Targeted drug introduction gouty arthritis treatment patch

Abstract

The present application relates to the technical field of traditional Chinese medicine, and relates to a targeted drug introduction treatment paste for treating Gouty Arthritis, and also relates to a preparation method of the treatment paste and application thereof. The targeted drug introduction treatment paste for treating Gouty Arthritis is prepared from the following components in parts: Radix Rehmanniae 15-30 parts, Radix Sophorae 15-30 parts, Radix Angelicae Pubescentis 15-30 parts, Radix Hedysari 15-30 parts, Ramulus Cinnamomi 15-30 parts, Herba Epimedii 30-60 parts, Radix Saposhnikoviae 10-20 parts, Radix Clematidis 15-30 parts, Radix Paeoniae Alba 15-30 parts, Radix Curculiginis 15-30 parts, Radix Cibotii 15-30 parts, Radix Pyrolae 15-30 parts, Carthami Flos 10-20 parts, Radix Angelicae Dahuricae 10-20 parts, and Borneolum Syntheticum 3-6 parts. The targeted drug introduction treatment paste for treating Gouty Arthritis further comprises a transdermal penetration enhancer, and the transdermal penetration enhancer is a combination of 1,2-propanediol, oleic acid and laurocapram (AGone). The treatment paste is combined with intelligent targeted drug treatment technology, so that the drug can directly reach deep lesions, reduce drug toxicity and side effects, maintain a high drug concentration at the lesion site, reduce the frequency of drug administration, improve the curative effect, shorten the treatment course, and greatly improve patient compliance.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, in particular to a targeted drug introduction treatment patch for treating arthritis, and also to the composition, treatment principle, preparation method and application of the treatment patch. Background Art

[0002] Wangbi (Wangbi) develops slowly and lingers repeatedly, often due to recurrent attacks of wind, cold, and dampness. Initially, symptoms include symmetrical pain and swelling in the small joints, often affecting the knuckles or back, morning stiffness, and difficulty moving. With prolonged illness, affected joints develop spindle-shaped swelling, tenderness that resists pressure, and pain during movement. In later stages, joints become deformed and stiff, and surrounding muscles atrophy. The tongue is pale and puffy, with a white coating that disappears, and a deep, weak pulse. Blood tests may test positive for rheumatoid factor, and the erythrocyte sedimentation rate may be elevated during attacks. X-rays may reveal osteoporosis.

[0003] This disease belongs to rheumatoid arthritis in Western medicine. Chinese medicine diagnosis includes wind-cold-dampness obstruction, rheumatic heat stagnation, phlegm and blood stasis, kidney deficiency and cold stagnation, liver and kidney yin deficiency, qi and blood deficiency and other syndromes. However, the syndromes are often complicated.

[0004] Etiology and pathogenesis: 1. Deficiency of vital energy. Deficiency of vital energy is the intrinsic factor and foundation of Bi disease. A weak constitution, loose pores, and a weakened defense system create conditions for the invasion of pathogenic factors. Therefore, the Treatise on the Origin and Symptoms of Various Diseases, Wind Diseases, and Rheumatism, states: "Due to deficiency of blood and qi, wind and rheumatism are caused." The Jisheng Fang, Bi, also states: "All of this is caused by a weak constitution, loose pores, and exposure to wind, cold, and dampness, leading to Bi." Insufficient vital energy is unable to expel pathogenic factors, allowing pathogenic factors to linger and the disease persists. 2. Invasion of exogenous pathogens. Exogenous pathogens are divided into two categories: wind, cold, and dampness, and wind, rheumatism, and heat. Exogenous wind, cold, and dampness are often caused by living in damp environments, wading through water and rain, sleeping in the wind, exposure to fog and dew, climate change, or alternating hot and cold weather, allowing wind, cold, and dampness to invade the body. As the Suwen Bi Lun states, "Wind, cold, and dampness, three elements, mixed together, combine to form Bi." Exposure to wind, rheumatism, and heat can result from working in a hot and humid environment, allowing the wind, rheumatism, and heat to invade. It can also occur when a person has a yang-heat constitution and yin-deficiency, which leads to internal heat, is further affected by wind, cold, and dampness, which transform into heat. Alternatively, the long-term accumulation of wind, cold, and dampness can transform into heat, leading to the development of wind, rheumatism, and heat.

[0005] Wind, cold, dampness, and heat often work together to cause illness. Wind, a yang pathogen, opens the pores and possesses penetrating power, allowing cold to invade internally. Wind, in turn, exploits the accumulation of cold to attach to the affected area, forming the basis for harm and illness. Dampness exploits the dispersing power of wind and the contracting power of cold to invade the bones, muscles, and tendons. Wind and cold, in turn, exploit the properties of dampness to cling to and become firmly lodged in the limbs. Both wind and heat are yang pathogens. When wind prevails, it transforms into heat, and when heat prevails, it generates wind. These two forces work in tandem: opening the pores allows dampness to enter, while dampness, in turn, prevents it from dissolving.

[0006] The fundamental pathogenesis of this disease is that wind, cold, dampness, and heat pathogens infect muscles, tendons, bones, and joints, causing obstruction of the meridians, poor circulation of qi and blood, and stiffness and malnutrition of the tendons and veins. However, each of these pathogens has its own specific focus. Severe wind pathogens can cause wandering lesions; severe cold pathogens can suppress yang qi and cause severe pain; severe dampness pathogens can cause clinging and solidifying lesions; and severe heat pathogens can burn yin fluids, causing heat, pain, and redness and swelling.

[0007] If arthritis does not heal over time, the pathological changes caused by poor circulation of qi, blood, and body fluids become increasingly serious, blood vessels become blocked, body fluids coagulate, phlegm and blood stasis form, meridians are blocked, and the disease penetrates deep into the bones and joints, resulting in skin ecchymosis, joint swelling and deformity, and even penetrates deep into the internal organs, resulting in symptoms of organ arthritis.

[0008] The initial illness is serious, but long-term illness will inevitably damage the vital energy and cause a mixture of deficiency and excess, accompanied by symptoms of qi and blood deficiency, and liver and kidney insufficiency.

[0009] Treatment Principles: This disease is caused by pathogenic qi obstructing the meridians, leading to poor circulation of qi and blood. Therefore, the principles of treatment are to dispel pathogenic qi, activate the meridians, and relieve pain. Because of the presence of mixed pathogenic qi, treatments such as dispelling wind, dispersing cold, removing dampness, clearing heat, removing phlegm, and removing blood stasis and unblocking the meridians should be considered in tandem. Because some pathogenic qi may be dominant, each has its own focus. Insufficient vital energy is a key cause of this disease. Long-term illness depletes vital energy, leading to a mixture of deficiency and excess. Strengthening vital energy and dispelling pathogenic qi is crucial, and strengthening vital energy helps eliminate pathogenic qi. For those with a preponderance of wind pathogens or those whose chronic illness has invaded the meridians, blood-nourishing herbs should be used as adjuvants. As the saying goes, "To treat wind, first treat the blood; once the blood circulates, the wind will naturally dissipate." For those with a preponderance of cold pathogens, herbs that support yang should be used to boost yang qi, thereby dispersing the cold and unblocking the meridians. For those with a preponderance of dampness pathogens, herbs that strengthen the spleen and replenish qi should be used to strengthen the spleen and overcome dampness. For those with a preponderance of heat pathogens, herbs that cool the blood and nourish yin should be used as adjuvants to prevent the heat from burning the yin meridians and causing a more severe and difficult-to-treat condition. Invigorating Qi and nourishing blood, and nourishing the liver and kidneys are important treatments for deficiency syndromes and stubborn arthritis.

[0010] Intelligent targeted drug delivery technology utilizes a comprehensive drug delivery device to achieve targeted drug delivery. This innovative treatment approach leverages advanced transdermal drug delivery technologies, including ultrasound transduction, ion permeation, targeted therapy, and intelligent control, to achieve optimal drug delivery. By integrating multiple technological innovations, including physical, chemical, and biological approaches, it has taken transdermal drug delivery to a new level. Intelligent targeted drug delivery technology precisely delivers drugs through the skin to the lesion site, achieving a depth of up to 8-12 cm, safely and efficiently.

[0011] Ultrasonic conduction targeted drug penetration therapy delivers traditional Chinese medicine directly to the affected area, significantly improving drug absorption and, consequently, therapeutic efficacy. Furthermore, since minimal drug enters the bloodstream, it prevents liver and kidney damage. Ultrasonic drug penetration therapy delivers effective traditional Chinese medicine compounds through intelligent ultrasonic conduction targeted drug penetration therapy, increasing drug permeability and achieving better therapeutic results.

[0012] Currently, most drugs for treating eczema on the market have side effects such as gastrointestinal adverse reactions, cardiotoxicity and neurotoxicity. The preparation of the present invention combined with intelligent drug delivery technology can not only improve the efficacy and safety, but also avoid the adverse reactions of traditional treatment methods.

[0013] There is no formula for the Wanbi treatment patch of the present invention in the prior art, nor is there any report on the combination of the treatment patch and intelligent targeted drug penetration treatment technology for the treatment of common chronic diseases such as Wanbi. Summary of the Invention

[0014] There are some drugs for treating Wangbi on the market. Most Western medicines only treat the symptoms and not the root cause, with poor efficacy. Long-term use will cause certain damage to liver and kidney function and digestive system. Most Chinese herbal compound prescriptions have poor efficacy and often cause side effects such as gastrointestinal reactions, heart and neurotoxicity.

[0015] To overcome the shortcomings of the existing technology, the present invention provides an ultrasound-targeted drug delivery patch for treating Wengbi. This patch combines a traditional Chinese medicine compound Wengbi patch with intelligent targeted drug delivery technology, offering definite efficacy with minimal side effects. It has the advantages of good clinical efficacy, a short treatment cycle, and the ability to be mass-produced.

[0016] To achieve the present invention, the present invention adopts the following technical solutions:

[0017] A targeted drug introduction patch for treating wanbi is prepared from the following raw materials: raw rehmannia root, radix polygoni multiflori, radix angelicae pubescens, rhizoma drynariae, cassia twig, epimedium, radix siler, radix clematis, thorn of honeysuckle, cibotium barometz, herba striatae, safflower, angelica dahurica, and borneol.

[0018] The weight proportions of the raw materials are as follows: 15-30 parts of Radix Rehmanniae, 15-30 parts of Radix Dipsaci, 15-30 parts of Radix Angelicae Pubescentis, 15-30 parts of Rhizoma Drynariae, 15-30 parts of Rhizoma Cinnamomi, 30-60 parts of Rhizoma Epimedii, 10-20 parts of Radix Saposhnikoviae, 15-30 parts of Radix Clematidis, 15-30 parts of Spina Gleditsiae, 15-30 parts of Cibotium Dogii, 15-30 parts of Herba Lycopodii, 15-30 parts of Carthamus Tinctorius, 10-20 parts of Radix Angelicae Dahuricae, 3-6 parts of Borneolum Syntheticum;

[0019] Furthermore, the weight proportions of the raw materials are as follows: 15-20 parts of Radix Rehmanniae, 15-20 parts of Radix Dipsaci, 15-20 parts of Radix Angelicae Pubescentis, 15-20 parts of Rhizoma Drynariae, 15-20 parts of Cinnamomum cassia, 30-40 parts of Epimedium, 10-15 parts of Saposhnikovia divaricata, 15-20 parts of Radix Clematidis, 15-20 parts of Spina Gleditsiae, 15-20 parts of Cibotium barometz, 15-20 parts of Herba Lycopodii, 15-20 parts of Carthamus tinctorius, 10-15 parts of Angelica dahurica, 3-5 parts of Borneolum;

[0020] Furthermore, the weight proportions of the raw materials are as follows: 15 parts of Rehmannia root, 15 parts of Dipsacus root, 15 parts of Angelica dahurica, 15 parts of Drynaria rhizome, 15 parts of Cinnamomum cassia twig, 30 parts of Epimedium, 10 parts of Saposhnikovia divaricata, 15 parts of Clemati radix, 15 parts of Gleditsia chinensis, 15 parts of Cibotium barometz, 15 parts of Lycopodiella cuneata, 15 parts of Semen Armeniacae Atractylodes, 10 parts of Carthamus tinctorius, 10 parts of Angelica dahurica, and 3 parts of Borneolum.

[0021] Or the weight proportions of the raw materials are: 20 parts of Radix Rehmanniae, 20 parts of Radix Dipsaci, 20 parts of Radix Angelicae Pubescentis, 20 parts of Rhizoma Drynariae, 20 parts of Cinnamomum cassiae, 40 parts of Epimedium, 15 parts of Saposhnikovia divaricata, 20 parts of Radix Clematidis, 20 parts of Spina Gleditsiae, 20 parts of Cibotium barometz, 20 parts of Herba Lycopodii, 15 parts of Safflower, 15 parts of Angelica dahurica, 5 parts of Borneolum Synonyms.

[0022] The solution is as follows:

[0023] Rehmannia root, sweet, bitter, and cold in flavor, has the effects of clearing heat, promoting fluid production, nourishing yin, and blood. It can also tonify the kidneys and guide fire back to the source. The Shennong's Herbal Classic states: "It treats fractures and broken tendons; internal injuries; dispels blood stasis; replenishes bone marrow; strengthens muscles; and when made into a soup, it dispels accumulation of cold and heat and eliminates numbness." The Mingyi Bielu states that it enters the heart, liver, and kidney meridians.

[0024] Dipsacus root is warm in nature, bitter, sweet, and pungent. Its primary functions are to nourish the liver and kidneys, strengthen the tendons and bones, and treat rheumatic pain, joint pain, and difficulty flexing and extending. The Shennong's Herbal Classic states that it "replenishes deficiencies, treats wounds, carbuncles, fractures, and heals tendons and bones." The Jingyue Complete Works states that its bitter and heavy flavor allows it to enter the bloodstream, regulate blood circulation, reduce swelling and poison, treat breast abscesses, scrofula, hemorrhoids, fistulas, treat injuries from metal wounds and falls, and heal tendons and bones."

[0025] Duhuo, with its warm nature and bitter taste, has the effects of dispelling wind and dampness, relieving numbness and relieving pain. It is commonly used to treat wind-cold-dampness arthritis, as well as cold pain in the waist and knees. Duhuo is active and good at treating pain in the lower body. "Ming Yi Bie Lu" says: "It can cure all kinds of wind-induced gout and all kinds of joint pain, regardless of whether it is new or long-standing."

[0026] Drynaria fortunei is bitter and warm in nature. Its bitter and warm properties enter the kidneys, promoting blood circulation, healing wounds, and strengthening the kidneys and bones. Its main component, dihydroflavonoid glycosides, have sedative and analgesic effects. "Compendium of Materia Medica" states: "It has a bitter taste and warm properties. It is non-toxic. It nourishes broken bones and joints, and treats pain caused by wind and blood accumulation."

[0027] Cinnamon twig is pungent, sweet, and warming. It enters the heart, lung, and bladder meridians. It warms the meridians, dredges blood vessels, dispels cold, and relieves pain. "Ming Yi Bie Lu" states: "It is non-toxic. It warms the tendons and dredges the meridians." "Compendium of Materia Medica" states: "It can relax muscles and dispel wind pathogens."

[0028] Epimedium is pungent, sweet, and warm in nature, and enters the liver and kidney meridians. It nourishes the kidneys and strengthens yang, dispels wind and dampness, and is used to treat wind-cold-damp arthritis or numbness of the limbs. "Ming Yi Bie Lu" states: "It strengthens tendons and bones and eliminates scrofula." "Compendium of Materia Medica" states: "Epimedium has a sweet and fragrant flavor, is warm without being cold, and can nourish essence and qi. It is a medicine for the hand and foot yangming meridians, triple energizer, and life gate. It is suitable for those with true yang deficiency." "Jing Yue Quan Shu" states: "It nourishes essence and qi, strengthens the will, and strengthens tendons and bones."

[0029] Saposhnikovia root is pungent, sweet, and slightly warm. It enters the bladder, liver, and spleen meridians. It has the effects of dispelling wind, relieving dampness, and alleviating pain. The "Shennong Bencao Jing" states: "It mainly treats severe wind, wind spreading throughout the body, numbness in the bones and joints, and fullness and irritability." The "Bencao Mengquan" states: "It treats all pains throughout the body and is a moisturizing agent among wind-clearing herbs. It is generally used to treat wind and dispel dampness." The "Jingyue Quanshu" states: "It is used to calm and dispel wind. Although it is a medicine for the bladder, spleen, and stomach meridians, it is a medicine for all meridians and affects all meridians. Its light aroma and flavor dispel wind evil, treat pains throughout the body, cure wind-induced eye problems, and stop cold tears. Wind can overcome dampness, so it also dispels dampness and eliminates dampness all over the body.

[0030] Clematidis is pungent, salty, and warm. It enters the Bladder Meridian. It has the effects of dispelling rheumatism, unblocking the meridians, and relieving pain. According to the "Pharmaceutical Chemical Meaning," it "opens the twelve meridians. It is primarily used to treat gout caused by wind, dampness, and phlegm stagnation in the meridians, resulting in gout, joint pain, swelling, or numbness."

[0031] The thorns of the honeysuckle tree are pungent and warm in nature. They can reduce swelling, expel toxins, and expel pus. "Compendium of Materia Medica Chongyuan" states: "It dispels wind and resolves phlegm, eliminates toxins, and attacks poisons."

[0032] Gou Ji (Dog spine) enters the liver and kidney meridians and can dispel rheumatism, nourish the liver and kidneys, and strengthen the waist and knees. It is very effective for lower back pain and stiff spine caused by liver and kidney deficiency, combined with wind, cold, and dampness, as well as rheumatic arthritis. The Shennong Herbal Classic states: "It is mainly used to treat stiff waist and back, slow and urgent joints, and knee pain caused by cold and dampness."

[0033] Slightly bitter, pungent, and warm, it enters the liver, spleen, and kidney meridians. It dispels wind and dampness, relaxes tendons and activates collaterals. It is used for joint pain and difficulty flexing and extending. "Essentials of Herbal Medicine" states: "It reduces swelling and dispels wind and heat. When soaked in wine, it relaxes tendons and activates collaterals. It can treat pain from qi stagnation, injuries, internal injuries from wounds, removes phlegm and relieves coughs, and treats sores and carbuncles on the hands and feet." "Medicinal Properties" states: "It can treat itching caused by blood stasis."

[0034] Safflower, with its pungent and warm flavor, has the effects of promoting blood circulation, removing blood stasis, and relieving pain. It is suitable for treating injuries to the tendons and bones, as well as swelling and pain caused by blood stasis. Compendium of Materia Medica states: "It promotes blood circulation, moisturizes dryness, relieves pain, dissipates swelling, and regulates menstruation."

[0035] Angelica dahurica has the effects of dispelling wind, relieving pain, and reducing swelling and draining pus. It is suitable for sores, carbuncles, swelling, and itching. "Compendium of Materia Medica" states: "It drains pus, promotes tissue regeneration, and relieves pain." "Jingyue Complete Works" states: "Its pungent and fragrant aroma reaches the surface, so it can treat sores, drain pus, relieve itching, and relieve pain."

[0036] Borneol has a bitter and slightly cold taste. It clears heat and relieves pain, and is suitable for sores, ulcers, and swellings. "Compendium of Materia Medica" states: "Its pungent and bitter flavor, its fragrance can penetrate the orifices, internally penetrate the bones to remove wind, disperse pathogenic factors, and externally clear the meridians and expel toxins." "Hui Yue Yi Jing" states: "It treats pain in the limbs." "Yi Fang Kao" states: "Borneol has a pungent and hot flavor with a refreshing fragrance, and can soften tendons."

[0037] These herbs, when combined and decocted, enhance their respective strengths and weaknesses, complementing each other and enhancing their effectiveness. Rehmannia root, Dipsacus root, Drynaria root, Epimedium, and Cibotium barometz nourish the liver and kidneys and strengthen the tendons and bones; Cassia twig, Saposhnikovia root, Angelica dahurica, Angelica dahurica, and Clematis root dispel wind, cold, dampness, and joints, alleviating pain; Herba Lycopodii and Carthamus tinctorius relax the tendons, activate blood circulation, and unclog the meridians; and Sophora flavescens and Borneol dispel toxins, reduce swelling, and relieve pain.

[0038] Furthermore, the targeted drug introduction patch for treating paralysis contains a transdermal penetration enhancer, which is 1,2-propylene glycol, oleic acid, and lauric nitrogen. The total weight of the transdermal penetration enhancer accounts for 8-19% of the total weight of the raw material extract, preferably 18-19%; the weight of each component accounts for the percentage of the total weight of the raw material extract as above: 1,2-propylene glycol 3% to 9%, oleic acid 2% to 8%, lauryl nitrogen Ketone (AGone) 3% to 5%, preferably: 1,2-propylene glycol 5% to 9%, oleic acid 5% to 8%, lauryl nitrogen Ketone (AGone) 5%.

[0039] Furthermore, the targeted drug introduction patch for treating paralysis contains a medical coupling agent, the amount of which is 8-10% of the total extract of the above raw materials.

[0040] The present invention provides a method for preparing the targeted drug introduction patch for treating paralysis, comprising the following steps:

[0041] 1. Mix the above medicinal materials and grind them into powder. Pass them through a 100-mesh sieve to prepare fine powder A of the raw material medicine.

[0042] 2. Pour 5-8 times the weight of raw material drug powder A into yellow rice wine and stir clockwise. Stir thoroughly, then heat and simmer for 10 minutes to obtain solution B. Yellow rice wine dispels cold and dampness, relaxes the meridians and activates blood circulation, and promotes blood circulation. When mixed with traditional Chinese medicine, it improves blood circulation and enhances its efficacy.

[0043] 3. Add 0.2-0.5 times the weight of the fine powder of API A to Solution B and continue decocting with stirring. Honey can nourish the middle part of the body and moisten dryness, and has analgesic and detoxifying effects. Decoction with Chinese herbs enhances their analgesic effects, promotes tissue regeneration, heals sores, and acts as a drug bond.

[0044] 4. After the decoction is completely boiled, the paste is uniform and free of particles, and small bubbles continue to appear on the surface. Turn off the heat and let it stand to obtain Solution C, which is the total extract of the raw materials.

[0045] 5. Add transdermal penetration enhancer to solution C to obtain solution D, stir well and set aside.

[0046] The transdermal penetration enhancer is a combination of 1,2-propylene glycol, oleic acid, and Azone, and the total amount thereof accounts for 8-19% by weight of solution C; the weight ratio of each component in the permeation enhancer combination to solution C is 3% to 9% of 1,2-propylene glycol, 2% to 8% of oleic acid, and lauric nitrogen. Ketone (AGone) 3% to 5%.

[0047] 6. Add the total extract of the raw material fine powder A, which is 8-10% of the medical coupling agent of solution C, to solution D, and stir evenly to obtain solution E, which is the medicinal solution of the Wengbi therapeutic patch.

[0048] The medical coupling agent is a medical ultrasonic coupling agent.

[0049] 7. Spray the liquid of the Wengbi Treatment Patch onto the patch that can load the medicine.

[0050] Furthermore, the present invention provides a method for using the targeted drug introduction Wengbi treatment patch, comprising:

[0051] (1) Use an automatic sprayer to spray the solution E onto the drug-loaded patch to obtain a Wenbi therapeutic patch.

[0052] (2) Use intelligent targeted drug-penetrating treatment equipment to introduce drugs into deep lesions.

[0053] The specific steps include:

[0054] 1) Clean and dry the surface of the treatment area. Choose a relatively flat and non-invasive area close to the lesion.

[0055] 2) Place the Wengbi Treatment Patch in a water-stopping bowl and then fix the patch on the treatment area;

[0056] 3) Tear off the adhesive on the back of the patch and fix the treatment head on the patch;

[0057] 4) Turn on the power switch of the intelligent targeted drug penetration treatment device and press the "Start / Pause" button to start treatment;

[0058] 5) After treatment, press the reset button and remove the patch.

[0059] The targeted drug introduction Wanbi therapeutic patch prepared by the present invention is used to treat rheumatoid arthritis, wind-cold-dampness obstruction, rheumatic heat stagnation, phlegm and blood stasis, kidney deficiency and cold stagnation, liver-kidney yin deficiency, qi and blood deficiency and other syndromes. Good effects can be achieved after 3-5 times for mild symptoms and 10 times for severe symptoms.

[0060] The present invention also provides a targeted drug introduction treatment system, including drugs, drug-loaded patches, and intelligent targeted drug penetration treatment equipment. The intelligent targeted drug penetration treatment equipment exerts its therapeutic effect through electroporation, conductivity, ultrasound, and iontophoresis. Among them, the electroporation pulse consists of six square waves with a duty cycle of 1:1 and a pulse width of 0.2±10%s; the frequency of the conductive wave group is 0.2-4.2Hz; and the output frequency of the ultrasonic wave group is 0.2-4.2Hz.

[0061] In traditional treatments, the toxic side effects of many drugs also cause great harm to the body, especially damage to liver and kidney function. Patients find it difficult to receive long-term treatment and are often forced to stop taking the drugs. In addition, most rheumatic autoimmune diseases require lifelong medication and are prone to recurring attacks. The present invention solves the clinical shortcomings of traditional treatment methods. The intelligent targeted drug penetration treatment technology does not pass through the "first-pass effect" of the liver and the damage to the gastrointestinal tract. The special-effect drugs directly reach deep lesions, reducing drug toxicity and side effects. The effective concentration of drugs at the lesion site is sustained, reducing the number of drug administrations, improving efficacy, shortening the course of treatment, and greatly improving patient compliance. DETAILED DESCRIPTION

[0062] Example 1:

[0063] Rehmannia root 15g, Dipsacus root 15g, Angelica dahurica 15g, Drynaria fortunei 15g, Cinnamon twig 15g, Epimedium 30g, Saposhnikovia divaricata 10g, Clemati radix 15g, Sophora flavescens 15g, Cibotium barometz 15g, Herba Lycopodii 15g, Safflower 10g, Angelica dahurica 10g, Borneol 3g

[0064] Combine the above medicinal ingredients, crush them, and pass through a 100-mesh sieve to obtain a fine powder of the raw material. Add 1000ml of rice wine, grind the fine powder, and stir clockwise. Stir thoroughly, then heat and boil. After boiling for 10 minutes, add 50g of honey and continue boiling, stirring. Once the paste is completely boiled and free of particles, with small bubbles forming on the surface, turn off the heat and let it stand.

[0065] Add a penetration enhancer combination, and the percentage of each component in the filtrate is as follows: 1,2-propylene glycol 9%, oleic acid 5%, lauryl nitrogen Ketone (AGone) 5%, stir well.

[0066] Add 10% medical ultrasonic coupling agent to the above solution, stir well and set aside.

[0067] Use an automatic sprayer to spray the above solution into each drug-loaded patch in an amount of 2 ml each time.

[0068] Example 2: Selection of combined penetration enhancers

[0069] The composition of the transdermal penetration enhancer was varied to determine the effect of different formulations on drug permeation. The results are shown in Table 1.

[0070] The experimental plan was to use a traditional vertical Franz diffusion cell, suckling pig skin for research, and the standard substance was icariin (C 33 H 40 O 15 ). Wash the skin tissue and apply the penetration enhancer formula in Table 1 respectively. After pretreatment for 40 minutes, place it in the middle of a Franz diffusion cell and apply 1.0 g of icariin (the active ingredient in Epimedium) on the stratum corneum. The circulating water temperature is 37±0.5℃ and the magnetic stirring is constant. Take out all the receiving fluid at 30min, 60min, 90min, 120min, 150min and 180min respectively, determine the content by HPLC and calculate the cumulative penetration amount. The chromatographic analysis conditions are as follows: octadecylsilane bonded silica gel as the filler; acetonitrile-water (30:70) as the mobile phase; and the detection wavelength is 207nm. The number of theoretical plates calculated based on the icariin peak should not be less than 1500. The content is calculated by the external standard method.

[0071] Table 1 Effects of different penetration enhancer formulations on drug permeability

[0072] 1,2-Propanediol (%) Oleic acid (%) <![CDATA[ AGone (%)]]> Dimethylformamide (%) 1,8-Cineole (%) Icariin penetration rate (%) 9 5 5 71.8 3 2 3 66.3 5 8 5 73.6 5 5 46.2 9 5 5 54.9 5 5 5 51.7 8 5 5 45.3 5 8 5 50.6

[0073] Each prescription is compared in the table 1, and the drug permeability of the prepared patch of selecting different penetration enhancers to combine is obviously different, when selecting 1, permeability is the highest when 2-propylene glycol, oleic acid, Azone share, and arbitrarily take a kind of and dimethyl formamide, 1 among the three, when 8-cineole is combined, its drug permeability is only 45-55%, and at dimethyl formamide, 1, under the identical situation of 8-cineole, use 1, when 2-propylene glycol and its consumption are increased to 9% by 5%, drug permeability is increased to 54.9% by 51.7%, has only improved 3.2%.As can be seen, 1, 2-propylene glycol and dimethyl formamide, 1, when 8-cineole is used in combination, can not obviously improve the permeability of medicine.

[0074] The combination of 1,2-propylene glycol, oleic acid and Azone significantly improves the drug permeability compared to other penetration enhancer combinations. When AGone is 3% to 5%, the drug penetration rate can reach more than 65%. When 1,2-propylene glycol, oleic acid, and Azone are combined, the total amount can reach 8-19% to achieve a good drug penetration rate. In order to improve the drug penetration rate and improve the drug efficacy, 1,2-propylene glycol 5%, oleic acid 8%, and lauryl nitrogen are selected. A combination of AGone 5% or 1,2-propylene glycol 9%, oleic acid 5%, lauryl nitrogen AGone 5% was used as the best transdermal penetration enhancer.

[0075] Similarly, referring to the above experimental method, the permeation rate of the active ingredients of Saposhnikovia divaricata, 5-O-methylvisamin glycoside, was determined. The results showed that the permeation rate of the active ingredients of Saposhnikovia divaricata, 5-O-methylvisamin glycoside, was determined by adding 3% to 9% of 1,2-propylene glycol, 2% to 8% of oleic acid, and 2% to 8% of lauric acid. When 3% to 5% of AGone was used as a combined penetration enhancer, the drug also showed a good permeability.

[0076] Example 3:

[0077] Rehmannia root 20g, Dipsacus root 20g, Angelica dahurica 20g, Drynaria fortunei 20g, Cinnamon twig 20g, Epimedium 40g, Saposhnikovia divaricata 15g, Clemati 20g, Sophora flavescens 20g, Cibotium barometz 20g, Herba Lycopodii 20g, Safflower 15g, Angelica dahurica 15g, Borneol 5g

[0078] The preparation method is the same as that of Example 1.

[0079] Example 4:

[0080] Rehmannia root 30g, Dipsacus root 30g, Angelica dahurica 30g, Drynaria fortunei 30g, Cinnamon twig 30g, Epimedium 60g, Saposhnikovia divaricata 20g, Clemati 30g, Sophora flavescens 30g, Cibotium barometz 30g, Herba Lycopodii 30g, Safflower 20g, Angelica dahurica 20g, Borneol 6g

[0081] The preparation method is the same as that of Example 1.

[0082] Example 5:

[0083] The drug permeability of icariin in Examples 1, 3, and 4 was determined by referring to the experimental method and determination method of drug permeability in Example 2. The results are shown in Table 2.

[0084] Table 2 Drug permeability of the patches of Examples 1, 3, and 4

[0085] Example 1 3 4 Drug permeability (%) 71.8 70.2 63.9

[0086] Example 6:

[0087] Clinical trials of Examples 1, 3, and 4:

[0088] Experimental plan: 150 patients with epilepsy were included, including 89 male patients and 61 female patients, aged between 35 and 58 years old, with most of them being middle-aged patients. They were randomly assigned into three groups. The three groups were comparable in terms of gender, age and disease course (P>0.05).

[0089] Diagnostic criteria:

[0090] (1) Western medicine diagnostic criteria: refer to the diagnostic criteria of the "Guidelines for the Diagnosis of Rheumatism"

[0091] ① Morning stiffness of joints lasting at least 1 hour and ≥ 6 weeks;

[0092] ②Swelling of three or more joints for ≥6 weeks;

[0093] ③ Swelling of the wrist, metacarpophalangeal, and proximal interphalangeal joints for ≥ 6 weeks;

[0094] ④ Symmetrical joint swelling, ≥ 6 weeks;

[0095] ⑤Subcutaneous nodules;

[0096] ⑥ X-ray changes of the hand (at least soft tissue swelling, osteoporosis and joint space narrowing);

[0097] ⑦ Rheumatoid factor is positive (quantitative titration method is used during detection).

[0098] The diagnosis can be made if 4 of the above 7 items are met.

[0099] (2) The standards for TCM syndrome differentiation (liver and kidney deficiency, blood stasis and collateral obstruction syndrome) refer to the standards of the "Guiding Principles for Clinical Research of New Chinese Medicines".

[0100] Ashi points or acupoints along the meridians were selected on the affected joints of the patients, and the Wengbi treatment patch was applied in combination with an intelligent targeted drug-penetrating treatment device (ultrasonic conductance directional drug-penetrating treatment device GH-UCDP-C01). Treatment was performed once a day, and the efficacy was observed after 8 consecutive weeks of treatment.

[0101] The method of using the targeted drug therapy device is as follows:

[0102] 1) Clean and dry the surface of the treatment area. Choose a relatively flat and non-invasive area close to the lesion.

[0103] 2) Place the Wengbi Treatment Patch in a water-stopping bowl and then fix the patch on the treatment area;

[0104] 3) Tear off the adhesive on the back of the patch and fix the treatment head on the patch;

[0105] 4) Turn on the power switch of the intelligent targeted drug penetration treatment device and press the "Start / Pause" button to start treatment;

[0106] 5) After treatment, press the reset button and remove the patch.

[0107] Criteria for judging the clinical efficacy of TCM Bi syndrome:

[0108] Cure means disappearance of symptoms, normal joint movement, and normal laboratory tests.

[0109] Improvement means that symptoms are significantly improved and laboratory tests have improved.

[0110] Uncured means no improvement in symptoms and laboratory tests.

[0111] The experimental results are shown in Table 3:

[0112] Table 3 Clinical trials of Examples 1, 3, and 4

[0113] Group n cure Improvement Not healed Total effective rate (%) Example 1 50 24 25 1 98.0 Example 3 50 21 27 2 96.0 Example 4 50 23 23 4 92.0

[0114] Example 7:

[0115] Clinical trials:

[0116] 150 patients were randomly divided into treatment group I, treatment group II and control group, with 50 cases in each group. There was no statistically significant difference in gender, age and disease course among the three groups (P>0.05), indicating comparability. Inclusion criteria (1) Western medicine diagnosis was consistent with the definition of knee osteoarthritis in the "Guidelines for the Diagnosis and Treatment of Osteoarthritis (Draft)"; TCM syndrome differentiation diagnosis was based on the criteria in the document "Guidelines for Clinical Research of New Chinese Medicines", with symptoms of recurrent knee pain, resting pain, knee weakness, and worse pain at night, accompanied by low back pain, tinnitus, white fur, dull tongue, and thin and wiry pulse; (2) patients were aware of the content of this study and signed the informed consent form; (3) this study was approved by the hospital ethics committee.

[0117] Treatment group I: The Wengbi therapeutic patch of Example 1 was used alone, once a day, one patch each time, 7 days as a course of treatment, and the therapeutic effect was observed after 8 weeks of treatment.

[0118] Treatment Group II: The Wengbi therapeutic patch of Example 1 was used in combination with an intelligent targeted drug penetration therapeutic device. The intelligent targeted drug penetration therapeutic device (ultrasonic conductance directional drug penetration therapeutic device GH-UCDP-C01) was used to introduce the drug into the lesion site, once a day, each time for 30 minutes, 7 days as a course of treatment, and the efficacy was observed after 8 weeks of treatment.

[0119] The method of using the targeted drug therapy device is as follows:

[0120] 1) Clean and dry the surface of the treatment area. Choose a relatively flat and non-invasive area close to the lesion.

[0121] 2) Place the Wengbi Treatment Patch in a water-stopping bowl and then fix the patch on the treatment area;

[0122] 3) Tear off the adhesive on the back of the patch and fix the treatment head on the patch;

[0123] 4) Turn on the power switch of the fourth-generation intelligent targeted drug-permeation treatment device and press the "Start / Pause" button to start treatment;

[0124] 5) After treatment, press the reset button and remove the patch.

[0125] Control group: give voltaren tablets (Beijing Novartis Co., Ltd., GMP H11021640) conventional treatment, 75mg / time, 1-2 times / d, continuous medication treatment for 8 weeks.

[0126] Observation index and evaluation standard: observe the clinical efficacy, adverse reactions and clinical symptom scores, pain scores, serum inflammatory factor changes of three groups before and after treatment. Before and after treatment, ISOA scoring method was used to observe and evaluate the clinical main symptoms of patients such as joint swelling, joint pain, morning stiffness time and walking ability, and the clinical efficacy was evaluated according to the relevant standards in “Diagnosis and Treatment Criteria of Traditional Chinese Medicine”:

[0127] Basic recovery: 2 total scores decreased by ≥85% compared with treatment;

[0128] Markedly effective: 2 total scores decreased by 60%-84% compared with treatment;

[0129] Effective: 2 total scores decreased by 25%-59% compared with treatment;

[0130] Ineffective: 2 total scores decreased by ≤25% compared with treatment;

[0131] The sum of effective, markedly effective and basic recovery is the total effective.

[0132] At the same time, the levels of CRP and ESR of the two groups were determined by immunoturbidimetry and automatic erythrocyte sedimentation determination instrument method before and after treatment, and the pain degree of patients was evaluated by VAS scale, O and 10 representing no pain and severe pain respectively. The occurrence of systemic and local adverse reactions of the three groups was recorded.

[0133] Statistical processing: the data obtained were processed by SPSS 18.0 statistical software, the measurement data were represented by , t test was used, the count data were represented by rate (%), x 2 test was used, P<0.05 was considered statistically significant.

[0134] Comparison of the efficacy of the three groups: the total effective rate of treatment group I was 92.0%, the total effective rate of treatment group II was 96.0%, and the total effective rate of control group was 62.0%, the difference between groups was statistically significant (P<0.05).

[0135] Comparison of clinical efficacy between treatment group I and control group is shown in table 4 and table 5.

[0136] Comparison of clinical efficacy between treatment group I and treatment group II is shown in table 6.

[0137] Table 4 Comparison of clinical efficacy between treatment group I and control group

[0138] Group basically recovered Significantly effective efficient invalid Total effective rate (%) Control group (n=50) 15 11 5 19 62.0 Treatment group I (n=50) 26 14 6 4 92.0 X 2 values 8.115 P-value ＜0.05

[0139] Table 5 Comparison of clinical indexes before and after treatment between the two groups

[0140] time Group CRP (mg / L) ESR (mm / h) VAS (points) ISOA (points) Before treatment Control group (n=50) 25.74±10.26 37.25±19.47 6.24±1.54 10.58±3.67 Treatment group I (n=50) 25.34±10.57 38.01±19.32 6.35±1.28 10.64±3.78 t-value 0.144 0.147 0.291 0.060 P-value ＞0.05 ＞0.05 ＞0.05 ＞0.05 After treatment Control group (n=50) 17.28±7.49 23.65±14.48 1.92±1.31 5.14±1.98 Treatment group I (n=50) 10.45±6.67 15.64±10.83 0.98±0.67 2.97±1.03 t-value 3.604 2.344 3.381 5.145 P-value ＜0.05 ＜0.05 ＜0.05 ＜0.05

[0141] Table 6 Comparison of clinical efficacy between treatment group I and treatment group II

[0142] Group basically recovered Significantly effective efficient invalid Total effective rate (%) Treatment group I (n=50) 26 14 6 4 92.0 Treatment group II (n=50) 33 10 5 2 96.0 <![CDATA[X 2 Value]]> 3.968 P-value ＜0.05

[0143] Conclusion: Clinical experimental data show that the total clinical efficacy of the targeted drug-introduced Wengbi treatment patch reached over 96%, far exceeding the 62% of the traditional Western medicine treatment group, achieving a breakthrough in the treatment of Wengbi.

Claims

1. Targeted drug introduction for treating paralysis, characterized in that: The product is prepared from the following raw materials: Radix Rehmanniae, Radix Dipsaci, Radix Angelicae Pubescentis, Rhizoma Drynariae, Rhizoma Cinnamomi, Rhizoma Epimedii, Rhizoma Saposhnikoviae, Radix Clematidis, Rhizoma Gleditsiae, Rhizoma Cibotii, Herba Lycopodii, Carthamus Tinctorius, Radix Angelicae Dahuricae, and Borneol; wherein the weight proportions of the raw materials are as follows: 15-30 parts of Radix Rehmanniae, 15-30 parts of Radix Dipsaci, 15-30 parts of Radix Angelicae Pubescentis, 15-30 parts of Rhizoma Drynariae, 15-30 parts of Cinnamomum cassia, 30-60 parts of Epimedium, 10-20 parts of Saposhnikovia divaricata, 15-30 parts of Radix Clematidis, 15-30 parts of Spina Gleditsiae, 15-30 parts of Cibotium barometz, 15-30 parts of Herba Lycopodii, 15-30 parts of Carthamus tinctorius, 10-20 parts of Angelica dahurica, 3-6 parts of Borneolum Syntheticum; It also contains a transdermal penetration enhancer, which is a combination of 1,2-propylene glycol, oleic acid, and laurocaprol; The weight percentages of the components of the transdermal penetration enhancer are as follows: 1,2-propylene glycol 3% to 9%, oleic acid 2% to 8%, and laurocaprol 3% to 5%; The transdermal penetration enhancer accounts for 8-19% of the total weight of the raw material extract; The targeted drug introduction Wanbi treatment patch is prepared by the following method: (1) Roots of Radix Rehmanniae, Radix Dipsaci, Radix Angelicae Pubescentis, Rhizoma Drynariae, Rhizoma Cinnamomi, Rhizoma Epimedii, Radix Saposhnikoviae, Radix Clematidis, Spina Gleditsiae, Rhizoma Cibotii, Herba Lycopodii, Flos Carthami, Radix Angelicae Dahuricae, and Borneol were mixed and ground, and passed through a 100-mesh sieve to prepare a raw material drug fine powder A; (2) adding yellow rice wine (5-8 times the weight of the raw material drug fine powder A) to the fine powder A obtained in step (1) and stirring, stirring evenly, heating and boiling for 10 minutes to obtain solution B; (3) Add honey (0.2-0.5 times the weight of the raw material powder A) to solution B and continue to boil with stirring. After the decoction is completely boiled and the paste is uniform and free of particles, small bubbles continue to appear on the surface. Turn off the heat and let it stand to obtain solution C. (4) adding a transdermal penetration enhancer to solution C to obtain solution D, stirring the solution evenly for later use; (5) Add medical coupling agent to solution D and stir evenly to obtain solution E; (6) Spray the solution E onto the patch that can be loaded with drugs.

2. The targeted drug introduction patch for treating paralysis according to claim 1, wherein: The weight parts of each raw material are: 15-20 parts of Radix Rehmanniae, 15-20 parts of Radix Dipsaci, 15-20 parts of Radix Angelicae Pubescentis, 15-20 parts of Rhizoma Drynariae, 15-20 parts of Cinnamomum cassia twig, 30-40 parts of Epimedium, 10-15 parts of Saposhnikovia divaricata, 15-20 parts of Radix Clematidis, 15-20 parts of Spina Gleditsiae, 15-20 parts of Cibotium barometz, 15-20 parts of Herba Lycopodii, 15-20 parts of Carthamus tinctorius, 10-15 parts of Angelica dahurica, 3-5 parts of Borneolum Syntheticum.

3. The targeted drug introduction patch for treating paralysis according to claim 1, wherein: The medical coupling agent is a medical ultrasonic coupling agent, and the medical coupling agent accounts for 8-10% of solution C.

4. Use of the targeted drug introduction patch for treating rheumatoid arthritis according to any one of claims 1 to 3 in the preparation of a medicament for treating rheumatoid arthritis.

5. The use according to claim 4, characterized in that Intelligent targeted drug-penetrating treatment equipment is used in conjunction with the Wangbi treatment patch.

6. A targeted drug introduction treatment system, comprising the Wengbi treatment patch, the drug-loaded patch, and the intelligent targeted drug-permeation treatment device as described in claim 1, wherein the intelligent targeted drug-permeation treatment device exerts its therapeutic effect through electroporation, conductivity, ultrasound, and iontophoresis, wherein: The electroporation pulse consists of six square waves with a duty cycle of 1:1 and a pulse width of 0.2±10%s; the frequency of the conductive wave group is 0.2-4.2Hz; and the frequency of the ultrasonic wave group output is 0.2-4.2Hz.

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