A Chinese medicine composition and pharmaceutical preparation and its preparation method and application

Abstract

The present invention relates to the field of traditional Chinese medicine, specifically providing a traditional Chinese medicine composition and pharmaceutical preparation, as well as a preparation method and application thereof. The traditional Chinese medicine composition is obtained through repeated optimization of the composition and content of the medicinal components in the compound through clinical and basic research. The prescription comprises Artemisia annua and Scutellaria baicalensis as the monarch medicinal components; Gypsum rotundus, Isatis indigotica, Honeysuckle, and Indigo naturalis as the assistant medicinal components; Poria cocos, Tangerine peel, Pinellia ternata, Rhizoma Anemarrhenae, Periostracum Cicadae, and Mentha arvense as the adjuvant medicinal components; and Licorice as the guiding medicinal component. The above medicinal components work together to clear the lungs and relieve heat, harmonize the stomach and eliminate dampness, and have strong antipyretic, fever-reducing, and expectorant effects.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition and pharmaceutical preparation as well as a preparation method and application thereof. Background Art

[0002] Colds (also known as acute upper respiratory tract infections) are common childhood exogenous illnesses characterized by fever, chills, headache, nasal congestion, runny nose, cough, and sneezing. Colds, also known as common colds, can be divided into two types: the common cold, caused by wind pathogens, is generally mild, primarily manifests in the lungs, and does not cause epidemics; the epidemic cold, caused by seasonal viruses, is more severe and has epidemic characteristics, known in Western medicine as influenza. The common cold is often accompanied by fever, sore throat, and a mild cough with sputum. A Traditional Chinese Medicine (TCM) symptom analysis of 2,502 patients with upper respiratory tract infection and fever in Guangdong Province found that 45.24% had exogenous wind-heat and dampness syndrome, characterized by fever, chills, headache, poor appetite, cough, heaviness in the head and body, sore throat, body aches, a red or pale red tongue, a white tongue coating, and a floating or rapid pulse (see "Analysis of Traditional Chinese Medicine Symptoms in 2,502 Patients with Upper Respiratory Tract Infection and Fever").

[0003] Over the past thousands of years, traditional Chinese medicine has played an important role in treating diseases. Therefore, giving full play to the advantages of traditional Chinese medicine and developing effective traditional Chinese medicines to treat colds, especially colds caused by exogenous wind-heat and dampness, has become an urgent issue that needs to be addressed. Summary of the Invention

[0004] Therefore, the object of the present invention is to provide a traditional Chinese medicine composition and a pharmaceutical preparation as well as a preparation method and application thereof, wherein the traditional Chinese medicine composition and / or pharmaceutical preparation has strong antipyretic, anti-inflammatory and expectorant effects, and can effectively treat colds, especially colds caused by exogenous wind-heat and dampness.

[0005] To this end, the present invention provides a traditional Chinese medicine composition, which includes the following raw materials in parts by weight: 100-300 parts of Artemisia annua, 100-300 parts of Scutellaria baicalensis, 100-450 parts of Poria cocos, 100-270 parts of dried tangerine peel, 100-270 parts of Rhizoma Anemarrhenae, 580-820 parts of Gypsum, 200-450 parts of Honeysuckle, 200-450 parts of Folium Isatidis, 100-300 parts of Pinellia ternata, 100-270 parts of Periostracum Cicadae, 100-270 parts of Menthol, 100-270 parts of Licorice and 20-180 parts of Indigo Naturalis.

[0006] In certain preferred embodiments, the traditional Chinese medicine composition includes the following raw materials, in parts by weight, 200-300 parts of Artemisia annua, 200-300 parts of Scutellaria baicalensis, 250-450 parts of Poria cocos, 150-270 parts of dried tangerine peel, 150-270 parts of Rhizoma Anemarrhenae, 700-820 parts of Gypsum, 300-450 parts of Honeysuckle, 300-450 parts of Folium Isatidis, 200-300 parts of Pinellia ternata, 150-270 parts of Periostracum Cicadae, 150-270 parts of Menthol, 150-270 parts of Licorice and 50-150 parts of Indigo Naturalis.

[0007] In certain preferred embodiments, the Chinese medicine composition includes the following raw materials, in parts by weight, 100-150 parts of Artemisia annua, 100-150 parts of Scutellaria baicalensis, 150-200 parts of Poria cocos, 100-150 parts of dried tangerine peel, 100-150 parts of Rhizoma Anemarrhenae, 580-700 parts of Gypsum, 200-300 parts of Honeysuckle, 200-300 parts of Folium Isatidis, 150-200 parts of Pinellia ternata, 100-150 parts of Periostracum Cicadae, 100-150 parts of Menthol, 100-150 parts of Licorice and 40-50 parts of Indigo Naturalis.

[0008] In certain preferred embodiments, the Chinese medicine composition comprises the following raw materials, in parts by weight, 250 parts of Artemisia annua, 250 parts of Scutellaria baicalensis, 375 parts of Poria cocos, 150 parts of dried tangerine peel, 150 parts of Rhizoma Anemarrhenae, 750 parts of Gypsum, 375 parts of Honeysuckle, 375 parts of Isatis indigotica, 250 parts of Pinellia ternata, 150 parts of Periostracum Cicadae, 150 parts of Mint, 150 parts of Licorice and 50 parts of Indigo Naturalis; or, the Chinese medicine composition comprises the following raw materials, 100 parts of Artemisia annua, 100 parts of Scutellaria baicalensis, 150 parts of Poria cocos, 100 parts of dried tangerine peel, 100 parts of Rhizoma Anemarrhenae, 580 parts of Gypsum, 200 parts of Honeysuckle, 200 parts of Isatis indigotica, 150 parts of Pinellia ternata, 100 parts of Periostracum Cicadae, 100 parts of Mint, 100 parts of Licorice. and 20 parts of Indigo Naturalis; or, the Chinese medicine composition includes the following raw materials: 200 parts of Artemisia annua, 250 parts of Scutellaria baicalensis, 170 parts of Poria cocos, 170 parts of dried tangerine peel, 170 parts of Rhizoma Anemarrhenae, 650 parts of Gypsum, 350 parts of Honeysuckle, 250 parts of Isatis indigotica, 200 parts of Pinellia ternata, 170 parts of Periostracum Cicadae, 170 parts of Menthol, 170 parts of Licorice and 120 parts of Indigo Naturalis; or, the Chinese medicine composition includes the following raw materials: 300 parts of Artemisia annua, 300 parts of Scutellaria baicalensis, 450 parts of Poria cocos, 270 parts of dried tangerine peel, 270 parts of Rhizoma Anemarrhenae, 820 parts of Gypsum, 450 parts of Honeysuckle, 450 parts of Isatis indigotica, 300 parts of Pinellia ternata, 270 parts of Periostracum Cicadae, 270 parts of Menthol, 170 parts of Licorice and 180 parts of Indigo Naturalis.

[0009] Furthermore, the Chinese medicine composition does not contain Jiao Sanxian.

[0010] The present invention also provides a method for preparing the traditional Chinese medicine composition, which is characterized in that: after mixing Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, bamboo shavings, gypsum, honeysuckle, isatis indigotica, pinellia ternata, cicada slough, mint and licorice, the mixture is extracted according to a conventional extraction method or after being extracted according to a conventional extraction method respectively, the mixture is mixed and then mixed with Indigo Naturalis to obtain the traditional Chinese medicine composition; or after mixing Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, bamboo shavings, gypsum, honeysuckle, isatis indigotica, pinellia ternata, cicada slough, mint, licorice and Indigo Naturalis, the mixture is extracted according to a conventional extraction method or after being extracted according to a conventional extraction method respectively, the mixture is mixed to obtain the traditional Chinese medicine composition.

[0011] Furthermore, the conventional extraction method includes one or more of decoction extraction, maceration extraction, percolation extraction, reflux extraction, ultrasonic extraction, and steam distillation extraction; the extraction solvent is selected from water or a 5-98% by volume alcohol solution; the extraction is repeated at least once; the extraction time is at least 10 minutes; and the ratio of the mass of the extraction solvent to the weight of the API is ≥2. Preferably, the alcohol solution is an aqueous ethanol solution or an aqueous methanol solution.

[0012] The present invention also provides a pharmaceutical preparation comprising the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method, and optionally one or more pharmaceutically acceptable excipients.

[0013] Preferably, the pharmaceutical preparation is in the form of micropills, tablets, capsules, powders, mixtures, granules, syrups, gels or decoctions;

[0014] Preferably, the pharmaceutically acceptable excipient is selected from at least one of pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, glidants, flavoring agents, preservatives, suspending agents, coating materials, anti-adhesives, penetration enhancers, pH regulators, and thickeners. Flavoring agents include sweeteners and / or sour agents.

[0015] For example, excipients may include flavoring agents such as steviol glycosides, citric acid, and fillers such as dextrin.

[0016] The present invention also provides a method for preparing the above-mentioned pharmaceutical preparation, comprising the following steps:

[0017] Decoction step: gypsum is decocted with an extraction solvent, and the decoction liquid and the medicinal residue are collected to obtain A; Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, bamboo shavings, honeysuckle, isatis indigotica, Pinellia ternata, cicada slough, mint, and liquorice are mixed, A is added, and the mixture is soaked with an extraction solvent, decocted and extracted, solid-liquid separation is performed, and the liquid is collected to obtain a medicinal solution;

[0018] The preparation steps of the pharmaceutical preparation are: concentrating and / or drying the medicinal solution, mixing it with Indigo Naturalis, adding or not adding auxiliary materials, and preparing the pharmaceutical preparation according to conventional process; or,

[0019] Decoction step: gypsum is decocted with an extraction solvent, and the decoction liquid and the medicinal residue are collected to obtain A; Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, bamboo shavings, honeysuckle, isatis indigotica, Pinellia ternata, cicada slough, mint, liquorice, and indigo naturalis are mixed, A is added, and the mixture is soaked with an extraction solvent, decocted and extracted, solid-liquid separation is performed, and the liquid is collected to obtain a medicinal solution;

[0020] The preparation steps of the pharmaceutical preparation are as follows: the pharmaceutical solution is concentrated and / or dried, excipients are added or not added, and the pharmaceutical preparation is prepared according to conventional processes.

[0021] Furthermore, the water decoction step includes taking gypsum, adding 3-6 times the weight of gypsum in water or 5-98% alcohol solution and decocting for 30-90 minutes, collecting the decoction and the residue to obtain A; taking Artemisia annua, Scutellaria baicalensis, Poria cocos, Tangerine peel, Rhizoma Anemarrhenae, Honeysuckle, Isatis indigotica, Pinellia ternata, Periostracum Cicadae, Mentha, and Licorice, mixing them, adding A, adding water to 5-12 times the weight of the medicinal materials in water or 5-98% alcohol solution, soaking for 30-120 minutes, decocting and extracting 1-4 times, the material-liquid mass ratio of each extraction being 1:6-15, the extraction time being 60-120 minutes, separating the solid and liquid, collecting the liquid, and obtaining the medicinal solution.

[0022] Furthermore, the auxiliary material includes a filler. The mass ratio of the dry drug powder obtained by mixing with Indigo Naturalis after drying to the filler is 8:2-7:3. The moisture content of the material after drying is 5%-6.5%.

[0023] Furthermore, the ratio of the mass of the finished pharmaceutical preparation to the mass of the raw materials used is 1000:1800-5000, preferably 1000:3425, wherein the mass of the raw materials is the sum of the masses of all raw materials.

[0024] Furthermore, the preparation method of the pharmaceutical preparation includes the following steps: adding 6 times the amount of water to gypsum, decocting for 30 minutes, collecting the decoction and the residue to obtain A; mixing Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Honeysuckle, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Menthol, and Licorice, adding A, replenishing water to 11.5 times the weight of the prescribed medicinal materials (except Indigo), soaking for 2 hours, decocting for 1.5 hours, filtering the decoction, and collecting the filtrate; adding 10 times the amount of water to the residue, decocting for 1.5 hours, filtering, combining the filtrate, and concentrating under reduced pressure to an extract with a relative density of 1.05 to 1.12 (60°C), spray drying into fine powder, adding the prescribed amount of Indigo and at least one auxiliary material selected from sweeteners, sour agents, and fillers, mixing evenly, and dry granulating to form granules.

[0025] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition prepared by the above-mentioned preparation method, the above-mentioned pharmaceutical preparation, or the pharmaceutical preparation prepared by the above-mentioned preparation method in preparing a medicine having at least one of the functions of relieving fever and removing phlegm.

[0026] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition prepared by the above-mentioned preparation method, the above-mentioned pharmaceutical preparation or the pharmaceutical preparation prepared by the above-mentioned preparation method in preparing drugs with anti-inflammatory effects.

[0027] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition prepared by the above-mentioned preparation method, the above-mentioned pharmaceutical preparation or the pharmaceutical preparation prepared by the above-mentioned preparation method in preparing medicines for preventing or treating colds.

[0028] The technical solution of the present invention has the following advantages:

[0029] 1. The Chinese medicine composition provided by the present invention was obtained through repeated optimization of the composition and content of the medicinal ingredients in the compound through clinical and basic research. The formula comprises Artemisia annua and Scutellaria baicalensis as the main medicinal ingredients; Gypsum follicles, Isatis indigotica, Honeysuckle, and Indigo naturalis as the auxiliary medicinal ingredients; Poria cocos, Tangerine peel, Pinellia ternata, Rhizoma Anemarrhenae, Periostracum Cicadae, and Mentha arvense as the adjuvant medicinal ingredients; and Licorice as the guiding medicinal ingredient. These medicinal ingredients work together to clear the lungs and relieve fever, harmonize the stomach, and eliminate dampness, exhibiting strong antipyretic, anti-inflammatory, laxative, and expectorant effects.

[0030] Among them, Artemisia annua is bitter, cold, and aromatic, clearing away pathogenic heat in the Shaoyang meridians. The "New Compendium of Materia Medica" describes it as "clearing heat and fire without depleting Qi and blood." Scutellaria baicalensis is bitter and cold, effectively clearing gallbladder heat and drying dampness. Together, these two herbs can clear damp-heat in the Shaoyang meridians and expel pathogenic heat, making it the monarch herb. Gypsum, with its pungent and cold properties, can reduce heat and clear lung and stomach fire. Isatis indigotica, with its bitter and cold properties, clears heat and detoxifies, cools blood, and eliminates freckles. Honeysuckle is sweet and cold, particularly effective at clearing heat and detoxifying, dispersing wind-heat. Indigo, with its salty and cold properties, clears heat and detoxifies, purging fire and calming nerves, making it the assistant herb. Poria cocos and dried tangerine peel invigorate the spleen and regulate Qi, Pinellia ternata and bamboo shavings resolve phlegm and relieve vomiting, while cicada sloughs and peppermint dissipate wind-heat, making them adjuvants. Licorice, with its heat-clearing and detoxifying properties, harmonizes the various herbs, making it the guiding herb. The combination of these medicines can clear the damp-heat in Shaoyang, expel the evil spirits, clear the fire in the lungs and stomach, clear away heat and detoxify, cool the blood and eliminate spots, disperse wind-heat, purge fire and calm the nerves, strengthen the spleen and regulate qi, resolve phlegm and stop vomiting. The coordination of these medicines can achieve the effect of clearing the lungs and relieving heat, harmonizing the stomach and eliminating dampness.

[0031] Therefore, it has significant effect on the treatment of exogenous wind-heat and dampness syndrome with symptoms such as fever, decreased appetite, bad breath, abdominal distension and vomiting, mild cough with sputum, sore throat, uncomfortable bowel movements, red tongue and greasy coating.

[0032] 2. The traditional Chinese medicine composition provided by the present invention has thirteen Chinese medicinal herbs in its formula, which complement each other and are indispensable. If other Chinese medicinal herbs with the effects of clearing heat and drying dampness, such as Coptis chinensis, are used to replace the baicalin of the present invention, or if other Chinese medicinal herbs with the effects of clearing deficiency heat, such as Phellodendron chinense or Bupleurum chinense, are used to replace the Artemisia annua of the present invention, the antipyretic and fever-reducing effects will be greatly affected. In addition, compared with other prescriptions, omitting Jiao Sanxian can greatly reduce the dosage for children, and its antipyretic and expectorant effects in animal experiments are significantly improved.

[0033] 3. The pharmaceutical preparations provided by the present invention can be prepared into various dosage forms according to practical applications, such as external use, injection, or oral administration, including, but not limited to, micropills, tablets, capsules, powders, mixtures, granules, syrups, gels, or decoctions. Granules are more convenient to use, have higher stability, are suitable for industrial production, and ensure the therapeutic effect and safety of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0035] Figure 1 This is the water absorption curve of Chinese medicinal materials in Experimental Example 1;

[0036] Figure 2 The effect of the powder of Example 5 in Experimental Example 3 on the body temperature of rats in the dry yeast solution-induced fever model;

[0037] Figure 3 The effects of the powders of different embodiments in Experimental Example 3 on the body temperature of rats in the dry yeast solution-induced fever model;

[0038] Figure 4 The effects of the powders of Example 5 and Comparative Example 1 on the body temperature of rats in a dry yeast solution-induced fever model are shown. DETAILED DESCRIPTION

[0039] The following examples are provided for a better understanding of the present invention and are not intended to limit the best mode of implementation. They do not limit the content and scope of protection of the present invention. Any product identical or similar to the present invention obtained by anyone under the guidance of the present invention or by combining the features of the present invention with other prior arts shall fall within the scope of protection of the present invention.

[0040] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments is not specified, they are all commercially available conventional reagents.

[0041] All medicinal materials have passed quality control and conform to the standards of the Pharmacopoeia of the People's Republic of China. Quantities are by weight. % ethanol refers to the volume percentage of ethanol in an ethanol-water solution.

[0042] Example 1 Particles

[0043] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 250g of Artemisia annua, 250g of Scutellaria baicalensis, 375g of Poria cocos, 150g of dried tangerine peel, 150g of Rhizoma Anemarrhenae, 750g of Gypsum, 375g of Honeysuckle, 375g of Isatis indigotica, 250g of Pinellia ternata, 150g of Periostracum cicadae, 150g of Menthol, 150g of Licorice and 50g of Indigo Naturalis.

[0044] This embodiment also provides granules of the above-mentioned Chinese medicine composition, and the preparation method thereof is as follows:

[0045] Add 6 times the amount of water to gypsum and boil for 30 minutes. Collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Mentha, and Glycyrrhizae, add A, add water to 11.5 times the weight of the prescribed medicinal materials (except Indigo Naturalis), soak for 2 hours, boil for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of water to the residue, boil for 1.5 hours, filter, combine the filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), spray-dry into a fine powder, add the prescribed amount of Indigo Naturalis, 5g of stevioside, 40g of citric acid, and an appropriate amount of dextrin, mix evenly, and dry granulate to prepare granules.

[0046] Example 2 Syrup

[0047] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 100g of Artemisia annua, 100g of Scutellaria baicalensis, 150g of Poria cocos, 100g of dried tangerine peel, 100g of Rhizoma Anemarrhenae, 580g of Gypsum, 200g of Honeysuckle, 200g of Isatis indigotica, 150g of Pinellia ternata, 100g of Periostracum cicadae, 100g of Menthol, 100g of Licorice and 20g of Indigo Naturalis.

[0048] This embodiment also provides a syrup of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0049] Add 6 times the weight of water to gypsum and boil for 30 minutes. Collect the decoction and residue to obtain A. Mix Artemisia annua, Scutellaria baicalensis, Poria cocos, Tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Mentha, Glycyrrhizae uralensis, and Indigo Naturalis, add A, add water to 11.5 times the weight of the prescribed medicinal materials, soak for 2 hours, boil for 1.5 hours, filter the decoction, and collect the filtrate. Add 10 times the weight of water to the residue, boil for 1.5 hours, filter, combine the filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C). Separately, take 2000 g of sucrose, add water, boil, dissolve, filter, and concentrate to obtain a syrup. Mix the mixture with the above concentrate, boil, cool, add a preservative and flavoring, and dilute with an appropriate amount of cold water to obtain a syrup.

[0050] Example 3 Tablets

[0051] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 300g of Artemisia annua, 300g of Scutellaria baicalensis, 450g of Poria cocos, 270g of dried tangerine peel, 270g of Rhizoma Anemarrhenae, 820g of Gypsum, 450g of Honeysuckle, 450g of Isatis indigotica, 300g of Pinellia ternata, 270g of Periostracum cicadae, 270g of Menthol, 270g of Licorice and 60g of Indigo Naturalis.

[0052] This embodiment also provides tablets of the above-mentioned Chinese medicine composition, and the preparation method thereof is as follows:

[0053] Add 6 times the amount of water to gypsum, decoct for 30 minutes, collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Mentha, and Glycyrrhizae, add A, add water to 11.5 times the weight of the prescribed medicinal materials (except Indigo Naturalis), soak for 2 hours, decoct for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of water to the residue, decoct for 1.5 hours, filter, combine the filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60° C.), spray-dry into a fine powder, add the prescribed amount of Indigo Naturalis and an appropriate amount of dextrin, mix evenly, dry granulate, and then add 0.5% magnesium stearate and 5% talc based on the mass of the granules, mix evenly, compress into tablets, and coat to obtain the product.

[0054] Example 4 Micropellets

[0055] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 200g of Artemisia annua, 200g of Scutellaria baicalensis, 250g of Poria cocos, 170g of dried tangerine peel, 170g of Rhizoma Anemarrhenae, 650g of Gypsum, 350g of Honeysuckle, 250g of Folium Isatidis, 200g of Pinellia ternata, 170g of Periostracum Cicadae, 170g of Menthol, 170g of Licorice and 40g of Indigo Naturalis.

[0056] This embodiment also provides pellets of the above-mentioned Chinese medicine composition, which are prepared as follows:

[0057] Add 6 times the amount of water to gypsum, decoct for 30 minutes, collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Honeysuckle, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Menthol, and Licorice, add A, add water to 11.5 times the weight of the prescribed medicinal materials (except Indigo), soak for 2 hours, decoct for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of water to the residue, decoct for 1.5 hours, filter, combine the filtrate, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), spray-dry into a fine powder, add the prescribed amount of Indigo and an appropriate amount of starch, mix evenly, use ethanol as a wetting agent, make micropills, and sieve; dry below 60°C to obtain micropills.

[0058] Example 5 Powder

[0059] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 12 kg of Artemisia annua, 12 kg of Scutellaria baicalensis, 18 kg of Poria cocos, 7.2 kg of dried tangerine peel, 7.2 kg of Rhizoma Anemarrhenae, 36 kg of Gypsum, 18 kg of Honeysuckle, 18 kg of Isatis indigotica, 12 kg of Pinellia ternata, 7.2 kg of Cicada Periostracum, 7.2 kg of Menthol, 7.2 kg of Licorice, and 2.4 kg of Indigo Naturalis.

[0060] This embodiment also provides a powder of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0061] Add 6 times the amount of water to gypsum and boil for 30 minutes. Collect the decoction and residue to obtain A. Mix Artemisia annua, Scutellaria baicalensis, Poria cocos, Tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Mentha, and Licorice, add A, add water to 11.5 times the weight of the prescribed medicinal materials (except Indigo), soak for 2 hours, boil for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of water to the residue, boil for 1.5 hours, filter, combine the filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), spray-dry into a fine powder, and mix evenly with Indigo to obtain a powder.

[0062] Example 6 Powder

[0063] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 250g of Artemisia annua, 250g of Scutellaria baicalensis, 375g of Poria cocos, 150g of dried tangerine peel, 150g of Rhizoma Anemarrhenae, 750g of Gypsum, 375g of Honeysuckle, 375g of Isatis indigotica, 250g of Pinellia ternata, 150g of Periostracum cicadae, 150g of Menthol, 150g of Licorice and 50g of Indigo Naturalis.

[0064] This embodiment also provides a powder of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0065] Add 6 times the amount of 30% ethanol to gypsum, decoct for 30 minutes, collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Menthol, and Glycyrrhizae, add A, add 30% ethanol to 11.5 times the weight of the prescribed medicinal materials (except Indigo Naturalis), soak for 2 hours, decoct for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of 30% ethanol to the residue, decoct for 1.5 hours, filter, combine the filtrate, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), spray-dry into a fine powder, and mix evenly with Indigo Naturalis to obtain a powder.

[0066] Example 7 Powder

[0067] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 250g of Artemisia annua, 250g of Scutellaria baicalensis, 375g of Poria cocos, 150g of dried tangerine peel, 150g of Rhizoma Anemarrhenae, 750g of Gypsum, 375g of Honeysuckle, 375g of Isatis indigotica, 250g of Pinellia ternata, 150g of Periostracum cicadae, 150g of Menthol, 150g of Licorice and 50g of Indigo Naturalis.

[0068] This embodiment also provides a powder of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0069] Add 6 times the amount of 50% ethanol to gypsum, decoct for 30 minutes, collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Menthol, and Glycyrrhizae, add A, add 50% ethanol to 11.5 times the weight of the prescribed medicinal materials (except Indigo Naturalis), soak for 2 hours, decoct for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of 50% ethanol to the residue, decoct for 1.5 hours, filter, combine the filtrate, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), spray-dry into a fine powder, and mix evenly with Indigo Naturalis to obtain a powder.

[0070] Example 8 Powder

[0071] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 250g of Artemisia annua, 250g of Scutellaria baicalensis, 375g of Poria cocos, 150g of dried tangerine peel, 150g of Rhizoma Anemarrhenae, 750g of Gypsum, 375g of Honeysuckle, 375g of Isatis indigotica, 250g of Pinellia ternata, 150g of Periostracum cicadae, 150g of Menthol, 150g of Licorice and 50g of Indigo Naturalis.

[0072] This embodiment also provides a powder of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0073] Add 6 times the amount of 75% ethanol to gypsum, decoct for 30 minutes, collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Menthol, and Licorice, add A, add 75% ethanol to 11.5 times the weight of the prescribed medicinal materials (except Indigo Naturalis), soak for 2 hours, decoct for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of 75% ethanol to the residue, decoct for 1.5 hours, filter, combine the filtrate, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), spray-dry into a fine powder, and mix evenly with Indigo Naturalis to obtain a powder.

[0074] Example 9 Capsules

[0075] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 100g of Artemisia annua, 120g of Scutellaria baicalensis, 125g of Poria cocos, 100g of dried tangerine peel, 110g of Rhizoma Anemarrhenae, 650g of Gypsum, 275g of Honeysuckle, 225g of Folium Isatidis, 280g of Pinellia ternata, 250g of Periostracum Cicadae, 110g of Menthol, 120g of Licorice and 30g of Indigo Naturalis.

[0076] This embodiment also provides a powder of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0077] Add 3 times the amount of 50% ethanol to gypsum, decoct for 30 minutes, collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Mentha, and Glycyrrhizae, add A, add 50% ethanol to 10 times the weight of the prescribed medicinal materials (except Indigo Naturalis), soak for 1.5 hours, decoct for 1 hour, filter the decoction, and collect the filtrate; add 10 times the amount of 50% ethanol to the residue, decoct for 1 hour, filter, combine the filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), spray-dry into a fine powder, mix evenly with Indigo Naturalis, granulate, and make into capsules.

[0078] Example 10 Composition

[0079] This embodiment provides a traditional Chinese medicine composition, comprising the following raw materials: 280g of Artemisia annua, 300g of Scutellaria baicalensis, 425g of Poria cocos, 260g of dried tangerine peel, 250g of Rhizoma Anemarrhenae, 800g of Gypsum, 425g of Honeysuckle, 425g of Isatis indigotica, 120g of Pinellia ternata, 110g of Periostracum cicadae, 250g of Menthol, 270g of Licorice and 170g of Indigo Naturalis.

[0080] This embodiment also provides a powder of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0081] Add 3 times the amount of water to gypsum, decoct for 30 minutes, collect the decoction and residue to obtain A; mix Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Mentha, Glycyrrhizae uralensis, and Indigo Naturalis, add A, add water to 10 times the weight of the prescribed medicinal materials, soak for 2 hours, decoct for 1.5 hours, filter the decoction, and collect the filtrate; add 10 times the amount of water to the residue, decoct for 1 hour, filter, combine the filtrates, concentrate under reduced pressure to an appropriate amount, add an appropriate amount of ethanol for precipitation, remove the supernatant, recover the ethanol under reduced pressure, add water, stir, and let stand; remove the supernatant, filter, concentrate the filtrate to 4000 ml, add an appropriate amount of preservative, and stir well to obtain the product.

[0082] Comparative Example 1 Powder

[0083] This comparative example provides a pharmaceutical composition and a preparation method thereof, comprising the following raw materials: 250g of Artemisia annua, 250g of Scutellaria baicalensis, 375g of Poria cocos, 150g of dried tangerine peel, 150g of Rhizoma Anemarrhenae, 750g of Gypsum, 375g of Flos Lonicerae, 375g of Folium Isatidis, 250g of Rhizoma Pinelliae, 150g of Periostracum Cicadae, 150g of Menthol, 150g of Licorice, 50g of Indigo Naturalis, and 250g each of the three roasted herbs (including 250g of roasted Hawthorn, 250g of roasted Malt, and 250g of roasted Shenqu).

[0084] This comparative example also provides a powder of the above-mentioned Chinese medicine composition, and its preparation method is as follows:

[0085] Add 6 times the amount of water to gypsum and boil for 30 minutes. Collect the decoction and residue to obtain A. Mix Artemisia annua, Scutellaria baicalensis, Poria cocos, Tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Mentha, Licorice, and Rhizoma Corydalis. Add A and add water to 11.5 times the weight of the prescribed medicinal materials (except Indigo Naturalis). Soak for 2 hours, boil for 1.5 hours, filter the decoction, and collect the filtrate. Add 10 times the amount of water to the residue, boil for 1.5 hours, filter, combine the filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C). Spray dry into a fine powder, and mix evenly with Indigo Naturalis to obtain a powder.

[0086] Experimental Example 1 Investigation of the Soaking Process

[0087] Weigh 12.37g of Artemisia annua, 12.37g of Scutellaria baicalensis, 18.56g of Poria cocos, 7.42g of dried tangerine peel, 7.42g of Rhizoma Anemarrhenae, 37.11g of Gypsum, 18.56g of Flos Lonicerae, 18.56g of Folium Isatidis, 12.37g of Rhizoma Pinelliae, 7.42g of Periostracum Cicadae, 7.42g of Mentha, and 7.42g of Radix Glycyrrhizae, with a total prescription of 167g (laboratory test), place them in a beaker, weigh them, add enough cold water to soak them, drain the water every 30 minutes and weigh them, then add enough water to soak them, repeat the above operation until all the medicinal materials are soaked and the total weight of the beaker and the soaked medicinal materials no longer increases. Repeat the test 3 times and calculate the water absorption rate of the medicinal materials. The results are shown in Table 1. Figure 1 .

[0088] Table 1 Investigation on water absorption rate of medicinal materials

[0089]

[0090] From the above table and Figure 1 It can be seen that when the medicinal materials are soaked in sufficient amount of cold water for 2 hours, their water absorption no longer increases significantly. Considering the actual production situation, the soaking time is preferably 2 hours. When the water absorption of the medicinal materials is close to 1.5 times the dry weight of the medicinal materials, the water absorption degree of the medicinal materials is basically saturated. Therefore, the water absorption of 1.5 times the dry weight of the medicinal materials needs to be supplemented before the first extraction.

[0091] Experimental Example 2 Investigation of Extraction Process

[0092] 1. Evaluation Criteria

[0093] The contents of baicalin in Scutellaria baicalensis and chlorogenic acid in Lonicera japonica were used as content determination evaluation indicators. Combined with the traditional water extraction process and the extract as the evaluation indicator, a multi-factor comprehensive evaluation method was adopted to optimize the extraction process parameters.

[0094] 2. Effects of gypsum decoction and extraction time on baicalin and its extracts

[0095] Since the prescription contains gypsum, according to the requirement of decocting gypsum first in the original prescription, the gypsum was decocted for different times and then other medicinal materials were added for extraction to investigate whether the decoction time has an effect on the extraction of baicalin and the extract. The prescription is consistent with the prescription of Experimental Example 1.

[0096] The effects of different gypsum decoction times on the extract were investigated. According to the proportion of each medicinal material in the prescription, twelve medicinal materials including Scutellaria baicalensis (also known as gypsum) were weighed separately. Gypsum was first added with 6 times the amount of water of the medicinal materials and decocted for 30, 60, and 90 minutes. The decoction and residue were collected to obtain A. Artemisia annua, Scutellaria baicalensis, Poria cocos, Tangerine peel, Rhizoma Anemarrhenae, Honeysuckle, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Mentha, and Licorice were mixed, added with A, and the amount of water was replenished to 11.5 times the weight of the prescribed medicinal materials (except Indigo). The mixture was soaked for 2 hours and decocted for 1.5 hours. The decoction was filtered and the filtrate was collected. The residue was added with 10 times the amount of water and decocted for 1.5 hours. The mixture was filtered, and the filtrate was combined and concentrated under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C). The extract was placed in an aluminum foil basin with a dry constant weight and dried in a freeze-vacuum drying oven. After drying, the extract was weighed, ground into powder, and the dry extract yield was calculated. The baicalin content and transfer rate were determined by weighing a certain amount of extract powder. The process conditions of each group of experiments were the same except for the gypsum decoction time. Three parallel experiments were conducted. The results are shown in Tables 2 and 3 below.

[0097] Table 2 Effect of gypsum decoction time on compound dry extract yield

[0098]

[0099] Table 3 Effect of gypsum decoction time on compound baicalin content and transfer rate

[0100]

[0101] From the data in the above table, it can be seen that with the extension of the gypsum pre-decoction time, the medicinal material extract rate, baicalin content and its transfer rate all increased, but the increase was not large, and the overall difference in the experimental results was not obvious. Therefore, from the perspective of saving cost and time, and considering that gypsum is non-toxic and does not require special decoction, the gypsum pre-decoction time is preferably set to 30 minutes.

[0102] 3. Single factor investigation of extraction process

[0103] According to the proportions of the various medicinal ingredients in the prescription, twelve medicinal ingredients, including Scutellaria baicalensis, were weighed, consistent with the recipe in Experimental Example 1, for a total of 167 g. Gypsum was first decocted with 6 times the weight of water for 30 minutes. The decoction and residue were collected to obtain A. A was added to the remaining eleven ingredients before the initial extraction, and water was added to 1.5 times the weight of the medicinal ingredients in the prescription (except Indigo Naturalis). The ingredients were soaked for 2 hours, followed by decoction. Extraction times of 30, 60, 90, and 120 minutes were tested; extractions were repeated 1, 2, 3, and 4 times; and the material-to-water ratios were 1:6, 1:8, 1:10, and 1:12. The combined extracts were concentrated under reduced pressure on a rotary evaporator to a thick paste. The paste was then placed in an aluminum foil basin to a constant dry weight and dried in a vacuum oven. After drying, the paste was weighed and ground into a fine powder. The moisture content was determined using a rapid moisture meter, and the dry paste yield was calculated. The single-factor experimental plan is shown in Table 4 below, and the results are shown in Table 5.

[0104] Table 4 Single factor experimental plan

[0105]

[0106] Table 5 Single factor test results

[0107]

[0108]

[0109] The experimental results showed that as the extraction time increased, the extract yield and baicalin transfer rate increased significantly, while the chlorogenic acid transfer rate decreased slightly with the extension of decoction time; as the material-water mass ratio increased, the extract yield and baicalin transfer rate increased slightly, while the chlorogenic acid transfer rate tended to decrease with the increase of the material-water mass ratio, which may be due to the extension of heating time; as the number of extractions increased, the extract yield, baicalin, and chlorogenic acid transfer rates increased with the increase of the number of extractions. Combined with the experimental results, considering the actual production situation, and the orthogonal test can further optimize the extraction process, the extraction time of 60, 90, and 120 min, the material-water mass ratio of 1:8, 1:10, and 1:12, and the number of extractions of 1, 2, and 3 were selected for the orthogonal test, with L9(3 4 ) were used to conduct orthogonal experiments to select the optimal extraction process parameters.

[0110] 4. Orthogonal experiment for optimization of water extraction process parameters (a) Orthogonal experiment design

[0111] According to the proportion of each medicinal material in the prescription, twelve medicinal materials such as Scutellaria baicalensis were weighed separately. The prescription was consistent with the prescription of Experimental Example 1, with a total prescription amount of 167 g. Gypsum was added with 6 times the amount of water and decocted for 30 minutes. The decoction and the residue were collected to obtain A; A was added before the first extraction of the remaining eleven herbs, and 1.5 times the weight of the medicinal material prescription (except Indigo) was supplemented with water. The mixture was soaked for 2 hours. The experimental extraction studies were carried out according to the factors and level conditions designed in Table 6. The extracts were combined and the volume of the extract was measured with a graduated cylinder. The orthogonal test is shown in Table 7.

[0112] Table 6 Factor levels of orthogonal experiment for water extraction process

[0113]

[0114] Table 7 Orthogonal test plan for water extraction process

[0115]

[0116] (b) Orthogonal test results and variance analysis

[0117] The variance analysis was performed on the comprehensive scoring results of the orthogonal test, and the results are shown in Table 8 and Table 9 for the variance analysis.

[0118] Table 8 Results of orthogonal test of water extraction process

[0119]

[0120]

[0121] Table 9 Analysis of variance table of orthogonal test of water extraction process

[0122]

[0123] Note: F(2.2)0.01=99, F(2.2)0.05=19; **P<0.01, *P<0.05

[0124] It can be seen from Tables 8 and 9 that when the extract yield is used as the evaluation index, factors A and B are statistically significant, while factor C is not statistically significant. The order of their importance is B>A>C, and the best extraction test plan is A3B3C3; when the baicalin transfer rate is used as the evaluation index, factor B is statistically significant, while factors A and C are not statistically significant. The order of their importance is B>A>C, and the best extraction test plan is A3B3C3; when the chlorogenic acid transfer rate is used as the evaluation index, factor B is statistically significant, while factors A and C are not statistically significant. The order of their importance is B>A>C, and the best extraction test plan is A2B2C3.

[0125] Combined with the results of variance analysis, according to the actual situation, the extraction time of factor A had little effect on the extract yield and the transfer rate of baicalin between A2 and A3 levels, and there was no significant difference in the chlorogenic acid transfer rate; the number of extractions of factor B had significant differences on the extract yield, baicalin and chlorogenic acid transfer rates, but the levels of B2 and B3 had little effect on the extract yield and the transfer rate of baicalin, and the chlorogenic acid transfer rate was significantly better than that of B3; the amount of solvent of factor C had no significant difference on the extract yield, baicalin and chlorogenic acid transfer rate. Combined with the variance analysis results of factors A and B and the actual situation in the production process, the best extraction scheme was finally selected as A2B2C2, that is, the extraction time was 1.5 hours, the number of extractions was 2 times, and the extraction material-water mass ratio was 1:10. It can not only effectively shorten the production cycle, save energy and protect the environment, but also meet the requirements of the best extraction process.

[0126] (c) Orthogonal test extraction process verification

[0127] According to the recipe in Experimental Example 1, four portions of twelve medicinal herbs, including Scutellaria baicalensis, were weighed, each weighing 167g. A validation test was conducted using the optimal process method determined by orthogonal experiment. The optimal process method was as follows: Gypsum was added to 6 times the weight of water and decocted for 30 minutes. The decoction and residue were collected to obtain A. Artemisia annua, Scutellaria baicalensis, Poria cocos, Tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Mentha, and Licorice were mixed, and A was added. The mixture was hydrated to 11.5 times the weight of the prescribed herbs (excluding Indigo naturalis). The mixture was soaked for 2 hours, decocted for 1.5 hours, the decoction was filtered, and the filtrate was collected. The residue was added to 10 times the weight of water, decocted for 1.5 hours, filtered, and the filtrate was combined and concentrated under reduced pressure to an extract with a relative density of 1.05-1.12 (60°C), and then dried. The results of the four batches of process validation for extract yield, baicalin, and chlorogenic acid transfer rates are shown in Table 10 below.

[0128] Table 10 Extraction process verification results

[0129]

[0130]

[0131] The experimental results showed that the extract yield of the four batches of process validation was approximately 21.50%, the average transfer rate of baicalin was 75.25%, and the average transfer rate of chlorogenic acid was 48.89%. The RSD values ​​for the extract yield, baicalin transfer rate, and chlorogenic acid transfer rate were less than 5%. The optimized process achieved satisfactory results for the content of each index component and the dry extract yield, which were generally consistent with the results obtained in the orthogonal experiment. This indicates that the extraction conditions screened by the orthogonal experiment are stable and reliable. Therefore, the optimal extraction process parameters are as follows: gypsum was first decocted for 0.5 hours. The liquid and residue were combined with the remaining eleven medicinal materials, and the water was added to 11.5 times the total weight of the medicinal materials. The mixture was soaked for 2 hours, and the first decoction was performed. The filtrate was collected. The residue was then decocted and extracted again with 10 times the amount of water, and each extraction lasted 1.5 hours.

[0132] Experimental Example 3 Effect of the Drug of the Present Invention on the Rat Fever Model Induced by Dry Yeast Solution

[0133] 1. Experimental Design

[0134] Colds are a common and frequently occurring illness in pediatric clinics, occurring in all seasons but more frequently in winter and spring. In Western medicine, they are classified as acute upper respiratory tract infections (AURIs) in children. Fever is the primary clinical symptom of colds in children. Western antipyretics act on the hypothalamic thermoregulatory center, causing peripheral vasodilation and increased blood circulation in the skin, thereby increasing heat dissipation and achieving a cooling effect. However, these drugs fail to selectively target the multiple causes of fever. Without addressing the underlying cause, fever is difficult to control and can easily relapse. Traditional Chinese medicine (TCM) treats exogenous fever by prioritizing the secondary and concurrent interference of multiple factors. Formulas used in TCM emphasize targeting the multiple contributing factors and central pathological mechanisms, employing complex mechanisms to eliminate the underlying causes and regulate physiological functions.

[0135] The drug of the present invention is composed of multiple medicinal materials, including Artemisia annua, honeysuckle, and scutellaria baicalensis. Artemisia annua is bitter, cold, and aromatic, and has the functions of clearing heat, cooling blood, and relieving fever, and is particularly effective in clearing heat from the liver, gallbladder, and blood. Scutellaria baicalensis is a heat-clearing and damp-drying herb, and is good at clearing damp-heat pathogenic fire from the upper and middle Jiao. The two herbs are paired, with Artemisia annua clearing away pathogenic heat from the Shaoyang meridians and Scutellaria baicalensis clearing away pathogenic heat from the gallbladder. They have the effects of clearing the lungs, relieving heat, and harmonizing the stomach to eliminate dampness. They are used to treat wind-heat exogenous infection with dampness in children, characterized by fever, sore throat, mild cough with sputum, dampness-induced bad breath, and wrist swelling and vomiting.

[0136] This study evaluated the antipyretic effects of the powders of Examples 5, 6, 7, and 8 on yeast-induced fever in young rats, providing a basis for clinical trials.

[0137] 2. Test Materials

[0138] 2.1 Test sample

[0139] 2.1.1 Basic Information

[0140] The powders prepared in Example 5, Example 6, Example 7, and Example 8 were used as test drugs.

[0141] 2.1.2 Preparation method

[0142] An appropriate amount of the powder prepared in Example 5 was weighed, ground uniformly, and then a small amount of ultrapure water was added to continue grinding. Finally, the volume was adjusted to the desired concentration with ultrapure water.

[0143] Appropriate amounts of the powders prepared in Example 6, Example 7, and Example 8 were weighed respectively, and firstly ground evenly, and then a small amount of ultrapure water was added to continue grinding, and finally the volume was adjusted to the required concentration with ultrapure water.

[0144] Use an electronic balance with an accuracy of 0.001g to weigh, prepare in a normal environment, and prepare before use.

[0145] 2.2 Reference substance 1

[0146] 2.2.1 Basic Information

[0147] Ibuprofen suspension, main ingredient: ibuprofen; properties: orange suspension; dosage: daily dose 32 mL (0.64 g), oral, four times a day; specifications: 100 mL: 2 g; storage conditions: protected from light, sealed; expiration date: 202411; manufacturer: Shanghai Johnson & Johnson Pharmaceutical Co., Ltd.; provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0148] 2.2.2 Preparation method

[0149] Ibuprofen suspension is available in 2g per 100mL, or 20mg / mL. Take an appropriate volume of ibuprofen suspension and add ultrapure water to the desired concentration. Prepare under normal conditions and prepare immediately before use.

[0150] 2.3 Reference substance 2

[0151] 2.3.1 Basic Information

[0152] Xiaoer Chiqiao Qingre Granules, main ingredients: Forsythia suspensa, light fermented black beans, mint, Schizonepeta tenuifolia, etc.; Appearance: Light yellow granules; Usage and Dosage: Daily dose: 15g, taken with boiled water, three times a day; Specification: 2g / bag; Storage: Protect from light; Batch number: 2207124; Expiration date: 202408; Manufacturer: Jichuan Pharmaceutical Group Co., Ltd.; Provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0153] 2.3.2 Preparation method

[0154] Weigh an appropriate amount of Xiaoer Chiqiao Qingre Granule powder and grind it evenly. Add a small amount of ultrapure water and continue grinding. Finally, dilute to the desired concentration with ultrapure water. Use an electronic balance with an accuracy of 0.001g. Prepare in a normal environment and prepare immediately before use.

[0155] 2.4 Main Reagents

[0156] Angel highly active dry yeast, properties: light yellow thin strips, storage conditions: cool and dry, specifications: 15g / bag, batch number: 20230103, shelf life: 12 months, manufacturer: Angel Yeast Co., Ltd., provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0157] Sodium chloride injection, properties: colorless liquid, storage conditions: sealed, specifications: 250mL / bottle, batch number: 2301253402, expiration date: 20250124, manufacturer: Shijiazhuang Siyao Co., Ltd., provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0158] 2.5 Main instruments

[0159] BT125D electronic balance: Sartorius Scientific Instruments (Beijing) Co., Ltd.

[0160] PL203 electronic balance: Mettler-Toledo Instruments (Shanghai) Co., Ltd.

[0161] DNA103A electronic balance: Nanjing Bonita Scientific Instrument Co., Ltd.

[0162] ECA522 electronic balance: Nanjing Bonita Scientific Instrument Co., Ltd.

[0163] ECC2201 electronic balance: Nanjing Bonita Scientific Instrument Co., Ltd.

[0164] BSA224S-CW electronic balance: Sartorius Scientific Instruments (Beijing) Co., Ltd.

[0165] OMRON electronic thermometer: OMRON (Dalian) Co., Ltd.

[0166] 2.6 Experimental Animals

[0167] 2.6.1 Basic Information

[0168] Species: SD rats, grade: SPF grade, weight / age: 140-160 g / 4-5 weeks old, sex: half male and half female, quantity: 200, quality certificate number: 110011231105520161 (male), 110011231105520075 (female), supplier: Beijing Weitonglihua Laboratory Animal Technology Co., Ltd., license number: SCXK (Beijing) 2021-0006.

[0169] 2.6.2 Animal facilities

[0170] Facility name: Animal Experiment Building of Tianjin Tiancheng New Drug Evaluation Co., Ltd., Facility address: No. 308, Huiren Road, Binhai Science and Technology Park, Binhai Hi-tech Zone, Tianjin, Experimental Animal Use License Number: SYXK(Jinbin)2021-0008, Issuing unit: Tianjin Binhai New Area Science and Technology Bureau.

[0171] 2.6.3 Animal feed

[0172] Feed name: SPF rat maintenance feed, sterilization method: 60 Co irradiation, supplier: Keao Xieli (Tianjin) Feed Co., Ltd., animal feed production license: Tianjin Feed Certificate (2020) 01005, issuing unit: Tianjin Municipal Agriculture and Rural Affairs Commission, Beijing Municipal Agriculture Bureau.

[0173] Feed testing: Each batch of feed has a quality certificate and a self-inspection report provided by the feed supplier. The feed supplier provides a recent third-party feed testing report every year.

[0174] Feed test results: All test indicators meet the requirements.

[0175] 2.6.4 Animal drinking water

[0176] Drinking water source: sterile water prepared by the experimental animal drinking machine MK-500R; drinking water method: directly filled with drinking bottles, and animals can drink freely.

[0177] Drinking water testing: Our company conducts self-inspection of microbial indicators of drinking water every quarter and sends it to a professional third-party testing agency for hygienic evaluation and testing every year.

[0178] Drinking water test results: All test indicators meet the requirements.

[0179] 2.6.5 Animal rearing conditions

[0180] Rats were housed in polypropylene rat cages with a cage size of 48 cm (length × width × height) × 35 cm × 20 cm. Males and females were housed separately, with a maximum of five animals per cage.

[0181] Temperature: Set the temperature range to 20-26°C, Humidity: Set the humidity range to 40%-70%, Ventilation rate: no less than 15 times of fresh air / hour, Light: 12 hours of light and 12 hours of dark alternating.

[0182] Feeding conditions test results: No abnormal conditions that affected the test results occurred during the test.

[0183] 2.6.6 Animal husbandry and management

[0184] Except for special requirements (such as fasting or water deprivation), animals were allowed to eat and drink freely. Drinking bottles and the drinking water in the bottles were changed daily and not reused. After use, the drinking bottles were sterilized in a pulse vacuum sterilizer before reuse.

[0185] The chassis of animal cages are replaced daily, cages are replaced weekly, and cage covers are replaced every two weeks. All cages are sterilized in a pulse vacuum sterilizer under high pressure before use in a barrier environment. Animal cages are cleaned, disinfected, and wiped once a week. Animal observation rooms are cleaned and disinfected daily, covering the floor, countertops, desktops, doors, windows, and air inlets and exhaust vents. The disinfectants used include: chlorhexidine solution with a solute-to-solvent ratio of 1:29, 1:149, and 1:249, peracetic acid solution, and 84 disinfectant. The three disinfectants are used in rotation, one per week, and cannot be mixed.

[0186] 2.6.7 Animal Receipt and Inspection

[0187] Laboratory animals are received by the experimenter, animal support staff, and veterinarians. Upon receipt, the transport vehicle is inspected to ensure compliance with requirements and the animal supplier's animal qualification certificate is provided. The certificate details are confirmed to be consistent with the species, grade, sex, and quantity of animals requested. Once the outer packaging meets requirements and is inspected, the animals are moved to the quarantine room.

[0188] In the quarantine room, the animals' packaging was opened and the number of animals of each sex was verified to be consistent with the information on the animal qualification certificate. Each animal was individually inspected (including sex, head, trunk, tail, limbs, fur, mental state, and activity). After quarantine, the animals were placed in animal cages, tagged, and placed on the cage racks in the quarantine room for the acclimatization period. No abnormal animals were found.

[0189] The animals were kept in an adaptive feeding and observation period of 4 days before the experiment. During the adaptation period, the animals were observed comprehensively every day. No abnormal animals were found during the adaptation period.

[0190] 2.6.8 Animal Identification

[0191] Individual identification: Animals were numbered and marked with animal marking fluid, with male and female animals in each group marked starting with number 1.

[0192] Cage identification: Cage labels should be hung on animal cages. The labels should include the project number, animal species, group, cage number, number of animals, animal number, gender, and project leader.

[0193] Identification of the feeding and observation room: Labels should be posted in the feeding and observation room, which should include the topic number, topic name, experimental stage, topic leader, main experimental personnel, etc.

[0194] 2.6.9 Animal Welfare

[0195] Our company is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) and has an Institutional Animal Care and Use Committee (IACUC) responsible for oversight, review, and guidance of animal welfare. The animal use methods used in this study were approved by the Institutional Animal Ethics Committee (IACUC). IACUC approval number is 2023052402.

[0196] 3. Test methods

[0197] 3.1 Model making

[0198] Two hundred healthy Sprague-Dawley rats, 4-5 weeks old, weighing 140-160 g (half male and half female), were selected and acclimated for four days. After the acclimation period, rectal temperature was measured twice daily to acclimate the rats to the environment and the temperature stimulus. Rats with rectal temperatures between 36.6 and 37.9°C (with a rectal temperature difference of no more than 0.5°C) for two consecutive days were selected and retained.

[0199] The retained rats were fasted overnight before the experiment. Rectal temperatures were measured twice on the day of the experiment, and the average was used as the baseline rectal temperature (before modeling). After the experiment, 10 rats were randomly selected as a normal control group based on the baseline rectal temperature. The remaining animals were subcutaneously injected with 10 mL / kg of a 20% yeast suspension for modeling. The injection site was massaged to ensure uniform subcutaneous diffusion of the suspension. Six hours after modeling, rectal temperatures were measured, and rats with a rectal temperature increase of 1.2°C or more were selected as qualified rats for modeling.

[0200] 3.2 Trial Grouping

[0201] Qualified rats were selected and randomly divided into groups according to the rectal temperature difference. See Table 10 and Table 11 for details.

[0202] Table 10 Effect of the powder of Example 5 on the fever model of rats induced by dry yeast solution Experimental groups and administration methods

[0203]

[0204] Note: n: number of animals

[0205] Table 11 Effects of the powders of Examples 5, 6, 7, and 8 on the fever model of rats induced by dry yeast solution Experimental groups and administration methods

[0206]

[0207] Note: n: number of animals

[0208] 3.3 Dosage setting and administration

[0209] Example 5: Example 5 is clinically applicable to children aged 3 to 12 years, with a daily dose of 137 g of crude drug / kg. Based on the average weight of 26.4 kg for eight-year-old children, the clinical equivalent dose in rats, calculated using the Meeh-Rubner formula based on body surface area, is 23.6 g of crude drug / kg. Based on the results of previous experiments, the doses of Example 5 in this experiment were set at 2, 1, and 0.5 times the clinical equivalent dose, to 47.2, 23.6, and 11.8 g of crude drug / kg, respectively.

[0210] Example 6: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 47.2 crude drug / kg in Example 5.

[0211] Example 7: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 47.2 crude drug / kg in Example 5.

[0212] Example 8: Referring to the experimental results of Example 5, the dosage setting was consistent with the high dose of 47.2 crude drug / kg in Example 5.

[0213] Ibuprofen suspension: The clinical daily dose of ibuprofen suspension for children aged 7 to 9 years is 0.64g. Based on the average weight of 26.4kg for eight-year-old children, the clinical equivalent dose for rats is 0.11g / kg, estimated by the Meeh-Rubner formula based on body surface area.

[0214] Pediatric Chiqiao Qingre Granules: The clinical daily dosage of Pediatric Chiqiao Qingre Granules for children aged 7 to 9 years is 15g. Based on the average weight of 26.4kg for eight-year-old children, the clinical equivalent dose for rats is 2.60g / kg estimated by the Meeh-Rubner formula based on body surface area.

[0215] The drug was administered orally in a manner similar to that used in clinical practice. Each dose group was given the drug by gavage, with a volume of 10 mL / kg per gavage. The normal control group and the model control group were given an equal volume of ultrapure water by gavage, once after the experimental grouping and 5 hours after the first dose.

[0216] 3.4 Detection indicators

[0217] Research indicators: Measure the basal rectal temperature (before modeling), before administration, and 1 to 11 hours after the first administration of rats. Measure once every hour and calculate the rectal temperature difference at each time point (rectal temperature difference = rectal temperature at each time point after administration - basal rectal temperature).

[0218] 3.5 Data Processing

[0219] The measurement data were expressed as mean ± standard deviation (mean ± SD) and statistically analyzed using SPSS 25.0 software. One-way analysis of variance was performed when the variances were equal. When there were significant differences in the one-way analysis of variance, the LSD test was used for pairwise comparisons. When there were unequal variances, the Kruskal-Wallis nonparametric test was performed, and when there were significant differences, pairwise comparisons were performed.

[0220] The test level was α=0.05, and P<0.05 indicated that the difference was statistically significant.

[0221] 4. Handling unexpected situations

[0222] During the experiment, the rectal temperature of the rats in the model control group showed a downward trend over time. To prevent the observation period from being shortened after the second drug administration, the second drug administration time was adjusted to 5 hours after the first administration. The original plan was to have a 6-hour interval between the two administrations.

[0223] 5. Test results

[0224] 5.1 Experimental results of the powder of Example 5 on the fever model of rats induced by dry yeast solution

[0225] The test results showed that 6 hours after the rats were subcutaneously injected with 20% yeast suspension, the rectal temperature of the rats in each dosage group was significantly increased compared with the normal group (P < 0.01), indicating that the model was successfully established. Compared with the model control group, Example 5 (23.6g, 47.2g crude drug / kg) can significantly reduce the rectal temperature of rats 3h after the first administration (P < 0.05, P < 0.01); Example 5 (11.8g crude drug / kg) can significantly reduce the rectal temperature of rats 7h to 9h after the first administration (P < 0.05); Ibuprofen suspension 0.11g / kg has a very significant effect of reducing the rectal temperature of rats 1h to 11h after the first administration (P < 0.01); Children's Chiqiao Qingre Granules 2.6g / kg can significantly reduce the rectal temperature of rats 5h after the first administration (P < 0.05, P < 0.01); Compared with Children's Chiqiao Qingre Granules, the rectal temperature of rats in Example 5 was significantly reduced at 6h to 10h (P < 0.05, P < 0.01). The test results are shown in Table 12, Table 13, Figure 2 .

[0226] Table 12 Effect of the powder of Example 5 on yeast-induced fever in young rats (Mean±SD, n)

[0227]

[0228] Note: Compared with the normal control group, ##P<0.01; compared with the model control group, *P<0.05; **P<0.01; compared with the Xiaoer Chiqiao Qingre Granule group, △P<0.05; △△P<0.05; n: number of animals

[0229] Table 13 Effect of the powder of Example 5 on yeast-induced fever in young rats (Mean±SD, n)

[0230]

[0231]

[0232] Note: Compared with the normal control group, ##P<0.01; compared with the model control group, *P<0.05; **P<0.01; compared with the Xiaoer Chiqiao Qingre Granule group, △P<0.05; △△P<0.05; n: number of animals

[0233] 5.2 Experimental results of the powders of Examples 5, 6, 7, and 8 on fever induced by dry yeast solution in rats

[0234] The test results showed that 6 hours after the rats were subcutaneously injected with 20% yeast suspension, the rectal temperature of the rats in each dosage group was significantly increased compared with the normal group (P < 0.01), indicating that the model was successfully established. Compared with the model control group, the powders of Example 5, Example 6, Example 7, and Example 8 were able to significantly reduce the rectal temperature of the rats 4 hours to 11 hours after the first administration (P < 0.05, P < 0.01); 0.11 g / kg of ibuprofen suspension had a very significant effect of reducing the rectal temperature of the rats 1 hour to 11 hours after the first administration (P < 0.01); there was no significant difference in the antipyretic effect between the powders of Example 5, Example 6, Example 7, and Example 8 (P > 0.05). The test results are detailed in Tables 14, 15, Figure 3 .

[0235] Table 14 Effects of the powders of Examples 5, 6, 7, and 8 on yeast-induced fever in young rats (Mean ± SD, n)

[0236]

[0237] Note: Compared with the normal control group, ##P<0.01; compared with the model control group, *P<0.05; **P<0.01;

[0238] Table 15 Effects of the powders of Examples 5, 6, 7, and 8 on yeast-induced fever in young rats (Mean ± SD, n)

[0239]

[0240] Note: Compared with the normal control group, ##P<0.01; compared with the model control group, *P<0.05; **P<0.01;

[0241] 6. Experimental Conclusion

[0242] The study showed that the powder of Example 5 (11.8, 23.6, 47.2 g crude drug / kg) had a significant antipyretic effect on yeast-induced fever in young rats. The powder of Example 5 had a faster onset of antipyretic effect and a better antipyretic effect than the Children's Chiqiao Qingre Granules. The powders of Example 5, Example 6, Example 7, and Example 8 all had a significant cooling effect on yeast-induced fever in young rats, and there was no significant difference between the different powders.

[0243] Experimental Example 4: Pharmacological Effect of the Drug of the Present Invention on Expectorant in Young Mice

[0244] 1. Experimental Design

[0245] This study observed the pharmacological effects of powders of different embodiments on the tracheal phenol red secretion model of young mice.

[0246] 2. Test Materials

[0247] 2.1 Test sample

[0248] 2.1.1 Basic Information

[0249] The powders prepared in Example 5, Example 6, Example 7, and Example 8 were used as test drugs.

[0250] 2.1.2 Preparation method

[0251] Formal test: Weigh an appropriate amount of the powder prepared in Example 5, grind it evenly, add a small amount of ultrapure water and continue grinding, and finally dilute to the required concentration with ultrapure water.

[0252] Example 6: Weigh an appropriate amount of the powder prepared in Example 6, grind it evenly, add a small amount of ultrapure water and continue grinding, and finally dilute to the required concentration with ultrapure water.

[0253] Example 7: Weigh an appropriate amount of the powder prepared in Example 7, grind it evenly, add a small amount of ultrapure water and continue grinding, and finally dilute to the required concentration with ultrapure water.

[0254] Example 8: Weigh an appropriate amount of the powder prepared in Example 8, grind it evenly, add a small amount of ultrapure water and continue grinding, and finally dilute to the required concentration with ultrapure water.

[0255] Use an electronic balance with an accuracy of 0.001g to weigh, prepare in a normal environment, and prepare before use.

[0256] 2.2 Reference substance 1

[0257] 2.2.1 Basic Information

[0258] Ambroxol oral solution, main ingredient: Ambroxol; Appearance: Colorless to slightly yellow clear liquid; Dosage: Daily dose: 15 mL (45 mg), orally, 2-3 times a day; Specification: 5 mL: 15 mg; Storage: Protect from light, sealed; Batch number: 202408; Expiration date: 202401; Manufacturer: Harbin Renhuang Pharmaceutical Co., Ltd.; Provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0259] 2.2.2 Preparation method

[0260] The dosage of ambroxol oral solution is 5mL:15mg, or 3mg / mL. Take an appropriate volume of ambroxol oral solution and add ultrapure water to the desired concentration. Prepare under normal conditions and prepare immediately before use.

[0261] 2.3 Reference substance 2

[0262] 2.3.1 Basic Information

[0263] Xiaoer Chiqiao Qingre Granules, main ingredients: Forsythia suspensa, light fermented black beans, mint, and Schizonepeta tenuifolia; Appearance: Light yellow to brown granules; Usage and Dosage: Daily dose: 15g, taken with boiled water, three times a day; Specification: 2g / bag; Storage: Protect from light; Batch Number: 2207124; Expiration Date: 202408; Manufacturer: Jichuan Pharmaceutical Group Co., Ltd.; Provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0264] 2.3.2 Preparation method

[0265] Weigh an appropriate amount of Xiaoer Chiqiao Qingre Granule powder and grind it evenly. Then add a small amount of ultrapure water and continue grinding. Finally, dilute to the desired concentration with 0.5% CMC-Na suspension. Use an electronic balance with an accuracy of 0.001g. Prepare in a normal environment and prepare immediately before use.

[0266] 2.4 Main Reagents

[0267] Phenol red, properties: red powder, storage conditions: dry and sealed, room temperature specifications: 25g / bottle, batch number: 20180314, validity period: long-term, production unit: Tianjin Chemical Reagent Supply and Marketing Company, provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0268] Physiological saline, properties: colorless liquid, storage conditions: sealed, specifications: 250mL: 2.25g, batch number: 2208113404, expiration date: 20240810, manufacturer: Shijiazhuang Siyao Co., Ltd., provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0269] Sodium bicarbonate (NaHCO3), properties: white powder, storage conditions: room temperature, dry, sealed; specifications: 500g / bottle, batch number: 20200812, validity period: long-term, manufacturer: Tianjin Bohai Chemical Reagent Co., Ltd., provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0270] 2.5 Main instruments

[0271] BT125D electronic balance: Sartorius Scientific Instruments (Beijing) Co., Ltd.

[0272] PL203 electronic balance: Mettler-Toledo Instruments (Shanghai) Co., Ltd.

[0273] DNA103A electronic balance: Nanjing Bonita Scientific Instrument Co., Ltd.

[0274] ECC2201 electronic balance: Nanjing Bonita Scientific Instrument Co., Ltd.

[0275] RT-6100 microplate reader: Shenzhen Raydu Life Sciences Co., Ltd.

[0276] 2.6 Experimental Animals

[0277] 2.6.1 Basic Information

[0278] Formal experiment: Species: ICR mice, Grade: SPF grade, Weight / Age: 18-20 g / 3-4 weeks, Gender: half male and half female, Quantity: 160 mice, Quality Certificate Number: 110011231101215917, 110011231101215828, Supplier: Beijing Weitonglihua Laboratory Animal Technology Co., Ltd., License Number: SCXK (Beijing) 2021-0006.

[0279] 2.6.2 Animal facilities

[0280] Same as Experimental Example 3.

[0281] 2.6.3 Animal feed

[0282] Feed name: SPF mouse maintenance feed, sterilization method: 60 Co irradiation, supplier: Keao Xieli (Tianjin) Feed Co., Ltd., animal feed production license: Tianjin Feed Certificate (2020) 01005, issuing unit: Tianjin Municipal Agriculture and Rural Affairs Commission, Beijing Municipal Agriculture Bureau.

[0283] Feed testing: Each batch of feed has a quality certificate and a self-inspection report provided by the feed supplier. The feed supplier provides a recent third-party feed testing report every year.

[0284] Feed test results: All test indicators meet the requirements.

[0285] 2.6.4 Animal drinking water

[0286] Same as Experimental Example 3.

[0287] 2.6.5 Animal bedding

[0288] Litter name: SPF corn cob litter, sterilization method: 60 Co irradiation, supplier: Dachang Hui Autonomous Region Chenfu Eden Garden litter processing plant.

[0289] Litter testing: Each batch of feed should have a quality certificate, and the feed supplier should provide at least one third-party feed testing report every year.

[0290] Litter test results: All test indicators meet the requirements.

[0291] 2.6.6 Animal breeding conditions

[0292] Mice were housed in polypropylene cages (length × width × height = 33 cm × 21 cm × 17 cm). Males and females were housed separately, with a maximum of five animals per cage.

[0293] Temperature: Set the temperature range to 20-26°C, Humidity: Set the humidity range to 40%-70%, Ventilation rate: no less than 15 times of fresh air / hour, Light: 12 hours of light and 12 hours of dark alternating.

[0294] Feeding conditions test results: No abnormal conditions that affected the test results occurred during the test.

[0295] 2.6.7 Animal husbandry and management

[0296] Same as Experimental Example 3.

[0297] 2.6.8 Animal Receipt and Inspection

[0298] Same as Experimental Example 3.

[0299] 2.6.9 Animal Identification

[0300] Same as Experimental Example 3.

[0301] 2.6.10 Animal Welfare

[0302] Same as Experimental Example 3.

[0303] 3. Test methods

[0304] 3.1 Experimental study on the efficacy of the powder of Example 5 in expectorating young mice

[0305] 3.1.1 Model making

[0306] Mice were fasted overnight. 30 minutes after the last dose, all animals in each group were intraperitoneally injected with 1% phenol red in saline at a volume of 20 mL / kg body weight. The animals were then killed by cervical dislocation 30 minutes after the injection. After blood coagulation in the mice, the neck skin was cut open to ensure no significant bleeding (to prevent phenol red in the blood from mixing with the lavage fluid). The trachea was isolated, and the trachea was cannulated and connected to a syringe. 5% NaHCO3 solution (0.8 mL) was slowly injected into the trachea and then gently aspirated. This process was repeated three times. The three lavage fluids were combined and allowed to stand for a period of time to allow impurities to settle. A transparent red supernatant was obtained. The absorbance was measured at a wavelength of 550 nm using a microplate reader, and the phenol red content was calculated based on the phenol red standard curve.

[0307] To prepare a phenol red standard curve: Weigh 1.95 mg of phenol red and dissolve it in 3.9 mL of 5% NaHCO₃ solution. Mix thoroughly to create a stock solution containing 0.5 mg / mL of phenol red. Add 0.1 mL of the stock solution to 3.9 mL of 5% NaHCO₃ solution to obtain a 12.5 μg / mL concentration. Dilute the solution sequentially to 10 μg / mL, 7.5 μg / mL, 5 μg / mL, 2.5 μg / mL, 1.25 μg / mL, and finally 0.625 μg / mL to prepare the desired standard solution.

[0308] 200 μL of the above standards were added to a 96-well plate (with duplicate wells) in order of concentration from low to high, and the absorbance was detected at a wavelength of 550 nm using a microplate reader to fit the phenol red standard curve.

[0309] 3.1.2 Trial Grouping

[0310] Mice were selected after the adaptation period and randomly divided into groups according to their body weight. See Tables 16 and 17 for details.

[0311] Table 16 Experimental grouping and administration method of Example 5

[0312]

[0313] Table 17 Experimental groups and administration methods for Example 5, Example 6, Example 7, and Example 8

[0314]

[0315] All groups were given drugs by gavage, with a volume of 20 mL / kg each time. The model control group was given an equal volume of ultrapure water by gavage. The drugs were given on the day of grouping and twice a day for 5 consecutive days.

[0316] 3.1.3 Dosage setting and administration

[0317] Example 5: Clinically applicable children are mostly aged 3 to 12 years. The daily dose is 137 g of crude drug. Based on the average weight of 8-year-old children (26.4 kg), the clinical equivalent dose in mice, calculated using the Meeh-Rubner formula based on body surface area, is 48.8 g of crude drug / kg. Therefore, the doses in Example 5 were set at 2, 1, and 0.5 times the clinical equivalent dose, to 97.6, 48.8, and 24.4 g of crude drug / kg, respectively.

[0318] Ambroxol oral solution: The clinical daily dose of ambroxol oral solution for children aged 6 to 12 years is 45 mg. Based on the average weight of 8-year-old children of 26.4 kg, the clinical equivalent dose for mice is estimated to be 16.0 mg / kg using the Meeh-Rubner formula based on body surface area. Therefore, the dose of ambroxol oral solution in this study was set at 16.0 mg / kg.

[0319] Pediatric Chiqiao Qingre Granules: The clinical daily dosage of Pediatric Chiqiao Qingre Granules for children aged 7 to 9 years is 15g. Based on the average weight of 8-year-old children of 26.4kg, the clinical equivalent dose of mice calculated using the Meeh-Rubner formula based on body surface area is 5.4g / kg. Therefore, the dosage of Pediatric Chiqiao Qingre Granules in this study was set at 5.4g / kg.

[0320] Example 6: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 97.6 crude drug / kg in Example 5.

[0321] Example 7: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 97.6 crude drug / kg in Example 5.

[0322] Example 8: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 97.6 crude drug / kg in Example 5.

[0323] The administration method was consistent with the intended clinical route. All groups were given the drug by gavage, with a volume of 20 mL / kg each time. The model control group was given an equal volume of ultrapure water by gavage. The drug was administered on the day of grouping and twice a day for 5 consecutive days.

[0324] 3.2 Detection indicators

[0325] Phenol red content in tracheal lavage fluid: Combine the tracheal lavage fluid from three times and allow it to settle for a certain period of time to allow impurities to precipitate. Take the transparent red supernatant and use a microplate reader to detect the absorbance at a wavelength of 550 nm to calculate the phenol red content.

[0326] 3.3 Data processing

[0327] The measurement data were expressed as mean ± standard deviation (mean ± SD) and statistically analyzed using SPSS 25.0 software. One-way analysis of variance was performed when the variances were equal. When there were significant differences in the one-way analysis of variance, the LSD test was used for pairwise comparisons. When there were unequal variances, the Kruskal-Wallis nonparametric test was performed, and when there were significant differences, pairwise comparisons were performed.

[0328] The test level was α=0.05, and P≤0.05 indicated that the difference was statistically significant.

[0329] 4. Handling unexpected situations

[0330] No unexpected situations occurred during the experiment.

[0331] 5. Test results

[0332] 5.1 Experimental study on the efficacy of the powder of Example 5 in expectorating young mice

[0333] The test results showed that after 5 days of administration, compared with the model control group, the phenol red content in the tracheal lavage fluid of mice in the powder preparation of Example 5 (96.7g crude drug / kg, 48.8g crude drug / kg) group was significantly increased (P < 0.01, P < 0.05), the phenol red content in the tracheal lavage fluid of mice in the ambroxol oral solution 16mg / kg group was also significantly increased (P < 0.01), and there was an increasing trend in the pediatric Chiqiao Qingre Granule, with no significant difference (P > 0.05); compared with the pediatric Chiqiao Qingre Granule group, the phenol red content in the tracheal lavage fluid of mice in the powder preparation of Example 5 (96.7g crude drug / kg, 48.8g crude drug / kg) group was significantly increased (P < 0.05). The test results are shown in Table 18 below.

[0334] Table 18 Effect of Example 5 on phenol red content in tracheal lavage fluid of young mice (Mean ± SD, n)

[0335]

[0336] Note: Compared with the model group, *P<0.05, **P<0.01; compared with Xiaoer Chiqiao Qingre Granules, # P<0.05, ## P<0.01.

[0337] 5.2 Experimental study on the expectorant efficacy of the powders of Examples 5, 6, 7 and 8 in young mice

[0338] The test results showed that after 5 days of administration, the powders of Examples 5, 6, 7, and 8 all significantly increased the phenol red content in the tracheal lavage fluid of mice compared with the model control group (P < 0.01). The phenol red content in the tracheal lavage fluid of mice in the 16 mg / kg ambroxol oral solution group was also significantly increased (P < 0.01). There was no significant difference between the powders of Examples 5, 6, 7, and 8 groups (P > 0.05). The test results are shown in Table 19 below.

[0339] Table 19 Effects of Examples 5, 6, 7, and 8 on the phenol red content in tracheal lavage fluid of young mice (Mean ± SD, n)

[0340]

[0341] Note: Compared with the model group, *P<0.05, **P<0.01;

[0342] 6. Experimental Conclusion

[0343] The powder of Example 5 (48.8, 97.6 g / crude drug / kg) had a significant expectorant effect when administered continuously for 5 days, and the expectorant effect was better than that of Xiaoer Chiqiao Qingre Granules; the powders of Examples 5, 6, 7, and 8 all had a significant expectorant effect when administered continuously for 5 days, and there was no significant difference in expectorant effect among the groups.

[0344] Experimental Example 5: Anti-inflammatory effect of the drug of the present invention on xylene-induced ear swelling in young mice

[0345] 1. Experimental Design

[0346] This study observed the anti-inflammatory effects of the powders of Examples 5, 6, 7, and 8 on xylene-induced ear swelling in young mice, evaluated their effects, and provided a reference for clinical practice.

[0347] 2. Test Materials

[0348] 2.1 Test sample

[0349] 2.1.1 Basic Information

[0350] The powders prepared in Example 5, Example 6, Example 7, and Example 8 were used as test drugs.

[0351] 2.1.2 Preparation method

[0352] An appropriate amount of the powder prepared in Example 5 was weighed, ground uniformly, and then a small amount of ultrapure water was added to continue grinding. Finally, the volume was adjusted to the desired concentration with ultrapure water.

[0353] Weigh an appropriate amount of the powder prepared in Example 6, grind it evenly, add a small amount of ultrapure water and continue grinding, and finally dilute to the required concentration with ultrapure water.

[0354] An appropriate amount of the powder prepared in Example 7 was weighed, and after first grinding it uniformly, a small amount of ultrapure water was added and continued to grind, and finally the volume was adjusted to the required concentration with ultrapure water.

[0355] Weigh an appropriate amount of the powder prepared in Example 8, grind it evenly, add a small amount of ultrapure water and continue grinding, and finally dilute to the required concentration with ultrapure water.

[0356] Use an electronic balance with an accuracy of 0.001g to weigh, prepare in a normal environment, and prepare before use.

[0357] 2.2 Reference substance 1

[0358] 2.2.1 Basic Information

[0359] Ibuprofen suspension, main ingredient: ibuprofen; properties: orange suspension; dosage: daily dose 32 mL (0.64 g), oral, four times a day; specifications: 100 mL: 2 g; storage conditions: protected from light, sealed; expiration date: 202411; manufacturer: Shanghai Johnson & Johnson Pharmaceutical Co., Ltd.; provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0360] 2.2.2 Preparation method

[0361] The specification for pediatric ibuprofen suspension is 2g per 100mL, or 20mg / mL. Take an appropriate volume of pediatric ibuprofen suspension and add ultrapure water to the desired concentration. Prepare under normal conditions and prepare immediately before use.

[0362] 2.3 Reference substance 2

[0363] 2.3.1 Basic Information

[0364] Xiaoer Chiqiao Qingre Granules, main ingredients: Forsythia suspensa, light fermented black beans, mint, Schizonepeta tenuifolia, etc.; Appearance: Light yellow granules; Usage and Dosage: Daily dose: 15g, taken with boiled water, three times a day; Specification: 2g / bag; Storage: Protect from light; Batch number: 2207124; Expiration date: 202408; Manufacturer: Jichuan Pharmaceutical Group Co., Ltd.; Provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0365] 2.3.2 Preparation method

[0366] Weigh an appropriate amount of Xiaoer Chiqiao Qingre Granule powder and grind it evenly. Add a small amount of ultrapure water and continue grinding. Finally, dilute to the desired concentration with ultrapure water. Use an electronic balance with an accuracy of 0.001g. Prepare in a normal environment and prepare immediately before use.

[0367] 2.4 Main Reagents

[0368] Xylene, properties: colorless liquid, storage conditions: cool, sealed, ventilated, room temperature specifications: 500mL / bottle, batch number: 20211208, validity period: long-term, manufacturer: Tianjin Bohai Chemical Reagent Co., Ltd., provider: Tianjin Tiancheng New Drug Evaluation Co., Ltd.

[0369] 2.5 Main instruments

[0370] BT125D electronic balance: Sartorius Scientific Instruments (Beijing) Co., Ltd.

[0371] PL203 electronic balance: Mettler-Toledo Instruments (Shanghai) Co., Ltd.

[0372] DNA103A electronic balance: Nanjing Bonita Scientific Instrument Co., Ltd.

[0373] ECC2201 electronic balance: Nanjing Bonita Scientific Instrument Co., Ltd.

[0374] BSA224S-CW electronic balance: Sartorius Scientific Instruments (Beijing) Co., Ltd.

[0375] 2.6 Experimental Animals

[0376] Same as Experimental Example 4.

[0377] 3. Test methods

[0378] 3.1 Model making

[0379] The mice were fasted but not watered overnight before the last administration. One hour after the last administration, 40uL of xylene was evenly applied on the inside and outside of the right ears of the mice in all groups except the normal control group to induce inflammation.

[0380] 3.2 Trial Grouping

[0381] Mice were randomly divided into groups according to their body weight after the adaptation period. See Tables 20 and 21 for details.

[0382] Table 20 Experimental grouping and administration method of Example 5

[0383]

[0384] Note: n: number of animals

[0385] Table 21 Experimental groups and administration methods for Example 5, Example 6, Example 7, and Example 8

[0386]

[0387] Note: n: number of animals

[0388] 3.3 Dosage setting and administration

[0389] Example 5: Clinically applicable children are mostly aged 3 to 12 years. The daily dose is 137 g of crude drug. Based on the average weight of 8-year-old children (26.4 kg), the clinical equivalent dose in mice, calculated using the Meeh-Rubner formula based on body surface area, is 48.8 g of crude drug / kg. Therefore, the doses in Example 5 were set at 2, 1, and 0.5 times the clinical equivalent dose, to 97.6, 48.8, and 24.4 g of crude drug / kg, respectively.

[0390] Example 6: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 97.6 crude drug / kg in Example 5.

[0391] Example 7: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 97.6 crude drug / kg in Example 5.

[0392] Example 8: Referring to the experimental results of Example 5, the dosage setting is consistent with the high dose of 97.6 crude drug / kg in Example 5.

[0393] Pediatric Ibuprofen Suspension: The clinical daily dose of pediatric ibuprofen suspension for children aged 7 to 9 years is 0.64g. Based on the average weight of 26.4kg for eight-year-old children, the clinical equivalent dose in mice is calculated to be 0.2g / kg using the Meeh-Rubner formula based on body surface area.

[0394] Pediatric Chiqiao Qingre Granules: The clinical daily dosage of Pediatric Chiqiao Qingre Granules for children aged 7 to 9 years is 15g. Based on the average weight of 8-year-old children of 26.4kg, the clinical equivalent dose of mice calculated using the Meeh-Rubner formula based on body surface area is 5.4g / kg. Therefore, the dosage of Pediatric Chiqiao Qingre Granules in this study was set at 5.4g / kg.

[0395] The administration method was consistent with the intended clinical route. All groups were given the drug by gavage, with a volume of 20 mL / kg each time. The normal control group and the model control group were given an equal volume of ultrapure water by gavage. The drugs were administered on the day of grouping and twice a day for 5 consecutive days.

[0396] 3.4 Detection indicators

[0397] Ear swelling degree (ear piece weight): On the day of the last administration, 1 hour after the mice were administered, 40uL of xylene was evenly applied to the inside and outside of the right ears of the mice in all groups except the normal control group to induce inflammation. After 30 minutes, the mice were killed by dislocation of the neck, and the left and right ears were cut off. The ear pieces at the same location were punched out with an 8mm diameter punch and weighed. The data were recorded, and the difference in weight between the two ears was used as the degree of ear swelling.

[0398] Ear swelling degree (ear piece weight) = right ear piece weight - left ear piece weight.

[0399] 3.5 Data Processing

[0400] The measurement data were expressed as mean ± standard deviation (mean ± SD) and statistically analyzed using SPSS 25.0 software. One-way analysis of variance was performed when the variances were equal. When there were significant differences in the one-way analysis of variance, the LSD test was used for pairwise comparisons. When there were unequal variances, the Kruskal-Wallis nonparametric test was performed, and when there were significant differences, pairwise comparisons were performed.

[0401] The test level was α=0.05, and P≤0.05 indicated that the difference was statistically significant.

[0402] 4. Handling unexpected situations

[0403] No unexpected situations occurred during the experiment.

[0404] 5. Test results

[0405] 5.1 Anti-inflammatory effect test of the powder of Example 5 on xylene-induced ear swelling in young mice

[0406] The test results showed that after 5 days of administration, compared with the normal control group, the ear swelling of the mice in the model control group was significantly increased (P≤0.01). Compared with the model control group, the ear swelling of the mice in the Example 5 (24.4, 48.8, 96.7g crude drug / kg) group was significantly reduced (P≤0.05), the ear swelling of the mice in the ibuprofen suspension 0.2g / kg group was significantly reduced (P≤0.01), and the ear swelling of the mice in the pediatric Chiqiao Qingre Granule 5.4g / kg group was significantly reduced (P≤0.05); compared with the pediatric Chiqiao Qingre Granule, the ear swelling of the mice in the Example 5 (48.8, 96.7g crude drug / kg) group was significantly reduced (P≤0.05). The test results are shown in Table 22.

[0407] Table 22 Effect of xylene on ear swelling in young mice (Mean ± SD, n) Example 5

[0408]

[0409] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, * P < 0.05; ** P<0.01; compared with the Xiaoer Chiqiao Qingre Granule group △ P < 0.05; △△ P<0.05; n: number of animals

[0410] 5.2 Anti-inflammatory effect test of the powders of Examples 5, 6, 7 and 8 on xylene-induced ear swelling in young mice

[0411] The test results showed that after 5 days of administration, the ear swelling of mice in the model control group was significantly increased compared with the normal control group (P < 0.01). Compared with the model control group, the powders of Examples 5, 6, 7, and 8 all significantly reduced the ear swelling of mice (P < 0.01). The ear swelling of mice in the ibuprofen suspension 0.2 g / kg group was significantly reduced (P ≤ 0.01). There was no significant difference between the powders of Examples 5, 6, 7, and 8 groups (P > 0.05). The test results are detailed in Table 23.

[0412] Table 23 Effects of Example 5, Example 6, Example 7, and Example 8 on ear swelling in young mice induced by xylene (Mean ± SD, n)

[0413]

[0414] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, * P < 0.05; ** P < 0.01;

[0415] 6. Experimental Conclusion

[0416] The powder of Example 5 (24.4, 48.8, 97.6 g / crude drug / kg) administered continuously for 5 days had a significant anti-inflammatory effect on xylene-induced acute exudative inflammation; compared with the Children's Chiqiao Qingre Granules, the powder of Example 5 (48.8, 97.6 g / crude drug / kg) group significantly reduced the degree of ear swelling in mice, and had a better anti-inflammatory effect; the powders of Examples 5, 6, 7, and 8 were all able to significantly reduce the degree of ear swelling in mice, and there was no significant difference among the powder groups.

[0417] Experimental Example 6

[0418] This experimental example provides antipyretic test of the powders prepared in Example 5 and Comparative Example 1 of the present invention. The test method is as follows:

[0419] Sixty mice that passed quarantine, half male and half female, weighing 20 ± 2 g, had undergone adaptive temperature measurement (basal body temperature maintained between 35.5 and 38 ° C) for the first three days and were randomly divided into five groups of 12 mice each, labeled as blank group, model group, positive drug (Qingkailing composition) control group, Example 5 group, and Comparative Example 1 group, weighed separately, and numbered with picric acid. Fasted for 16 hours before the experiment and had free access to water. Basal body temperature was measured before modeling. The model group, Example 5 group, positive drug control group, and Comparative Example 1 group were lightly anesthetized with anhydrous ether and injected subcutaneously with 15% dry yeast suspension at a dose of 0.5 ml / 100 g on the back to establish a rat fever model.

[0420] The powder prepared in Example 5 was ground and dissolved in water to prepare a drug solution with a concentration of 2.400 g crude drug / mL. The powder prepared in Comparative Example 1 was ground and dissolved in water to prepare a drug solution with a concentration of 2.877 g crude drug / ml. Qingkailing granules were ground and dissolved in water to prepare a Qingkailing granule solution with a mass concentration of 0.16 g / ml.

[0421] Five hours after modeling, the Example 5 group was gavaged with the drug solution of Example 5 at a dose of 47.20 g crude drug / kg. The Comparative Example 1 group was gavaged with the drug solution of Comparative Example 1 at a dose of 57.54 g crude drug / kg, and the positive control group was gavaged with the Qingkailing granule solution at a dose of 3.2 g / kg, divided into two gavages (the second dose was given 5 hours after the first dose). The blank group and the model group were gavaged with the same volume of water for injection.

[0422] In this experiment, the rectal temperature measured before modeling was used as the basal body temperature. The rectal temperature of each group of rats was measured once at 3h and 5h after modeling, and once at 4h, 5h, 6h, 7h, 8h, 9h, 10h, and 11h after administration, for a total of 10 measurements. The temperature difference ΔT (ΔT = measured body temperature - basal body temperature) of each group of rats at each monitoring time point was calculated, and a time-temperature curve was drawn to investigate the antipyretic effect of Example 5 and Comparative Example 1. The results are shown in Tables 24 and 25. Figure 4 .

[0423] Table 24 Effects of the powders of Example 5 and Comparative Example 1 on yeast-induced fever in young rats (Mean ± SD, n)

[0424]

[0425] Note: Compared with the blank group, △△ P<0.01; compared with the model group, *P<0.05, **P<0.01; compared with comparative example 1, # P<0.05, ## P < 0.05;

[0426] Table 25 Effects of Example 5 and Comparative Example 1 on yeast-induced fever in young rats (Mean±SD, n)

[0427]

[0428] Note: Compared with the blank group, △△ P<0.01; compared with the model group, *P<0.05, **P<0.01; compared with comparative example 1, # P<0.05, ## P < 0.05;

[0429] The experimental results showed that after subcutaneous injection of dry yeast solution, rats experienced trembling, huddling, and lethargy, with some even lying motionless. Compared with the blank group, the body temperature of the model group rats was significantly higher from 3 hours after modeling. After 5 hours, the high temperature persisted and remained essentially constant, indicating that the rat fever model was successfully established. Compared with the model group, the rectal temperature of the rats in the Example 5 group was significantly reduced 3h to 11h after administration (P < 0.05, P < 0.01); the rectal temperature of the rats in the comparative example 1 group was significantly reduced 5h to 10h after administration (P < 0.05, P < 0.01), and the Qingkailing granules 3.2g / kg was significantly reduced 4h to 9h after administration (P < 0.05, P < 0.01); compared with the comparative example 1 group, the rectal temperature of the rats in the Example 5 group was significantly reduced 4h to 9h (P < 0.05, P < 0.01); through comparative experiments, it was confirmed that the powder prepared in Example 5 was faster than the powder prepared in the comparative example 1 and had a better cooling effect.

[0430] Experimental Example 7

[0431] This experimental example provides an expectorant test of the powders prepared in Example 5 and Comparative Example 1 of the present invention. The test method is as follows:

[0432] 48 ICR mice that passed the quarantine, half male and half female, with a weight / week age of 20-24 g / 3-4 weeks, were randomly divided into 4 groups, 12 mice in each group, and marked as model group, positive drug (ambroxol oral solution) control group, Example 5 group, and Comparative Example 1 group, respectively. They were weighed and numbered with picric acid.

[0433] The powder prepared in Example 5 was ground and dissolved in water to obtain a drug solution with a concentration of 2.400g crude drug / mL. The powder prepared in Comparative Example 1 was ground and dissolved in water to obtain a drug solution with a concentration of 2.975g crude drug / mL. The positive control group took an appropriate amount of ambroxol oral solution and added ultrapure water to dilute it to 0.4mg / mL of ambroxol oral solution. The Example 5 group and the Comparative Example 1 group were gavaged and given the drug solutions of Example 5 and Comparative Example 1, respectively, at dosages of 48.80g crude drug / kg and 59.49g crude drug / kg, respectively. The positive control group was gavaged and given the diluted ambroxol oral solution at a dosage of 16mg / kg.

[0434] Each group was administered the drug twice daily for five consecutive days. The model group rats were gavaged with the same volume of ultrapure water. Mice were fasted overnight after the fourth day of dosing. Thirty minutes after the final dose on the fifth day, each group received an intraperitoneal injection of 1% phenol red in saline at a volume of 20 mL / kg body weight. The animals were then sacrificed by dislocation 30 minutes after the injection. After blood coagulation in the mice, the neck skin was cut open to ensure no significant bleeding (to prevent phenol red from mixing into the lavage fluid). The trachea was isolated, and the trachea was cannulated and connected to a syringe. 5% NaHCO₃ solution (0.8 mL) was slowly injected into the trachea, followed by gentle aspiration. This process was repeated three times. The combined lavage fluids from the three washes were allowed to stand for a period of time to allow impurities to settle, yielding a transparent red supernatant. The absorbance was measured at 550 nm using a microplate reader, and the phenol red content was calculated based on a phenol red standard curve.

[0435] To prepare a phenol red standard curve: Weigh 1.95 mg of phenol red and dissolve it in 3.9 mL of 5% NaHCO₃ solution. Mix thoroughly to create a stock solution containing 0.5 mg / mL of phenol red. Add 0.1 mL of the stock solution to 3.9 mL of 5% NaHCO₃ solution to obtain a 12.5 μg / mL concentration. Dilute the solution sequentially to 10 μg / mL, 7.5 μg / mL, 5 μg / mL, 2.5 μg / mL, 1.25 μg / mL, and finally 0.625 μg / mL to prepare the desired standard solution.

[0436] 200 μL of the above standards were added to a 96-well plate (with duplicate wells) in order of concentration from low to high, and the absorbance was detected at a wavelength of 550 nm using a microplate reader to fit the phenol red standard curve.

[0437] Table 26 Effect of the powder of Example 5 on the phenol red content of tracheal lavage fluid in young mice (Mean ± SD, n)

[0438]

[0439] Note: Compared with the model group, *P < 0.01, **P < 0.01; compared with comparative example 1, # P<0.05; n: number of animals

[0440] Compared with the model control group, Example 5, Comparative Example 1, and ambroxol oral solution were all administered continuously for 5 days to significantly increase the tracheal phenol red excretion of mice (P<0.01 or P<0.05); compared with the Comparative Example 1 group, the tracheal phenol red excretion of mice in the Example 5 group was significantly increased (P<0.05), and the expectorant effect of the powder of Example 5 was better than that of Comparative Example 1.

[0441] Obviously, the above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will readily appreciate that other variations or modifications based on the above descriptions are possible. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition, characterized in that The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 100-300 parts of Artemisia annua, 100-300 parts of Scutellaria baicalensis, 100-450 parts of Poria cocos, 100-270 parts of dried tangerine peel, 100-270 parts of Rhizoma Anemarrhenae, 580-820 parts of Gypsum, 200-450 parts of Honeysuckle, 200-450 parts of Folium Isatidis, 100-300 parts of Pinellia ternata, 100-270 parts of Periostracum Cicadae, 100-270 parts of Menthol, 100-270 parts of Licorice and 20-180 parts of Indigo Naturalis.

2. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition is prepared from the following raw materials in parts by weight: 200-300 parts of Artemisia annua, 200-300 parts of Scutellaria baicalensis, 250-450 parts of Poria cocos, 150-270 parts of dried tangerine peel, 150-270 parts of Rhizoma Anemarrhenae, 700-820 parts of Gypsum, 300-450 parts of Honeysuckle, 300-450 parts of Folium Isatidis, 200-300 parts of Pinellia ternata, 150-270 parts of Periostracum Cicadae, 150-270 parts of Menthol, 150-270 parts of Licorice and 50-150 parts of Indigo Naturalis.

3. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition is prepared from the following raw materials in parts by weight: 100-150 parts of Artemisia annua, 100-150 parts of Scutellaria baicalensis, 150-200 parts of Poria cocos, 100-150 parts of dried tangerine peel, 100-150 parts of Rhizoma Anemarrhenae, 580-700 parts of Gypsum, 200-300 parts of Honeysuckle, 200-300 parts of Folium Isatidis, 150-200 parts of Pinellia ternata, 100-150 parts of Periostracum Cicadae, 100-150 parts of Mint, 100-150 parts of Licorice and 40-50 parts of Indigo Naturalis.

4. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition is prepared from the following raw materials in parts by weight: 250 parts of Artemisia annua, 250 parts of Scutellaria baicalensis, 375 parts of Poria cocos, 150 parts of dried tangerine peel, 150 parts of Rhizoma Anemarrhenae, 750 parts of Gypsum, 375 parts of Honeysuckle, 375 parts of Folium Isatidis, 250 parts of Pinellia ternata, 150 parts of Periostracum Cicadae, 150 parts of Menthol, 150 parts of Licorice and 50 parts of Indigo Naturalis; or, The Chinese medicine composition is prepared from the following raw materials: 100 parts of Artemisia annua, 100 parts of Scutellaria baicalensis, 150 parts of Poria cocos, 100 parts of dried tangerine peel, 100 parts of Rhizoma Anemarrhenae, 580 parts of Gypsum, 200 parts of Flos Lonicerae, 200 parts of Folium Isatidis, 150 parts of Rhizoma Pinelliae, 100 parts of Periostracum Cicadae, 100 parts of Menthol, 100 parts of Licorice and 20 parts of Indigo Naturalis; or, The Chinese medicine composition is prepared from the following raw materials: 200 parts of Artemisia annua, 250 parts of Scutellaria baicalensis, 170 parts of Poria cocos, 170 parts of dried tangerine peel, 170 parts of Rhizoma Anemarrhenae, 650 parts of Gypsum, 350 parts of Flos Lonicerae, 250 parts of Folium Isatidis, 200 parts of Rhizoma Pinelliae, 170 parts of Periostracum Cicadae, 170 parts of Menthol, 170 parts of Licorice and 120 parts of Indigo Naturalis; or, The traditional Chinese medicine composition is prepared from the following raw materials: 300 parts of Artemisia annua, 300 parts of Scutellaria baicalensis, 450 parts of Poria cocos, 270 parts of dried tangerine peel, 270 parts of Rhizoma Anemarrhenae, 820 parts of Gypsum, 450 parts of Honeysuckle, 450 parts of Folium Isatidis, 300 parts of Pinellia ternata, 270 parts of Cicada Periostracum, 270 parts of Menthol, 170 parts of Licorice and 180 parts of Indigo Naturalis.

5. A method for preparing the Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The product can be obtained by mixing Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Gypsum, Honeysuckle, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Mentha arvense and Licorice, then extracting according to a conventional extraction method or extracting them separately according to a conventional extraction method and then mixing them, and then mixing in Indigo Naturalis. Alternatively, the product can be obtained by mixing Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Gypsum, Honeysuckle, Folium Isatidis, Pinellia ternata, Periostracum Cicadae, Mentha arvense, Licorice and Indigo Naturalis, then extracting according to a conventional extraction method or extracting them separately according to a conventional extraction method and then mixing them.

6. The method for preparing the Chinese medicine composition according to claim 5, wherein: The conventional extraction method includes one or more of decoction extraction, maceration extraction, percolation extraction, reflux extraction, ultrasonic extraction and steam distillation extraction; the extraction solvent is selected from water or an alcohol solution with a volume percentage of 5-98%; the number of extractions is at least one; the extraction time is at least 10 minutes; and the ratio of the mass of the extraction solvent to the weight of the raw material is ≥2.

7. A pharmaceutical preparation, characterized in that The invention relates to a Chinese medicine composition comprising the Chinese medicine composition according to any one of claims 1 to 4 or the Chinese medicine composition prepared by the preparation method of the Chinese medicine composition according to claim 5 or 6, and optionally one or more pharmaceutically acceptable excipients.

8. The pharmaceutical preparation according to claim 7, characterized in that The pharmaceutical preparation is in the form of micropills, tablets, capsules, powders, mixtures, granules, syrups, gels or decoctions.

9. The pharmaceutical preparation according to claim 7, characterized in that The pharmaceutically acceptable excipient is selected from at least one of pharmaceutically acceptable solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, glidants, flavoring agents, preservatives, suspending agents, coating materials, anti-adhesives, penetration enhancers, pH regulators and thickeners.

10. A method for preparing the pharmaceutical preparation according to any one of claims 7 to 9, characterized in that: The steps include: Decoction step: gypsum is decocted with an extraction solvent, and the decoction liquid and the medicinal residue are collected to obtain A; Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, bamboo shavings, honeysuckle, isatis indigotica, Pinellia ternata, cicada slough, mint, and liquorice are mixed, A is added, and the mixture is soaked with an extraction solvent, decocted and extracted, solid-liquid separation is performed, and the liquid is collected to obtain a medicinal solution; The preparation steps of the pharmaceutical preparation are: concentrating and / or drying the medicinal solution, mixing it with Indigo Naturalis, adding or not adding auxiliary materials, and preparing the pharmaceutical preparation according to conventional process; or, Decoction step: gypsum is decocted with an extraction solvent, and the decoction liquid and the medicinal residue are collected to obtain A; Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, bamboo shavings, honeysuckle, isatis indigotica, Pinellia ternata, cicada slough, mint, liquorice, and indigo naturalis are mixed, A is added, and the mixture is soaked with an extraction solvent, decocted and extracted, solid-liquid separation is performed, and the liquid is collected to obtain a medicinal solution; The preparation steps of the pharmaceutical preparation are as follows: the pharmaceutical solution is concentrated and / or dried, excipients are added or not added, and the pharmaceutical preparation is prepared according to conventional processes.

11. The method for preparing the pharmaceutical preparation according to claim 10, characterized in that: The decoction step comprises: taking gypsum, adding water 3-6 times the weight of the gypsum or a 5-98% alcohol solution, and decocting for 30-90 minutes, collecting the decoction and the residue to obtain A; taking Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, bamboo shavings, honeysuckle, isatis indigotica, Pinellia ternata, cicada shell, mint, and liquorice, mixing, adding A, adding water to 5-12 times the weight of the medicinal materials in water or a 5-98% alcohol solution, soaking for 30-120 minutes, decoct and extract 1-4 times, the material-liquid mass ratio of each extraction being 1:6-15, the extraction time being 60-120 minutes, separating the solid and liquid, collecting the liquid, and obtaining the medicinal solution.

12. The method for preparing the pharmaceutical preparation according to claim 11, characterized in that: The preparation method of the pharmaceutical preparation comprises the following steps: adding 6 times the amount of water to gypsum, decocting for 30 minutes, collecting the decoction and the residue to obtain A; mixing Artemisia annua, Scutellaria baicalensis, Poria cocos, dried tangerine peel, Rhizoma Anemarrhenae, Flos Lonicerae, Folium Isatidis, Rhizoma Pinelliae, Periostracum Cicadae, Mentha, and Glycyrrhizae, adding A, replenishing water to 11.5 times the weight of the medicinal materials in the prescription except Indigo Naturalis, soaking for 2 hours, decocting for 1.5 hours, filtering the decoction, and collecting the filtrate; adding 10 times the amount of water to the residue, decocting for 1.5 hours, filtering, combining the filtrate, and concentrating under reduced pressure to obtain an extract, wherein the relative density of the extract measured at 60° C. is 1.05-1.12, spray drying into fine powder, adding the prescribed amount of Indigo Naturalis and at least one auxiliary material selected from a sweetener, an acidulant, and a filler, mixing, and dry granulating to prepare granules.

13. Use of the Chinese medicine composition according to any one of claims 1 to 4, the Chinese medicine composition prepared by the method for preparing the Chinese medicine composition according to claim 5 or 6, the pharmaceutical preparation according to any one of claims 7 to 9, or the pharmaceutical preparation prepared by the method for preparing the pharmaceutical preparation according to any one of claims 10 to 12 in the preparation of a medicament having at least one of the effects of relieving fever and removing phlegm.

14. Use of the Chinese medicine composition according to any one of claims 1 to 4, the Chinese medicine composition prepared by the method for preparing the Chinese medicine composition according to claim 5 or 6, the pharmaceutical preparation according to any one of claims 7 to 9, or the pharmaceutical preparation prepared by the method for preparing the pharmaceutical preparation according to any one of claims 10 to 12 in the preparation of a drug having an anti-inflammatory effect.

15. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4, the traditional Chinese medicine composition prepared by the method for preparing the traditional Chinese medicine composition according to claim 5 or 6, the pharmaceutical preparation according to any one of claims 7 to 9, or the pharmaceutical preparation prepared by the method for preparing the pharmaceutical preparation according to any one of claims 10 to 12 in the preparation of a medicament for preventing or treating colds.

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