A sterile powder of shuanghuanglian for injection and a preparation method thereof

Abstract

The application discloses a sterile double-huanglian powder for injection and a preparation method thereof. The effective component content of the extract is improved by extracting honeysuckle through an auxiliary agent and extracting forsythia through a polymerization inhibitor. Finally, the residual auxiliary agent and polymerization inhibitor are removed through a purifying agent, and the high-efficiency sterile double-huanglian powder is prepared.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical processing, and more specifically to a sterile Shuanghuanglian powder for injection and its preparation method. Background Technology

[0002] With the continuous development of animal husbandry and the adjustment of industrial structure, my country's poultry industry is developing rapidly towards intensification and large-scale operation. As a result, the types, scope, and causes of poultry diseases have also changed significantly. Due to the increasing number of diseases, chronic diseases, and foreign diseases caused by mixed infections and secondary infections of various viruses and bacteria, the poultry industry is facing enormous operational pressure.

[0003] In this context, the excessive use of chemical agents and antibiotics for prevention, and even their abuse, has led to the development and increasing trend of pathogen resistance. As a result, drug residues are difficult to control and are prone to serious exceedances, ultimately endangering human health. Therefore, the need to use traditional Chinese medicine to prepare veterinary drugs to replace chemical agents and antibiotics is becoming increasingly urgent.

[0004] Shuanghuanglian powder for injection is a sterile powder for injection obtained by extracting and refining the traditional Chinese medicines honeysuckle, forsythia, and scutellaria. Honeysuckle and forsythia can both dispel wind-heat to relieve exterior syndromes and clear heat and detoxify to soothe the throat; the addition of bitter and cold scutellaria clears lung heat and upper burner heat to stop coughing. The three herbs work together to relieve exterior syndromes, clear heat, and detoxify. It is commonly used for lung-heat cough, damp-heat diarrhea, damp-heat jaundice, etc., and has good anti-inflammatory, anti-allergic, antimicrobial, antipyretic, and sedative effects. It has also become one of the drugs used in clinical treatment of pneumonia and upper respiratory tract infections nationwide. Therefore, its application as a veterinary drug in animal husbandry for the treatment of infectious bronchitis in chickens is consistent with the indications and has reliable efficacy.

[0005] However, the extraction of active ingredients from raw materials during the preparation of sterile Shuanghuanglian powder for injection results in significant losses, leading to low content and difficulty in completely eliminating bacterial toxins during the formulation process. To address these issues, this invention provides a method for preparing a high-purity, low-toxin, and highly stable sterile Shuanghuanglian powder. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a method for preparing a sterile Shuanghuanglian powder with high purity, low toxicity and high stability.

[0007] To solve the above-mentioned technical problems, the technical solution provided by the present invention includes the following steps:

[0008] 1. A sterile Shuanghuanglian powder for injection, the preparation steps of which are as follows:

[0009] (1) Take 5 parts of dried honeysuckle medicinal material, add 100 parts of deionized water, soak in cold water for 12 hours, add 5-15 parts of auxiliary agent, extract by ultrasonication 3 times, filter for 25 minutes each time, combine the filtrates, concentrate under reduced pressure to 1:1, add an equal volume of 30% ethanol solution for alcohol precipitation for 24 hours, filter by suction, dry the filtrate to obtain a gel-like mixture, wash three times with 85% ethanol, dry at 20℃ and 30Kpa to obtain powdered honeysuckle extract;

[0010] (2) Take 10 parts of dried Forsythia suspensa and put them into an extraction vessel. Add 50 parts of ethanol and 3-7 parts of polymerization inhibitor. Extract at a pressure of 27 MPa and a temperature of 60°C. Pass CO2 through at a flow rate of 25 parts / h. The pressure of the analysis vessel I is 15 MPa and the temperature is 65°C. The pressure of the analysis vessel II is 6 MPa and the temperature is 50°C. Extract for 5 hours. Obtain the extract from the outlet of analysis vessel I and analysis vessel II. Fractionate the extract to recover the alcohol and polymerization inhibitor. The remaining powder is the Forsythia suspensa extract.

[0011] (3) Take 5 parts of dried Scutellaria baicalensis, cut into pieces with a thickness of 0.6~0.9 mm, soak in 200 parts of deionized water for 2 hours, extract in a shaker at 40 kHz and 60 ℃ for 15 minutes, heat and decoct for 1.5 hours, concentrate at low temperature to ρ=1.05, adjust to 1 with concentrated hydrochloric acid, heat to 80 ℃ and keep warm for 0.5 hours, filter and keep the precipitate, add 20 parts of distilled water and adjust the pH to 7 with 40% sodium hydroxide solution, add an equal amount of 85% ethanol solution to the mixture, stir and let stand for 2 hours, filter and keep the filtrate, adjust the pH to 1 with concentrated hydrochloric acid, let stand for 2 hours, filter and keep the precipitate, wash the precipitate with distilled water, wash twice with 85% ethanol solution, and dry at 20 ℃ and 30 kPa to obtain Scutellaria baicalensis extract;

[0012] (4) The extracts were mixed in a mass ratio of honeysuckle extract: scutellaria extract: forsythia extract = 1:1:2, then ground and sieved through a 200-mesh sieve;

[0013] (5) Add 45 parts of deionized water, 1w% sodium carboxymethyl cellulose, and 5-15 parts of purifying agent to 20 parts of mixed powder, mix thoroughly, and then spray granulate.

[0014] (6) Wash the particles twice with ethanol, and dry them to remove the ethanol to obtain a powdered product;

[0015] (7) Dispense the powdered finished product into sterile ampoules to obtain Shuanghuanglian sterile powder;

[0016] 2. Further, the auxiliary agent in the preparation method is sodium alkylphenol ether sulfosuccinate;

[0017] 3. Further, the polymerization inhibitor mentioned in the preparation method is methoxyacetonitrile;

[0018] 4. Further, the purifying agent mentioned in the preparation method is silver diethyldithiocarbamate;

[0019] The beneficial effects of this invention are as follows:

[0020] 1) Alkylphenol ether sulfosuccinate sodium salt has both polar and nonpolar groups, which can adhere to the surface of honeysuckle in ultrasonic extraction to assist in the dissolution of active ingredients. At the same time, the sulfosuccinate group has excellent penetrating effect, which enhances the penetration of solvents, adjuvants and drug components into the solvent, so that the medicinal material is dispersed in the solvent and effectively increases the content of active ingredients in the extract.

[0021] 2) Methoxyacetonitrile can prevent the formation of large particles, colloids or precipitates in medicinal materials due to their high coagulation properties, increase the contact area between the medicinal materials and the solvent and increase the permeation efficiency of CO2 in the system, thereby improving the efficiency of supercritical extraction and increasing the content of the product to a greater extent.

[0022] 3) Methoxyacetonitrile can also protect free radicals in medicinal materials and increase the content of extracted components. In addition, its boiling point is much different from that of ethanol, which makes it easy to separate and recover and reuse after extraction.

[0023] 4) Silver diethyldithiocarbamate, which contains both active sulfur and free silver, can effectively bind to the proteins in bacterial cell membranes, destroy the integrity of bacterial cell membranes, and lead to cell death, thus achieving highly efficient sterilization.

[0024] 5) The high solubility and dissolution rate of silver diethyldithiocarbamate in ethanol make it easy to remove with ethanol after sterilization, while still maintaining sterile conditions during the removal process.

[0025] 6) Silver diethyldithiocarbamate can complex with methoxyacetonitrile and alkylphenol ether sulfosuccinate sodium salt in ethanol solution system, which can identify whether there are any residues. It can also remove any residues that may not be completely removed during the cleaning process. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to the embodiments.

[0027] Unless otherwise specified, the raw materials or chemical reagents used in the embodiments of this invention are obtained through conventional commercial channels.

[0028] Example 1

[0029] 1. Take 5 parts of dried honeysuckle, add 100 parts of deionized water, soak for 12 hours, add 10 parts of sodium alkylphenol ether sulfosuccinate, and extract by ultrasonication 3 times, 25 minutes each time. Filter, combine the filtrates, concentrate under reduced pressure to 1:1, add an equal volume of 30% ethanol solution for alcohol precipitation for 24 hours, filter, dry the filtrate to obtain a gel-like mixture, wash three times with 85% ethanol, and dry at 20℃ and 30Kpa to obtain powdered honeysuckle extract;

[0030] 2. Take 10 parts of dried Forsythia suspensa and put them into an extraction vessel. Add 50 parts of ethanol and 5 parts of methoxyacetonitrile. Extract at a pressure of 27 MPa and a temperature of 60°C. Pass CO2 through the vessel at a flow rate of 25 parts / h. The pressure of the analysis vessel I is 15 MPa and the temperature is 65°C. The pressure of the analysis vessel II is 6 MPa and the temperature is 50°C. Extract for 5 hours. Obtain the extract from the outlets of analysis vessel I and analysis vessel II. Fractionate the extract to recover the alcohol and polymerization inhibitor. The remaining powder is the Forsythia suspensa extract.

[0031] 3. Take 5 parts of dried Scutellaria baicalensis, cut into 0.75 mm thick slices, soak in 200 parts of deionized water for 2 hours, extract in a shaker at 40 kHz and 60 ℃ for 15 minutes, heat and decoct for 1.5 hours, concentrate at low temperature to ρ=1.05, adjust to 1 with concentrated hydrochloric acid, heat to 80 ℃ and keep warm for 0.5 hours, filter and collect the precipitate, add 20 parts of distilled water and adjust the pH to 7 with 40% sodium hydroxide solution, add an equal volume of 85% ethanol solution to the mixture, stir and let stand for 2 hours, filter and collect the filtrate, adjust the pH to 1 with concentrated hydrochloric acid, let stand for 2 hours, filter and collect the precipitate, wash the precipitate with distilled water, wash twice with 85% ethanol solution, and dry at 20 ℃ and 30 kPa to obtain Scutellaria baicalensis extract;

[0032] 4. The extracts were mixed in a mass ratio of honeysuckle extract: scutellaria extract: forsythia extract = 1:1:2, then ground and sieved through a 200-mesh sieve;

[0033] 5. Add 45 parts of deionized water, 1w% sodium carboxymethyl cellulose, and 10 parts of silver diethyldithiocarboxylate to 20 parts of mixed powder, mix thoroughly, and then spray granulate.

[0034] 6. Wash the granules twice with ethanol, and dry them to remove the ethanol to obtain a powdered product;

[0035] 7. Dispense the powdered finished product into sterile ampoules to obtain Shuanghuanglian sterile powder;

[0036] Example 2

[0037] 1. Take 5 parts of dried honeysuckle, add 100 parts of deionized water, soak for 12 hours, add 5 parts of sodium alkylphenol ether sulfosuccinate, extract by ultrasonication 3 times, 25 minutes each time, filter, combine the filtrates, concentrate under reduced pressure to 1:1, add an equal volume of 30% ethanol solution for alcohol precipitation for 24 hours, filter, dry the filtrate to obtain a gel-like mixture, wash three times with 85% ethanol, dry at 20℃ and 30Kpa to obtain powdered honeysuckle extract;

[0038] 2. Take 10 parts of dried Forsythia suspensa and put them into an extraction vessel. Add 50 parts of ethanol and 7 parts of methoxyacetonitrile. Extract at a pressure of 27 MPa and a temperature of 60°C. Pass CO2 through the vessel at a flow rate of 25 parts / h. The pressure of the analysis vessel I is 15 MPa and the temperature is 65°C. The pressure of the analysis vessel II is 6 MPa and the temperature is 50°C. Extract for 5 hours. Obtain the extract from the outlets of analysis vessel I and analysis vessel II. Fractionate the extract to recover the alcohol and polymerization inhibitor. The remaining powder is the Forsythia suspensa extract.

[0039] 3. Take 5 parts of dried Scutellaria baicalensis, cut into 0.6 mm thick slices, soak in 200 parts of deionized water for 2 hours, extract in a shaker at 40 kHz and 60 ℃ for 15 minutes, heat and decoct for 1.5 hours, concentrate at low temperature to ρ=1.05, adjust to pH 1 with concentrated hydrochloric acid, heat to 80 ℃ and keep warm for 0.5 hours, filter and collect the precipitate, add 20 parts of distilled water and adjust the pH to 7 with 40% sodium hydroxide solution, add an equal volume of 85% ethanol solution to the mixture, stir and let stand for 2 hours, filter and collect the filtrate, adjust the pH to 1 with concentrated hydrochloric acid, let stand for 2 hours, filter and collect the precipitate, wash the precipitate with distilled water, wash twice with 85% ethanol solution, and dry at 20 ℃ and 30 kPa to obtain Scutellaria baicalensis extract;

[0040] 4. The extracts were mixed in a mass ratio of honeysuckle extract: scutellaria extract: forsythia extract = 1:1:2, then ground and sieved through a 200-mesh sieve;

[0041] 5. Add 45 parts of deionized water, 1w% sodium carboxymethyl cellulose, and 15 parts of silver diethyldithiocarboxylate to 20 parts of mixed powder, mix thoroughly, and then spray granulate.

[0042] 6. Wash the granules twice with ethanol, and dry them to remove the ethanol to obtain a powdered product;

[0043] 7. Dispense the powdered finished product into sterile ampoules to obtain Shuanghuanglian sterile powder;

[0044] Example 3

[0045] 1. Take 5 parts of dried honeysuckle, add 100 parts of deionized water, soak for 12 hours, add 15 parts of sodium alkylphenol ether sulfosuccinate, and extract by ultrasonication 3 times, 25 minutes each time. Filter, combine the filtrates, concentrate under reduced pressure to 1:1, add an equal volume of 30% ethanol solution for alcohol precipitation for 24 hours, filter, dry the filtrate to obtain a gel-like mixture, wash three times with 85% ethanol, and dry at 20℃ and 30Kpa to obtain powdered honeysuckle extract;

[0046] 2. Take 10 parts of dried Forsythia suspensa and put them into an extraction vessel. Add 50 parts of ethanol and 3 parts of methoxyacetonitrile. Extract at a pressure of 27 MPa and a temperature of 60°C. Pass CO2 through the vessel at a flow rate of 25 parts / h. The pressure of the analysis vessel I is 15 MPa and the temperature is 65°C. The pressure of the analysis vessel II is 6 MPa and the temperature is 50°C. Extract for 5 hours. Obtain the extract from the outlets of analysis vessel I and analysis vessel II. Fractionate the extract to recover alcohol and polymerization inhibitor. The remaining powder is the Forsythia suspensa extract.

[0047] 3. Take 5 parts of dried Scutellaria baicalensis, cut into 0.9 mm thick slices, soak in 200 parts of deionized water for 2 hours, extract in a shaker at 40 kHz and 60 ℃ for 15 minutes, heat and decoct for 1.5 hours, concentrate at low temperature to ρ=1.05, adjust to pH 1 with concentrated hydrochloric acid, heat to 80 ℃ and keep warm for 0.5 hours, filter and collect the precipitate, add 20 parts of distilled water and adjust the pH to 7 with 40% sodium hydroxide solution, add an equal volume of 85% ethanol solution to the mixture, stir and let stand for 2 hours, filter and collect the filtrate, adjust the pH to 1 with concentrated hydrochloric acid, let stand for 2 hours, filter and collect the precipitate, wash the precipitate with distilled water, wash twice with 85% ethanol solution, and dry at 20 ℃ and 30 kPa to obtain Scutellaria baicalensis extract;

[0048] 4. The extracts were mixed in a mass ratio of honeysuckle extract: scutellaria extract: forsythia extract = 1:1:2, then ground and sieved through a 200-mesh sieve;

[0049] 5. Add 45 parts of deionized water, 1w% sodium carboxymethyl cellulose, and 5 parts of silver diethyldithiocarboxylate to 20 parts of mixed powder, mix thoroughly, and then spray granulate.

[0050] 6. Wash the granules twice with ethanol, and dry them to remove the ethanol to obtain a powdered product;

[0051] 7. Dispense the powdered finished product into sterile ampoules to obtain Shuanghuanglian sterile powder;

[0052] Comparative Example 1

[0053] The difference between this comparative example and Example 1 is that step 1 is as follows:

[0054] 1. Take 5 parts of dried honeysuckle medicinal material, add 100 parts of deionized water, soak in cold water for 12 hours, extract by ultrasonication 3 times, filter for 25 minutes each time, combine the filtrates, concentrate under reduced pressure to 1:1, add an equal volume of 30% ethanol solution for alcohol precipitation for 24 hours, filter by suction, dry the filtrate to obtain a gel-like mixture, wash three times with 85% ethanol, dry at 20℃ and 30Kpa to obtain powdered honeysuckle extract;

[0055] Comparative Example 2

[0056] The difference between this comparative example and Example 1 is that the sodium alkylphenol ether sulfosuccinate in step 1 is sodium fatty alcohol polyoxyethylene ether sulfate, and the rest of the implementation is the same as in Example 1.

[0057] Comparative Example 3

[0058] The difference between this comparative example and Example 1 is that step 2 is as follows:

[0059] 2. Take 10 parts of dried Forsythia suspensa and put them into an extraction vessel. Add 50 parts of ethanol and extract at a pressure of 27 MPa and a temperature of 60°C. Pass CO2 through at a flow rate of 25 parts / h. The pressure of the analysis vessel I is 15 MPa and the temperature is 65°C. The pressure of the analysis vessel II is 6 MPa and the temperature is 50°C. Extract for 5 hours. Obtain the extract from the outlets of analysis vessel I and analysis vessel II. Fractionate the extract to recover alcohol and polymerization inhibitor. The remaining powder is the Forsythia suspensa extract.

[0060] Comparative Example 4

[0061] The difference between this comparative example and Example 1 is that the methoxyacetonitrile in step 2 is acetylcyanide, and the rest of the implementation is the same as in Example 1.

[0062] Comparative Example 5

[0063] The difference between this comparative example and Example 1 is that step 5 is as follows:

[0064] 5. Add 45 parts of deionized water and 1w% sodium carboxymethyl cellulose to 20 parts of mixed powder, mix thoroughly, and then spray granulate;

[0065] Comparative Example 6

[0066] The difference between this comparative example and Example 1 is that the silver diethyldithiocarbamate in step 5 is sodium methyldithiocarbamate, and the rest of the implementation methods are the same as in Example 1.

[0067] Product testing: Powder injections were prepared according to Examples 1-3 and Comparative Examples 1-6, respectively.

[0068] 1) According to the Chinese Pharmacopoeia, the contents of chlorogenic acid and forsythoside were determined by high performance liquid chromatography (General Rule 0512): Preparation of reference solutions: Accurately weigh 40 mg of chlorogenic acid and forsythoside reference standards, place them separately in 100 ml volumetric flasks, dissolve them in methanol to the mark, and shake well to obtain the chlorogenic acid and forsythoside reference solutions; Preparation of experimental solutions: Accurately weigh 40 mg each of the powder injections prepared in Examples 1-3 and Comparative Examples 1-6, place the samples in 100 ml volumetric flasks, add 50 ml of 50% methanol, sonicate for 10 min, cool, add 50% methanol to the mark, and shake well to obtain the experimental solutions; Accurately pipette 10 μl each of the reference standard and test solutions, inject them into the liquid chromatograph for determination. The chromatographic conditions were: Packed ODS-AC column. 18 The column (250 mm x 4.6 mm, 5 μm) was filled with octadecylsilane-bonded silica gel; the mobile phase was methanol-water-phosphoric acid (47:53:0.2); the detection wavelength was 280 nm; the theoretical plate number, calculated based on the baicalin peak, should be no less than 2500; the measured data are shown in Table 1.

[0069] 2) Determination of impurity (auxiliary agents and polymerization inhibitors) content: Prepare a series of standard solutions of auxiliary agents and polymerization inhibitors with known concentrations, and perform liquid chromatography tests to establish a standard curve. Weigh 10 mg of each of the powder injections prepared in Examples 1-3 and Comparative Examples 1-6, dissolve them in 20 ml of 50% ethanol solution to prepare samples, and analyze the samples using a liquid chromatography instrument. By measuring the peak areas of auxiliary agents and polymerization inhibitors in the samples and comparing them with the standard curve, the content of impurities in the mixture can be determined. The measured data are shown in Table 1.

[0070] 3) Determination of bacterial endotoxin content: The turbidimetric method was used to determine the endotoxin content by detecting the turbidity change during the reaction between the Limulus amebocyte lysate (LAL) reagent and the endotoxin. The sensitivity of the LAL reagent was combined before the test, and a highly sensitive LAL reagent with a sensitivity of up to 0.03 EU / ml was used for testing. The bacterial endotoxin results for each case are shown in Table 1.

[0071] 4) Treatment efficacy test: 180 healthy laying hens of similar weight were randomly divided into 9 groups. Each group was injected with 0.2 ml of pathogenic E. coli. The hens were kept in the same chicken house, and the house was kept humid for 3 hours daily without heating for 3 consecutive days. After 3 days, the hens began to show obvious symptoms. 1.2 g of sterile Shuanghuanglian powder prepared in Examples 1-3 and Comparative Examples 1-6 was dissolved in 200 ml of physiological saline and administered intramuscularly to the 9 groups of hens. The frequency of administration was twice daily, 1 ml per bird, for 3 consecutive days. All groups were kept under the same environmental conditions. From the first day after administration, the changes in clinical symptoms of the chickens were observed and recorded daily, mainly including lethargy, head retraction and closed eyes, increased water intake, decreased feed intake, diarrhea, greenish-white watery feces, and death. All dead chickens underwent necropsy to determine the cause of death. The clinical efficacy results were statistically analyzed after 10 days and are shown in Table 2.

[0072] Clinical efficacy evaluation criteria:

[0073] Recovery: The chicken is alive and energetic, and its appetite is normal;

[0074] Significant effect: The chickens are alive and energetic, but their appetite has not yet fully returned to normal;

[0075] Ineffective: The chicken died, and necropsy revealed infectious bronchitis lesions;

[0076] Effective rate = (Number of cured cases + Number of cases showing significant improvement) / 20 × 100%

[0077] Table 1. Results of Powder Injection Test

[0078] Chlorogenic acid content (%) Forsythoside content (%) Impurity content (%) Bacterial endotoxin content (EU / ml) Example 1 1.62 0.55 0.00 0.0133 Example 2 1.58 0.56 0.00 0.0141 Example 3 1.66 0.53 0.00 0.0138 Comparative Example 1 0.31 0.47 0.00 0.0148 Comparative Example 2 0.72 0.47 0.00 0.0152 Comparative Example 3 1.40 0.21 0.00 0.0154 Comparative Example 4 1.36 0.36 0.00 0.0149 Comparative Example 5 1.42 0.48 0.03 Exceeding the standard Comparative Example 6 1.39 0.46 0.02 0.0258

[0079] Table 2 Treatment Efficacy Table

[0080] Number of cured Effective number Effectiveness (%) Example 1 14 5 95 Example 2 12 6 90 Example 3 15 4 95 Comparative Example 1 5 10 75 Comparative Example 2 8 8 80 Comparative Example 3 4 11 75 Comparative Example 4 8 9 85 Comparative Example 5 2 6 40 Comparative Example 6 4 9 65

Claims

1. A sterile Shuanghuanglian powder for injection, characterized in that: The preparation steps are as follows: (1) Take 5 parts of dried honeysuckle medicinal material, add 100 parts of deionized water, soak for 12 hours, add 5-15 parts of auxiliary agent, extract by ultrasonication 3 times, filter for 25 minutes each time, combine the filtrates, concentrate under reduced pressure to 1:1, add an equal volume of 30% ethanol solution for alcohol precipitation for 24 hours, filter, dry the filtrate to obtain a gel-like mixture, wash three times with 85% ethanol, dry at 20℃ and 30Kpa to obtain powdered honeysuckle extract; the auxiliary agent is sodium alkylphenol ether sulfosuccinate; (2) Take 10 parts of dried Forsythia suspensa and put them into an extraction vessel. Add 50 parts of ethanol and 3-7 parts of polymerization inhibitor. Extract at a pressure of 27 MPa and a temperature of 60°C. Pass CO2 through at a flow rate of 25 parts / h. The pressure of the analysis vessel I is 15 MPa and the temperature is 65°C. The pressure of the analysis vessel II is 6 MPa and the temperature is 50°C. Extract for 5 hours. Obtain the extract from the outlets of analysis vessel I and analysis vessel II. Fractionate the extract to recover the ethanol and polymerization inhibitor. The remaining powder is the Forsythia suspensa extract. The polymerization inhibitor is methoxyacetonitrile. (3) Take 5 parts of dried Scutellaria baicalensis, cut into pieces with a thickness of 0.6~0.9 mm, soak in 200 parts of deionized water for 2 hours, extract in a shaker at 40 kHz and 60 ℃ for 15 minutes, heat and decoct for 1.5 hours, concentrate at low temperature to ρ=1.05, adjust to 1 with concentrated hydrochloric acid, heat to 80 ℃ and keep warm for 0.5 hours, filter and keep the precipitate, add 20 parts of distilled water and adjust the pH to 7 with 40% sodium hydroxide solution, add an equal amount of 85% ethanol solution to the mixture, stir and let stand for 2 hours, filter and keep the filtrate, adjust the pH to 1 with concentrated hydrochloric acid, let stand for 2 hours, filter and keep the precipitate, wash the precipitate with distilled water, wash twice with 85% ethanol solution, and dry at 20 ℃ and 30 kPa to obtain Scutellaria baicalensis extract; (4) The extracts were mixed in a mass ratio of honeysuckle extract: scutellaria extract: forsythia extract = 1:1:2, then ground and sieved through a 200-mesh sieve; (5) Add 45 parts of deionized water, 1w% sodium carboxymethyl cellulose, and 5-15 parts of purifying agent to 20 parts of mixed powder, mix thoroughly, and then spray granulate; the purifying agent is silver diethyldithiocarboxylate. (6) Wash the particles twice with ethanol, and dry them to remove the ethanol to obtain a powdered product; (7) Dispense the powdered finished product into sterile ampoules to obtain Shuanghuanglian sterile powder.