Preparation of external use traditional Chinese medicine preparation and application thereof in treatment of arthritis

Abstract

This invention belongs to the field of traditional Chinese medicine technology, specifically relating to the preparation of a topical Chinese medicine preparation and its application in the treatment of arthritis. The Chinese medicine preparation comprises the following raw materials in parts by weight: 30-35 parts of *Clematis chinensis*, 28-32 parts of *Curcuma zedoaria*, 26-31 parts of *Sinomenium acutum*, 25-30 parts of processed *Arisaema heterophyllum*, 23-30 parts of *Tripterygium wilfordii*, 18-22 parts of mulberry twigs, 17-20 parts of *Lysimachia christinae*, 13-16 parts of *Ligusticum chuanxiong*, 12-15 parts of *Cremastra appendiculata*, 10-15 parts of *Smilax china*, 12-18 parts of *Angelica sinensis*, 8-14 parts of *Chrysanthemum indicum*, 7-13 parts of vinegar-processed myrrh, 8-12 parts of processed *Pinellia ternata*, 6-10 parts of vinegar-processed frankincense, and 3-7 parts of licorice. The experimental results show that the topical Chinese medicine preparation of the present invention can be applied directly to the affected area, effectively relieve arthritis scores in rats with rheumatoid arthritis, reduce the diameter and thickness of toe joints, and reduce serum TNF-α and IL-6 levels, thereby improving the body's joint inflammation response.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to the preparation of a topical Chinese medicine preparation and its application in the treatment of arthritis. Background Technology

[0002] Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by erosive, symmetrical polyarthritis. Its pathological features include synovitis and pannus formation. As the disease progresses, it can lead to the destruction of articular cartilage and bone, ultimately resulting in joint deformities and loss of function, severely impacting patients' quality of life. Modern medical research indicates that the pathogenesis of RA is complex and closely related to factors such as autoimmune disorders, genetic susceptibility, and microbial infections. Overexpression of pro-inflammatory cytokines such as TNF-α and IL-6 is key to triggering joint inflammation and accelerating bone destruction.

[0003] Currently, Western medicine treatments for rheumatoid arthritis (RA) are mainly divided into four categories, but all have significant limitations: Non-steroidal anti-inflammatory drugs (NSAIDs) can quickly relieve symptoms but cannot stop disease progression, and long-term use leads to significant gastrointestinal side effects. Disease-modifying antirheumatic drugs (DMARDs) can delay joint damage, but their onset of action is slow and they are difficult to control acute symptoms. Glucocorticoids have a rapid onset of action, but long-term use has significant side effects and relapse is common upon discontinuation. Biologics are effective, but they are expensive and carry risks of infection and tumors. Because RA requires long-term or even lifelong treatment, the contradiction between efficacy and safety of existing chemical drugs is prominent, seriously affecting patient medication adherence. Finding safe and effective treatment methods has become an urgent clinical problem to be solved.

[0004] Traditional Chinese medicine (TCM) has a long history of treating rheumatoid arthritis (RA), boasting advantages such as multi-target targeting, holistic regulation, and high safety. Topical TCM preparations, in particular, can be absorbed directly through the skin to reach the affected area, avoiding the first-pass effect of the liver and gastrointestinal irritation, offering unique advantages in relieving joint swelling and pain and improving synovial inflammation. However, existing topical TCM preparations generally suffer from problems such as a lack of systematic formulation, unclear mechanisms of action, and inconsistent efficacy evaluation standards, making it difficult to achieve a comprehensive treatment. Therefore, developing topical TCM preparations with rigorous formulation, scientific compatibility, definite efficacy, and clear mechanisms, capable of effectively reducing serum pro-inflammatory factor levels, improving joint function, and possessing good safety profiles, is of significant practical importance and application value for improving the clinical treatment of RA. Summary of the Invention

[0005] The primary objective of this invention is to provide a method for preparing a topical traditional Chinese medicine preparation.

[0006] The second objective of this invention is to provide the application of the preparation of topical traditional Chinese medicine preparations in the preparation of drugs for treating arthritis.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing a topical traditional Chinese medicine preparation, specifically including the following steps: (1) Weigh out each raw material according to the following proportions: 30-35 parts of Clematis chinensis, 28-32 parts of Curcuma zedoaria, 26-31 parts of Sinomenium acutum, 25-30 parts of processed Arisaema heterophyllum, 23-30 parts of Tripterygium wilfordii, 18-22 parts of Morus alba, 17-20 parts of Dendrobium nobile, 13-16 parts of Ligusticum chuanxiong, 12-15 parts of Cremastra appendiculata, 10-15 parts of Smilax china, 12-18 parts of Angelica sinensis, 8-14 parts of Chrysanthemum indicum, 7-13 parts of vinegar-processed Commiphora myrrha, 8-12 parts of processed Pinellia ternata, 6-10 parts of vinegar-processed Boswellia carterii, and 3-7 parts of Glycyrrhiza uralensis; Tripterygium wilfordii is processed with vinegar, dried, and then pulverized to obtain Tripterygium wilfordii powder for later use; the remaining raw materials are pulverized and sieved to obtain powder for later use. (2) The powders of Curcuma zedoaria, Ligusticum chuanxiong, Angelica sinensis, vinegar-processed frankincense, and vinegar-processed myrrh were extracted by steam distillation and the volatile oils were collected. The powders of Clematis chinensis, Sinomenium acutum, Morus alba, Smilax china, Chrysanthemum morifolium, and Tripterygium wilfordii were extracted by reflux with ethanol to obtain an alcohol extract. The powders of Pyrrosia lingua, Glycyrrhiza uralensis, processed Arisaema heterophyllum, Pseudobulbus Cremastrae sibiricum, and processed Pinellia ternata were decocted with water, and the decoction was concentrated and then subjected to alcohol precipitation to obtain an aqueous extract. (3) Combine the alcohol extract and water extract from step (2) to obtain a mixture, remove impurities by activated carbon adsorption, and then concentrate it to a thick paste. (4) Heat and melt beeswax and yellow petrolatum, stir evenly; after cooling, add the volatile oil collected in step (2) and the thick paste obtained in step (3), keep warm and stir, and cool into a paste.

[0008] Further, in step (1), the following raw materials are weighed according to their weight proportions: 32 parts of Clematis chinensis, 30 parts of Curcuma zedoaria, 28 parts of Sinomenium acutum, 28 parts of processed Arisaema heterophyllum, 26 parts of Tripterygium wilfordii, 20 parts of mulberry twigs, 18 parts of Dendrobium nobile, 14 parts of Ligusticum chuanxiong, 13 parts of Pseudobulbus Cremastrae, 12 parts of Smilax china, 15 parts of Angelica sinensis, 11 parts of Chrysanthemum indicum, 10 parts of vinegar-processed Myrrh, 10 parts of processed Pinellia ternata, 8 parts of vinegar-processed Boswellia carterii, and 5 parts of Glycyrrhiza uralensis.

[0009] Further, the mesh size of the sieve in step (1) is 60-80; the vinegar preparation step is as follows: take Tripterygium wilfordii, add rice vinegar of 10% of the weight of Tripterygium wilfordii, mix well, let it soak for 2 hours, steam for 1 hour, dry and then pulverize.

[0010] Further, in step (2) steam distillation, the amount of water added is 6-8 times the total weight of the Chinese herbal powder, and the extraction time is 2-3 hours; the ethanol is 60%-75% (v / v) ethanol, the amount of ethanol added is 6-10 times the total weight of the Chinese herbal powder, and reflux extraction is performed twice, each time for 1.5-2.0 hours; in the decoction, the amount of water added is 8-10 times the total weight of the Chinese herbal powder, and decoction is performed twice, each time for 1-2 hours, and alcohol precipitation is performed by adding ethanol to a concentration of 50%-60% (v / v) for alcohol precipitation.

[0011] Further, the addition amount of activated carbon in step (3) is 0.2%-0.5% (w / v) of the volume of the mixed solution; the adsorption time is 30-45min, and the adsorption temperature is 60-70°C; the mixture is concentrated into a thick paste with a relative density of 1.25-1.35.

[0012] Further, in the step (4), the weight ratio of beeswax to yellow vaseline is 1:(6-10); the weight ratio of the total weight of beeswax and yellow vaseline to the weight of the thick paste is (6-10):1; the heating melting temperature is 70-80°C, and the temperature after cooling is 40-50°C; the weight ratio of the volatile oil to the thick paste is 1:(8-15), the heat preservation stirring temperature is 40-60°C, and the heat preservation stirring time is 10-20min.

[0013] An external traditional Chinese medicinal preparation prepared by the preparation method described in any one of the above items.

[0014] Use of the above external traditional Chinese medicinal preparation in the preparation of a medicament for treating arthritis.

[0015] To facilitate understanding of the present invention, the efficacies of the various raw materials in the present invention are described herein: Caulis Sinomenii: bitter and pungent in flavor, neutral in property, acts on the liver and spleen meridians. Functions and indications: dispelling wind-damp, and dredging meridians. It is recorded in Compendium of Materia Medica that it is used in wine and medicaments for wind-damp flow, bi-disease involving all joints with deformed swollen knee, numbness and pruritus, traumatic injury and sore swelling.

[0016] Herba Speranskiae Tuberculatae: pungent in flavor, warm in property, acts on the liver and kidney meridians. Functions and indications: dispelling wind and removing dampness, relaxing tendons and activating collaterals, dispersing blood stasis and reducing swelling. It is recorded in Supplement to Compendium of Materia Medica that it is used for treating wind-induced pain, regardless of how long the condition has lasted.

[0017] Tripterygium Wilfordii: bitter and pungent in flavor, cool in property, acts on the liver and kidney meridians. Functions and indications: dispelling wind-damp, activating blood and dredging collaterals, reducing swelling and relieving pain. It is recorded in Supplement to Compendium of Materia Medica that it is used for treating abdominal distension, edema, mass in abdomen, yellowish-white pox, chronic lingering malaria, venereal sore, leprosy and bi-disease, and traumatic injury.

[0018] Curcuma Zedoaria: pungent and bitter in flavor, warm in property, acts on the liver and spleen meridians. Functions and indications: moving qi and breaking blood, resolving stagnation and relieving pain. It is recorded in Rihuazi Bencao that it can stimulate appetite, promote digestion, unblock menstruation, resolve blood stasis, stop pain and bleeding from traumatic injury, and internal damage with vicious blood stasis and bleeding etc.

[0019] Processed Arisaematis Rhizome: bitter and pungent in flavor, warm in property, acts on the lung, liver and spleen meridians. Functions and indications: dispelling wind to stop spasm, dispersing stagnation and reducing swelling. It is recorded in Kaibao Bencao that it mainly treats apoplexy with numbness, can resolve phlegm and descend qi, soothe chest diaphragm, break hard mass, resolve carbuncle and swelling, disperse blood stasis and induce abortion.

[0020] Brucea javanica: sweet and bland in flavor, cold in property, acts on the stomach and large intestine meridians. Functions and indications: clearing heat and removing toxicity, activating blood and dispersing stasis, reducing swelling and relieving pain. It is recorded in Wanxian Materia Medica that it can clear heat and remove toxicity, activate blood and move stasis.

[0021] Mulberry twigs: Slightly bitter, neutral in nature. Enters the Liver meridian. Functions and indications: Dispels wind and unblocks the meridians, promotes diuresis and reduces swelling. The *Compendium of Materia Medica* records: Benefits joints, nourishes body fluids, promotes diuresis and dispels wind.

[0022] Chuanxiong (Ligusticum striatum): pungent, warm. Enters the liver and gallbladder meridians. Functions and indications: invigorates blood circulation, promotes qi flow, dispels wind, and relieves pain. The Chinese Pharmacopoeia records its use for rheumatic pain.

[0023] Mountain Pseudobulbus: Sweet, slightly pungent, and cool in nature. It enters the Liver and Spleen meridians. Functions and indications: Dissipates nodules and reduces swelling. According to *Diannan Materia Medica*, it eliminates phlegm in the Yin aspect, stops coughs, treats sore throat, and relieves pharyngitis. It treats boils and carbuncles, and can be applied to various sores and swellings; it ulcerates those with pus and reduces those without.

[0024] Smilax china: Sweet, slightly bitter, astringent, neutral. It enters the liver and kidney meridians. Functions and indications: dispels wind and promotes diuresis. The *Mingyi Bielu* records: it treats cold pain in the lower back, wind-dampness, nourishes blood and qi, and stops frequent urination.

[0025] Chrysanthemum indicum: Cool in nature, sweet and neutral in flavor. Functions and indications: Moistens the lungs and kidneys, cools the blood and reduces swelling. According to *Sheng Cao Yao Xing Bei Yao* (Essentials of Herbal Properties), it relieves cough and phlegm, moistens the lungs and kidneys.

[0026] Vinegar and Myrrh: Bitter, pungent, neutral. Enters the Heart, Liver, and Spleen meridians. Functions and indications: Promotes blood circulation, relieves pain, reduces swelling, and promotes tissue regeneration. The *Treatise on the Nature of Medicinal Herbs* records: It can treat injuries from falls, muscle and bone pain due to blood stasis, and unbearable pain from injuries caused by metal weapons.

[0027] Pinellia ternata (processed): pungent, warm. Enters the spleen, stomach, and lung meridians. Functions and indications: strengthens the spleen and dries dampness. According to *Compendium of Materia Medica*: dries dampness and phlegm, moistens kidney dryness, and promotes the flow of yin and yang.

[0028] Angelica sinensis: Sweet, pungent, and warm. It enters the liver, heart, and spleen meridians. Functions and indications: Nourishes and invigorates blood, regulates menstruation, and relieves pain. The Compendium of Materia Medica records: Treats headaches, various abdominal pains, and moistens the intestines, stomach, muscles, bones, and skin.

[0029] Vinegar-processed frankincense: pungent, bitter, and warm. It enters the heart, liver, and spleen meridians. Functions and indications: invigorates blood circulation, promotes qi flow, relieves pain, reduces swelling, and promotes tissue regeneration. The *Mingyi Bielu* records: slightly warm. It treats edema caused by wind and dampness, and removes foul odors. It also treats itchy rashes caused by wind and dampness.

[0030] Licorice: Sweet in taste and neutral in nature. It enters the heart, lung, spleen, and stomach meridians. Functions and indications: Tonifies the spleen and replenishes qi, clears heat and detoxifies, and harmonizes the effects of other herbs.

[0031] The Compendium of Materia Medica records that among all medicines, licorice is the chief herb, treating seventy-two kinds of mineral poisoning, detoxifying one thousand two hundred kinds of herbal poisoning, and harmonizing various medicines; hence, it is called the "Elder of the Nation." Compared with the prior art, the main advantages of the present invention are as follows: This invention provides a preparation and application of a topical traditional Chinese medicine preparation. The preparation uses five herbs—*Sinomenium acutum*, *Clematis chinensis*, *Tripterygium wilfordii*, *Curcuma zedoaria*, and processed Arisaema heterophyllum—as the principal herbs, which have the effects of dispelling wind and dampness, clearing the meridians, and relieving pain. Five herbs—*Lysimachia christinae*, *Morus alba* twigs, *Ligusticum chuanxiong*, *Cremastra appendiculata*, and *Smilax china*—as the assistant herbs, which assist the principal herbs and have the effects of promoting qi circulation, relieving pain, invigorating blood, and promoting diuresis. Five adjuvant herbs—*Chrysanthemum indicum*, vinegar-processed myrrh, processed Pinellia ternata, Angelica sinensis, and vinegar-processed frankincense—are combined to have the effects of regulating and tonifying the kidneys and spleen, reducing swelling, and promoting tissue regeneration. Licorice is used as the guiding herb to harmonize the other herbs and direct them to the meridians. The combined effects of these herbs are to dispel wind and dampness, promote qi circulation and blood circulation, resolve blood stasis and dissipate nodules, and clear the meridians and relieve pain. Experimental results show that the topical Chinese medicine preparation of this invention can be applied directly to the affected area, effectively alleviating arthritis scores in rats with rheumatoid arthritis, reducing the diameter and thickness of toe joints, and decreasing serum TNF-α and IL-6 levels, thereby improving the body's joint inflammation response. Furthermore, this topical Chinese medicine preparation is convenient to use, has no obvious side effects, is safe and highly effective, and has good prospects for clinical application. Attached Figure Description

[0032] Figure 1 The effect of different groups of topical Chinese medicine preparations on the serum TNF-α content of rats; Figure 2 The effect of different groups of topical Chinese medicine preparations on the serum IL-6 content in rats. Detailed Implementation

[0033] The technical solution of the present invention will be further described below with reference to specific embodiments. However, those skilled in the art should understand that the following embodiments are only for illustrating the present invention and should not be regarded as limiting the present invention. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the reagents or instruments used are all conventional products obtained through commercial channels.

[0034] Example 1 Preparation of a topical Chinese medicine preparation, the topical Chinese medicine preparation comprising the following raw materials in parts by weight: 32 parts of Clematis chinensis, 30 parts of Curcuma zedoaria, 28 parts of Sinomenium acutum, 28 parts of processed Arisaema heterophyllum, 26 parts of Tripterygium wilfordii, 20 parts of Morus alba twigs, 18 parts of Ligusticum striatum, 14 parts of Ligusticum chuanxiong, 13 parts of Cremastra appendiculata, 12 parts of Smilax china, 15 parts of Angelica sinensis, 11 parts of Chrysanthemum indicum, 10 parts of vinegar-processed Commiphora myrrha, 10 parts of processed Pinellia ternata, 8 parts of vinegar-processed Boswellia carterii, and 5 parts of Glycyrrhiza uralensis.

[0035] A method for preparing a topical traditional Chinese medicine preparation, specifically including the following steps: (1) Weigh out each raw material according to the following weight proportions: 32 parts of Clematis chinensis, 30 parts of Curcuma zedoaria, 28 parts of Sinomenium acutum, 28 parts of processed Arisaema heterophyllum, 26 parts of Tripterygium wilfordii, 20 parts of mulberry twig, 18 parts of Dendrobium nobile, 14 parts of Ligusticum chuanxiong, 13 parts of Pseudobulbus Cremastrae, 12 parts of Smilax china, 15 parts of Angelica sinensis, 11 parts of Chrysanthemum indicum, 10 parts of vinegar-processed Commiphora myrrha, 10 parts of processed Pinellia ternata, 8 parts of vinegar-processed Boswellia carterii, and 5 parts of Glycyrrhiza uralensis; take Tripterygium wilfordii, add 10% of the weight of Tripterygium wilfordii in rice vinegar, mix well, let it sit for 2 hours, steam for 1 hour, dry and then pulverize to obtain Tripterygium wilfordii Chinese medicine powder for later use; pulverize the remaining raw materials and pass them through a 70-mesh sieve to obtain Chinese medicine powder for later use. (2) The Chinese herbal powders of Curcuma zedoaria, Ligusticum chuanxiong, Angelica sinensis, vinegar-processed frankincense, and vinegar-processed myrrh were extracted by steam distillation. The extract was then extracted with water at a ratio of 7 times the total weight of the Chinese herbal powders for 2 hours, and the volatile oil was collected. The Chinese herbal powders of Clematis chinensis, Sinomenium acutum, Morus alba, Smilax china, Chrysanthemum indicum, and Tripterygium wilfordii were extracted twice by reflux with 67% ethanol for 1.7 hours each time. The amount of ethanol added was 8 times the total weight of the Chinese herbal powders, and the alcohol extract was obtained. The Chinese herbal powders of Lonicera japonica, Glycyrrhiza uralensis, Arisaema heterophyllum, Pseudobulbus Cremastrae sibiricum, and Pinellia ternata were decocted twice with water at a ratio of 9 times the total weight of the Chinese herbal powders for 1 hour each time. The decoction was concentrated and ethanol was added to a concentration of 55% ethanol for alcohol precipitation, and the water extract was obtained. (3) Combine the alcohol extract and water extract from step (2) to obtain a mixture. After removing impurities by adsorption with activated carbon at 65°C for 37 min, the amount of activated carbon added is 0.4 w / v% of the volume of the mixture. Concentrate to a thick paste with a relative density of 1.30. (4) Melt beeswax and yellow petrolatum at 75°C. The weight ratio of beeswax to yellow petrolatum is 1:8. Stir evenly. After cooling to 45°C, add the volatile oil collected in step (2) and the thick paste obtained in step (3). The total weight ratio of beeswax and yellow petrolatum to the weight ratio of the thick paste is 8:1. The weight ratio of volatile oil to the thick paste is 1:11. Keep warm at 50°C and stir for 15 minutes. Cool to form a paste.

[0036] Example 2 Preparation of a topical traditional Chinese medicine preparation, the topical traditional Chinese medicine preparation comprising the following raw materials in parts by weight: 30-35 parts of Clematis chinensis, 28 parts of Curcuma zedoaria, 26 parts of Sinomenium acutum, 25 parts of processed Arisaema heterophyllum, 23 parts of Tripterygium wilfordii, 18 parts of Morus alba twigs, 17 parts of Dendrobium nobile, 13 parts of Ligusticum chuanxiong, 12 parts of Cremastra appendiculata, 10 parts of Smilax china, 12 parts of Angelica sinensis, 8 parts of Chrysanthemum indicum, 7 parts of vinegar-processed Commiphora myrrha, 8 parts of processed Pinellia ternata, 6 parts of vinegar-processed Boswellia carterii, and 3 parts of Glycyrrhiza uralensis.

[0037] A method for preparing a topical traditional Chinese medicine preparation, specifically including the following steps: (1) Weigh out each raw material according to the following weight proportions: 30 parts of Clematis chinensis, 28 parts of Curcuma zedoaria, 26 parts of Sinomenium acutum, 25 parts of processed Arisaema heterophyllum, 23 parts of Tripterygium wilfordii, 18 parts of Morus alba, 17 parts of Dendrobium nobile, 13 parts of Ligusticum chuanxiong, 12 parts of Pseudobulbus Cremastrae, 10 parts of Smilax china, 12 parts of Angelica sinensis, 8 parts of Chrysanthemum indicum, 7 parts of vinegar-processed Commiphora myrrha, 8 parts of processed Pinellia ternata, 6 parts of vinegar-processed Boswellia carterii, and 3 parts of Glycyrrhiza uralensis; Take Tripterygium wilfordii, add 10% of the weight of Tripterygium wilfordii in rice vinegar, mix well, let it sit for 2 hours, steam for 1 hour, dry and then pulverize to obtain Tripterygium wilfordii Chinese medicine powder for later use; Pulverize the remaining raw materials and pass them through a 60-mesh sieve to obtain Chinese medicine powder for later use. (2) Extract the Chinese herbal powders of Curcuma zedoaria, Ligusticum chuanxiong, Angelica sinensis, vinegar-processed frankincense, and vinegar-processed myrrh by steam distillation. Add water equal to 6 times the total weight of the Chinese herbal powders and extract for 2 hours, then collect the volatile oil. Add 60 v / v% ethanol to the Chinese herbal powders of Clematis chinensis, Sinomenium acutum, Morus alba, Smilax china, Chrysanthemum indicum, and Tripterygium wilfordii and reflux extract twice for 1.5 hours each time. The amount of ethanol added is 6-10 times the total weight of the Chinese herbal powders to obtain the alcohol extract. Add 8-10 times the total weight of water to the Chinese herbal powders of Lonicera japonica, Glycyrrhiza uralensis, processed Arisaema heterophyllum, Pseudobulbus Cremastrae sibiricum, and processed Pinellia ternata and decoct twice for 1 hour each time. Concentrate the decoction and add ethanol to a concentration of 50 v / v% for alcohol precipitation to obtain the water extract. (3) Combine the alcohol extract and water extract from step (2) to obtain a mixture. After removing impurities by adsorption with activated carbon at 60°C for 30 min, the amount of activated carbon added is 0.2 w / v% of the volume of the mixture. Concentrate to a thick paste with a relative density of 1.25. (4) Melt beeswax and yellow petrolatum at 70°C. The weight ratio of beeswax to yellow petrolatum is 1:6. Stir evenly. After cooling to 40°C, add the volatile oil collected in step (2) and the thick paste obtained in step (3). The total weight ratio of beeswax and yellow petrolatum to the weight ratio of the thick paste is 6:1. The weight ratio of volatile oil to the thick paste is 1:8. Keep warm at 40°C and stir for 10 minutes. Cool to form a paste.

[0038] Example 3 Preparation of a topical Chinese medicine preparation, the topical Chinese medicine preparation comprising the following raw materials in parts by weight: 35 parts of Clematis chinensis, 32 parts of Curcuma zedoaria, 31 parts of Sinomenium acutum, 30 parts of processed Arisaema heterophyllum, 30 parts of Tripterygium wilfordii, 22 parts of Morus alba twigs, 20 parts of Dendrobium nobile, 16 parts of Ligusticum chuanxiong, 15 parts of Cremastra appendiculata, 15 parts of Smilax china, 18 parts of Angelica sinensis, 14 parts of Chrysanthemum indicum, 13 parts of vinegar-processed Commiphora myrrha, 12 parts of processed Pinellia ternata, 10 parts of vinegar-processed Boswellia carterii, and 7 parts of Glycyrrhiza uralensis.

[0039] A method for preparing a topical traditional Chinese medicine preparation, specifically including the following steps: (1) Weigh out each raw material according to the following weight proportions: 35 parts of Clematis chinensis, 32 parts of Curcuma zedoaria, 31 parts of Sinomenium acutum, 30 parts of processed Arisaema heterophyllum, 30 parts of Tripterygium wilfordii, 22 parts of Morus alba, 20 parts of Dendrobium nobile, 16 parts of Ligusticum chuanxiong, 15 parts of Pseudobulbus Cremastrae, 15 parts of Smilax china, 18 parts of Angelica sinensis, 14 parts of Chrysanthemum indicum, 13 parts of vinegar-processed Commiphora myrrha, 12 parts of processed Pinellia ternata, 10 parts of vinegar-processed Boswellia carterii, and 7 parts of Glycyrrhiza uralensis; Take Tripterygium wilfordii, add 10% of the weight of Tripterygium wilfordii in rice vinegar, mix well, let it sit for 2 hours, steam for 1 hour, dry and then pulverize to obtain Tripterygium wilfordii Chinese medicine powder for later use; Pulverize the remaining raw materials and pass them through a 60-80 mesh sieve to obtain Chinese medicine powder for later use. (2) Extract the Chinese herbal powders of Curcuma zedoaria, Ligusticum chuanxiong, Angelica sinensis, vinegar-processed frankincense, and vinegar-processed myrrh by steam distillation. Add water equal to 8 times the total weight of the Chinese herbal powders and extract for 3 hours. Collect the volatile oil. Add 75 v / v% ethanol to the Chinese herbal powders of Clematis chinensis, Sinomenium acutum, Morus alba, Smilax china, Chrysanthemum indicum, and Tripterygium wilfordii and reflux extract twice for 2 hours each time. The amount of ethanol added is 10 times the total weight of the Chinese herbal powders. Obtain the alcohol extract. Add 8-10 times the total weight of water to the Chinese herbal powders of Lonicera japonica, Glycyrrhiza uralensis, processed Arisaema heterophyllum, Pseudobulbus Cremastrae spp. and processed Pinellia ternata and decoct twice for 2 hours each time. Concentrate the decoction and add ethanol to the alcohol content to 60 v / v% for alcohol precipitation treatment. Obtain the water extract. (3) Combine the alcohol extract and water extract from step (2) to obtain a mixture. After removing impurities by adsorption with activated carbon at 70°C for 45 min, the amount of activated carbon added is 0.5 w / v% of the volume of the mixture. Concentrate to a thick paste with a relative density of 1.35. (4) Melt beeswax and yellow petrolatum at 80°C. The weight ratio of beeswax to yellow petrolatum is 1:10. Stir evenly. After cooling to 50°C, add the volatile oil collected in step (2) and the thick paste obtained in step (3). The total weight ratio of beeswax and yellow petrolatum to the weight ratio of the thick paste is 10:1. The weight ratio of volatile oil to the thick paste is 1:15. Keep warm at 60°C and stir for 20 minutes. Cool to form a paste.

[0040] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that the ingredient of one external Chinese medicine preparation, *Lysimachia christinae*, is omitted; otherwise, they are the same as in Example 1.

[0041] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that the ingredient of one external Chinese medicine preparation, *Gynostemma pentaphyllum*, is omitted; otherwise, they are the same as in Example 1.

[0042] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that the ingredient of a topical Chinese medicine preparation, *Lysimachia christinae*, is replaced with *Panax notoginseng*. All other aspects are the same as in Example 1.

[0043] Experimental Example 1 The following are the experimental results of a topical traditional Chinese medicine preparation obtained in Examples 1-3 and Comparative Examples 1-3: (1) One hundred and thirty female Wistar rats aged 6-8 weeks were selected for the experiment. After one week of acclimatization, ten rats were randomly selected as the blank control group, and the remaining rats were used to establish a rheumatoid arthritis model. The modeling method was as follows: Bovine type II collagen was fully emulsified with an equal amount of complete Freund's adjuvant to prepare a type II collagen solution with a final concentration of 2 mg / ml as the primary immunization inducer. 0.2 mL was injected subcutaneously into the tail root of each rat. Seven days later, another injection point was selected near the site of the first immunization, and a collagen solution fully emulsified with bovine type II collagen and an equal amount of incomplete Freund's adjuvant was administered for a second immunization. 0.1 mL was injected into each rat. The blank control group rats were injected subcutaneously with an equal amount of physiological saline at the same site. About seven days after the second immunization, the rats' toe joints were observed. The rats were considered to have successfully established the model if at least one toe joint showed redness and swelling. Eighty rats that successfully established the model were randomly divided into a positive control group, a model group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group, with 10 rats in each group.

[0044] (2) Intervention began 7 days after the second immunization. Each test drug was applied to a clean three-layer gauze pad and then placed on the affected area of ​​the rat's hind paw joint, once daily for 30 minutes each time, for 14 consecutive days. The external dose for rats was calculated as 6 times the intended clinical dose for humans (based on body surface area). Specific grouping and treatment were as follows: Blank control group: Gauze without medication was applied topically once a day for 30 minutes each time, for 14 consecutive days.

[0045] Model group: The patient was given a drug-free gauze dressing once a day for 30 minutes each time for 14 consecutive days.

[0046] Positive control group: Diclofenac diethylamine emulsion was applied topically once a day for 30 minutes each time, for 14 consecutive days.

[0047] Examples 1-3: The topical Chinese medicine preparations prepared in Examples 1-3 were applied topically once a day for 30 minutes each time, for 14 consecutive days.

[0048] Comparative Examples 1-3: The topical Chinese medicine preparations prepared in Comparative Examples 1-3 were applied topically once a day for 30 minutes each time, for 14 consecutive days.

[0049] (3) After the administration of the drug, the joint swelling was evaluated according to the 5-point scoring method. The specific criteria are shown in Table 1. The scores of the left and right hind ankle joints of each rat were calculated and added together to form the arthritis index of the rat. The highest score was 8 points. The results are shown in Table 2.

[0050] Table 1. Joint Swelling Scoring Criteria Table 2. Effects of different groups of topical Chinese medicine preparations on joint swelling scores in rats. The results are shown in Table 2, which illustrates the effects of different groups of topical Chinese medicine preparations on joint swelling scores in rats. Table 2 shows that compared to the blank control group, the joint swelling scores of the model group rats were significantly increased, indicating successful establishment of the rheumatoid arthritis model. Two weeks after administration, compared to the model group, Comparative Example 1, Comparative Example 2, and Comparative Example 3, the Chinese medicine preparations prepared in Examples 1-3 of this invention significantly reduced the joint swelling scores in rats. This indicates that the Chinese medicine preparations prepared in this invention have a clear therapeutic effect on rheumatoid arthritis.

[0051] (4) After the administration of the drug, all rats were fasted but allowed free access to water. The following day, they were weighed, anesthetized by intraperitoneal injection of 2% sodium pentobarbital, their abdominal fur was clipped, and after disinfection with 75% alcohol, the abdomen was opened, and blood was collected from the aorta. The blood was centrifuged at 3000 rpm for 10 minutes at 4°C, and the supernatant serum was collected. The levels of TNF-α and IL-6 in the serum of each group of rats were detected using ELISA. The results are as follows: Figure 1 , Figure 2 As shown.

[0052] The results are as follows Figure 1 , Figure 2 The figures show the effects of different groups of topical traditional Chinese medicine preparations on the levels of TNF-α and IL-6 in rat serum. Compared with the blank control group, the levels of TNF-α and IL-6 in the serum of rats in the model group were significantly increased, indicating that the rheumatoid arthritis model was successfully established. Two weeks after administration, compared with the model group, comparative group 1, comparative group 2, and comparative group 3, the traditional Chinese medicine preparations prepared in Examples 1-3 of this invention could significantly reduce the levels of TNF-α and IL-6 in rat serum. This indicates that the traditional Chinese medicine preparations of this invention may exert their therapeutic effect on rheumatoid arthritis by downregulating the expression of key pro-inflammatory cytokines such as TNF-α and IL-6.

[0053] (5) After the administration was completed, the diameter and thickness of the hind paw joints of rats in each group were measured with vernier calipers to evaluate the effect of different groups of traditional Chinese medicine preparations on the degree of swelling of rat paws. The results are shown in Table 3.

[0054] Table 3. Effects of different groups of topical Chinese medicine preparations on the diameter and thickness of rat toes. The results are shown in Table 3, illustrating the effects of different groups of topical Chinese medicine preparations on the diameter and thickness of rat toes. Compared with the blank control group, the diameter and thickness of the toe joints in the model group rats were significantly increased, indicating successful establishment of the rheumatoid arthritis model. Two weeks after administration, compared with the model group, Comparative Example 1, Comparative Example 2, and Comparative Example 3, the Chinese medicine preparations prepared in Examples 1-3 of this invention significantly reduced the diameter and thickness of the toe joints in rats. This indicates that the Chinese medicine preparations prepared in this invention can effectively alleviate the swelling of the toe joints in rats with collagen-induced arthritis.

[0055] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.

Claims

1. A method for preparing a topical traditional Chinese medicine preparation, characterized in that, Specifically, the following steps are included: (1) Weigh out each raw material according to the following proportions: 30-35 parts of Clematis chinensis, 28-32 parts of Curcuma zedoaria, 26-31 parts of Sinomenium acutum, 25-30 parts of processed Arisaema heterophyllum, 23-30 parts of Tripterygium wilfordii, 18-22 parts of Morus alba, 17-20 parts of Dendrobium nobile, 13-16 parts of Ligusticum chuanxiong, 12-15 parts of Cremastra appendiculata, 10-15 parts of Smilax china, 12-18 parts of Angelica sinensis, 8-14 parts of Chrysanthemum indicum, 7-13 parts of vinegar-processed Commiphora myrrha, 8-12 parts of processed Pinellia ternata, 6-10 parts of vinegar-processed Boswellia carterii, and 3-7 parts of Glycyrrhiza uralensis; Tripterygium wilfordii is processed with vinegar, dried, and then pulverized to obtain Tripterygium wilfordii powder for later use; the remaining raw materials are pulverized and sieved to obtain powder for later use. (2) The powders of Curcuma zedoaria, Ligusticum chuanxiong, Angelica sinensis, vinegar-processed frankincense, and vinegar-processed myrrh were extracted by steam distillation and the volatile oils were collected. The powders of Clematis chinensis, Sinomenium acutum, Morus alba, Smilax china, Chrysanthemum morifolium, and Tripterygium wilfordii were extracted by reflux with ethanol to obtain an alcohol extract. The powders of Pyrrosia lingua, Glycyrrhiza uralensis, processed Arisaema heterophyllum, Pseudobulbus Cremastrae sibiricum, and processed Pinellia ternata were decocted with water, and the decoction was concentrated and then subjected to alcohol precipitation to obtain an aqueous extract. (3) Combine the alcohol extract and water extract from step (2) to obtain a mixture, remove impurities by activated carbon adsorption, and then concentrate it to a thick paste. (4) Heat and melt beeswax and yellow petrolatum, stir evenly; after cooling, add the volatile oil collected in step (2) and the thick paste obtained in step (3), keep warm and stir, and cool into a paste.

2. The method for preparing a topical traditional Chinese medicine preparation according to claim 1, characterized in that, In step (1), the following raw materials are weighed according to their weight proportions: 32 parts of Clematis chinensis, 30 parts of Curcuma zedoaria, 28 parts of Sinomenium acutum, 28 parts of processed Arisaema heterophyllum, 26 parts of Tripterygium wilfordii, 20 parts of mulberry twigs, 18 parts of Dendrobium nobile, 14 parts of Ligusticum chuanxiong, 13 parts of Pseudobulbus Cremastrae, 12 parts of Smilax china, 15 parts of Angelica sinensis, 11 parts of Chrysanthemum indicum, 10 parts of vinegar-processed Commiphora myrrha, 10 parts of processed Pinellia ternata, 8 parts of vinegar-processed Boswellia carterii, and 5 parts of Glycyrrhiza uralensis.

3. The method for preparing a topical traditional Chinese medicine preparation according to claim 1, characterized in that, The mesh size of the sieve in step (1) is 60-80; the vinegar preparation step is as follows: take Tripterygium wilfordii, add rice vinegar of 10% of the weight of Tripterygium wilfordii, mix well, let it soak for 2 hours, steam for 1 hour, dry and then crush.

4. The method for preparing a topical traditional Chinese medicine preparation according to claim 1, characterized in that, In step (2), the amount of water added in the steam distillation method is 6-8 times the total weight of the Chinese herbal powder, and the extraction time is 2-3 hours; the ethanol is 60%-75% (v / v) ethanol, the amount of ethanol added is 6-10 times the total weight of the Chinese herbal powder, and the reflux extraction is performed twice, each time for 1.5-2.0 hours; in the decoction, the amount of water added is 8-10 times the total weight of the Chinese herbal powder, the decoction is performed twice, each time for 1-2 hours, and the alcohol precipitation treatment is to add ethanol to the alcohol content to 50%-60% (v / v) for alcohol precipitation.

5. The method for preparing a topical traditional Chinese medicine preparation according to claim 1, characterized in that, In step (3), the amount of activated carbon added is 0.2%-0.5% (w / v) of the volume of the mixed liquid; the adsorption time is 30-45 min, the adsorption temperature is 60-70℃; and it is concentrated to a thick paste with a relative density of 1.25-1.

35.

6. The method for preparing a topical traditional Chinese medicine preparation according to claim 3, characterized in that, In step (4), the weight ratio of beeswax to yellow petrolatum is 1:(6-10); the total weight of beeswax and yellow petrolatum to the weight ratio of the thick paste is (6-10):1; the heating and melting temperature is 70-80℃, and the temperature after cooling is 40-50℃; the weight ratio of the volatile oil to the thick paste is 1:(8-15); the temperature for heat preservation and stirring is 40-60℃, and the time for heat preservation and stirring is 10-20min.

7. A topical traditional Chinese medicine preparation, characterized in that, It is prepared according to any one of claims 1-6.

8. The application of the topical traditional Chinese medicine preparation according to claim 7 in the preparation of drugs for treating arthritis.

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