Preparation process of sunscreen medicine

Abstract

The invention discloses a preparation process of a sunscreen medicine, and relates to the technical field of medicines. The sunscreen medicine consists of honeysuckle, perfoliote knotweed herb, sedum sarmentosum, dayflower, radix polygonati officinalis, lithospermum, aloe, asparagus fern, lucid ganoderma, coix seed and bee pollen, and is one of representative products of Guizhou Miao medicine brands. The preparation process comprises the following steps: taking medicinal materials, performing supercritical fluid extraction, performing water extraction, removing impurities, purifying, concentrating and forming a preparation. Through a large number of condition investigation tests, the preparation process of the sunscreen medicine is improved, the extraction rate of effective components is increased, the variety and the dosage of preparation forming auxiliary materials are optimized, and the process difficulty and the production cost are greatly reduced.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to a preparation process of a sunscreen medicine. Background Art

[0002] Sunburn prevention cream (Drug approval number: National Medicine Standard Z20025534) is one of the representative products of Guizhou Miao medicine brand. It has the effects of clearing away heat and detoxifying, cooling blood and removing spots. It is used to prevent and treat sunburn caused by heat and toxicity. The product has significant clinical efficacy and is favored by patients and doctors.

[0003] The sunscreen prevention and treatment ointment prescription is composed of honeysuckle, angelica sinensis, creeping vine, communis herb, polygonatum, lithospermum officinale, aloe, asparagus cochinchinensis, ganoderma lucidum, coix seed, and bee pollen. The original preparation process is: among the eleven medicinal materials in the prescription, ganoderma lucidum is used as 80% ethanol as a solvent, and after being immersed for 12 hours, it is slowly percolated at a rate of 1 to 3 mL per minute, the percolated liquid is collected, the ethanol is recovered under reduced pressure, and concentrated to a clear paste with a relative density of 1.15 (50°C); except for aloe, the other nine herbs are decocted twice with water, the first time for 2 hours and the second time for 1.5 hours, the decoctions are combined, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.05 (60°C). Take sorbitol, sodium alginate, glycerin, beta-cyclodextrin, titanium dioxide and aloe vera, add to the above-mentioned Ganoderma lucidum fluid extract and traditional Chinese medicine concentrate, and heat (80°C) to dissolve; separately take stearic acid, monoglyceride, vaseline, octadecyl alcohol, polysorbate-80, Span-80, lanolin, sucrose stearate, and emulsified silicone oil, heat (80°C) to melt, mix the above two solutions and emulsify for 15 minutes, keep at 80°C for 30 minutes, add benzoic acid and ethylparaben, mix well, and obtain the product.

[0004] As a drug, according to Article 5 of the "Administrative Measures for Post-Marketing Changes of Drugs (Trial)": "The holder shall take the initiative to conduct post-marketing research on drugs to achieve full life cycle management of drugs. Holders are encouraged to use new production technologies, new methods, new equipment, and new scientific and technological achievements to continuously improve and optimize production processes, continuously improve drug quality, and enhance drug safety, effectiveness, and quality controllability." With the continuous development of science and technology, the present invention team believes that the following problems existing in the original preparation process should be improved:

[0005] (1) Traditional Chinese medicine is not a single component, but a collection of many active ingredients. Modern pharmacological studies have shown that the ingredients in the prescription that have preventive and therapeutic effects on sunburn include chlorogenic acid, an effective ingredient in honeysuckle, quercetin and kaempferol, an effective ingredient in scutellaria baicalensis, β,β'-dimethylacryloyl akanin, an effective ingredient in lithospermum officinale, quercetin, an effective ingredient in radix scutellariae, and ganoderma lucidum polysaccharide, an effective ingredient in ganoderma lucidum. In the original preparation process, honeysuckle, scutellaria baicalensis, radix scutellariae, and lithospermum officinale were all extracted with water. However, studies have shown that the extraction rate of the active ingredients in the above four medicinal materials is not high through a simple water extraction process. Ganoderma lucidum is extracted by percolation of an alcohol solution, but the solubility of ganoderma lucidum polysaccharide in alcohol is low, and the extraction rate is not high, which will inevitably lead to waste of medicinal materials. It is necessary to optimize the extraction process.

[0006] (2) The original preparation process used a total of 16 excipients in the ointment base, which was too complicated and resulted in high costs. With the emergence of new materials and new processes, it is necessary to optimize the types and amounts of excipients.

[0007] Based on this, the present invention has improved and optimized the preparation process of the sunscreen drug through a large number of condition investigation experiments, aiming to simplify the production process, reduce production costs, and improve product quality and production efficiency. Summary of the invention

[0008] The purpose of the present invention is to provide a preparation process of a sunscreen medicine.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0010] The preparation process of the sunscreen medicine of the present invention comprises the following steps:

[0011] S1 Take herbs:

[0012] 40 parts of Flos Lonicerae, 40 parts of Radix Angelicae Pubescentiss, 30 parts of Herba Codonopsis Tremellaes, 30 parts of Herba Commelinae, 40 parts of Polygonatum odoratum, 20 parts of Radix Lithospermi, 5 parts of Aloe, 40 parts of Asparagus cochinchinensis, 40 parts of Ganoderma lucidum, 20 parts of Semen Coicis, and 10 parts of Bee Pollen.

[0013] S2 Supercritical Fluid Extraction:

[0014] The five medicinal materials of honeysuckle, Radix Angelicae Pubescentis, Herba Lycopodii, Radix Lithospermi and Ganoderma Lucidum were subjected to supercritical CO2-ethanol extraction, after the extraction, the pressure was reduced, and the precipitated extract was recovered for standby use;

[0015] S3 Water Extract:

[0016] Add water to decoct the five herbs of Commelina communis, Polygonatum odoratum, Asparagus cochinchinensis, Coix seeds and Bee pollen twice, combine the decoctions, filter and concentrate the filtrate to a clear paste with a relative density of 1.05;

[0017] S4 impurity removal and purification:

[0018] Add ZTC clarifier B solution to the clear paste obtained by water extraction, stir evenly, and keep warm; then add ZTC clarifier A solution, stir evenly, keep warm, let stand for 24 hours, filter, and use the filtrate for later use;

[0019] S5 Concentrate:

[0020] The extract obtained by supercritical fluid extraction and the filtrate obtained after impurity removal and purification are combined and concentrated to a clear paste;

[0021] S6 preparation molding:

[0022] Add 2-4 parts of triethanolamine, 15 parts of glycerol, 1 part of ethylparaben, 1 part of sodium benzoate, aloe vera and appropriate amount of distilled water to the concentrated clear paste, and heat to 80°C as the water phase; mix 25 parts of glyceryl monostearate, 40-80 parts of stearic acid, 20-40 parts of liquid paraffin and 45 parts of stearyl alcohol, and heat to 80°C to melt as the oil phase; slowly pour the water phase into the oil phase at 80°C, stirring while adding, stir and emulsify for 20 minutes, keep warm, and make 1000 parts.

[0023] In the preparation process of the sunscreen drug of the present invention, the pressure of the supercritical CO2-ethanol extraction in step S2 is 10-40 MPa, the temperature is 40-60° C., the CO2-ethanol flow rate is 5-9 L / h, and the extraction time is 2-6 h.

[0024] Preferably, in the preparation process of the sunscreen drug of the present invention, the pressure of the supercritical CO2-ethanol extraction in step S2 is 30 MPa, the temperature is 50° C., the CO2-ethanol flow rate is 7 L / h, and the extraction time is 4 h.

[0025] In the preparation process of the sunscreen medicine of the present invention, the decoction in step S3 is specifically as follows: the decoction time is 2 hours for the first time and 1.5 hours for the second time, and 6 times the amount of water of the medicinal material is added each time.

[0026] In the preparation process of the sunscreen medicine of the present invention, the relative density in step S3 is a value measured at 60°C.

[0027] In the preparation process of the sunscreen drug of the present invention, the specific process of impurity removal and purification in step S4 is: adding 2% to 4% ZTC clarifier B solution to the clear paste obtained by water extraction, stirring evenly, and keeping warm at 40°C to 60°C for 20min to 40min; adding 1% to 3% ZTC clarifier A solution, stirring evenly, keeping warm at 40°C to 60°C for 20min to 40min, standing for 24h, filtering, and using the filtrate for later use.

[0028] Preferably, in the preparation process of the sunscreen drug of the present invention, the specific process of impurity removal and purification in step S4 is: adding 3% ZTC clarifier B solution to the clear paste obtained by water extraction, stirring evenly, and keeping warm at 40°C for 20 minutes; adding 2% ZTC clarifier A solution, stirring evenly, keeping warm at 40°C for 20 minutes, standing for 24 hours, filtering, and using the filtrate for later use.

[0029] In the preparation process of the sunscreen medicine of the present invention, the concentration to a clear paste in step S5 specifically refers to concentration to a clear paste with a mass ratio of 1:1 to the medicinal material.

[0030] Preferably, in the preparation process of the sunscreen drug of the present invention, the amount of triethanolamine added in step S6 is 4 parts, the amount of stearic acid added is 80 parts, and the amount of liquid paraffin added is 40 parts.

[0031] In the preparation process of the sunscreen medicine of the present invention, the insulation condition in step S6 is 80° C. for 30 minutes.

[0032] Beneficial effects of the present invention:

[0033] Through experimental research, the present invention extracts sunscreen drug prescriptions in groups, improves the extraction rate of effective ingredients, and optimizes the preparation molding auxiliary materials. Compared with the original preparation method, the present invention has the following beneficial effects:

[0034] (1) The original process extract has a chlorogenic acid content of 0.96 mg / mL, a quercetin content of 0.18 mg / mL, a kaempferol content of 0.018 mg / mL, a β,β'-dimethylacryloyl akanin content of 0.08 mg / mL, and a ganoderma lucidum polysaccharide content of 0.43 mg / mL; the present invention uses supercritical fluid extraction to extract five medicinal materials, namely, honeysuckle, scutellaria baicalensis, radix lithospermi and ganoderma lucidum in the sunscreen drug prescription, so that the chlorogenic acid content in the dilution is 1.76 mg / mL, the quercetin content is 0.39 mg / mL, the kaempferol content is 0.040 mg / mL, the β,β'-dimethylacryloyl akanin content is 0.17 mg / mL, and the ganoderma lucidum polysaccharide content is 1.03 mg / mL, thereby greatly increasing the content of the effective ingredients.

[0035] (2) The original preparation process used 16 kinds of auxiliary materials in total for the ointment base. After the improvement of the present invention, the ointment base only used 8 kinds of auxiliary materials in total, which greatly reduced the process difficulty and production cost.

[0036] (3) The results of pharmacological experiments showed that the new process group had the same therapeutic effect as the original process group in the mouse solar dermatitis model when the dosage was only 80% of that of the original process group, indicating that the present invention can reduce the dosage of medicinal materials and save medicinal material resources. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 This is the standard curve diagram for polysaccharide content determination; DETAILED DESCRIPTION

[0038] The technical solution of the present invention is described in detail below in conjunction with specific embodiments. The following embodiments are only used for explanation and illustration, and do not constitute a limitation on the technical solution of the present invention.

[0039] Example 1

[0040] The preparation process of sunscreen medicine is as follows:

[0041] 1) Take herbs

[0042] According to the prescription ratio, weigh 40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Codonopsis pilosulae, 30g of Herba Commelinae, 40g of Polygonatum odoratum, 20g of Lithospermum officinale, 5g of Aloe vera, 40g of Asparagus cochinchinensis, 40g of Ganoderma lucidum, 20g of Coix seeds, and 10g of Bee Pollen.

[0043] 2) Supercritical fluid extraction

[0044] The five medicinal materials of honeysuckle, Radix Angelicae Pubescentis, Herba Lycopodii, Radix Lithospermi and Ganoderma Lucidum were subjected to supercritical extraction at a pressure of 30 MPa, a temperature of 50°C, and a CO2-ethanol flow rate of 7 L / h for 4 hours. After the extraction was completed, the pressure was reduced, and the precipitated extract was recovered and set aside.

[0045] 3) Water extraction

[0046] Add water to decoct the five ingredients of Commelina communis, Polygonatum odoratum, Asparagus cochinchinensis, Coix seeds and Bee pollen for two times, the first time for 2 hours and the second time for 1.5 hours, adding 6 times the amount of water of the medicinal materials each time. Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of about 1.05 (60°C).

[0047] 4) Impurity removal and purification

[0048] Add 3% ZTC clarifier B solution to the clear paste obtained by the water extraction, stir evenly, and keep warm at 40°C for 20 minutes; then add 2% ZTC clarifier A solution, stir evenly, and keep warm at 40°C for 20 minutes; let stand for 24 hours, filter, and use the filtrate for later use.

[0049] 5) Concentration

[0050] The extract extracted by supercritical fluid extraction and the filtrate after impurity removal and purification are combined and concentrated to a clear paste with a mass ratio of 1:1 to the medicinal material.

[0051] 6) Preparation molding

[0052] Add 4g of triethanolamine, 15g of glycerol, 1g of ethylparaben, 1g of sodium benzoate, 5g of aloe vera, and distilled water to a total of 810g, and heat to 80°C as the aqueous phase. Add 25g of monostearate, 80g of stearic acid, 40g of liquid paraffin, and 45g of stearyl alcohol, and heat to 80°C to melt as the oil phase. Slowly pour the aqueous phase into the oil phase at 80°C, stirring while adding, stirring and emulsifying for 20min, and keep warm at 80°C for 30min to make 1000g.

[0053] Example 2

[0054] The preparation process of sunscreen medicine is as follows:

[0055] 1) Take herbs

[0056] According to the prescription ratio, weigh 40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Codonopsis pilosulae, 30g of Herba Commelinae, 40g of Polygonatum odoratum, 20g of Lithospermum officinale, 5g of Aloe vera, 40g of Asparagus cochinchinensis, 40g of Ganoderma lucidum, 20g of Coix seeds, and 10g of Bee Pollen.

[0057] 2) Supercritical fluid extraction

[0058] The five medicinal materials of honeysuckle, Radix Angelicae Pubescentis, Herba Lycopodii, Radix Lithospermi and Ganoderma Lucidum were subjected to supercritical extraction at a pressure of 30 MPa, a temperature of 50°C, and a CO2-ethanol flow rate of 7 L / h for 4 hours. After the extraction was completed, the pressure was reduced, and the precipitated extract was recovered and set aside.

[0059] 3) Water extraction

[0060] Add water to decoct the five ingredients of Commelina communis, Polygonatum odoratum, Asparagus cochinchinensis, Coix seeds and Bee pollen for two times, the first time for 2 hours and the second time for 1.5 hours, adding 8 times the amount of water of the medicinal materials each time. Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of about 1.05 (60°C).

[0061] 4) Impurity removal and purification

[0062] Add 3% ZTC clarifier B solution to the clear paste obtained by the water extraction, stir evenly, and keep warm at 40°C for 20 minutes; then add 2% ZTC clarifier A solution, stir evenly, and keep warm at 40°C for 20 minutes; let stand for 24 hours, filter, and use the filtrate for later use.

[0063] 5) Concentration

[0064] The extract extracted by supercritical fluid extraction and the filtrate after impurity removal and purification are combined and concentrated to a clear paste with a mass ratio of 1:1 to the medicinal material.

[0065] 6) Preparation molding

[0066] Add 4g of triethanolamine, 15g of glycerol, 1g of ethylparaben, 1g of sodium benzoate, 5g of aloe vera, and distilled water to a total of 810g, and heat to 80°C as the aqueous phase. Add 25g of monostearate, 80g of stearic acid, 40g of liquid paraffin, and 45g of stearyl alcohol, and heat to 80°C to melt as the oil phase. Slowly pour the aqueous phase into the oil phase at 80°C, stirring while adding, stirring and emulsifying for 20min, and keep warm at 80°C for 30min to make 1000g.

[0067] Example 3

[0068] The preparation process of sunscreen medicine is as follows:

[0069] 1) Take herbs

[0070] According to the prescription ratio, weigh 40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Codonopsis pilosulae, 30g of Herba Commelinae, 40g of Polygonatum odoratum, 20g of Lithospermum officinale, 5g of Aloe vera, 40g of Asparagus cochinchinensis, 40g of Ganoderma lucidum, 20g of Coix seeds, and 10g of Bee Pollen.

[0071] 2) Supercritical fluid extraction

[0072] The five medicinal materials of honeysuckle, Radix Angelicae Pubescentis, Herba Lycopodii, Radix Lithospermi and Ganoderma Lucidum were subjected to supercritical extraction under the conditions of pressure of 10MPa, temperature of 40°C, CO2-ethanol flow rate of 5L / h, and extraction time of 6h. After the extraction was completed, the pressure was reduced, and the precipitated extract was recovered and set aside.

[0073] 3) Water extraction

[0074] Add water to decoct the five ingredients of Commelina communis, Polygonatum odoratum, Asparagus cochinchinensis, Coix seeds and Bee pollen for two times, the first time for 2 hours and the second time for 1.5 hours, adding 6 times the amount of water of the medicinal materials each time. Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of about 1.05 (60°C).

[0075] 4) Impurity removal and purification

[0076] Add 2% ZTC clarifier B solution to the clear paste obtained by the water extraction, stir evenly, and keep warm at 40°C for 40 minutes; then add 1% ZTC clarifier A solution, stir evenly, and keep warm at 40°C for 40 minutes; let stand for 24 hours, filter, and use the filtrate for later use.

[0077] 5) Concentration

[0078] The extract extracted by supercritical fluid extraction and the filtrate after impurity removal and purification are combined and concentrated to a clear paste with a mass ratio of 1:1 to the medicinal material.

[0079] 6) Preparation molding

[0080] Add 4g of triethanolamine, 15g of glycerol, 1g of ethylparaben, 1g of sodium benzoate, 5g of aloe vera, and distilled water to a total of 810g, and heat to 80°C as the aqueous phase. Add 25g of monostearate, 80g of stearic acid, 40g of liquid paraffin, and 45g of stearyl alcohol, and heat to 80°C to melt as the oil phase. Slowly pour the aqueous phase into the oil phase at 80°C, stirring while adding, stirring and emulsifying for 20min, and keep warm at 80°C for 30min to make 1000g.

[0081] Example 4

[0082] The preparation process of sunscreen medicine is as follows:

[0083] 1) Take herbs

[0084] According to the prescription ratio, weigh 40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Codonopsis pilosulae, 30g of Herba Commelinae, 40g of Polygonatum odoratum, 20g of Lithospermum officinale, 5g of Aloe vera, 40g of Asparagus cochinchinensis, 40g of Ganoderma lucidum, 20g of Coix seeds, and 10g of Bee Pollen.

[0085] 2) Supercritical fluid extraction

[0086] The five medicinal materials of honeysuckle, Radix Angelicae Pubescentis, Herba Lycopodii, Radix Lithospermi and Ganoderma Lucidum were subjected to supercritical extraction at a pressure of 40 MPa, a temperature of 60°C, and a CO2-ethanol flow rate of 9 L / h for 2 h. After the extraction was completed, the pressure was reduced, and the precipitated extract was recovered and set aside.

[0087] 3) Water extraction

[0088] Add water to decoct the five ingredients of Commelina communis, Polygonatum odoratum, Asparagus cochinchinensis, Coix seeds and Bee pollen for two times, the first time for 2 hours and the second time for 1.5 hours, adding 6 times the amount of water of the medicinal materials each time. Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of about 1.05 (60°C).

[0089] 4) Impurity removal and purification

[0090] Add 4% ZTC clarifier B solution to the clear paste obtained by the water extraction, stir evenly, and keep warm at 60°C for 20 minutes; then add 3% ZTC clarifier A solution, stir evenly, and keep warm at 60°C for 20 minutes; let stand for 24 hours, filter, and use the filtrate for later use.

[0091] 5) Concentration

[0092] The extract extracted by supercritical fluid extraction and the filtrate after impurity removal and purification are combined and concentrated to a clear paste with a mass ratio of 1:1 to the medicinal material.

[0093] 6) Preparation molding

[0094] Add 2g of triethanolamine, 15g of glycerol, 1g of ethylparaben, 1g of sodium benzoate, 5g of aloe vera, and distilled water to a total of 870g, and heat to 80°C as the aqueous phase. Add 25g of glyceryl monostearate, 40g of stearic acid, 20g of liquid paraffin, and 45g of stearyl alcohol, and heat to 80°C to melt as the oil phase. Slowly pour the aqueous phase into the oil phase at 80°C, stirring while adding, stirring and emulsifying for 20min, and keep warm at 80°C for 30min to make 1000g.

[0095] In order to further verify the reliability of the present invention and screen out the best solution, the inventor conducted a series of experiments, the excerpts of which are as follows:

[0096] 1. Instruments and reagents

[0097] 1.1 Main instruments

[0098] LC-2010AHT fully automatic high performance liquid chromatograph (Shimadzu, Japan); TU-1001 UV-visible spectrophotometer (Beijing Puxi); HH-4 digital display constant temperature water bath (Changzhou Putian Instrument Manufacturing Co., Ltd.); ultrasonic cleaning machine (Shanghai Shangyi).

[0099] 1.2 Main Reagents

[0100] Chlorogenic acid reference substance (batch number: 110753-202201), quercetin reference substance (batch number: 100081-202107), kaempferol reference substance (batch number: 110861-202214), and β,β'-dimethylacryloyl akanin reference substance (batch number: 111689-202203) were provided by the China Food and Drug Inspection Institute; ZTC clarifier (Beijing Zhengtiancheng), methanol (chromatographic grade, Tiandi Co., Ltd., USA), and water (Yibo purified water); all medicinal materials used in the experiment were purchased from Guizhou Tongjitang Decoction Pieces Co., Ltd.

[0101] 2. Investigation of extraction methods

[0102] The sunscreen drug prescription is composed of honeysuckle, angelica sinensis, scutellaria baicalensis, commelina, polygonatum, lithospermum officinale, aloe, asparagus cochinchinensis, ganoderma lucidum, coix seed, and bee pollen. The effective ingredients of honeysuckle, scutellaria baicalensis, lithospermum officinale, angelica sinensis, etc. in the prescription have a low extraction rate by water extraction, and the effective ingredients of ganoderma lucidum have a low extraction rate by alcohol extraction. In order to improve the extraction efficiency of effective ingredients, it is necessary to extract these 5 medicines in groups using appropriate methods. The present invention team takes the content of chlorogenic acid, quercetin, kaempferol, β, β'-dimethylacryloyl akanin and polysaccharides in the extract as the investigation index, and compares four different extraction processes such as water extraction process, alcohol extraction process, enzyme extraction process and supercritical fluid extraction extraction process through experiments, and finally selects the best extraction process.

[0103] 2.1 Experimental methods

[0104] 2.1.1 Preparation of test solution

[0105] (1) Water extraction method

[0106] Weigh the medicinal materials (40 g of honeysuckle, 40 g of Radix Angelicae Pubescentis, 30 g of Herba Creepersii, 20 g of Lithospermum officinale and 40 g of Ganoderma lucidum) according to the formula ratio, add water 6 times the weight of the medicinal materials, heat and extract for 1 h, filter, concentrate the filtrate and make up to 500 mL.

[0107] (2) Alcohol extraction method

[0108] Weigh the medicinal materials according to the formula ratio (same as water extraction method), add 60% ethanol solution with 6 times the weight of the medicinal materials, heat and extract for 1 hour, filter, concentrate the filtrate and make up to 500 mL.

[0109] (3) Supercritical fluid extraction

[0110] Weigh the medicinal materials according to the proportion of the formula (same as water extraction method), carry out supercritical extraction under the conditions of pressure 30MPa, temperature 50℃, CO2-ethanol flow rate of 7L / h, and extraction time of 4h. After the extraction is completed, reduce the pressure, recover the precipitated extract, dilute it with methanol and make it up to 500mL.

[0111] (4) Enzymatic hydrolysis

[0112] Weigh the medicinal materials according to the formula ratio (same as water extraction method), add water 6 times the weight of the medicinal materials and 2% cellulase, extract at 50°C and pH 5.0 for 2 hours, filter after boiling, concentrate the filtrate and make up to 500 mL.

[0113] 2.1.2 Preparation of reference solution

[0114] 2.1.2.1 Preparation of chlorogenic acid, quercetin, kaempferol, and β,β'-dimethylacryloyl-arcanin reference solution

[0115] Take chlorogenic acid, quercetin, kaempferol, and β,β'-dimethylacryloyl akanin reference substances, add methanol to make solutions containing 40μg, 80μg, 60μg, and 0.1mg per 1mL, respectively.

[0116] 2.1.2.2 Preparation of polysaccharide reference solution

[0117] Take 33 mg of anhydrous glucose reference substance dried to constant weight at 105°C, accurately weigh it, place it in a 100 mL volumetric flask, add water to dissolve and dilute to the scale, shake well, and obtain (each 1 mL contains 0.33 mg of anhydrous glucose).

[0118] 2.1.3 Content determination

[0119] The contents of chlorogenic acid, quercetin, kaempferol and β,β'-dimethylacryloylarachidonic acid were determined by HPLC, and the content of polysaccharides was determined by spectrophotometry.

[0120] 2.1.3.1 Determination of chlorogenic acid, quercetin, kaempferol and β,β'-dimethylacryloylarachidonic acid

[0121] Chromatographic operating conditions: chromatographic column (250×4.6 mm, 5 μm) with octadecylsilane bonded silica as filler; mobile phase: methanol as mobile phase A, 0.05% formic acid solution as mobile phase B, gradient elution program see Table 1; detection wavelength: 250 nm; flow rate: 1.0 mL / min; injection volume: 10 μL. The theoretical plate number calculated based on the chlorogenic acid peak is not less than 5000.

[0122] Table 1 Gradient elution program

[0123]

[0124] 2.1.3.2 Determination of polysaccharide content

[0125] (1) Preparation of standard curve

[0126] Accurately measure 0.1mL, 0.2mL, 0.3mL, 0.4mL, 0.5mL, and 0.6mL of the reference solution, and place them in 10mL stoppered graduated test tubes respectively. Add water to 2.0mL each, shake well, and slowly add 0.2% anthrone-sulfuric acid solution to the scale in an ice water bath, mix well, let cool, and keep warm in a water bath for 10 minutes. Take out, immediately cool in an ice water bath for 10 minutes, take out, and use the corresponding reagent as the blank. Measure the absorbance at a wavelength of 582nm according to the UV-Vis spectrophotometry method (General Chapter 0401 of the Chinese Pharmacopoeia). Draw a standard curve with absorbance as the ordinate and concentration as the abscissa. The results are shown in the table below. Figure 1 .

[0127] (2) Determination method

[0128] Accurately measure 5 mL of the extract and place it in a 25 mL volumetric flask. According to the method under the standard curve preparation, starting from "add water to 2.0 mL", determine the absorbance according to the law, read the weight (mg) of anhydrous glucose in the test solution from the standard curve, and calculate the result.

[0129] 2.2 Results and Discussion

[0130] The results show that the extraction effects of the four extraction methods are ranked as follows: supercritical fluid extraction > water extraction > enzymatic hydrolysis > alcohol extraction, so supercritical fluid extraction was selected as the extraction method. The results of the determination of the active ingredient content in the extracts of different extraction methods are shown in Table 2.

[0131] Table 2 Results of determination of active ingredient contents in extracts using different extraction methods

[0132]

[0133] 3. Investigation of process parameters of supercritical fluid extraction

[0134] 3.1 Experimental methods

[0135] 3.1.1 Extraction pressure investigation

[0136] Weigh 4 portions of medicinal materials according to the formula ratio (40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Lycopodiellae, 20g of Lithospermum officinale and 40g of Ganoderma lucidum), and perform supercritical extraction at 10, 20, 30 and 40MPa pressures, 50°C and 7L / h of CO2-ethanol flow rate, respectively, for 4h. After the extraction is completed, reduce the pressure, recover the precipitated extract, dilute it with methanol and make it up to 500mL, use the solution under "2.1.2 Preparation of reference solution" as the reference solution, use the method under "2.1.3 Content determination" to perform content analysis, and calculate the content of each active ingredient.

[0137] 3.1.2 Extraction temperature investigation

[0138] Weigh 3 portions of medicinal materials according to the formula ratio (40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Coptidis, 20g of Lithospermum officinale and 40g of Ganoderma lucidum), and perform supercritical extraction at 40℃, 50℃ and 60℃, respectively, under the conditions of 30MPa pressure and 7L / h CO2-ethanol flow rate, and the extraction time is 4h. After the extraction is completed, reduce the pressure, recover the precipitated extract, dilute it with methanol and make it up to 500mL, use the solution under "2.1.2 Preparation of reference solution" as the reference solution, use the method under "2.1.3 Content determination" to perform content analysis, and calculate the content of each active ingredient.

[0139] 3.1.3 Extraction time investigation

[0140] Weigh 5 portions of medicinal materials according to the formula ratio (40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Lycopodiellae, 20g of Lithospermum officinale and 40g of Ganoderma lucidum), and perform supercritical extraction at a temperature of 50°C, a pressure of 30MPa, and a CO2-ethanol flow rate of 7L / h. The extraction time is 2, 3, 4, 5, and 6h, respectively. After the extraction is completed, the pressure is reduced, the precipitated extract is recovered, and it is diluted with methanol and fixed to 500mL. The solution under "2.1.2 Preparation of reference solution" is used as the reference solution, and the content analysis is performed using the method under "2.1.3 Content determination", and the content of each active ingredient is calculated.

[0141] 3.1.4 CO2-ethanol flow rate investigation

[0142] Weigh 5 portions of medicinal materials according to the formula ratio (40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Lycopodiellae, 20g of Lithospermum officinale and 40g of Ganoderma lucidum), and perform supercritical extraction at a temperature of 50°C, a pressure of 30MPa, and a CO2-ethanol flow rate of 5, 6, 7, 8, and 9L / h, respectively. The extraction time is 4h. After the extraction is completed, the pressure is reduced, the precipitated extract is recovered, and it is diluted with methanol and fixed to 500mL. The solution under "2.1.2 Preparation of reference solution" is used as the reference solution, and the content analysis is performed using the method under "2.1.3 Content determination", and the content of each active ingredient is calculated.

[0143] 3.2 Results and Discussion

[0144] 3.2.1 Extraction pressure investigation

[0145] The results show that the contents of chlorogenic acid, quercetin, kaempferol, β,β'-dimethylacryloylarachidonic acid and polysaccharides continue to increase with the increase of extraction pressure, but when the pressure exceeds 30MPa, the increase in content slows down, and the requirements of high pressure on instruments and equipment gradually increase. Therefore, 30MPa is selected as the optimal process parameter for extraction pressure. The results of determination of effective ingredient content under different extraction pressures are shown in Table 3.

[0146] Table 3 Results of determination of effective ingredient content under different extraction pressures

[0147]

[0148] 3.2.2 Extraction temperature investigation

[0149] The results show that when the extraction temperature is 50℃, the contents of chlorogenic acid, quercetin, kaempferol, β,β'-dimethylacryloyl akanin and Ganoderma lucidum polysaccharide are the highest, so 50℃ is selected as the optimal process parameter for extraction temperature. The results of the determination of the effective ingredient content at different extraction temperatures are shown in Table 4.

[0150] Table 4 Results of determination of effective ingredient content at different extraction temperatures

[0151]

[0152] 3.2.3 Extraction time investigation

[0153] The results show that with the increase of extraction time, the content of chlorogenic acid, quercetin, kaempferol, β,β'-dimethylacryloyl akanin and polysaccharide showed an upward trend. After 4 hours of extraction, the content increase slowed down, so 4 hours was selected as the optimal process parameter for extraction time. The results of the determination of the content of active ingredients at different extraction times are shown in Table 5.

[0154] Table 5 Results of determination of effective ingredient content at different extraction times

[0155]

[0156] 3.2.4 CO2-ethanol flow rate investigation

[0157] The results show that when the flow rate is between 5L / h and 7L / h, the contents of chlorogenic acid, quercetin, kaempferol, β,β'-dimethylacryloyl akanin and polysaccharides gradually increase. When the flow rate is 7L / h and 8L / h, the contents are similar. When the flow rate is 9L / h, the contact time between the extract and the supercritical fluid is reduced, the mass transfer process is insufficient, and the content is reduced. Therefore, 7L / h is selected as the optimal process parameter for CO2-ethanol flow rate. The results of the determination of the content of effective ingredients at different CO2-ethanol flow rates are shown in Table 6.

[0158] Table 6 Results of determination of effective ingredient content at different CO2-ethanol flow rates

[0159]

[0160] 4. Investigation of impurity removal and purification methods

[0161] In the prescription, Commelina, Polygonatum, Asparagus cochinchinensis, Coix seeds and bee pollen are processed by water extraction. Since the water extract contains more impurities, it is necessary to perform purification treatment. In order to determine the optimal purification process, the present invention compares the alcohol precipitation method, ZTC clarifier method and chitosan flocculation precipitation method with the retention rate and impurity removal rate of total polysaccharides in the extract as indicators.

[0162] Weigh the medicinal materials (90g of Commelina, 120g of Polygonatum odoratum, 120g of Asparagus cochinchinensis, 60g of Coix seeds, and 30g of Bee Pollen) according to the formula ratio, add water and boil twice, the first time for 2 hours and the second time for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of about 1.05 (60°C), determine the polysaccharide content and solid content, and divide the solution into 3 parts on average. Prepare the test solution according to the following method, and determine the polysaccharide retention rate and impurity removal rate.

[0163] 4.1 Experimental methods

[0164] 4.1.1 Sample preparation method

[0165] (1) Alcohol precipitation method

[0166] Take 1 portion of the clear paste, add ethanol to make the alcohol content reach 60%, stir while adding, let stand for 24 hours, filter, concentrate the filtrate and make up to 500 mL.

[0167] (2) ZTC clarifier method

[0168] Take 1 portion of the clear paste, add 3% ZTC clarifier B solution, stir evenly, keep warm at 40℃ for 20min, then add 2% ZTC clarifier A solution, stir evenly, keep warm at 40℃ for 20min, let stand for 24h, filter, concentrate the filtrate and make up to 500mL.

[0169] (3) Chitosan flocculation precipitation method

[0170] Take 1 portion of the clear paste, add 1% acetic acid solution containing 1% chitosan, set the flocculation temperature at 40°C, stir for 10 min, let stand for 24 h, filter, concentrate the filtrate and make up to 500 mL.

[0171] 4.1.2 Determination of polysaccharide retention rate

[0172] Determine the polysaccharide content in the concentrate before and after impurity removal according to the method in "2.1.3.2 Determination of polysaccharide content", and calculate the polysaccharide retention rate according to the following formula:

[0173]

[0174] 4.1.3 Determination of impurity removal rate

[0175] Accurately pipette 25 mL of the paste before and after impurity removal and the clear paste respectively, place them in an evaporating dish that has been dried to constant weight, evaporate to dryness in a water bath, dry the residue at 105°C for 3 h, take it out, place it in a desiccator for 30 min, weigh it, calculate the amount of dry paste, and calculate the impurity removal rate according to the following formula:

[0176]

[0177] 4.2 Results and Discussion

[0178] The results showed that the chitosan flocculation precipitation method had the highest impurity removal rate, but the ZTC clarifier method had the highest polysaccharide retention rate after treatment, indicating that the chitosan flocculation precipitation method had the greatest loss of effective ingredients while removing impurities. After comprehensive consideration, the ZTC clarifier method was selected as the best purification process. The total polysaccharide retention rate and impurity removal rate after treatment with different purification methods are shown in Table 7.

[0179] Table 7 Total polysaccharide retention rate and impurity removal rate after treatment with different purification methods

[0180]

[0181] 5. Investigation of process parameters of ZTC clarifier method

[0182] The factors that affect the purification effect of ZTC clarifier are mainly the dosage of ZTC clarifier A, the dosage of ZTC clarifier B, the holding temperature and the holding time. This experiment intends to investigate these four main factors separately to optimize the best impurity removal process parameters.

[0183] 5.1 Experimental Methods

[0184] Medicinal materials (450 g of Commelina, 600 g of Polygonatum odoratum, 600 g of Asparagus cochinchinensis, 300 g of Coix lachryma-jobi, and 150 g of Bee Pollen) were weighed according to the formula ratio, decocted twice with water, the first time for 2 hours and the second time for 1.5 hours, the decoctions were combined, filtered, and the filtrate was concentrated to a clear paste with a relative density of about 1.05 (60°C), which was evenly divided into 12 portions, and the test solutions were prepared according to the following methods to determine the total polysaccharide retention rate and impurity removal rate.

[0185] 5.1.1 Investigation of dosage of ZTC clarifier B

[0186] Take 3 portions of clear paste, add 2%, 3% and 4% ZTC clarifier B solution respectively, stir, keep warm at 40℃ for 20min, then add 2% ZTC clarifier A solution, keep warm at 40℃ for 20min, let stand for 24h, concentrate the filtrate and make up to 500mL.

[0187] 5.1.2 Investigation of dosage of ZTC clarifier A

[0188] Take 3 portions of clear paste, add 3% ZTC clarifier B solution, stir, keep warm at 40℃ for 20min, then add 1%, 2% and 3% ZTC clarifier A solution respectively, keep warm at 40℃ for 20min, let stand for 24h, concentrate the filtrate and make up to 500mL.

[0189] 5.1.3 Insulation temperature investigation

[0190] Take 3 portions of clear paste, add 3% ZTC clarifier B solution, stir, keep warm at 40℃, 50℃ and 60℃ for 20min, then add 2% ZTC clarifier A solution, keep warm at 40℃, 50℃ and 60℃ for 20min, let stand for 24h, concentrate the filtrate and make up to 500mL.

[0191] 5.1.4 Insulation time inspection

[0192] Take 3 portions of clear paste, add 3% ZTC clarifier B solution, stir, and keep warm at 40℃ for 20min, 30min and 40min respectively, then add 2% ZTC clarifier A solution, keep warm at 40℃ for 20min, 30min and 40min respectively, let stand for 24h, concentrate the filtrate and make up to 500mL.

[0193] 5.1.5 Determination of total polysaccharide content and impurity removal rate

[0194] The total polysaccharide content and impurity removal rate were determined according to the method under “4. Investigation of impurity removal and purification methods”, and the total polysaccharide retention rate and impurity removal rate were calculated.

[0195] 5.2 Results and Discussion

[0196] 5.2.1 Investigation of dosage of ZTC clarifier B

[0197] The results show that when the dosage of ZTC clarifier B is 4%, the impurity removal rate is improved, but the total polysaccharide retention rate is greatly reduced. After comprehensive consideration, the dosage of ZTC clarifier B is selected to be 3%. The results of total polysaccharide retention rate and impurity removal rate under different ZTC clarifier B dosages are shown in Table 8.

[0198] Table 8 Total polysaccharide retention rate and impurity removal rate at different ZTC clarifier B dosages

[0199]

[0200] 5.2.2 Investigation of dosage of ZTC clarifier A

[0201] The results show that when the dosage of ZTC clarifier A is 3%, the impurity removal rate is improved, but the total polysaccharide retention rate is greatly reduced. After comprehensive consideration, the dosage of ZTC clarifier A is selected to be 2%. The results of total polysaccharide retention rate and impurity removal rate under different ZTC clarifier A dosages are shown in Table 9.

[0202] Table 9 Total polysaccharide retention rate and impurity removal rate at different ZTC clarifier A dosages

[0203]

[0204] 5.2.3 Insulation temperature investigation

[0205] The results show that the total polysaccharide retention rate and impurity removal rate at each temperature are not much different. After comprehensive consideration, 40°C is selected as the process parameter for the insulation temperature. The total polysaccharide retention rate and impurity removal rate under different insulation temperature conditions are shown in Table 10.

[0206] Table 10 Total polysaccharide retention rate and impurity removal rate at different insulation temperatures

[0207]

[0208] 5.2.4 Insulation time inspection

[0209] The results show that the total polysaccharide retention rate and impurity removal rate under different insulation time conditions are not much different. After comprehensive consideration, 20 minutes is selected as the process parameter for insulation time. The total polysaccharide retention rate and impurity removal rate under different insulation time conditions are shown in Table 11.

[0210] Table 11 Total polysaccharide retention rate and impurity removal rate at different insulation times

[0211]

[0212] 6. Matrix Optimization

[0213] The original sunscreen drug preparation molding process is: extract the medicinal materials into a clear paste according to the prescription ratio, take sorbitol, sodium alginate, glycerin, beta-cyclodextrin, titanium dioxide and aloe vera, add them to the above-mentioned Ganoderma lucidum fluid extract and Chinese medicine concentrate, heat (80°C) to dissolve; separately take stearic acid, monoglyceride, vaseline, octadecyl alcohol, polysorbate 80, Span 80, lanolin, sucrose stearate, emulsified silicone oil and heat (80°C) to melt, mix the above two solutions for emulsification for 15 minutes, keep them at 80°C for 30 minutes, add benzoic acid and ethyl hydroxybenzoate, mix well, and the product is obtained. This process uses a large variety of excipients, which is not conducive to the quality control of the preparation and has too high a cost.

[0214] In this study, triethanolamine, glycerol, glyceryl monostearate, stearic acid, liquid paraffin and stearyl alcohol were selected as o / w type matrices, and ethyl paraben and sodium benzoate were added as preservatives to carry out research on the formulation molding process.

[0215] 6.1 Preferred indicators and scoring criteria

[0216] 6.1.1 Appearance and shape

[0217] The full score is 20 points, and the examination includes color, texture, consistency, spreading and dispersion, and the presence or absence of granularity, with each item accounting for 4 points.

[0218] 6.1.2 Centrifugal stability

[0219] The full score is 20 points. Each group of ointments was placed in a centrifuge tube and centrifuged at 2500 r / min. －1 Centrifuge for 30 minutes and observe for abnormal phenomena such as stratification, agglomeration, foaming or water discharge.

[0220] 6.1.3 Cold resistance test

[0221] The full score is 10 points. A certain amount of ointment from each group was placed in a plastic sample cup in a 4°C refrigerator for 1 month to observe whether there were any abnormal phenomena such as stratification, agglomeration, or water leakage.

[0222] 6.1.4 Heat resistance test

[0223] The full score is 10 points. A certain amount of ointment from each group was placed in a plastic sample cup and placed in a constant temperature oven at 40°C for 1 month to observe whether there were any abnormal phenomena such as stratification, discoloration, mildew, etc.

[0224] 6.1.5 Ductility

[0225] The full score is 20 points. Take two clean glass plates of 10cm×10cm, one of which weighs 125g (add weights to make up for the lack of mass). Weigh 1g of each group of ointments that have been placed at room temperature for 24 hours and place them between the two glass plates. After 1 minute, use a ruler to measure the diameter of the ointment after extension, and take the average value of the ratio of the maximum diameter to the minimum diameter.

[0226] 6.1.6 pH value

[0227] The full score is 20. Take 5g of each ointment in a small beaker, add an equal amount of distilled water to fully dissolve, stir evenly, and measure the pH of each group with a pH meter. The full score is 6-8, and the rest is zero.

[0228] 6.2 Orthogonal Experimental Design

[0229] Three factors that have a greater impact on the physical and chemical properties of the matrix, namely, the amount of triethanolamine (A), the amount of stearic acid (B) and the amount of liquid paraffin (C), were selected as the factors to be investigated. Based on the preliminary data, each factor was selected at 3 levels for orthogonal experiments. The factor level table is shown in Table 12.

[0230] Table 12. Orthogonal test factors and levels for matrix investigation

[0231]

[0232] 6.3 Results and Discussion

[0233] From the results, it can be seen that the influence of each factor on the matrix molding effect is A>B>C, and A3>A2>A1, B3>B2>B1, C3>C1>C2, and the optimal matrix ratio parameter is A3B3C3. Combined with the variance analysis, it can be seen that the three factors have significant effects, so the optimal matrix ratio parameter is: triethanolamine: stearic acid: liquid paraffin = 4:80:40. The orthogonal experimental design and results of the matrix investigation are shown in Table 13, and the variance analysis of the matrix investigation is shown in Table 14.

[0234] Table 13 Orthogonal experimental design and results of matrix investigation

[0235]

[0236]

[0237] Table 14 Matrix Investigation Variance Analysis

[0238]

[0239] 7. Verification of optimal process parameters

[0240] 7.1 Experimental Methods

[0241] (1) Obtaining medicinal materials

[0242] According to the prescription ratio, weigh 40g of honeysuckle, 40g of Radix Angelicae Pubescentis, 30g of Herba Codonopsis pilosulae, 30g of Herba Commelinae, 40g of Polygonatum odoratum, 20g of Lithospermum officinale, 5g of Aloe vera, 40g of Asparagus cochinchinensis, 40g of Ganoderma lucidum, 20g of Coix seeds, and 10g of Bee Pollen.

[0243] (2) Supercritical fluid extraction

[0244] The five medicinal materials of honeysuckle, Radix Angelicae Pubescentis, Herba Lycopodii, Radix Lithospermi and Ganoderma Lucidum were subjected to supercritical extraction under the conditions of pressure of 30MPa, temperature of 50℃, CO2-ethanol flow rate of 7L / h, and extraction time of 4h. After the extraction was completed, the pressure was reduced, and the precipitated extract was recovered and set aside.

[0245] (3) Water extraction

[0246] Add water to decoct the five ingredients of Commelina communis, Polygonatum odoratum, Asparagus cochinchinensis, Coix seeds and Bee pollen for two times, the first time for 2 hours and the second time for 1.5 hours, adding 6 times the amount of water of the medicinal materials each time. Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of about 1.05 (60°C).

[0247] (4) Impurity removal and purification

[0248] Add 3% ZTC clarifier B solution to the clear paste obtained by the water extraction, stir evenly, and keep warm at 40°C for 20 minutes; then add 2% ZTC clarifier A solution, stir evenly, and keep warm at 40°C for 20 minutes; let stand for 24 hours, filter, and use the filtrate for later use.

[0249] (5) Concentration

[0250] The extract extracted by supercritical fluid extraction and the filtrate after impurity removal and purification are combined and concentrated to a clear paste with a mass ratio of 1:1 to the medicinal material.

[0251] (6) Preparation molding

[0252] In the above concentrated clear paste, add 4g of triethanolamine, 15g of glycerol, 1g of ethylparaben, 1g of sodium benzoate, 5g of aloe, add distilled water to a total amount of 810g, and heat to 80°C as the aqueous phase. 25g of glyceryl monostearate, 80g of stearic acid, 40g of liquid paraffin, and 45g of stearyl alcohol are heated to 80°C and melted as the oil phase. At 80°C, the aqueous phase is slowly poured into the oil phase while stirring. Stir and emulsify for 20 minutes, and keep warm at 80°C for 30 minutes to make 1000g.

[0253] (7) Verification test

[0254] Three batches of samples were prepared according to the above optimal parameters and scored according to the indicators and scoring criteria under “6. Matrix Optimization”.

[0255] 7.2 Results and Discussion

[0256] The results show that the sunscreen drug prepared according to the optimal process parameters provided by the present invention has good indicators and a stable process. The verification results of the optimal process parameters are shown in Table 15.

[0257] Table 15 Optimal process parameter verification results

[0258]

[0259] 8. Drug efficacy verification test

[0260] 8.1 Mouse model of solar dermatitis

[0261] 8.1.1 Experimental Materials

[0262] ① Animals: 70 specific pathogen-free BALB / c female mice, weighing 18-20 g.

[0263] ② Drugs and reagents: sunscreen drug samples prepared according to the preparation method of the present invention; sunscreen drugs (Guizhou Green Sun Pharmaceutical Co., Ltd.); 5% sodium chloride solution; calamine lotion; enzyme-linked immunosorbent assay kit; electric constant temperature water bath; electric constant temperature blast drying oven; hand-held shaver; high-speed refrigerated centrifuge; surgical scissors; microplate reader.

[0264] 8.1.2 Experimental methods

[0265] ① Modeling and grouping and drug administration: 50 mice were divided into 7 groups, with 10 mice in each group. A flat area of ​​4 cm × 4 cm on the back was selected for hair removal using a handheld shaver. The mice in the blank control group were not treated after hair removal; the mice in the animal model group were given 0.1 mL / cm2 of normal saline within the hair removal area. 2 , once a day; the original process group evenly applied 0.1g / cm 2 , Group 1 of the present invention is evenly applied with 0.1g / cm 2 (same dosage as the original process), the present invention group 2 is evenly applied with 0.08g / cm 2 (0.8 times the dosage of the original process) and the present invention group 3 are evenly applied with 0.1g / cm 2 (0.6 times the original dosage), once a day; Calamine lotion group evenly applied 0.1mL / cm 2 , once a day, for 8 consecutive days according to the above scheme. On the 6th day, the 5 groups of mice were placed at a distance of 10 cm from the 308nm ultraviolet rays for 1.5 hours. After irradiation, the mice were given the corresponding drugs according to the previous doses. After the model was successfully established, the experimental results were observed. After the mice in the animal model group were continuously smeared with normal saline for 6 days, they were irradiated with ultraviolet rays under the same conditions and methods as other drug groups. Skin redness and swelling appeared after a 48-hour incubation period, indicating that the mouse model of solar dermatitis was successfully established.

[0266] ② Visual observation: One hour after the last day of drug administration, the drug was removed, the back skin was cleaned, and the skin was scored according to the following criteria: 0 point, normal color, no redness or swelling; 1 point, slight redness or swelling; 2 points, redness or swelling, dryness or wrinkles; 3 points, exudation of fluid, scratching of the back skin, and restlessness.

[0267] ③ Determination of NO, NOS and TNF-α contents in mouse skin: After observing the intuitive morphological changes of the mouse skin in the depilated area, the skin of the corresponding irradiated area was taken with surgical scissors, and the removed skin tissue was homogenized at 3000r / min for 10 minutes, and the levels of nitric oxide (NO), nitric oxide synthase (NOS) and TNF-α were detected by enzyme-linked immunosorbent assay.

[0268] ④Statistical methods: SPSS17.0 statistical software was used for data processing. The data were expressed as x±s. The t-test was used for comparison between groups. The Ridit test was used for rank data. P < 0.01 was considered statistically significant.

[0269] 8.2 Results and Discussion

[0270] ① Effect on the mouse solar dermatitis model: The blank group was normal locally. After Ridit test, compared with the blank group, the model group showed significant local swelling and exudation (P < 0.01); compared with the model group, the original process group, the present invention group 1, the present invention group 2 and the calamine lotion group all significantly inhibited skin swelling, exudation and the like (P < 0.01), among which the present invention group 2 and the original process group had the same improvement effect, and the amount of medicinal materials used in the present invention group 2 was only 80% of that in the original process group, indicating that the present invention can reduce the amount of medicinal materials used. The results are shown in Table 16.

[0271] Table 16 Effects of sunscreen drugs on mouse skin scores (n=10)

[0272]

[0273]

[0274] ② Effect on NO, NOS, TNF-α content in mouse skin: Compared with the blank group, the levels of TNF-α, NOS, and NO in the model group were significantly increased (P<0.01); compared with the model group, the original process group, calamine lotion group, present invention group 1, present invention group 2, and present invention group 3 could significantly reduce the levels of TNF-α, NOS, and NO (P<0.01); the present invention group 2 had a similar reduction compared with the original process group, which again showed that the present invention can reduce the amount of medicinal materials used. See Table 17.

[0275] Table 17 Effects of each test group on TNF-α, NOS, and NO levels in the mouse photodermatitis model (x±s, n=10)

[0276]

[0277] Although the present invention has been described in detail above by means of general description, specific implementation methods and experiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims

1. A process for preparing a sunscreen drug, characterized in that: The steps include: S1 Take herbs: 40 parts of honeysuckle, 40 parts of Radix Angelicae Pubescentis, 30 parts of Herba Codonopsise, 30 parts of Commelinae, 40 parts of Polygonatum odoratum, 20 parts of Lithospermum officinale, 5 parts of Aloe, 40 parts of Asparagus cochinchinensis, 40 parts of Ganoderma lucidum, 20 parts of Coix seeds, and 10 parts of Bee Pollen; S2 Supercritical Fluid Extraction: The five medicinal materials of honeysuckle, Radix Angelicae Pubescentis, Herba Lycopodii, Radix Lithospermi and Ganoderma Lucidum were subjected to supercritical CO2-ethanol extraction, after the extraction, the pressure was reduced, and the precipitated extract was recovered for standby use; S3 Water Extract: Add water to decoct the five herbs of Commelina communis, Polygonatum odoratum, Asparagus cochinchinensis, Coix seeds and Bee pollen twice, combine the decoctions, filter and concentrate the filtrate to a clear paste with a relative density of 1.05; S4 impurity removal and purification: Add ZTC clarifier B solution to the clear paste obtained by water extraction, stir evenly, and keep warm; then add ZTC clarifier A solution, stir evenly, keep warm, let stand for 24 hours, filter, and use the filtrate for later use; S5 Concentrate: The extract obtained by supercritical fluid extraction and the filtrate obtained after impurity removal and purification are combined and concentrated to a clear paste; S6 preparation molding: Add 2-4 parts of triethanolamine, 15 parts of glycerol, 1 part of ethylparaben, 1 part of sodium benzoate, aloe vera and appropriate amount of distilled water to the concentrated clear paste, and heat to 80°C as the water phase; mix 25 parts of glyceryl monostearate, 40-80 parts of stearic acid, 20-40 parts of liquid paraffin and 45 parts of stearyl alcohol, and heat to 80°C to melt as the oil phase; slowly pour the water phase into the oil phase at 80°C, stirring while adding, stir and emulsify for 20 minutes, keep warm, and make 1000 parts.

2. The preparation process according to claim 1, characterized in that: The supercritical CO2-ethanol extraction in step S2 has a pressure of 10-40 MPa, a temperature of 40-60° C., a CO2-ethanol flow rate of 5-9 L / h, and an extraction time of 2-6 h.

3. The preparation process according to claim 2, characterized in that: The supercritical CO2-ethanol extraction in step S2 has a pressure of 30 MPa, a temperature of 50° C., a CO2-ethanol flow rate of 7 L / h, and an extraction time of 4 h.

4. The preparation process according to claim 1, characterized in that: The conditions for decocting in step S3 are as follows: the decocting time is 2 hours for the first time and 1.5 hours for the second time, and 6 to 8 times the weight of the medicinal material is added in water each time.

5. The preparation process according to claim 1, characterized in that: The relative density in step S3 is a value measured at 60°C.

6. The preparation process according to claim 1, characterized in that: The specific process of impurity removal and purification in step S4 is as follows: add 2% to 4% ZTC clarifier B solution to the clear paste obtained by water extraction, stir evenly, and keep warm at 40°C to 60°C for 20min to 40min; add 1% to 3% ZTC clarifier A solution, stir evenly, keep warm at 40°C to 60°C for 20min to 40min, let stand for 24h, filter, and use the filtrate for later use.

7. The preparation process according to claim 6, characterized in that: The specific process of impurity removal and purification in step S4 is as follows: add 3% ZTC clarifier B solution to the clear paste obtained by water extraction, stir evenly, and keep warm at 40°C for 20 minutes; add 2% ZTC clarifier A solution, stir evenly, keep warm at 40°C for 20 minutes, let stand for 24 hours, filter, and use the filtrate for later use.

8. The preparation process according to claim 1, characterized in that: The concentration to a clear paste in step S5 specifically refers to concentration to a clear paste having a mass ratio of 1:1 to the medicinal material.

9. The preparation process according to claim 1, characterized in that: In step S6, the amount of triethanolamine added is 4 parts, the amount of stearic acid added is 80 parts, and the amount of liquid paraffin added is 40 parts.

10. The preparation process according to claim 1, characterized in that: The insulation conditions in step S6 are: 80° C., insulation for 30 minutes.

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