A pharmaceutical composition, a plaster, and its preparation method and application

Abstract

The present invention relates to the technical field of production technology of traditional Chinese medicine compositions, and specifically to a pharmaceutical composition, a plaster, and its preparation method and application. The formula comprises 18 to 35 parts of Aconitum kusnezoffii, 18 to 35 parts of Rhizoma Aconiti Kusnezoffii, 35 to 65 parts of Radix Saposhnikoviae, 35 to 65 parts of Cortex Periplocae, 65 to 85 parts of Angelica dahurica, 18 to 35 parts of Cloves, 35 to 115 parts of Belladonna fluid extract powder, 15 to 40 parts of Rutaecarpa extract powder, and 25 to 45 parts of methyl salicylate. The composition is obtained through the research on reducing the formula of Musk Wind-Chasing and Pain-Relieving Plaster, reducing the raw materials of medicinal materials from more than 20 to nine, so that it can still achieve the ideal therapeutic effect, realize component optimization and medicinal material saving. By further adding Strychnos nux vomica or a transdermal auxiliary composition, the therapeutic effect can be further enhanced. The present technical solution can solve the technical problems of Musk Wind-Chasing and Pain-Relieving Plaster in the prior art, such as the complex processing technology and high production cost, caused by the complex raw material components, and has great prospects for promotion and application.

Description

Technical Field

[0001] The present invention relates to the technical field of production technology of traditional Chinese medicine compositions, and in particular to a medicine composition, a plaster, and a preparation method and application thereof. Background Art

[0002] Rheumatoid arthritis (RA), with a global prevalence of 0.46%, is a chronic, systemic, autoimmune disease characterized by synovial inflammation and proliferation, pannus formation, autoantibody production (rheumatoid factor, anti-citrullinated protein), cartilage destruction, and cardiovascular disease. RA presents with diverse clinical manifestations, and the pathogenesis and clinical presentation vary between individuals. Common clinical manifestations include morning stiffness, pain, joint swelling, joint deformities, osteoporosis, subcutaneous nodules, interstitial lung disease, pericarditis, pleurisy, and rheumatoid vasculitis, accompanied by systemic complications such as weight loss, low-grade fever, and fatigue. RA is a chronic, intractable disease with a high disability rate. Without appropriate treatment, it can lead to a decline in patients' quality of life and work capacity, placing a significant emotional and financial burden on patients and their families.

[0003] Currently, the main clinical treatments for RA are chemical drugs (such as glucocorticoids, nonsteroidal anti-inflammatory drugs, and disease-modifying antirheumatic drugs) and biologics. However, RA treatment is a long-term process, and long-term use of chemical drugs can have significant side effects or lead to other diseases, including immunosuppression, gastrointestinal ulcers, osteoporosis, nausea, fatigue, cytopenia, rashes, liver damage, infections, and psoriasis. Furthermore, biologics are complex to prepare and expensive, placing a heavy financial burden.

[0004] Traditional Chinese Medicine (TCM) has a long history of treating RA, boasting extensive experience and strategies, demonstrating significant clinical advantages. Within the framework of traditional Chinese medicine (TCM) theory, RA falls under the category of "bi disease." In the Yellow Emperor's Classic of Internal Medicine, the earliest classic treatise on TCM, RA is classified as a "bi syndrome," caused by the combined presence of three major pathogenic qi (wind, cold, and dampness). Therefore, wind, cold, and dampness are key contributing factors to RA. Based on the different pathogenic factors, RA is further categorized as "xingbi," "tongbi," and "zhuobi." Xingbi refers to excessive wind exposure, resulting in changes in the mobility and shape of affected joints; tongbi generally refers to severe pain in fixed joints, which is exacerbated by exposure to cold; and zhuobi refers to an arthritis syndrome caused by excessive dampness. Furthermore, the causative factors vary across different stages of RA. For example, in the late stages of bi syndrome, pathological products such as phlegm and blood stasis can block meridians, muscles, and joints, hindering recovery or increasing the risk of recurrence.

[0005] Traditional Chinese medicine (TCM) is a complex, multi-ingredient system with advantages such as a wide range of sources, rich variety, and low price. It boasts multiple components, multiple pathways, and multiple targets. Compared to Western medicine, TCM has relatively fewer toxic side effects, making it suitable for long-term clinical use. Musk Wind-Chasing and Pain-Relieving Plaster can dispel wind and dampness, dispel cold, and relieve pain. It is used to treat joint and muscle pain and sprains caused by cold-dampness. Chinese invention patent publication number CN 108392610 B discloses a Musk Wind-Chasing and Pain-Relieving Plaster with excellent therapeutic efficacy, strong breathability, no allergic irritation, and easy removal. The powdered plaster in the Musk Wind-Chasing and Pain-Relieving Plaster's medicinal layer is primarily composed of raw Radix Aconiti Kusnezoffii, raw Radix Aconiti Chuanxiong, frankincense, myrrh, raw Strychnos nux vomica, cloves, cinnamon bark, schizonepeta tenuifolia, siler, geranium, cyperus rotundus, Centella asiatica, Rhizoma Drynariae, Angelica dahurica, Kaempferia galanga, dried ginger, musk, Rutaecarpa extract powder, Solanum melongena fluid extract powder, and wintergreen oil. The Musk Wind-Chasing Pain-Relieving Ointment has a significant therapeutic effect on joint pain, tenderness, flexion and extension problems, and morning stiffness caused by rheumatism. However, the Musk Wind-Chasing Pain-Relieving Ointment provided by this solution has too many medicinal ingredients, which increases the cost of raw materials and may cause waste of medicinal resources. How to reduce the number of medicinal ingredients, reduce the cost and complexity of the preparation process, and reduce the waste of medicinal resources while ensuring the therapeutic effect of the drug is an urgent problem to be solved in the clinical expansion of the application of this product. However, due to the large number of medicinal ingredients and complex mechanism of action of the Musk Wind-Chasing Pain-Relieving Ointment, it is difficult to simplify the formula through some existing rules and experience, which has led to the research on reducing the prescription of Musk Wind-Chasing Pain-Relieving Ointment has been stagnant. Summary of the Invention

[0006] The present invention aims to provide a pharmaceutical composition to solve the technical problems of the Musk Wind-Chasing and Pain-Relieving Ointment in the prior art, such as the complex processing technology and high production cost caused by the complex raw material components.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides a pharmaceutical composition, the medicinal raw materials of which include, by weight, 18 to 35 parts of Aconitum kusnezoffii, 18 to 35 parts of Chuanwuji, 35 to 65 parts of Saposhnikovia divaricata, 35 to 65 parts of Periploca rotundus, 65 to 85 parts of Angelica dahurica, 18 to 35 parts of Cloves, 35 to 115 parts of Belladonna fluid extract powder, 15 to 40 parts of Rutaecarpa extract powder, and 25 to 45 parts of methyl salicylate.

[0009] Further preferably, a pharmaceutical composition, whose medicinal raw materials include, by weight, 20-30 parts of Aconitum kusnezoffii, 20-30 parts of Chuanwuji, 40-60 parts of Saposhnikovia divaricata, 40-60 parts of Periploca rotundus, 70-80 parts of Angelica dahurica, 20-30 parts of cloves, 50-100 parts of Belladonna fluid extract powder, 25-35 parts of Rutaecarpa extract powder and 30-40 parts of methyl salicylate.

[0010] Most preferably, a pharmaceutical composition, in terms of weight parts, its medicinal raw materials include 25 parts of Aconitum kusnezoffii, 25 parts of Chuanwu, 50 parts of Saposhnikovia divaricata, 50 parts of Periploca serrata, 75 parts of Angelica dahurica, 25 parts of Cloves, 75 parts of Belladonna fluid extract powder, 30 parts of Rutaecarpa extract powder and 35 parts of methyl salicylate.

[0011] Preferably, the medicinal raw material further comprises 18 to 35 parts of Strychnos nux vomica in parts by weight.

[0012] More preferably, the medicinal raw material further comprises 20 to 30 parts of Strychnos nux vomica in parts by weight.

[0013] Most preferably, the medicinal raw material further comprises 25 parts of Strychnos nux vomica in parts by weight.

[0014] In a second aspect, the present invention further provides an external preparation comprising the pharmaceutical composition, wherein the external preparation is any one of an ointment, cream, paste, spray, aerosol, gel, paint, film coating, liniment, tincture, patch, plaster, mixture, plaster, fluid extract, or extract.

[0015] Preferably, the external preparation further comprises a transdermal auxiliary composition; the transdermal auxiliary composition comprises, by weight, 40 to 60 parts of camphor, 15 to 25 parts of borneol and 40 to 60 parts of menthol.

[0016] In a third aspect, the present invention further provides a method for preparing an external preparation, which is prepared according to the following method:

[0017] S1: using an ethanol solution as a solvent to perform heat reflux extraction on Aconitum kusnezoffii and Aconitum carmichaelii to obtain a first mixed extract and a first mixed medicinal residue; after alkalizing, extracting and drying the first mixed extract, obtaining an extract powder;

[0018] S2: steam distilling cloves to obtain clove volatile oil, clove extract, and clove residue; steam distilling angelica to obtain angelica volatile oil, angelica extract, and angelica residue; concentrating the clove extract and angelica extract to obtain clove concentrate and angelica concentrate, respectively;

[0019] S3: mixing the clove residue and the angelica dahurica residue from S2 with the siler and the cortex scutellariae, and performing hot reflux extraction using an ethanol solution as a solvent to obtain a second mixed extract and a second mixed residue; and concentrating the second mixed extract to obtain a first concentrated solution;

[0020] S4: mixing the first mixed medicinal residue of S1 and the second mixed medicinal residue of S3, decocting and extracting the mixture with water, and concentrating the filtrate to obtain a second concentrated solution;

[0021] S5: mixing the clove concentrate obtained in S2, the angelica concentrate, the first concentrate in S3, and the second concentrate in S4, and concentrating them into an extract;

[0022] S6: mixing the extract powder of S1 with the powder of belladonna fluid extract and the powder of rue extract, and adding the mixture to the extract prepared in S5, spraying the volatile oil of angelica dahurica and the volatile oil of clove prepared in S2, and adding methyl salicylate to prepare a musk wind-chasing composition;

[0023] S7: Add pharmaceutical excipients and / or bases to the above musk wind-chasing composition, and prepare it into an external preparation for clinical use.

[0024] Preferably, the matrix is ​​selected from a mixture of any one or more of sodium polyacrylate, sodium carboxymethyl cellulose, gelatin, glycerin, micropowdered silica gel, rubber, thermoplastic rubber, rosin, rosin derivatives, vaseline, lanolin, zinc oxide, pressure-sensitive adhesive or liquid paraffin; more preferably, the matrix is ​​a mixture of rubber, rosin, zinc oxide, vaseline, lanolin and liquid paraffin.

[0025] Preferably, in S1, ethanol solution is used as a solvent to perform heat reflux extraction on Strychnos nux vomica, Aconitum kusnezoffii and Aconitum carmichaelii to obtain a first mixed extract and a first mixed medicinal residue; after the first mixed extract is alkalized, extracted and dried, an extract powder is obtained.

[0026] Preferably, in S6, camphor, borneol and menthol are added in addition to methyl salicylate.

[0027] In a fourth aspect, the present invention also provides a use of a pharmaceutical composition in the preparation of a medicament for treating rheumatoid arthritis.

[0028] The principles and beneficial effects of this solution are:

[0029] The main ingredients of Musk Wind-Chasing and Pain-Relieving Ointment include Musk Wind-Chasing and Pain-Relieving Fluid Extract, Rutaecarpa Extract, Belladonna Fluid Extract and other effective ingredients; transdermal auxiliary ingredients such as borneol, menthol, camphor and methyl salicylate; and other excipients (matrix ingredients) for preparing the patch, including rubber, rosin, petrolatum and liquid paraffin. The raw materials of Musk Wind-Chasing and Pain-Relieving Fluid Extract are relatively complex, including 17 complex raw materials: Aconitum kusnezoffii, Aconitum carmichaelii, frankincense, myrrh, Strychnos nux vomica, cloves, cinnamon bark, Schizonepeta tenuifolia, Saposhnikovia divaricata, Geranium officinale, Perennial Herb, Centella asiatica, Drynaria fortunei, Angelica dahurica, Kaempferia galanga, dried ginger and musk. This makes the production process complicated and increases the cost of the drug.

[0030] The inventor has been looking for a method that can simplify the formulation composition and maintain or enhance the drug effect. After a lot of exploration, the formula shown in this patent application was discovered. The inventor first analyzed the active ingredients in each raw material of Musk Wind-Removing and Pain-Relieving Fluid Extract, Rue Extract and Belladonna Fluid Extract that have the effects of reducing swelling and relieving pain, and treating rheumatoid arthritis. It is planned to select medicinal flavors with significant above-mentioned effects by means of active ingredient analysis. However, through literature mining and experimental research (for example, using chromatography to measure the content of active substances in various medicinal materials or semi-finished products), it was found that almost all raw medicinal materials or semi-finished products (extracts, fluid extracts) contain a certain amount of active ingredients with the effects of reducing swelling and relieving pain, reducing inflammation and relieving pain, and treating rheumatoid arthritis. For example, frankincense contains a large amount of eucalyptol, myrrh contains a large amount of testosterone, and geranium contains a large amount of quercetin, etc., which have anti-inflammatory and analgesic effects. The phenylpropane derivatives contained in Schizonepeta tenuifolia have a strong inhibitory effect on 3-α-hydroxysteroid dehydrogenase, which can promote the production of corticosteroids and exert anti-inflammatory and analgesic effects. Centella asiatica contains a variety of α-amyrin-type triterpenoids, which can clear heat and dampness, promote blood circulation and stop bleeding, and detoxify and reduce swelling. The anti-inflammatory, analgesic, and rheumatoid arthritis effects of the ingredients in Musk Wind-Chasing Pain-Relieving Ointment are not listed here. As we can see, it is difficult to simplify the formula of Musk Wind-Chasing Pain-Relieving Ointment through research on active ingredients, and this research approach has been proven to be unfeasible.

[0031] The inventor has only another way to find research, because this medicine is transdermal administration, transdermal effect is the key that affects the effect.So, the inventor has then carried out the research of transdermal effect to each medicinal material of Musk Chasing Wind and Pain Relief Plaster.The study found that the transdermal effect of the extracts of Radix Saposhnikoviae, Radix Aconiti Kusnezoffii, Solanum Belladonna, Clove, Cortex Perfoliatae, and Radix Angelicae Dahuricae are better, and it is thought that this may be the key ingredient of Musk Chasing Wind and Pain Relief Plaster.But, the inventor uses these medicinal materials as raw materials, prepares ointment (Comparative Example 6), but finds that the therapeutic effect of ointment is not ideal.So by screening and simplifying the formula by the transdermal ability of medicine, feasibility is also more limited.

[0032] The inventors have conducted a large number of studies on the various ingredients of Musk Wind-Chasing Pain-Relieving Ointment, including analysis of efficacy compounds, transdermal experimental studies, etc., in order to achieve a reduction in the number of medicinal flavors. However, actual studies have found that each medicinal flavor in Musk Wind-Chasing Pain-Relieving Ointment has different degrees of anti-inflammatory and analgesic effects and the efficacy of treating rheumatoid arthritis, making it difficult to achieve a reduction in prescriptions through analysis of efficacy components. Through research on a large number of different drug combinations, the inventors unexpectedly discovered that the combined use of several medicinal raw materials, including Radix Aconiti Kusnezoffii, Radix Aconiti Chuanxiong, Radix Saposhnikoviae, Cortex Perfoliatae, Angelica Dahuricae, Cloves, Solanum Belladonna Extract Powder, and Rutaecarpa Extract Powder, can achieve an effect similar to that of the existing Musk Wind-Chasing Pain-Relieving Ointment on the basis of significantly reducing the medicinal flavor. This new formula reduces the number of medicinal raw materials from more than 20 to 9, achieving component optimization and medicinal material conservation. Moreover, if Strychnos nux vomica or a transdermal auxiliary composition (menthol, camphor, and borneol) is further added, the therapeutic effect can be further enhanced. DETAILED DESCRIPTION

[0033] The following examples are intended only to more clearly illustrate the technical solutions of the present invention and are therefore provided as examples only and are not intended to limit the scope of protection of the present invention. The specific embodiments listed herein are merely exemplary of the present invention and are not intended to limit the scope of protection of the present invention. For those skilled in the art, any equivalent modifications and substitutions made to the embodiments described below are also within the scope of the present invention. Therefore, equivalent transformations and modifications made without departing from the spirit and scope of the present invention should be encompassed within the scope of the present invention. To better illustrate the present invention, numerous specific details are provided in the following specific embodiments. Those skilled in the art should understand that the present invention can be practiced without certain specific details. In other embodiments, methods, means, equipment, and steps well known to those skilled in the art are not described in detail in order to highlight the main points of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. Unless otherwise specified, the units used in this specification are international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production. Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the materials, reagents or instruments used without indicating the manufacturer are all reagents and materials that can be obtained from commercial channels. If no specific conditions are specified in the examples, they are all carried out according to conventional conditions or conditions recommended by the manufacturer. At the same time, the present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are all common commercial products in this technical field.

[0034] It should be noted that the names of the medicinal materials used in the following examples and their quality standards are uniformly described in Table 1:

[0035] Table 1: Names and quality standards of various raw medicinal materials

[0036]

[0037] The following are preparation examples of the present invention:

[0038] The preparation process of the plaster containing the above composition is as follows:

[0039] S1: Take the formulated amount of Aconitum kusnezoffii and Aconitum chuanxiong, add 70% to 80% ethanol in an amount 10 to 15 times the weight of the medicinal materials, heat and reflux and extract twice, each time for 1.5 to 2 hours, combine the extracts, alkalize, and perform conventional chloroform extraction. Collect the chloroform layer and evaporate to dryness to obtain an extract powder for later use; retain the extracted medicinal residue for later use (the first mixed medicinal residue). If Strychnos nux vomica is required to be added to the formula, the mixed medicinal materials formed by Strychnos nux vomica, Aconitum kusnezoffii, and Aconitum chuanxiong can be extracted using the above method.

[0040] In subsequent specific experimental tests, the specific operation method adopted in this step is: using 75% ethanol in an amount 15 times the weight of the medicinal materials, heating and refluxing extraction twice, each time for 2 hours.

[0041] S2: Perform conventional steam distillation extraction on cloves to obtain clove volatile oil, and filter the mixture of the medicinal material and water after steam distillation to obtain clove extract and clove residue; perform conventional steam distillation extraction on angelica dahurica to obtain angelica dahurica volatile oil, angelica dahurica extract and angelica dahurica residue; filter and heat-concentrate the clove extract and angelica dahurica extract respectively to obtain clove concentrate and angelica dahurica concentrate.

[0042] S3: The clove residues and angelica dahurica residues of S2 are mixed with the formulated amount of siler and cortex cyperi, and reflux extraction is performed using 85% to 95% ethanol solution in an amount of 10 to 15 times the weight of the medicinal materials as a solvent (heating reflux extraction 2 times, each time for 1.5 to 2 hours). The extracts are combined to obtain a second mixed extract and a second mixed residue; the second mixed extract is conventionally concentrated and the ethanol is recovered to obtain a first concentrated solution.

[0043] In subsequent specific experimental tests, the specific operation method adopted in this step is: using 90% ethanol in an amount 15 times the weight of the medicinal materials, heating and refluxing extraction twice, each time for 1.5 hours.

[0044] S4: The first mixed medicinal residue of S1 and the second mixed medicinal residue of S3 are mixed, and the mixture is boiled and extracted twice with water in an amount of 6 to 8 times the weight of the medicinal residue, each time for 1 hour, and the filtrate is filtered and combined, and the filtrate is concentrated to obtain a second concentrated solution.

[0045] In subsequent specific experimental tests, the specific operation method adopted in this step is: using 8 times the weight of the medicinal residue in water for decoction and extraction.

[0046] S5: The clove concentrate and angelica concentrate of S2, the first concentrate of S3, and the second concentrate of S4 are mixed and evenly mixed to obtain a mixed concentrated medicinal solution, which is concentrated under reduced pressure to an extract with a relative density of 1.05 to 1.15 (60° C.).

[0047] S6: Mix the extract powder of S1 with belladonna fluid extract powder and rue extract powder, add the mixture to the extract of S5, spray the volatile oil of angelica dahurica and volatile oil of clove from S2, and add a transdermal auxiliary composition to obtain a mixture of pharmaceutical active ingredients; then add a matrix, mix, apply an ointment in a conventional manner, cut into sections, cover with a backing, and cut into pieces to obtain the product. The transdermal auxiliary composition is selected from a mixture of at least one or more of methyl salicylate, camphor, borneol, and menthol.

[0048] The above-described formulations and processes were used to prepare plasters of the pharmaceutical compositions of this embodiment, including several examples and comparative examples. The specific formulations for each example and comparative example are detailed in Tables 2 and 3. Some comparative examples contain increased amounts of medicinal ingredients (e.g., frankincense, myrrh, cinnamon bark, schizonepeta tenuifolia, geranium, centella asiatica, drynaria root, kaempferia galanga, and dried ginger). These increased medicinal ingredients were added in step S3 of the preparation process, mixed with siler and cortex cyperi, and then subjected to alcohol extraction. Musk added to the comparative examples was mixed uniformly with a belladonna fluid extract powder, rue extract powder, and the like in step S6 before being added to the extract in step S5.

[0049] Table 2 Composition of each embodiment

[0050]

[0051] Table 3 Comparative Examples

[0052] Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Aconitum kusnezoffii (g) 35 35 35 35 35 35 35 35 Chuanwu (g) 35 35 35 35 35 / / 35 Windproof(g) 65 65 65 65 65 65 65 65 Perilla frutescens peel (g) 65 65 65 65 65 65 65 65 Angelica dahurica (g) 85 85 85 85 85 85 85 85 Cloves (g) 35 35 35 35 35 35 35 35 Nux vomica (g) / 35 / / / / 35 35 Belladonna fluid extract (g) 115 115 115 115 115 115 115 115 Rutaecarpa extract (g) 40 40 40 40 40 / / 40 Methyl salicylate (g) 45 45 45 45 45 45 45 45 mastic 35 35 / / / / / 35 Myrrh 35 35 / / / / / 35 Cinnamon / / / / / / / 65 Schizonepeta / / 65 / / / / 65 Geranium / / 65 / / / / 65 Centella asiatica / / / / 65 / / 65 Drynaria fortunei / / / / 65 / / 65 Shannai / / / 85 / / / 85 dried ginger / / / 85 / / / 85 Musk / / / / / / / 1

[0053] Experimental Example 1

[0054] (1) Acute toxicity test

[0055] Experimental method: Healthy white guinea pigs (weighing 220±20 g), half male and half female, were randomly divided into two large groups, each group was divided into 8 groups, each group had 12 guinea pigs, half male and half female, respectively, normal skin group (blank control group, high-dose group of Example 7, low-dose group of Example 7, high-dose group of Example 8, low-dose group of Example 8, high-dose group of Example 9, low-dose group of Example 9) and damaged skin group (blank control group, high-dose group of Example 7, low-dose group of Example 7, high-dose group of Example 8, low-dose group of Example 8, high-dose group of Example 9, low-dose group of Example 9).

[0056] Guinea pigs were depilated 24 hours prior to the experiment. The depilated skin was inspected for integrity and no damage. Guinea pigs with intact skin were selected for the experiment. A #-shaped wound was inscribed in the depilated area using a No. 7 needle, avoiding dermal damage, oozing blood, and no significant bleeding. Each group of animals was treated with ointment of varying concentrations (low-dose and high-dose doses were 0.175 g / animal and 0.700 g / animal, respectively). The ointment consisted of a uniform mixture of drug powder and a transdermal adjuvant composition, i.e., a mixture of active ingredients prepared according to the method described above, without the addition of a matrix). The blank group received no treatment and animals were housed individually.

[0057] Each group of guinea pigs received a single dose. Following dosing, activity, hair gloss, and mortality were observed and recorded daily. Body weight changes were recorded before dosing (day 0, d0) and on days 7 and 14 after dosing (d7 and d14). On day 14 after dosing, gross anatomical examinations were performed on each group of guinea pigs. Changes in the appearance of organs, including the heart, liver, spleen, lungs, kidneys, thymus, adrenal glands, brain, testes, epididymis, and ovaries, were observed. Organs were weighed and calculated using the formula: Organ Index = Organ Mass (mg) / Body Mass (g). For experimental results, see Tables 4, 5, and 6.

[0058] Table 4 Changes in body weight of guinea pigs in each group in acute toxicity test ( n=6,g)

[0059]

[0060] Table 5 Comparison of organ indices of female guinea pigs in each group in acute toxicity test ( n=6, mg / g)

[0061]

[0062] Table 6 Comparison of organ indices of male guinea pigs in each group in acute toxicity test ( n=6, mg / g)

[0063]

[0064] The above experimental results show that after administration, the guinea pigs were observed and found that after treatment with the ointment, a few guinea pigs in the Example group experienced mild redness and swelling at the administration site. The redness and swelling at the administration site of the guinea pigs decreased approximately 2 hours after administration and completely disappeared after 6-8 hours, essentially returning to normal. No abnormalities were observed in the guinea pigs in the blank group during this process. All rats survived and showed no other abnormalities from day 14 after administration. There was no significant difference in the body weight of the guinea pigs in the treatment groups compared to the blank group.

[0065] The female guinea pigs in each dosing group showed no obvious abnormal lesions in their internal organs, and compared with the blank group, the organ indexes of the guinea pigs in each example group showed no significant changes. The male guinea pigs in each dosing group showed no obvious abnormal lesions in their internal organs, and compared with the blank group, the organ indexes of the guinea pigs in each example group showed no significant changes. The results show that the patch does not produce toxic reactions even when the dosage is increased.

[0066] (2) Acute skin irritation test

[0067] Experimental Methods: Healthy white guinea pigs (250 ± 20 g), half male and half female, were randomly divided into two large groups, each group consisting of 8 subgroups, each with 12 guinea pigs (half male and half female), including normal skin groups (blank control group, Example 7 group, Example 8 group, Example 9 group) and damaged skin groups (blank control group, Example 7 group, Example 8 group, Example 9 group). The administered drug was an ointment uniformly mixed with a drug powder and a transdermal auxiliary composition, i.e., a mixture of pharmaceutical active ingredients prepared according to the method described above, without the addition of a matrix.

[0068] 24 hours before the experiment, the guinea pigs' abdomens were depilated and the skin was inspected for integrity and no damage. Guinea pigs with intact skin were selected for the experiment. A #7 needle was used to create a "#"-shaped wound in the depilated area, ensuring no dermal damage, no oozing, and no obvious bleeding. Using the left-side self-comparison method, the drug active ingredient mixture was applied to the left side of the guinea pig's skin at a normal dosage, ensuring a consistent dosage for each guinea pig. Simultaneously, an equal area of ​​medical tape was applied to the right side of the guinea pig's skin as a control. The tape was secured and the ointment was washed off after 24 hours. The skin was visually observed 1 hour, 24 hours, 48 ​​hours, and 72 hours after ointment removal, and the presence of erythema and edema at the application site was recorded.

[0069] Experimental results: Scoring was performed according to the "Skin Irritation Reaction Scoring Standards" and the average score of each group of animals was calculated according to the following formula:

[0070] Average reaction score = total irritation reaction score / number of animals;

[0071] Among them, the total score of irritation reaction = total score of erythema formation ± total score of edema formation;

[0072] The irritation reaction scoring standard is shown in Table 7, the skin irritation intensity evaluation standard is shown in Table 8, and the average irritation reaction score is shown in Table 9.

[0073] Table 7 Irritation reaction scoring criteria

[0074]

[0075] Table 8 Evaluation criteria for skin irritation intensity

[0076]

[0077] Table 9 Results of local skin irritation test on guinea pigs (n=12)

[0078]

[0079] The above experimental results show that observation of the guinea pigs after administration of the ointment revealed that some guinea pigs in both the intact and damaged skin groups developed barely noticeable edema or erythema 24 hours after treatment, which resolved and fully recovered after 24 hours. The remaining test animals did not experience skin erythema or edema. The average irritation intensity score for both the intact and damaged skin groups was less than 0.49, indicating a non-irritating rating. This result demonstrates that the pharmaceutical active ingredient mixtures prepared in Examples 7-9 are non-irritating.

[0080] Experimental Example 2

[0081] Experimental Materials

[0082] Healthy male Sprague-Dawley (SD) rats (150, weighing 180-220 g, SPF grade) were purchased from Chongqing Medical University. During the experiment, the animals were kept in a standard animal room (temperature 20-25°C, humidity 26%-40%, 12-h light, and free access to drinking water).

[0083] Experimental methods

[0084] After one week of adaptive feeding, healthy male SD rats were used to establish a collagen-induced arthritis (CIA) rat model. A 2 mg / mL bovine type II collagen solution and equal volumes of CFA were mixed to create a 1 mg / mL bovine type II collagen / CFA emulsion. The rats were injected with 0.2 mL of bovine type II collagen / CFA emulsion on both sides of the back and the sole of the right foot, and 0.1 mL of bovine type II collagen / CFA emulsion 2 cm from the base of the tail for the first immunization. Seven days later, a second immunization was performed using the same method. A normal control group was injected with an equal volume of saline at the same time and site. Seven days after the second immunization, the model was established. Successful modeling rats were randomly divided into 20 groups: blank group, model group, blank matrix group, Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, Example 7, Example 8, Example 9, Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4, Comparative Example 5, Comparative Example 6, Comparative Example 7, and Comparative Example 8, with 6 rats in each group. All rats were given normal diet and drinking water during the experiment.

[0085] The drug was administered 7 days after the secondary immunization. The administration scheme was as follows: each embodiment group and the comparative example group applied one patch [0.035g / (kg·d), i.e., each patch contained 0.035g of a mixture of medicinal ingredients, and rubber, rosin, zinc oxide, vaseline, lanolin, and liquid paraffin were mixed in a mass ratio of 3:3:4:0.6:0.3:0.3 as a matrix, and the mixture of medicinal ingredients and the matrix was prepared in a mass ratio of 1:4] on the depilatory joint muscle of the right hind foot of the rat; the blank matrix group was given a blank matrix control at the same position; the model group and the blank group were raised normally and were not given any drug treatment. Each drug administration group was administered once a day for 24 consecutive days, and was observed at any time after application. When the patch fell off, it was promptly patched.

[0086] Experimental results

[0087] (1) General observation and weight measurement

[0088] The changes in local inflammatory response, behavior and dietary status of rats in each group were observed before drug intervention (d0) and after drug intervention (d6, d12, d18, d24), and their body weight was measured and the results were recorded (see Table 10).

[0089] Table 10 Body weight changes of rats in each group ( n=6)

[0090]

[0091] In the experiment, the rats in each group were in good health before modeling, with smooth and shiny hair, active behavior, normal diet and drinking water. After modeling, the rats in each group showed reduced activity and diet compared with the blank group, dull and rough hair, slightly yellowed, lazy and sloppy movements, swollen toes, and typical "redness, swelling, heat, and pain" phenomena at the modeling site. The inflammatory symptoms were severe, activity was limited, and there was no death. The changes in the weight of the rats in each group are shown in Table 10. The experimental results show that the blank group rats had normal food and water intake, and their weight increased steadily and grew rapidly. The weight gain of the remaining rats in each group was relatively slow after modeling, especially the model group and the blank matrix group rats had the slowest weight gain. The growth rate of the weight of the mice in Example 1-9 was improved relative to the model group and the blank matrix group, indicating that the prescription of this technical solution has a certain promoting effect on alleviating collagen-induced arthritis. As can be seen from the comparison of Example 1-3 and Example 4-6, the addition of Strychnos nux vomica can improve the weight growth rate of rats to a certain extent. There are significant differences between Examples 1-3 and 4-6 compared with the model group or the blank matrix group, indicating that the formula of this solution can significantly improve the negative effects of arthritis. In addition, Example 5 is compared with the original recipe (Comparative Example 8), and the rat weight growth rate is even slightly improved, indicating that the formula after the reduction of the present technical solution and the existing complete Musk Chasing Wind Pain Relief Paste formula effect have even improved. If other medicinal flavors in the original recipe are further added on the basis of Example 2 or Example 5, for example, Comparative Examples 1 and 2 add frankincense and myrrh, which will make the drug effect worse. Comparative Examples 3-5, on the basis of Example 2, add Herba Schizonepetae and Geranium, Kaempferia galanga and dried ginger, Centella asiatica and Bone-breaking, and the rat weight growth rate is almost the same as Example 2. This shows that the composition of the Musk Chasing Wind Pain Relief Fluid Extract of Example 3 is the core component of this party, and adding other components except Strychnos nux vomica on the basis of this core component can not effectively improve the drug effect. Example 7-9 further adds the auxiliary component that promotes transdermal penetration on the basis of Example 6, which can further enhance the drug effect.

[0092] (2) Toe thickness measurement

[0093] The thickness of the right hind paw of each rat in each group was measured in parallel using an electronic vernier caliper before (d0) and after (d6, d12, d18, and d24) drug treatment intervention. The right hind paw of the rat was marked 1 cm from the heel with a marker pen, and additional markings were made in real time to ensure consistent measurement locations. The experimental results are shown in Table 11.

[0094] Table 11 Changes in toe thickness of rats in each group ( n=6)

[0095]

[0096] Note: ** Compared with the blank control group, p < 0.01;## For comparison with the model control group, p < 0.01; & Compared with control group 8, p < 0.05; && Compared with the control group 8, p < 0.01

[0097] The experimental results showed that compared with the blank control group (d0), the plantar thickness of rats in each modeling group was significantly increased before drug intervention (p < 0.01), but there was no statistical difference between the modeling groups (p > 0.05), indicating that the modeling was successful and the uniformity between the modeling groups was good.

[0098] Within 24 days of administration, the model group remained essentially stable. Except for the blank matrix group, the plantar thickness of rats in all other drug-treated groups showed a decreasing trend from the start of drug intervention, with extremely significant statistical significance compared to the model group (p < 0.01). Compared to the comparative example 8 group (original complete formula), the plantar thickness of the Example 7, Example 8, and Example 9 groups were all extremely significantly reduced (p < 0.01). In summary, each example group and the comparative example group had a certain inhibitory effect on the thickness of the rat toes, among which the inhibitory effect of the Example 7, Example 8, and Example 9 groups was superior to that of the other examples and comparative example groups.

[0099] Regarding the effect of the tested drug on reducing the thickness of the toes of CIA model mice, a more detailed analysis is as follows:

[0100] Embodiment 1-3 adopts Radix Aconiti Kusnezoffii, Radix Aconiti Chuanxiong, Radix Saposhnikoviae, Cortex Periplocae, Radix Angelicae Dahuricae, Clove, Solanum Belladonna Fluid Extract, Rutaecarpa Extract, Methyl Salicylate. Embodiment 4-6 adds Semen Strychnos nux vomica on the basis of embodiment 1-3. Comparative Example 8 is the original formula of Musk Wind-Chasing Pain-Relieving Paste, and adds ingredients such as frankincense, myrrh, cinnamon bark, herba schizonepetae, herba geranium, herba centellae, rhizoma drynariae, galangal, dried ginger, musk on the basis of embodiment 4-6. The experimental results show that there is no significant difference between the effect of the original formula (Comparative Example 8) and embodiment 1-3. When a large amount of original formula ingredients are omitted, the formula of embodiment 1-3 obtains an effect that is almost the same as the original formula. The various medicinal flavors omitted all have different degrees of detumescence, anti-inflammatory, and analgesic reports. Omitting these ingredients can still achieve ideal therapeutic effects, which is unpredictable by the prior art. There is a significant difference between the effect of the original formula (Comparative Example 8) and embodiment 4-6. When a large number of original formula components are omitted, the formulas of Examples 4-6 can obtain a therapeutic effect that exceeds the original formula. Further addition of Strychnos nux vomica on the basis of the formulas of Examples 1-3 can significantly enhance the drug effect. However, on the basis of the formulas of Examples 1-3, it is not the case that any increase in the taste of the medicine can enhance the effect of the overall formula. For example, frankincense and myrrh were added on the basis of Example 2 or Example 5 (Comparative Examples 1 and 2), which had basically no effect on the drug effect. Comparative Examples 3-5, on the basis of Example 2, added Schizonepeta tenuifolia and Geranium, Kaempferia galanga and dried ginger, Centella asiatica and Boneless Bone Broth, which had basically no effect on the drug effect. This shows that the drug composition of Examples 1-3 is the core component of this scheme. Adding other ingredients except Strychnos nux vomica on the basis of this core component cannot effectively improve the drug effect. Examples 7-9 further added auxiliary ingredients that promote transdermal penetration on the basis of Example 5, which can further enhance the drug effect. Comparative Examples 6 and 7 omitted Rutaecarpa extract and Rhizoma Aconiti Lateralis Preparata on the basis of Examples 2 and 5, and the therapeutic effect dropped significantly, which shows that Rutaecarpa extract and Rhizoma Aconiti Lateralis Preparata are one of the indispensable ingredients in this formula. The inventors attempted comparative examples 6 and 7 because previous studies found that the active ingredients in Radix Aconiti Kusnezoffii, Radix Saposhnikoviae, Cortex Perforatum, Angelica Dahuricae, Cloves, and Atropaeolum had very ideal transdermal effects, surpassing other ingredients in the original Musk Wind-Chasing Pain-Relieving Ointment. Since the active ingredients of the drugs are more easily absorbed transdermally, they may be the core ingredients of the Musk Wind-Chasing Pain-Relieving Ointment. However, actual research results show that it is not feasible to screen the core ingredients based solely on transdermal effects. It is necessary to add Rutaecarpa Extract and Radix Aconiti Lateralis Preparata, which have less ideal transdermal effects, to the formula to maximize the therapeutic effect.

[0101] (3) Determination of immune organ coefficient

[0102] Rats were sacrificed by cervical dislocation, and the thymus and spleen were carefully removed with forceps. The blood on the surface was washed with 0.9% saline and the water was dried with filter paper. The wet weight was measured using an electronic analytical balance, and the thymus coefficient and spleen coefficient were calculated according to the following formula:

[0103] Thymus coefficient = thymus (mg) / body weight (g);

[0104] Spleen coefficient = spleen weight (mg) / body weight (g);

[0105] The experimental results are shown in Table 12.

[0106] Table 12 Changes in immune organ coefficients of rats in each group ( n=6)

[0107]

[0108] Note: ** Compared with the blank control group, p < 0.01; ## For comparison with the model control group, p < 0.01; & Compared with control group 8, p < 0.05; && Compared with the control group 8, p < 0.01

[0109] The experimental results showed that compared with the blank control group, the thymus coefficient and spleen coefficient of the rats in the model group and the blank matrix group were significantly increased (P < 0.01). Compared with the model group, the thymus coefficient and spleen coefficient of each drug intervention group were extremely significantly reduced (P < 0.01), and the blank matrix group had no reducing effect on the thymus coefficient and spleen coefficient of the rats (P > 0.05). Compared with the comparative example 8 group (original complete formula), the spleen coefficient of Example 7, Example 8, and Example 9 groups was significantly reduced (p < 0.05), the thymus coefficient of Example 7 and Example 8 groups was significantly reduced (p < 0.05), and the thymus coefficient of Example 9 group was extremely significantly reduced (p < 0.01). In summary, each example group and the comparative example group had a certain reducing effect on the rat immune organ coefficient, among which the reducing effect of Example 7, Example 8, and Example 9 groups was better than that of the other examples and comparative example groups. The experimental data also show that the core ingredients of this solution in Examples 1-3 can achieve the same effect as the existing formula (Comparative Example 8), and by reducing the formula in large quantities, similar effects can be achieved as the original formula, which is also unpredictable through existing reports.

[0110] (4) Determination of serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-ɑ), interleukin-17 (IL-17), rheumatoid factor (RF), serotonin (5-HT), prostaglandin E2 (PGE-2), and β-endorphin (β-EP) levels

[0111] After anesthesia, blood was collected from the abdominal aorta of rats. After standing at room temperature for 2 hours, the blood was centrifuged at 3500 rpm for 10 minutes to separate the serum. The enzyme-linked immunosorbent assay (ELISA) method was used to detect the levels of IL-6, TNF-α, IL-17, RF, 5-HT, PGE-2 and β-EP in the rat serum. The specific operation was carried out according to the instructions of the kit. The experimental results are shown in Tables 13 and 14.

[0112] Table 13 The contents of IL-6, TNF-α, IL-17 and RF in the serum of rats in each group ( n=6)

[0113]

[0114] Note: ** Compared with the blank control group, p < 0.01; ## For comparison with the model control group, p < 0.01; & Compared with control group 8, p < 0.05; && Compared with the control group 8, p < 0.01

[0115] Table 14 The contents of 5-HT, PGE-2 and β-EP in the serum of rats in each group ( n=6)

[0116]

[0117] Note: ** Compared with the blank control group, p < 0.01; ## For comparison with the model control group, p < 0.01; & Compared with control group 8, p < 0.05; && Compared with the control group 8, p < 0.01

[0118] The experimental results showed that compared with the blank control group, the serum IL-6, TNF-ɑ, IL-17, RF, 5-HT and PGE2 levels of rats in the model group and blank matrix group were significantly increased, while the serum β-EP content was significantly decreased, with extremely significant statistical significance (p < 0.01); after drug intervention, compared with the model group, the serum IL-6, TNF-ɑ, RF and PGE2 levels of the control group 6 were significantly decreased (p < 0.05 or p < 0.01), and the β-EP content was extremely significantly increased (p < 0.01), but there was no significant effect on reducing the serum IL-17 and 5-HT levels (p > 0.05); the serum IL-6, TNF-ɑ, IL-17, RF, 5-HT and PGE2 levels of the other drug intervention groups were significantly decreased compared with the model control group (p < 0.05 or p < 0.01), and the β-EP content was extremely significantly increased compared with the model control group (p < 0.01). Compared with the control group 8 (original complete formula), the serum IL-6, TNF-ɑ, RF, 5-HT and PGE2 levels of the Example 7 group were significantly reduced (p < 0.05 or p < 0.01), and the β-EP content was significantly increased (p < 0.05), but there was no effect on significantly reducing the serum IL-17 content (p > 0.05); the serum IL-6 content of the Example 6 group was significantly lower than that of the control group 8 (p < 0.05); the serum IL-6, TNF-ɑ, IL-17, RF, 5-HT and PGE2 levels of the Example 8 and Example 9 groups were significantly lower than those of the control group 8 (p < 0.05 or p < 0.01), and the β-EP content was significantly increased compared with the control group 8 (p < 0.05). In summary, each embodiment group and the comparative example group all had certain anti-inflammatory and analgesic effects on rats, among which the anti-inflammatory and analgesic effects of the embodiment 7, embodiment 8, and embodiment 9 groups were better than those of the other embodiments and comparative example groups. The experimental data also showed that the core components of the present solution of Examples 1-3 can achieve the same anti-inflammatory and analgesic effects as the existing formula (Comparative Example 8), and that similar effects as the original formula can be achieved by reducing the formula in large quantities, which is unpredictable by existing reports.

[0119] From the above examples, comparative examples and experimental data, it can be seen that:

[0120] The inventors conducted extensive research on the combination and separation of the ingredients in Musk Wind-Chasing Pain-Relieving Ointment and unexpectedly discovered that the formula (Examples 1-3) consisting of Aconitum kusnezoffii, Radix Aconiti Kusnezoffii, Radix Saposhnikoviae, Cortex Periplocae, Angelica dahurica, Clove, Solanum belladonna fluid extract powder, Rutaecarpa extract powder, and methyl salicylate essentially achieved the same therapeutic effect for rheumatoid arthritis as the original complete formula (see Comparative Example 8). The number of ingredients in Musk Wind-Chasing Pain-Relieving Ointment was reduced from 17 to 6, significantly optimizing the formula while maintaining similar therapeutic effects.

[0121] In addition, on the basis of Examples 1-3, the addition of Strychnos nux vomica (Examples 4-6) can further enhance the therapeutic effect, and its technical effect is better than that of Comparative Example 8. On the basis of Examples 1-6, the addition of transdermal promoting substances (menthol, camphor and borneol) can further enhance the effect of the drug, and its effect is further improved compared with Comparative Example 8.

[0122] On the contrary, on the basis of the formula of embodiment 2, add frankincense, myrrh (comparative example 1), or increase herba schizonepetae, herba geraniums (comparative example 3), or increase galangal, dried ginger (comparative example 4), or increase centella asiatica, rhizoma drynariae (comparative example 5), the therapeutic effect of the plaster obtained is not effectively improved. On the basis of the formula of embodiment 5, add frankincense, myrrh (comparative example 2), the effect of medicine is not significantly improved either. Just after adding strychnine (example 5) on the basis of embodiment 1-3 of this program, the therapeutic effect of plaster is just improved. The medicinal materials in the formula of comparative example 6, through early stage inventor's experimental verification, the effective component transdermal effect of their extract is all more ideal. But, if only use Aconitum kusnezoffii, Radix Saposhnikoviae, Cortex Perfoliatae, Radix Angelicae Dahuricae, Cloves and Solanum belladonna as effective component, the therapeutic effect obtained is significantly decreased than embodiment 2, so transdermal effect can not be used as the reference basis of reducing prescription design. The above-mentioned results of the study illustrate that the first formula (embodiments 1-3) is the core component of Musk Wind-Chasing Pain-Relief Plaster, and the core component combines strychnine to obtain the effect exceeding the original formula. The first formulation of this solution is the minimum formula that can achieve the same therapeutic effect as the entire formula. This first formulation not only saves on medicinal ingredients, reduces costs and process complexity, but also achieves the same therapeutic effect as the original formulation. If the first formulation lacks one ingredient, the efficacy will be difficult to guarantee; if one ingredient is added (except for Strychnos nux vomica), the efficacy will hardly be improved. This demonstrates that the first formulation of this solution achieves an unexpected technical effect.

[0123] The above is only an embodiment of the present invention, and the common knowledge such as the specific technical solutions and / or characteristics in the solution are not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the description can be used to interpret the content of the claims.

Claims

1. A pharmaceutical composition for treating rheumatoid arthritis, characterized in that: The medicinal raw materials are composed of 18-35 parts of Aconitum kusnezoffii, 18-35 parts of Radix Aconiti Kusnezoffii, 35-65 parts of Radix Saposhnikoviae, 35-65 parts of Periploca rotundifolia, 65-85 parts of Angelica dahurica, 18-35 parts of Clove, 35-115 parts of Belladonna fluid extract powder, 15-40 parts of Rutaecarpa extract powder and 25-45 parts of methyl salicylate according to parts by weight. Alternatively, the medicinal raw materials are composed of 18-35 parts of Aconitum kusnezoffii, 18-35 parts of Chuanwuji, 35-65 parts of Saposhnikovia divaricata, 35-65 parts of Periploca rotundus, 65-85 parts of Angelica dahurica, 18-35 parts of Clove, 35-115 parts of Belladonna fluid extract powder, 15-40 parts of Rutaecarpa extract powder, 25-45 parts of methyl salicylate and 18-35 parts of Strychnos nux vomica.

2. A pharmaceutical composition for treating rheumatoid arthritis according to claim 1, characterized in that: The medicinal raw materials are composed of 20-30 parts of Aconitum kusnezoffii, 20-30 parts of Chuanwu, 40-60 parts of Saposhnikovia divaricata, 40-60 parts of Periploca rotundus, 70-80 parts of Angelica dahurica, 20-30 parts of Clove, 50-100 parts of Belladonna fluid extract powder, 25-35 parts of Rutaecarpa extract powder and 30-40 parts of methyl salicylate according to weight parts; Alternatively, the medicinal raw materials are composed of 20-30 parts of Aconitum kusnezoffii, 20-30 parts of Chuanwuji, 40-60 parts of Saposhnikovia divaricata, 40-60 parts of Periploca rotundus, 70-80 parts of Angelica dahurica, 20-30 parts of Clove, 50-100 parts of Belladonna fluid extract powder, 25-35 parts of Rutaecarpa extract powder, 30-40 parts of methyl salicylate and 20-30 parts of Strychnos nux vomica.

3. A pharmaceutical composition for treating rheumatoid arthritis according to claim 2, characterized in that: According to weight parts, the medicinal raw materials are composed of 25 parts of Radix Aconiti Kusnezoffii, 25 parts of Radix Aconiti Chuanxiong, 50 parts of Radix Saposhnikoviae, 50 parts of Cortex Periplocae, 75 parts of Angelica Dahurica, 25 parts of Clove, 75 parts of Belladonna fluid extract powder, 30 parts of Rutaecarpa extract powder and 35 parts of methyl salicylate; Alternatively, the medicinal raw materials are composed of 25 parts of Radix Aconiti Kusnezoffii, 25 parts of Radix Aconiti Chuanxiong, 50 parts of Radix Saposhnikoviae, 50 parts of Cortex Periplocae, 75 parts of Radix Angelicae Dahuricae, 25 parts of Cloves, 75 parts of Belladonna fluid extract powder, 30 parts of Rutaecarpa extract powder, 35 parts of methyl salicylate and 25 parts of Strychnos nux vomica.

4. The external preparation prepared from the pharmaceutical composition according to any one of claims 1 to 3, characterized in that The external preparation is any one of an ointment, a cream, a paste, a spray, an aerosol, a gel, a paint, a film coating, a liniment, a tincture, a patch, a plaster, a fluid extract or an extract.

5. The external preparation according to claim 4, characterized in that The invention also comprises a transdermal auxiliary composition, wherein the components of the transdermal auxiliary composition are 40 to 60 parts of camphor, 15 to 25 parts of borneol and 40 to 60 parts of menthol in parts by weight.

6. The method for preparing the external preparation according to claim 4, wherein: It is prepared according to the following method: S1: using an ethanol solution as a solvent to perform heat reflux extraction on Aconitum kusnezoffii and Aconitum carmichaelii to obtain a first mixed extract and a first mixed medicinal residue; after alkalizing, extracting and drying the first mixed extract, obtaining an extract powder; S2: steam distilling cloves to obtain clove volatile oil, clove extract, and clove residue; steam distilling angelica to obtain angelica volatile oil, angelica extract, and angelica residue; concentrating the clove extract and angelica extract to obtain clove concentrate and angelica concentrate, respectively; S3: mixing the clove residue and the angelica dahurica residue from S2 with the siler and the cortex scutellariae, and performing hot reflux extraction using an ethanol solution as a solvent to obtain a second mixed extract and a second mixed residue; and concentrating the second mixed extract to obtain a first concentrated solution; S4: mixing the first mixed medicinal residue of S1 and the second mixed medicinal residue of S3, decocting and extracting the mixture with water, and concentrating the filtrate to obtain a second concentrated solution; S5: mixing the clove concentrate obtained in S2, the angelica concentrate, the first concentrate in S3, and the second concentrate in S4, and concentrating them into an extract; S6: mixing the extract powder of S1 with the powder of belladonna fluid extract and the powder of rue extract, and adding the mixture to the extract prepared in S5, spraying the volatile oil of angelica dahurica and the volatile oil of clove prepared in S2, and adding methyl salicylate to prepare a musk wind-chasing composition; S7: Add pharmaceutical excipients to the above musk wind-chasing composition and prepare it into an external preparation for clinical use.

7. The method for preparing the external preparation according to claim 6, wherein In S1, ethanol solution is used as a solvent to perform heat reflux extraction on Strychnos nux vomica, Aconitum kusnezoffii and Aconitum carmichaelii to obtain a first mixed extract and a first mixed medicinal residue; the first mixed extract is alkalized, extracted and dried to obtain an extract powder.

8. The method for preparing the external preparation according to claim 6, wherein In S6, in addition to methyl salicylate, 40-60 parts of camphor, 15-25 parts of borneol, and 40-60 parts of menthol are added.

9. Use of a pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a medicament for treating rheumatoid arthritis.

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