Application of traditional Chinese medicine composition as medicine for treating rheumatoid arthritis and preparation method of traditional Chinese medicine composition

Abstract

The invention discloses application of a traditional Chinese medicine composition as a medicine for treating rheumatoid arthritis and a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10-25 parts of flos rhododendri mollis (prepared), 10-25 parts of radix angelicae sinensis, 10-25 parts of flos carthami, 10-25 parts of radix angelicae, 10-25 parts of pollen typhae, 5-15 parts of frankincense (prepared), 5-15 parts of myrrh (prepared) and 0.5-1 part of borneol. The traditional Chinese medicine composition has the effects of dispelling wind, eliminating dampness, promoting blood circulation to remove blood stasis, dredging arthralgia and relieving pain, and the traditional Chinese medicine composition is prepared into an external gel emplastrum for treating rheumatoid arthritis.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to the use and preparation method of a traditional Chinese medicine composition as a drug for treating rheumatoid arthritis. Background Technology

[0002] Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by erosive arthritis. The peak age of onset is 45-60 years, but it can occur at any age. Epidemiological surveys show that the global incidence of RA is 0.5%-1%, while the incidence in my country is 0.42%. The basic pathological changes in RA include synovitis and pannus formation, which gradually leads to the destruction of articular cartilage and bone, ultimately resulting in joint deformities and loss of function. RA is a highly disabling disease and a significant cause of disability in my country; the disability rate increases with the progression of the disease. In addition, RA can also lead to complications such as pulmonary and cardiovascular diseases, osteoporosis, and malignant tumors, causing not only a decline in patients' physical function, quality of life, and social participation, but also imposing a huge economic burden on their families and society.

[0003] The primary treatment goal of rheumatoid arthritis (RA) is to maximize the patient's long-term quality of life by controlling inflammatory symptoms, preventing joint destruction, maintaining joint function, and sustaining normal social activities. Eliminating inflammation is paramount in achieving this goal. Currently, the main clinical treatments include: ① Traditional synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, sulfasalazine, and leflunomide. While these are effective at suppressing inflammation and immune responses, they have limitations in comprehensively improving joint function and repairing damaged cartilage and bone tissue, and they also have significant adverse effects; ② Biologics, such as tumor necrosis factor-alpha inhibitors and interleukin-6 receptor antagonists; ③ Small molecule targeted therapies, such as JAK inhibitors, but their overall usage rate is low. Biologics and targeted drugs are expensive, placing a heavy financial burden on health insurance systems and individual patients.

[0004] Traditional Chinese medicine (TCM) considers rheumatoid arthritis (RA) to fall under the category of "Bi syndrome," particularly known as "Wang Bi" or "Li Jie Feng." Its core pathogenesis involves wind, cold, and dampness invading the muscles and bones, obstructing the meridians, leading to poor blood and qi circulation. Prolonged illness can penetrate the collaterals, causing phlegm and blood stasis, resulting in severe joint pain, swelling, stiffness, and even deformity. Treatment focuses on strong analgesia to address the symptoms, while promoting blood circulation, removing blood stasis, dispelling wind, and eliminating dampness to address the root cause. TCM external application ointments are based on the principles of meridians in TCM. Through the synergistic effect of various medications, they combine to exert therapeutic effects. These ointments often contain strongly scented aromatic drugs, which penetrate the skin to produce anti-inflammatory, analgesic, and blood-activating effects, helping to relieve the pain and swelling symptoms of rheumatism.

[0005] The traditional Chinese medicine prescription for "Qiongye Ointment" in the Qing Dynasty medical text *Yizong Jinjian* consists of eight herbs: Rhododendron molle, Angelica sinensis (tail), Carthamus tinctorius, Angelica dahurica, Typha orientalis, Frankincense, Myrrh, and Borneol. It was used to treat "injuries from sprains and beatings, and skin and flesh abrasions." No research reports have been found on its use in treating "Bi syndrome" (rheumatoid arthritis). Furthermore, the "Qiongye Ointment" in *Yizong Jinjian* is a traditional ointment, described as follows: "Angelica sinensis (tail), Rhododendron molle, Carthamus tinctorius, Angelica dahurica, and Typha orientalis are soaked in sesame oil for seven days, then fried until withered and the residue removed; white wax and yellow wax are added, melted completely, and filtered through silk; slightly warmed, borneol, Myrrh, and Frankincense powder, six qian each, are added, stirred well, and applied." This method of preparation, involving high-temperature frying, significantly affects the medicinal components, especially some volatile and heat-instantaneous components. In addition, traditional ointments are inconvenient for patients to use. Based on the above background, this invention, based on the traditional Chinese medicine prescription of "Qiongye Ointment" in "Yizong Jinjian", determines that Rhododendron molle is a wine-steamed product and Frankincense and Myrrh are vinegar-processed products for use in medicine, and invents a method for preparing a new type of external gel plaster, which is used for the first time in the treatment of arthralgia (rheumatoid arthritis). Summary of the Invention

[0006] The purpose of this invention is to provide a traditional Chinese medicine composition for treating rheumatoid arthritis and its preparation method.

[0007] To achieve the objectives of this invention, the following implementation scheme is provided.

[0008] In one embodiment, the present invention provides the use of a traditional Chinese medicine composition as a medicament for treating rheumatoid arthritis, the traditional Chinese medicine composition comprising processed rhododendron molle, Angelica sinensis tail, safflower, Angelica dahurica, Typha pollen, processed frankincense, processed myrrh, and borneol.

[0009] In some embodiments, the above-described uses of the present invention, wherein the traditional Chinese medicine composition comprises, by weight, 10-25 parts of processed Rhododendron molle, 10-25 parts of Angelica sinensis tail, 10-25 parts of Carthamus tinctorius, 10-25 parts of Angelica dahurica, 10-25 parts of Typha pollen, 5-15 parts of processed Boswellia carterii, 5-15 parts of processed Commiphora myrrha, and 0.5-1 parts of Borneol.

[0010] In some preferred embodiments, the above-described uses of the present invention, wherein the traditional Chinese medicine composition comprises 18 parts by weight of processed Rhododendron molle, 18 parts by weight of Angelica sinensis tail, 18 parts by weight of Carthamus tinctorius, 18 parts by weight of Angelica dahurica, 18 parts by weight of Typha pollen, 5 parts by weight of processed Boswellia carterii, 5 parts by weight of processed Commiphora myrrha, and 0.5 parts by weight of Borneol.

[0011] In some embodiments, the present invention provides a traditional Chinese medicine composition for treating rheumatoid arthritis, comprising processed rhododendron flower, Angelica sinensis tail, safflower, Angelica dahurica, Typha pollen, processed frankincense, processed myrrh, and borneol.

[0012] In some embodiments, the traditional Chinese medicine composition of the present invention comprises, by weight, 10-25 parts of processed Rhododendron molle, 10-25 parts of Angelica sinensis tail, 10-25 parts of Carthamus tinctorius, 10-25 parts of Angelica dahurica, 10-25 parts of Typha orientalis, 5-15 parts of processed Boswellia carterii, 5-15 parts of processed Commiphora myrrha, and 0.5-1 parts of Borneol.

[0013] In a preferred embodiment, the traditional Chinese medicine composition of the present invention comprises 18 parts by weight of processed Rhododendron molle, 18 parts by weight of Angelica sinensis tail, 18 parts by weight of Carthamus tinctorius, 18 parts by weight of Angelica dahurica, 18 parts by weight of Typha pollen, 5 parts by weight of processed Boswellia carterii, 5 parts by weight of processed Commiphora myrrha, and 0.5 parts by weight of Borneol.

[0014] In one embodiment, the present invention also provides a topical preparation comprising 100 parts of the active ingredient of the traditional Chinese medicine composition of the present invention and pharmaceutical excipients, wherein the pharmaceutical excipients comprise 7.5-47.5 parts by weight of sodium polyacrylate, 350-550 parts of glycerin, 0.5-1.5 parts of aluminum glycine, 0.5-2.5 parts of tartaric acid, 5-45 parts of carbomer, and 400-800 parts of purified water.

[0015] In a preferred embodiment, the topical formulation of the present invention comprises, by weight, 30 parts sodium polyacrylate, 400 parts glycerin, 1 part aluminum glycinate, 1 part tartaric acid, 40 parts carbomer, and 600 parts purified water.

[0016] In a preferred embodiment, the topical preparation of the present invention contains a traditional Chinese medicine active ingredient that is a powder, granules, extract, or paste of the traditional Chinese medicine composition of the present invention.

[0017] In a preferred embodiment, the topical formulation of the present invention is a topical gel or a gel patch.

[0018] In one embodiment, the present invention also provides a method for preparing a topical formulation, comprising the following steps: S1: Take the prescribed amount of medicinal materials except for borneol, dry them, and pulverize them into ultrafine powder. Grind the borneol into fine powder using a mortar and pestle. Mix the ultrafine powder and borneol powder evenly to make Chinese medicine powder for later use. S2: Mix the prepared traditional Chinese medicine powder, sodium polyacrylate, aluminum glycinate, and glycerol evenly to form phase A; S3: Mix tartaric acid, carbomer, and purified water thoroughly to form phase B; S4: Mix phase A and phase B evenly, and perform cross-linking treatment to obtain a gel material.

[0019] In some embodiments, the preparation method of the present invention further involves coating the gel material onto one side of a base layer and covering it with a protective layer to obtain a gel patch.

[0020] In some embodiments, the preparation method of the present invention preferably uses a nonwoven fabric as the base layer and a polyethylene film as the protective layer.

[0021] In one specific embodiment, the present invention provides a gel patch for treating rheumatoid arthritis, comprising a base layer, a gel layer containing traditional Chinese medicine ingredients, and a protective layer stacked sequentially; the base layer is preferably a non-woven fabric, and the protective layer is preferably a polyethylene film.

[0022] The gel patch of the present invention comprises 7.5-47.5 parts of sodium polyacrylate, preferably 17.5-37.5 parts, and more preferably 30 parts, as the excipients of the gel layer. The sodium polyacrylate is preferably sodium polyacrylate NP700, which serves as a skeleton material and its function is to form a gel patch matrix with a three-dimensional network structure.

[0023] The gel patch of the present invention further includes 350-550 parts of glycerin, preferably 350-450 parts, and more preferably 400 parts, as an excipient in the gel layer. Glycerin mainly functions as a moisturizer, which helps maintain the moisture content of the gel patch matrix and improves skin hydration.

[0024] The gel patch of the present invention further includes 0.5-1.5 parts of aluminum glycinate, preferably 0.75-1.25 parts, and more preferably 1.0 part, as an excipient in the gel layer. Aluminum glycinate acts as a crosslinking agent, participating in the crosslinking reaction and facilitating the formation of the three-dimensional network structure of the gel patch matrix.

[0025] The gel patch of the present invention further includes 0.5-2.5 parts of tartaric acid, preferably 0.5-1.0 parts, and more preferably 1.0 part, in the excipients of the gel layer. Tartaric acid acts as a crosslinking regulator, which can regulate the rate of crosslinking reaction and is beneficial to controlling the forming time of the patch.

[0026] The gel patch of the present invention further includes 5-45 parts of carbomer, preferably 25-45 parts, and more preferably 40 parts, as an excipient in the gel layer. The carbomer is a thickener that can improve and increase the viscosity of the matrix, and also has emulsifying and stabilizing effects.

[0027] The gel patch of the present invention further includes 400-800 parts of water in the gel layer, preferably 500-700 parts, and more preferably 600 parts.

[0028] Specifically, the gel patch of the present invention, by weight parts, comprises the following: the gel layer includes 100 parts of medicinal powder, 7.5-47.5 parts of sodium polyacrylate, 350-550 parts of glycerin, 0.5-1.5 parts of aluminum glycinate, 0.5-2.5 parts of tartaric acid, 5-45 parts of carbomer, and 400-800 parts of purified water. Preferably, it comprises: 100 parts of medicinal powder, 17.5-37.5 parts of sodium polyacrylate, 350-550 parts of glycerin, 0.75-1.25 parts of aluminum glycinate, 0.5-1.0 part of tartaric acid, 25.00-45.00 parts of carbomer, and 500-700 parts of purified water. More preferably, it comprises: 100 parts of traditional Chinese medicine powder, 30 parts of sodium polyacrylate, 400 parts of glycerin, 1 part of aluminum glycinate, 1 part of tartaric acid, 40 parts of carbomer, and 600 parts of purified water. The gel ointment prepared according to this formula has good pharmaceutical properties such as formability and adhesion.

[0029] Terminology: "Rhododendron molle (processed)" refers to the wine-steamed products of Rhododendron molle; "Frankincense (processed)" and "Myrrh (processed)" both refer to vinegar-processed products.

[0030] The present invention relates to a traditional Chinese medicine composition for treating rheumatoid arthritis. Processed *Rhododendron molle* is the principal ingredient; it is pungent, warm, and highly toxic, representing a type of antirheumatic herb. It excels at dispelling wind and dampness, dispersing blood stasis, and relieving pain. The *Shennong Bencao Jing* records that it "treats wind-dampness in the skin, causing persistent pain, malaria, malignant sores, and various types of numbness." Yellow rice wine has the effect of promoting blood circulation and removing blood stasis. The *Compendium of Materia Medica* records that "*Rhododendron molle* treats wind-dampness in the skin causing persistent pain, rheumatic pain, and speech impairment; it is steamed with wine, powdered, and taken with milk wine." Processing with wine enhances its synergistic effect. Safflower, processed frankincense, and processed myrrh are the assistant ingredients. Safflower is pungent and warm, dispersing and promoting blood circulation, dispersing blood stasis, and relieving pain. Frankincense and myrrh form a blood-activating and pain-relieving pair, promoting blood circulation, dispersing blood stasis, relieving pain, reducing swelling, and promoting tissue regeneration. Processing with vinegar enhances its swelling-reducing and pain-relieving effects. Angelica sinensis (tail), Angelica dahurica, and Typha pollen are used as adjuvant herbs. Angelica sinensis is sweet, pungent, and warm, and is used to nourish and invigorate blood; the tail of Angelica sinensis has a stronger blood-invigorating effect. Angelica dahurica is pungent and warm, and dispels wind and cold, dries dampness and reduces swelling, and relieves pain. Its strong pungent aroma can penetrate the skin and is good at removing wind, cold, and dampness from the skin, muscles, and bones. Typha pollen is sweet and neutral, and can resolve blood stasis, stop bleeding, and promote urination. Its main function is to disperse blood stasis and relieve pain, and it can eliminate dampness from the joints. Borneol is used as the guiding herb. It is bitter, pungent, and slightly cold, and has a fragrant and penetrating nature. It clears heat and relieves pain, and can penetrate the skin and guide the medicine directly to the affected area. This Chinese herbal composition is mainly based on pungent, fragrant, warm, invigorating, blood-activating, and analgesic properties. The whole formula works together to open up obstructions, reduce swelling, and relieve pain, and is used for "Bi syndrome" (rheumatoid arthritis).

[0031] The traditional Chinese medicine composition of this invention treats rheumatoid arthritis using an external treatment method. It is applied as a gel patch to the affected area of ​​rheumatoid arthritis, which improves symptoms, inhibits the release of inflammatory factors, and alleviates bone destruction, with high safety. The dosage range is 6.94–8.38 g crude drug / kg body weight / day, preferably 8.33–8.38 g crude drug / kg body weight / day. Attached Figure Description

[0032] Figure 1 The Arthritis Index (AI) scores and joint swelling of rats in each experimental group of Example 7 are shown. Figure 2 The bar chart shows the serum levels of inflammatory factors IL-1β, IL-6, and NF-κB in rats from each experimental group in Example 7. Figure 3 The images show HE staining, Safranin-Fix Green staining, and Trap staining of the rat ankle joints in each experimental group of Example 7. Figure 4 The bar chart shows the Micro-CT images of rat joints and changes in bone microstructure in each experimental group of Example 7. Figure 5 The images show the changes in liver and kidney function indicators and HE staining of liver and kidney tissues in each experimental group of Example 7. Detailed Implementation

[0033] The following embodiments are provided to describe the present invention in more detail. However, these embodiments are provided only to help further understand the present invention and are not intended to limit the present invention. Those skilled in the art should understand that equivalent substitutions or corresponding improvements made to the content of the present invention still fall within the protection scope of the present invention.

[0034] Experimental medicinal materials and excipients: Safflower (batch number 240350412), Angelica sinensis tail (batch number 240860763), Angelica dahurica (batch number 231110644), vinegar-processed frankincense (batch number 240610431), and vinegar-processed myrrh (batch number 240610428) were all purchased from Chongqing Chinese Medicine Slices Factory Co., Ltd., Typha pollen powder (batch number 2404120212) was purchased from Sichuan Qingshen Kanghua Pharmaceutical Co., Ltd., Borneol (batch number Z51022577) was purchased from Sichuan Qingshen Kanghua Pharmaceutical Co., Ltd., and processed Rhododendron molle (JZ20240424) was provided by the processing base of Chongqing Traditional Chinese Medicine Hospital. Tartaric acid (batch number C2201334) and aluminum glycine (batch number C2020139) were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., carbomer (batch number C03220220901) was purchased from Guizhou Xinzihong Pharmaceutical Excipients Co., Ltd., glycerol (batch number 20240101) was purchased from Nanchang Baiyun Pharmaceutical Co., Ltd., and sodium polyacrylate NP700 (batch number 2Z2470B) was purchased from Chongqing Lisiman Trading Co., Ltd.

[0035] Example 1: Traditional Chinese Medicine Gel Patch Prescription (by weight): 18 parts of processed Rhododendron molle, 18 parts of Angelica sinensis tail, 18 parts of Carthamus tinctorius, 18 parts of Angelica dahurica, 18 parts of Typha pollen, 5 parts of processed Boswellia carterii, 5 parts of processed Commiphora myrrha, and 0.5 parts of Borneol.

[0036] Preparation process: S1: Accurately weigh 18 parts of processed Rhododendron molle, 18 parts of Angelica sinensis tail, 18 parts of Carthamus tinctorius, 18 parts of Angelica dahurica, 18 parts of Typha pollen, 5 parts of processed Boswellia carterii, and processed Commiphora myrrha according to the prescription, dry them, and pulverize them into ultrafine powder; grind borneol into fine powder using a mortar and pestle, and set aside. S2: Mix 30 parts of sodium polyacrylate NP700, 1 part of aluminum glycine and 400g of glycerin evenly, then add 100 parts of traditional Chinese medicine powder and mix evenly to obtain phase A; S3: Dissolve 1 part tartaric acid and 40 parts carbomer in 600 parts purified water to form phase B; S4: Mix phase A and phase B evenly, and stir at 120 rpm for 10 min in a water bath at 50°C to obtain a gel material (viscous semi-solid fluid). S5: Coat the gel material onto one side of the nonwoven base layer with a coating thickness of 1 mm, then cover with a polyethylene film protective layer. After shaping, a gel layer is formed between the base layer and the protective layer. After punching (12cm×8cm), allow it to stand naturally at room temperature in a cool place for 2 days to allow the gel material to form a gel layer, thus obtaining a gel plaster. Examples 2-5 The gel plaster was prepared according to the method of Example 1, except that the composition of the Chinese herbal powder and the amount of excipients were different, as detailed in Table 1.

[0037] Table 1. Formulations of the gel patches in each embodiment

[0038] Example 6 Quality Evaluation According to the adhesion test of gel patches in Part IV of the 2025 edition of the Pharmacopoeia of the People's Republic of China, and based on preliminary experiments and relevant literature reports, initial tack, holding power, and comprehensive sensory score were used as evaluation indicators for gel patches.

[0039] ① Initial tack: The rolling ball ramp stop method is used for determination. The test method is followed, and the largest steel ball number that the tack surface of the test sample can stick to is observed and recorded.

[0040] ② Holding power: The test is conducted using a holding power colorimeter. The test sample is longitudinally adhered to the middle of the test steel plate, and a fixed-weight roller is used to roll it back and forth three times at a uniform speed. The sample is then hung on the test frame, and a weight of specified mass is hung vertically on the test plate. The time it takes for the gel patch to completely fall off is recorded.

[0041] ③ Overall sensory evaluation: (a) Appearance evaluation: uniformity of appearance, softness and hardness of paste, etc., divided into 5 levels (good, better, average, poor, poor, each level differs by 2 points, with a full score of 10 points).

[0042] (b) Residue: After the ointment is applied to the skin and removed, the degree of residue is observed and divided into 5 levels (none, little, moderate, more, and much, with each level differing by 2 points, for a maximum of 10 points).

[0043] (c) Skin adherence: Apply the cream firmly to the arm and shake it vigorously 10 times. Observe whether the cream falls off. If it falls off, score 0 points; if it does not fall off, score 10 points. The total score for the overall sensory evaluation is 30 points.

[0044] The performance test results of the gel patches in Examples 1-5 are shown in Table 2. As can be seen from Table 2, the gel patches in Examples 1-5, based on initial tack, holding power, and comprehensive sensory evaluation, meet the product performance requirements for all indicators.

[0045] Table 2. Overall Score of Molding in Examples

[0046] Example 7: Pharmacodynamic Evaluation of Anti-rheumatoid Arthritis (1) Experimental instruments: PV-200 toe volume measuring instrument (Chengdu Taimeng Software Co., Ltd.), Chemray 240 fully automated biochemical analyzer (Shenzhen Leidu Life Science and Technology), Donatello pathological tissue dehydrator (Italy DIAPATH), E100 microscope (Japan Nikon), Epoch enzyme-linked immunosorbent assay (BioTeK), SkyScan1276 Micro-CT (Germany Bruker).

[0047] (2) Experimental consumables: Bovine type II collagen solution (batch number 240382) and incomplete adjuvant (batch number 240467) were purchased from Chondrex. Universal tissue fixative (batch number GP24113050942), EDTA decalcification solution (batch number GC2501011), HE staining solution (batch number G1003), and Safranin-Fix-Green staining solution (batch number G1053) were purchased from Wuhan Saiwei Biotechnology Co., Ltd. IL-2 kit (batch number JM-02503M1), IL-6 kit (batch number JM-02501M1), and NF-κB kit (batch number JM-02501M1) were purchased from Jingmei.

[0048] (3) Animal grouping and administration: SPF-grade male Wistar rats, 7 weeks old, with a body weight of (170 ± 30) g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., license number: SCXK (Beijing) 2021–0006. All rats were randomly divided into 4 groups: blank group, model group, positive group, and 5 test groups (testing Examples 1–5 respectively), with 8 rats in each group. Except for the blank group, rats in the other groups were subcutaneously injected at the tail with bovine type II collagen and incomplete adjuvant after emulsification to establish a CIA rat model, and a 5-grade scoring method was used to evaluate the model (see Table 3). The administration regimens for each group are shown in Table 4. One day before medication, the ankles of rats in all groups were depilated with a hair removal machine, and medication was administered continuously for 10 days. Changes in body weight, arthritis index, and foot swelling degree of each group were recorded. The swollen parts of the ankles and toes were covered with a hydrogel plaster (area size 4 cm × 6 cm) and fixed with medical tape. Medication was administered once a day, and each application was maintained for 8 h (rats wore Elizabethan collars to prevent them from biting off the hydrogel plaster).

[0049] Table 3. Arthritis index score of rats

[0050] Table 4. Grouping and administration regimen

[0051] (4) Observation indicators and results ① Changes in arthritis index, foot swelling degree, etc. of rats During the medication period, the arthritis index (AI) score and joint swelling degree of rats were measured every other day. The results showed that: the western medicine positive group and each example group could improve the inflammatory state of CIA rats to varying degrees, reduce the arthritis score and foot swelling degree, especially the positive group, Example 1, and Example 2 groups were the most obvious. See Figure 1 .

[0052] ② Serum inflammatory factor levels After the experiment, blood was collected from the abdominal aorta under anesthesia, centrifuged, and serum was collected. ELISA was used to detect the levels of serum inflammatory indicators (IL-1β, IL-6, NF-κB). The results showed that each administration group could inhibit the levels of inflammatory factors TNF-α, IL-1β, and NF-κB in serum to varying degrees. Among them, the positive group, Example 1, and Example 2 had the best effects, followed by Example 5. See Figure 2 .

[0053] ③ Observation of pathological tissues of rat ankles After blood collection, rats were euthanized, and the left hind limb ankle joint was harvested. Fur, muscle, and adipose tissue were removed, and the joint was immediately fixed in 4% paraformaldehyde for at least 24 hours. Decalcification was then complete using EDTA decalcification solution. The joint was washed twice with PBS buffer, dehydrated using an automatic dehydrator, embedded in paraffin, and sectioned. Hematoxylin-eosin (HE), safranin-fast green, and trap staining were performed, and histopathological changes were observed under a light microscope. Results showed that the positive control drug and the drugs in each example could improve synovial hyperplasia, reduce inflammatory cell count and angiogenesis in the ankle joint tissue to varying degrees, improve articular cartilage erosion, and inhibit bone destruction. The positive control group, Example 1, and Example 2 showed the most significant effects. Figure 3 .

[0054] ④ Micro-CT imaging and changes in bone microstructure The right ankle and toe joints of rats were harvested, and the fur, muscle, and adipose tissue were removed. The rats were immediately immersed in 4% paraformaldehyde for fixation for at least 24 hours, followed by micro-computed tomography (Micro-CT) scanning. Scanning parameters: X-ray tube current 200 μA, voltage 85 kV, scanning the entire object, scanning resolution 10.133345 μm, exposure time 384 ms, and scanning angle 180°. ROI analysis was performed using CTAnalyser, and parameters such as bone mineral density (BMD) and bone-to-tissue volume ratio (BV / TV) were calculated. Results showed that all treatment groups improved bone microstructure in CIA rats to varying degrees, with the positive control group and Example 1 significantly increasing BMD. p <0.05); the positive drug, Example 1, and Example 2 all increased BV / TV ( p <0.05), reduce BS / BV level ( p <0.05). See Figure 4 .

[0055] ⑤ Safety evaluation Serum samples were collected from rats in each group, and liver and kidney function-related indicators were detected using an automated biochemical analyzer. Liver and kidney tissues from rats in each group were fixed in 4% paraformaldehyde for more than 24 hours, dehydrated, embedded in paraffin, sectioned, dewaxed, stained with hematoxylin and eosin (HE), and observed under a microscope. Results showed no abnormalities in serum ALT, AST, TBIL, BUN, CREA, and UA levels in the drug-treated groups, and pathological analysis of liver and kidney tissues revealed normal cell structure, indicating that the drug did not cause liver or kidney damage and had good safety. See results below. Figure 5 .

[0056] In summary, this invention is the first to discover that the gel plaster prepared from this combination of traditional Chinese medicines can improve arthritis symptoms in CIA model rats, inhibit the release of inflammatory factors, reduce inflammatory tissue damage, inhibit bone destruction, and thus delay the progression of rheumatoid arthritis, with good safety.

[0057] Example 8: Clinical observation of the treatment of rheumatoid arthritis (1) Research data Thirty-five patients with acute rheumatoid arthritis (cold-dampness obstruction type) who visited the Department of Orthopedics and Traumatology at Chongqing Traditional Chinese Medicine Hospital from April 2024 to July 2025 were selected as the study subjects. They were randomly divided into a control group and an observation group. The control group consisted of 17 patients (8 males and 9 females), aged 39-68 years (mean 57.33±7.18 years), with a disease duration of 4-13 years (mean 5.12±2.55 years). The observation group consisted of 18 patients (8 males and 10 females), aged 40-73 years (mean 55.38±6.91 years), with a disease duration of 2-10 years (mean 5.07±2.22 years). There were no statistically significant differences in general characteristics between the two groups. p >0.05), indicating comparability between groups.

[0058] (2) Diagnostic criteria Western medicine diagnostic criteria: Rheumatoid arthritis can be diagnosed if the patient meets the diagnostic criteria for RA proposed by the American College of Rheumatology (ACR) in 2010, namely: joint involvement (small, medium and large) score of 0-5, serological markers (RF, anti-CCP) score of 0-3, duration of synovial inflammation (6 weeks) score of 0-1, acute phase reactants (CRP, ESR) score of 0-1, and a total score of ≥6.

[0059] Traditional Chinese Medicine Diagnostic Criteria: Based on the "Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis Combining Disease and Syndrome" issued by the China Association of Traditional Chinese Medicine in 2018, the following criteria were used to identify rheumatoid arthritis of the cold-dampness obstruction type (main symptoms: joints are cold, painful and swollen, pain increases with cold and decreases with heat, difficulty in flexion and extension of joints, morning stiffness, joint deformity; secondary symptoms: bland taste in the mouth and no thirst, aversion to wind and cold, worsening on rainy days, heaviness in the limbs; tongue and pulse: pale tongue, white coating, wiry and tight pulse).

[0060] (3) Inclusion and exclusion criteria Inclusion criteria: ① Active rheumatoid arthritis (DAS28 score > 2.6), with TCM diagnosis of cold-dampness obstruction type; ② Informed consent to this study and signed a written consent form.

[0061] Exclusion criteria: ① Joint deformities that prevent patients from living independently; ② Patients with other types of rheumatic diseases; ③ Patients with heart, liver, or kidney dysfunction; ④ Patients allergic to the drugs used in the study; ⑤ Patients who have used hormones or nonsteroidal anti-inflammatory drugs within the past two weeks; ⑥ Pregnant or breastfeeding women.

[0062] (4) Treatment methods Patients in the control group used loxoprofen sodium gel patches (batch number 32501107, provided by Hunan Jiudian Pharmaceutical Co., Ltd.); patients in the observation group used the pilot-scale product of Implementation Case 1 (provided by the Preparation Center of Chongqing Municipal Hospital of Traditional Chinese Medicine). Patients applied the corresponding medication directly to the affected area once a day for 8 hours each time, for two consecutive weeks.

[0063] (5) Observation indicators and results ① Clinical observation According to the American College of Rheumatology (ACR) criteria for improvement in rheumatoid arthritis, including ACR20, ACR50, and ACR70, treatment was considered effective when the improvement rate reached or exceeded ACR20; otherwise, it was considered ineffective. Results showed that after 2 weeks of treatment, the overall effective rate in the observation group (94.44%) was significantly higher than that in the control group (82.35%), and the difference was statistically significant. p <0.05), see Table 5.

[0064] Table 5. Comparison of clinical efficacy between the two groups (%)

[0065] Note: Compared with the control group, * p <0.05 ② Disease activity score Visual analog scale (VAS) scores for pain were calculated for both groups before and after treatment. The scores were expressed in centimeters (cm) and ranged from 0 to 10 (0 for no pain, 10 for severe pain). The DAS28 score was calculated for 28 joints: DAS28 ≤ 2.6 indicated disease relief, 2.6 < DAS28 ≤ 3.2 indicated mild activity, 3.2 < DAS28 ≤ 5.1 indicated moderate activity, and DAS28 > 5.1 indicated high activity. A difference of > 0.6 between two scores indicated moderate improvement, and a difference of > 1.2 indicated significant improvement. The DAS28 score was calculated as: DAS28 score = 0.56 × sqrt (number of painful joints) + 0.28 × sqrt (number of swollen joints) + 0.70 × ln (erythrocyte sedimentation rate) + 0.014 × (VAS score). Results: Before treatment, there were no statistically significant differences in joint VAS scores or DAS28 scores between the two groups. P >0.05); Comparing before and after treatment, the disease activity in both groups was significantly lower than before treatment ( P <0.05 indicates that both drugs improved disease activity in patients. After treatment, the VAS and DAS28 scores in the observation group were significantly lower than those in the control group ( p <0.05), see Table 6.

[0066] Table 6. Comparison of VAS and DAS28 scores of the joints before and after treatment in the two groups ( )

[0067] Note: Comparison before and after treatment within the same group. # p <0.05; compared with the control group, the observation group, * p <0.05 ③ Traditional Chinese Medicine Syndrome Scoring The primary symptoms included joint pain and swelling that worsened with cold and warmth, limited joint flexion and extension, morning stiffness, and joint deformity, scored as 0, 1, 2, and 3 points respectively (none, mild, moderate, and severe). Secondary symptoms included a bland taste in the mouth without thirst, aversion to wind and cold that worsened on rainy days, and heaviness in the limbs, scored as 0 and 1 points respectively (present and absent). Results: Before treatment, there was no statistically significant difference in TCM syndrome scores between the two groups. p >0.05); comparison before and after treatment showed that both groups of drugs could improve joint pain and swelling ( p <0.05), and the observation group also improved patients' morning stiffness and cold intolerance ( p <0.05), see Table 7.

[0068] Table 7. Comparison of TCM syndrome scores between the two groups ( )

[0069] Note: Comparison before and after treatment within the same group. # p <0.05; compared with the control group, the observation group, * p <0.05 ④ Adverse reactions Closely observe the skin reactions of both groups of patients, including allergic or irritant symptoms such as redness, swelling, itching, rash, blisters, or ulceration; and systemic reactions, including systemic discomfort symptoms such as fever, dizziness, fatigue, nausea, and vomiting. Results are shown in Table 8. One case of mild local skin allergy occurred in the control group; one case of mild skin itching occurred in the observation group. There was no statistically significant difference in the incidence of adverse reactions between the two groups. p >0.05).

[0070] Table 8. Incidence of adverse reactions in the two groups (%)

[0071] In summary, after treatment, the total effective rate, DAS28 score, VAS score, and TCM syndrome score (cold intolerance and morning stiffness) in the observation group were all higher than those in the control group. p (<0.05), this traditional Chinese medicine composition gel patch is superior to loxoprofen sodium gel in improving RA symptoms, and is worthy of further clinical promotion and application.

Claims

1. The use of a traditional Chinese medicine composition in the manufacture of a medicament for treating rheumatoid arthritis, said traditional Chinese medicine composition comprising processed rhododendron molle, Angelica sinensis tail, safflower, Angelica dahurica, Typha pollen, processed frankincense, processed myrrh, and borneol.

2. As described in claim 1, the traditional Chinese medicine composition comprises, by weight, 10-25 parts of processed Rhododendron molle, 10-25 parts of Angelica sinensis (tail), 10-25 parts of Carthamus tinctorius, 10-25 parts of Angelica dahurica, 10-25 parts of Typha orientalis, 5-15 parts of processed Boswellia carterii, 5-15 parts of processed Commiphora myrrha, and 0.5-1 parts of Borneol.

3. As described in claim 2, the traditional Chinese medicine composition comprises 18 parts by weight of processed Rhododendron molle, 18 parts by weight of Angelica sinensis tail, 18 parts by weight of Carthamus tinctorius, 18 parts by weight of Angelica dahurica, 18 parts by weight of Typha pollen, 5 parts by weight of processed Boswellia carterii, 5 parts by weight of processed Commiphora myrrha, and 0.5 parts by weight of Borneol.

4. A traditional Chinese medicine composition for treating rheumatoid arthritis, comprising processed rhododendron flower, Angelica sinensis tail, safflower, Angelica dahurica, Typha pollen, processed frankincense, processed myrrh, and borneol.

5. The traditional Chinese medicine composition according to claim 4, comprising, by weight, 10-25 parts of processed Rhododendron molle, 10-25 parts of Angelica sinensis tail, 10-25 parts of Carthamus tinctorius, 10-25 parts of Angelica dahurica, 10-25 parts of Typha orientalis, 5-15 parts of processed Boswellia carterii, 5-15 parts of processed Commiphora myrrha, and 0.5-1 parts of Borneol.

6. The traditional Chinese medicine composition as described in claim 5, comprising 18 parts by weight of processed Rhododendron molle, 18 parts by weight of Angelica sinensis tail, 18 parts by weight of Carthamus tinctorius, 18 parts by weight of Angelica dahurica, 18 parts by weight of Typha pollen, 5 parts by weight of processed Boswellia carterii, 5 parts by weight of processed Commiphora myrrha, and 0.5 parts by weight of Borneol.

7. A topical preparation comprising 100 parts of the active ingredient of any one of the traditional Chinese medicine compositions according to claims 4-6 and pharmaceutical excipients, wherein the pharmaceutical excipients comprise 7.5-47.5 parts by weight of sodium polyacrylate, 350-550 parts of glycerin, 0.5-1.5 parts of aluminum glycine, 0.5-2.5 parts of tartaric acid, 5-45 parts of carbomer, and 400-800 parts of purified water.

8. The topical preparation according to claim 7, wherein the pharmaceutical excipients comprise 30 parts by weight of sodium polyacrylate, 400 parts of glycerin, 1 part of aluminum glycinate, 1 part of tartaric acid, 40 parts of carbomer, and 600 parts of purified water.

9. A method for preparing a topical formulation according to claim 7 or 8, comprising the following steps: S1: Take the prescribed amount of medicinal materials except for borneol, dry them, and pulverize them into ultrafine powder. Grind the borneol into fine powder using a mortar and pestle. Mix the ultrafine powder and fine powder evenly to make Chinese medicine powder for later use. S2: Mix the prepared traditional Chinese medicine powder, sodium polyacrylate, aluminum glycinate, and glycerol evenly to form phase A; S3: Mix tartaric acid, carbomer, and purified water thoroughly to form phase B; S4: Mix phase A and phase B evenly, and perform cross-linking treatment to obtain a gel material or gelling agent.

10. The preparation method according to claim 9, further comprising coating the gel material onto one side of the base layer and covering it with a protective layer to obtain a gel patch.

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