Traditional Chinese medicine gel preparation for treating paronychia and preparation method thereof

Abstract

The invention belongs to medical preparations characterized by gel, and particularly relates to a traditional Chinese medicine gel preparation for treating paronychia and a preparation method thereof. The traditional Chinese medicine composition disclosed by the invention is an oil-in-water emulsion type traditional Chinese medicine composition which is obtained by extracting formononeflower by adopting a deep eutectic solvent, performing enzymolysis on rhizoma picrorhizae and the like, compounding with beta-cyclodextrin, and treating with polyoxyethylene lauryl ether, has the effects of resisting fungi, relieving swelling and pain and the like, and is relatively good in skin permeation and absorption effect. In the presence of oxalic acid and dimethyl sulfoxide, low-methoxyl pectin from rhubarb petioles and ethyl cinnamate are subjected to an esterification reaction, the obtained product, carbomer and the like are prepared into a gel carrier, and the gel carrier can cooperate with a traditional Chinese medicine composition to play a role. The traditional Chinese medicine gel preparation obtained by the invention has the advantages of relatively great advantages in preparation form, relatively short film forming time, low adhesion, certain tensile strength and uniform overall texture, has relatively high inhibition on various paronychia-related pathogenic bacteria, and is beneficial to fading of red and swollen wounded parts and relieving of pain.

Description

Technical Field

[0001] The invention belongs to a pharmaceutical preparation characterized by gel, and in particular relates to a traditional Chinese medicine gel preparation for treating paronychia and a preparation method thereof. Background Art

[0002] Paronychia is an inflammation of the nail groove tissue on both sides of the nail (toe) caused by bacteria invading the subcutaneous tissue through tiny damage to the skin around the nail due to various factors and multiplying. It is usually manifested as redness, swelling and pain in the affected area, accompanied by inflammatory exudation and hyperplasia of granulation tissue. It is a common surgical disease that often occurs in adolescents. Paronychia can cause patients to be unable to carry out many daily activities, affecting their study, work and life. Clinically, paronychia is divided into 4 stages, namely stage 1 (redness and swelling stage), stage 2 (inflammatory stage), stage 3 (granulation stage) and stage 4 (chronic ingrown toenail paronychia formation stage). Paronychia has the characteristics of high incidence and high recurrence rate. If acute paronychia is not treated in time, it can develop into purulent dactylitis and even cause osteomyelitis of the finger (toe) bones. It can also become chronic paronychia and not heal for a long time. The causes of paronychia usually involve bacterial infection, local injury, improper manicure, low immunity, chemical stimulation and genetic factors. Cleaning staff, chefs, dishwashers, fishmongers and other people who often work for long periods of time in humid environments are also susceptible to paronychia.

[0003] Treatments for paronychia can be divided into non-invasive and invasive treatments. Non-invasive treatments are commonly used for stage 1 and stage 2 paronychia infection, and degree 1 and 2 paronychia of ingrown nail type. The specific methods are as follows: iodine immersion or wet compress, oral or intravenous antibiotics, drainage with levnol gauze, gradient scraping, etc. When paronychia infection becomes more severe, stage 3 and 4 paronychia and refractory paronychia often require invasive treatments. The specific methods of invasive treatments are as follows: complete or partial nail removal, partial nail bed removal, structural reconstruction, laser treatment, etc. Traditional Chinese medicine treatment is a non-invasive treatment, and the specific forms include traditional Chinese medicine rubbing, traditional Chinese medicine external application, traditional Chinese medicine fumigation and washing, and fire needles, bloodletting, acupuncture, etc. Folk treatment remedies include external application of live snails and borneol, external application of verbena and salt, etc. With the development of research methods and preparation of pharmaceuticals, the specific mechanism of action of drugs has gradually become clear, which has put forward higher requirements for the form of pharmaceuticals to achieve stable efficacy, etc. The common dosage forms of Chinese medicine for the treatment of paronychia are pastes or solutions. Pastes are often thick and easily stained with shoes and socks, while solutions consume a lot of energy. Therefore, the preparation of new forms of paronychia medicines has a broad application prospect. Summary of the invention

[0004] Based on the above problems, the present invention provides a Chinese medicine gel preparation for treating paronychia, comprising a Chinese medicine composition and a gel carrier, etc. The Chinese medicine composition is to extract Formononeta flower using a deep eutectic solvent, and to compound picrorhizon and the like with β-cyclodextrin after enzymatic hydrolysis, and to obtain a Chinese medicine composition in the form of an oil-in-water emulsion after polyoxyethylene lauryl ether treatment, and the Chinese medicine composition has the effects of antifungal, detumescence and pus discharge, blood circulation and stasis removal, and better skin penetration and absorption effect. The gel carrier is low methoxy pectin obtained from rhubarb petiole after enzymatic hydrolysis, and low methoxy pectin and ethyl cinnamate undergo esterification reaction in the presence of oxalic acid and dimethyl sulfoxide, and the obtained substance 2 is mixed with carbomer and the like to obtain a gel carrier that not only has good film-forming properties, but also can cooperate with the Chinese medicine composition to exert an antifungal effect. The Chinese medicine gel preparation obtained by the present invention has a great advantage in the form of preparation, short film-forming time, low adhesion, certain tensile strength, uniform overall texture, and can have a high inhibition on a variety of paronychia-related pathogens, which helps to reduce redness and swelling of the affected area and relieve pain.

[0005] The invention provides a traditional Chinese medicine gel preparation for treating paronychia, comprising the following raw materials in parts by mass: 8-12 parts of a traditional Chinese medicine composition, 30-40 parts of a gel carrier, and 1-3 parts of a skin penetration enhancer.

[0006] The preparation method of the Chinese medicine composition is as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1-1.2 to obtain a mixture 1, deionized water was added, the mixture was heated to 60-70°C and stirred continuously until the mixture was evenly dispersed, and the mixture was naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 50-80 mg:1-3 mL, and ultrasonically treated at a power of 250-300 W and a temperature of 50-60°C for 30-60 min, and then centrifuged at a centrifugal force of 7000-8000 g for 10-15 min, and the supernatant was vacuum concentrated to 3-4 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, pass through a 2-mesh sieve and weigh according to the mass ratio of 1-3:1:1-2:2-4 to obtain a mixed powder, add deionized water according to the material-liquid ratio of 1:8-10g / mL, add composite hydrolase, homogenize, heat to 40-50℃ and stir at 200-250rpm for 2-3h, inactivate the enzyme at high temperature, cool naturally to room temperature, and centrifuge at 8000-10000g for 8-12m in, after the end, retain the upper liquid, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 10-15g:30-50mL:1-2mL:5-10mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, continue stirring at 30-40°C and 100-150rpm for 2-4h, and stand at 4°C after the end to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.2-1.5:1:0.3-0.6, and high-speed shear at 1200-1500 rpm for 3-5 minutes at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

[0007] Preferably, the amount of deionized water added in step L1 is 8-10 times the mass of mixture 1, and petals of Formononeta are preferably used.

[0008] Preferably, in step L2, the composite hydrolase is composed of equal weight portions of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000 U / mL, and the amount of the composite hydrolase added is 5-8% of the volume of deionized water.

[0009] The preparation method of the gel carrier is as follows: S1. Dry the petiole of rhubarb and crush it into powder, pass it through a 2-mesh sieve to obtain the rhubarb petiole powder, weigh the rhubarb petiole powder, deionized water and pectinase according to the mass volume ratio of 1g:50-60mL:1-2g, heat it to 40-50℃, stir it at a speed of 150-200rpm for 3-5h, and then kill the enzyme at high temperature to obtain a mixture 4, cool it to room temperature, add a 60% volume fraction ethanol solution, let it stand for 10-15h, and then centrifuge it at a centrifugal force of 4000-5000g for 20-30min, wash the precipitate with deionized water, centrifuge it again and dry it to obtain substance 1; S2. Weigh the substance 1 obtained in step S1, oxalic acid and dimethyl sulfoxide according to the mass volume ratio of 1g:1-1.2g:35-40mL, heat to 120-130°C and maintain for 10-20min to obtain a mixture 5, then add ethyl cinnamate, maintain the heating temperature and stir at a speed of 100-150rpm for 1-1.5h to obtain a mixture 6, add the mixture 6 to an isopropanol solution, stir until uniformly dispersed, let stand for 8-10h, filter after complete precipitation, wash the precipitate with an isopropanol solution, and dry the precipitate at 45-55°C to obtain a substance 2; S3. Weigh carbomer, substance 2 obtained in step S2, ethyl acetate, and anhydrous ethanol according to a mass ratio of 1:2-3:0.8-1.2:10-15, and stir until uniformly dispersed to obtain a gel carrier.

[0010] Preferably, in step S1, the pectinase preferably has an enzyme activity of 500 U / g, and the amount of ethanol solution added is 3-5 times the volume of the mixture 4.

[0011] Preferably, the amount of ethyl cinnamate added in step S2 is 0.1-0.15 times the volume of mixture 5, the volume ratio of mixture 6: isopropanol solution is 1:5-6, and the volume fraction of isopropanol solution is preferably 80%.

[0012] The skin penetration enhancer is selected from one of oleic acid, Tween-80 and N-methylpyrrolidone.

[0013] The present invention also provides a method for preparing a traditional Chinese medicine gel preparation for treating paronychia, and the specific steps are as follows: The Chinese medicine composition, gel carrier and skin penetration enhancer are weighed according to their mass fractions, stirred until uniformly dispersed, and lactic acid is added to adjust the viscosity to 1000-1500 cP to obtain a Chinese medicine gel preparation for treating paronychia.

[0014] The beneficial effects of the present invention are as follows: The invention selects formononete, picrorhizome, turmeric, angelica dahurica and forsythia to prepare a Chinese medicine composition, wherein formononete has high antifungal performance and can inhibit the formation of biofilm of Candida strains, picrorhizome can relieve swelling and pain, turmeric can be used for swelling and pain caused by falls, promoting blood circulation and removing blood stasis, angelica dahurica can reduce swelling and discharge pus, forsythia can reduce swelling and disperse nodules, etc. Specifically, a deep eutectic solvent is used to extract formononete to obtain its effective biologically active ingredients, picrorhizome and the like are enzymatically hydrolyzed and then compounded with beta-cyclodextrin, which is helpful for stabilizing and retaining the active substances of picrorhizome and the like, and after being treated with polyoxyethylene lauryl ether, a Chinese medicine composition in the form of an oil-in-water emulsion is obtained, and this form is helpful for the penetration and absorption of the active substances. At the same time, the present invention prepares a gel carrier, and low-methoxy pectin from rhubarb petioles is obtained after enzymatic extraction. In the presence of oxalic acid and dimethyl sulfoxide, low-methoxy pectin and ethyl cinnamate undergo esterification reaction, and the obtained substance 2 improves the solubility of low-methoxy pectin, etc., and has the antifungal properties of ethyl cinnamate at the same time. After being mixed with carbomer, ethyl acetate, and anhydrous ethanol, the gel carrier finally obtained not only has good film-forming properties, but also can cooperate with the Chinese medicine composition to play an antifungal effect. After lactic acid adjusts the viscosity, the obtained Chinese medicine gel preparation has a short film-forming time, low adhesion, and a certain tensile strength, which can meet certain water vapor penetration, and there will be a certain degree of expansion under a hot and humid environment, and the overall texture is uniform, with a certain transparency, which can meet the naked eye observation of the affected part. At the same time, the Chinese medicine gel preparation of the present invention, compared with paste / solution, has a greater advantage in the form of preparation, can have a higher inhibition on a variety of paronychia-related pathogens, and helps the redness and swelling of the affected part to subside and relieve pain. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings: Figure 1 This is a film-forming effect diagram of the traditional Chinese medicine gel preparation of Example 8; Figure 2 This is a chart evaluating the relief of paronychia. DETAILED DESCRIPTION

[0016] In order to more clearly explain the overall concept of the present application, the following is described in detail in conjunction with the accompanying drawings of the specification by way of embodiment. In the following description, a large number of specific details are provided to provide a more thorough understanding of the present invention. However, it is obvious to those skilled in the art that the present invention can be implemented without one or more of these details. In other examples, in order to avoid confusion with the present invention, some technical features well known in the art are not described.

[0017] Embodiment 1: This embodiment provides a method for preparing a Chinese medicine composition, and the specific steps are as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1 to obtain a mixture 1, deionized water was added in an amount of 8 times the mass of the mixture 1, the mixture was heated to 60°C and stirred continuously until uniformly dispersed, and the mixture was naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower (petals) was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 50 mg:1 mL, and ultrasonically treated at a power of 250 W and a temperature of 50°C for 30 min, and then centrifuged at a centrifugal force of 7000 g for 10 min, and the supernatant was vacuum concentrated to 3 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, pass through a 2-mesh sieve, weigh according to the mass ratio of 1:1:1:2 to obtain a mixed powder, add deionized water according to the material-liquid ratio of 1:8g / mL, add composite hydrolase, the composite hydrolase is composed of equal weight parts of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000U / mL, and the amount of composite hydrolase added is 5% of the volume of deionized water. After homogenization, heat to 40℃ and stir at a speed of 200rpm. Stir for 2 hours, inactivate the enzyme at high temperature, cool naturally to room temperature, centrifuge at 8000g for 8 minutes, retain the upper liquid after centrifugation, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 10g:30mL:1mL:5mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, continue stirring at 30°C and 100rpm for 2 hours, and stand at 4°C after the end to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.2:1:0.3, and high-speed shear at 1200 rpm for 3 minutes at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

[0018] Embodiment 2: This embodiment provides a method for preparing a Chinese medicine composition, and the specific steps are as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1.1 to obtain a mixture 1, deionized water was added in an amount of 9 times the mass of the mixture 1, the mixture was heated to 65°C and stirred continuously until uniformly dispersed, and the mixture was naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower (petals) was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 60 mg:2 mL, and ultrasonically treated at a power of 280 W and a temperature of 55°C for 45 min, and then centrifuged at a centrifugal force of 7600 g for 13 min, and the supernatant was vacuum concentrated to 3.5 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, pass through a 2-mesh sieve and weigh according to the mass ratio of 2:1:1.5:3 to obtain a mixed powder, add deionized water according to the material-liquid ratio of 1:9 g / mL, add composite hydrolase, the composite hydrolase consists of equal parts of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000 U / mL, and the amount of composite hydrolase added is 6% of the volume of deionized water. After homogenization, heat to 45°C and stir at a speed of 220 rpm for 2 hours. .5h, after inactivating the enzyme at high temperature, naturally cool to room temperature, centrifuge at 9000g for 10min, retain the upper liquid after the centrifugation, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 12g:40mL:1.5mL:8mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, continue stirring at 35°C and 120rpm for 3h, and stand at 4°C after the end to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.4:1:0.5, and high-speed shear at 1300 rpm for 4 minutes at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

[0019] Embodiment 3: This embodiment provides a method for preparing a Chinese medicine composition, and the specific steps are as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1.2 to obtain a mixture 1, deionized water was added in an amount of 10 times the mass of the mixture 1, the mixture was heated to 70°C and stirred continuously until uniformly dispersed, and the mixture was naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower (petals) was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 80 mg:3 mL, and ultrasonically treated at a power of 300 W and a temperature of 60°C for 60 min, and then centrifuged at a centrifugal force of 8000 g for 15 min, and the supernatant was vacuum concentrated to 4 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, pass through a 2-mesh sieve and weigh according to the mass ratio of 3:1:2:4 to obtain a mixed powder, add deionized water according to the material-liquid ratio of 1:10 g / mL, add composite hydrolase, the composite hydrolase is composed of equal weight parts of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000 U / mL, and the amount of composite hydrolase added is 8% of the volume of deionized water. After homogenization, heat to 50°C and stir at a speed of 250 rpm. 3h, after inactivating the enzyme at high temperature, naturally cool to room temperature, centrifuge at 10000g for 12min, retain the upper liquid after the centrifugation, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 15g:50mL:2mL:10mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, continue stirring at 40℃ and 150rpm for 4h, and let stand at 4℃ after the end to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.5:1:0.6, and high-speed shear at 1500 rpm for 5 minutes at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

[0020] Embodiment 1: This embodiment provides a method for preparing a Chinese medicine composition, and the specific steps are as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1 to obtain a mixture 1, deionized water was added in an amount of 8 times the mass of the mixture 1, the mixture was heated to 60°C and stirred continuously until uniformly dispersed, and the mixture was naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower (petals) was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 50 mg:1 mL, and ultrasonically treated at a power of 250 W and a temperature of 50°C for 30 min, and then centrifuged at a centrifugal force of 7000 g for 10 min, and the supernatant was vacuum concentrated to 3 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, pass through a 2-mesh sieve, weigh according to the mass ratio of 1:1:1:2 to obtain a mixed powder, add deionized water according to the material-liquid ratio of 1:8g / mL, add composite hydrolase, the composite hydrolase is composed of equal weight parts of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000U / mL, and the amount of composite hydrolase added is 5% of the volume of deionized water. After homogenization, heat to 40℃ and stir at a speed of 200rpm. Stir for 2 hours, inactivate the enzyme at high temperature, cool naturally to room temperature, centrifuge at 8000g for 8 minutes, retain the upper liquid after centrifugation, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 10g:30mL:1mL:5mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, continue stirring at 30°C and 100rpm for 2 hours, and stand at 4°C after the end to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.2:1:0.3, and high-speed shear at 1200 rpm for 3 minutes at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

[0021] Embodiment 2: This embodiment provides a method for preparing a Chinese medicine composition, and the specific steps are as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1.1 to obtain a mixture 1, deionized water was added in an amount of 9 times the mass of the mixture 1, the mixture was heated to 65°C and stirred continuously until uniformly dispersed, and the mixture was naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower (petals) was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 60 mg:2 mL, and ultrasonically treated at a power of 280 W and a temperature of 55°C for 45 min, and then centrifuged at a centrifugal force of 7600 g for 13 min, and the supernatant was vacuum concentrated to 3.5 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, pass through a 2-mesh sieve and weigh according to the mass ratio of 2:1:1.5:3 to obtain a mixed powder, add deionized water according to the material-liquid ratio of 1:9 g / mL, add composite hydrolase, the composite hydrolase consists of equal parts of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000 U / mL, and the amount of composite hydrolase added is 6% of the volume of deionized water. After homogenization, heat to 45°C and stir at a speed of 220 rpm for 2 hours. .5h, after inactivating the enzyme at high temperature, naturally cool to room temperature, centrifuge at 9000g for 10min, retain the upper liquid after the centrifugation, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 12g:40mL:1.5mL:8mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, continue stirring at 35°C and 120rpm for 3h, and stand at 4°C after the end to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.4:1:0.5, and high-speed shear at 1300 rpm for 4 minutes at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

[0022] Embodiment 3: This embodiment provides a method for preparing a Chinese medicine composition, and the specific steps are as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1.2 to obtain a mixture 1, deionized water was added in an amount of 10 times the mass of the mixture 1, the mixture was heated to 70°C and stirred continuously until uniformly dispersed, and the mixture was naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower (petals) was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 80 mg:3 mL, and ultrasonically treated at a power of 300 W and a temperature of 60°C for 60 min, and then centrifuged at a centrifugal force of 8000 g for 15 min, and the supernatant was vacuum concentrated to 4 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, pass through a 2-mesh sieve and weigh according to the mass ratio of 3:1:2:4 to obtain a mixed powder, add deionized water according to the material-liquid ratio of 1:10 g / mL, add composite hydrolase, the composite hydrolase is composed of equal weight parts of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000 U / mL, and the amount of composite hydrolase added is 8% of the volume of deionized water. After homogenization, heat to 50°C and stir at a speed of 250 rpm. 3h, after inactivating the enzyme at high temperature, naturally cool to room temperature, centrifuge at 10000g for 12min, retain the upper liquid after the centrifugation, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 15g:50mL:2mL:10mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, continue stirring at 40℃ and 150rpm for 4h, and let stand at 4℃ after the end to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.5:1:0.6, and high-speed shear at 1500 rpm for 5 minutes at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

[0023] Embodiment 4: This embodiment provides a method for preparing a gel carrier, and the specific steps are as follows: S1. Dry the petiole of rhubarb and crush it into powder, pass it through a 2-mesh sieve to obtain the petiole powder of rhubarb, weigh the petiole powder of rhubarb, deionized water and pectinase according to the mass volume ratio of 1g:50mL:1g, the pectinase is a product with an enzyme activity of 500U / g, heat it to 40℃, stir it at a speed of 150rpm for 3h, and then kill the enzyme at high temperature to obtain mixture 4, cool it to room temperature, add 60% ethanol solution by volume, the amount of ethanol solution added is 3 times the volume of mixture 4, let it stand for 10h, centrifuge it at a centrifugal force of 4000g for 20min, wash the precipitate with deionized water, centrifuge it again and dry it to obtain substance 1; S2. Weigh the substance 1 obtained in step S1, oxalic acid and dimethyl sulfoxide according to the mass volume ratio of 1g:1g:35mL, heat to 120°C and keep for 10min to obtain mixture 5, then add ethyl cinnamate, the amount of ethyl cinnamate added is 0.1 times the volume of mixture 5, keep the heating temperature and stir at a speed of 100rpm for 1h to obtain mixture 6, add mixture 6 to a 50% volume fraction isopropanol solution, the volume ratio of mixture 6:isopropanol solution is 1:5, stir until uniformly dispersed, let stand for 8h, filter after complete precipitation, wash the precipitate with isopropanol solution, dry the precipitate at 45°C to obtain substance 2; S3. Weigh carbomer, substance 2 obtained in step S2, ethyl acetate, and anhydrous ethanol in a mass ratio of 1:2:0.8:10, and stir until uniformly dispersed to obtain a gel carrier.

[0024] Embodiment 5: This embodiment provides a method for preparing a gel carrier, and the specific steps are as follows: S1. Dry the petiole of rhubarb and crush it into powder, pass it through a 2-mesh sieve to obtain the petiole powder of rhubarb, weigh the petiole powder of rhubarb, deionized water and pectinase according to the mass volume ratio of 1g:55mL:1.5g, the pectinase is a product with an enzyme activity of 500U / g, heat it to 45℃, stir it at a speed of 180rpm for 4h, and then kill the enzyme at high temperature to obtain mixture 4, cool it to room temperature, add 60% ethanol solution by volume, the amount of ethanol solution added is 4 times the volume of mixture 4, let it stand for 12h, centrifuge it at a centrifugal force of 4500g for 25min, wash the precipitate with deionized water, centrifuge it again and dry it to obtain substance 1; S2. Weigh the substance 1 obtained in step S1, oxalic acid and dimethyl sulfoxide according to the mass volume ratio of 1g:1.2g:38mL, heat to 125°C and keep for 15min to obtain mixture 5, then add ethyl cinnamate, the amount of ethyl cinnamate added is 0.12 times the volume of mixture 5, keep the heating temperature and stir at a speed of 120rpm for 1.2h to obtain mixture 6, add mixture 6 to an isopropanol solution with a volume fraction of 80%, the volume ratio of mixture 6:isopropanol solution is 1:5.5, stir until uniformly dispersed, let stand for 9h, filter after complete precipitation, wash the precipitate with isopropanol solution, dry the precipitate at 50°C to obtain substance 2; S3. Weigh carbomer, substance 2 obtained in step S2, ethyl acetate, and anhydrous ethanol in a mass ratio of 1:2.5:1:12, and stir until uniformly dispersed to obtain a gel carrier.

[0025] Embodiment 6: This embodiment provides a method for preparing a gel carrier, and the specific steps are as follows: S1. Dry the petiole of rhubarb and crush it into powder, pass it through a 2-mesh sieve to obtain the petiole powder of rhubarb, weigh the petiole powder of rhubarb, deionized water and pectinase according to the mass volume ratio of 1g:60mL:2g, the pectinase is a product with an enzyme activity of 500U / g, heat it to 50℃, stir it at a speed of 200rpm for 5h, and then kill the enzyme at high temperature to obtain mixture 4, cool it to room temperature, add 60% ethanol solution by volume, the amount of ethanol solution added is 5 times the volume of mixture 4, let it stand for 15h, centrifuge it at a centrifugal force of 5000g for 30min, wash the precipitate with deionized water, centrifuge it again and dry it to obtain substance 1; S2. Weigh the substance 1 obtained in step S1, oxalic acid and dimethyl sulfoxide according to the mass volume ratio of 1g:1.2g:40mL, heat to 130°C and keep for 20min to obtain mixture 5, then add ethyl cinnamate, the amount of ethyl cinnamate added is 0.15 times the volume of mixture 5, keep the heating temperature and stir at a speed of 150rpm for 1.5h to obtain mixture 6, add mixture 6 to an isopropanol solution with a volume fraction of 80%, the volume ratio of mixture 6:isopropanol solution is 1:6, stir until uniformly dispersed, let stand for 10h, filter after complete precipitation, wash the precipitate with isopropanol solution, dry the precipitate at 55°C to obtain substance 2; S3. Weigh carbomer, substance 2 obtained in step S2, ethyl acetate, and anhydrous ethanol in a mass ratio of 1:3:1.2:15, and stir until uniformly dispersed to obtain a gel carrier.

[0026] Example 7: This example provides a method for preparing a traditional Chinese medicine gel preparation for treating paronychia, the specific contents are as follows: The Chinese medicine gel preparation for treating paronychia in this embodiment comprises the following raw materials in parts by weight: 8 parts of a Chinese medicine composition, 30 parts of a gel carrier, and 1 part of a skin penetration enhancer, wherein the Chinese medicine composition is prepared by Example 1, the gel carrier is prepared by Example 4, and the skin penetration enhancer is oleic acid; The above-mentioned traditional Chinese medicine composition, gel carrier, and skin penetration enhancer are weighed, stirred until uniformly dispersed, and lactic acid is added to adjust the viscosity to 1000 cP to obtain a traditional Chinese medicine gel preparation for treating paronychia.

[0027] Example 8: This example provides a method for preparing a traditional Chinese medicine gel preparation for treating paronychia, the specific contents are as follows: The Chinese medicine gel preparation for treating paronychia in this embodiment comprises the following raw materials in parts by weight: 10 parts of a Chinese medicine composition, 35 parts of a gel carrier, and 2 parts of a skin penetration enhancer, wherein the Chinese medicine composition is prepared by Example 2, the gel carrier is prepared by Example 5, and the skin penetration enhancer is Tween-80; The above-mentioned traditional Chinese medicine composition, gel carrier, and skin penetration enhancer are weighed, stirred until uniformly dispersed, and lactic acid is added to adjust the viscosity to 1200 cP to obtain a traditional Chinese medicine gel preparation for treating paronychia.

[0028] Example 9: This example provides a method for preparing a traditional Chinese medicine gel preparation for treating paronychia, the specific contents are as follows: The Chinese medicine gel preparation for treating paronychia in this embodiment comprises the following raw materials in parts by weight: 12 parts of a Chinese medicine composition, 40 parts of a gel carrier, and 3 parts of a skin penetration enhancer, wherein the Chinese medicine composition is prepared by Example 3, the gel carrier is prepared by Example 6, and the skin penetration enhancer is N-methylpyrrolidone; The above-mentioned traditional Chinese medicine composition, gel carrier, and skin penetration enhancer are weighed, stirred until uniformly dispersed, and lactic acid is added to adjust the viscosity to 1500 cP to obtain a traditional Chinese medicine gel preparation for treating paronychia.

[0029] Comparative Example 1: This comparison provides a preparation for treating paronychia and a preparation method thereof, the specific contents are as follows: Weigh equal parts of coptis root, phellodendron, turmeric, angelica and rehmannia, add 5 times the weight of water of the above Chinese medicinal materials, boil for 6 hours, filter, and concentrate the filtrate to obtain a paste, add 0.3 times the weight of vaseline of the paste, mix well, and obtain the preparation of this comparative example.

[0030] Comparative Example 2: This comparative example provides a preparation for treating paronychia and a preparation method thereof, the specific contents are as follows: The Chinese medicine composition obtained in Example 1 was mixed with vaseline in an amount 0.3 times the mass of the Chinese medicine composition to obtain a paste, which was the preparation of this comparative example.

[0031] Comparative Example 3: This comparative example provides a preparation for treating paronychia and a preparation method thereof, the specific contents are as follows: Weigh equal parts of dandelion, wild chrysanthemum and gentian, add water 5 times the mass of the above Chinese medicinal materials, boil for 6 hours, filter and concentrate the filtrate to half of the original volume to obtain the preparation of this comparative example.

[0032] Experimental test: 1. Quality effect evaluation of gel preparations: 1. Drying experiment: The Chinese medicine gel preparation for treating paronychia prepared in Examples 7-9 was evenly spread in a culture dish with a diameter of 90 mm, with thicknesses of 0.6 mm and 1.5 mm respectively, and the time required for film formation was recorded at a temperature of 37±2°C. When the film was completely formed, there was no liquid / gel residue on the culture dish.

[0033] 2. Adhesion evaluation: After the gel preparation is completely dried, it is lightly touched with cotton wool. If a large amount of cotton fibers remain, it is considered to have high adhesion, if a small amount of fibers remain, it is considered to have medium adhesion, and if no fibers remain at all, it is considered to have low adhesion.

[0034] 3. Flexibility evaluation: The flexibility of the film was evaluated by tensile test using a texture analyzer (model CT3 4500, Brookfield). The tensile test was performed by attaching a 65 mm × 30 mm film from both ends to clamps on opposite sides with a spacing of about 3 cm. The clamps were fixed on a metal base. One of the clamps was locked and the other could be moved. During the measurement, the mobile clamp pulled the film upward. The tensile speed was 6 mm / s and the lifting distance of the mobile clamp was 150 mm. The tensile strength was measured when the film was torn and was calculated according to the following formula: Tensile strength (N / mm 2 ) = maximum tensile force (N) / original cross-sectional area of ​​the film (mm 2 ).

[0035] 4. Penetration and expansion assessment: Place the film at one end of a plastic tube with a diameter of 30 mm, which contains 8 mL of distilled water. Then put the plastic tube into an incubator and keep it at 38 ± 2 °C and 60 ± 5% humidity for 24 hours. Calculate the water vapor transmission rate: Water vapor transmission rate (g / (cm 2 ·d) = mass difference (g) / (sample area (cm 2 ) × test time (d); Immerse a 2cm×2cm film in a solution consisting of 0.184g calcium chloride, 4.149g sodium chloride and 1L ultrapure water. Record the weight change every 15 minutes for a total of 8 times. Each time you record, wipe the film lightly with filter paper to remove excess solution, then weigh it and calculate the expansion index: Swelling index (%) = (weight of membrane after hydration (g) - mass of membrane before hydration (g)) / mass of membrane before hydration (g) × 100%.

[0036] The experimental results are recorded as follows: Table 1 Quality evaluation results of gel preparations

[0037] As can be seen from Table 1, the gel preparations obtained in Examples 7-9 have better film-forming properties, have lower adhesion after film formation, and are not easy to adhere to clothing materials. At the same time, they can meet the basic degree of stretching, have good air permeability, and will expand to a certain extent in a humid and hot environment. Figure 1 The film-forming effect of the gel preparation obtained in Example 8 is shown. It can be seen that the film is relatively uniform and has a certain degree of transparency, which can meet the needs of naked eye observation of the affected area.

[0038] Evaluation of use effect: 1. Evaluation of antifungal effects of different forms of preparations: Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Candida albicans, and Streptococcus pyogenes were used for the test. The above strains were all from ATCC model strains. MIC and MFC (mg / mL) were determined by serial dilution technique using a 96-well microtiter plate. The preparations obtained in Examples 7-9 and Comparative Examples 1-3 were placed in 5% DMSO, bifonazole and ketoconazole were used as positive controls, and 5% dimethyl sulfoxide aqueous solution was used as a negative control. The results are as follows: Table 2 Antifungal effects of different forms of preparations

[0039] The inhibitory effects of different forms of preparations on common pathogens are shown in Table 2. It can be seen from Table 2 that the Chinese medicine gel preparations prepared in Examples 7-9 have good inhibitory effects on Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Candida albicans, and Streptococcus pyogenes. After conversion to paste, some effects are weakened, such as the MFC value of Staphylococcus aureus and the MIC value of Proteus vulgaris, etc., proving that in the Chinese medicine gel preparations prepared by the present invention, it is not only the Chinese medicine composition that exerts the antifungal effect, but the gel carrier not only provides a better film-forming effect, but also can work together with the Chinese medicine composition. In contrast, the paste / solution preparations obtained from other Chinese medicine components have different effects. For example, the paste preparation of Comparative Example 1 has the same ability to resist Streptococcus pyogenes as the gel preparation obtained in Examples 7-9, and the solution preparation obtained in Comparative Example 3 has the same MFC value as the gel preparation obtained in Examples 7-9 for Pseudomonas aeruginosa.

[0040] 2. Evaluation of the effect of relieving paronychia symptoms: Volunteers were recruited, and screening conditions were set according to the diagnostic criteria for paronychia in the "Chinese Journal of Clinical Dermatology". Volunteers who were indeed suffering from paronychia and had not received any treatment in the past month were excluded. Volunteers who dropped out midway were finally found to have 43 effective cases, including 11 cases corresponding to Example 7, 10 cases corresponding to Example 8, 12 cases corresponding to Example 9, and 10 cases in the control group. Among them, the scheme corresponding to Examples 7-9 was to apply the Chinese medicine gel preparation to the affected area, and keep it on for 6 hours after film formation, once a day, while the control group was to apply 1% iodine tincture externally for 10 minutes each time, twice a day, and the overall cycle was 90 days.

[0041] According to the recovery area of ​​the diseased nail, there are 4 levels of evaluation standards: 1) No obvious diseased nail involvement is considered cured; 2) > 60% of the diseased nail area recovers to normal appearance is considered effective; 3) 20%-60% of the diseased nail area recovers to normal appearance is considered improvement; 4) < 20% of the diseased nail area recovers to normal appearance is considered ineffective.

[0042] The results are as follows Figure 2 As shown by Figure 2It can be seen that the Chinese medicine gel preparations obtained in Examples 7-9 all have a good alleviating effect on paronychia, are helpful in reducing redness and swelling, relieving pain, and inhibiting fungi, and a large number of people have recovered.

[0043] The above are only several embodiments of the present invention and are not intended to limit the present invention in any form. Although the present invention is disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Any technician familiar with the profession, without departing from the scope of the technical solution of the present invention, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the protection scope of the technical solution of the present invention.

Claims

1. A Chinese medicine gel preparation for treating paronychia, characterized in that: The invention comprises the following raw materials in parts by weight: 8-12 parts of a traditional Chinese medicine composition, 30-40 parts of a gel carrier, and 1-3 parts of a skin penetration enhancer.

2. The Chinese medicine gel preparation for treating paronychia according to claim 1, characterized in that: The preparation method of the Chinese medicine composition is as follows: L1. Betaine hydrochloride and tartaric acid were weighed in a molar ratio of 1:1-1.2 to obtain a mixture 1, deionized water was added, heated and stirred until uniformly dispersed, and naturally cooled to room temperature to obtain a solvent 1, the Formononetes flower was washed and dried, and vacuum freeze-dried to obtain Formononetes pollen, and the Formononetes pollen and solvent 1 were weighed in a mass volume ratio of 50-80 mg:1-3 mL, ultrasonically treated, centrifuged after completion, and the supernatant was vacuum concentrated to 3-4 times the original volume to obtain a mixture 2; L2. Crush picrorhizome, turmeric, angelica dahurica and forsythia suspensa into powder, sieve and weigh according to the mass ratio of 1-3:1:1-2:2-4 to obtain a mixed powder, add deionized water according to the solid-liquid ratio of 1:8-10g / mL, add composite hydrolase, homogenize, heat and stir, inactivate the enzyme at high temperature, naturally cool to room temperature, centrifuge, retain the upper liquid after completion, weigh β-cyclodextrin, deionized water, upper liquid and anhydrous ethanol according to the mass volume ratio of 10-15g:30-50mL:1-2mL:5-10mL, mix β-cyclodextrin and deionized water and stir until uniformly dispersed, then add the upper liquid and anhydrous ethanol, stir, and stand at 4°C after completion to obtain mixture 3; L3. Weigh the mixture 2 obtained in step S1, the mixture 3 in step S2 and polyoxyethylene lauryl ether according to the volume ratio of 1.2-1.5:1:0.3-0.6, and high-speed shear at room temperature to obtain a Chinese medicine composition, which is stored at 4°C for later use.

3. The Chinese medicine gel preparation for treating paronychia according to claim 2, characterized in that: The amount of deionized water added in step L1 is 8-10 times the mass of mixture 1.

4. The Chinese medicine gel preparation for treating paronychia according to claim 3, characterized in that: In step L2, the composite hydrolase is composed of equal parts of arabinanase, hemicellulase and xylanase, the enzyme activity of the composite hydrolase is 4000 U / mL, and the amount of the composite hydrolase added is 5-8% of the volume of deionized water.

5. The Chinese medicine gel preparation for treating paronychia according to claim 4, characterized in that: The preparation method of the gel carrier is as follows: S1. Dry the petiole of rhubarb and crush it into powder, sieve to obtain the rhubarb petiole powder, weigh the rhubarb petiole powder, deionized water and pectinase according to the mass volume ratio of 1g:50-60mL:1-2g, heat and stir, and kill the enzyme at high temperature to obtain mixture 4, cool to room temperature, add 60% ethanol solution by volume, let it stand, centrifuge after the end, wash the precipitate with deionized water, centrifuge again and dry to obtain substance 1; S2. Weigh the substance 1 obtained in step S1, oxalic acid and dimethyl sulfoxide according to the mass volume ratio of 1g: 1-1.2g: 35-40mL, heat and maintain, obtain a mixture 5, then add ethyl cinnamate, maintain the heating temperature and stir to obtain a mixture 6, add the mixture 6 to the isopropanol solution, stir until it is evenly dispersed, let it stand, filter after the precipitation is complete, wash the precipitate with an isopropanol solution, dry the precipitate, and obtain a substance 2; S3. Weigh carbomer, substance 2 obtained in step S2, ethyl acetate, and anhydrous ethanol according to a mass ratio of 1:2-3:0.8-1.2:10-15, and stir until uniformly dispersed to obtain a gel carrier.

6. The Chinese medicine gel preparation for treating paronychia according to claim 5, characterized in that: The amount of ethanol solution added in step S1 is 3-5 times the volume of mixture 4.

7. The Chinese medicine gel preparation for treating paronychia according to claim 6, characterized in that: In step S2, the amount of ethyl cinnamate added is 0.1-0.15 times the volume of mixture 5, the volume ratio of mixture 6: isopropanol solution is 1:5-6, and the volume fraction of isopropanol solution is 80%.

8. The Chinese medicinal gel preparation for treating paronychia according to claim 7, characterized in that The skin penetration enhancer is selected from one of oleic acid, Tween-80 and N-methylpyrrolidone.

9. A method for preparing a traditional Chinese medicine gel preparation for treating paronychia according to any one of claims 1 to 8, characterized in that: The specific steps are as follows: The Chinese medicine composition, gel carrier and skin penetration enhancer are weighed according to their mass fractions, stirred until uniformly dispersed, and lactic acid is added to adjust the viscosity to 1000-1500 cP to obtain a Chinese medicine gel preparation for treating paronychia.

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