (2) and the soaking water to the decoction container in step (3), add an appropriate amount of water, and decoct. (5) Add later: 5-10 minutes before the end of step (4) of simmering, open the lid of the pot, add the artemisia that was picked out in step (1), cover the pot immediately, and continue to simmer until the time is up; (6) Filtration: Stop heating and filter to obtain the first decoction; (7) Second decoction: Add water to the dregs, bring to a boil over high heat, then simmer over low heat for 15-30 minutes, and filter to obtain the second decoction. (8) Mixing: Mix the first decoction with the second decoction to obtain the final product.

[0018] Preferably, the soaking time in step (2) is 30-60 minutes.

[0019] Preferably, the simmering time in step (3) is 30-40 minutes, preferably 40 minutes.

[0020] Preferably, the downtime in step (5) is 5 minutes.

[0021] Preferably, the total simmering time for the first decoction is 50-60 minutes.

[0022] A third aspect of the invention relates to a formulation comprising the above-described composition, the formulation further comprising pharmaceutically acceptable excipients.

[0023] Preferably, the dosage form of the preparation is tablets, capsules, granules, ointments, pills, or oral liquids.

[0024] A fourth aspect of the invention relates to the use of the above-described composition or formulation in the preparation of a medicament for rheumatoid arthritis.

[0025] The present invention has at least the following beneficial effects: Compared with the prior art, the beneficial effects of the present invention are: (1) The composition of the present invention is simple and consists of only 9 raw materials; (2) The dosage is small, and the daily dosage of raw materials is only 96g; (3) The composition obtained by the present invention through specific raw material composition and specific raw material dosage ratio has a better therapeutic effect on rheumatoid arthritis and the effect is better than that of each comparative ratio. Attached Figure Description

[0026] Figure 1 Results of the effects of different drug groups on related inflammatory factors in macrophages (RAW); Figure 2 Results of the effects of different drug groups on related inflammatory factors in synovial fibroblasts (FLS); Figure 3 Representative images of rats from different groups after the experiment. Detailed Implementation

[0027] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0028] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0029] Example 1: A composition for rheumatoid arthritis, said composition being prepared from the following raw materials in parts by weight: 12 parts of *Sinomenium acutum*, 10 parts of *Artemisia annua*, 6 parts of *Atractylodes lancea*, 10 parts of *Phellodendron chinense*, 12 parts of *Coix lacryma-jobi*, 9 parts of *Gentiana macrophylla*, 15 parts of *Lonicera japonica*, 10 parts of *Dipsacus asper*, and 12 parts of *Taxillus chinensis*.

[0030] Preparation method: (1) Soaking: Soak the Qingfengteng in 8 times the amount of cold water for 30 minutes. Mix the Cangzhu, Huangbai, Yiyiren, Qinjiu, Rendongteng, Xuduan, and Sangjisheng, and soak them in 8 times the amount of cold water for 30 minutes. (2) First decoction: Add the soaked Qingfengteng to the decoction container and decoct for 30 minutes. Then add the soaked Atractylodes lancea, Phellodendron chinense, Coix lacryma-jobi, Gentiana macrophylla, Lonicera japonica, Dipsacus asper, and Taxillus chinensis mixed herbs and continue to decoct for 20 minutes. Add Artemisia annua and decoct for 5 minutes (added later). Filter to obtain the first decoction. (3) Second decoction: Add 6 times the amount of water to the dregs, bring to a boil over high heat, then simmer over low heat for 15 minutes, and filter to obtain the second decoction. (4) Mixing: Mix the first decoction with the second decoction to obtain the final product.

[0031] Example 2: A composition for rheumatoid arthritis, said composition being prepared from the following raw materials in parts by weight: 10 parts of *Sinomenium acutum*, 12 parts of *Artemisia annua*, 3 parts of *Atractylodes lancea*, 12 parts of *Phellodendron chinense*, 10 parts of *Coix lacryma-jobi*, 12 parts of *Gentiana macrophylla*, 12 parts of *Lonicera japonica*, 12 parts of *Dipsacus asper*, and 10 parts of *Taxillus chinensis*.

[0032] The preparation method is the same as in Example 1.

[0033] Example 3: A composition for rheumatoid arthritis, said composition being prepared from the following raw materials in parts by weight: 15 parts of *Sinomenium acutum*, 8 parts of *Artemisia annua*, 8 parts of *Atractylodes lancea*, 6 parts of *Phellodendron chinense*, 15 parts of *Coix lacryma-jobi*, 6 parts of *Gentiana macrophylla*, 18 parts of *Lonicera japonica*, 8 parts of *Dipsacus asper*, and 15 parts of *Taxillus chinensis*.

[0034] The preparation method is the same as in Example 1.

[0035] Comparative Example 1: The only difference from Example 1 is that the *Sinomenium acutum* is replaced with an equal amount of *Stephania tetrandra*, and the rest is the same as in Example 1.

[0036] In the preparation method, Qingfengteng was replaced with Fangji, and the rest was the same as in Example 1.

[0037] Comparative Example 2: The only difference from Example 1 is that Gentiana macrophylla is replaced with an equal amount of Clematis chinensis, and the rest is the same as Example 1.

[0038] In the preparation method, Gentiana macrophylla was replaced with Clematis chinensis, and the rest was the same as in Example 1.

[0039] Comparative Example 3: The only difference from Example 1 is that Artemisia annua is replaced with an equal amount of Scutellaria baicalensis, and the rest is the same as in Example 1.

[0040] In the preparation method, Artemisia annua was replaced with Scutellaria baicalensis, and the rest was the same as in Example 1.

[0041] Comparative Example 4: A composition for rheumatoid arthritis, said composition being prepared from the following raw materials in parts by weight: 6 parts of Sinomenium acutum, 16 parts of Artemisia annua, 13.5 parts of Atractylodes lancea, 14.5 parts of Phellodendron chinense, 12 parts of Coix lacryma-jobi, 4.5 parts of Gentiana macrophylla, 7.5 parts of Lonicera japonica, 10 parts of Dipsacus asper, and 12 parts of Taxillus chinensis.

[0042] The preparation method is the same as in Example 1.

[0043] Comparative Example 5: A composition for rheumatoid arthritis, said composition being prepared from the following raw materials in parts by weight: 12 parts of *Sinomenium acutum*, 5 parts of *Artemisia annua*, 3 parts of *Atractylodes lancea*, 5 parts of *Phellodendron chinense*, 17 parts of *Coix lacryma-jobi*, 9 parts of *Gentiana macrophylla*, 15 parts of *Lonicera japonica*, 13 parts of *Dipsacus asper*, and 17 parts of *Taxillus chinensis*.

[0044] The preparation method is the same as in Example 1.

[0045] Experiment Example 1: Cell Experiment Changes in various inflammatory factors in macrophages (RAW) and synovial fibroblasts (FLS) in each group Experimental procedure: ①Resuscitation: Remove the frozen cells from liquid nitrogen, thaw them rapidly in a 37°C water bath, transfer them to centrifuge tubes containing pre-warmed incomplete culture medium (DMEM), centrifuge at 1000 rpm for 5 min, discard the supernatant, resuspend the cells, and then seed them into culture flasks. Incubate at 37°C with 5% CO2. ② Culture and passage: Change the medium the next day. When the cell density reaches 80%-90%, passage: discard the old culture medium, gently scrape off the cells with a cell scraper (do not use trypsin), disperse them, and passage at a ratio of 1:3-1:4; ③ Plating: Take cells in the logarithmic growth phase, scrape them off, count them, and adjust the density to seed them into 6-well plates (e.g., 5×10⁻⁶). 5 (cells / well), culture overnight to allow them to adhere; ④ Drug intervention: Discard the old culture medium and add fresh culture medium containing drugs or stimulants (LPS+IFN-γ). Each group is given the corresponding drug-containing serum for intervention, and culture is continued for a set time (e.g., 6-24h). ⑤ RNA extraction and detection: Transfer cells to a 15mL centrifuge tube, centrifuge at 1000rpm for 5min, discard the supernatant, add 450μL of Lysis Buffer from the RNA extraction kit for 1min lysis, then add 450μL of anhydrous ethanol, transfer to a centrifuge column, centrifuge at 12000rpm for 1min, discard the waste liquid, add 500μL of Wash Buffer, centrifuge again, discard the waste liquid, and centrifuge the empty column again. Transfer the centrifuge column to a 1.5mL EP tube, open the cap and let it air dry, then add 10-20μL of Elution Buffer, centrifuge again, and measure the RNA concentration. Perform cDNA reverse transcription based on the RNA concentration, and detect by RT-qPCR.

[0046] Changes in RAW inflammation-related factors in each group are as follows: Figure 1 As shown, compared with the Control group, ### P <0.001; compared with the Model group, P<0.001; compared with Example 1, the differences between the drug administration groups && P <0.01, &&& P <0.001. According to Figure 1 The results showed that although each group could reduce RAW-related inflammatory markers in RAW, they failed to reach the levels of Examples 1-3, indicating that the combination and dosage of the compound in the examples of the present invention had a better anti-inflammatory effect on macrophages (RAW) than MTX and each comparison ratio.

[0047] The results of changes in FLS-related factors in each group are as follows: Figure 2 As shown, compared with the Control group, ### P <0.001; compared with the Model group, P <0.001; Compared with Example 1, the differences between the drug administration groups... P <0.001. According to Figure 2 The results showed that although each group could reduce FLS-related inflammatory markers in FLS, they failed to reach the level of the embodiments of the present invention. This indicates that the compatibility and dosage of the compound in the embodiments of the present invention have a better anti-inflammatory effect on synovial fibroblasts (FLS) than MTX and each comparison ratio.

[0048] Experimental Example 2: CIA Model Rats Experiment Experimental grouping and drug administration: Male SD rats, weighing 160-180g, were acclimatized and then randomly divided into groups of 8 rats each, according to their body weight.

[0049] Grouping: (1) Control group: Distilled water was administered by gavage, 1.5 mL / 100 g; (2) Model group: Distilled water was administered by gavage, 1.5 mL / 100 g; (3) MTX group: Methotrexate was administered by gavage at a dose of 1.5 mg / kg, dissolved in purified water before gavage, with a gavage volume of 2 mL / animal; (4) Examples 1-3, Comparative Examples 1-5: The corresponding Chinese medicine composition was administered by gavage at a dose of 17g crude drug / kg bw and a gavage volume of 0.75mL / 100g bw.

[0050] Experimental methods and observation indicators: Bovine type II collagen was thawed and thoroughly emulsified with an equal volume of incomplete Freund's adjuvant. No modeling was performed in the normal group, while all other groups received an injection of 100 μL of the emulsion per rat at the tail base to induce inflammation. A second immunization was administered on day 7 post-modeling, with each rat receiving an intradermal injection of 50 μL of the emulsion at the tail base. On day 10 (D0), after successful modeling, gavage treatment began, administered once daily in the morning for 28 days. Rats were sacrificed at the end of the experiment.

[0051] Hind limb swelling measurement: The hind limbs of rats were measured using vernier calipers before modeling, on day 10 after modeling, and at the end of the experiment.

[0052] Arthritis Index (AI) Scoring: Joint index scores were assessed before modeling, on day 10 of modeling, and at the end of the experiment. Systemic lesions were evaluated using a 5-point scoring system. The AI ​​score was calculated by accumulating the scores based on the severity of lesions in the remaining three limbs (those not injected with adjuvant). 0 points: No redness or swelling; 1 point: Redness and swelling of the little toe joint; 2 points: Swelling of the toe joints and toes; 3 points: Swelling of the paws below the ankle joint; 4 points: Swelling of both hind paws, including the ankle joint. The AI ​​score for each rat was calculated by summing the scores of each joint.

[0053] Experimental results: Representative hindlimb swelling in each group of rats, as shown below. Figure 3 As shown in Table 1, the thickness of the hind limbs of rats in each group was measured.

[0054] Table 1: Results of hindlimb thickness measurement in each group of rats

[0055] Note: Compared to the Control group, ### P <0.001; compared with the Model group, P <0.05, P <0.01, P <0.001; Compared with Example 1, the differences between the drug administration groups... P <0.001.

[0056] Ten days after modeling, the rats showed significant swelling in their hind paws, which was highly different from the control group. P <0.001); After 28 days of administration, the swelling in the traditional Chinese medicine composition group of this invention significantly decreased, showing a highly significant difference compared with the Model group ( P<0.001); Comparative Examples 1-5 also showed some inhibitory effect on paw swelling in model mice, but the effect was not as good as that of the Examples, suggesting that the important composition of the present invention can more effectively reduce the degree of hind limb swelling in CIA rats. The composition of the present invention has a better effect under certain drug composition and certain raw material dosage ratio.

[0057] The effect on the arthritis index in rats is shown in Table 2.

[0058] Table 2: AI scores of rats in each group

[0059] Note: Compared to the Control group, ### P <0.001; compared with the Model group, P <0.01, P <0.001; Compared with Example 1, the differences between the drug administration groups... P <0.001.

[0060] Ten days after modeling, the arthritis index of rats increased significantly, showing a highly significant difference compared with the control group. P <0.001); After 28 days of administration, the arthritis index of each treatment group decreased significantly, with significant or highly significant differences compared to the Model group ( P <0.01 or P <0.001), but the effects of the traditional Chinese medicine composition group in the embodiments of the present invention are significantly better than those of the positive drug group and comparative examples 1-5. The traditional Chinese medicine composition of the present invention can reduce the arthritis index of CIA rats, and Example 1 has the best effect.

[0061] The above detailed description is a specific illustration of one feasible embodiment of the present invention, and this embodiment is not intended to limit the patent scope of the present invention. It should be noted that all equivalent implementations or modifications made without departing from the present invention should be included within the scope of the technical solution of the present invention. Therefore, the protection scope of the present invention should be determined by the appended claims.

Claims

1. A composition for treating rheumatoid arthritis, characterized in that, The composition is prepared from the following raw materials in parts by weight: 10-15 parts of *Sinomenium acutum*, 8-12 parts of *Artemisia annua*, 3-8 parts of *Atractylodes lancea*, 6-12 parts of *Phellodendron chinense*, 10-15 parts of *Coix lacryma-jobi*, 6-12 parts of *Gentiana macrophylla*, 12-18 parts of *Lonicera japonica*, 8-12 parts of *Dipsacus asper*, and 10-15 parts of *Taxillus chinensis*.

2. The composition according to claim 1, characterized in that, The composition is prepared from the following raw materials in parts by weight: 12 parts of *Sinomenium acutum*, 10 parts of *Artemisia annua*, 6 parts of *Atractylodes lancea*, 10 parts of *Phellodendron chinense*, 12 parts of *Coix lacryma-jobi*, 9 parts of *Gentiana macrophylla*, 15 parts of *Lonicera japonica*, 10 parts of *Dipsacus asper*, and 12 parts of *Taxillus chinensis*.

3. A method for preparing the composition according to any one of claims 1-2, the method comprising the following steps: (1) Pretreatment: Pick out Qingfengteng and Qinghao separately for later use, and mix the remaining medicinal materials, Atractylodes lancea, Phellodendron chinense, Coix lacryma-jobi, Gentiana macrophylla, Lonicera japonica, Dipsacus asper, and Taxillus chinensis for later use; (2) Soaking: Soak the mixed medicinal materials and the separately picked Qingfengteng in cold water; (3) First decoction: Add the soaked Qingfengteng along with the soaking water to the decoction container, add water and decoct first; (4) Combined decoction: Add the mixed medicinal materials soaked in step (2) and the soaking water to the decoction container in step (3), add an appropriate amount of water, and decoct. (5) Add last: Add Artemisia annua last before the end of step (4) of decoction, cover immediately and continue to decoct until the time is up; (6) Filtration: Stop heating and filter to obtain the first decoction; (7) Second decoction: Add water to the dregs, bring to a boil over high heat, then simmer over low heat for 15-30 minutes, and filter to obtain the second decoction. (8) Mixing: Mix the first decoction with the second decoction to obtain the final product.

4. The preparation method according to claim 3, characterized in that, The soaking time in step (2) is 30-60 minutes.

5. The preparation method according to claim 3, characterized in that, The simmering time mentioned in step (3) is 30-40 minutes.

6. The preparation method according to claim 3, characterized in that, The time for adding Artemisia annua in step (5) is 5-10 minutes.

7. The preparation method according to claim 3, characterized in that, The total simmering time for the first decoction is 50-60 minutes.

8. A formulation comprising the composition according to any one of claims 1-2 or the composition prepared by the preparation method according to any one of claims 3-7, characterized in that, The formulation also includes pharmaceutically acceptable excipients.

9. The formulation according to claim 8, characterized in that, The dosage form of the preparation is tablets, capsules, granules, ointments, pills, or oral liquids.

10. The use of a composition according to any one of claims 1-2, a composition prepared by any one of claims 3-7, or an formulation according to any one of claims 8-9 in the preparation of a medicament for treating rheumatoid arthritis.

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