Preparation method of Qingre Jiedu oral liquid

Abstract

This invention discloses a method for preparing a heat-clearing and detoxifying oral liquid. Honeysuckle and Scutellaria baicalensis are pulverized and sieved, then enzymatically hydrolyzed with water, ultrasonically extracted, and filtered to obtain extract A. Scrophularia ningpoensis, Rehmannia glutinosa, Forsythia suspensa, Gardenia jasminoides, Viola yedoensis, Gentiana scabra, Isatis indigotica, Anemarrhena asphodeloides, and Ophiopogon japonicus are warm-soaked in water and flash-extracted, then filtered to obtain extract B. Gypsum is crushed, decocted with water, and filtered to obtain extract C. The extracts are combined, concentrated, and sequentially clarified using a flocculant, followed by inorganic ceramic membrane microfiltration and organic ultrafiltration. The clarified liquid is then concentrated, flavoring agents and preservatives are added, the pH is adjusted, the volume is adjusted, filtered, filled, and sterilized to obtain the finished product. This invention utilizes a composite clarification process—low-temperature ultrasonic-enzymatic extraction of honeysuckle and Scutellaria baicalensis, clarification using a flocculant, inorganic ceramic membrane microfiltration, and organic ultrafiltration—to improve the extraction rate of effective components, effectively remove large molecular impurities such as tannins, proteins, and pectin, and significantly improve the clarity and stability of the product.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to a method for preparing a heat-clearing and detoxifying oral liquid. Background Technology

[0002] Qingre Jiedu Oral Liquid is a classic traditional Chinese medicine preparation included in the Chinese Pharmacopoeia. It has the effects of clearing heat and detoxifying, and is clinically used for symptoms such as fever, flushed face, irritability, thirst, sore throat, influenza, and upper respiratory tract infection caused by excessive heat and toxins. The prescription consists of twelve medicinal materials: gypsum, honeysuckle, scrophularia, rehmannia, forsythia, gardenia, violet, scutellaria, gentian, isatis root, anemarrhena, and ophiopogon. Among them, honeysuckle and scutellaria are the principal herbs, containing key active ingredients such as chlorogenic acid and baicalin, respectively.

[0003] The method for preparing the oral liquid for clearing heat and detoxifying in the Chinese Pharmacopoeia is as follows: Soak ten herbs, excluding honeysuckle and scutellaria, such as gypsum, in water for 1 hour. Then decoct twice (adding honeysuckle and scutellaria after boiling), the first time for 1 hour and the second time for 40 minutes. Filter, combine the filtrates, concentrate the filtrate to a relative density of approximately 1.17 (80℃), add ethanol to achieve an alcohol content of 65%–70%, refrigerate for 48 hours, filter, recover the ethanol from the filtrate, add an appropriate amount of flavoring agent, add 5g of activated charcoal, heat for 30 minutes, filter, add water to 1000ml, filter, fill, seal, and sterilize to obtain the final product.

[0004] Chlorogenic acid is the main active ingredient in honeysuckle. In the above preparation method, prolonged high-temperature decoction easily hydrolyzes chlorogenic acid, leading to a significant decrease in its content and reduced efficacy. Baicalin, under high-temperature and prolonged decoction conditions, is easily hydrolyzed into baicalein. Baicalein contains an ortho-triphenol hydroxyl structure, is chemically reactive, and is easily oxidized to form quinone-like colored substances, causing the decoction to turn green or black. This not only affects the product's appearance but also results in the loss of active ingredients and reduces clinical efficacy.

[0005] The above preparation method uses alcohol precipitation and activated carbon adsorption to remove impurities. Although alcohol precipitation can precipitate some large molecular impurities, its removal rate for impurities such as tannins, proteins, and pectin is limited. Activated carbon adsorption has poor selectivity, and while adsorbing impurities, it also adsorbs some active ingredients, such as chlorogenic acid and baicalin, resulting in a loss of efficacy. If tannins, proteins, pectin, etc., are not completely removed, they will slowly accumulate during the storage period of the oral liquid, forming precipitates, leading to decreased product clarity, discoloration, and the appearance of flocculent matter, seriously affecting product stability and shelf life.

[0006] Chinese patent CN106938001A discloses a heat-clearing and detoxifying oral liquid and its preparation process. The traditional decoction method makes the heat-sensitive components chlorogenic acid and baicalin easily hydrolyzed and oxidized under high temperature and long-term decoction conditions, resulting in the loss of effective components. Moreover, it only uses a single clarifying agent for flocculation and clarification, which does not completely remove large molecular impurities, and the clarity and long-term stability of the product need to be improved. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a method for preparing a heat-clearing and detoxifying oral liquid.

[0008] This invention provides a method for preparing a heat-clearing and detoxifying oral liquid to solve the technical problems of degradation of heat-sensitive components, large loss due to alcohol precipitation, and poor clarity in the prior art.

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

[0010] The preparation method of the heat-clearing and detoxifying oral liquid includes the following steps:

[0011] a. Grind and sieve the clean honeysuckle and scutellaria baicalensis, add water for enzymatic hydrolysis, and extract by ultrasonication to obtain extract A;

[0012] b. Take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola, Gentian, Isatis root, Anemarrhena, and Ophiopogon, add water and soak at a warm temperature, perform flash extraction, and filter to obtain extract B;

[0013] c. Crush the gypsum medicinal material, add water and decoct, then filter to obtain extract C;

[0014] d. Combine extracts A, B, and C, concentrate them, and then sequentially clarify them using a flocculant, followed by microfiltration using an inorganic ceramic membrane and fine filtration using an organic ultrafiltration membrane. Concentrate the clarified liquid, add flavoring agents and preservatives, adjust the pH value, make up to volume, filter, fill, and sterilize to obtain the finished product.

[0015] Further, in step a, the amount of water added is 8-12 times the total weight of honeysuckle and scutellaria; the enzymatic hydrolysis is based on the total weight of honeysuckle and scutellaria, with the addition of 0.2-0.4% cellulase, 0.1-0.3% pectinase, and 0.05-0.15% papain, the enzymatic hydrolysis temperature is 40-50℃, the enzymatic hydrolysis time is 1-2 hours, and the pH value of the enzymatic hydrolysis is 4.5-5.0.

[0016] The inventors unexpectedly discovered that enzymatic hydrolysis and ultrasonic synergistic extraction of honeysuckle and scutellaria under weakly acidic conditions of pH 4.5-5.0, combined with the chitosan-gelatin flocculation and membrane filtration process in subsequent step d, created a synergistic effect: the weakly acidic environment not only helps cellulase and pectinase maintain their activity and promotes cell wall rupture to release effective components, but also allows acidic components such as chlorogenic acid and baicalin to exist in molecular form, reducing ionization loss.

[0017] Furthermore, the ultrasonic extraction power is 200-400W, the ultrasonic frequency is 20-40kHz, the temperature is 40-50℃, and the time is 20-40 minutes.

[0018] Step a of this invention employs a combined low-temperature ultrasonic and enzymatic extraction method, extracting honeysuckle and scutellaria baicalensis at a low temperature of 40-50℃. This effectively increases the extraction rate of chlorogenic acid and baicalin, while avoiding the generation of high-temperature hydrolysis products.

[0019] Further, in step b, take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola, Gentian, Isatis root, Anemarrhena, and Ophiopogon, add 6-10 times the amount of water, and soak for 20-40 minutes.

[0020] Furthermore, the flash extraction is performed at a speed of 6000-8000 rpm, an extraction time of 2-4 minutes, and an extraction temperature of 50-60℃; the extraction is performed 1-2 times.

[0021] Step b of this invention employs flash extraction to rapidly extract nine medicinal herbs—Scrophularia, Rehmannia, Forsythia, Gardenia, Viola yedoensis, Gentiana, Isatis root, Anemarrhena, and Ophiopogon japonicus—at a low temperature. Through high-speed mechanical shearing force and molecular penetration, the herbal tissues are thoroughly broken down in a short time, allowing for efficient dissolution of the active ingredients. The temperature is controlled within the range of 50-70℃, which avoids the degradation of heat-sensitive components and excessive dissolution of impurities caused by traditional long-term high-temperature decoction, and significantly shortens the extraction cycle and reduces energy consumption.

[0022] Further, in step c, the gypsum is crushed, 8-12 times the amount of water is added, and it is decocted for 0.5-1.5 hours; the extract C is obtained by filtration.

[0023] In step c of this invention, gypsum is crushed and then boiled with water for extraction. Mechanical crushing increases the specific surface area of ​​the mineral medicinal material, promoting the full dissolution of calcium ions and sulfate ions in hydrated calcium sulfate. Boiling alone for 0.5-1.5 hours ensures the complete extraction of the medicinal components of gypsum for clearing heat, purging fire, relieving irritability, and quenching thirst. At the same time, it avoids pH changes when its weakly alkaline decoction is mixed with the extracts of acidic components such as honeysuckle and scutellaria, thus preventing the degradation or precipitation of effective components such as chlorogenic acid and baicalin due to changes in the acid-base environment, ensuring the stability of the overall formula and its clinical efficacy.

[0024] Further, in step d, extracts A, B, and C are combined and concentrated to a relative density of 1.05-1.15 before being clarified using a flocculant.

[0025] Furthermore, in step d, a chitosan-gelatin composite flocculant is used, with chitosan accounting for 0.10-0.20% and gelatin accounting for 0.05-0.15%, the flocculation temperature being 40-50℃ and the standing time being 1.5-2.5 hours.

[0026] Furthermore, in step d, the inorganic ceramic membrane has a pore size of 100-200 nm, is made of α-Al2O3, operates at a pressure of 0.15-0.25 MPa, and is at a temperature of 35-45 °C.

[0027] Furthermore, in step d, the organic ultrafiltration membrane has a molecular cutoff of 5-10 kDa, is made of polyethersulfone or polysulfone, operates at a pressure of 0.10-0.15 MPa, and is at a temperature of 30-40°C.

[0028] Furthermore, in step d, the clarified liquid is concentrated at a temperature of 45-55℃ and a vacuum degree of -0.08~-0.09MPa until the relative density is 1.17-1.20.

[0029] In step d of this invention, extracts A, B, and C are combined and then subjected to a composite clarification process consisting of flocculant clarification, inorganic ceramic membrane microfiltration, and organic ultrafiltration membrane fine filtration. This process effectively removes macromolecular impurities such as tannins, proteins, and pectin, significantly improving the clarity and stability of the product.

[0030] Further, in step d, the pH value is adjusted to 5.0-6.0.

[0031] The beneficial effects of this invention are:

[0032] This invention improves the preparation method of a heat-clearing and detoxifying oral liquid. First, honeysuckle and scutellaria are extracted using low-temperature ultrasonic and enzymatic hydrolysis, increasing the extraction rates of chlorogenic acid, baicalin, and forsythoside. Decoction of gypsum separately ensures complete extraction of its medicinal components and avoids pH changes when the weakly alkaline decoction is mixed with the acidic extracts of honeysuckle and scutellaria, thus preventing degradation or precipitation of chlorogenic acid, baicalin, and other effective components due to changes in the acid-base environment. This invention employs a composite clarification process using flocculants, inorganic ceramic membrane microfiltration, and organic ultrafiltration membrane filtration, effectively removing large molecular impurities such as tannins, proteins, and pectin, significantly improving the clarity and stability of the product. The finished product prepared by this method has higher contents of baicalin, chlorogenic acid, and forsythoside than those obtained using the pharmacopoeia method, and also improves the extraction rate of the effective components of the heat-clearing and detoxifying oral liquid. The finished product obtained using this method has good clarity and stability, and has broad application prospects. Detailed Implementation

[0033] The present invention will be further described in detail below through specific embodiments. All raw materials and reagents involved in the embodiments are commercially available. Experimental methods not specified in the embodiments are generally performed under conventional conditions.

[0034] Example 1

[0035] Prescription: Honeysuckle 174.2g, Scutellaria baicalensis 87.1g, Scrophularia ningpoensis 139.1g, Rehmannia glutinosa 104g, Forsythia suspensa 87.1g, Gardenia jasminoides 87.1g, Viola yedoensis 87.1g, Gentiana scabra 87.1g, Isatis indigotica 87.1g, Anemarrhena asphodeloides 70.2g, Ophiopogon japonicus 70.2g, Gypsum fibrosum 871g.

[0036] a. According to the above prescription, put clean honeysuckle and scutellaria into the extraction tank, add 8 times the amount of purified water, adjust the pH to 4.8, add 0.2% cellulase, 0.1% pectinase and 0.06% papain, and enzymatically hydrolyze at 40℃ for 1 hour. The pH of the enzymatic hydrolysis is 4.6. The stirring speed is 60 rpm. After enzymatic hydrolysis, raise the temperature to 40℃, start the ultrasonic generator, ultrasonic temperature 40℃, ultrasonic power 200W, ultrasonic frequency 20kHz, and ultrasonic extraction for 25 minutes. Filter to obtain extract A.

[0037] b. Take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola, Gentian, Isatis root, Anemarrhena, and Ophiopogon and put them into a flash extractor. Add 6 times the amount of water and soak for 20 minutes. Perform flash extraction at a speed of 6000 rpm for 2 minutes at a temperature of 50°C. The extraction is performed once. Filter to obtain extract B.

[0038] c. Crush the gypsum medicinal material and put it into a decoction pot. Add 8 times the amount of water and decoct for 1 hour. Filter to obtain extract C.

[0039] d. Combine extracts A, B, and C, concentrate to a relative density of 1.1 (60℃), clarify using chitosan-gelatin flocculant (0.1% chitosan, 0.05% gelatin), stir at 40℃ for 20 minutes, let stand for 1.5 hours, centrifuge, and take the supernatant. Use an α-Al₂O₃ ceramic membrane with a pore size of 150 nm, operating pressure 0.18 MPa, temperature 35℃ for ultrafiltration, then use a polyethersulfone ultrafiltration membrane with a molecular weight cutoff of 6 kDa, operating pressure 0.12 MPa, temperature 30℃ to obtain a clarified liquid. Concentrate the clarified liquid at 45℃ under a vacuum of -0.08 MPa to a relative density of 1.18 measured at 80℃. Add appropriate amounts of stevioside and potassium sorbate as usual, adjust the pH to 5.6 with citrate-sodium citrate buffer, make up to volume, filter using a 0.22 μm microporous membrane, fill, and sterilize to obtain the finished product.

[0040] Example 2

[0041] Prescription: Honeysuckle 174.2g, Scutellaria baicalensis 87.1g, Scrophularia ningpoensis 139.1g, Rehmannia glutinosa 104g, Forsythia suspensa 87.1g, Gardenia jasminoides 87.1g, Viola yedoensis 87.1g, Gentiana scabra 87.1g, Isatis indigotica 87.1g, Anemarrhena asphodeloides 70.2g, Ophiopogon japonicus 70.2g, Gypsum fibrosum 871g.

[0042] a. According to the above prescription, put clean honeysuckle and scutellaria into the extraction tank, add 10 times the amount of purified water, adjust the pH value to 4.8, add 0.3% cellulase, 0.2% pectinase and 0.10% papain, and enzymatically hydrolyze at 45℃ for 1 hour. The pH value of the enzymatic hydrolysis is 5.0. The stirring speed is 60 rpm. After enzymatic hydrolysis, raise the temperature to 45℃, start the ultrasonic generator, ultrasonic temperature 45℃, ultrasonic power 300W, ultrasonic frequency 30kHz, and ultrasonic extraction for 30 minutes. Filter to obtain extract A.

[0043] b. Take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola yedoensis, Gentian, Isatis root, Anemarrhena, and Ophiopogon japonicus and put them into a flash extractor. Add 8 times the amount of water and soak for 30 minutes. Perform flash extraction at a speed of 7000 rpm for 3 minutes at a temperature of 55°C. The extraction is performed twice. Filter to obtain extract B.

[0044] c. Crush the gypsum medicinal material and put it into a decoction pot. Add 10 times the amount of water and decoct for 1.2 hours. Filter to obtain extract C.

[0045] d. Combine extracts A, B, and C, concentrate to a relative density of 1.12 (60℃), clarify using chitosan-gelatin flocculant (0.15% chitosan, 0.10% gelatin), stir at 45℃ for 20 minutes, let stand for 2 hours, centrifuge, and take the supernatant. Use an α-Al₂O₃ ceramic membrane with a pore size of 200 nm, operating pressure 0.20 MPa, temperature 40℃ for ultrafiltration, then use a polyethersulfone ultrafiltration membrane with a molecular weight cutoff of 8 kDa, operating pressure 0.13 MPa, temperature 35℃ to obtain a clarified liquid. Concentrate the clarified liquid at 50℃ under a vacuum of -0.08 MPa to a relative density of 1.19 at 80℃. Add appropriate amounts of stevioside and potassium sorbate as usual, adjust the pH to 5.6 with citrate-sodium citrate buffer, make up to volume, filter using a 0.22 μm microporous membrane, fill, and sterilize to obtain the finished product.

[0046] Example 3

[0047] Prescription: Honeysuckle 174.2g, Scutellaria baicalensis 87.1g, Scrophularia ningpoensis 139.1g, Rehmannia glutinosa 104g, Forsythia suspensa 87.1g, Gardenia jasminoides 87.1g, Viola yedoensis 87.1g, Gentiana scabra 87.1g, Isatis indigotica 87.1g, Anemarrhena asphodeloides 70.2g, Ophiopogon japonicus 70.2g, Gypsum fibrosum 871g.

[0048] a. According to the above prescription, put clean honeysuckle and scutellaria into the extraction tank, add 12 times the amount of purified water, adjust the pH to 4.8, add 0.4% cellulase, 0.3% pectinase and 0.15% papain, and enzymatically hydrolyze at 50℃ for 2 hours. The pH of the enzymatic hydrolysis is 4.5. The stirring speed is 60 rpm. After enzymatic hydrolysis, raise the temperature to 50℃, start the ultrasonic generator, ultrasonic temperature 50℃, ultrasonic power 350W, ultrasonic frequency 40kHz, and ultrasonic extraction for 40 minutes. Filter to obtain extract A.

[0049] b. Take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola yedoensis, Gentian, Isatis root, Anemarrhena, and Ophiopogon japonicus and put them into a flash extractor. Add 10 times the amount of water and soak for 40 minutes. Perform flash extraction at a speed of 8000 rpm for 4 minutes at a temperature of 60°C. Extract twice and filter to obtain extract B.

[0050] c. Crush the gypsum medicinal material and put it into a decoction pot. Add 10 times the amount of water and decoct for 1.2 hours. Filter to obtain extract C.

[0051] d. Combine extracts A, B, and C, concentrate to a relative density of 1.12 (60℃), clarify using chitosan-gelatin flocculant (0.15% chitosan, 0.10% gelatin), stir at 45℃ for 20 minutes, let stand for 2 hours, centrifuge, and take the supernatant. Use an α-Al₂O₃ ceramic membrane with a pore size of 200 nm, operating pressure 0.20 MPa, temperature 40℃ for ultrafiltration, then use a polyethersulfone ultrafiltration membrane with a molecular weight cutoff of 10 kDa, operating pressure 0.13 MPa, temperature 35℃ to obtain a clarified liquid. Concentrate the clarified liquid at 50℃ under a vacuum of -0.08 MPa to a relative density of 1.19 measured at 80℃. Add appropriate amounts of stevioside and potassium sorbate as usual, adjust the pH to 5.6 with citrate-sodium citrate buffer, make up to volume, filter using a 0.22 μm microporous membrane, fill, and sterilize to obtain the finished product.

[0052] Comparative Example 1: Prepared according to Method I of the 2025 Edition of the Chinese Pharmacopoeia

[0053] Prescription: Honeysuckle 134g, Scutellaria baicalensis 67g, Scrophularia ningpoensis 107g, Rehmannia glutinosa 80g, Forsythia suspensa 67g, Gardenia jasminoides 67g, Viola yedoensis 67g, Gentiana scabra 67g, Isatis indigotica 67g, Anemarrhena asphodeloides 54g, Ophiopogon japonicus 54g, Gypsum 670g.

[0054] Of the twelve ingredients listed above, except for honeysuckle and scutellaria, the remaining ten ingredients, including gypsum, are first soaked in water at a warm temperature for 1 hour, then decocted twice (honeysuckle and scutellaria are added after boiling), the first time for 1 hour and the second time for 40 minutes. The decoction is then filtered, the filtrates are combined, and the filtrate is concentrated to a relative density of approximately 1.17 (80℃). Ethanol is added to bring the alcohol content to 65%–70%, and the mixture is refrigerated for 48 hours. The decoction is then filtered, the ethanol is recovered from the filtrate, an appropriate amount of flavoring agent is added, 5g of activated carbon is added, the mixture is heated for 30 minutes, filtered, water is added to 1000ml, filtered, bottled, and sterilized to obtain the final product.

[0055] Comparative Example 2

[0056] It was prepared according to the preparation method of Example 1 of Chinese Patent CN106938001A.

[0057] Comparative Example 3

[0058] Prescription: Honeysuckle 174.2g, Scutellaria baicalensis 87.1g, Scrophularia ningpoensis 139.1g, Rehmannia glutinosa 104g, Forsythia suspensa 87.1g, Gardenia jasminoides 87.1g, Viola yedoensis 87.1g, Gentiana scabra 87.1g, Isatis indigotica 87.1g, Anemarrhena asphodeloides 70.2g, Ophiopogon japonicus 70.2g, Gypsum fibrosum 871g.

[0059] a. According to the above prescription, put clean honeysuckle and scutellaria into an ultrasonic extractor, add 10 times the amount of purified water, heat to 45°C, start the ultrasonic generator, ultrasonic temperature 45°C, ultrasonic power 300W, ultrasonic frequency 30kHz, ultrasonic extraction for 30 minutes, and filter to obtain extract A. The remaining steps are the same as in Example 2.

[0060] Comparative Example 4

[0061] Prescription: Honeysuckle 174.2g, Scutellaria baicalensis 87.1g, Scrophularia ningpoensis 139.1g, Rehmannia glutinosa 104g, Forsythia suspensa 87.1g, Gardenia jasminoides 87.1g, Viola yedoensis 87.1g, Gentiana scabra 87.1g, Isatis indigotica 87.1g, Anemarrhena asphodeloides 70.2g, Ophiopogon japonicus 70.2g, Gypsum fibrosum 871g.

[0062] a. According to the above prescription, put clean honeysuckle and scutellaria into an extraction tank, add 10 times the amount of purified water, adjust the pH to 4.8, add 0.3% cellulase, 0.2% pectinase, and 0.10% papain, and enzymatically hydrolyze at 45°C for 1 hour with a stirring speed of 60 rpm. After enzymatic hydrolysis, filter to obtain extract A. The remaining steps are the same as in Example 2.

[0063] Comparative Example 5

[0064] Prescription: Honeysuckle 174.2g, Scutellaria baicalensis 87.1g, Scrophularia ningpoensis 139.1g, Rehmannia glutinosa 104g, Forsythia suspensa 87.1g, Gardenia jasminoides 87.1g, Viola yedoensis 87.1g, Gentiana scabra 87.1g, Isatis indigotica 87.1g, Anemarrhena asphodeloides 70.2g, Ophiopogon japonicus 70.2g, Gypsum fibrosum 871g.

[0065] d. Combine extracts A, B, and C, concentrate to a relative density of 1.12 (60℃), clarify using a chitosan-gelatin flocculant (0.15% chitosan, 0.10% gelatin), stir at 45℃ for 20 minutes, let stand for 2 hours, centrifuge, and concentrate the supernatant at 50℃ under a vacuum of -0.08 MPa to a relative density of 1.19 at 80℃. Add appropriate amounts of stevioside and potassium sorbate as usual, adjust the pH to 5.6 with citrate-sodium citrate buffer, bring to volume, filter using a 0.22 μm microporous membrane, fill, and sterilize to obtain the finished product. The remaining steps are the same as in Example 2.

[0066] Comparative Example 6

[0067] Prescription: Honeysuckle 174.2g, Scutellaria baicalensis 87.1g, Scrophularia ningpoensis 139.1g, Rehmannia glutinosa 104g, Forsythia suspensa 87.1g, Gardenia jasminoides 87.1g, Viola yedoensis 87.1g, Gentiana scabra 87.1g, Isatis indigotica 87.1g, Anemarrhena asphodeloides 70.2g, Ophiopogon japonicus 70.2g, Gypsum fibrosum 871g.

[0068] b. Take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola, Gentian, Isatis root, Anemarrhena, and Ophiopogon. Add 8 times the amount of water, soak for 30 minutes, heat to boiling, decoct for 1 hour, and filter through 120 mesh. Add 6 times the amount of water again, decoct for 40 minutes, filter through 120 mesh, combine the filtrates, and obtain extract B.

[0069] The remaining steps are the same as in Example 2.

[0070] Experimental Example

[0071] 1. Content detection

[0072] Baicalin content detection:

[0073] The contents of the oral liquid prepared in Examples 1-3 and Comparative Examples 1-6 were determined according to the method under the "Determination of Content" section of Part I of the Chinese Pharmacopoeia 2025 edition.

[0074] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; methanol-water-phosphoric acid (50:50:0.3) was used as the mobile phase; the detection wavelength was 276 nm. The theoretical plate number, calculated based on the baicalin peak, should not be less than 1000.

[0075] Preparation of reference solution: Take an appropriate amount of baicalin reference standard, accurately weigh it, and add 70% ethanol to prepare a solution containing 20 μg per 1 mL.

[0076] Preparation of the test solution: Accurately measure 2 mL of this product and place it in a 100 mL volumetric flask. Add an appropriate amount of 70% ethanol, shake, dilute to the mark with 70% ethanol, shake well, let stand, filter, and take the filtrate to obtain the test solution.

[0077] Determination method: Accurately pipette 10 μL each of the reference solution and the test solution into the liquid chromatograph and determine the result.

[0078] Chlorogenic acid content determination:

[0079] The content of honeysuckle in Shuanghuanglian oral liquid was determined according to the method described in the 2020 edition of the Chinese Pharmacopoeia, Part I.

[0080] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; methanol-water-glacial acetic acid (20:80:1) was used as the mobile phase; the detection wavelength was 324 nm. The theoretical plate number, calculated based on the chlorogenic acid peak, should be no less than 6000.

[0081] Preparation of reference solution: Weigh an appropriate amount of chlorogenic acid reference standard accurately, place it in a brown volumetric flask, and add water to prepare a solution containing 40 μg per 1 mL.

[0082] Preparation of the test solution: Accurately measure 2 mL of this product and place it in a 50 mL brown volumetric flask. Dilute with water to the mark and shake well to obtain the test solution.

[0083] Assay: Accurately pipette 10 μL of the reference solution and 10-20 μL of the test solution into the liquid chromatograph and determine the result.

[0084] Forsythoside content determination:

[0085] The method was formulated with reference to the Forsythia section of the "Content Determination" in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0086] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; acetonitrile-water (25:75) was used as the mobile phase; the detection wavelength was 278 nm. The theoretical plate number, calculated based on the forsythoside peak, should be no less than 6000.

[0087] Preparation of reference solution: Take an appropriate amount of forsythoside reference standard, accurately weigh it, and add 50% methanol to prepare a solution containing 60 μg per 1 mL.

[0088] Preparation of the test solution: Accurately measure 1 mL of this product and add it to a neutral alumina column (100-120 mesh, 6 g, inner diameter 1 cm). Elute with 40 mL of 70% ethanol, collect the eluent, concentrate to dryness, add an appropriate amount of 50% methanol to the residue, warm to dissolve, transfer to a 5 mL volumetric flask, dilute to the mark, and shake well to obtain the test solution.

[0089] The assay involves precisely pipetting 10 μL each of the reference solution and the test solution into a liquid chromatograph and measuring the results.

[0090] The measurement results are shown in Table 1.

[0091]

[0092] As shown in Table 1, the baicalin content determined in Examples 1-3 of this invention was 44.8%~60.0% higher than that determined by the pharmacopoeia method (comparative example), the chlorogenic acid content was 41.6%~46.9% higher, and the forsythoside content was 50%~71.4% higher. The effective component content of Comparative Example 5 was similar to that of the examples, but the filtration was incomplete, and the removal of large molecular impurities was incomplete, resulting in a significant decrease in clarity and stability.

[0093] 2. Extraction rate

[0094] (1) Determination of the content of effective components in medicinal materials

[0095] The prescribed amounts of honeysuckle, scutellaria, and forsythia were taken, and the contents of chlorogenic acid, baicalin, and forsythoside were determined according to the methods specified in Part I of the 2025 edition of the Chinese Pharmacopoeia, respectively, as the theoretical basis for calculating the extraction rate.

[0096] Honeysuckle: Determined by high performance liquid chromatography according to General Rule 0512, using octadecylsilane-bonded silica gel as the stationary phase; acetonitrile-0.4% phosphoric acid solution (13:87) as the mobile phase; detection wavelength 327 nm. Calculated on a dried basis, it contains chlorogenic acid (C... 16 H 18 O9) shall not be less than 1.5%.

[0097] Scutellaria baicalensis: Determined by high performance liquid chromatography according to General Rule 0512, using octadecylsilane-bonded silica gel as the stationary phase; methanol-water-phosphoric acid (47:53:0.2) as the mobile phase; detection wavelength 280 nm. Calculated on a dried basis, it contains baicalin (C... 21 H 18 O 11 () shall not be less than 9.0%.

[0098] Forsythia: Determined by high performance liquid chromatography according to General Rule 0512, using octadecylsilane-bonded silica gel as the stationary phase; acetonitrile-water (25:75) as the mobile phase; detection wavelength 277 nm. Calculated on a dried basis, it contains forsythoside (C... 27 H34 O 11 (It shall not be less than 0.15%).

[0099] The chlorogenic acid content in honeysuckle was determined to be 2.85%; the baicalin content in scutellaria baicalensis was 12.5%; and the forsythoside content in forsythia suspensa was 0.82%.

[0100] (2) Determination of the content of active ingredients in the preparation

[0101] Take the products prepared in Examples 1-3 and Comparative Examples 1-6, and determine the contents of baicalin, chlorogenic acid, and forsythoside according to the method under "Experimental Example 1 Content Detection" in this instruction manual.

[0102] Calculated according to the extraction rate formula:

[0103]

[0104] The results are shown in Table 2.

[0105]

[0106] 3. Clarity Measurement

[0107] Referring to the Clarity Test Method in General Chapter 0902 of Part IV of the 2020 Edition of the Chinese Pharmacopoeia, a comprehensive evaluation was conducted using Method 1 (visual inspection) and Method 2 (turbidimeter method). The results are shown in Table 3.

[0108]

[0109] As shown in Table 3, the turbidity of Examples 1-3 was all <1.0 NTU, and the solutions were clear and transparent, significantly better than the pharmacopoeia method of Comparative Example 1 (3.85 NTU). The turbidity of Comparative Example 5 increased to 2.56 NTU, proving the necessity of the three-stage composite clarification method of flocculation-ceramic membrane-ultrafiltration membrane in this invention.

[0110] 4. Stability

[0111] The stability tests were conducted on the samples from Example 2 and the comparative example at 25°C and 60% relative humidity for 3, 6, and 9 months, respectively. The results are shown in Table 4.

[0112]

[0113] As shown in Table 4, in Example 2 of the present invention, after being placed at 25°C and 60% relative humidity for 9 months, the turbidity remained within the range of 0.62~0.70 NTU, with a variation of only 0.08 NTU. Visual inspection showed that it was a clear brownish-red liquid with no sediment or flocculent matter, demonstrating stable clarity.

Claims

1. A method for preparing a heat-clearing and detoxifying oral liquid, characterized in that: Includes the following steps: a. Grind and sieve the clean honeysuckle and scutellaria baicalensis, add water for enzymatic hydrolysis, extract by ultrasonication, and filter to obtain extract A; b. Take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola, Gentian, Isatis root, Anemarrhena, and Ophiopogon, add water and soak at a warm temperature, perform flash extraction, and filter to obtain extract B; c. Crush the gypsum medicinal material, add water and decoct, then filter to obtain extract C; d. Combine extracts A, B, and C, concentrate them, and then sequentially clarify them using a flocculant, followed by microfiltration using an inorganic ceramic membrane and fine filtration using an organic ultrafiltration membrane. Concentrate the clarified liquid, add flavoring agents and preservatives, adjust the pH value, make up to volume, filter, fill, and sterilize to obtain the finished product.

2. The preparation method according to claim 1, characterized in that: In step a, the amount of water added is 8-12 times the total weight of honeysuckle and scutellaria; for enzymatic hydrolysis, based on the total weight of honeysuckle and scutellaria, 0.2-0.4% cellulase, 0.1-0.3% pectinase, and 0.05-0.15% papain are added. The enzymatic hydrolysis temperature is 40-50℃, and the enzymatic hydrolysis time is 1-2 hours; the pH value for enzymatic hydrolysis is 4.5-5.

0.

3. The preparation method according to claim 2, characterized in that: In step a, the ultrasonic extraction power is 200-400W, the ultrasonic frequency is 20-40kHz, the temperature is 40-50℃, and the time is 20-40 minutes.

4. The preparation method according to claim 1, characterized in that: In step b, take clean Scrophularia, Rehmannia, Forsythia, Gardenia, Viola, Gentian, Isatis root, Anemarrhena, and Ophiopogon, add 6-10 times the amount of water, and soak for 20-40 minutes.

5. The preparation method according to claim 1, characterized in that: In step b, the flash extraction speed is 6000-8000 r / min, the extraction time is 2-4 minutes, the extraction temperature is 50-60℃, and the extraction is performed 1-2 times.

6. The preparation method according to claim 1, characterized in that: In step c, crush the gypsum, add 8-12 times the amount of water, and decoct for 0.5-1.5 hours; filter to obtain extract C.

7. The preparation method according to claim 1, characterized in that: In step d, a chitosan-gelatin composite flocculant is used, with chitosan dosage of 0.10-0.20% and gelatin dosage of 0.05-0.15%, flocculation temperature of 40-50℃, and standing time of 1.5-2.5 hours.

8. The preparation method according to claim 1, characterized in that: In step d, the inorganic ceramic membrane has a pore size of 100-200 nm, is made of α-Al2O3, operates at a pressure of 0.15-0.25 MPa, and is at a temperature of 35-45 °C.

9. The preparation method according to claim 1, characterized in that: In step d, the organic ultrafiltration membrane has a molecular cutoff of 5-10 kDa, is made of polyethersulfone or polysulfone, operates at a pressure of 0.10-0.15 MPa, and is at a temperature of 30-40°C.

10. The preparation method according to claim 1, characterized in that: In step d, the clarified liquid is concentrated at a temperature of 45-55℃ and a vacuum degree of -0.08~-0.09MPa until the relative density is 1.17-1.20.

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