Preparation method of veterinary drug compound preparation containing radix sophorae flavescentis

Abstract

The invention relates to the technical field of traditional Chinese veterinary medicine preparations, and provides a preparation method of a veterinary medicine compound preparation containing radix sophorae flavescentis, which comprises the following steps: S1, infiltrating a radix sophorae flavescentis medicinal material with a sodium hydroxide solution to obtain a liquid medicine; s2, mixing the liquid medicine with water, artemisia apiacea, radix bupleuri, antifebrile dichroa and lalang grass rhizome, decocting, collecting decoction, concentrating, filtering, and collecting clear paste; and S3, mixing the clear paste with cane sugar and dextrin, granulating, and drying to obtain the veterinary drug compound preparation containing radix sophorae flavescentis. According to the technical scheme, the problem that oxymatrine identification of the five-ingredient evergreen granules is unstable in the prior art is solved.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese veterinary medicine preparations, and in particular to a method for preparing a veterinary medicine compound preparation containing Sophora flavescens. Background Art

[0002] Sophora flavescens is a commonly used medicinal material in the field of veterinary preparations. It has the effects of clearing away heat and dampness, killing insects and promoting diuresis. It is often used to treat heat dysentery, blood in stool, jaundice and urine retention, eczema, wet sores, skin itching, scabies and leprosy, etc. Take Wuwei Changqing Granules as an example. The product is included in the 2017 edition of the Chinese medicine volume of the "Quality Standards for Veterinary Drugs". It is composed of Artemisia annua, Bupleurum, Sophora flavescens, Dichroa and Imperata root, and is used to treat chicken coccidiosis. The following problems exist in product production and inspection: After the Wuwei Changqing Granules are prepared according to the [Preparation Method] in the Chinese Medicine Volume of the 2017 Edition of the "Quality Standards for Veterinary Drugs", during the [Identification 2] test, the size of the oxidized matrine spots is uneven compared with the reference product, or even no oxidized matrine spots are shown, resulting in the product being unqualified. The Sophora flavescens medicinal materials used in the product all meet the quality standard requirements of Part II of the 2020 Edition of the "Chinese Veterinary Pharmacopoeia". According to the physical and chemical properties of oxidized matrine, it is easily soluble in solvents such as water, methanol, chloroform, and benzene. In large-scale production, the use of aqueous phase production extraction is in line with its extraction method. However, there are few reports on the relevant research on the identification of Sophora flavescens in Wuwei Changqing Granules in the field of veterinary preparations. In view of the above problems, in order to solve the problem of unstable identification of oxidized matrine in the product, it is of great significance to seek a stable product preparation method that can meet the actual large-scale production. Summary of the invention

[0003] The invention provides a method for preparing a compound veterinary medicine preparation containing sophora flavescens, which solves the problem of unstable identification of oxidized matrine in Wuwei Changqing granules in the related art.

[0004] The technical solution of the present invention is as follows: A method for preparing a veterinary compound preparation containing Sophora flavescens, comprising the following steps: S1, soaking the Sophora flavescens medicinal material with a sodium hydroxide solution to obtain a medicinal solution; S2, mixing the medicinal liquid with water, Artemisia annua, Bupleurum Root, Dichroa Root and Imperata Rhizome, decocting, collecting the decoction, concentrating, filtering, and collecting the clear paste; S3, mixing the clear paste with sucrose and dextrin, granulating, and drying to obtain a veterinary drug compound preparation containing Sophora flavescens.

[0005] As a further technical solution, the mass concentration of the sodium hydroxide solution in S1 is 0.05%~0.1%.

[0006] As a further technical solution, the pH of the drug solution infiltrated in S1 is 5.5-6.5.

[0007] As a further technical solution, the mass volume ratio of the Sophora flavescens medicinal material to the sodium hydroxide solution in S1 is 1kg:2L~4L.

[0008] The present invention uses 0.05wt% to 0.1wt% sodium hydroxide solution, controls the mass volume ratio of Sophora flavescens medicinal materials to the sodium hydroxide solution to be 1kg:2L to 4L, adjusts the pH value of the medicinal solution to 5.5 to 6.5, and provides stable and uniform identification indexes of oxymatrine in Wuwei Changqing granules. This avoids the problem that the terpene lactones (artemisinin) in the Artemisia annua medicinal materials and the terpenes and organic acid components in the Imperata cylindrica roots are easily decomposed in an alkaline environment, resulting in non-compliance with regulations for product identification and detection and changes in product efficacy.

[0009] As a further technical solution, the mass and volume ratio of the Sophora flavescens medicinal materials, Artemisia annua, Bupleurum chinense, Dichroa febrifuga and Imperata cylindrica to water is 1kg:8L~10L.

[0010] As a further technical solution, after the decoction, a second decoction is also included. The second decoction is specifically as follows: after the decoction is completed, the decoction liquid is transferred, water is continuously added for a second decoction, the second decoction liquid is collected, and the two decoction liquids are combined.

[0011] As a further technical solution, during the secondary decoction, the amount of water added is calculated based on the mass of Sophora flavescens, Artemisia annua, Bupleurum chinense, Dichroa febrifuga and Imperata cylindrica to the volume ratio of water to be 1kg:8L~10L.

[0012] As a further technical solution, the concentration in S2 includes primary concentration and secondary concentration. The primary concentration is specifically: negative pressure concentration to a relative density of 1.08-1.15, and the secondary concentration is specifically: negative pressure concentration to a relative density of 1.28-1.30.

[0013] As a further technical solution, the decoction time is 2 to 3 hours, and the secondary decoction time is 1 to 2 hours.

[0014] As a further technical solution, the mass ratio of the clear paste to sucrose and dextrin in S3 is 1:3~4:1~2.

[0015] The working principle and beneficial effects of the present invention are: In the present invention, sodium hydroxide is used as a regulator to regulate the redox system in the Sophora flavescens medicinal material, thereby preventing oxymatrine from being converted into matrine in the Sophora flavescens medicinal material. The oxymatrine identification index of the provided Wuwei Changqing granules is stable and uniform, and the solubility index of the product meets the requirements, thereby meeting the actual large-scale production needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0017] Figure 1 The thin layer chromatograms of Wuwei Changqing granules prepared in Comparative Examples 1 and 3-4 of the present invention; In the figure: 1 is a matrine reference substance, 2 is an oxymatrine reference substance, 3 is a comparative example 3, 4 is a comparative example 1, and 5 is a comparative example 4; Figure 2 The thin layer chromatograms of Wuwei Changqing granules prepared in Examples 1-2 and Comparative Examples 1-2 of the present invention; In the figure: 1 is comparative example 1, 2 is embodiment 1, 3 is embodiment 2, 4 is matrine reference substance, 5 is oxymatrine reference substance, 6 is comparative example 2, 7 is embodiment 1, and 8 is embodiment 2; Figure 3 The results of the detection of Artemisia annua in Wuwei Changqing Granules prepared with different concentrations of sodium hydroxide solution; Figure 4 These are the detection results of Sophora flavescens in Wuwei Changqing granules prepared with different concentrations of sodium hydroxide solution. DETAILED DESCRIPTION

[0018] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0019] In the following examples and comparative examples: Batch 240629004 of Sophora flavescens was purchased from Anguo Dinghong Biotechnology Co., Ltd., with an oxymatrine content of 1.30%; Batch 240509002 of Sophora flavescens was purchased from Anguo Dinghong Biotechnology Co., Ltd., with an oxymatrine content of 1.22%; Batch 240710005 of Sophora flavescens was purchased from Anguo Dinghong Biotechnology Co., Ltd., with an oxymatrine content of 1.77%; Artemisia annua was purchased from Youyang County Tenglong Ecological Agriculture Development Co., Ltd.; Bupleurum was purchased from Longxi County Longgang Chinese Medicinal Materials Purchasing and Sales Co., Ltd.; Changshan was purchased from Anguo Huihan Chinese Medicinal Materials Sales Co., Ltd.; Imperata rhizome was purchased from Anguo Juge Chinese Medicinal Materials Management Co., Ltd.

[0020] Example 1 S1. Add 185 kg of Sophora flavescens medicinal materials (batch 240629004) into the extraction tank, add 370 L of sodium hydroxide solution with a mass concentration of 0.1%, and completely soak the Sophora flavescens medicinal materials until the pH of the soaking solution is 6.5; S2. Add 5720L of water to the extraction tank, add 100kg of Artemisia annua, 90kg of Bupleurum chinense, 250kg of Dichroa chinensis, and 90kg of Imperata cylindrica to the extraction tank, and boil for 2h; S3, the decoction liquid is pumped into the storage tank, and then 5720L of water is added to the extraction tank, and the liquid is pumped into the storage tank after boiling and decoction for 1 hour; S4. Combine the two decoctions, filter and pump into a double-effect concentrator. Stop concentrating when the liquid is concentrated under negative pressure to a relative density of 1.08 (60°C); S5, filtering the liquid in step S4, pumping it into a scraper concentrator, concentrating it under negative pressure to a relative density of 1.28 (60°C), and filtering it while hot to obtain a clear paste; S6. In the granulation workshop, the clear paste, sucrose and dextrin are made into granules in a mass ratio of 1:3.5:1, and dried to obtain 350 kg of Wuwei Changqing granules.

[0021] Example 2 S1. Add 185 kg of Sophora flavescens medicinal materials (batch 240629004) into the extraction tank, add 740 L of sodium hydroxide solution with a mass concentration of 0.05%, and completely soak the Sophora flavescens medicinal materials until the pH of the soaking solution is 5.5; S2, add 7150L of water to the extraction tank, take 100kg of Artemisia annua, 90kg of Bupleurum chinense, 250kg of Dichroa chinensis, and 90kg of Imperata cylindrica into the extraction tank, and boil for 3h; S3, the decoction liquid is pumped into the storage tank, and then 7150L of water is added to the extraction tank, and the liquid is pumped into the storage tank after boiling and decoction for 2h; S4. Combine the two decoctions, filter and pump into a double-effect concentrator. Stop concentrating when the liquid is concentrated under negative pressure to a relative density of 1.15 (60°C); S5, filtering the liquid in step S4, pumping it into a scraper concentrator, concentrating it under negative pressure to a relative density of 1.30 (60°C), and filtering it while hot to obtain a clear paste; S6. In the granulation workshop, the clear paste, sucrose and dextrin are made into granules in a mass ratio of 1:3.5:1, and dried to obtain 350 kg of Wuwei Changqing granules.

[0022] Comparative Example 1 S1. Take 100kg of Artemisia annua, 90kg of Bupleurum chinense, 185kg of Sophora flavescens (batch 240629004), 250kg of Dichroa chinensis and 90kg of Imperata cylindrica into an extraction tank, add 5720L of water, and boil for 2h; S2, the decoction liquid is pumped into the storage tank, and then 5720L of water is added to the extraction tank, and the liquid is pumped into the storage tank after boiling and decoction for 1 hour; S3, combine the two decoctions, filter and pump into the double-effect concentrator, and stop concentrating when the liquid is concentrated under negative pressure to a relative density of 1.08 (60°C); S4, filtering the liquid in step S3, pumping it into a scraper concentrator, concentrating it under negative pressure to a relative density of 1.28 (60°C), and filtering it while hot to obtain a clear paste; S5. In the granulation workshop, clear paste, sucrose and dextrin are made into granules in a mass ratio of 1:3.5:1, dried, and 350 kg of Wuwei Changqing granules are obtained.

[0023] Comparative Example 2 S1. Add 185 kg of Sophora flavescens medicinal materials (batch 240629004) into the extraction tank, add 370 L of water, and completely soak the Sophora flavescens medicinal materials for 1 hour; S2. Add 5720L of water to the extraction tank, add 100kg of Artemisia annua, 90kg of Bupleurum chinense, 250kg of Dichroa chinensis, and 90kg of Imperata cylindrica to the extraction tank, and boil for 2h; S3, the decoction liquid is pumped into the storage tank, and then 5720L of water is added to the extraction tank, and the liquid is pumped into the storage tank after boiling and decoction for 1 hour; S4. Combine the two decoctions, filter and pump into a double-effect concentrator. Stop concentrating when the liquid is concentrated under negative pressure to a relative density of 1.08 (60°C); S5, filtering the liquid in step S4, pumping it into a scraper concentrator, concentrating it under negative pressure to a relative density of 1.28 (60°C), and filtering it while hot to obtain a clear paste; S6. In the granulation workshop, the clear paste, sucrose and dextrin are made into granules in a mass ratio of 1:3.5:1, and dried to obtain 350 kg of Wuwei Changqing granules.

[0024] Comparative Example 3 The only difference from Comparative Example 1 is that the Sophora flavescens medicinal material is batch 240509002, and the content of oxymatrine is 1.22%.

[0025] Comparative Example 4 The only difference from Comparative Example 1 is that the Sophora flavescens medicinal material is batch 240710005, and the content of oxymatrine is 1.77%.

[0026] The Wuwei Changqing granules obtained in Examples 1-2 and Comparative Examples 1-4 were tested according to Wuwei Changqing granules [Identification 2] in the 2017 edition of the Chinese medicine volume of the "Quality Standards for Veterinary Drugs", as follows: Take 5g of finely ground powder of Wuwei Changqing granules, add 20% sodium hydroxide solution to moisten it, add 30mL of chloroform and reflux for 1h, filter the filtrate and evaporate to dryness, add 5mL of chloroform to the residue to dissolve it, and use it as the test solution. Separately take matrine reference substance and oxymatrine reference substance and add chloroform to make solutions containing 1mg per 1mL, as the reference solution. According to the thin layer chromatography method (Appendix 0502), take 5μL of each of the above two solutions and spot them on the same silica gel G thin layer plate, use chloroform-methanol-concentrated ammonia test solution (volume ratio 9:1:0.5) as the developing agent, develop it, take it out and dry it, and spray it with modified potassium bismuth iodide test solution. In the chromatogram of the test sample, spots of the same color appear at the corresponding position of the chromatogram of the reference substance. The test figure is as shown in the figure below. Figure 1~2 shown.

[0027] Depend on Figure 1 It can be seen that the sizes of the oxidized matrine spots in the Wuwei Changqing Granule products prepared in Comparative Examples 1 and Comparative Examples 3-4 are uneven compared with those of the oxidized matrine reference substance, and no oxidized matrine spots were found in the Wuwei Changqing Granule product prepared in Comparative Example 1. This means that even if the oxidized matrine content in Sophora flavescens medicinal materials meets the standard, the Wuwei Changqing Granule product prepared by the method of Comparative Example 1 will have the problem of unstable identification of oxidized matrine or even undetectable during testing, and cannot be generally used.

[0028] Depend on Figure 2 It can be seen that the oxidized matrine spots in the Wuwei Changqing granules prepared in Examples 1-2 of the present invention are uniform in size compared with the control, while the oxidized matrine in the Wuwei Changqing granules prepared in Comparative Examples 1-2 shows no spots, indicating that the oxidized matrine in the Wuwei Changqing granules prepared by the preparation method of the veterinary compound preparation containing Sophora flavescens provided by the present invention has stable and uniform identification indicators, and the solubility indicators of the product meet the requirements, which can meet the actual large-scale production needs.

[0029] Sophora flavescens was soaked in a sodium hydroxide solution with a mass concentration of 0.1%, and the soaking time and the pH value of the solution were investigated. The results are shown in Table 1.

[0030] Table 1 Immersion time and pH value of 0.1wt% sodium hydroxide solution for medicinal materials at a mass volume ratio of 1kg:2L

[0031] Sophora flavescens was soaked in a sodium hydroxide solution with a mass concentration of 0.05%, and the changes in the soaking time and the pH value of the solution were investigated. The results are shown in Table 2.

[0032] Table 2 Immersion time and pH value of 0.05wt% sodium hydroxide solution for medicinal materials at a mass volume ratio of 1kg:2L

[0033] It can be seen from Tables 1-2 that after 20 minutes of immersion in 0.1wt% sodium hydroxide solution, the infiltration solution gradually turns to acidic, and after 10 minutes of immersion in 0.05wt% sodium hydroxide solution, the infiltration solution gradually turns to acidic.

[0034] Detection method of Artemisia annua: Take 10g of finely ground powder of Wuwei Changqing granules, add 25mL of water to dissolve, add 15mL of ether to shake and extract, separate the ether layer, evaporate the ether, add 2mL of ether to dissolve the residue, and use it as the test solution. Take another 1g of Artemisia annua control medicinal material, add 10mL of ether, soak overnight, filter, evaporate the ether, add 5mL of ether to dissolve the residue, and use it as the control medicinal material solution. According to the thin layer chromatography method (Appendix 0502), take 5μL of each of the above two solutions, spot them on the same silica gel G thin layer plate, use chloroform-ether (volume ratio 2:1) as the developing agent, develop, take out, dry, spray with 10wt% sulfuric acid ethanol solution, and heat at 105°C until the spots are clearly colored. In the chromatogram of the test sample, spots of the same color appear at the corresponding position of the chromatogram of the control medicinal material. The results are as follows Figure 3 shown.

[0035] Depend on Figure 3 It can be seen that the artemisinin identification index of the Wuwei Changqing Granules provided by using 0.05wt% sodium hydroxide solution and 0.1wt% sodium hydroxide solution is stable and uniform, which can effectively avoid the problem that the terpene lactones (artemisinin) in the Artemisia annua medicinal material are easily decomposed in an alkaline environment, resulting in product identification testing not meeting regulations and changes in product efficacy.

[0036] Wuwei Changqing Granules Sophora flavescens identification, sample 1 was treated with 0.1wt% NaOH solution, sample 2 was treated with 0.05wt% NaOH solution, sample 3 was matrine, sample 4 was oxidized matrine, sample 5 was without NaOH, and sample 6 was treated with 0.01wt% NaOH solution. The results are as follows Figure 4 shown.

[0037] Depend on Figure 4 It can be seen that after treatment with 0.01wt% NaOH solution, the identification of oxymatrine in Wuwei Changqing granules is unstable or even undetectable.

[0038] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a veterinary drug compound preparation containing Sophora flavescens, characterized in that: The following steps are involved: S1, soaking the Sophora flavescens medicinal material with a sodium hydroxide solution to obtain a medicinal solution; S2, mixing the medicinal liquid with water, Artemisia annua, Bupleurum Root, Dichroa Root and Imperata Rhizome, decocting, collecting the decoction, concentrating, filtering, and collecting the clear paste; S3, mixing the clear paste with sucrose and dextrin, granulating, and drying to obtain a veterinary drug compound preparation containing Sophora flavescens.

2. The method for preparing a veterinary compound preparation containing Sophora flavescens according to claim 1, characterized in that: The mass concentration of the sodium hydroxide solution in S1 is 0.05% to 0.1%.

3. The method for preparing a veterinary compound preparation containing Sophora flavescens according to claim 1, characterized in that: The pH of the drug solution infiltrated in the S1 is 5.5-6.

5.

4. The method for preparing a veterinary compound preparation containing Sophora flavescens according to claim 1, characterized in that: The mass volume ratio of the Sophora flavescens medicinal material to the sodium hydroxide solution in S1 is 1kg:2L~4L.

5. The method for preparing a veterinary compound preparation containing Sophora flavescens according to claim 1, characterized in that: The mass and volume ratio of the Sophora flavescens medicinal materials, Artemisia annua, Bupleurum chinense, Dichroa febrifuga and Imperata cylindrica to water is 1kg:8L-10L.

6. The method for preparing a veterinary compound preparation containing Sophora flavescens according to claim 1, characterized in that: After the decoction, a second decoction is further included. The second decoction is specifically as follows: after the decoction is completed, the decoction liquid is transferred, water is continuously added for a second decoction, the second decoction liquid is collected, and the two decoction liquids are combined.

7. The method for preparing a veterinary drug compound containing Sophora flavescens according to claim 6, characterized in that: During the secondary decoction, the amount of water added is calculated based on the mass of Sophora flavescens, Artemisia annua, Bupleurum chinense, Dichroa febrifuga and Imperata cylindrica to the volume ratio of water to 1kg:8L-10L.

8. The method for preparing a veterinary drug compound preparation containing Sophora flavescens according to claim 1, characterized in that: The concentration in S2 includes primary concentration and secondary concentration. The primary concentration is specifically: negative pressure concentration to a relative density of 1.08-1.15, and the secondary concentration is specifically: negative pressure concentration to a relative density of 1.28-1.

30.

9. The method for preparing a veterinary compound preparation containing Sophora flavescens according to claim 6, characterized in that: The decoction time is 2 to 3 hours, and the secondary decoction time is 1 to 2 hours.

10. The method for preparing a veterinary compound preparation containing Sophora flavescens according to claim 1, characterized in that: The mass ratio of the clear paste to sucrose and dextrin in S3 is 1:3-4:1-2.

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