Traditional Chinese medicine gel plaster for treating gouty arthritis and preparation method thereof

Abstract

The invention provides a traditional Chinese medicine gel patch for treating gouty arthritis and a preparation method thereof. The traditional Chinese medicine gel patch for treating gouty arthritis comprises at least a gel layer loaded with traditional Chinese medicine extracts; the traditional Chinese medicine extracts comprise the following raw materials: coix seed, phellodendron amurense, clematis root, radix scutellariae, atractylodes lancea, radix ophiopogonis, radix scutellariae, acer scutellariae, radix scutellariae, radix aconiti kusnezoffii, radix strychnii, frankincense, myrrh, angelica sinensis, safflower, cyathula root, radix paeoniae rubra, radix smilacis gracile, radix striatae, eucalyptus glomeratae, sophora flavescens, andrographis paniculatae, radix lobeliae, rhizoma coptidis, radix scutellariae, cassia twig, zanthoxylum bungeanum, and borneol; and a matrix of the gel layer comprises the following raw materials in parts by weight: silk fibroin, polyvinyl pyrrolidone, azido-polyethylene glycol-carboxylic acid, 1-ethynylcyclopropylcarboxylic acid, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol. The traditional Chinese medicine gel plaster of the present invention can achieve good therapeutic effects through percutaneous absorption.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, in particular to a traditional Chinese medicine gel plaster for treating gouty arthritis and a preparation method thereof. Background Art

[0002] Gouty arthritis (GA) is a chronic metabolic inflammatory disease characterized by purine metabolism disorders and significantly elevated blood uric acid levels. It often induces an inflammatory response due to the deposition of sodium urate crystals in the joints and surrounding tissues. Multiple inflammation-related signaling pathways act individually or synergistically to promote the release of inflammatory factors, mediate the inflammatory cascade reaction, and cause joint damage such as arthritis, synovitis, and articular cartilage inflammation, which may eventually lead to joint dysfunction and even disability.

[0003] In recent years, the increasing aging of my country's population has further contributed to an increase in the number of GA patients, with the number of young people suffering from the disease also increasing year by year. Current treatments for gout primarily focus on lowering serum uric acid levels and relieving inflammatory pain in the affected area. Western medicine typically combines XOD inhibitors (such as allopurinol and febuxostat) with antipyretics and analgesics such as berberine and nonsteroidal anti-inflammatory drugs. While these medications are effective in lowering uric acid, they have no significant effect on joint symptoms and other concurrent symptoms, and are associated with numerous side effects, such as liver and kidney damage and gastrointestinal discomfort.

[0004] Traditional Chinese Medicine (TCM) excels at treating both the symptoms and the root cause, and has outstanding advantages in the overall therapeutic effect on gouty joint symptoms and other concurrent symptoms. Ancient physicians believed that gouty arthritis fell under the category of "arthritis" and "white tiger calendar wind," while modern physicians have proposed names such as "gouty arthritis" and "turbid stasis arthritis." The main pathogenesis can be summarized as "spleen deficiency and dampness, accumulation of damp-heat, phlegm and blood stasis, and liver and kidney deficiency," with spleen deficiency and dampness as the root cause, accumulation of damp-heat as the main cause, phlegm and blood stasis as the manifestation, and liver and kidney deficiency as the result. The initial manifestations are red, swollen, hot, and painful joints, and the symptoms recur; subsequently, it manifests as localized hard nodules or dark red skin, recurrent joint swelling and pain, which do not heal over time, and obvious tophi; in the later stages, the patient suffers from recurrent joint pain, stiffness or deformity, and even edema, with severe renal impairment. The entire course of the disease is a mixture of deficiency and excess, with deficiency in the root cause and excess in the symptoms. Therefore, Traditional Chinese Medicine (TCM) focuses on treating both the symptoms and the root cause, treating the symptoms first in emergencies. It treats the symptoms by dispelling pathogenic factors, activating blood circulation, and unblocking the meridians. It primarily regulates the liver and kidneys, restores fluid metabolism, and inhibits the production of damp-heat, phlegm, and blood stasis. Common TCM therapies include oral and topical Chinese medicine, acupuncture, and massage, supplemented by dietary adjustments to control the condition. Among these, powders are the primary topical Chinese medicine preparations for gouty arthritis, but their transdermal penetration is poor, resulting in suboptimal therapeutic effects. Summary of the Invention

[0005] The purpose of the present invention is to provide a traditional Chinese medicine gel plaster for treating gouty arthritis and a preparation method thereof, so as to solve the problems of poor transdermal effect and unsatisfactory therapeutic effect of the traditional Chinese medicine gel plaster for treating gouty arthritis in the prior art.

[0006] The present invention provides the following technical solutions:

[0007] A traditional Chinese medicine gel patch for treating gouty arthritis, comprising at least a gel layer loaded with a traditional Chinese medicine extract;

[0008] The Chinese herbal extracts include the following raw materials: coix seed, phellodendron, clematis root, radix strychnifoliae, atractylodes, radix scutellariae, radix scutellariae, radix scutellariae, radix scutellariae, radix aconiti kusnezoffii, radix strychnifoliae, frankincense, myrrh, angelica, safflower, cyathula, radix peonyii, radix smilax, radix striatae, radix eucalyptus, radix sophorae flavescentis, radix andrographis paniculatae, radix lobeliae, radix coptidis, radix scutellariae, radix cinnamon, radix prickly ash, and borneol;

[0009] The matrix of the gel layer comprises the following raw materials in parts by weight:

[0010] 100-120 parts of silk fibroin, 20-40 parts of polyvinyl pyrrolidone, 5-8 parts of azide-polyethylene glycol-carboxylic acid, 6-10 parts of 1-ethynylcyclopropylcarboxylic acid, 5-10 parts of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and 80-100 parts of glycerol.

[0011] Preferably, the Chinese herbal medicine extract comprises the following raw materials in parts by weight:

[0012] 20-40 parts of coix seed, 5-15 parts of phellodendron, 5-15 parts of clematis root, 10-20 parts of diatomaceous earth, 5-16 parts of atractylodes, 10-20 parts of radix polygoni multiflori, 20-40 parts of safflower, 1-5 parts of octagonal maple, 10-20 parts of truncatum, 1-3 parts of aconite, 1-3 parts of kusnezoffii, 0.1-0.5 parts of strychnine, 1-10 parts of frankincense, 1-10 parts of myrrh, 5-15 parts of angelica, 5-15 parts of safflower, 10-20 parts of safflower, 10-20 parts of radix polygoni multiflori, 10-20 parts of radix polygoni multiflori, 10-3 parts of radix polygoni multiflori, 10-20 parts of radix polygoni multiflori, 10-3 parts of radix polygoni multiflori, 10-10 parts of radix polygoni multiflori, 10-2 ...20 parts of 5-15 parts of knee, 5-15 parts of red peony root, 20-40 parts of rhizoma smilacis, 5-15 parts of herba lycopersicum, 1-10 parts of daylily roots, 20-40 parts of weeping willow branches, 20-40 parts of three-branched bitter herbs, 10-20 parts of large-leaved eucalyptus, 1-20 parts of sophora flavescens, 1-20 parts of andrographis paniculata, 10-20 parts of lobelia, 1-10 parts of coptis root, 1-20 parts of smilax glabra, 5-15 parts of cassia twig, 1-15 parts of zanthoxylum bungeanum, and 0.1-0.5 parts of borneol.

[0013] Preferably, the raw materials of the Chinese herbal medicine extract further include 1-10 parts of Arisaema.

[0014] Preferably, the gel layer further comprises 5-8 parts of calcium lignin sulfonate and / or 0.2-1.2 parts of tannic acid.

[0015] Preferably, in the gel layer, the weight ratio of the matrix to the traditional Chinese medicine extract is (3-5):1.

[0016] Preferably, the matrix first undergoes a click chemistry reaction between the azide-polyethylene glycol-carboxylic acid and the 1-ethynylcyclopropyl carboxylic acid to obtain a first reaction product; then the first reaction product is mixed with the silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol, so that the carboxyl group of the first reaction product and the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene react with the amino group of the silk fibroin to form a structure blended with the polyvinyl pyrrolidone and glycerol.

[0017] That is, the carboxyl group of the first reaction product, the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene and the amino group of the silk fibroin react to form an amide bond, thereby cross-linking to form a network structure, and physically blending with the polyvinyl pyrrolidone to form a network structure in which the molecular chains are entangled or interpenetrating with each other.

[0018] The present invention also provides a method for preparing the traditional Chinese medicine gel plaster for treating gouty arthritis, comprising the following steps:

[0019] (1) dissolving azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid in a solvent and reacting to obtain a first reaction product;

[0020] (2) uniformly mixing the first reaction product with silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, glycerol, and a Chinese herbal medicine extract, and reacting to obtain a mixed solution;

[0021] (3) The mixed solution is evenly coated and allowed to stand for aging to obtain a gel layer loaded with the Chinese herbal medicine extract.

[0022] Preferably, the preparation method of the traditional Chinese medicine gel plaster for treating gouty arthritis specifically comprises the following steps:

[0023] (1) dissolving azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid in a solvent of dimethyl sulfoxide and water in a weight ratio of 1: (0.8-1.2), adjusting the pH value to 8-9 with sodium hydroxide, stirring and reacting at 30-50°C for 3-5 hours, then adjusting the pH value to 3-4 with hydrochloric acid, adding ether at 0-4°C, stirring for 20-60 minutes, and after precipitation, performing solid-liquid separation, washing, and drying to obtain a first reaction product;

[0024] Wherein, the weight ratio of the solvent to the azide-polyethylene glycol-carboxylic acid is (3-5):1; the volume ratio of the ether to the solvent is (2-3):1;

[0025] (2) uniformly mixing the first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 20-40° C. for 1-2 hours, then adding a mixture of glycerol and a Chinese herbal medicine extract, stirring and reacting for 1-2 hours to obtain a mixed solution;

[0026] Wherein, in the aqueous solution of the silk fibroin, the concentration of the silk fibroin is 2-5wt%;

[0027] (3) The mixed solution is evenly coated and allowed to stand at 20-40°C for 8-12 hours to obtain a gel layer loaded with the Chinese herbal medicine extract.

[0028] Preferably, the method for preparing the traditional Chinese medicine gel patch for treating gouty arthritis further comprises the step of activating the first reaction product:

[0029] adding the first reaction product to a PBS solution with a pH value of 6.0-6.5, adding EDC and NHS thereto, and stirring at 20-30° C. for 20-40 minutes to obtain an activated first reaction product;

[0030] The weight ratio of the first reaction product, EDC, and NHS is 1:(0.08-0.20):(0.08-0.20); and the concentration of the first reaction product in the PBS solution is 1-3 mg / ml.

[0031] Preferably, step (2) further comprises the step of adding calcium lignin sulfonate and / or tannic acid to the glycerol and the Chinese herbal medicine extract and mixing them uniformly.

[0032] Preferably, the Chinese herbal medicine extract is obtained by the following method:

[0033] Grind coix seed, clematis root, atractylodes, angelica root, safflower, red peony root, andrographis paniculata, daylily root, and trillium into powder, extract with ethanol, and filter and concentrate the alcohol extract to obtain a clear paste with a relative density of 1.28-1.32, which is the alcohol extract;

[0034] Take Phellodendron chinense, Radix Codonopsis pilosulae, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Salix Achyranthis Bidens, Radix Tripterygii, Eucalyptus globulus, Radix Sophorae Flavescentis, Radix Lobelia, Rhizoma Coptidis, Acer octagonalis, and Semen Strychnos nux vomica, decoct them in water, and filter and concentrate the aqueous extract to obtain a clear paste with a relative density of 1.28-1.32, which is the aqueous extract;

[0035] Take Radix Dioscoreae, Rhizoma Smilacis Glabrae, Rhizoma Arisaematis, Radix Aconiti Kusnezoffii, and Grind them into powder to obtain medicinal powder;

[0036] Take cinnamon twig, Zanthoxylum bungeanum, frankincense and myrrh, use 2-3 times the amount of sesame oil for oil extraction, and then add borneol to obtain an oily substance;

[0037] The alcohol extract, water extract, medicinal powder and oily substance are mixed evenly to obtain the product.

[0038] The above solution of the present invention includes at least the following beneficial effects:

[0039] (1) The Chinese medicine gel patch for treating gouty arthritis of the present invention comprises at least a gel layer loaded with Chinese medicine extracts; the Chinese medicine extracts comprise the following raw materials: coix seed, phellodendron amurense, clematis root, radix scutellariae, atractylodes lancea, radix scutellariae, radix scutellariae, radix scutellariae, radix scutellariae, radix scutellariae, radix aconiti kusnezoffii, radix strychnii, frankincense, myrrh, angelica sinensis, safflower, cyathula root, radix peonyii, radix smilax, radix striatae, radix dayliliese, twigs of willow, radix striatae, radix eucalyptus , Sophora flavescens, Andrographis paniculata, Lobelia chinensis, Coptis chinensis, Trillium gracile, Cinnamon twig, Zanthoxylum bungeanum, Borneolum; the matrix of the gel layer comprises the following raw materials in parts by weight: 100-120 parts of silk fibroin, 20-40 parts of polyvinyl pyrrolidone, 5-8 parts of azide-polyethylene glycol-carboxylic acid, 6-10 parts of 1-ethynylcyclopropylcarboxylic acid, 5-10 parts of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and 80-100 parts of glycerol. The traditional Chinese medicine gel patch for treating gouty arthritis of the present invention loads the traditional Chinese medicine extract in the gel layer and is applied in the form of a traditional Chinese medicine gel patch for external application. It is absorbed through the skin to achieve a good therapeutic effect and can greatly improve the joint swelling, local pain, and limited movement problems of patients with gouty arthritis.

[0040] The Chinese herbal extract is extracted from an empirical formula and reuses herbs from the Lingnan region that are used to clear away heat, dampness, and numbness. The whole formula is composed mainly of herbs that clear away heat, dampness, reduce swelling, and relieve pain, supplemented by herbs that promote blood circulation and smooth the meridians, to achieve a comprehensive therapeutic effect of treating both the symptoms and the root causes.

[0041] Among them, coix seed, phellodendron, clematis root, and radix scutellariae are the main herbs, targeting the core pathogenesis. Coix seed strengthens the spleen and eliminates dampness, clears heat and discharges pus, targeting the root cause of damp-heat obstruction. Phellodendron chinense, with its bitter and cold properties, clears damp-heat in the lower burner, purging fire and eliminating steam. Clematid clematis flows through the twelve meridians, dispels rheumatism, and unclogs the meridians, effectively treating limb numbness and joint discomfort. Radix scutellariae dispels wind and dampness, unblocks the meridians and relieves pain, specifically targeting pathogens deeply embedded in the tendons and bones. Together, these four herbs clear heat and dampness, dispel wind and unclog the meridians, directly attacking the core pathogenesis of damp-heat obstruction and meridian blockage.

[0042] Atractylodes lancea, Radix Dioscoreae, Radix Aconiti Kusnezoffii, Radix Aconiti Kusnezoffii, Arisaema consanguineum, Radix Aconiti Kusnezoffii, Radix Aconiti Kusnezoffii, frankincense, myrrh, angelica sinensis, and safflower serve as assistant herbs to enhance the efficacy of the main herbs and treat multiple symptoms. Atractylodes lancea and Radix Dioscoreae dehumidify and strengthen the spleen, separating the clear from the turbid, and assisting coix seed and Phellodendron chinense in dispelling dampness. Radix Aconiti Kusnezoffii, Radix Aconiti Kusnezoffii, and Radix Aconiti Kusnezoffii dispel wind and dampness, activate blood circulation and unclog the meridians, and synergize with Radix Clematis chinensis and Radix Aconiti Kusnezoffii to penetrate the tendons and bones. Arisaema consanguineum, Radix Aconiti Kusnezoffii, and Radix Aconiti Kusnezoffii warm the meridians and relieve pain, unblocking the meridians and dispersing stagnation. Their combined use can dissolve blood stasis and relieve severe pain, specifically targeting stubborn arthralgia. Frankincense, myrrh, angelica sinensis, and safflower invigorate blood circulation, dissipate stasis, promote qi circulation, and relieve pain, alleviating localized blood stasis and swelling, while supporting the main and assistant herbs in promoting joint function. The combination of these medicines enhances the ability to remove dampness and dredge the meridians, and targets the poor flow of qi and blood caused by damp-heat obstruction, while also relieving pain.

[0043] The adjuvant herbs include Cyathula, Paeonia lactiflora, Smilax glabra, Herba Lycopodii, Hemerocallis radix, Willow twig, Tripterygium wilfordii, Eucalyptus globulus, Sophora flavescens, Andrographis paniculata, Lobelia chinensis, Coptis chinensis, Tripterygium wilfordii, Cinnamon twig, and Zanthoxylum bungeanum as adjuvants, complementing the principal and secondary herbs and harmonizing their properties. Cyathula, Paeonia lactiflora, and Smilax glabra guide the herbs downward, clearing heat and cooling the blood, detoxifying and relieving dampness, and are effective for lower limb joint swelling and pain. Herba Lycopodii, Willow twig, and Hemerocallis radix relax the tendons and activate the collaterals, relieving muscle spasms. Tripterygium wilfordii, Eucalyptus globulus, Sophora flavescens, Andrographis paniculata, Lobelia chinensis, and Coptis chinensis clear heat and detoxify, drying dampness and relieving itching, preventing and treating damp-heat detoxification. Tripterygium wilfordii resolves phlegm and resolves carbuncle and swelling, helping to resolve phlegm and blood stasis in the joints. Cinnamon twig and Zanthoxylum bungeanum warm the meridians, dispel cold and relieve pain, and also counteract the cold properties of Phellodendron chinense and Coptis chinensis. The combination of hot and cold herbs balances the overall formula. Multi-dimensional auxiliary medicine, taking into account clearing heat, unblocking meridians, detoxification, and dispersing nodules, and preventing dry and strong drugs from damaging yin and toxic drugs from damaging the body, removing the properties and retaining the benefits.

[0044] Borneol is used as a guiding drug to guide the meridians and coordinate the efficacy of the drugs. Its aromatic medicinal properties can open the orifices and penetrate the meridians, leading all the drugs directly to the site of the disease.

[0045] (2) The Chinese medicine gel patch for treating gouty arthritis of the present invention, wherein the gel matrix includes silk fibroin, polyvinyl pyrrolidone, azide-polyethylene glycol-carboxylic acid, 1-ethynylcyclopropyl carboxylic acid, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol.

[0046] The azide group of the azide-polyethylene glycol-carboxylic acid and the alkyne group of the 1-ethynylcyclopropyl carboxylic acid can generate a first reaction product having a triazole ring and containing carboxyl groups at both ends through a click chemistry reaction. The carboxyl group of the first reaction product can undergo a condensation reaction with the amino group of the silk fibroin to form an amide bond. At the same time, the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene also undergoes a condensation reaction with the amino group of the silk fibroin to form a chemical cross-linked structure. During the reaction, the polyvinyl pyrrolidone is physically blended with the chemical cross-linked structure to form a network structure in which the molecular chains are entangled or interpenetrated. The glycerol has good compatibility with other ingredients, and has a small molecular weight and flexible molecular chains. It can penetrate into the network structure and act as a flexible node to improve the flexibility of the material. It also has hygroscopicity, which helps the traditional Chinese medicine gel patch to maintain a gel state.

[0047] The triazole ring generated by the azide-alkynyl click reaction is a rigid five-membered heterocycle with excellent chemical stability. This restricts the conformational freedom of the nitrogen atom with a lone pair of electrons, enabling efficient loading of polar components (such as flavonoid glycosides, saponins, and polysaccharides) in the traditional Chinese medicine extract through hydrogen bonding while limiting their excessive aggregation, achieving a sustained-release effect. The flexible polyethylene glycol chain introduced by the azide-polyethylene glycol-carboxylic acid can increase the water content of the stratum corneum and reduce transdermal resistance. The cyclopropyl group introduced by the 1-ethynylcyclopropyl carboxylic acid resists swelling and collapse of the gel material, improving the material's anti-swelling properties. The angular tension of the cyclopropyl group is transferred to the alkynyl group via the adjacent σ bond, making it more susceptible to reaction with the azide group.

[0048] The amide bond formed after the reaction of the first reaction product with the silk fibroin, as a strong chemical bond, can improve the mechanical strength and stability of the material, induce the silk fibroin to form a honeycomb network structure, increase the drug loading, and can continuously release the active ingredients of the traditional Chinese medicine extract by hydrolysis, thereby prolonging the action time of the traditional Chinese medicine extract. The thiophene ring and ethylenedioxy group introduced by the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene can enhance the material's lipophilic drug component loading capacity and increase the loading capacity of the non-polar components in the traditional Chinese medicine extract. At the same time, the ethylenedioxy group, amide group, and thiophene ring can form an amphiphilic unit, which enhances the fit and adhesion of the matrix to the stratum corneum of the skin, and serves as a channel for lipophilic components to promote their transdermal efficiency. In addition, the ethylenedioxythiophene group is conjugated, and the delocalized π bond of the conjugated system can improve the stability of volatile aromatic active ingredients, reduce volatility losses, and prolong their retention time at the site of action. The polyvinyl pyrrolidone has good film-forming properties and can improve the bioadhesion of the material. While the silk fibroin reacts with the first reaction product and the 1-ethynylcyclopropyl carboxylic acid, it is physically blended with them to form a network structure in which the molecular chains are intertwined or interpenetrating with each other, limiting the penetration of water molecules into a single polymer chain, reducing the swelling and collapse of the gel, and promoting the stable release of the drug. The above substances cooperate with each other to ensure the continuous diffusion of the traditional Chinese medicine extract through the gel matrix. Multiple mechanisms work together to improve the transdermal effect of the drug and achieve good efficacy. DETAILED DESCRIPTION

[0049] In the examples of the present invention, if specific conditions are not specified, the experiments were carried out under conventional conditions or the conditions recommended by the manufacturer. Reagents or instruments used without specifying the manufacturer are all commercially available conventional products. Raw materials of different manufacturers and types do not affect the implementation of the technical solutions of the present invention and the achievement of the technical effects.

[0050] In the following examples, the CAS number of the silk fibroin is 96690-41-4; the CAS number of the azide-polyethylene glycol-carboxylic acid, also known as N3-PEG1-COOH, is 1393330-34-1;

[0051] The CAS number of the 1-ethynylcyclopropylcarboxylic acid is 933755-97-6, and it has the following structure:

[0052]

[0053] The CAS number of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene is 18361-03-0, and it has the following structure:

[0054]

[0055] The CAS number of the calcium lignin sulfonate is 8061-52-7; the CAS number of the tannic acid is 1401-55-4.

[0056] The PBS solution refers to a phosphate-buffered saline solution, and its components are conventional in the art, providing a relatively stable acid-base environment. EDC stands for 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, a carboxylic acid activator; and NHS refers to N-hydroxysuccinimide.

[0057] Job's tears seed has a sweet and mild taste and is cool in nature. It enters the spleen, stomach, and lung meridians. It has the effects of strengthening the spleen and dispelling dampness, clearing heat and discharging pus, removing numbness, and promoting diuresis.

[0058] Huangbai, containing berberine, is cold in nature and bitter in taste; it enters the kidney meridian and bladder meridian; it has the effects of clearing heat and dampness, purging fire and removing steam, detoxifying and treating sores.

[0059] Clematis chinensis Osbeck (scientific name: Clematis chinensis Osbeck) tastes spicy and salty, and is warm in nature. It has the effects of dispelling rheumatism and unblocking meridians.

[0060] Radix Glehniae, Schisandraceae, is pungent in taste and warm in nature; it has the effects of dispelling wind and activating blood circulation, detoxifying and reducing swelling, and stopping bleeding.

[0061] Atractylodes lancea is pungent, bitter, and warm in nature. It enters the spleen, stomach, and liver meridians and can be used to treat abdominal distension and pain, diarrhea, edema, rheumatic pain, beriberi, colds, and nystagmus.

[0062] Powdery Radix Dichroae, also known as Radix Dichroae and Radix Dichroae, tastes bitter and is neutral in nature; it enters the liver meridian, stomach meridian, and bladder meridian; it has the effects of promoting diuresis, dispelling wind, and removing dampness.

[0063] Psychotria rubra (Lour.) Poir., bitter in taste and cold in nature, has the effects of clearing away heat, detoxifying, reducing swelling and removing toxins.

[0064] Alangium chinense (scientific name: Alangium chinense) is warm in nature and pungent and bitter in taste. It has the effects of dispelling wind and dampness, relaxing muscles and tendons, dispersing blood stasis and relieving pain.

[0065] Piper melongena has a pungent and bitter taste and is slightly warm in nature. It enters the liver meridian and has the effects of removing rheumatism, unblocking meridians, and relieving pain.

[0066] Chuanwu tastes pungent and bitter, and is hot in nature; it enters the heart, liver, kidney, and spleen meridians; it has the effects of dispelling wind and dampness, warming the meridians and relieving pain.

[0067] Aconitum kusnezoffii tastes pungent and bitter, and is hot in nature; it enters the heart, liver, kidney, and spleen meridians; it has the effects of dispelling wind and dampness, warming the meridians and relieving pain.

[0068] Strychnos nux vomica is bitter in taste and warm in nature; it enters the liver and spleen meridians; it has the effects of stimulating the stomach, reducing swelling and toxins, and cooling the blood.

[0069] Frankincense tastes bitter and is warm in nature; it enters the heart, liver, and spleen meridians; it has the effects of regulating qi and activating blood circulation, relieving pain, and expelling toxins.

[0070] Myrrh is bitter in taste and neutral in nature; it enters the heart, liver and spleen meridians; it has the effects of promoting blood circulation, relieving pain, reducing swelling and promoting tissue regeneration.

[0071] Angelica sinensis tastes sweet and spicy, and is warm in nature. It enters the liver, heart, and spleen meridians. It has the effects of nourishing blood, activating blood circulation, regulating menstruation and relieving pain, and moisturizing and lubricating the intestines.

[0072] Safflower is pungent and warm in nature; it enters the heart and liver meridians; it has the effects of promoting blood circulation, dredge menstruation, remove blood stasis and relieve pain.

[0073] Sichuan Achyranthes bidentata tastes sweet and slightly bitter, and is neutral in nature; it enters the liver and kidney meridians; it has the effects of removing blood stasis, dredging menstruation, unblocking joints, and promoting diuresis and relieving stranguria.

[0074] Red peony root is bitter in taste and slightly cold in nature; it enters the liver meridian; it has the effects of clearing heat and cooling blood, dispersing blood stasis and relieving pain.

[0075] Smilax glabra has a sweet and light taste and is neutral in nature. It enters the liver and stomach meridians and has the effects of clearing away heat, detoxifying, removing dampness and dredging the meridians.

[0076] Herba Lycopodii has a bitter and pungent taste and is warm in nature. It enters the liver meridian and has the effects of dispelling wind and cold, removing dampness and reducing swelling, and relaxing muscles and tendons.

[0077] Daylily root is cool in nature and sweet in taste; it has the effects of clearing heat, promoting diuresis, cooling blood and stopping bleeding.

[0078] Weeping willow branches, also known as willow branches, are bitter and cold in nature; they enter the stomach and liver meridians; they have the effects of dispelling wind and dampness, detoxifying and reducing swelling.

[0079] Tripterygium wilfordii, also known as Tripterygium wilfordii and Tripterygium wilfordii, tastes bitter and is cold in nature; it enters the heart and liver meridians; it has the effects of clearing away heat and detoxifying, dispelling wind and dampness, reducing swelling and relieving pain.

[0080] Eucalyptus globulus is slightly pungent, slightly bitter and neutral in nature. It has the effects of dispelling wind and relieving fever, inhibiting bacteria and inflammation, and preventing and treating itching.

[0081] Sophora flavescens, bitter in taste and cold in nature, can treat symptoms such as gas stagnation in the heart and abdomen, masses, accumulation, jaundice, residual urine, diuresis, carbuncle, etc.

[0082] Andrographis paniculata is bitter and cold in nature. It enters the heart, lung, large intestine and bladder meridians. It has the effects of clearing away heat and detoxifying, cooling blood and reducing swelling.

[0083] Lobelia chinensis has a sweet taste and a neutral nature, and has the effect of clearing away heat and detoxifying.

[0084] Coptis chinensis is bitter and cold in nature; it enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians; it has the effects of clearing heat and dampness, purging fire and detoxifying.

[0085] Trillium gracile tastes sweet, slightly spicy and cool in nature; it has the effects of clearing away heat and detoxifying, eliminating carbuncles and dispersing nodules.

[0086] Cinnamon twig tastes spicy and sweet, and is warm in nature; it enters the lung, heart, and bladder meridians; it has the effects of inducing sweating and relieving muscles, warming the meridians, and assisting yang and transforming qi.

[0087] Zanthoxylum bungeanum is spicy and warm in nature; it enters the spleen, stomach and kidney meridians; it has the effects of warming the middle and relieving pain, killing insects and relieving itching.

[0088] Borneol tastes bitter and is cool in nature; it enters the heart and lung meridians; it has the effects of opening all orifices, dispersing stagnant heat, removing cataracts and improving eyesight, reducing swelling and relieving pain.

[0089] Arisaema is warm in nature, bitter and pungent in taste; it enters the lung meridian, liver meridian and spleen meridian; it has the effects of drying dampness and resolving phlegm, dispelling wind and stopping spasms, and dispersing stagnation and reducing swelling.

[0090] The above raw materials are all commercially available products and can be obtained through purchase.

[0091] Example 1

[0092] The Chinese medicine gel patch for treating gouty arthritis of this embodiment comprises at least a gel layer loaded with a Chinese medicine extract; in the gel layer, the weight ratio of the matrix to the Chinese medicine extract is 3:1;

[0093] The matrix of the gel layer comprises the following raw materials in parts by weight:

[0094] 100 parts of silk fibroin, 30 parts of polyvinyl pyrrolidone, 5 parts of azide-polyethylene glycol-carboxylic acid, 8 parts of 1-ethynylcyclopropylcarboxylic acid, 5 parts of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and 90 parts of glycerol.

[0095] The Chinese herbal medicine extract comprises the following raw materials in parts by weight:

[0096] 20 parts of coix seeds, 10 parts of phellodendron chinense, 5 parts of clematis root, 15 parts of radix strychni, 5 parts of atractylodes, 15 parts of rhizoma strychni, 20 parts of rhizoma strychni, 3 parts of octagonal maple, 10 parts of caulis daffodils, 5 parts of arisaema, 3 parts of radix aconiti kusnezoffii, 3 parts of kusnezoffii, 0.1 parts of strychnine seeds, 5 parts of frankincense, 1 part of myrrh, 15 parts of angelica sinensis, 5 parts of safflower, 15 parts of cyathula, 5 parts of red peony root, 40 parts of rhizoma smilacis, 10 parts of herba lycopodii, 5 parts of daylily roots, 20 parts of twig of weeping willow, 40 parts of eucalyptus glomerata, 20 parts of sophora flavescens, 1 part of andrographis paniculata, 15 parts of herba lobeliae, 10 parts of coptis root, 10 parts of pleurotus eryngii, 5 parts of cassia twig, 8 parts of zanthoxylum bungeanum, 0.1 parts of borneol.

[0097] In this embodiment, the matrix first undergoes a click chemistry reaction with the azide-polyethylene glycol-carboxylic acid and the 1-ethynylcyclopropyl carboxylic acid to obtain a first reaction product; then the first reaction product is mixed with the silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol, so that the carboxyl group of the first reaction product and the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene react with the amino group of the silk fibroin to form a structure blended with the polyvinyl pyrrolidone and glycerol, that is, an entangled or interpenetrating network structure.

[0098] In this embodiment, the preparation method of the traditional Chinese medicine gel plaster for treating gouty arthritis specifically comprises the following steps:

[0099] (1) Azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid are dissolved in a solvent of dimethyl sulfoxide and water in a weight ratio of 1:0.8, and the pH value is adjusted to 8.5 with sodium hydroxide. The reaction is stirred at 30°C for 4 hours, and then the pH value is adjusted to 3 with hydrochloric acid. Ether is added at 2°C and stirred for 20 minutes. After precipitation, solid-liquid separation, washing, and drying are performed to obtain a first reaction product;

[0100] Wherein, the weight ratio of the solvent to the azide-polyethylene glycol-carboxylic acid is 5:1; the volume ratio of the ether to the solvent is 2:1;

[0101] The first reaction product was added to a PBS solution with a pH value of 6.2, and EDC and NHS were added thereto, and the mixture was stirred at 20° C. for 30 minutes to obtain an activated first reaction product;

[0102] The weight ratio of the first reaction product, EDC, and NHS is 1:0.08:0.08; and the concentration of the first reaction product in the PBS solution is 2 mg / ml.

[0103] (2) uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 20° C. for 1.5 h, then adding a mixture of glycerol and Chinese herbal medicine extracts, stirring and reacting for 1 h to obtain a mixed solution;

[0104] Wherein, in the aqueous solution of the silk fibroin, the concentration of the silk fibroin is 3wt%;

[0105] (3) The mixed solution is evenly coated and allowed to stand at 20°C for 10 hours to obtain a gel layer loaded with the Chinese herbal medicine extract.

[0106] In this embodiment, the Chinese herbal extract is obtained by the following method:

[0107] Grind coix seed, clematis root, atractylodes, angelica root, safflower, red peony root, andrographis paniculata, daylily root, and trillium into powder, extract with ethanol, and filter and concentrate the alcohol extract to obtain a clear paste with a relative density of 1.30, which is the alcohol extract;

[0108] Take Phellodendron chinense, Radix Codonopsis pilosulae, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Salix Achyranthis Bidens, Radix Tripterygii, Eucalyptus globulus, Radix Sophorae Flavescentis, Herba Lobeliae, Rhizoma Coptidis, Acer octagonalis, and Semen Strychnos nux vomica, decoct them in water, and filter and concentrate the aqueous extract to obtain a clear paste with a relative density of 1.30, which is the aqueous extract;

[0109] Take Radix Dioscoreae, Rhizoma Smilacis Glabrae, Rhizoma Arisaematis, Radix Aconiti Kusnezoffii, and Grind them into powder to obtain medicinal powder;

[0110] Take cinnamon twig, Zanthoxylum bungeanum, frankincense and myrrh, use 2 times the amount of sesame oil for oil extraction, then add borneol to obtain an oily substance;

[0111] The alcohol extract, water extract, medicinal powder and oily substance are mixed evenly to obtain the product.

[0112] It should be noted that the Chinese medicine extract can be extracted using methods in the prior art, such as by conventional methods such as alcohol extraction, water extraction, supercritical extraction, ultrasonic extraction, and reflux extraction. In the present embodiment, only a specific implementation is provided, and those skilled in the art can select the corresponding extraction method according to the characteristics of each Chinese medicine component. In addition, the operating conditions in the above method are also conventional means of the prior art. For example, when preparing the alcohol extract, the amount of ethanol, the number and time of alcohol extraction, the temperature of heating, etc. can be determined by those skilled in the art according to actual conditions, and will not be repeated hereafter.

[0113] Example 2

[0114] The Chinese medicine gel patch for treating gouty arthritis of this embodiment comprises at least a gel layer loaded with a Chinese medicine extract; in the gel layer, the weight ratio of the matrix to the Chinese medicine extract is 4:1;

[0115] The matrix of the gel layer comprises the following raw materials in parts by weight:

[0116] 120 parts of silk fibroin, 40 parts of polyvinyl pyrrolidone, 8 parts of azide-polyethylene glycol-carboxylic acid, 10 parts of 1-ethynylcyclopropylcarboxylic acid, 10 parts of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and 80 parts of glycerol.

[0117] The Chinese herbal medicine extract comprises the following raw materials in parts by weight:

[0118] 40 parts of coix seeds, 15 parts of phellodendron chinense, 15 parts of clematis root, 10 parts of radix strychni, 16 parts of atractylodes, 20 parts of rhizoma schizonepetae, 40 parts of mountain dayan, 5 parts of maple, 20 parts of caulis daffodils, 10 parts of rhizoma aconiti kusnezoffii, 10 parts of rhizoma aconiti kusnezoffii, 1 part of strychnos nux vomica, 10 parts of frankincense, 10 parts of myrrh, 15 parts of angelica, 15 parts of safflower, 10 parts of cyathula, 10 parts of red peony root, 20 parts of rhizoma smilacis, 5 parts of herba lycopodii, 10 parts of daylily roots, 40 parts of twig of weeping willow, 30 parts of trifoliate bitter herbs, 10 parts of eucalyptus, 1 part of sophora flavescens, 20 parts of herba andrographis, 20 parts of herba lobelia, 1 part of coptis root, 20 parts of pleurotus eryngii, 15 parts of cassia twig, 15 parts of zanthoxylum bungeanum, and 0.3 part of borneol.

[0119] In this embodiment, the matrix first undergoes a click chemistry reaction with the azide-polyethylene glycol-carboxylic acid and the 1-ethynylcyclopropyl carboxylic acid to obtain a first reaction product; then the first reaction product is mixed with the silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol, so that the carboxyl group of the first reaction product and the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene react with the amino group of the silk fibroin to form a structure blended with the polyvinyl pyrrolidone and glycerol, that is, an entangled or interpenetrating network structure.

[0120] In this embodiment, the preparation method of the traditional Chinese medicine gel plaster for treating gouty arthritis specifically comprises the following steps:

[0121] (1) Azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid are dissolved in a solvent of dimethyl sulfoxide and water in a weight ratio of 1:1.2, and the pH value is adjusted to 9 with sodium hydroxide. The reaction is stirred at 50°C for 5 hours, and then the pH value is adjusted to 4 with hydrochloric acid. Ether is added at 4°C and stirred for 60 minutes. After precipitation, solid-liquid separation, washing, and drying are performed to obtain a first reaction product;

[0122] Wherein, the weight ratio of the solvent to the azide-polyethylene glycol-carboxylic acid is 4:1; the volume ratio of the ether to the solvent is 3:1;

[0123] adding the first reaction product to a PBS solution with a pH value of 6.5, adding EDC and NHS thereto, and stirring at 25° C. for 40 minutes to obtain an activated first reaction product;

[0124] The weight ratio of the first reaction product, EDC, and NHS is 1:0.20:0.14; and the concentration of the first reaction product in the PBS solution is 3 mg / ml.

[0125] (2) uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 40° C. for 2 h, and then adding a mixture of glycerol and Chinese herbal medicine extracts thereto, stirring and reacting for 2 h to obtain a mixed solution;

[0126] Wherein, in the aqueous solution of the silk fibroin, the concentration of the silk fibroin is 5wt%;

[0127] (3) The mixed solution is evenly coated and allowed to stand at 40°C for 8 hours to obtain a gel layer loaded with the Chinese herbal medicine extract.

[0128] In this embodiment, the Chinese herbal medicine extract is obtained by the same method as in Example 1.

[0129] Example 3

[0130] The Chinese medicine gel patch for treating gouty arthritis of this embodiment comprises at least a gel layer loaded with a Chinese medicine extract; in the gel layer, the weight ratio of the matrix to the Chinese medicine extract is 5:1;

[0131] The matrix of the gel layer comprises the following raw materials in parts by weight:

[0132] 110 parts of silk fibroin, 20 parts of polyvinyl pyrrolidone, 6 parts of azide-polyethylene glycol-carboxylic acid, 6 parts of 1-ethynylcyclopropylcarboxylic acid, 7 parts of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and 80 parts of glycerol.

[0133] The Chinese herbal medicine extract comprises the following raw materials in parts by weight:

[0134] 30 parts of coix seeds, 5 parts of phellodendron chinense, 10 parts of clematis root, 20 parts of radix scutellariae, 10 parts of atractylodes, 10 parts of rhizoma scutellariae, 30 parts of safflower, 1 part of maple, 15 parts of caulis daffodils, 1 part of aconite, 2 parts of kusnezoffii, 1 part of strychnos nux vomica, 0.3 part of strychnos nux vomica, 1 part of frankincense, 5 parts of myrrh, 5 parts of angelica, 10 parts of safflower, 5 parts of cyathula, 15 parts of red peony root, 30 parts of rhizoma smilacis, 15 parts of herba lycopodii, 1 part of daylily root, 30 parts of twig of willow, 20 parts of schizonepeta tenuifolia, 15 parts of eucalyptus glomerata, 10 parts of sophora flavescens, 10 parts of herba andrographis, 10 parts of herba lobeliae, 5 parts of coptis root, 1 part of pleurotus eryngii, 10 parts of cassia twig, 1 part of zanthoxylum bungeanum, and 0.5 part of borneol.

[0135] In this embodiment, the matrix first undergoes a click chemistry reaction with the azide-polyethylene glycol-carboxylic acid and the 1-ethynylcyclopropyl carboxylic acid to obtain a first reaction product; then the first reaction product is mixed with the silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol, so that the carboxyl group of the first reaction product and the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene react with the amino group of the silk fibroin to form a structure blended with the polyvinyl pyrrolidone and glycerol, that is, an entangled or interpenetrating network structure.

[0136] In this embodiment, the preparation method of the traditional Chinese medicine gel plaster for treating gouty arthritis specifically comprises the following steps:

[0137] (1) Azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid are dissolved in a solvent of dimethyl sulfoxide and water in a weight ratio of 1:1.0, and the pH value is adjusted to 8 with sodium hydroxide. The reaction is stirred at 40°C for 3 hours, and then the pH value is adjusted to 3.5 with hydrochloric acid. Ether is added at 0°C and stirred for 40 minutes. After precipitation, solid-liquid separation, washing, and drying are performed to obtain a first reaction product;

[0138] Wherein, the weight ratio of the solvent to the azide-polyethylene glycol-carboxylic acid is 3:1; the volume ratio of the ether to the solvent is 2.5:1;

[0139] adding the first reaction product to a PBS solution with a pH value of 6.0, adding EDC and NHS thereto, and stirring at 30° C. for 20 minutes to obtain an activated first reaction product;

[0140] The weight ratio of the first reaction product, EDC, and NHS is 1:0.14:0.20; and the concentration of the first reaction product in the PBS solution is 1 mg / ml.

[0141] (2) uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 30° C. for 1 hour, and then adding a mixture of glycerol and Chinese herbal medicine extracts thereto, stirring and reacting for 1.5 hours to obtain a mixed solution;

[0142] Wherein, in the aqueous solution of the silk fibroin, the concentration of the silk fibroin is 2 wt %;

[0143] (3) The mixed solution is evenly coated and allowed to stand at 30°C for 12 hours to obtain a gel layer loaded with the Chinese herbal medicine extract.

[0144] In this embodiment, the Chinese herbal medicine extract is obtained by the same method as in Example 1.

[0145] Example 4

[0146] The Chinese medicine gel patch for treating gouty arthritis of this embodiment comprises at least a gel layer loaded with a Chinese medicine extract; in the gel layer, the weight ratio of the matrix to the Chinese medicine extract is 4:1;

[0147] The matrix of the gel layer comprises the following raw materials in parts by weight:

[0148] 120 parts of silk fibroin, 40 parts of polyvinyl pyrrolidone, 6 parts of azide-polyethylene glycol-carboxylic acid, 10 parts of 1-ethynylcyclopropylcarboxylic acid, 8 parts of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and 90 parts of glycerol.

[0149] The Chinese herbal medicine extract comprises the following raw materials in parts by weight:

[0150] 30 parts of coix seeds, 10 parts of phellodendron chinense, 10 parts of clematis root, 15 parts of radix strychnifoliae, 9 parts of atractylodes, 15 parts of rhizoma strychni, 30 parts of safflower, 1.5 parts of acer octagonalis, 15 parts of caulis damiana, 5 parts of rhizoma aconiti kusnezoffii, 1.5 parts of kusnezoffii, 0.3 parts of strychnos nux vomica, 5 parts of frankincense, 5 parts of myrrh, 10 parts of angelica sinensis, 10 parts of safflower, 10 parts of cyathula, 10 parts of red peony root, 30 parts of rhizoma smilacis, 10 parts of herba lycopodii, 6 parts of daylily roots, 30 parts of twig of willow, 30 parts of eucalyptus glomerata, 15 parts of eucalyptus glomerata, 9 parts of sophora flavescens, 9 parts of herba andrographis paniculatae, 15 parts of herba lobeliae, 5 parts of coptis root, 9 parts of pleurotus strychnos, 10 parts of cassia twig, 6 parts of zanthoxylum bungeanum, and 0.3 parts of borneol.

[0151] In this embodiment, the matrix first undergoes a click chemistry reaction with the azide-polyethylene glycol-carboxylic acid and the 1-ethynylcyclopropyl carboxylic acid to obtain a first reaction product; then the first reaction product is mixed with the silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol, so that the carboxyl group of the first reaction product and the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene react with the amino group of the silk fibroin to form a structure blended with the polyvinyl pyrrolidone and glycerol, that is, an entangled or interpenetrating network structure.

[0152] In this embodiment, the preparation method of the traditional Chinese medicine gel plaster for treating gouty arthritis specifically comprises the following steps:

[0153] (1) Azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid are dissolved in a solvent of dimethyl sulfoxide and water in a weight ratio of 1:1, and the pH value is adjusted to 8.5 with sodium hydroxide. The reaction is stirred at 40°C for 5 hours, and then the pH value is adjusted to 3.5 with hydrochloric acid. Ether is added at 0°C and stirred for 50 minutes. After precipitation, solid-liquid separation, washing, and drying are performed to obtain a first reaction product;

[0154] Wherein, the weight ratio of the solvent to the azide-polyethylene glycol-carboxylic acid is 4:1; the volume ratio of the ether to the solvent is 3:1;

[0155] The first reaction product was added to a PBS solution with a pH value of 6.2, and EDC and NHS were added thereto, and the mixture was stirred at 25° C. for 30 minutes to obtain an activated first reaction product;

[0156] The weight ratio of the first reaction product, EDC, and NHS is 1:0.1:0.1; and the concentration of the first reaction product in the PBS solution is 3 mg / ml.

[0157] (2) uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 30° C. for 1.5 h, then adding a mixture of glycerol and Chinese herbal medicine extracts, stirring and reacting for 1.5 h to obtain a mixed solution;

[0158] Wherein, in the aqueous solution of the silk fibroin, the concentration of the silk fibroin is 4 wt %;

[0159] (3) The mixed solution is evenly coated and allowed to stand at 30°C for 12 hours to obtain a gel layer loaded with the Chinese herbal medicine extract.

[0160] In this embodiment, the Chinese herbal extract is obtained by the following method:

[0161] Grind coix seed, clematis root, atractylodes, angelica root, safflower, red peony root, andrographis paniculata, daylily root, and trillium into powder, extract with ethanol, and filter and concentrate the alcohol extract to obtain a clear paste with a relative density of 1.30, which is the alcohol extract;

[0162] Take Phellodendron chinense, Radix Codonopsis pilosulae, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Salix Achyranthis Bidens, Radix Tripterygii, Eucalyptus globulus, Radix Sophorae Flavescentis, Herba Lobeliae, Rhizoma Coptidis, Acer octagonalis, and Semen Strychnos nux vomica, decoct them in water, and filter and concentrate the aqueous extract to obtain a clear paste with a relative density of 1.30, which is the aqueous extract;

[0163] Take Radix Dioscoreae, Rhizoma Smilacis Glabrae, Rhizoma Arisaematis, Radix Aconiti Kusnezoffii, and Grind them into powder to obtain medicinal powder;

[0164] Take cinnamon twig, Zanthoxylum bungeanum, and 2-3 times the amount of sesame oil at 200°C for oil extraction, filter, heat to 100°C, add frankincense, myrrh, and borneol, stir evenly, and obtain an oily substance;

[0165] The alcohol extract, water extract, medicinal powder and oily substance are mixed evenly to obtain the product.

[0166] It should be noted that the Chinese herbal medicine extract can be extracted using methods in the prior art, such as by conventional methods such as alcohol extraction, water extraction, supercritical extraction, ultrasonic extraction, and reflux extraction. In this embodiment, only a specific implementation is provided, and those skilled in the art can select the corresponding extraction method according to the characteristics of each Chinese herbal medicine component. In addition, the operating conditions in the above method are also conventional means of the prior art. For example, when preparing the alcohol extract, the amount of ethanol, the number and time of alcohol extraction, the temperature of heating, etc. can be determined by those skilled in the art according to actual conditions.

[0167] Example 5

[0168] The Chinese medicine gel patch for treating gouty arthritis in this embodiment uses the same raw materials and the same amounts of raw materials as those in Example 4, and is prepared using the same preparation method, with the only difference being that the raw materials of the Chinese medicine extract do not include Arisaema consanguineum.

[0169] Example 6

[0170] The Chinese medicine gel patch for treating gouty arthritis of this embodiment uses the same raw materials and the same amounts of raw materials as those in Example 4, and is prepared using the same method. The only difference is that the gel layer further includes 6 parts of calcium lignin sulfonate.

[0171] The step (2) specifically comprises: uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 30° C. for 1.5 hours, then adding a mixture of glycerol, a Chinese herbal medicine extract, and calcium lignin sulfonate thereto, stirring and reacting for 1.5 hours to obtain a mixed solution.

[0172] Example 7

[0173] The Chinese medicine gel patch for treating gouty arthritis of this embodiment uses the same raw materials and the same amounts of raw materials as those in Example 4, and is prepared using the same method, with the only difference being that the gel layer further includes 0.8 parts of tannic acid.

[0174] The step (2) specifically comprises: uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 30° C. for 1.5 hours, then adding a mixture of glycerol, Chinese herbal medicine extract, and tannic acid, stirring and reacting for 1.5 hours to obtain a mixed solution.

[0175] Example 8

[0176] The Chinese medicine gel patch for treating gouty arthritis of this embodiment uses the same raw materials and the same amounts of raw materials as those in Example 4, and is prepared using the same method. The only difference is that the gel layer further includes 6 parts of calcium lignin sulfonate and 0.8 parts of tannic acid.

[0177] The step (2) specifically comprises: uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 30° C. for 1.5 hours, then adding a mixture of glycerol, Chinese herbal medicine extract, calcium lignin sulfonate, and tannic acid, stirring and reacting for 1.5 hours to obtain a mixed solution.

[0178] Comparative Example 1

[0179] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as those used in Example 8, and is prepared using the same preparation method. The only difference is that the matrix of the gel layer does not include azide-polyethylene glycol-carboxylic acid.

[0180] Comparative Example 2

[0181] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as those used in Example 8, with the only difference being that the azide-polyethylene glycol-carboxylic acid in the matrix of the gel layer is replaced by carboxylic acid-polyethylene glycol-carboxylic acid.

[0182] Comparative Example 3

[0183] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as those used in Example 8, with the only difference being that the azide-polyethylene glycol-carboxylic acid in the matrix of the gel layer is replaced by polyethylene glycol.

[0184] Comparative Example 4

[0185] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as those used in Example 8, with the only difference being that the matrix of the gel layer does not include 1-ethynylcyclopropylcarboxylic acid.

[0186] Comparative Example 5

[0187] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as those used in Example 8, with the only difference being that the matrix of the gel layer does not include 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene.

[0188] Comparative Example 6

[0189] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as those used in Example 8, with the only difference being that 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene in the matrix of the gel layer is replaced by 2,5-dicarboxylic acid thiophene.

[0190] Comparative Example 7

[0191] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as those used in Example 8, with the only difference being that the matrix of the gel layer does not contain polyvinyl pyrrolidone.

[0192] Comparative Example 8

[0193] The Chinese medicine gel patch for treating gouty arthritis in this comparative example uses the same raw materials and the same amounts of raw materials as Example 8, with the only difference being that the Chinese medicine extract is not included. That is, the gel layer does not contain the Chinese medicine extract and serves as a blank matrix.

[0194] Effect Experiment Example

[0195] To verify the technical effect of the Chinese medicine gel plaster for treating gouty arthritis described in the present invention, the following experiments were conducted:

[0196] The following experiments were conducted using the Chinese medicine gel plasters for treating gouty arthritis obtained in Examples 1-8 and Comparative Examples 1-7:

[0197] 1. Swelling reduction experiment

[0198] Healthy male mature SD rats were randomly divided into 17 groups, namely, Example 1-8 group, Comparative Example 1-7 group, blank group, and control group, with 10 rats in each group. The blank group was given distilled water for gavage and the gel patch in Comparative Example 8 was applied externally; the control group was given berberine at a drug dose of 0.28 mg / kg and the gel patch in Comparative Example 8 was applied externally; the Example 1-8 group and the Comparative Example 1-7 group were given 0.28 mg / kg berberine and the corresponding Chinese medicine gel patch was applied externally, once a day for 7 consecutive days. On the 5th day of administration, the rats were anesthetized with 45 mg / kg of 2% sodium pentobarbital, fixed on the operating table in a supine position, and the right knee joint was depilated under sterile conditions. The knee joints of the rats in the control group, Example 1-8 group, and Comparative Example 1-7 group were slightly flexed, and a needle was inserted through the middle of the joint. 0.2 mL of 25 g / L sodium urate solution was injected into the right knee joint cavity to prepare a gout model. 0.2 mL of normal saline was injected into the articular cavity of the blank group, and the drug was continued for 2 days after modeling.

[0199] Before modeling and 4h, 8h, 12h, 24h and 48h after modeling, the knee circumference of rats in each group was measured 0.5mm below the right knee joint using a stainless steel caliper and a 2mm-3mm wide paper strip, the knee joint swelling was calculated, and the average value of each group was taken as the result.

[0200] The degree of knee joint swelling = (joint diameter after modeling - joint diameter before modeling) / joint diameter before modeling.

[0201] After testing, the results are as follows:

[0202] Table 1 Results of rat knee joint swelling reduction experiment

[0203]

[0204] 2. Transdermal Experiment

[0205] A matrix of the gel layer was prepared according to the method in Examples 1-8 and Comparative Examples 1-7, and the traditional Chinese medicine extract was replaced with a mixed extract obtained by mixing the Phellodendron chinense extract and the Andrographis paniculata extract in a weight ratio of 1:1; the weight ratio of the matrix to the mixed extract was 4:1 to obtain a traditional Chinese medicine gel patch.

[0206] The Franz diffusion cell method was used to determine the transdermal efficacy of berberine and andrographolide in the above-mentioned traditional Chinese medicine gel patch. The treated rat back skin was fixed to the interface of the diffusion cell, with the stratum corneum facing the donor cell and the dermis facing the receptor cell. The traditional Chinese medicine gel patch was applied to the skin surface of the donor cell and fixed with stainless steel mesh or tape. Physiological saline was added to the receptor cell. The effective diffusion area was 2.34 cm. 2 The magnetic stirring speed of the transdermal diffusion tester was 200 rpm, and the water bath temperature was (32 ± 0.2) °C. Samples were taken from the receiving cell at 1, 3, and 12 o'clock, and the concentrations of berberine (hydrophilic component) and andrographolide (lipophilic component) were determined by high performance liquid chromatography. The cumulative permeation amount per unit area (unit: μg / cm) was calculated. 2 ).

[0207] After testing, the results are as follows:

[0208] Table 2 Results of berberine and andrographolide transdermal test

[0209]

[0210] According to the above results, the traditional Chinese medicine gel patch for treating gouty arthritis of the present invention achieves a good therapeutic effect through percutaneous absorption, and can greatly improve the problems of joint swelling, local pain, and limited movement in patients with gouty arthritis.

[0211] According to the results of Examples 1-5, the blank group, and the model group, the Chinese medicine gel patch for treating gouty arthritis of the present invention has a significant swelling-reducing effect on gouty arthritis, and the effect is even better when the Arisaema is added.

[0212] The results of Examples 4, 6-8 show that, compared with Example 4, the addition of calcium ligninsulfonate alone (Example 6) improved the detumescence effect of the traditional Chinese medicine gel patch in the initial stage of use, but the detumescence effect after 12 hours was less than ideal. It also enhanced the transdermal effect of andrographolide and increased the cumulative permeation of berberine. However, the cumulative permeation at 1 hour, 3 hours, and 12 hours showed that berberine was rapidly released initially, but its release rate significantly decreased after 3 hours. Compared with Example 4, the addition of tannic acid alone (Example 7) showed little change in the detumescence effect, and even slightly decreased. The cumulative permeation of andrographolide and berberine at 12 hours also slightly decreased. However, when calcium ligninsulfonate and tannic acid were used together (Example 8), the detumescence effect was significantly greater than that of either alone, and the transdermal effect of andrographolide and berberine was significantly improved. In particular, the problem of rapid initial release of berberine was resolved, resulting in a relatively stable release rate over 12 hours. It can be seen that when used alone, tannic acid does not improve transdermal penetration or achieve sustained drug release, but rather produces an inhibitory effect to a certain extent. Although calcium lignin sulfonate can increase the cumulative permeation of berberine, the release rate is not stable. When tannic acid and calcium lignin sulfonate are used together, the two synergistically improve the overall effect of the traditional Chinese medicine gel patch.

[0213] The results of Example 8 and Comparative Examples 1-4 indicate that the combined use of azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid significantly enhances the detumescent effect of a traditional Chinese medicine gel patch, significantly impacts the transdermal effect of berberine, and relatively minimizes the transdermal effect of andrographolide. This indicates that the introduction of a triazole ring and a cyclopropyl group significantly impacts the overall efficacy of a traditional Chinese medicine gel patch.

[0214] The results of Example 8 and Comparative Examples 5-6 show that the introduction of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene significantly affects the detumescent effect of the traditional Chinese medicine gel patch and has a significant impact on the transdermal effect of andrographolide. However, the simple introduction of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene (i.e., thiophene ring) does not significantly enhance the detumescent effect of the traditional Chinese medicine gel patch. It slightly enhances the transdermal effect of fat-soluble andrographolide, but the effect is still unsatisfactory.

[0215] According to the results of Example 8 and Comparative Example 7, the addition of polyvinyl pyrrolidone to form a network structure of molecular chain entanglement or interpenetration will also have a significant impact on the comprehensive effect of the traditional Chinese medicine gel patch.

[0216] It is understood from common knowledge in the art that the present invention may be implemented by other embodiments that do not depart from its spirit or essential features. Therefore, the embodiments disclosed above are, in all respects, illustrative only and not exclusive. All modifications within the scope of the present invention or equivalent to the scope of the present invention are intended to be encompassed by the present invention.

Claims

1. A Chinese medicine gel plaster for treating gouty arthritis, characterized in that: At least comprising a gel layer loaded with a Chinese herbal medicine extract; The Chinese medicine extract is prepared from the following raw materials: 20-40 parts of coix seed, 5-15 parts of phellodendron, 5-15 parts of clematis root, 10-20 parts of radix scutellariae, 5-16 parts of atractylodes, 10-20 parts of radix scutellariae, 20-40 parts of rhizoma scutellariae, 1-5 parts of acer scutellariae, 10-20 parts of scutellariae, 1-3 parts of aconite, 1-3 parts of aconite, 0.1-0.5 parts of strychnine, 1-10 parts of frankincense, 1-10 parts of myrrh, 5-15 parts of angelica, 5 parts of safflower, 1-20 parts of safflower, 1-3 parts of radix scutellariae, 1-10 parts of safflower, 1-2 ... -15 parts, 5-15 parts of Cyathula, 5-15 parts of Red Peony Root, 20-40 parts of Smilax Glycyrrhiza, 5-15 parts of Streptomyces glutinosus, 1-10 parts of Hemerocallis Root, 20-40 parts of Salix babylonica, 20-40 parts of Tripterygium wilfordii, 10-20 parts of Eucalyptus globulus, 1-20 parts of Sophora flavescens, 1-20 parts of Andrographis paniculata, 10-20 parts of Lobelia chinensis, 1-10 parts of Coptis chinensis, 1-20 parts of Psoralea corylifolia, 5-15 parts of Cassia twig, 1-15 parts of Zanthoxylum bungeanum, 0.1-0.5 parts of Borneolum; The matrix of the gel layer is prepared from the following raw materials: 100-120 parts of silk fibroin, 20-40 parts of polyvinyl pyrrolidone, 5-8 parts of azide-polyethylene glycol-carboxylic acid, 6-10 parts of 1-ethynylcyclopropylcarboxylic acid, 5-10 parts of 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, 80-100 parts of glycerol, 5-8 parts of calcium lignin sulfonate, and 0.2-1.2 parts of tannic acid; The matrix first undergoes a click chemistry reaction with the 1-ethynylcyclopropyl carboxylic acid through the azide-polyethylene glycol-carboxylic acid to obtain a first reaction product; then the first reaction product is mixed with the silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, and glycerol, so that the carboxyl group of the first reaction product and the carboxyl group of the 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene react with the amino group of the silk fibroin to form a structure blended with the polyvinyl pyrrolidone and glycerol.

2. The Chinese medicine gel plaster for treating gouty arthritis according to claim 1, characterized in that: The raw materials of the Chinese medicine extract further contain 1-10 parts of Arisaema.

3. The Chinese medicine gel plaster for treating gouty arthritis according to claim 2, characterized in that: In the gel layer, the weight ratio of the matrix to the traditional Chinese medicine extract is (3-5):

1.

4. A method for preparing the traditional Chinese medicine gel plaster for treating gouty arthritis according to any one of claims 1 to 3, characterized in that: The steps include: (1) dissolving azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid in a solvent and reacting to obtain a first reaction product; (2) uniformly mixing the first reaction product with silk fibroin, polyvinyl pyrrolidone, 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, glycerol, and a Chinese herbal medicine extract, and reacting to obtain a mixed solution; (3) applying the mixed solution evenly and allowing it to stand for aging to obtain a gel layer loaded with the Chinese herbal medicine extract; Step (2) further includes adding calcium lignin sulfonate and tannic acid to the glycerol and the Chinese herbal medicine extract and mixing them evenly.

5. The method for preparing the Chinese medicine gel plaster for treating gouty arthritis according to claim 4, wherein: The specific steps include: (1) dissolving azide-polyethylene glycol-carboxylic acid and 1-ethynylcyclopropylcarboxylic acid in a solvent of dimethyl sulfoxide and water in a weight ratio of 1: (0.8-1.2), adjusting the pH value to 8-9 with sodium hydroxide, stirring and reacting at 30-50°C for 3-5 hours, then adjusting the pH value to 3-4 with hydrochloric acid, adding ether at 0-4°C, stirring for 20-60 minutes, and after precipitation, performing solid-liquid separation, washing, and drying to obtain a first reaction product; Wherein, the weight ratio of the solvent to the azide-polyethylene glycol-carboxylic acid is (3-5):1; the volume ratio of the ether to the solvent is (2-3):1; (2) uniformly mixing the activated first reaction product with an aqueous solution of silk fibroin, polyvinyl pyrrolidone, and 2,5-dicarboxylic acid-3,4-ethylenedioxythiophene, stirring and reacting at 30° C. for 1.5 h, and then adding a mixture of glycerol, Chinese herbal medicine extract, calcium lignin sulfonate, and tannic acid, stirring and reacting for 1.5 h to obtain a mixed solution; Wherein, in the aqueous solution of the silk fibroin, the concentration of the silk fibroin is 2-5wt%; (3) The mixed solution is evenly coated and allowed to stand at 20-40°C for 8-12 hours to obtain a gel layer loaded with the Chinese herbal medicine extract.

6. The method for preparing the Chinese medicine gel plaster for treating gouty arthritis according to claim 5, wherein: The steps of activating the first reaction product are as follows: adding the first reaction product to a PBS solution with a pH value of 6.0-6.5, adding EDC and NHS thereto, and stirring at 20-30° C. for 20-40 minutes to obtain an activated first reaction product; The weight ratio of the first reaction product, EDC, and NHS is 1:(0.08-0.20):(0.08-0.20); and the concentration of the first reaction product in the PBS solution is 1-3 mg / ml.

7. The method for preparing the Chinese medicine gel plaster for treating gouty arthritis according to claim 6, wherein: The Chinese medicine extract is obtained by the following method: Grind coix seed, clematis root, atractylodes, angelica root, safflower, red peony root, andrographis paniculata, daylily root, and trillium into powder, extract with ethanol, and filter and concentrate the alcohol extract to obtain a clear paste with a relative density of 1.28-1.32, which is the alcohol extract; Take Phellodendron chinense, Radix Codonopsis pilosulae, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Achyranthis Bidens, Radix Salix Achyranthis Bidens, Radix Tripterygii, Eucalyptus globulus, Radix Sophorae Flavescentis, Radix Lobelia, Rhizoma Coptidis, Acer octagonalis, and Semen Strychnos nux vomica, decoct them in water, and filter and concentrate the aqueous extract to obtain a clear paste with a relative density of 1.28-1.32, which is the aqueous extract; Take cinnamon twig, Zanthoxylum bungeanum, frankincense and myrrh, use 2-3 times the amount of sesame oil for oil extraction, and then add borneol to obtain an oily substance; Taking the remaining raw materials of the Chinese herbal medicine extract, crushing them to obtain medicinal powder; The alcohol extract, water extract, medicinal powder and oily substance are mixed evenly to obtain the product.

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