Chaihuang heat-clearing granules as well as preparation method and application thereof

Abstract

The invention relates to a firewood-huang heat-clearing granule as well as a preparation method and application thereof. The radix bupleuri and rhizoma anemarrhenae heat-clearing granules are prepared from 8-25 parts of radix bupleuri, 6-20 parts of rhizoma anemarrhenae, 8-25 parts of radix scutellariae, 8-25 parts of folium isatidis, 8-25 parts of mint and 20-50 parts of rhizoma phragmitis, and the preparation method comprises the steps of raw material pretreatment, alcohol extraction, concentration and drying, granulation and the like. The traditional Chinese medicine composition is suitable for diseases such as pneumonia, acute bronchitis, epidemic cerebrospinal meningitis, epidemic encephalitis B, gastrointestinal type cold and the like. Animal experiments prove that the granule has a remarkable antipyretic effect, is exact in curative effect, good in safety and good in stability, and has important clinical application value.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a Chaihuang Qingre granule, its preparation method, and its application. Background Technology

[0002] Pneumonia, acute bronchitis, epidemic cerebrospinal meningitis, epidemic encephalitis B, and gastroenteritis are common and frequently occurring diseases in clinical practice. They are mainly caused by viruses or bacteria and are clinically manifested as fever, cough, headache, body aches, and difficulty breathing. In severe cases, they can be life-threatening.

[0003] Traditional Chinese medicine (TCM) has unique advantages in treating the above-mentioned diseases. For pneumonia, TCM believes it is mostly caused by external wind-evil or phlegm-heat obstructing the lungs, and treatment often employs methods of relieving exterior symptoms with pungent and cooling herbs, clearing heat and resolving phlegm. For acute bronchitis, which is mostly caused by wind-evil or phlegm-heat invading the lungs, treatment often focuses on dispersing lung pathogens, clearing heat and resolving phlegm. Meningitis falls under the category of spring fever, generally caused by warm-heat pathogens in spring, and can be treated with methods of clearing heat and detoxifying, cooling the blood and calming the liver. Japanese encephalitis falls under the category of summer fever, caused by summer heat and epidemic toxins, and treatment should focus on clearing heat and detoxifying, opening the orifices and restoring consciousness. It is evident that the above diseases are mostly caused by external wind-heat, phlegm-heat invading the lungs, or epidemic toxins, and clearing heat is a common treatment principle.

[0004] Currently, there are some traditional Chinese medicine preparations for clearing heat on the market, such as Yinqiao Jiedu Pills, Banlangen Granules, Sangju Drink, Qingwen Baidu Drink, and Qingkailing. However, these preparations still have shortcomings in terms of ingredient compatibility, preparation process, and efficacy stability, making it difficult to meet clinical needs. Therefore, developing a traditional Chinese medicine preparation with a reasonable process, definite efficacy, and good safety is of great significance. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a traditional Chinese medicine granule with reasonable process, definite curative effect and good safety, as well as its preparation method and application.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A type of Chaihuang Qingre Granules is made from the following raw materials in parts by weight: Bupleurum chinense 8-25 parts, Anemarrhena asphodeloides 6-20 parts, Scutellaria baicalensis 8-25 parts, Isatis indigotica 8-25 parts, Mentha haplocalyx 8-25 parts, and Phragmites communis 20-50 parts.

[0007] Preferably, the weight parts of each raw material are: Bupleurum chinense 10-20 parts, Anemarrhena asphodeloides 8-15 parts, Scutellaria baicalensis 10-20 parts, Isatis indigotica 10-20 parts, Mentha haplocalyx 10-20 parts, and Phragmites communis 25-45 parts.

[0008] Preferably, the weight parts of each raw material are: Bupleurum chinense 15-18 parts, Anemarrhena asphodeloides 10-15 parts, Scutellaria baicalensis 15-18 parts, Isatis indigotica 15-18 parts, Mentha haplocalyx 15-18 parts, and Phragmites communis 30-45 parts.

[0009] Preferably, the weight parts of each raw material are: 18 parts Bupleurum chinense, 12 parts Anemarrhena asphodeloides, 18 parts Scutellaria baicalensis, 18 parts Isatis indigotica, 18 parts Mentha haplocalyx, and 40 parts Phragmites communis.

[0010] Preferably, the weight parts of each raw material are: 15 parts Bupleurum, 10 parts Anemarrhena, 15 parts Scutellaria, 15 parts Isatis leaf, 15 parts Mentha, and 35 parts Phragmites rhizome.

[0011] Preferably, the weight parts of each raw material are: 12 parts Bupleurum, 8 parts Anemarrhena, 12 parts Scutellaria, 12 parts Isatis leaf, 12 parts Mentha, and 27 parts Phragmites rhizome.

[0012] Preferably, the weight parts of each raw material are: 10 parts Bupleurum, 12 parts Anemarrhena, 6 parts Scutellaria, 9 parts Isatis leaf, 4 parts Mentha, and 23 parts Phragmites rhizome.

[0013] The preparation method of the Chaihuang Qingre Granules includes the following steps: (1) Raw material pretreatment: Wash, dry and crush each raw material to 60-80 mesh; (2) Alcohol extraction: Mix the pulverized raw materials in proportion, add 8-12 times the amount of 60-80% ethanol, and reflux extract 2-3 times, each time for 1.5-2.5 hours; (3) Concentration and drying: Combine the extracts, concentrate under reduced pressure to 60℃ and measure the relative density to be 1.10-1.20, then spray dry to obtain a dry powder; (4) Granulation: Mix the dry powder with an appropriate amount of excipients, granulate, dry and granulate to obtain the final product.

[0014] The excipients are one or more of dextrin, starch, and microcrystalline cellulose.

[0015] The particles have a particle size of 14-40 mesh and a moisture content of ≤8.0%.

[0016] This invention also provides the application of Chaihuang Qingre Granules in the preparation of drugs for treating pneumonia, acute bronchitis, epidemic cerebrospinal meningitis, epidemic encephalitis B, and gastroenteritis.

[0017] The drug is an oral preparation, including any one or more of granules, tablets, capsules, pills, and oral liquids.

[0018] The efficacy of the traditional Chinese medicine raw materials in this invention is as follows: Bupleurum: pungent, bitter, slightly cold. It disperses and reduces fever, soothes the liver and relieves depression, and raises yang qi.

[0019] Anemarrhena asphodeloides: bitter, sweet, and cold. It clears heat and drains fire, nourishes yin and moistens dryness.

[0020] Scutellaria baicalensis: bitter, cold. Clears heat and dries dampness, drains fire and detoxifies, stops bleeding, and calms the fetus.

[0021] Isatis leaf: bitter, cold. Clears heat and detoxifies, cools the blood and eliminates spots.

[0022] Peppermint: pungent, cool. It disperses wind-heat, clears the head and eyes, soothes the throat, promotes rash eruption, and soothes the liver and regulates qi.

[0023] Reed rhizome: sweet, cold, enters the lung and stomach meridians. Clears heat, generates fluids, quenches thirst, and promotes urination.

[0024] Based on the treatment principle of "clearing heat and detoxifying, and expelling pathogens externally" in febrile diseases, this formula uses Bupleurum, which is bitter, pungent, and slightly cold, to harmonize the exterior and interior and reduce fever. Scutellaria baicalensis works with Bupleurum to clear heat from the Shaoyang gallbladder and directly suppress lung and stomach fire, especially effective in clearing lung heat in the upper burner and relieving cough, wheezing, and yellow phlegm. Anemarrhena asphodeloides clears excess heat in the lungs and stomach while generating fluids and moistening dryness, preventing heat from damaging Yin. Isatis tinctoria clears heat and toxins from epidemic diseases and cools the blood. Mentha haplocalyx assists Bupleurum in expelling pathogens externally, relieving headache, sore throat, and clearing the lungs to stop cough. Phragmites communis clears heat, generates fluids, and promotes urination, preventing thirst caused by febrile diseases. The entire formula works synergistically to clear heat and detoxify, dispel wind and release the exterior, clear the lungs and stop cough, and is suitable for exogenous febrile diseases manifested as fever, cough, yellow phlegm, chest pain, headache, sore throat, bitter taste in the mouth, red tongue with yellow coating, and rapid pulse, especially suitable for acute cases with intense heat and toxins.

[0025] The beneficial effects of this invention are: (1) Combination of Chinese herbs: Bupleurum and peppermint expel external pathogens, while Scutellaria, Anemarrhena, and Isatis leaf clear internal heat. This formula addresses both the exterior and interior by simultaneously relieving external pathogens and clearing heat. Scutellaria clears heat from the lung and stomach, Isatis leaf cools the blood and detoxifies, and Anemarrhena moistens the lungs and protects yin, thus treating the internal transmission of heat toxins to the blood and achieving the effect of clearing both qi and blood. Reed rhizome clears heat and generates fluids, preventing discomfort such as thirst and oliguria after fever subsides, and ensuring the overall balance of the formula.

[0026] (2) Preparation process: The alcohol extraction process is adopted, which can fully extract the effective components and improve bioavailability; the spray drying technology is adopted to ensure the stability of product quality.

[0027] (3) Therapeutic effect: Animal experiments have shown that the Chaihuang Qingre Granules of the present invention have a significant antipyretic effect.

[0028] (4) Safety: The selected raw materials are all traditional Chinese medicines, which are highly safe. Detailed Implementation

[0029] To better illustrate the objectives, technical solutions, and advantages of this invention, the invention will be further described below in conjunction with specific embodiments. However, this invention is not limited thereto. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without inventive effort are within the scope of protection of this invention.

[0030] Example 1: Preparation of Chaihuang Qingre Granules Ingredient ratio: Bupleurum chinense 18 parts, Anemarrhena asphodeloides 12 parts, Scutellaria baicalensis 18 parts, Isatis indigotica 18 parts, Mentha haplocalyx 18 parts, Phragmites communis 40 parts.

[0031] Preparation method: (1) Raw material pretreatment: Wash, dry and crush each raw material to 60-80 mesh; (2) Alcohol extraction: Mix the pulverized raw materials in proportion, add 10 times the amount of 70% ethanol, and reflux extract 2-3 times, each time for 1.5-2.5 hours; (3) Concentration and drying: Combine the extracts, concentrate under reduced pressure to 60℃ and measure the relative density to be 1.10-1.20, then spray dry to obtain a dry powder; (4) Granulation: Mix the dry powder with an appropriate amount of microcrystalline cellulose, granulate, dry and granulate to obtain the final product.

[0032] The resulting Chaihuang Qingre granules are brownish-yellow granules with a particle size of 14-40 mesh, a moisture content of 6.2%, and a solubility of ≤60 seconds.

[0033] Example 2: Preparation of Chaihuang Qingre Granules Ingredient ratio: Bupleurum chinense 15 parts, Anemarrhena asphodeloides 10 parts, Scutellaria baicalensis 15 parts, Isatis indigotica 15 parts, Mentha haplocalyx 15 parts, Phragmites communis 35 parts.

[0034] The preparation method is the same as in Example 1. The resulting Chaihuang Qingre granules are brownish-yellow granules with a particle size of 14-40 mesh, a moisture content of 6.5%, and a solubility of ≤60 seconds.

[0035] Example 3: Preparation of Chaihuang Qingre Granules Ingredient ratio: Bupleurum chinense 12 parts, Anemarrhena asphodeloides 8 parts, Scutellaria baicalensis 12 parts, Isatis indigotica 12 parts, Mentha haplocalyx 12 parts, Phragmites communis 27 parts.

[0036] The preparation method is the same as in Example 1. The resulting Chaihuang Qingre granules are brownish-yellow granules with a particle size of 14-40 mesh, a moisture content of 6.0%, and a solubility of ≤65 seconds.

[0037] Comparative Example 1 Ingredient ratio: Bupleurum chinense 18 parts, Anemarrhena asphodeloides 12 parts, Scutellaria baicalensis 18 parts, Isatis indigotica 18 parts, Mentha haplocalyx 18 parts, Phragmites communis 40 parts.

[0038] Preparation method: (1) Raw material pretreatment: Wash, dry and crush each raw material to 60-80 mesh; (2) Water extraction: Mix the pulverized raw materials in proportion, add 10 times the amount of water, and reflux extract 2-3 times, each time for 1.5-2.5 hours; (3) Concentration and drying: Combine the extracts, concentrate under reduced pressure to 60℃ and measure the relative density to be 1.10-1.20, then spray dry to obtain a dry powder; (4) Granulation: Mix the dry powder with an appropriate amount of microcrystalline cellulose, granulate, dry and granulate to obtain the final product.

[0039] The resulting Chinese medicine granules are brownish-yellow granules with a particle size of 14-40 mesh, a moisture content of 6.5%, and a solubility of ≤60 seconds.

[0040]

Experimental Example

[0041] Testing items: content determination, moisture content, solubility, microbial limits, and appearance.

[0042] Experimental results: All indicators met the requirements in the accelerated test (6 months) and the long-term test (36 months).

[0043] Recommended shelf life: 36 months. Storage conditions: sealed, store in a cool, dry place.

[0044] Table 1 Stability Test

[0045] Experiment Example 2: Antipyretic Effect Experiment [Equipment and Reagents] Electronic balance, rectal thermometer, syringe, gavage needle, volumetric flask.

[0046] Dry yeast powder, physiological saline, petroleum jelly, and medication (acetaminophen, Chaihuang Qingre Granules in Example 1, and Chinese herbal granules in Comparative Example 1).

[0047] Example 1 Preparation of high, medium and low dose groups: The Chaihuang Qingre Granules of Example 1 were ground into powder in a mortar. 24.0g was weighed and diluted to a volumetric flask of 50mL. After dilution, the high, medium and low dose group solutions were obtained as 0.48g / mL, 0.24g / mL and 0.12g / mL, respectively, for later use.

[0048] Comparative Example 1: The Chinese herbal granules were prepared into a 0.24 g / mL solution using the method described above, and then set aside for later use.

[0049] [Animals and Grouping] Healthy SD rats, weighing 180-220g, were used. For the first 7 days of the experiment, the rats were acclimatized (environmental temperature 25±2℃, relative humidity 50±5%) to allow them to adapt to the environment and temperature stimulation. A small amount of petroleum jelly-soaked electronic thermometer was inserted 2cm into the rat's anus to measure its temperature once daily for 3 consecutive days. On the day of the experiment, the temperature was measured hourly for 3 consecutive hours. Rats with a temperature change not exceeding 0.3℃ were retained, and the average temperature was used as the basal body temperature. The rats were randomly divided into groups of 10 each (half male, half female) based on their body temperature and weight. These groups included a blank control group, a model group, a positive control group (acetaminophen), and treatment groups (high, medium, and low dose groups in Example 1, and Comparative Example 1).

[0050] [Modeling and Drug Administration] In the normal control group, rats were subcutaneously injected with saline in their backs. In the other groups, a yeast pyrogenic model was established by subcutaneously injecting yeast suspension (20% yeast powder + saline) in the backs of rats at a dose of 5 mL / kg. Four hours after modeling, the body temperature of rats in each group was monitored to be at least 0.6℃ higher. The positive control group and the drug-treated group were administered the corresponding drugs by gavage, while the blank control group and the model group were administered an equal volume of saline by gavage at 10 mL / kg.

[0051] Four hours after administration, rectal temperature was measured once, and temperature changes were recorded to compare differences between groups.

[0052] Statistical Analysis Data were analyzed using SPSS 26.0 statistical software. Analysis of variance was performed on each group of data. P <0.05 is considered statistically significant.

[0053]

result

[0054] Table 2. Effects of each group on body temperature in yeast-induced pyrogenic rats (°C, ± s, n=10) Group Basal body temperature Post-modeling body temperature Body temperature after medication Blank control group 37.51±0.33 37.80±0.21 37.71±0.23 Model group 37.47±0.27 39.08±0.29## 39.70±0.35## Positive control group 37.53±0.30 39.13±0.27## 38.28±0.37** Example 1 High-dose group 37.48±0.25 38.91±0.23## 38.17±0.36** In Example 1, the dosage group 37.42±0.33 38.92±0.20## 38.65±0.29** Example 1 Low-dose group 37.51±0.38 39.02±0.28## 38.84±0.33* Comparative Example 1 37.50±0.31 39.03±0.35## 38.95±0.35 Note: Compared with the blank control group, ##: P <0.01; compared with the model group, *: P <0.05, **: P <0.01.

[0055] There was no significant difference in basal body temperature among the groups of rats. After yeast-induced pyrogenic modeling, the body temperature of rats in the model group was significantly higher than that in the normal group. P<0.01), indicating successful model establishment. Compared with the model group, the high, medium and low dose groups of Example 1 (using alcohol extraction process) all showed good antipyretic effects, while the efficacy of the control group (using water extraction process) was not as good as that of the alcohol extraction group. It can be seen that the alcohol extraction process improves the heat-clearing effect.

[0056]

discuss

[0057] In the early stages of exogenous febrile diseases, pathogenic factors often invade the lung and wei levels (Wei level syndrome). Heat-clearing drugs, through their pungent and cool exterior-releasing or heat-clearing and detoxifying effects, allow the pathogenic factors to be expelled from the exterior. Representative drugs include Bupleurum and Mentha, which are pungent and cool, dispel wind-heat, open the pores, and expel the pathogenic factors through sweating.

[0058] If pathogenic factors penetrate the Qi level, the heat intensifies, leading to symptoms such as high fever, thirst, sweating, and a rapid, forceful pulse. In such cases, heat-clearing and fire-purging herbs are needed to directly clear and purge the excess heat in the Qi level. Anemarrhena asphodeloides is sweet and cold, clearing heat in the Qi level and generating fluids to quench thirst. Scutellaria baicalensis clears heat and dries dampness, its bitter and cold nature directly suppressing the fire in the lungs and stomach.

[0059] If the heat toxicity is severe, it can penetrate into the blood level, leading to serious conditions such as delirium, rashes, hematemesis, and epistaxis. In such cases, cooling and detoxifying herbs are needed to clear the heat from the blood level. Isatis leaf (Daqingye) clears heat and detoxifies, cools the blood and eliminates rashes, inhibits epidemic toxins, and treats febrile diseases with rashes.

[0060] Heat syndromes easily deplete body fluids, leading to symptoms of yin deficiency such as dry mouth and throat, red tongue with little coating, and scanty urine. It is necessary to combine these with sweet and cold yin-nourishing herbs, such as anemarrhena and reed rhizome.

[0061] The effects of heat-clearing drugs not only conform to traditional Chinese medicine theory, but modern research has also confirmed that they exert their therapeutic effects through a multi-target synergistic pathway, including antiviral / bacterial, anti-inflammatory and immunomodulatory, antipyretic and analgesic, and antioxidant effects.

[0062] By combining syndrome differentiation and treatment with modern research, heat-clearing drugs can effectively treat exogenous heat syndromes and reduce the occurrence of complications (such as pneumonia, encephalitis, and gastroenteritis).

[0063] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A type of Chaihuang Qingre Granules, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: Bupleurum chinense 8-25 parts, Anemarrhena asphodeloides 6-20 parts, Scutellaria baicalensis 8-25 parts, Isatis indigotica 8-25 parts, Mentha haplocalyx 8-25 parts, and Phragmites communis 20-50 parts.

2. The Chaihuang Qingre Granules according to claim 1, characterized in that, The weight parts of each ingredient are as follows: Bupleurum chinense 10-20 parts, Anemarrhena asphodeloides 8-15 parts, Scutellaria baicalensis 10-20 parts, Isatis indigotica 10-20 parts, Mentha haplocalyx 10-20 parts, and Phragmites communis 25-45 parts.

3. The Chaihuang Qingre Granules according to claim 1, characterized in that, The weight parts of each ingredient are as follows: Bupleurum chinense 18 parts, Anemarrhena asphodeloides 12 parts, Scutellaria baicalensis 18 parts, Isatis indigotica 18 parts, Mentha haplocalyx 18 parts, and Phragmites communis 40 parts.

4. The Chaihuang Qingre Granules according to any one of claims 1-3, characterized in that, The method for preparing the particles includes the following steps: (1) Raw material pretreatment: Wash and dry each raw material separately, and pulverize it to 60-80 mesh; (2) Alcohol extraction: Mix the pulverized raw materials in proportion, add 8-12 times the amount of 60-80% ethanol, and reflux extract 2-3 times, each time for 1.5-2.5 hours; (3) Concentration and drying: Combine the extracts, concentrate under reduced pressure to 60℃ and measure the relative density to be 1.10-1.20, then spray dry to obtain a dry powder; (4) Granulation: Mix the dry powder with an appropriate amount of excipients, granulate, dry and granulate to obtain the final product.

5. The Chaihuang Qingre Granules according to claim 4, characterized in that, The excipients are one or more of dextrin, starch, and microcrystalline cellulose.

6. The Chaihuang Qingre Granules according to claim 4, characterized in that, The particles have a particle size of 14-40 mesh and a moisture content of ≤8.0%.

7. A method for preparing Chaihuang Qingre Granules, characterized in that, Includes the following steps: (1) Raw material pretreatment: According to any of the raw material ratios in claims 1-3, each raw material is washed, dried, and pulverized to 60-80 mesh; (2) Alcohol extraction: Mix the pulverized raw materials in proportion, add ethanol, and reflux extract 2-3 times, each time for 1.5-2.5 hours; (3) Concentration and drying: Combine the extracts, concentrate under reduced pressure to 60℃ and measure the relative density to be 1.10-1.20, then spray dry to obtain a dry powder; (4) Granulation: Mix the dry powder with an appropriate amount of excipients, granulate, dry and granulate to obtain the final product.

8. The preparation method of Chaihuang Qingre Granules according to claim 7, characterized in that, Add 8-12 times the amount of 60-80% ethanol during the alcohol extraction step.

9. The preparation method of Chaihuang Qingre Granules according to claim 7, characterized in that, The particles have a particle size of 14-40 mesh and a moisture content of ≤8.0%.

10. The use of the Chaihuang Qingre Granules according to any one of claims 1-6 in the preparation of drugs for treating pneumonia, acute bronchitis, epidemic cerebrospinal meningitis, epidemic encephalitis B, and gastroenteritis.

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