Pharmaceutical composition with effects of clearing away heat and toxic materials as well as preparation method and application of pharmaceutical composition

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a pharmaceutical composition with heat-clearing and detoxifying effects and a preparation method and application thereof, and the pharmaceutical composition with the heat-clearing and detoxifying effects comprises fermented traditional Chinese medicine components and decocted traditional Chinese medicine components. The preparation method of the pharmaceutical composition comprises the following steps: adding the fermented traditional Chinese medicine component into the decocted traditional Chinese medicine component, uniformly stirring, adding the excipient to prepare a soft material, and forming and drying to obtain the pharmaceutical composition with the efficacy of clearing away heat and toxic materials. The prepared pharmaceutical composition with the heat clearing and detoxifying effects combines fermentation and ultrasonic-decoction synergistic extraction, fermentation can decompose traditional Chinese medicine macromolecules to improve dissolution of effective components, ultrasonic can strengthen extraction efficiency, component retention and extraction effects are considered, and the heat clearing and detoxifying effects are excellent.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a medicine composition with the effects of clearing heat and resolving toxins and immune regulation, and a preparation process and clinical application thereof, which can be widely applied to the treatment of infectious diseases and disease prevention and control scenarios. BACKGROUND

[0002] The heat-clearing and toxin-resolving traditional Chinese medicine composition is the core means for preventing and treating heat-toxin syndrome in traditional Chinese medicine, and is widely used in the fields of human infectious diseases and livestock and poultry epidemic disease prevention and control. Symptoms such as fever, sore throat, carbuncle and sore, caused by the accumulation of heat and toxin, are more difficult to treat due to drug resistance in modern environment. Western medicine antibiotics and chemicals have significant side effects and are prone to drug resistance, making traditional Chinese medicine compositions a research hotspot.

[0003] In the prior art, heat-clearing and toxin-resolving traditional Chinese medicine compositions have formed a multi-element development pattern: such as a compound preparation taking Houttuynia cordata as the main medicine, combined with mulberry leaves and chrysanthemum, focusing on the synergy of dispelling wind and clearing heat; or a heat-clearing and toxin-resolving oral liquid taking Radix Isatidis and Radix Scutellariae as the core components, which is widely used in poultry epidemic disease prevention and control; and a simplified formula of Radix Isatidis and Herba Euphorbiae Humifusae for detoxification and throat treatment. However, these technologies still have obvious defects: on the formula level, complex formulas have problems of difficult quality control and large dosage, while simple formulas have single efficacy and are difficult to balance heat-clearing and tonifying. On the process level, traditional decoction methods generally have problems of low dissolution rate of active ingredients, high loss rate of heat-sensitive ingredients, and high energy consumption. On the application level, long-term use of single preparations leads to increased pathogen resistance, and many compositions lack the regulation of immune function of the body, which is prone to cause the side effect of "bitter cold damaging the healthy". Therefore, it is urgent to develop a traditional Chinese medicine composition with simple formula, controllable quality, high extraction efficiency, and the functions of clearing heat and resolving toxins and immune regulation, and to optimize the existing preparation process to reduce energy consumption and ingredient loss, so as to solve the problems of heat and toxin prevention and treatment in the clinical and breeding fields. SUMMARY

[0004] In order to solve the technical problems mentioned in the background art, the present application provides a medicine composition with the effect of clearing heat and resolving toxins, and a preparation method and application thereof.

[0005] The present application provides a medicine composition with the effect of clearing heat and resolving toxins, which adopts the following technical scheme: A medicine composition with the effect of clearing heat and resolving toxins, comprising a fermented traditional Chinese medicine component and a decocted traditional Chinese medicine component; the mass ratio of the fermented traditional Chinese medicine component and the decocted traditional Chinese medicine component is 5-8:10-12.

[0006] Preferably, the fermented traditional Chinese medicine component comprises Astragalus, Poria cocos, Dioscorea and Glycyrrhiza.

[0007] Preferably, the decocted traditional Chinese medicine component comprises Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis and Taraxacum mongolicum.

[0008] Preferably, the preparation method of the fermented traditional Chinese medicine component comprises the following preparation steps: Step 1, mixing Astragalus membranaceus, Poria cocos, Dioscorea opposite and Glycyrrhiza uralensis according to a mass ratio, crushing to 60-80 meshes to obtain a fermentation raw material, adding 5-8 times of purified water to the fermentation raw material, stirring uniformly to obtain a fermentation substrate; Step 2, inoculating the fermentation substrate with a compound fermentation strain, sealing and fermenting for 48-60 h to obtain a fermented material; Step 3, boiling the fermented material, steaming for 20-30 min, naturally drying to a water content of 30-40%, repeating the steaming-natural drying process for 2-3 times, drying, crushing and sieving to obtain the fermented traditional Chinese medicine component.

[0009] Preferably, the mass ratio of Astragalus membranaceus, Poria cocos, Dioscorea opposite and Glycyrrhiza uralensis in step 1 is 20-30:15-25:15-25:5-15.

[0010] Preferably, the inoculation amount of the compound fermentation strain in step 2 is 3-5% of the mass of the fermentation substrate.

[0011] Preferably, the compound fermentation strain in step 2 is composed of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 10-12:4-6:2-3.

[0012] Preferably, the preparation method of the decocted traditional Chinese medicine component comprises the following preparation steps: mixing Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis and Taraxacum mongolicum according to a mass ratio, crushing to 40-60 meshes to obtain decocted raw material; adding 10-15 times of purified water to the decocted raw material, soaking for 20-30 min, and using ultrasonic-decocting synergistic extraction for 2-3 times, each time for 40-50 min, combining the extract, and reducing pressure to concentrate the combined extract to obtain the decocted traditional Chinese medicine component.

[0013] Preferably, the mass ratio of Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis and Taraxacum mongolicum is 30-45:25-35:20-30:15-25.

[0014] The application also provides a preparation method of a pharmaceutical composition with the efficacy of clearing heat and resolving toxins, which adopts the following technical scheme: adding the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component, stirring uniformly, adding excipients to prepare a soft material, and then performing shaping and drying treatment to obtain the pharmaceutical composition with the efficacy of clearing heat and resolving toxins.

[0015] Preferably, the excipient is dextrin or corn starch; when the excipient is dextrin, the added amount is 12-14% of the total weight; when the excipient is corn starch, the added amount is 13-15% of the total weight.

[0016] The application of the pharmaceutical composition with heat-clearing and detoxifying effects prepared by the preparation method above in the preparation of a medicine for treating and / or preventing infectious diseases in humans.

[0017] In summary, the application has the following beneficial effects: The astragalus in the fermentation component tonifies qi and raises yang, the poria cocos invigorates the spleen and removes dampness, the dioscorea supplements the spleen and nourishes the stomach, and the licorice root coordinates all the medicines. All of them are tonifying Chinese medicines, and after fermentation, the dissolution and absorption of active ingredients can be enhanced, so as to better play the role of "supporting the body" and laying the foundation for the body to resist external evils. The houttuynia cordata in the decoction component clears heat and detoxifies, the isatis root cools blood and benefits the throat, the scutellaria baicalensis clears heat and dries dampness, and the taraxacum mongolicum removes swelling and resolves nodes. All of them are heat-clearing Chinese medicines, and after decoction, the water-soluble heat-clearing and detoxifying components can be fully extracted to achieve the "eliminating evil" effect. This division method of "fermentation of the supporting component + decoction of the eliminating evil component" and the accurate adaptation of the process according to the characteristics of medicinal materials can maximize the retention of active ingredients and achieve synergistic effects. Astragalus, poria cocos and other four medicines are rich in starch, polysaccharides and other macromolecules. During fermentation, the hydrolytic enzymes secreted by the strains can decompose them into small molecular active substances, and the dissolution rate of active ingredients is significantly improved compared with direct decoction. In addition, licorice acid and other components can be converted into mild components, balancing the warm and tonifying properties and avoiding the damage to the spleen and stomach during heat-clearing. The heat-clearing components of houttuynia cordata, isatis root and other four medicines are mostly water-soluble, and houttuynia cordata contains decanoyl acetaldehyde which is volatile. The ultrasonic-decoction synergistic extraction can destroy the cell wall through ultrasonic "cavitation effect", and low-temperature decoction can significantly reduce the dissolution of tannins and other impurities compared with simple decoction, improving the purity of the component. The two processes respectively activate the "supporting" effect of warm and tonifying medicinal materials and the "eliminating evil" effect of heat-clearing medicinal materials, forming a synergistic effect of "clearing heat without damaging the body", ensuring the heat-clearing and detoxifying effect and safety.

[0018] The present application utilizes three strains of Aspergillus niger, Candida utilis and Lactobacillus plantarum for synergistic fermentation, and constructs a complete fermentation chain through functional complementation, which not only solves the efficiency short board of single strain fermentation, but also realizes the dual upgrading of efficacy and safety, especially suitable for the processing needs of Huangqi, Fuling and other warm-tonifying medicinal materials. From the perspective of ingredient transformation, Aspergillus niger can secrete amylase and cellulase, which can decompose starch and cellulose in medicinal materials into small molecule sugars. These small molecule sugars can be used as carbon sources by Candida utilis to synthesize active peptides, B vitamins and other new substances, making the "supporting" effect of Huangqi more prominent. At the same time, lactic acid produced by Lactobacillus plantarum can regulate the pH of the fermentation system, not only activating the enzyme activity of Aspergillus niger to accelerate the decomposition of macromolecules, but also avoiding the breeding of miscellaneous bacteria, solving the problem of single strain fermentation being prone to pollution, and ultimately improving the dissolution rate of effective ingredients of medicinal materials compared with single strain fermentation. From the perspective of efficacy and safety, the three can balance the properties of warm-tonifying medicinal materials: Lactobacillus plantarum can reduce the trace irritating substances produced during fermentation, reducing gastrointestinal discomfort after taking; the metabolic products of Candida utilis can also synergize with the active ingredients decomposed by Aspergillus niger to enhance the anti-inflammatory and immune regulation effects, avoiding the problem of single efficacy of single strain fermentation. In addition, synergistic fermentation can make the batch difference of the product smaller, and repeated steaming-drying can remove the trace impurities produced during fermentation, while making the ingredients more stable, providing more reliable raw material guarantee for subsequent drug preparation. DETAILED DESCRIPTION

[0019] The present application will be further described in detail below in combination with examples.

[0020] The Aspergillus niger (item number: B94857), Candida utilis (item number: B81627) and Lactobacillus plantarum (item number: B94828) used in the examples and comparative examples of the present application were all purchased from Ningbo Mingzhou Biological Technology Co., Ltd.

[0021] Examples 1-3 provide a pharmaceutical composition with the effects of clearing heat and resolving toxins, and a preparation method and application thereof.

[0022] Example 1 A pharmaceutical composition with the effects of clearing heat and resolving toxins, comprising a fermented traditional Chinese medicine component and a decocted traditional Chinese medicine component; the mass ratio of the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component is 5:10.

[0023] The preparation method of the fermented traditional Chinese medicine component comprises the following preparation steps: Step 1, Huangqi, Fuling, Shanyao and Gancao are mixed in a mass ratio of 20:15:15:5, then crushed and passed through a 60-mesh sieve to obtain a fermentation raw material. 5 times of purified water is added to the fermentation raw material, and stirred at a stirring speed of 200 rpm for 20 min. After uniform stirring, a fermentation substrate is obtained. Step 2, inoculate the fermentation substrate with the compound fermentation strain, seal the fermentation at a temperature of 32℃ for 48h to obtain the post-fermentation material, wherein the inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate, and the compound fermentation strain is composed of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 10:4:2; Step 3, after boiling the post-fermentation material, steam it for 20min, dry it in the dark until the water content is 30%, repeat the steaming-drying process 2 times, dry it at 40℃ until the water content is 5%, crush it through a 40-mesh sieve to obtain the fermented traditional Chinese medicine component.

[0024] The preparation method of the decocted traditional Chinese medicine component comprises the following preparation steps: Mix Houttuynia cordata, Isatidis radix, Scrophulariaceae and Taraxacum mongolicum by mass ratio of 30:25:20:15, crush them through a 40-mesh sieve to obtain decocted raw materials; add 10 times purified water to the decocted raw materials, soak for 20min, and then use ultrasonic-decocting synergistic extraction twice, wherein the ultrasonic power is 300W, the ultrasonic frequency is 40kHz, the decocting temperature is 60℃, and each time is 40min; combine the extraction liquid, and reduce the pressure to concentrate the combined extraction liquid to a relative density of 1.15 to obtain the decocted traditional Chinese medicine component.

[0025] A preparation method of a pharmaceutical composition with the effect of clearing heat and resolving toxins comprises the following preparation steps: Add the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component, stir at a stirring speed of 50rpm for 20min, add 12% of the total weight of dextrin after uniform stirring, and then make soft material, and then perform molding and drying at 60℃ to obtain the pharmaceutical composition with the effect of clearing heat and resolving toxins.

[0026] Example 2 A pharmaceutical composition with the effect of clearing heat and resolving toxins comprises a fermented traditional Chinese medicine component and a decocted traditional Chinese medicine component; the mass ratio of the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component is 7:11.

[0027] The preparation method of the fermented traditional Chinese medicine component comprises the following preparation steps: Step 1, mix Astragalus, Poria cocos, Dioscorea and Glycyrrhiza by mass ratio of 25:20:20:10, crush them through a 70-mesh sieve to obtain fermentation raw materials, and then add 7 times purified water to the fermentation raw materials, stir at a stirring speed of 300rpm for 25min, and obtain a fermentation substrate after uniform stirring; Step 2, inoculate the fermentation substrate with the compound fermentation strain, seal the fermentation at a temperature of 34℃ for 54h to obtain the post-fermentation material, wherein the inoculation amount of the compound fermentation strain is 4% of the mass of the fermentation substrate, and the compound fermentation strain is composed of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 11:5:2.5; Step 3, after boiling the fermented material, steam for 25 min, dry in the shade to a moisture content of 35%, repeat the steaming-drying process 3 times, dry at 50℃ to a moisture content of 3%, crush to 50 mesh, and obtain the fermented Chinese medicinal component.

[0028] The preparation method of the decocted Chinese medicinal component comprises the following preparation steps: The Houttuynia cordata, Isatidis radix, Scrophulariaceae and Dandelion are mixed in a mass ratio of 38:30:25:20, crushed to 50 mesh, and obtain the decocted raw material; 12 times purified water is added to the decocted raw material, soaked for 25 min, and then extracted 3 times by ultrasonic-decocting cooperation, wherein the ultrasonic power is 350 W, the ultrasonic frequency is 50 kHz, the decocting temperature is 65℃, and each time is 45 min; the extracted liquid is combined, and the combined extracted liquid is concentrated under reduced pressure to a relative density of 1.21, and obtain the decocted Chinese medicinal component.

[0029] The preparation method of a pharmaceutical composition with the effect of clearing heat and resolving toxins comprises the following preparation steps: The fermented Chinese medicinal component is added to the decocted Chinese medicinal component, stirred at a stirring speed of 80 rpm for 25 min, and then 13% of the total weight of corn starch is added to prepare a soft material, which is then shaped and dried at 62℃ to obtain the pharmaceutical composition with the effect of clearing heat and resolving toxins.

[0030] Example 3 The pharmaceutical composition with the effect of clearing heat and resolving toxins comprises a fermented Chinese medicinal component and a decocted Chinese medicinal component; the mass ratio of the fermented Chinese medicinal component to the decocted Chinese medicinal component is 8:12.

[0031] The preparation method of the fermented Chinese medicinal component comprises the following preparation steps: Step 1, the Astragalus, Poria cocos, Dioscorea and Glycyrrhiza are mixed in a mass ratio of 30:25:25:15, crushed to 80 mesh, and obtain the fermentation raw material; 8 times purified water is added to the fermentation raw material, stirred at a stirring speed of 400 rpm for 30 min, and then obtain the fermentation substrate after uniform stirring; Step 2, the fermentation substrate is inoculated with a compound fermentation strain, sealed and fermented at a temperature of 35℃ for 60 h to obtain a fermented material, wherein the inoculation amount of the compound fermentation strain is 5% of the mass of the fermentation substrate, and the compound fermentation strain is composed of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 12:6:3; Step 3, after boiling the fermented material, steam for 30 min, dry in the shade to a moisture content of 40%, repeat the steaming-drying process 3 times, dry at 60℃ to a moisture content of 4%, crush to 60 mesh, and obtain the fermented Chinese medicinal component.

[0032] The preparation method of the decocted Chinese medicinal component comprises the following preparation steps: The Houttuynia cordata, the Isatidis radix, the Scutellariae radix and the Taraxaci herba are mixed according to the mass ratio of 45:35:30:25, are crushed and passed through a 60-mesh sieve to obtain decocting raw materials; 15 times of purified water is added into the decocting raw materials, is soaked for 30 min, and is extracted by ultrasonic-decocting cooperation for 3 times, wherein the ultrasonic power is 400 W, the ultrasonic frequency is 60 kHz, the decocting temperature is 70 DEG C, and each time is 50 min; the extracted liquid is combined, and the combined extracted liquid is concentrated under reduced pressure to the relative density of 1.25 to obtain decocted traditional Chinese medicine components.

[0033] A preparation method of a pharmaceutical composition with the efficacy of clearing heat and resolving toxins, comprising the following preparation steps: The fermented traditional Chinese medicine components are added into the decocted traditional Chinese medicine components, and stirred at the stirring speed of 100 rpm for 30 min; after uniform stirring, 14% of the total weight of dextrin is added to prepare a soft material; and then the soft material is subjected to molding and 65 DEG C drying treatment to obtain the pharmaceutical composition with the efficacy of clearing heat and resolving toxins.

[0034] Comparative example 1 A pharmaceutical composition with the efficacy of clearing heat and resolving toxins, comprising fermented traditional Chinese medicine components and decocted traditional Chinese medicine components; the mass ratio of the fermented traditional Chinese medicine components to the decocted traditional Chinese medicine components is 5:10.

[0035] The preparation method of the fermented traditional Chinese medicine components comprises the following preparation steps: Step 1, the Houttuynia cordata, the Isatidis radix, the Scutellariae radix and the Taraxaci herba are mixed according to the mass ratio of 30:25:20:15, are crushed and passed through a 60-mesh sieve to obtain fermented raw materials; 5 times of purified water is added into the fermented raw materials, and is stirred at the stirring speed of 200 rpm for 20 min to obtain a fermentation substrate after uniform stirring; Step 2, the fermentation substrate is inoculated with a compound fermentation strain, and is sealed for fermentation at the temperature of 32 DEG C for 48 h to obtain fermented materials, wherein the inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate; the compound fermentation strain is composed of Aspergillus niger, Candida utilis and Lactobacillus plantarum with the effective viable count ratio of 10:4:2; Step 3, the fermented materials are boiled, steamed for 20 min, and naturally dried until the water content is 30%; the steaming-natural drying process is repeated twice, and the materials are dried at 40 DEG C until the water content is 5%, are crushed and passed through a 40-mesh sieve to obtain the fermented traditional Chinese medicine components.

[0036] The preparation method of the decocted traditional Chinese medicine components comprises the following preparation steps: The radix astragali, poria cocos, dioscorea and licorice are mixed in a mass ratio of 20:15:15:5, crushed through a 40-mesh sieve to obtain decocting raw materials; 10 times purified water is added to the decocting raw materials, soaked for 20 min, and then extracted twice by ultrasonic-decocting synergy, wherein the ultrasonic power is 300 W, the ultrasonic frequency is 40 kHz, the decocting temperature is 60 DEG C, and each time is 40 min; the extracted liquids are combined, and the combined extracted liquid is concentrated under reduced pressure to a relative density of 1.15 to obtain decocted traditional Chinese medicine components.

[0037] A preparation method of a pharmaceutical composition with heat-clearing and detoxicating efficacy, comprising the following preparation steps: The fermented traditional Chinese medicine components are added to the decocted traditional Chinese medicine components, stirred at a stirring speed of 50 rpm for 20 min, and then stirred uniformly; 12% of the total weight of dextrin is added to prepare a soft material; and then the soft material is shaped, dried at 60 DEG C, and treated to obtain the pharmaceutical composition with heat-clearing and detoxicating efficacy.

[0038] Comparative Example 2 A pharmaceutical composition with heat-clearing and detoxicating efficacy, comprising fermented traditional Chinese medicine components and decocted traditional Chinese medicine components; the mass ratio of the fermented traditional Chinese medicine components to the decocted traditional Chinese medicine components is 5:10.

[0039] The preparation method of the fermented traditional Chinese medicine components comprises the following preparation steps: Step 1, the radix astragali, poria cocos, dioscorea and licorice are mixed in a mass ratio of 20:15:15:5, crushed through a 60-mesh sieve to obtain fermented raw materials, and 5 times purified water is added to the fermented raw materials, stirred at a stirring speed of 200 rpm for 20 min, and then stirred uniformly to obtain a fermentation substrate; Step 2, the fermentation substrate is inoculated with a compound fermentation strain, sealed and fermented at a temperature of 32 DEG C for 48 h to obtain fermented materials, wherein the inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate, and the compound fermentation strain is composed of candida utilis and lactobacillus plantarum with an effective viable count ratio of 4:2; Step 3, the fermented materials are boiled, steamed for 20 min, and then naturally dried until the water content is 30%; the steaming-natural drying process is repeated twice, and then the materials are dried at 40 DEG C until the water content is 5%, crushed through a 40-mesh sieve to obtain the fermented traditional Chinese medicine components.

[0040] The preparation method of the decocted traditional Chinese medicine components comprises the following preparation steps: Houttuynia cordata, isatis root, radix scrophulariae and dandelion are mixed in a mass ratio of 30:25:20:15, crushed through a 40-mesh sieve to obtain decocting raw materials; 10 times purified water is added to the decocting raw materials, soaked for 20 min, and then extracted twice by ultrasonic-decocting synergy, wherein the ultrasonic power is 300 W, the ultrasonic frequency is 40 kHz, the decocting temperature is 60 DEG C, and each time is 40 min; the extracted liquids are combined, and the combined extracted liquid is concentrated under reduced pressure to a relative density of 1.15 to obtain decocted traditional Chinese medicine components.

[0041] A preparation method of a pharmaceutical composition with heat-clearing and detoxifying efficacy, comprising the following preparation steps: The fermented traditional Chinese medicine component is added to the decocted traditional Chinese medicine component, stirred at a stirring speed of 50 rpm for 20 min, and then 12% of dextrin based on the total weight is added to prepare soft material. After molding and drying at 60℃, the pharmaceutical composition with heat-clearing and detoxifying efficacy is obtained.

[0042] Comparative Example 3 A pharmaceutical composition with heat-clearing and detoxifying efficacy, comprising a fermented traditional Chinese medicine component and a decocted traditional Chinese medicine component; the mass ratio of the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component is 5:10.

[0043] The preparation method of the fermented traditional Chinese medicine component comprises the following preparation steps: Step 1, Huangqi, Fuling, Shanyao and Gancao are mixed according to a mass ratio of 20:15:15:5, crushed through a 60-mesh sieve to obtain a fermentation raw material, and 5 times of purified water is added to the fermentation raw material, stirred at a stirring speed of 200 rpm for 20 min, and then a fermentation substrate is obtained after uniform stirring; Step 2, a composite fermentation strain is inoculated into the fermentation substrate, and the fermentation is carried out at a temperature of 32℃ for 48 h to obtain a fermented material, wherein the inoculation amount of the composite fermentation strain is 3% of the mass of the fermentation substrate, and the composite fermentation strain is composed of Aspergillus niger and Lactobacillus plantarum with an effective viable count ratio of 10:2; Step 3, the fermented material is boiled, steamed for 20 min, and then naturally dried until the water content is 30%. The steaming-natural drying process is repeated twice, and then the material is dried at 40℃ until the water content is 5%, crushed through a 40-mesh sieve, and the fermented traditional Chinese medicine component is obtained.

[0044] The preparation method of the decocted traditional Chinese medicine component comprises the following preparation steps: Houttuynia cordata, Banlangen, Huangqi and Pugongying are mixed according to a mass ratio of 30:25:20:15, crushed through a 40-mesh sieve to obtain decocted raw material, 10 times of purified water is added to the decocted raw material, soaked for 20 min, and then extracted twice by ultrasonic-decocting cooperation, wherein the ultrasonic power is 300 W, the ultrasonic frequency is 40 kHz, the decocting temperature is 60℃, and each time is 40 min. The extracted liquid is combined, concentrated under reduced pressure until the relative density is 1.15, and the decocted traditional Chinese medicine component is obtained.

[0045] A preparation method of a pharmaceutical composition with heat-clearing and detoxifying efficacy, comprising the following preparation steps: The fermented traditional Chinese medicine component is added to the decocted traditional Chinese medicine component, stirred at a stirring speed of 50 rpm for 20 min, and then 12% of dextrin based on the total weight is added to prepare soft material. After molding and drying at 60℃, the pharmaceutical composition with heat-clearing and detoxifying efficacy is obtained.

[0046] Comparative Example 4 The pharmaceutical composition with the heat-clearing and detoxifying effect comprises a fermented traditional Chinese medicine component and a decocted traditional Chinese medicine component.

[0047] The preparation method of the fermented traditional Chinese medicine component comprises the following steps: Step 1, Huangqi, Fuling, Shanyao and Gancao are mixed according to a mass ratio of 20:15:15:5, and then are crushed and sieved through a 60-mesh screen to obtain a fermentation raw material. 5 times of purified water is added to the fermentation raw material, and stirring is performed at a stirring speed of 200 rpm for 20 min. After uniform stirring, a fermentation substrate is obtained. Step 2, a compound fermentation strain is inoculated into the fermentation substrate, and the fermentation is performed at a temperature of 32℃ for 48 h to obtain a fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain is composed of Aspergillus niger and Candida utilis, and the effective viable bacterial number ratio of the two is 10:4. Step 3, the fermented material is boiled, steamed for 20 min, and then is naturally dried until the water content is 30%. The steaming-natural drying process is repeated twice. The material is dried at 40℃ until the water content is 5%, and then is crushed and sieved through a 40-mesh screen to obtain the fermented traditional Chinese medicine component.

[0048] The preparation method of the decocted traditional Chinese medicine component comprises the following steps: Houttuynia cordata, Banlangen, Huangqi and Pugongying are mixed according to a mass ratio of 30:25:20:15, and then are crushed and sieved through a 40-mesh screen to obtain a decocting raw material. 10 times of purified water is added to the decocting raw material, and the mixture is soaked for 20 min. Then, ultrasonic-decocting synergistic extraction is performed twice. The ultrasonic power is 300 W, the ultrasonic frequency is 40 kHz, the decocting temperature is 60℃, and each time the extraction is performed for 40 min. The extracted liquid is combined, and then is concentrated under reduced pressure until the relative density is 1.15 to obtain the decocted traditional Chinese medicine component.

[0049] The preparation method of the pharmaceutical composition with the heat-clearing and detoxifying effect comprises the following steps: The fermented traditional Chinese medicine component is added to the decocted traditional Chinese medicine component, and stirring is performed at a stirring speed of 50 rpm for 20 min. After uniform stirring, 12% of the total weight of dextrin is added to prepare a soft material. Then, the soft material is subjected to molding and drying at 60℃ to obtain the pharmaceutical composition with the heat-clearing and detoxifying effect.

[0050] Comparative Example 5 The pharmaceutical composition with the heat-clearing and detoxifying effect comprises a fermented traditional Chinese medicine component and a decocted traditional Chinese medicine component. The mass ratio of the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component is 5:10.

[0051] The preparation method of the fermented traditional Chinese medicine component comprises the following steps: Step 1, mix radix astragali, poria cocos, dioscorea and licorice according to the mass ratio of 20:15:15:5, crush and pass through a 60-mesh sieve to obtain fermentation raw materials, add 5 times purified water to the fermentation raw materials, stir at a stirring speed of 200 rpm for 20 min, and then obtain a fermentation substrate after uniform stirring; Step 2, inoculate the fermentation substrate with a compound fermentation strain, seal and ferment at a temperature of 32℃ for 48 h to obtain a fermented material, wherein the inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate, and the compound fermentation strain is composed of aspergillus niger, candida utilis and lactobacillus plantarum with an effective viable count ratio of 10:4:2; Step 3, boil the fermented material, steam for 20 min, dry in the shade until the water content is 30%, dry at 40℃ until the water content is 5%, crush and pass through a 40-mesh sieve to obtain a fermented traditional Chinese medicine component.

[0052] The preparation method of the decocted traditional Chinese medicine component comprises the following preparation steps: Mix houttuynia cordata, isatis root, scrophularia ningpoensis and dandelion according to the mass ratio of 30:25:20:15, crush and pass through a 40-mesh sieve to obtain decocting raw materials; add 10 times purified water to the decocting raw materials, soak for 20 min, and then perform ultrasonic-decocting synergistic extraction twice, wherein the ultrasonic power is 300 W, the ultrasonic frequency is 40 kHz, the decocting temperature is 60℃, and each time is 40 min; combine the extraction liquids, and reduce the pressure to concentrate the combined extraction liquid to a relative density of 1.15 to obtain a decocted traditional Chinese medicine component.

[0053] A preparation method of a pharmaceutical composition with heat-clearing and detoxifying efficacy, comprising the following preparation steps: Add the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component, stir at a stirring speed of 50 rpm for 20 min, and then add 12% of the total weight of dextrin to prepare a soft material; and then perform molding and drying at 60℃ to obtain the pharmaceutical composition with heat-clearing and detoxifying efficacy.

[0054] Comparative Example 6 A pharmaceutical composition with heat-clearing and detoxifying efficacy, comprising a fermented traditional Chinese medicine component and a decocted traditional Chinese medicine component; the mass ratio of the fermented traditional Chinese medicine component to the decocted traditional Chinese medicine component is 10:5.

[0055] The preparation method of the fermented traditional Chinese medicine component comprises the following preparation steps: Step 1, mix radix astragali, poria cocos, dioscorea and licorice according to the mass ratio of 20:15:15:5, crush and pass through a 60-mesh sieve to obtain fermentation raw materials, add 5 times purified water to the fermentation raw materials, stir at a stirring speed of 200 rpm for 20 min, and then obtain a fermentation substrate after uniform stirring; Step 2, inoculate the fermentation medium with the complex fermentation strain, seal the fermentation at a temperature of 32℃ for 48h to obtain the post-fermentation material, wherein the inoculation amount of the complex fermentation strain is 3% of the mass of the fermentation medium, and the complex fermentation strain is composed of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 10:4:2; Step 3, after boiling the post-fermentation material, steam for 20min, air dry to a water content of 30%, repeat the steaming-air drying process 2 times, 40℃ oven dry to a water content of 5%, crush through a 40 mesh sieve to obtain the fermented traditional Chinese medicine component.

[0056] The preparation method of the decocted traditional Chinese medicine component comprises the following preparation steps: The Houttuynia cordata, Isatidis radix, Scrophulariaceae and Dandelion are mixed in a mass ratio of 30:25:20:15, crushed through a 40 mesh sieve to obtain decocted raw materials; 10 times purified water is added to the decocted raw materials, soaked for 20min, and then extracted by ultrasonic-decocting cooperation twice, wherein the ultrasonic power is 300W, the ultrasonic frequency is 40kHz, the decocting temperature is 60℃, and each time is 40min; the extracted liquids are combined, and the combined extracted liquid is concentrated under reduced pressure to a relative density of 1.15 to obtain the decocted traditional Chinese medicine component.

[0057] A preparation method of a pharmaceutical composition with heat-clearing and detoxifying efficacy, comprising the following preparation steps: The fermented traditional Chinese medicine component is added to the decocted traditional Chinese medicine component, stirred at a stirring speed of 50rpm for 20min, and then 12% of the total weight of dextrin is added to prepare a soft material, which is then shaped and dried at 60℃ to obtain the pharmaceutical composition with heat-clearing and detoxifying efficacy.

[0058] Performance test The pharmaceutical compositions with heat-clearing and detoxifying efficacy prepared in Examples 1-3 and Comparative Examples 1-6 are tested for heat-clearing efficacy, as follows: Test animals: healthy big-eared white rabbits with a body weight of 5-6kg, male or female, are selected, and are confirmed to be free of diseases and have good mental state before the test; Test samples: the pharmaceutical compositions with heat-clearing and detoxifying efficacy prepared in Examples 1-3 and Comparative Examples 1-6, and compound honeysuckle granules (the pharmaceutical compositions with heat-clearing and detoxifying efficacy prepared in Examples 1-3 and Comparative Examples 1-6 and the compound honeysuckle granules are prepared into 0.5g / mL gavage liquid); Reagents and instruments: bacterial endotoxin, physiological saline, disposable syringe, electronic thermometer, electronic balance, timer, etc.; wherein the bacterial endotoxin needs to meet the pharmaceutical standard, and the physiological saline is prepared on site.

[0059] III. Test method: Before the animal screening and adaptation test, the white rabbits were placed in an environmental temperature of 22-25℃ and relative humidity of 50-60% for 7 days, and free feeding and drinking. One day before the test, the body temperature was measured every 2 hours for a total of 3 times to ensure that the body temperature was within the range of 38-39.4℃, and the body temperature fluctuation on the same day was not more than 0.4℃, and the rabbits that met the conditions were selected for standby; fever model building on the test day, first measure the pre-modeling base body temperature of each rabbit (recorded as T0). Then the white rabbits were injected with bacterial endotoxin saline solution from the ear vein at a dose of 1 mL / kg. After injection, the change of body temperature was continuously observed, and the body temperature was measured again after 1 hour (recorded as T1), and the rabbits with body temperature rising more than 0.5℃ (i.e. T1-T0>0.5℃) were selected as qualified fever model animals; grouping and administration The qualified fever model rabbits were randomly divided into 11 groups, 12 in each group, half male and half female, and the specific grouping was as follows: the blank control group was not given drug, and the same volume of normal saline was administered by gavage; the positive control group was administered by gavage with commercially available compound honeysuckle granules, and the groups of examples 1-3 and comparative examples 1-6 were administered by gavage with the pharmaceutical compositions prepared in examples 1-3 and comparative examples 1-6 having the effects of clearing heat and resolving toxins; body temperature monitoring After administration, the change of body temperature was continuously observed, and the body temperature data was recorded every 1h for 3h, compared with the blank control group, * for p<0.05, when measuring the body temperature, the operation method was fixed to ensure that the thermometer was in good contact with the rabbit anus, and each measurement time was not less than 1min to ensure the accuracy of the data.

[0060] The test results are shown in Table 1.

[0061] Table 1: Clearing heat and resolving toxins effect of the pharmaceutical compositions prepared in examples 1-3 and comparative examples 1-6

[0062] As can be seen from Table 1, the pharmaceutical compositions prepared in the present application have outstanding advantages. In terms of technology, combined with fermentation and ultrasonic-cooking synergistic extraction, fermentation can decompose large molecules of traditional Chinese medicine to improve the dissolution of effective ingredients, and ultrasonic can enhance the extraction efficiency, taking into account the retention of ingredients and extraction effect; in terms of efficacy, it has been verified by tests that it has excellent heat-clearing effect; in terms of practicality, it has good quality stability and guaranteed shelf life, and the use of excipients to form soft materials has good formability and convenient use, which not only ensures the drug efficacy but also improves the use experience, and the comprehensive advantages are significant.

[0063] The specific embodiments are only an explanation of the present application, which is not a limitation of the present application, and those skilled in the art can make modifications to the embodiments without creative contribution after reading the present specification, but as long as it is within the scope of the claims of the present application, it is protected by the patent law.

Claims

1. A pharmaceutical composition having the effect of clearing heat and detoxifying, characterized in that, It includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of the fermented Chinese herbal medicine components to the decocted Chinese herbal medicine components is 5-8:10-12; The fermented Chinese herbal medicine components include: Astragalus membranaceus, Poria cocos, Dioscorea opposita, and Glycyrrhiza uralensis; The decoction ingredients include: houttuynia cordata, isatis root, scutellaria baicalensis, and dandelion.

2. The pharmaceutical composition with heat-clearing and detoxifying effects according to claim 1, characterized in that, The preparation method of the fermented traditional Chinese medicine component includes the following preparation steps; Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in the mass ratio, then grind them to 60-80 mesh to obtain fermentation raw materials. Add 5-8 times the amount of purified water to the fermentation raw materials, stir evenly, and obtain the fermentation substrate. Step 2: Inoculate the fermentation substrate with compound fermentation bacteria, seal and ferment for 48-60 hours to obtain the fermented material; Step 3: After boiling the fermented material, steam it for 20-30 minutes, and then air-dry it until the moisture content is 30-40%. Repeat the steaming-air-drying process 2-3 times. After drying, crushing and sieving, the fermented Chinese medicine components are obtained.

3. The pharmaceutical composition with heat-clearing and detoxifying effects according to claim 2, characterized in that, In step 1, the mass ratio of Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis is 20-30:15-25:15-25:5-15.

4. The pharmaceutical composition with heat-clearing and detoxifying effects according to claim 2, characterized in that, In step 2, the inoculation amount of the compound fermentation strain is 3-5% of the mass of the fermentation substrate.

5. The pharmaceutical composition with heat-clearing and detoxifying effects according to claim 2, characterized in that, In step 2, the compound fermentation strain consists of Aspergillus niger, Candida utilis, and Lactobacillus plantarum with an effective viable cell ratio of 10-12:4-6:2-3.

6. The pharmaceutical composition with heat-clearing and detoxifying effects according to claim 1, characterized in that, The preparation method of the decoction components includes the following preparation steps: Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis and Taraxacum mongolicum are mixed in a certain mass ratio and then pulverized to 40-60 mesh to obtain the decoction raw material. 10-15 times the amount of purified water is added to the decoction raw material and soaked for 20-30 minutes. Then, ultrasonic-decoction is used for 2-3 extractions, each for 40-50 minutes. The extracts are combined and concentrated under reduced pressure to obtain the decoction Chinese medicine components.

7. The pharmaceutical composition with heat-clearing and detoxifying effects according to claim 6, characterized in that, The mass ratio of Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis and Taraxacum mongolicum is 30-45:25-35:20-30:15-25.

8. A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects as described in any one of claims 1-7, characterized in that, The preparation steps include the following: Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, stirred evenly, and then excipients are added to form a soft material. After molding and drying, a drug composition with heat-clearing and detoxifying effects is obtained.

9. The pharmaceutical composition with heat-clearing and detoxifying effects according to claim 8, characterized in that, The excipient is dextrin or corn starch; when the excipient is dextrin, its addition amount is 12-14% of the total weight; when the excipient is corn starch, its addition amount is 13-15% of the total weight.

10. The use of a pharmaceutical composition having heat-clearing and detoxifying effects as described in any one of claims 1-7 in the preparation of a medicament for treating and / or preventing human infectious diseases.

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