Artemisia apiacea antifebrile dichroa granule and preparation

Abstract

The invention provides sweet wormwood and antifebrile dichroa granules and a preparation method thereof. The sweet wormwood and antifebrile dichroa granules are prepared from, by weight, 300 g of sweet wormwood, 300 g of antifebrile dichroa, 200 g of Chinese pulsatilla roots and 200 g of hairyvein agrimony, wherein the auxiliary materials comprise 1-5 g of PEG-400, 5-10 g of ZTC-II clarifying agent, 10-30 g of beta-dextrin and 400-600 g of cane sugar. The product provided by the invention has strong stability, and changes the high-temperature decoction process under pressure and normal pressure in the traditional extraction tank, so that the energy can be saved, the dosage of a water solvent is reduced, the post-treatment process is simple and convenient, the storage process is reduced, the energy is saved, the process is simple, the operation is convenient, and the method is suitable for industrial production, popularization and application.

Description

Technical Field

[0001] This invention relates to a method for preparing Artemisia annua and Dichroa febrifuga granules. Background Technology

[0002] A type of Artemisia annua and Dichroa febrifuga granule drug preparation, based on the formulation of the Chinese Veterinary Pharmacopoeia, contains Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, and Astragalus membranaceus. Its main functions and indications are: clearing heat, cooling blood, stopping dysentery, and treating coccidiosis in chickens.

[0003] The functions of each Chinese herb in the formula are as follows:

[0004] Artemisia annua functions: clears heat and relieves summer heat, reduces deficiency heat, and kills protozoa; main indications: exogenous summer heat, yin deficiency fever, damp-heat jaundice, babesiosis, and coccidiosis.

[0005] Changshan's functions: insecticidal, expectorant, and digestive; main indications: coccidiosis, stagnant grass, and phlegm accumulation.

[0006] Functions of Pulsatilla chinensis: Clears heat and detoxifies, cools blood and stops dysentery; Indications: Dysentery due to heat toxin and blood stasis, and jaundice due to damp-heat.

[0007] Astragalus membranaceus (Huang Qi) functions: tonifies Qi and raises Yang, strengthens the exterior and stops sweating, promotes diuresis and reduces swelling, promotes pus drainage and detoxification, and promotes tissue regeneration and wound healing. It is indicated for: deficiency of lung and spleen Qi, sinking of middle Qi, spontaneous sweating due to exterior deficiency, edema due to Qi deficiency, and carbuncles and boils that are difficult to heal. Based on the original formula, Astragalus membranaceus is removed and Agrimonia pilosa (Xiang He Cao) is added. Agrimonia pilosa (Xiang He Cao) functions: tonifies kidney Yang, strengthens tendons and bones, and dispels wind and dampness. It is indicated for: hematochezia, hematuria, hematemesis, epistaxis, bloody dysentery, carbuncles and boils. It can enhance the anti-dysentery and anti-coccidial effects.

[0008] Traditional extraction methods for Artemisia annua and Dichroa febrifuga granules include decoction, filtration, and alcohol precipitation. These methods result in low extraction rates of active ingredients, and the filtration and alcohol precipitation processes lead to excessive loss of active ingredients, high energy consumption, and long processing times. The purpose of this invention is to provide a method for preparing Artemisia annua and Dichroa febrifuga granules that has high active ingredient content and low energy consumption.

[0009] To achieve the above objectives, the technical solution adopted in this invention is: a method for preparing Artemisia annua and Dichroa febrifuga granules, which simultaneously performs the extraction and concentration processes of Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, and Agrimonia pilosa. This method changes the traditional high-temperature decoction process under pressure and at normal pressure in the extraction tank, and adds PEG-400 solvent and ZTC-II clarifying agent to reduce the excessive loss of effective components in the traditional extraction and precipitation process. Summary of the Invention

[0010] The purpose of this invention is to provide a method for preparing Artemisia annua and Dichroa febrifuga granules. These granules are prepared from Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, Agrimonia pilosa, sucrose, and dextrin as the main raw materials. The specific preparation method is as follows:

[0011] The preparation method of Artemisia annua granules as described above includes the following steps:

[0012] A kind of Artemisia annua and Dichroa febrifuga granules, the raw materials of the present invention are: Artemisia annua 300g, Dichroa febrifuga 300g, Pulsatilla chinensis 200g, Agrimonia pilosa 200g. The excipients are: PEG-400 1-5g, ZTC-II clarifying agent 5-10g, β-dextrin 10-30g, sucrose 400-600g.

[0013] Preferably, it is prepared from the following raw materials and excipients by weight;

[0014] Ingredients: 300g Artemisia annua, 300g Dichroa febrifuga, 200g Pulsatilla chinensis, 200g Agrimonia pilosa

[0015] Excipients: PEG-400 5g, ZTC-Ⅱ clarifying agent 10g, β-dextrin 30g, sucrose 600g.

[0016] The preparation method of Artemisia annua granules as described above includes the following steps:

[0017] Preparation of Artemisia annua and Dichroa febrifuga granules extract: Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, and Agrimonia pilosa are pulverized and placed in an extraction tank to form a herb layer. 8-12 times the amount of water is added to cover the herb layer and soak for 2.0-3.0 hours. Then, the working temperature of the extraction tank is adjusted to 60-80℃ for extraction. During the extraction process, part of the extract is discharged from the bottom of the extraction tank for vacuum concentration at a temperature of 50-70℃. The steam generated during concentration is condensed and returned to the extraction tank as a new solvent to extract the herb layer again. This process is repeated for 2-3 hours to obtain the concentrated extract.

[0018] Artemisia annua and Dichroa febrifuga granule extract processing: Add 5g of PEG-400 to the extract to fully dissolve the effective components, then add 10g of ZTC-II clarifying agent to remove impurities and precipitates from the extract, and take the supernatant to obtain Artemisia annua and Dichroa febrifuga granule extract.

[0019] The sucrose excipient is pulverized and mixed with dextrin, then added to a granulator to obtain Artemisia annua and Changshan granules.

[0020] This invention combines the advantages of decoction extraction, secondary extraction, countercurrent extraction, and reflux extraction. It adds a solubilizer and flocculant to replace traditional filtration and alcohol precipitation, and performs the extraction and concentration processes of Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, and Agrimonia pilosa simultaneously. It changes the traditional high-temperature decoction process under pressure and at atmospheric pressure in the extraction tank. The solubilizer and ZTC-II clarifying agent reduce the loss of effective components in alcohol precipitation during traditional extraction, greatly reducing costs, which is currently in demand in the veterinary drug market. Detailed Implementation

[0021] Example 1

[0022] A type of Artemisia annua and Dichroa febrifuga granules is prepared from the following raw materials and excipients by weight: Raw materials: Artemisia annua 300g, Dichroa febrifuga 300g, Pulsatilla chinensis 200g, Agrimonia pilosa 200g Excipients: β-dextrin 10g, sucrose 400g.

[0023] The preparation method of Artemisia annua granules as described above includes the following steps;

[0024] Preparation of Artemisia annua and Dichroa febrifuga granule extract: Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, and Agrimonia pilosa are pulverized and placed in an extraction tank to form a herb layer. 8-12 times the amount of water is added to cover the herb layer and soak for 2.0-3.0 hours. Then, the working temperature of the extraction tank is adjusted to 60-80℃ for extraction. During the extraction process, part of the extract is discharged from the bottom of the extraction tank for vacuum concentration at a temperature of 50-70℃. The steam generated during concentration is condensed and returned to the extraction tank as a new solvent to extract the herb layer again. This process is repeated for 2-3 hours to obtain the concentrated extract.

[0025] Treatment of Artemisia annua and Dichroa febrifuga granule extract: Add 5g of ZTC-II clarifying agent to the extract to precipitate impurities in the extract, and obtain the supernatant as Artemisia annua and Dichroa febrifuga granule extract;

[0026] Preparation of Artemisia annua and Dichroa febrifuga granules: β-dextrin and pulverized sucrose were mixed evenly, and then all the extract was added as a soft material. Granulation was carried out by spray drying to obtain Artemisia annua and Dichroa febrifuga granules.

[0027] Example 2

[0028] An Artemisia annua and Dichroa febrifuga granules are prepared from the following raw materials and excipients by weight;

[0029] Ingredients: 300g Artemisia annua, 300g Dichroa febrifuga, 200g Pulsatilla chinensis, 200g Agrimonia pilosa. Excipients: 20g β-dextrin, 500g sucrose.

[0030] The preparation method of the Qiqing Baidu Granules as described above includes the following steps;

[0031] Preparation of Artemisia annua and Dichroa febrifuga granule extract: Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, and Agrimonia pilosa are pulverized and placed in an extraction tank to form a herb layer. 8-12 times the amount of water is added to cover the herb layer and soak for 2.0-3.0 hours. Then, the working temperature of the extraction tank is adjusted to 60-80℃ for extraction. During the extraction process, part of the extract is discharged from the bottom of the extraction tank for vacuum concentration at a temperature of 50-70℃. The steam generated during concentration is condensed and returned to the extraction tank as a new solvent to extract the herb layer again. This process is repeated for 2-3 hours to obtain the concentrated extract.

[0032] Treatment of Artemisia annua and Dichroa febrifuga granule extract: Add 10g of ZTC-II clarifying agent to the extract to precipitate impurities and obtain the supernatant, which is the Artemisia annua and Dichroa febrifuga granule extract.

[0033] Preparation of Artemisia annua and Dichroa febrifuga granules: β-dextrin and pulverized sucrose were mixed evenly, and then all the extract was added as a soft material. Granulation was carried out by spray drying to obtain Artemisia annua and Dichroa febrifuga granules.

[0034] Example 3

[0035] An Artemisia annua and Dichroa febrifuga granules are prepared from the following raw materials and excipients by weight;

[0036] Ingredients: 300g Artemisia annua, 300g Dichroa febrifuga, 200g Pulsatilla chinensis, 200g Agrimonia pilosa; Excipients: 30g β-dextrin, 600g sucrose.

[0037] The preparation method of the Qiqing Baidu Granules as described above includes the following steps;

[0038] Preparation of Artemisia annua and Dichroa febrifuga granule extract: Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis, and Agrimonia pilosa are pulverized and placed in an extraction tank to form a herb layer. 8-12 times the amount of water is added to cover the herb layer and soak for 2.0-3.0 hours. Then, the working temperature of the extraction tank is adjusted to 60-80℃ for extraction. During the extraction process, part of the extract is discharged from the bottom of the extraction tank for vacuum concentration at a temperature of 50-70℃. The steam generated during concentration is condensed and returned to the extraction tank as a new solvent to extract the herb layer again. This process is repeated for 2-3 hours to obtain the concentrated extract.

[0039] Treatment of Artemisia annua and Dichroa febrifuga granule extract: Add 10g of ZTC-II clarifying agent to the extract to precipitate impurities and obtain the supernatant, which is the Artemisia annua and Dichroa febrifuga granule extract.

[0040] Preparation of Artemisia annua and Dichroa febrifuga granules: β-dextrin and pulverized sucrose were mixed evenly, and then all the extract was added as a soft material. Granulation was carried out by spray drying to obtain Artemisia annua and Dichroa febrifuga granules.

[0041] The following are specific experimental results.

[0042] Experiment 1: Detection of Pulsatilla saponin content

[0043] The saponins of Pulsatilla chinensis were determined by high performance liquid chromatography.

[0044] Chromatographic conditions and system suitability tests were conducted using octadecylsilane-bonded silica gel as the stationary phase; methanol-water (64:36) as the mobile phase; and a detection wavelength of 201 nm. The theoretical plate number, calculated based on the peak of Pulsatilla chinensis saponin B4, was not less than 3000.

[0045] Preparation of the reference solution: Take an appropriate amount of Pulsatilla saponin B4 reference standard, accurately weigh it, and add methanol to prepare a solution containing 0.1 mg per ml.

[0046] Preparation of the test solution: Accurately weigh 2g of this product (finely ground), place it in a stoppered conical flask, add 10ml of methanol, seal tightly, sonicate (150W power, 40kHz frequency) for 25 minutes, cool, filter, place the filtrate in a 250ml volumetric flask, wash the container and residue with a small amount of mobile phase, add the washings to the same volumetric flask, add mobile phase to the mark, and shake well. See Table 1 for specific results.

[0047] Table 1. Results of the test on saponin content in Pulsatilla chinensis.

[0048]

[0049] The results show that the content of Pulsatilla saponins in the Artemisia annua granules provided by the present invention is significantly higher than that in commercially available Artemisia annua granules, indicating that the present invention is superior to commercially available Artemisia annua granules.

[0050] Experiment 2: Artemisinin content detection experiment

[0051] Artemisinin was determined by high performance liquid chromatography.

[0052] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the packing material; the mobile phase was acetonitrile-water (60:40); the flow rate was 1.0 ml / min; the detection wavelength was 203 nm; and the column temperature was 30 °C.

[0053] Preparation of the reference solution: Accurately weigh approximately 20 mg of artemisinin reference standard and place it in a 100 mL brown bottle. Dissolve and dilute to the mark with 50% acetone, and shake well to obtain the reference standard stock solution. Accurately measure 3 mL of the reference standard stock solution and place it in a 10 mL brown volumetric flask. Add 50% acetone to the mark and shake well to obtain the reference solution.

[0054] Preparation of the test solution: Take 2g of this product (finely ground), accurately weigh it, place it in a stoppered conical flask, accurately add 20mL of 50% acetone, weigh it, sonicate for 1h, cool it, weigh it again, replenish the lost weight with 50% acetone, shake well, filter it, and take the filtrate to obtain the test solution.

[0055] For the assay, accurately pipette 10 μL each of the reference solution and the test solution and inject them into the liquid chromatograph for determination. Calculate the content and the specific results are shown in Table 2.

[0056] Table 2. Results of Artemisinin Content Test

[0057]

[0058] The results show that the artemisinin content of the Artemisia annua and Dichroa febrifuga granules provided by the present invention is significantly higher than that of commercially available Artemisia annua and Dichroa febrifuga granules, indicating that the present invention is superior to commercially available Artemisia annua and Dichroa febrifuga granules.

[0059] Experiment 3: Results of Accelerated Testing

[0060] control group

[0061] Artemisia annua and Changshan granules sold in a certain city

[0062] Experimental method: Artemisia annua granules provided in Examples 1-3 and the control group were used as the research objects. They were placed in an incubator at (40±2℃) and (75±5)% relative humidity and tested at 0, 1, 2, 3 and 6 months respectively.

[0063] The results are shown in Table 3:

[0064] Table 3 Accelerated Test Results

[0065]

[0066] The results showed that the Artemisia annua and Dichroa febrifuga granules of the present invention were stable in high temperature and high humidity environments, while the content of commercially available Artemisia annua and Dichroa febrifuga granules decreased significantly. The Artemisia annua and Dichroa febrifuga granules in Example 3 showed good stability.

[0067] Experiment 3: Stability Test

[0068] Comparison Group 1

[0069] Artemisia annua and Changshan granules sold in a certain city

[0070] Experiment 1: Stability Test

[0071] Experimental Method: Using Examples 1-3 and commercially available Artemisia annua granules as comparative studies, the stability of the samples under high temperature (30℃) and high humidity (65%) conditions was evaluated by examining their properties. Normal results indicated no discoloration or clumping, while clumping indicated abnormality. Specific results are shown in Table 4.

[0072] Table 4. Stability of Artemisia annua particles

[0073] time Example 1 Example 2 Example 3 Commercially available samples October normal normal normal normal January normal normal normal normal March normal normal normal normal June normal normal normal normal September normal normal normal normal December normal normal normal clumping 18 months normal normal normal clumping 24 months Slight caking Slight caking normal clumping

[0074] The results show that the Artemisia annua and Dichroa febrifuga granules of the present invention have good stability in high temperature and high humidity environments, while commercially available Artemisia annua and Dichroa febrifuga granules clump together.

[0075] Test 4: Water Solubility Test

[0076] Experimental Method: Commercially available Artemisia annua and Dichroa febrifuga granules from Examples 1-3 and Control Group 1 were subjected to water solubility tests at ratios of 1:10, 1:20, and 1:50. After thorough mixing, the mixtures were allowed to stand for observation to assess their water solubility stability. Results are shown in Table 5.

[0077] Table 5. Results of water solubility test of Artemisia annua and Dichroa febrifuga granules.

[0078]

[0079]

[0080] The results show that the Artemisia annua and Dichroa febrifuga granules provided by this invention have better solubility than commercially available Artemisia annua and Dichroa febrifuga granules. After 8 hours of observation, there was no precipitation or drug exudation, while commercially available samples precipitated after 4 hours, indicating that this aqueous solution has excellent stability and is suitable for large-scale aquaculture.

[0081] Trial 5: Clinical Treatment Trial

[0082] Experimental animals: A batch of 20-day-old broiler chickens from a chicken farm exhibited symptoms such as leg and wing paralysis, retracted neck and closed eyes in a dozing state, anemia, dehydration, sunken eyes, emaciation, and bloody diarrhea. The diagnosis was coccidiosis in chicks.

[0083] Experimental design and methods: 300 sick chickens from the chicken farm were randomly selected.

[0084] In experimental group 1, commercially available Artemisia annua and Dichroa febrifuga granules were used. The dosage was 1.5g per 1L of drinking water for poultry, and the treatment was continued for 3 days.

[0085] Experimental group 2, the drug group of Example 3 of this invention, was administered to poultry via drinking water at a dose of 1.5g per 1L of water for 3 consecutive days. Specific groupings are shown in Table 6.

[0086] Table 6 Clinical Treatment Trial Grouping

[0087] Group Quantity (pieces) Test drug Dosage and administration Medication time 1 150 Commercially available 1.5g per 1L of water 3 days 2 150 This invention 1.5g per 1L of water 3 days

[0088] Efficacy evaluation criteria

[0089] Cure rate: The percentage of chickens in the group whose clinical symptoms, such as sunken eyes, emaciation, and bloody stools, completely returned to normal after the trial.

[0090] Effectiveness: The percentage of chickens whose clinical symptoms, such as sunken eyes, emaciation, and bloody diarrhea, significantly improved after the experiment out of the total number of chickens in the group.

[0091] Inefficiency: The proportion of chickens that died during the trial and whose condition did not improve after medication out of the total number of chickens in the group. See Table 7 for specific results.

[0092] Table 7 Results of Clinical Treatment Trials

[0093] Group Cured (only) Valid (only) Death (only) cure rate efficiency 1 106 12 32 70.6％ 78.6％ 2 121 13 16 80.6％ 89.3％

[0094] Conclusion: As shown in the table above, the Artemisia annua and Dichroa febrifuga granules of the present invention have a significant effect on chicken coccidiosis, and the curative effect is significantly higher than that of commercially available Artemisia annua and Dichroa febrifuga granules. Moreover, the drug has a longer duration of action. The extraction method used in the present invention is simple, easy to operate, and the process is stable, making it suitable for industrial production and widespread application.

[0095] Note that the above are merely preferred embodiments and the technical principles employed in this application. Those skilled in the art will understand that this application is not limited to the specific embodiments described herein, and various obvious changes, readjustments, and substitutions can be made without departing from the scope of protection of this application. Therefore, although this application has been described in detail through the above embodiments, this application is not limited to the above embodiments. Many other equivalent embodiments may be included without departing from the technical concept of this application, all of which fall within the scope of protection of this application.

Claims

1. A kind of Artemisia annua and Dichroa febrifuga granules, characterized in that, It is prepared from the following parts by weight of raw materials and excipients: Ingredients: 300g Artemisia annua, 300g Dichroa febrifuga, 200g Pulsatilla chinensis, 200g Agrimonia pilosa; Excipients: PEG-400 1-5g, ZTC-Ⅱ clarifying agent 5-10g, β-dextrin 10-30g, sucrose 400-600g.

2. A method for preparing Artemisia annua and Dichroa febrifuga granules, characterized in that, Includes the following steps: (1) Preparation of Artemisia annua and Dichroa febrifuga granules extract: Artemisia annua, Dichroa febrifuga, Pulsatilla chinensis and Agrimonia pilosa are crushed and placed in an extraction tank to form a medicinal material layer. 8 to 12 times the amount of water is added to cover the medicinal material layer and soak for 2.0 hours. Then the working temperature of the extraction tank is adjusted to 60 to 80℃ for extraction. During the extraction process, part of the extract is taken out from the bottom of the extraction tank for vacuum concentration. The concentration temperature is 50 to 70℃. The steam generated by concentration is condensed and returned to the extraction tank as a new solvent to extract the medicinal material layer again. This process is repeated for 2 to 3 hours to obtain the concentrated extract. (2) Treatment of Artemisia annua and Dichroa febrifuga granule extract: After dissolving the extract with PEG-400, ZTC-II clarifying agent is added to remove macromolecular substances such as proteins, tannins, and resins, so that the effective components of the extract are fully dissolved and impurities are precipitated. The supernatant is then taken to obtain Artemisia annua and Dichroa febrifuga granule extract. (3) After crushing the excipient sucrose, mix it with β-dextrin and add it to a granulator for boiling and drying to obtain Artemisia annua granules.

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