A patch medicine for treating gouty arthritis and its preparation method and application

Abstract

The present invention provides a kind of patch medicine for treating gouty arthritis and its preparation method and application, the patch medicine is composed of drug medium, drug and drug-loaded fiber layer, and the drug contains raw material components such as multiple Chinese herbal medicine and anti-inflammatory regulating microcapsule powder; Anti-inflammatory regulating microcapsule powder is made of specific anti-inflammatory regulator and emulsifier; The drug medium is made of azone, menthol and borneol nanoparticles, and the drug-loaded fiber layer is prepared on the drug-loaded fiber membrane by electrostatic adsorption of tourmaline stone powder, and the design of the drug medium and the drug-loaded fiber layer enhances the permeability and stability of the drug. During preparation, the drug is prepared by steps such as reflux extraction, ultrasonic extraction, supercritical extraction, water extraction, and then the drug is stirred and mixed with the drug medium and coated on the drug-loaded fiber layer. The patch medicine can be used to prevent the recurrence of gouty arthritis, reduce patient inflammation indicators, such as C-reactive protein and erythrocyte sedimentation rate, effectively prevent disease recurrence, and provide new options for the treatment of gouty arthritis.

Description

Technical Field

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

[0002] Gout arthritis is an inflammatory joint disease caused by the deposition of monosodium urate (MSU) crystals in the joint capsule, bursa, cartilage, bone and other tissues. It is directly related to hyperuricemia caused by purine metabolism disorders and / or decreased uric acid excretion. It is often manifested as redness, swelling, heat, pain and dysfunction of the joints, causing great pain to patients and seriously affecting their quality of life.

[0003] At present, the clinical treatment methods for gouty arthritis mainly include drug therapy and non-drug therapy. In terms of drug therapy, commonly used are non-steroidal anti-inflammatory drugs, colchicine, glucocorticoids, uric acid-lowering drugs, etc. However, these drugs have certain limitations during use.

[0004] Although nonsteroidal anti-inflammatory drugs can relieve pain and inflammation, long-term use may cause adverse gastrointestinal reactions such as indigestion, stomach pain, gastric bleeding, etc., and may also cause damage to liver and kidney function. Colchicine has a narrow therapeutic window, and the effective dose is close to the toxic dose, which can easily cause gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal pain, as well as adverse reactions such as bone marrow suppression and liver and kidney damage. Although glucocorticoids have powerful anti-inflammatory effects, long-term or large-scale use can lead to serious complications such as water and sodium retention, hypertension, diabetes, osteoporosis, and infection. Uric acid-lowering drugs may induce acute gout attacks due to fluctuations in blood uric acid levels in the early stages of use, and some patients do not respond well to uric acid-lowering drug treatment or have drug intolerance.

[0005] In terms of non-drug treatment, physical therapy such as cold compress, hot compress, electrotherapy, magnetic therapy, etc., although can relieve symptoms to a certain extent, the effect is often not long-lasting and it is difficult to solve the problem fundamentally.

[0006] In addition, some existing topical drugs, such as patches and ointments, still have many deficiencies in formulation design, preparation process and drug release mechanism of existing gouty arthritis patch drugs; some patch drugs contain only a single or a few active ingredients, which are difficult to fully cover the complex pathogenesis of gouty arthritis; and due to the poor permeability and weak targeting of drug ingredients, the concentration of drugs in the lesion site is low, the efficacy cannot be fully exerted, and the treatment effect is unsatisfactory. Moreover, the drug loading system and drug release mechanism of existing patch drugs are not ideal, the drug release rate is unstable, and it is difficult to maintain an effective therapeutic concentration, which also limits its clinical application. Summary of the invention

[0007] In view of this, the present invention proposes a patch medicine for treating gouty arthritis and a preparation method and application thereof to solve the above problems.

[0008] The technical scheme of the present invention is implemented as follows: a patch medicine for treating gouty arthritis, comprising a medicine medium, a medicine and a medicine-carrying fiber layer; the medicine comprises the following raw materials in parts by weight: 25-35 parts of rhubarb, 15-25 parts of coptis root, 15-25 parts of scutellaria baicalensis, 15-25 parts of gardenia, 25-35 parts of phellodendron, 25-35 parts of processed arisaema, 53-68 parts of angelica dahurica, 55-69 parts of trichosanthes root, 28-35 parts of liquorice, 26-33 parts of stir-fried atractylodes lancea, 12-25 parts of pearl powder, 12-25 parts of aspleniopsis pilosula, 12-25 parts of scutellaria baicalensis ... 18-25 parts, 3-8 parts of Callicarpa nudiflora, 6-12 parts of Acer truncatum, 3-9 parts of Polygonum hydropiper, 25-33 parts of anti-inflammatory regulating microcapsule powder, and 3-8 parts of bamboo salt; the anti-inflammatory regulating microcapsule powder is specifically prepared by diluting the anti-inflammatory regulator with anhydrous ethanol to a concentration of 70-90%, mixing it with an emulsifier in a volume ratio of 1:1-5, homogenizing it at a speed of 8000-12000rpm for 3-5min to obtain an anti-inflammatory emulsion, degassing it under vacuum conditions for 2-5min, and spray drying it to obtain the anti-inflammatory regulating microcapsule powder.

[0009] Furthermore, the medicine includes the following raw materials in parts by weight: 30 parts of rhubarb, 20 parts of coptis chinensis, 20 parts of scutellaria baicalensis, 20 parts of gardenia jasminoides, 30 parts of phellodendron chinense, 30 parts of processed arisaema, 60 parts of angelica dahurica, 60 parts of root of trichosanthes, 30 parts of licorice, 30 parts of stir-fried atractylodes lancea, 20 parts of pearl powder, 22 parts of aspleniaceae, 5 parts of callicarpa nudiflora, 10 parts of scutellaria baicalensis, 7 parts of polygonum hydropiper, 28 parts of anti-inflammatory regulating microcapsule powder, and 5 parts of bamboo salt.

[0010] Furthermore, the anti-inflammatory regulator is caryophyllene, gingerol A, and humulene in a volume ratio of (22-30):(18-35):(6-15); the emulsifier is prepared by mixing the wall material with deionized water at a mass volume ratio of g / mL of 3-5:15, and stirring and dissolving at 1000-5000 rpm, and the wall material is selected from any one or a combination of modified starch, gum arabic, octenyl succinate starch ester, β-cyclodextrin, and maltodextrin.

[0011] Furthermore, the drug medium is selected from azone, menthol and borneol in a mass ratio of (3.5-5.5):(10.2-22.5):(23.1-30.5) to prepare nanoparticles with a particle size of less than 10 nm.

[0012] Furthermore, the drug-loaded fiber layer is obtained by electrostatically adsorbing tourmaline powder on a drug-loaded fiber membrane, pressing and cutting, the tourmaline powder particle size is 1-100 μm, the electrostatic adsorption voltage is 5-30 kV, the current is 8-20 μA, the temperature is 30-50° C., and the humidity is 30-60%.

[0013] Furthermore, the drug-loaded fiber membrane includes but is not limited to chitosan drug-loaded fiber membrane, collagen drug-loaded fiber membrane, polylactic acid (PLA) drug-loaded fiber membrane, polyglycolic acid (PGA) drug-loaded fiber membrane, polyvinyl alcohol (PVA) drug-loaded fiber membrane, and silk fibroin drug-loaded fiber membrane.

[0014] Furthermore, a method for preparing a patch medicine for treating gouty arthritis comprises the following steps:

[0015] S1. According to the formula, rhubarb, coptis root, phellodendron, scutellaria, gardenia, processed arisaema, angelica dahurica, root of trichosanthes, and stir-fried atractylodes are mixed, and the mixture is ground to a fineness of 40-60 mesh. 12-14 times by volume of ethanol with a mass concentration of 40-60% is added to the mixture, and then refluxed for 1-3h after soaking for 30-40min. Reflux extraction is continued for 2-4 times, and the extracts are combined and concentrated to obtain filtrate I.

[0016] S2. Take the above extracted medicinal residue and continue to add 8-10 times the volume of 40-60% ethanol, perform ultrasonic extraction for 20-30 minutes at an ultrasonic frequency of 20-50 kHz, an ultrasonic power of 300-500 W, and a temperature of 40-50° C., and filter to obtain filtrate II.

[0017] S3. Crush Callicarpa nudiflora, Acer truncatum, Polygonum hydropiper, Aspleniaceae, and Glycyrrhiza uralensis, mix and grind them through a 100-120 mesh sieve, and perform CO2 supercritical extraction at an extraction pressure of 27-37 MPa, an extraction temperature of 30-60° C., and an extraction time of 1.0-1.5 h, and collect the volatile oil and extract respectively.

[0018] S4. Add 6-10 times the mass of water to the extract for water extraction at a temperature of 80-90°C for 1-2h. Extract 1-3 times with water, combine the extracts, and obtain filtrate III.

[0019] S5. Take pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt, dry them and grind them to a fineness of 80-120 mesh and set aside.

[0020] S6. The filtrates I, II and III are mixed and stirred, and volatile oil is added while stirring. The mixture is concentrated under reduced pressure to a relative density of 1.18-1.22, and ground pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt are added in sequence and stirred to obtain the medicine.

[0021] S7. Stir and mix the drug and drug medium with a mass ratio of 5-10:1 under pulse pneumatic conditions, the gas is nitrogen, the pulse frequency is 0.1-10Hz, the pulse width is 100-500ms, the gas pressure is 0.1-1MPa, the gas flow rate is 1-3L / min, the stirring rate is 600-1000rpm, the stirring time is 4-8h, and the mixture is dried and coated on the drug-loaded fiber layer to obtain a patch drug.

[0022] Furthermore, the patch medicine for treating gouty arthritis is used in the preparation of a medicine for preventing the recurrence of gouty arthritis.

[0023] Furthermore, the patch medicine is used in the preparation of a medicine for reducing inflammatory indicators in patients with acute gouty arthritis.

[0024] Furthermore, the patch medicine is used in the preparation of a medicine for reducing C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in patients with acute gouty arthritis.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1. The prescription of the present invention is in accordance with the principle of monarch-minister-assistant-assistant compatibility. The four medicines of Rhubarb, Coptis chinensis, Phellodendron chinense and Scutellaria baicalensis are used together, and the power of clearing away heat and purging fire, drying dampness and detoxifying is very strong. It targets the heat toxicity and damp-heat pathogenesis of gouty arthritis and directly breaks its disease situation. They are all monarch medicines; Gardenia, processed Arisaema, Angelica dahurica, Radix Trichosanthis and Rhizoma Atractylodis Macrocephalae are mutually ministerial medicines, which assist the monarch medicine in enhancing the power of clearing heat and purging fire, drying dampness and detoxifying, and relieving swelling and relieving pain, while taking into account aspects such as resolving phlegm, dispelling wind and strengthening the spleen, so that the evil is removed and the body is at peace; Callicarpa nudiflora can strengthen the effects of clearing heat and detoxifying, astringing and stopping bleeding, help the monarch and minister medicines to alleviate joint inflammation and bleeding, Acer truncatum can invigorate blood circulation and dredge collaterals, resolve blood stasis and relieve pain, help improve the blood circulation of local joints, promote the disappearance of swelling and pain, Polygonum pekinensis dispels wind and dampness to remove dampness in joints, disperses blood stasis and relieves pain to relieve joint pain, Styplenia acuminata has the effects of clearing heat and dampness, detoxifying and relieving swelling, and assists other drugs in exerting therapeutic effects, and Licorice can It can clear away heat and detoxify, and can also reconcile various medicines, alleviate the toxicity and potency of drugs, make the whole prescription more peaceful, and serve as an adjuvant to assist the monarch and minister drugs in exerting their therapeutic effects, while controlling the harshness of the monarch and minister drugs, or playing a counter-adjuvant role to prevent drug-disease rejection; pearl powder can promote the repair and regeneration of local joint skin and improve skin resistance; anti-inflammatory regulating microcapsule powder has better stability and targeting, can accurately act on the inflammatory site, enhance the anti-inflammatory effect of the whole prescription, guide various medicines to reach the diseased area directly, and improve the efficacy; bamboo salt guides the medicine into the interior, enhances the heat-clearing, fire-purging, detoxifying and swelling-reducing power of the whole prescription, reconciles various medicines, makes the medicines in the medicine-guided prescription reach the diseased area directly, reconciles various medicines, enhances the efficacy of the medicines or plays a role in guiding the meridians and reporting; this prescription can relieve gouty arthritis caused by damp-heat accumulation and heat-toxic blood stasis, with symptoms such as red, swollen, hot and painful joints, poor flexion and extension, limited movement, thirst and irritability, yellow and red urine, and dry stools.

[0027] The present invention also includes a drug medium made of azone, menthol and borneol in the form of nanoparticles, which can promote transdermal absorption of drugs and increase the concentration of drugs at the lesion site. The drug-loaded fiber layer is prepared on the drug-loaded fiber membrane by electrostatically adsorbing tourmaline powder, which can not only increase the loading amount and stability of the drugs, but also give play to the far-infrared radiation and negative ion release functions of the tourmaline powder, promote local blood circulation, accelerate the absorption and metabolism of drugs, and improve the treatment effect. The design of the drug medium and the drug-loaded fiber layer enhances the permeability and stability of the drugs.

[0028] The preparation method of the present invention fully extracts the effective ingredients in the medicinal materials through multiple extraction methods such as reflux extraction, ultrasonic extraction, supercritical extraction and water extraction, thereby improving the utilization rate and efficacy of the medicine. The medicine and the drug medium are stirred and mixed under pulse pneumatics to uniformly mix the medicine and the medium to ensure the quality and stability of the medicine. The patch medicine has a significant effect in preventing the recurrence of gouty arthritis. External application can significantly improve the patient's clinical symptoms and reduce the blood uric acid level, reduce the inflammatory indicators of patients with acute and chronic gouty arthritis, such as C-reactive protein and erythrocyte sedimentation rate, effectively control the disease, and improve the patient's quality of life, providing a safe and effective new option for the treatment of gouty arthritis. DETAILED DESCRIPTION

[0029] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0030] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0031] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0032] The following introduces the basic information of the main raw materials based on the "Chinese Pharmacopoeia", "Chinese Materia Medica Dictionary" and "Chinese Herbal Medicine".

[0033]

rhubarb

[0034] Nature and flavor: bitter, cold. Enters the spleen, stomach, large intestine, liver, and pericardium meridians.

[0035] Functions and indications: purgative, heat-clearing and fire-purging, cooling blood and detoxifying, promoting blood circulation and removing blood stasis. Used to treat constipation, oral sores, sore throat, red and painful eyes, jaundice, damp-heat dysentery, traumatic injuries, etc.

[0036]

Coptis chinensis

[0037] Nature and flavor: bitter, cold. Enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians.

[0038] Functions and indications: clearing away heat and drying dampness, purging fire and detoxifying. Used to treat damp-heat fullness, vomiting and acid regurgitation, diarrhea, jaundice, high fever and coma, hyperactivity of heart fire, restlessness and insomnia, palpitations, vomiting and bleeding due to blood heat, red eyes, toothache, etc.

[0039]

Phellodendron chinense

[0040] Nature and flavor: bitter, cold. Enters the kidney, bladder, and large intestine meridians.

[0041] Functions and indications: clearing away heat and drying dampness, purging fire and detoxifying, and removing bone steaming. It is used to treat damp-heat, yellow, turbid and foul-smelling vaginal discharge, short, red, hot and painful urination, damp-heat jaundice, diarrhea, damp-heat beriberi, impotence, bone steaming and fatigue fever, night sweats, spermatorrhea, sores, swelling and pain, etc.

[0042]

Scutellaria baicalensis

[0043] Nature and flavor: bitter, cold. Enters the lung, gallbladder, spleen, large intestine and small intestine meridians.

[0044] Functions and indications: clearing away heat and dampness, purging fire and detoxifying, stopping bleeding and stabilizing pregnancy. Used to treat damp-heat, summer heat, chest tightness and nausea, damp-heat fullness, diarrhea and jaundice, lung heat cough, high fever and thirst, blood heat vomiting and bleeding, carbuncle, sore and toxicity, and restless fetus.

[0045]

Gardenia

[0046] Nature and flavor: bitter, cold. Enters the heart, lung and triple burner meridians.

[0047] Functions and indications: purging fire and relieving restlessness, clearing away heat and dampness, cooling blood and detoxifying. Used to treat fever, restlessness, raging fire poison, high fever and restlessness, coma and delirium, jaundice, short and dark urine, vomiting and bleeding due to blood heat, red and swollen eyes, etc.

[0048]

Processed Arisaema

[0049] Nature and flavor: bitter, pungent, warm. Enters the lung, liver and spleen meridians.

[0050] Functions and indications: Drying dampness and resolving phlegm, dispelling wind and relieving spasms, dispersing stagnation and reducing swelling. Used to treat cough, wheezing, chest tightness, excessive thin white sputum, carbuncle, snake bite, phlegm nodule, scrofula, etc.

[0051] Angelica dahurica

[0052] Nature and flavor: Pungent, warm. Enters the lung and stomach meridians.

[0053] Functions and indications: dispel wind and relieve symptoms, relieve pain, reduce swelling, discharge pus, dry dampness and stop leukorrhea. Used to treat colds, headaches, nasal congestion, toothaches, sores, swelling and pain, and leucorrhea in women.

[0054]

Trichosanthes powder

[0055] Nature and flavor: sweet, slightly bitter, slightly cold. Enters the lung and stomach meridians.

[0056] Functions and indications: Clears away heat and purges fire, promotes the production of body fluids and quenches thirst, discharges pus and reduces swelling. Used to treat fever, thirst, lung heat and dry cough, internal heat and thirst, sores and swelling, etc.

[0057]

Stir-fried Atractylodes macrocephala with bran

[0058] Nature and flavor: pungent, bitter, warm. Enters the spleen, stomach and liver meridians.

[0059] Functions and indications: Drying dampness and strengthening the spleen, dispelling wind and cold, improving eyesight. Used to treat dampness blocking the middle jiao, abdominal distension, diarrhea, edema, beriberi, rheumatic arthralgia, colds, night blindness, etc.

[0060]

Nude Flower Purple Bead

[0061] Nature and flavor: bitter, slightly pungent, neutral. Enters the liver, spleen, and stomach meridians.

[0062] Functions and indications: Anti-inflammatory, detoxifying, astringent, hemostatic. Used to treat inflammation caused by bacterial infection, acute infectious hepatitis, respiratory and digestive tract bleeding, etc.

[0063]

Maple

[0064] Nature and flavor: bitter, pungent, cool. Enters the liver and large intestine meridians.

[0065] Functions and indications: clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, reducing swelling and relieving pain. Used to treat acute hepatitis, chronic tracheitis, metrorrhagia, thrombocytopenic purpura, constipation, etc.

[0066]

Polygonum hydropiper

[0067] Nature and flavor: Pungent, warm. Enters the lung, liver and large intestine meridians.

[0068] Functions and indications: dispel wind and dampness, relieve blood stasis and relieve pain, detoxify and reduce swelling, kill insects and relieve itching. Used to treat dysentery, gastroenteritis, rheumatic joint pain, swelling and pain caused by falls, functional uterine bleeding, etc.

[0069] Licorice

[0070] Nature and flavor: sweet, neutral. Enters the heart, lung, spleen and stomach meridians.

[0071] Functions and indications: tonifying the spleen and replenishing qi, clearing away heat and detoxifying, removing phlegm and relieving cough, relieving urgency and relieving pain, and harmonizing various medicines. It is used for spleen and stomach weakness, fatigue, palpitations and shortness of breath, cough with sputum, cramps and pain in the abdomen and limbs, carbuncle, sore and ulcer, and relieving drug toxicity and potency.

[0072]

Pearl powder

[0073] Nature and flavor: sweet, salty, cold. Enters the heart and liver meridians.

[0074] Functions and indications: calm the mind and calm the nerves, improve eyesight and eliminate cataracts, detoxify and promote tissue regeneration, moisturize the skin and remove freckles. Used for palpitations, insomnia, convulsions, epilepsy, red eyes, cataracts, sores that do not heal, and skin spots.

[0075]

Bamboo Salt

[0076] Nature and flavor: salty, cold.

[0077] Functions and indications: vomiting, clearing heat, cooling blood, detoxifying, softening hard masses, killing insects, and relieving itching. Example 1

[0078] A patch medicine for treating gouty arthritis comprises a medicine medium, a medicine and a medicine-carrying fiber layer.

[0079] The drug medium is selected from azone, menthol and borneol in a mass ratio of 3.5:10.2:23.1 to prepare nanoparticles with a particle size of less than 10 nm.

[0080] The medicine includes the following raw materials by weight: 25 grams of rhubarb, 15 grams of coptis chinensis, 15 grams of scutellaria baicalensis, 15 grams of gardenia, 25 grams of phellodendron, 25 grams of processed arisaema, 53 grams of angelica dahurica, 55 grams of root of trichosanthes, 28 grams of licorice, 26 grams of stir-fried atractylodes, 12 grams of pearl powder, 18 grams of asplenium nudiflorum, 3 grams of callicarpa nudiflora, 6 grams of acer truncatum, 3 grams of polygonum hydropiper, 25 grams of anti-inflammatory regulating microcapsule powder, and 3 grams of bamboo salt.

[0081] The above-mentioned anti-inflammatory regulating microcapsule powder is specifically prepared by diluting the anti-inflammatory regulator with anhydrous ethanol to a concentration of 70%, mixing it with an emulsifier in a volume ratio of 1:1, homogenizing it at a rotation speed of 8000rpm for 3min to obtain an anti-inflammatory emulsion, degassing it under vacuum conditions for 2min, and spray drying it to obtain an anti-inflammatory regulating microcapsule powder; the anti-inflammatory regulator is caryophyllene, gingerol A, and humulene in a volume ratio of 22:18:6, and the emulsifier is prepared by mixing modified starch and deionized water in a mass volume ratio of g / mL of 3:15, and stirring and dissolving them at 1000rpm.

[0082] The drug-loaded fiber layer is obtained by adsorbing tourmaline powder on a chitosan drug-loaded fiber membrane through electrostatic adsorption, pressing and cutting. The average particle size of the tourmaline powder is 10 μm, the electrostatic adsorption voltage is 5 kV, the current is 8 μA, the temperature is 30° C., and the humidity is 30%. Example 2

[0083] A patch medicine for treating gouty arthritis comprises a medicine medium, a medicine and a medicine-carrying fiber layer.

[0084] The drug medium is selected from azone, menthol and borneol in a mass ratio of 5.5:22.5:30.5 to prepare nanoparticles with a particle size of less than 10 nm.

[0085] The medicine includes the following raw materials by weight: 35 grams of rhubarb, 25 grams of coptis chinensis, 25 grams of scutellaria baicalensis, 25 grams of gardenia, 35 grams of phellodendron, 35 grams of processed arisaema, 68 grams of angelica dahurica, 69 grams of root of trichosanthes, 35 grams of licorice, 33 grams of stir-fried atractylodes, 25 grams of pearl powder, 25 grams of asplenium wilfordii, 8 grams of callicarpa nudiflora, 12 grams of acer truncatum, 9 grams of polygonum hydropiper, 33 grams of anti-inflammatory regulating microcapsule powder, and 8 grams of bamboo salt.

[0086] The above-mentioned anti-inflammatory regulating microcapsule powder is specifically prepared by diluting the anti-inflammatory regulator with anhydrous ethanol to a concentration of 90%, mixing it with an emulsifier in a volume ratio of 1:5, homogenizing it at a rotation speed of 12000rpm for 5min to obtain an anti-inflammatory emulsion, degassing it under vacuum conditions for 5min, and spray drying it to obtain an anti-inflammatory regulating microcapsule powder; the anti-inflammatory regulator is caryophyllene, gingerol A, and humulene in a volume ratio of 30:35:15, and the emulsifier is prepared by mixing gum arabic and deionized water in a mass volume ratio of g / mL of 5:15, and stirring and dissolving them at 5000rpm.

[0087] The drug-loaded fiber layer is obtained by adsorbing tourmaline powder on a collagen drug-loaded fiber membrane through electrostatic adsorption, pressing and cutting. The average particle size of the tourmaline powder is 100 μm, the electrostatic adsorption voltage is 30 kV, the current is 20 μA, the temperature is 50° C., and the humidity is 60%. Example 3

[0088] A patch medicine for treating gouty arthritis comprises a medicine medium, a medicine and a medicine-carrying fiber layer.

[0089] The drug medium is selected from azone, menthol and borneol in a mass ratio of 4.5:15:27.5 to prepare nanoparticles with a particle size of less than 10 nm.

[0090] The medicine includes the following raw materials by weight: 30 grams of rhubarb, 20 grams of coptis chinensis, 20 grams of scutellaria baicalensis, 20 grams of gardenia, 30 grams of phellodendron, 30 grams of processed arisaema, 60 grams of angelica dahurica, 60 grams of trichosanthes, 30 grams of licorice, 30 grams of stir-fried atractylodes, 22 grams of pearl powder, 23 grams of asplenium nudiflorum, 5 grams of callicarpa nudiflora, 10 grams of acer truncatum, 7 grams of polygonum hydropiper, 30 grams of anti-inflammatory regulating microcapsule powder, and 5 grams of bamboo salt.

[0091] The above-mentioned anti-inflammatory regulating microcapsule powder is specifically prepared by diluting the anti-inflammatory regulator with anhydrous ethanol to a concentration of 80%, mixing it with an emulsifier in a volume ratio of 1:3, homogenizing it at a rotation speed of 10000rpm for 4min to obtain an anti-inflammatory emulsion, degassing it under vacuum conditions for 3min, and spray drying it to obtain an anti-inflammatory regulating microcapsule powder; the anti-inflammatory regulator is caryophyllene, gingerol A, and humulene in a volume ratio of 28:25:12, and the emulsifier is prepared by mixing octenyl succinic acid starch ester with deionized water in a mass volume ratio of g / mL of 4:15, and stirring and dissolving it at 3000rpm.

[0092] The drug-loaded fiber layer is obtained by adsorbing tourmaline powder on a polylactic acid (PLA) drug-loaded fiber membrane through electrostatic adsorption, pressing and cutting. The average particle size of the tourmaline powder is 50 μm, the electrostatic adsorption voltage is 22 kV, the current is 15 μA, the temperature is 40° C., and the humidity is 50%.

[0093] The above examples 1-3 adopt the following preparation method:

[0094] S1. According to the formula, rhubarb, coptis root, phellodendron, scutellaria, gardenia, processed arisaema, angelica dahurica, root of trichosanthes, and stir-fried atractylodes were mixed, and the mixture was ground to a fineness of 50 mesh. 13 times by volume of 50% ethanol was added to the mixture, and then refluxed for 2 h after soaking for 35 min. Refluxed for 3 times in succession, the extracts were combined and concentrated to obtain filtrate I.

[0095] S2. Take the above extracted medicinal residue and continue to add 9 times the volume of 50% ethanol, perform ultrasonic extraction for 25 minutes under the conditions of ultrasonic frequency of 30 kHz, ultrasonic power of 400 W and temperature of 45°C, and filter to obtain filtrate II.

[0096] S3. Crush Callicarpa nudiflora, Acer truncatum, Polygonum hydropiper, Aspleniaceae, and Glycyrrhiza uralensis, mix and grind them through a 110-mesh sieve, and perform supercritical CO2 extraction at an extraction pressure of 32 MPa, an extraction temperature of 45°C, and an extraction time of 1.3 h, and collect the volatile oil and extract respectively.

[0097] S4. The extract was added with 8 times the mass of water for water extraction at 85°C for 2 hours. The water extraction was repeated twice, and the extracts were combined to obtain filtrate III.

[0098] S5. Take pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt, dry them and grind them to a fineness of 100 mesh and set aside.

[0099] S6. The filtrates I, II and III are mixed and stirred, and volatile oil is added while stirring. The mixture is concentrated under reduced pressure to a relative density of 1.2, and ground pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt are added in sequence and stirred to obtain the medicine.

[0100] S7. Stir and mix the drug and drug medium in a mass ratio of 8:1 under pulse pneumatic conditions. The gas is nitrogen, the pulse frequency is 5 Hz, the pulse width is 300 ms, the gas pressure is 0.5 MPa, the gas flow rate is 2 L / min, the stirring rate is 800 rpm, the stirring time is 6 h, and the mixture is dried. The mixed drug is coated on the drug-loaded fiber layer to obtain a patch drug. Example 4

[0101] A patch medicine for treating gouty arthritis comprises a medicine medium, a medicine and a medicine-carrying fiber layer.

[0102] The drug medium is selected from azone, menthol and borneol in a mass ratio of 4.5:15:27.5 to prepare nanoparticles with a particle size of less than 10 nm.

[0103] The medicine includes the following raw materials by weight: 30 grams of rhubarb, 20 grams of coptis chinensis, 20 grams of scutellaria baicalensis, 20 grams of gardenia, 30 grams of phellodendron, 30 grams of processed arisaema, 60 grams of angelica dahurica, 60 grams of trichosanthes, 30 grams of licorice, 30 grams of stir-fried atractylodes, 22 grams of pearl powder, 23 grams of asplenium nudiflorum, 5 grams of callicarpa nudiflora, 10 grams of acer truncatum, 7 grams of polygonum hydropiper, 30 grams of anti-inflammatory regulating microcapsule powder, and 5 grams of bamboo salt.

[0104] The above-mentioned anti-inflammatory regulating microcapsule powder is specifically prepared by diluting the anti-inflammatory regulator with anhydrous ethanol to a concentration of 80%, mixing it with an emulsifier in a volume ratio of 1:3, homogenizing it at a rotation speed of 10000rpm for 4min to obtain an anti-inflammatory emulsion, degassing it under vacuum conditions for 3min, and spray drying it to obtain an anti-inflammatory regulating microcapsule powder; the anti-inflammatory regulator is caryophyllene, gingerol A, and humulene in a volume ratio of 28:25:12, and the emulsifier is prepared by mixing octenyl succinic acid starch ester with deionized water in a mass volume ratio of g / mL of 4:15, and stirring and dissolving it at 3000rpm.

[0105] The drug-loaded fiber layer is obtained by adsorbing tourmaline powder on a polylactic acid (PLA) drug-loaded fiber membrane through electrostatic adsorption, pressing and cutting. The average particle size of the tourmaline powder is 50 μm, the electrostatic adsorption voltage is 22 kV, the current is 15 μA, the temperature is 40° C., and the humidity is 50%.

[0106] The above-mentioned Example 4 adopts the following preparation method:

[0107] S1. According to the formula, rhubarb, coptis root, phellodendron, scutellaria, gardenia, processed arisaema, angelica dahurica, root of trichosanthes, and stir-fried atractylodes are mixed, and the mixture is ground to a fineness of 40 mesh. 12 times by volume of 40% ethanol is added to the mixture, and then refluxed for 1 hour after soaking for 30 minutes. Reflux extraction is repeated twice, and the extracts are combined and concentrated to obtain filtrate I.

[0108] S2. Take the above extracted medicinal residue and continue to add 8 times the volume of 40% ethanol, perform ultrasonic extraction for 20 minutes under the conditions of ultrasonic frequency of 20 kHz, ultrasonic power of 300 W and temperature of 40°C, and filter to obtain filtrate II.

[0109] S3. Crush Callicarpa nudiflora, Acer truncatum, Polygonum hydropiper, Aspleniaceae, and Glycyrrhiza uralensis, mix and grind them through a 100-mesh sieve, and perform supercritical CO2 extraction at an extraction pressure of 27 MPa, an extraction temperature of 30°C, and an extraction time of 1.0 h, and collect the volatile oil and extract respectively.

[0110] S4. Add 6 times the mass of water to the extract for water extraction at 80°C for 1 h. Extract once, combine the extracts to obtain filtrate III.

[0111] S5. Take pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt, dry them and grind them to a fineness of 80 mesh and set aside.

[0112] S6. The filtrates I, II and III are mixed and stirred, and volatile oil is added while stirring. The mixture is concentrated under reduced pressure to a relative density of 1.18, and ground pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt are added in sequence and stirred to obtain the medicine.

[0113] S7. Stir and mix the drug and drug medium in a mass ratio of 5:1 under pulse pneumatic conditions. The gas is nitrogen, the pulse frequency is 0.1 Hz, the pulse width is 100 ms, the gas pressure is 0.1 MPa, the gas flow rate is 1 L / min, the stirring rate is 600 rpm, the stirring time is 4 h, and the mixture is dried. The mixed drug is coated on the drug-loaded fiber layer to obtain a patch drug. Example 5

[0114] A patch medicine for treating gouty arthritis comprises a medicine medium, a medicine and a medicine-carrying fiber layer.

[0115] The drug medium is selected from azone, menthol and borneol in a mass ratio of 4.5:15:27.5 to prepare nanoparticles with a particle size of less than 10 nm.

[0116] The medicine includes the following raw materials by weight: 30 grams of rhubarb, 20 grams of coptis chinensis, 20 grams of scutellaria baicalensis, 20 grams of gardenia, 30 grams of phellodendron, 30 grams of processed arisaema, 60 grams of angelica dahurica, 60 grams of trichosanthes, 30 grams of licorice, 30 grams of stir-fried atractylodes, 22 grams of pearl powder, 23 grams of asplenium nudiflorum, 5 grams of callicarpa nudiflora, 10 grams of acer truncatum, 7 grams of polygonum hydropiper, 30 grams of anti-inflammatory regulating microcapsule powder, and 5 grams of bamboo salt.

[0117] The above-mentioned anti-inflammatory regulating microcapsule powder is specifically prepared by diluting the anti-inflammatory regulator with anhydrous ethanol to a concentration of 80%, mixing it with an emulsifier in a volume ratio of 1:3, homogenizing it at a rotation speed of 10000rpm for 4min to obtain an anti-inflammatory emulsion, degassing it under vacuum conditions for 3min, and spray drying it to obtain an anti-inflammatory regulating microcapsule powder; the anti-inflammatory regulator is caryophyllene, gingerol A, and humulene in a volume ratio of 28:25:12, and the emulsifier is prepared by mixing octenyl succinic acid starch ester with deionized water in a mass volume ratio of g / mL of 4:15, and stirring and dissolving it at 3000rpm.

[0118] The drug-loaded fiber layer is obtained by adsorbing tourmaline powder on a polylactic acid (PLA) drug-loaded fiber membrane through electrostatic adsorption, pressing and cutting. The average particle size of the tourmaline powder is 50 μm, the electrostatic adsorption voltage is 22 kV, the current is 15 μA, the temperature is 40° C., and the humidity is 50%.

[0119] The above-mentioned Example 5 adopts the following preparation method:

[0120] S1. According to the formula, rhubarb, coptis root, phellodendron, scutellaria, gardenia, processed arisaema, angelica dahurica, root of trichosanthes, and stir-fried atractylodes were mixed, and the mixture was ground to a fineness of 60 mesh. 14 times by volume of 60% ethanol was added to the mixture, and then refluxed for 3 hours after soaking for 40 minutes. Refluxed for 4 times in succession, the extracts were combined and concentrated to obtain filtrate I.

[0121] S2. Take the above extracted medicinal residue and continue to add 10 times the volume of 60% ethanol, perform ultrasonic extraction for 30 minutes at an ultrasonic frequency of 50 kHz, an ultrasonic power of 500 W, and a temperature of 50° C., and filter to obtain filtrate II.

[0122] S3. Grind Callicarpa nudiflora, Acer truncatum, Polygonum hydropiper, Aspleniaceae and Glycyrrhiza uralensis, mix and grind them through a 120-mesh sieve, and perform supercritical CO2 extraction at an extraction pressure of 37 MPa, an extraction temperature of 60°C and an extraction time of 1.5 h, and collect the volatile oil and extract respectively.

[0123] S4. The extract was added with 10 times the mass of water for water extraction at 90°C for 2 h. The water extraction was repeated 3 times. The extracts were combined to obtain filtrate III.

[0124] S5. Take pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt, dry them and grind them to a fineness of 120 mesh and set aside.

[0125] S6. The filtrates I, II and III are mixed and stirred, and volatile oil is added while stirring. The mixture is concentrated under reduced pressure to a relative density of 1.22, and ground pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt are added in sequence and stirred to obtain the medicine.

[0126] S7. Stir and mix the drug and drug medium in a mass ratio of 10:1 under pulse pneumatic conditions. The gas is nitrogen, the pulse frequency is 10 Hz, the pulse width is 500 ms, the gas pressure is 1 MPa, the gas flow rate is 3 L / min, the stirring rate is 1000 rpm, the stirring time is 8 h, and the mixture is dried. The mixed drug is coated on the drug-loaded fiber layer to obtain a patch drug. Comparative Example 1

[0127] The difference between this comparative example and Example 3 is that the medicine includes the following raw materials by weight: 12 grams of rhubarb, 10 grams of coptis chinensis, 11 grams of scutellaria baicalensis, 30 grams of gardenia, 20 grams of phellodendron, 12 grams of processed arisaema, 20 grams of angelica dahurica, 70 grams of trichosanthes, 22 grams of licorice, 35 grams of stir-fried atractylodes, 36 grams of pearl powder, 10 grams of asplenium nudiflorum, 1 gram of callicarpa nudiflora, 15 grams of scutellaria baicalensis, 2 grams of polygonum hydropiper, 22 grams of anti-inflammatory regulating microcapsule powder, and 10 grams of bamboo salt. Comparative Example 2

[0128] The difference between this comparative example and Example 3 is that the medicine includes the following raw materials by weight: 40 grams of rhubarb, 33 grams of coptis chinensis, 28 grams of scutellaria baicalensis, 30 grams of gardenia, 38 grams of phellodendron, 40 grams of processed arisaema, 22 grams of angelica dahurica, 20 grams of trichosanthes, 20 grams of licorice, 25 grams of stir-fried atractylodes, 10 grams of pearl powder, 30 grams of asplenium wilfordii, 10 grams of callicarpa nudiflora, 1 gram of scutellaria baicalensis, 15 grams of polygonum hydropiper, 50 grams of anti-inflammatory regulating microcapsule powder, and 1 gram of bamboo salt. Comparative Example 3

[0129] The difference between this comparative example and Example 3 is that the drug raw material does not contain anti-inflammatory regulating microcapsule powder. Comparative Example 4

[0130] The difference between this comparative example and Example 3 is that no drug medium is added to the patch drug. Comparative Example 5

[0131] The difference between this comparative example and Example 3 is that the preparation method of the patch medicine is to mix rhubarb, coptis chinensis, phellodendron, scutellaria baicalensis, gardenia jasminoides, processed arisaema, angelica dahurica, root of trichosanthes, stir-fried atractylodes, aspleniaceae, callicarpa nudiflora, acer truncatum, and polygonum hydropiper according to the formula, and decoct in water to obtain a decoction, and after concentrating, add anti-inflammatory regulating microcapsule powder, bamboo salt and pearl powder, and stir evenly to obtain the medicine. Comparative Example 6

[0132] The difference between this comparative example and Example 3 is that in S7 of the method for preparing the patch medicine, pulse pneumatic stirring is not performed. Specifically, the medicine and the medicine medium with a mass ratio of 8:1 are stirred and mixed at a stirring rate of 800 rpm for 6 hours.

[0133] Test Example 1 - Animal Experiment

[0134] 1. Experimental animals: 260 healthy male Wistar rats weighing 180-220 g were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd.

[0135] 2. Drugs and reagents:

[0136] Test drugs: the patch drugs prepared in the above Examples 1-5 and Comparative Examples 1-6.

[0137] Positive control group: colchicine tablets (purchased from Yunnan Xishuangbanna Banna Pharmaceutical Co., Ltd.).

[0138] Sodium urate crystals (MSU): purchased from Shanghai Jingkang Bioengineering Co., Ltd.

[0139] Uric acid detection kit, inflammatory factor detection kit (purchased from Shanghai Yueteng Biotechnology Co., Ltd.)

[0140] 3. Experimental methods:

[0141] Animal grouping: Wistar rats were randomly divided into 13 groups, 20 rats in each group, namely:

[0142] 1). Blank control group: no treatment.

[0143] 2). Model group: establish gouty arthritis model and give blank patch.

[0144] 3)-7).: Example 1-5 group: gouty arthritis model was established, and patch medication was administered (dose: 10 g / patch).

[0145] 8)-13). Comparative Example 1-6 groups: Gouty arthritis model was established and the patch drug dosage was 10 g / patch).

[0146] (2) Establishment of gouty arthritis model

[0147] Except for the blank control group, the rats in the other groups were induced with sodium urate crystals to establish gouty arthritis models. The specific methods are as follows:

[0148] 1). Prepare a 25 mg / ml sodium urate crystal suspension with normal saline, incubate in a 60°C water bath for 30 min until the crystals are completely dissolved, and then cool naturally to room temperature.

[0149] 2). After local disinfection of the dorsal side of the right ankle joint of the rat, 0.1 ml of sodium urate crystal suspension was injected into the ankle joint cavity using a microsyringe to induce a gouty arthritis model.

[0150] (3) Method of administration

[0151] 1). Blank control group and model group: blank patch was applied once a day, each time for 6 hours, for 7 consecutive days.

[0152] 2). Drug patch group: Patches of corresponding doses were given once a day, each time for 6 hours, for 7 consecutive days.

[0153] (4) Index test

[0154] 1). Ankle joint swelling measurement

[0155] The circumference of the right ankle joint of the rats was measured with a vernier caliper before modeling, 24h, 48h, 72h after modeling, and on the 3rd, 5th, and 7th day after treatment, and the swelling degree of the ankle joint was calculated.

[0156] Ankle joint swelling degree (%) = (ankle joint circumference after modeling or treatment - ankle joint circumference before modeling) / ankle joint circumference before modeling × 100%.

[0157] 2). Gait scoring

[0158] 24 hours after modeling and 7 days after treatment, the gait of the rats was observed and scored. The scoring criteria are as follows:

[0159] 0 points: normal walking, no limp.

[0160] 1 point: Mild limp, the ankle touches the ground but there is slight abnormality when walking.

[0161] 2 points: moderate lameness, the ankle joint does not fully touch the ground, and there are obvious abnormalities when walking.

[0162] 3 points: severe lameness, the ankle joint cannot touch the ground, and walking is difficult.

[0163] 3). Determination of blood uric acid level

[0164] On the 7th day after treatment, the rats were fasted for 12 hours, blood was collected from the orbital venous plexus, serum was separated by centrifugation, and the blood uric acid level was measured using a uric acid detection kit.

[0165] 3). Determination of inflammatory factor levels

[0166] On the 7th day after treatment, the synovial tissues of the rat ankle joints were obtained, and the levels of inflammatory factors (IL-1β, TNF-α) were determined using ELISA kits.

[0167] 4. Experimental data processing and statistical analysis

[0168] The experimental data were expressed as mean ± standard deviation (x ± s), and SPSS 22.0 statistical software was used for data analysis. One-way ANOVA was used for comparison among multiple groups, and LSD method was used for comparison between two groups. P < 0.05 indicated that the difference was statistically significant.

[0169] 5. Experimental Results

[0170]

[0171] From the above results, it can be seen that the ankle swelling, gait score, blood uric acid level, IL-1β and TNF-α index values ​​of the model group were significantly higher than those of the blank control group, indicating that the gouty arthritis model established by inducing sodium urate crystals was successful, and the inflammatory response of the model group was strong, the blood uric acid level was significantly increased, and the joint swelling and gait abnormalities were obvious.

[0172] In each treatment group, the results of Example 1-5 groups showed that all indicators showed a good improvement trend. The ankle swelling, gait score, blood uric acid level and inflammatory factor (IL-1β, TNF-α) levels of Example 1-5 groups were significantly lower than those of the model group, indicating that the patch medicine for treating gouty arthritis in this experiment has a certain therapeutic effect on gouty arthritis.

[0173] In the comparative examples 1-6, the therapeutic effects of comparative examples 1 and 2 are relatively good, but compared with the example group, the effects of reducing ankle swelling, improving gait, reducing blood uric acid levels and inflammatory factor levels are still slightly inferior, indicating that a specific raw material ratio can achieve better results. The values ​​of various indicators of comparative examples 3-6 are relatively high, indicating that their therapeutic effects are not as good as those of the example group. The example group in this experiment, especially the corresponding patch drug formula and dosage of Example 3, showed a more significant effect in the treatment of gouty arthritis.

[0174] Test Example 2-Clinical Trial

[0175] 1. Clinical data: 350 patients with gouty arthritis were selected, aged between 18 and 65 years old, regardless of gender, who met the diagnostic criteria for gouty arthritis established by the American College of Rheumatology (ACR), were in the acute attack stage, and the skin of the affected joints was intact without damage, infection, ulcers, etc. The patients voluntarily participated in the trial and signed the informed consent form.

[0176] 2. Exclusion criteria: patients who are allergic to the trial drugs or their components; patients with severe heart, liver, kidney, blood system diseases or malignant tumors; patients who have used other drugs or therapies for gouty arthritis in the past month (such as non-steroidal anti-inflammatory drugs, colchicine, glucocorticoids, uric acid-lowering drugs, physical therapy, etc.); pregnant or lactating women; patients with mental illness or cognitive impairment who cannot cooperate with treatment and follow-up.

[0177] 3. Trial grouping and intervention: Patients who met the inclusion criteria were randomly divided into 7 groups, with 50 cases in each group:

[0178] ① Experimental groups 1-5: The patch drugs prepared in Example 3 and Comparative Examples 3-6 were used once a day, each time for 5 hours, for 7 consecutive days.

[0179] ② Positive control group: Flurbiprofen cataplasm was used for patch application, and the usage and dosage were the same as those of the experimental group.

[0180] ③ Placebo group: Use a patch that is the same in appearance as the test group and the positive control group but does not contain active drug ingredients. The usage and dosage are the same as the test group.

[0181] 4. Observation indicators

[0182] (1) Main efficacy indicators

[0183] ① Visual Analog Scale (VAS) for pain: Before treatment, and on the 3rd, 7th, and 14th days after treatment, patients were asked to rate their pain on a visual analog scale of 0-10 based on their own pain perception, with 0 indicating no pain and 10 indicating severe pain.

[0184] ② Joint swelling degree: Use a soft ruler to measure the circumference of the affected joints before treatment and on the 3rd, 7th and 14th day after treatment, and record the changes in the degree of joint swelling.

[0185] (2) Secondary efficacy indicators

[0186] ① Joint mobility: The range of motion of the affected joints was measured using a protractor before treatment, on the 7th day, and on the 14th day after treatment, and the changes in joint mobility were recorded.

[0187] ② Serum uric acid level: Fasting venous blood was collected from patients before treatment and on the 7th and 14th days after treatment to detect serum uric acid levels.

[0188] ③Inflammatory indicators: Fasting venous blood was collected from patients before treatment and on the 7th and 14th days after treatment to detect serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels.

[0189] (3) Safety indicators

[0190] ①During the treatment, regularly check the patient's blood routine, urine routine, liver and kidney function, etc. to observe whether there are any abnormal changes.

[0191] ② Observe and record whether the patient has any adverse reactions such as allergies, redness, swelling, itching, blisters, etc. on the local skin during treatment, as well as any adverse reactions such as nausea, vomiting, diarrhea, headache, dizziness, etc. on the whole body.

[0192] 5. Efficacy criteria

[0193] (1) Clinical cure:

[0194] Joint pain and swelling completely disappeared, and joint range of motion returned to normal.

[0195] Serum uric acid levels dropped to the normal range (<420 μmol / L in men and <360 μmol / L in women).

[0196] Inflammatory markers (CRP, ESR) returned to normal.

[0197] (2) Significant effect:

[0198] Joint pain was significantly relieved, VAS score decreased by ≥70%, swelling was significantly reduced, and joint range of motion was significantly improved.

[0199] The serum uric acid level decreased by ≥30% compared with before treatment.

[0200] Inflammatory indicators (CRP, ESR) decreased by ≥50% compared with before treatment.

[0201] (3) Effective

[0202] Joint pain was relieved, VAS score decreased by ≥30% but <70%, swelling was reduced, and joint range of motion was improved.

[0203] The serum uric acid level decreased by ≥20% but <30% compared with before treatment.

[0204] Inflammatory markers (CRP, ESR) decreased by ≥30% but <50% compared with before treatment.

[0205] (4) Invalid

[0206] There was no significant improvement in joint pain, swelling, and range of motion, and the VAS score decreased by <30%.

[0207] The serum uric acid level decreased by <20% compared with that before treatment.

[0208] Inflammatory indicators (CRP, ESR) decreased by <30% compared with before treatment.

[0209] 6. Results

[0210] Grouping Number of cases Clinical cure (cases) Significantly effective (example) Valid (Example) Invalid (Example) Cure rate (%) Effectiveness (%) Example 3 50 15 20 12 3 30.00 94.00 Comparative Example 3 50 10 12 21 7 20.00 86.00 Comparative Example 4 50 11 11 18 10 22.00 80.00 Comparative Example 5 50 9 13 16 12 18.00 76.00 Comparative Example 6 50 10 15 14 11 20.00 78.00 Positive control group 50 7 8 22 13 14.00 74.00 Placebo group 50 0 0 12 38 0.00 24.00

[0211] It can be seen from the above results that compared with the control group and the placebo group, both the embodiments and the comparative examples have certain effects in treating gouty arthritis, among which the therapeutic effect of Example 3 is the most outstanding.

[0212] Compared with Example 3, the present invention uses microencapsulation technology to prepare anti-inflammatory regulating microcapsule powders by anti-inflammatory regulating modulators, so that the drug components exist in the form of microcapsules, which can achieve targeted drug delivery, so that the drug can reach the inflammatory site of gouty arthritis more accurately, improve the concentration and action efficiency of the drug in the lesion site, and control the release rate and release time of the drug. After being applied to the skin, the drug in the microcapsule powder can be continuously and stably released, maintaining an effective drug concentration, prolonging the action time of the drug, thereby achieving a lasting therapeutic effect; the active ingredients in the anti-inflammatory regulating microcapsule powder can inhibit the activation of inflammatory cells and the release of inflammatory mediators, reduce inflammatory reactions, and act on the nerve endings of the skin at the same time, stimulate nerve conduction, release neurotransmitters such as endorphins, produce analgesic effects, and reduce the patient's pain perception.

[0213] Embodiment 3 is compared with comparative example 4, and the drug medium made of azone, menthol and borneol of the present invention can cooperate with each other, improve the transdermal absorption efficiency of the drug, enable the therapeutic ingredients in the patch medicine to enter the joint tissue faster and more, thereby enhancing the therapeutic effect of the drug, better play the effects of anti-inflammatory, analgesic, detumescence, etc., and can promote the dissolution of urate in the drug, reduce the deposition of urate in the joint, thereby relieving the symptoms of gouty arthritis; menthol and borneol have the effects of cooling and relieving, can quickly play the effects of local cooling and soothing, reduce the pain and burning sensation in the joint part, and provide instant symptom relief for the patient; can increase the blood circulation of the joint part. Better blood circulation helps to take away inflammatory mediators and metabolic waste, while accelerating the delivery and metabolism of drugs, promoting the disappearance of inflammation and the repair of tissues.

[0214] Compared with Example 5, Example 3 shows that the preparation method of the drug of the present invention is carried out in steps. S1 and S2 extract the active ingredients of the main drug, and S3 adopts the method of supercritical CO2 extraction after crushing to completely retain and extract the active ingredients, thereby improving the quality and efficacy of the drug; the extract after supercritical extraction is subjected to water extraction (step S4) to further extract the water-soluble active ingredients therein to ensure the comprehensive efficacy of the drug; during the entire preparation process, a variety of extraction methods and sophisticated processing techniques are used to ensure that the active ingredients in the drug exist in an appropriate form, which is beneficial for the drug to penetrate the skin into the lesion site.

[0215] Compared with Example 6, Example 3, S7 stirs and mixes the drug and the drug medium under pulse pneumatic stirring. Pulse pneumatic stirring can make the mixture between the drug and the medium more uniform and delicate. The pulse action of the gas helps to break the agglomeration phenomenon during the mixing process, making the drug dispersed more uniformly in the medium, and improving the quality stability and use effect of the patch drug; nitrogen is used as the gas for pulse pneumatic stirring. Nitrogen is an inert gas and will not react with the drug ingredients during the stirring process, ensuring the stability of the drug. And the optimized stirring parameters help to form a patch drug with excellent performance, improve the transdermal absorption efficiency and bioavailability of the drug, and enhance the therapeutic effect.

[0216] Typical Case 1

[0217] 1. Patient information: Mr. Zhang, 68 years old, retired teacher, medical history: long-term history of gout, intermittent pain in multiple joints, blood uric acid level fluctuates between 480-580μmol / L, and was recently admitted to the hospital due to worsening swelling and pain in both ankles and knees for 2 days.

[0218] 2. Diagnosis:

[0219] Western medicine diagnosis: chronic gouty arthritis.

[0220] Traditional Chinese Medicine diagnosis: Arthralgia (rheumatic heat arthralgia).

[0221] 3 Treatment options:

[0222] Patch medicine: the patch medicine of Example 3 of the present invention.

[0223] Application site: Apply the medicine to the joint of the patient.

[0224] Dosing frequency: Change the medication patch every 12 hours.

[0225] 4. Treatment Effects:

[0226] After 7 consecutive days of treatment, Mr. Zhang's symptoms of redness, swelling, heat and pain in both ankles and knees were significantly relieved, his blood uric acid was controlled at <300μmol / L, his pain score was 0, and he was discharged from the hospital on the 7th day.

[0227] Follow-up showed that the patient's symptoms remained stable without recurrence.

[0228] Typical Case 2

[0229] 1. Patient information: Ms. Li, age 45, medical history: gouty arthritis for 3 years. Recently, she came to the hospital for treatment due to sudden redness, swelling and pain in the first metatarsal toe of her left foot for 1 day.

[0230] 2. Diagnosis:

[0231] Western medicine diagnosis: acute attack of gouty arthritis.

[0232] TCM diagnosis: Bi disease (obstruction of dampness and heat).

[0233] 3. Treatment options:

[0234] Patch medicine: the patch medicine of Example 3 of the present invention.

[0235] Application site: Apply the drug to the patient's first metatarsophalangeal joint.

[0236] Dosing frequency: Change the medication patch every 12 hours.

[0237] Treatment effect: After three consecutive days of treatment, Ms. Li's symptoms of redness, swelling, heat and pain in the first metatarsal toe of her left foot were significantly relieved, and she was able to walk normally.

[0238] Recheck of blood uric acid returned to normal range and the symptoms did not recur.

[0239] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A patch medicine for treating gouty arthritis, characterized in that: The invention comprises a drug medium, a drug and a drug-carrying fiber layer; the raw materials of the drug, measured by weight, include: 25-35 parts of rhubarb, 15-25 parts of coptis root, 15-25 parts of scutellaria baicalensis, 15-25 parts of gardenia, 25-35 parts of phellodendron, 25-35 parts of processed arisaema, 53-68 parts of angelica dahurica, 55-69 parts of trichosanthes root, 28-35 parts of liquorice, 26-33 parts of fried atractylodes lancea with bran, 12-25 parts of pearl powder, 18-25 parts of aspleniaceae, and 3-8 parts of callicarpa nudiflora. , 6-12 parts of Acer truncatum, 3-9 parts of Polygonum hydropiper, 25-33 parts of anti-inflammatory regulating microcapsule powder, and 3-8 parts of bamboo salt; the anti-inflammatory regulating microcapsule powder is specifically prepared by diluting the anti-inflammatory regulator with anhydrous ethanol to a concentration of 70-90%, mixing with the emulsifier in a volume ratio of 1:1-5, homogenizing at a speed of 8000-12000 rpm for 3-5 minutes to obtain an anti-inflammatory emulsion, degassing under vacuum conditions for 2-5 minutes, and spray drying to obtain the anti-inflammatory regulating microcapsule powder; The anti-inflammatory regulator is caryophyllene, gingerol A, and humulene in a volume ratio of (22-30):(18-35):(6-15); the emulsifier is prepared by mixing the wall material with deionized water at a mass volume ratio of 3-5:15 g / mL, and stirring and dissolving at 1000-5000 rpm, and the wall material is selected from any one or a combination of modified starch, gum arabic, β-cyclodextrin, and maltodextrin; The drug medium is selected from azone, menthol and borneol in a mass ratio of (3.5-5.5):(10.2-22.5):(23.1-30.5) to prepare nanoparticles with a particle size of less than 10 nm; The preparation method of the patch medicine comprises the following steps: S1, according to the formula, rhubarb, coptis root, phellodendron, scutellaria, gardenia, arisaema, angelica dahurica, radix trichosanthis, bran fried atractylodes are mixed, ground to a fineness of 40-60 mesh, add 12-14 times the volume of ethanol with a mass concentration of 40-60% to the mixture, soak for 30-40min, then reflux and extract for 1-3h, continue reflux extraction 2-4 times, combine the extracts and concentrate to obtain filtrate I; S2, take the above extracted medicinal residue and continue to add 8-10 times the volume of 40-60% ethanol, ultrasonically extract for 20-30 minutes at an ultrasonic frequency of 20-50kHz, an ultrasonic power of 300-500W, and a temperature of 40-50°C, and filter to obtain filtrate II; S3, grind Callicarpa nudiflora, Acer truncatum, Polygonum hydropiper, Aspleniaceae, and Glycyrrhiza uralensis, mix and grind, pass through a 100-120 mesh sieve, perform CO2 supercritical extraction, extraction pressure 27-37 MPa, extraction temperature 30-60° C., extraction time 1.0-1.5 h, collect volatile oil and extract respectively; S4, adding 6-10 times the mass of water to the extract for water extraction, the extraction temperature is 80-90°C, the extraction time is 1-2h, the water extraction is performed 1-3 times, and the extracts are combined to obtain filtrate III; S5, take pearl powder, anti-inflammatory regulating microcapsule powder, and bamboo salt, dry them, and grind them to a fineness of 80-120 mesh, and set aside; S6, the filtrates I, II and III are mixed and stirred, volatile oil is added while stirring, and the mixture is concentrated under reduced pressure to a relative density of 1.18-1.22, and ground pearl powder, anti-inflammatory regulating microcapsule powder and bamboo salt are added in sequence and stirred to obtain the medicine; S7. Stir and mix the drug and drug medium with a mass ratio of 5-10:1 under pulse pneumatic conditions, the gas is nitrogen, the pulse frequency is 0.1-10Hz, the pulse width is 100-500ms, the gas pressure is 0.1-1MPa, the gas flow rate is 1-3L / min, the stirring rate is 600-1000rpm, the stirring time is 4-8h, and the mixture is dried and coated on the drug-loaded fiber layer to obtain a patch drug.

2. A patch medicine for treating gouty arthritis according to claim 1, characterized in that: The raw materials of the medicine are measured by weight and include: 30 parts of rhubarb, 20 parts of coptis root, 20 parts of scutellaria, 20 parts of gardenia, 30 parts of phellodendron, 30 parts of processed arisaema, 60 parts of angelica dahurica, 60 parts of trichosanthes, 30 parts of liquorice, 30 parts of stir-fried atractylodes, 20 parts of pearl powder, 22 parts of aspleniaceae, 5 parts of callicarpa nudiflora, 10 parts of scutellaria baicalensis, 7 parts of polygonum hydropiper, 28 parts of anti-inflammatory regulating microcapsule powder, and 5 parts of bamboo salt.

3. The patch medicine for treating gouty arthritis according to claim 1, characterized in that: The modified starch is selected from octenyl succinate starch.

4. The patch medicine for treating gouty arthritis according to claim 1, characterized in that: The drug-loaded fiber layer is obtained by adsorbing tourmaline powder on a drug-loaded fiber membrane through electrostatic adsorption, pressing and cutting. The particle size of the tourmaline powder is 1-100 μm, the electrostatic adsorption voltage is 5-30 kV, the current is 8-20 μA, the temperature is 30-50° C., and the humidity is 30-60%.

5. A patch medicine for treating gouty arthritis as claimed in claim 4, characterized in that: The drug-loaded fiber membranes include chitosan drug-loaded fiber membranes, collagen drug-loaded fiber membranes, polylactic acid drug-loaded fiber membranes, polyglycolic acid drug-loaded fiber membranes, polyvinyl alcohol drug-loaded fiber membranes, and silk fibroin drug-loaded fiber membranes.

6. Use of the patch medicine for treating gouty arthritis according to any one of claims 1 to 5 in the preparation of a medicine for preventing the recurrence of gouty arthritis.

7. The use according to claim 6, characterized in that: The application of the patch medicine in the preparation of a medicine for reducing inflammation indicators in patients with acute or / and chronic gouty arthritis.

8. The use according to claim 7, characterized in that: The application of the patch medicine in the preparation of medicine for reducing C-reactive protein and erythrocyte sedimentation rate in patients with acute or / and chronic gouty arthritis.

Images