Preparation method of Qiqing toxin-vanquishing granules
The effective components of Polygonum cuspidatum and Isatis indigotica were extracted by ethanol extraction and combined with the aqueous extract, which solved the problem of insufficient efficacy in the existing technology and achieved higher efficacy and stability.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- LUOYANG RUIHUA ANIMAL HEALTH PROD
- Filing Date
- 2024-11-04
- Publication Date
- 2026-05-08
AI Technical Summary
The existing preparation method for Qiqing Baidu Granules fails to effectively extract the active ingredients from Polygonum cuspidatum and Isatis indigotica, resulting in insufficient efficacy.
The active ingredients in Polygonum cuspidatum and Isatis indigotica were extracted separately using ethanol extraction. The extracts were then combined with the aqueous extracts of other medicinal materials, and a stabilizer was added to form granules to ensure that the active ingredients were not lost.
It increases the content of active ingredients in Polygonum cuspidatum and Isatis indigotica, enhances the efficacy, improves the stability of the product, and significantly improves the cure rate and effectiveness.
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Figure BDA0005116584150000071
Abstract
Description
Technical Field
[0001] This invention belongs to the field of veterinary drugs in the biomedical field, and relates to a method for preparing Qiqing Baidu Granules. Background Technology
[0002] The 2020 edition of the *Veterinary Pharmacopoeia of the People's Republic of China*, Volume II, includes the prescription for Qiqing Baidu Granules: Scutellaria baicalensis 100g, Polygonum cuspidatum 100g, Pulsatilla chinensis 80g, Sophora flavescens 80g, Isatis indigotica 100g, Dryopteris crassirhizoma 60g, and Isatis tinctoria 40g. These seven ingredients are decocted twice with water, the first time for 2 hours and the second time for 1 hour. The decoction is filtered, the filtrates are combined, and concentrated under reduced pressure below 80℃ to a relative density of 1.30–1.35 (at 55℃) to obtain a clear extract. Appropriate amounts of sucrose and dextrin are added, mixed well, granulated, dried, and the product is obtained in 560g portions. This product is mainly used to treat damp-heat diarrhea and white diarrhea in chicks. However, the effective components of Polygonum cuspidatum and Isatis tinctoria were not well extracted from the finished product using this method.
[0003] The effective components of Polygonum cuspidatum, such as emodin and chrysophanol, are obtained more by ethanol extraction than by decoction with water. Indigofera tinctoria, the main component of Isatis indigotica, is almost insoluble in water but slightly soluble in ethanol. Ethanol extraction can better extract the effective components of Polygonum cuspidatum and Isatis indigotica.
[0004] Therefore, we have developed a new preparation method that can better extract the active ingredients from Polygonum cuspidatum and Isatis indigotica without reducing or improving the original efficacy. Summary of the Invention
[0005] The present invention adopts the following technical solution:
[0006] This invention provides a method for preparing Qiqing Baidu Granules, which exhibits good stability and yields granules with enhanced efficacy. The method involves separately extracting and concentrating Isatis tinctoria leaves and Polygonum cuspidatum with ethanol, then adding a stabilizer to prevent loss of active ingredients. The extracts are then combined with aqueous extracts from other medicinal materials, and appropriate amounts of sucrose and dextrin are added, mixed thoroughly, granulated, and dried to obtain the final product.
[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: it is composed of the following parts by weight: 15-18 parts of Scutellaria baicalensis, 15-18 parts of Polygonum cuspidatum, 12-15 parts of Pulsatilla chinensis, 12-15 parts of Sophora flavescens, 15-18 parts of Isatis indigotica, 8-10 parts of Dryopteris crassirhizoma, 6-8 parts of Isatis tinctoria, 93-95 parts of sucrose, 4-6 parts of dextrin, and 0.2-0.5 parts of stabilizer.
[0008] The present invention discloses a method for preparing Qiqing Baidu Granules, comprising the following steps:
[0009] Step 1. Grind the five Chinese herbs, Scutellaria baicalensis, Pulsatilla chinensis, Sophora flavescens, Isatis indigotica, and Dryopteris crassirhizoma, into powder, add 8 times the amount of water to extract the extract, simmer for 1 hour, then add 8 times the amount of water again and simmer for 1 hour. Combine the decoctions, filter and concentrate to obtain the extract, and set aside.
[0010] Step 2. After pulverizing the two Chinese herbs, Polygonum cuspidatum and Isatis indigotica, add 8 times the amount of 60% ethanol and reflux at 80°C for 2 hours. Then add 8 times the amount of 60% ethanol and reflux at 80°C for 1 hour. Combine the extracts, filter and concentrate to obtain an extract for later use.
[0011] Step 3. Add the stabilizer to the extract from Step 2 and combine it with Extract 1 for later use;
[0012] Step 4. Weigh out the sucrose, grind it, pass it through a 60-mesh sieve, and mix it evenly with the dextrin. Set aside.
[0013] Step 5. Spray the extract evenly onto the surface of the mixture, dry it, and granulate it for later use;
[0014] Step 6. Mix the obtained granules evenly, and package them in aluminum foil bags to obtain the final product. Detailed Implementation
[0015] Example 1
[0016] Step 1. Grind 15-18 parts of Scutellaria baicalensis, 12-15 parts of Pulsatilla chinensis, 12-15 parts of Sophora flavescens, 15-18 parts of Isatis indigotica, and 8-10 parts of Dryopteris crassirhizoma into powder, soak in 8 times the amount of water for 1 hour, decoct for 2 hours, then add 8 times the amount of water and decoct for another hour. Combine the decoctions, filter and concentrate to obtain an extract for later use.
[0017] Step 2. Grind 15-18 parts of Polygonum cuspidatum and 6-8 parts of Isatis indigotica into powder, add 8 times the amount of 60% ethanol and reflux at 80°C for 2 hours, then add 8 times the amount of 60% ethanol and reflux at 80°C for 1 hour. Combine the extracts, filter and concentrate to obtain an extract for later use.
[0018] Step 3. Add 0.2-0.5 parts of sodium carboxymethyl cellulose to the extract from Step 2 and combine it with extract 1 for later use.
[0019] Step 4. Weigh 93-95 parts of sucrose, grind it through a 60-mesh sieve, and mix it with 4-6 parts of dextrin until homogeneous. Set aside.
[0020] Step 5. Spray the extract evenly onto the surface of the mixture, dry it, and granulate it for later use.
[0021] Step 6. Mix the obtained granules evenly, and package them in aluminum foil bags to obtain the final product.
[0022] Example 2
[0023] Step 1. Grind 15-18 parts of Scutellaria baicalensis, 12-15 parts of Pulsatilla chinensis, 12-15 parts of Sophora flavescens, 15-18 parts of Isatis indigotica, and 8-10 parts of Dryopteris crassirhizoma into powder, soak in 8 times the amount of water for 1 hour, decoct for 2 hours, then add 8 times the amount of water and decoct for another hour. Combine the decoctions, filter and concentrate to obtain an extract for later use.
[0024] Step 2. Grind 15-18 parts of Polygonum cuspidatum and 6-8 parts of Isatis indigotica into powder, add 8 times the amount of 60% ethanol and reflux at 80°C for 2 hours, then add 8 times the amount of 60% ethanol and reflux at 80°C for 1 hour. Combine the extracts, filter and concentrate to obtain an extract for later use.
[0025] Step 3. Add 0.2-0.5 parts of β-cyclodextrin to the extract in Step 2 and combine it with Extract 1 for later use.
[0026] Step 4. Weigh 93-95 parts of sucrose, grind it through a 60-mesh sieve, and mix it with 4-6 parts of dextrin until homogeneous. Set aside.
[0027] Step 5. Spray the extract evenly onto the surface of the mixture, dry it, and granulate it for later use.
[0028] Step 6. Mix the obtained granules evenly, and package them in aluminum foil bags to obtain the final product.
[0029] Example 3
[0030] Step 1. Grind 15-18 parts of Scutellaria baicalensis, 12-15 parts of Pulsatilla chinensis, 12-15 parts of Sophora flavescens, 15-18 parts of Isatis indigotica, 8-10 parts of Dryopteris crassirhizoma, and 15-18 parts of Polygonum cuspidatum into powder, soak in 8 times the amount of water for 1 hour, decoct for 2 hours, then add 8 times the amount of water and decoct for another hour. Combine the decoctions, filter and concentrate to obtain an extract for later use.
[0031] Step 2. Crush 6-8 parts of Isatis tinctoria leaves, add 8 times the amount of 60% ethanol and reflux at 80°C for 2 hours, then add 8 times the amount of 60% ethanol and reflux at 80°C for 1 hour. Combine the extracts, filter and concentrate to obtain the extract, and set aside for later use.
[0032] Step 3. Combine the extract from Step 2 with Extract 1 and set aside.
[0033] Step 4. Weigh 93-95 parts of sucrose, grind it through a 60-mesh sieve, and mix it with 4-6 parts of dextrin until homogeneous. Set aside.
[0034] Step 5. Spray the extract evenly onto the surface of the mixture, dry it, and granulate it for later use.
[0035] Step 6. Mix the obtained granules evenly, and package them in aluminum foil bags to obtain the final product.
[0036] Example 4
[0037] Step 1. Grind 15-18 parts of Scutellaria baicalensis, 12-15 parts of Pulsatilla chinensis, 12-15 parts of Sophora flavescens, 15-18 parts of Isatis indigotica, 8-10 parts of Dryopteris crassirhizoma, and 6-8 parts of Isatis tinctoria into powder, soak in 8 times the amount of water for 1 hour, decoct for 2 hours, then add 8 times the amount of water and decoct for another hour. Combine the decoctions, filter and concentrate to obtain an extract for later use.
[0038] Step 2. Crush 15-18 parts of Polygonum cuspidatum, add 8 times the amount of 60% ethanol and reflux at 80°C for 2 hours, then add 8 times the amount of 60% ethanol and reflux at 80°C for 1 hour. Combine the extracts, filter and concentrate to obtain the extract, and set aside for later use.
[0039] Step 3. Combine the extract from Step 2 with Extract 1 and set aside.
[0040] Step 4. Weigh 93-95 parts of sucrose, grind it through a 60-mesh sieve, and mix it with 4-6 parts of dextrin until homogeneous. Set aside.
[0041] Step 5. Spray the extract evenly onto the surface of the mixture, dry it, and granulate it for later use.
[0042] Step 6. Mix the obtained granules evenly, and package them in aluminum foil bags to obtain the final product.
[0043] Example 5
[0044] Step 1. Grind 15-18 parts of Scutellaria baicalensis, 12-15 parts of Pulsatilla chinensis, 12-15 parts of Sophora flavescens, 15-18 parts of Isatis indigotica, 8-10 parts of Dryopteris crassirhizoma, 6-8 parts of Isatis tinctoria, and 15-18 parts of Polygonum cuspidatum into powder, soak in 8 times the amount of water for 1 hour, decoct for 2 hours, then add 8 times the amount of water and decoct for another hour. Combine the decoctions, filter, and concentrate under reduced pressure at below 80℃ to a relative density of 1.30-1.35 to obtain the extract for later use.
[0045] Step 2. Weigh 93-95 parts of sucrose, grind it through a 60-mesh sieve, and mix it with 4-6 parts of dextrin until homogeneous. Set aside.
[0046] Step 3. Spray the extract evenly onto the surface of the mixture, dry it, and granulate it for later use.
[0047] Step 4. Mix the obtained granules evenly, and package them in aluminum foil bags to obtain the final product.
[0048] The following specific experiments will verify the effectiveness.
[0049] Example 6
[0050] Experiment 1: Sample Inspection
[0051] Experimental Methods: The Qiqing Baidu Granules product provided in Examples 1-5 were used as the research object. The experiments were conducted according to the quality standards of Part II of the 2020 edition of the Veterinary Pharmacopoeia of the People's Republic of China.
[0052] The detection method is as follows:
[0053] Appearance: This product is a yellowish-brown to brownish-black granule; taste: bitter.
[0054] Identification (1) Take 15g of finely ground powder of this product, add 50ml of methanol, sonicate for 20 minutes, filter, evaporate the filtrate to dryness, dissolve the residue in 2ml of methanol, and use it as the test solution. Take another baicalin reference standard, add methanol to prepare a solution containing 1mg per 1ml, and use it as the reference solution. Perform thin-layer chromatography test, take 5ul of each of the above two solutions, and spot them separately on the same silica gel G thin-layer plate with a carboxymethyl cellulose sodium solution containing 4% sodium acetate as a binder, use ethyl acetate-butanone-formic acid-water (5:3:1:1) as the developing solvent, pre-saturate in the developing tank for 30 minutes, develop, remove, air dry, and spray with 1% ferric chloride ethanol solution. In the chromatogram of the test sample, spots of the same color appear at the corresponding positions as in the chromatogram of the reference standard.
[0055] (2) Take 8g of the finely ground powder of this product, add 25ml of chloroform, sonicate for 20 minutes, filter, evaporate the filtrate to dryness, dissolve the residue in 0.5ml of methanol, and use it as the test solution. Take 0.1g of Polygonum cuspidatum reference material and prepare a reference material solution in the same way. Take rhein reference standard and prepare a solution containing 1mg per ml with methanol, and use it as the reference solution. Perform thin-layer chromatography test, take 5ul of each of the above three solutions, spot them separately on the same silica gel G thin-layer plate, use toluene-ethyl acetate-formic acid (15:2:1) as the developing solvent, develop, remove, air dry, and examine under ultraviolet light (365nm). In the chromatogram of the test sample, orange-yellow fluorescent spots appear at the corresponding positions of the chromatograms of the reference material and the reference standard. After being exposed to ammonia vapor, the spots turn red when examined under sunlight.
[0056] (3) Take 15g of the finely ground powder of this product, add 30ml of chloroform, heat under reflux for 1 hour, filter, and concentrate the filtrate to 0.5ml to obtain the test solution. Separately, take indigo reference standard and indirubin reference standard, add chloroform to prepare a mixed solution containing 1mg of each per 1ml, as the reference solution. Perform thin-layer chromatography, take 5ul of each of the above two solutions, and spot them separately on the same silica gel G thin-layer plate. Use benzene-chloroform-acetone (5:4:1) as the developing solvent, develop, remove, and observe immediately. In the chromatogram of the test sample, blue spots and light purple-red spots appear at the corresponding positions as in the chromatogram of the reference standards, respectively.
[0057] Solubility: Take 10g of this product, add 200ml of hot water, stir for 5 minutes, and observe immediately. It should be completely dissolved or slightly turbid, but there should be no foreign matter.
[0058] The content was determined by high performance liquid chromatography (HPLC). The chromatographic conditions and system suitability test used octadecylsilane-bonded silica gel as the stationary phase and methanol-water-phosphoric acid (41:59:0.2) as the mobile phase; the detection wavelength was 280 nm. The theoretical plate number, calculated based on the baicalin peak, should be no less than 2500.
[0059] Preparation of the reference solution: Accurately weigh an appropriate amount of baicalin reference standard, add methanol to prepare a solution containing 50 μg per ml. Preparation of the test solution: Accurately weigh approximately 0.5 g of the finely ground powder of this product, place it in a 50 ml volumetric flask, add an appropriate amount of methanol, sonicate for 30 minutes, cool, add methanol to the mark, shake well, and filter. Assay: Accurately pipette 10 μl each of the reference solution and the test solution into the liquid chromatograph and determine the concentration. Specification: Each 1 g of this product contains baicalin (C... 21 H 18 O 11 The total dose shall not be less than 5.0 mg.
[0060] The properties and solubility of Examples 1-5 are not significantly different; in Identification 1, the size and color of the spots in Examples 1-5 are basically the same; in Identification 2, the spots in Example 1 are the most obvious, the spots in Examples 2 and 4 are relatively obvious, and the spots in Examples 3 and 5 are less obvious; in Identification 3, the spots in Example 1 are the most obvious, the spots in Examples 2 and 3 are relatively obvious, and the spots in Examples 4 and 5 are less obvious; Examples 1-5 have basically no effect on the content.
[0061] The results are shown in Table 1:
[0062] Table 1. Experimental Results
[0063]
[0064]
[0065] The results showed that the product prepared using this invention had a higher content of Polygonum cuspidatum and Isatis indigotica than similar commercially available products.
[0066] Example 7
[0067] Experiment 2: Stability Test of Samples from Examples 1-6
[0068] The stability of a sample under high temperature (30℃) and high humidity (65%) conditions is evaluated by examining its properties. If the sample does not change color or clump, it is considered normal; if it clumps, it is considered abnormal.
[0069] The results are shown in Table 2:
[0070] Table 2 Experimental Results
[0071] time Example 1 Example 2 Example 3 Example 4 Example 5 October normal normal normal normal normal January normal normal normal normal normal March normal normal normal normal normal June normal normal normal normal normal September normal normal normal normal normal December normal normal normal normal clumping 18 months normal normal Slight caking clumping clumping 24 months normal Slight caking clumping clumping clumping
[0072] The results showed that no clumping occurred after the sample was stored under high temperature and high humidity conditions for 24 months with a certain amount of sodium carboxymethyl cellulose added, indicating that the product prepared by the method of the present invention has better stability.
[0073] Example 8
[0074] Trial 3: Clinical Trial
[0075] A batch of 20-day-old broiler chickens at a chicken farm in Henan Province exhibited lethargy, ruffled feathers, decreased feed intake, elevated body temperature, shivering, huddling together, and drowsiness with closed eyes. They also suffered from diarrhea, passing watery droppings containing bubbles that gradually turned grayish-white. Some chicks also showed swollen joints and difficulty walking. Necropsy revealed pericardial effusion, enlarged liver, congested and hemorrhagic kidneys, enlarged gallbladder, and swollen cecum, leading to a diagnosis of pullorum disease in chicks. 500 sick chickens from the farm were randomly selected. Experimental group 1 received a small sample of Qiqing Baidu Granules (Example 1), mixed in the drinking water at a dose of 2.5g per liter of water, for 3 consecutive days. Experimental group 2 received a small sample of Qiqing Baidu Granules (Example 5), mixed in the drinking water at a dose of 2.5g per liter of water, for 3 consecutive days. Experimental Group 3 involved the combined use of a small sample of Qiqing Baidu Granules and enrofloxacin soluble powder, as described in Example 1. The Qiqing Baidu Granules were administered in the drinking water at a rate of 2.5g per liter of water for poultry, for 3 consecutive days. The enrofloxacin soluble powder was administered in the drinking water at a rate of 25-75mg per liter of water for chickens, twice daily for 3 consecutive days. Experimental Group 4 involved the combined use of a small sample of Qiqing Baidu Granules and enrofloxacin soluble powder, as described in Example 2. The Qiqing Baidu Granules were administered in the drinking water at a rate of 2.5g per liter of water for poultry, for 3 consecutive days. The enrofloxacin soluble powder was administered in the drinking water at a rate of 25-75mg per liter of water for chickens, twice daily for 3 consecutive days.
[0076] Efficacy evaluation criteria
[0077] Cure rate: The percentage of chickens whose mental state, appetite, and clinical symptoms completely returned to normal after the trial. Effectiveness rate: The percentage of chickens whose mental state, appetite, and clinical symptoms significantly improved after the trial. Ineffectiveness rate: The percentage of chickens that died during the trial and did not improve after medication.
[0078] The results are shown in Table 3:
[0079] Table 3. Experimental Results
[0080] experimental group Cured (only) Valid (only) Invalid (only) Cure rate (%) Effectiveness (%) Experimental group 1 78 14 8 78 92 Experimental group 2 70 11 19 70 81 Experimental group 3 93 6 1 93 99 Experimental group 4 85 9 6 85 94
[0081] The results showed that the product prepared by the present invention had a significantly higher cure rate and efficacy rate than the product prepared by conventional methods. The product prepared by the present invention, when used in combination with enrofloxacin soluble powder, showed a significantly higher cure rate than the product prepared by conventional methods when used in combination with enrofloxacin soluble powder.
Claims
1. A Qiqing Baidu Granule, characterized in that: It contains the following components by weight: 15-18 parts of Scutellaria baicalensis, 15-18 parts of Polygonum cuspidatum, 12-15 parts of Pulsatilla chinensis, 12-15 parts of Sophora flavescens, 15-18 parts of Isatis indigotica, 8-10 parts of Dryopteris crassirhizoma, 6-8 parts of Isatis tinctoria, 93-95 parts of sucrose, 4-6 parts of dextrin, and 0.2-0.5 parts of stabilizer.
2. The Qiqing Baidu Granules according to claim 1, characterized in that, The stabilizer is β-cyclodextrin and sodium carboxymethyl cellulose.
3. The Qiqing Baidu Granules according to claim 2, characterized in that, The stabilizer is sodium carboxymethyl cellulose.
4. A method for preparing Qiqing Baidu Granules, comprising the following steps: Step 1. Pulverize the five Chinese medicinal herbs, namely Scutellaria baicalensis, Pulsatilla chinensis, Sophora flavescens, Isatis indigotica, and Dryopteris crassirhizoma, and extract them with water to obtain extract 1, which is ready for use. Step 2. After pulverizing the two Chinese herbs, Polygonum cuspidatum and Isatis indigotica, extract them with alcohol to obtain extract 2, which is then set aside. Step 3. Combine the extract 2 obtained in step 2) with the extract 1 obtained in step 1) and set aside; Step 4. Weigh out the sucrose powder and mix it evenly with the dextrin, then set aside. Step 5. Spray the combined extract from step 3) evenly onto the surface of the sucrose and dextrin mixture obtained in step 4), dry it, and granulate it for later use. Step 6. Mix the obtained granules evenly, and package them in aluminum foil bags to obtain the final product.
5. The preparation method of Qiqing Baidu Granules according to claim 4, characterized in that, The five herbs mentioned in step 1) are decocted in water to extract their flavor.
6. The method for preparing Qiqing Baidu Granules according to claim 4, characterized in that, After pulverizing the two Chinese herbs, Polygonum cuspidatum and Isatis indigotica, add 8 times the amount of 60% ethanol and reflux at 80°C for 2 hours, then add 8 times the amount of 60% ethanol and reflux at 80°C for 1 hour. Combine the extracts, filter and concentrate to obtain an extract for later use.
7. The preparation method of Qiqing Baidu Granules according to claim 4, characterized in that, In step 2), a stabilizer is added to the extracts of Polygonum cuspidatum and Isatis indigotica.
8. The method for preparing Qiqing Baidu Granules according to claim 4, characterized in that, Step 4) Grind the sucrose through a 60-mesh sieve.