A pharmaceutical composition with heat-clearing and detoxicating effects, and a preparation method and application thereof

Abstract

The application relates to the technical field of traditional Chinese medicine preparations, in particular to a medicine composition with heat-clearing and detoxicating effects, a preparation method and application thereof, wherein the medicine composition with heat-clearing and detoxicating effects comprises fermented traditional Chinese medicine components and decocted traditional Chinese medicine components. The preparation method of the medicine composition is as follows: the fermented traditional Chinese medicine components are added into the decocted traditional Chinese medicine components, the mixture is stirred uniformly, excipients are added, soft materials are prepared, and then the soft materials are subjected to shaping and drying treatment, so that the medicine composition with heat-clearing and detoxicating effects is obtained. The medicine composition with heat-clearing and detoxicating effects prepared by the application is extracted by combining fermentation with ultrasonic-decocting, fermentation can decompose traditional Chinese medicine macromolecules to improve the dissolution of effective components, ultrasonic can strengthen the extraction efficiency, the component reservation and the extraction effect are considered, and the heat-clearing and detoxicating effect is excellent.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to a pharmaceutical composition that combines the effects of clearing heat and detoxifying with immune regulation, as well as the preparation process and clinical application of the composition, which can be widely applied to the treatment and prevention of human infectious diseases. Background Technology

[0002] Traditional Chinese medicine (TCM) compositions for clearing heat and detoxifying are a core method in TCM for preventing and treating heat-toxin syndromes, and are widely used in the prevention and control of human infectious diseases and livestock and poultry diseases. Symptoms such as fever, sore throat, carbuncles, and boils caused by the accumulation of heat toxins are increasingly difficult to treat in the modern environment due to drug resistance. Western medicine antibiotics and chemical drugs have limitations such as significant side effects and a tendency to induce drug resistance, making TCM compositions a research hotspot.

[0003] In existing technologies, traditional Chinese medicine compositions for clearing heat and detoxifying have formed a diversified development pattern: for example, compound preparations with Houttuynia cordata as the main ingredient, combined with mulberry leaves, chrysanthemum, etc., focus on the synergistic effect of dispelling wind and heat and clearing heat; or oral liquid for clearing heat and detoxifying with Isatis indigotica and Scutellaria baicalensis as core ingredients, which is widely used in the prevention and control of poultry diseases; and simplified formulations of Isatis indigotica and dandelion, used for detoxification and soothing the throat. However, these technologies still have obvious defects: at the formulation level, complex formulas have problems such as difficulty in quality control and large dosage, while simple formulas have a single therapeutic effect and are difficult to balance clearing heat and supporting the body's resistance. At the process level, traditional decoction methods generally have problems such as low dissolution rate of active ingredients, high loss rate of heat-sensitive components, and high energy consumption. At the application level, long-term use of single preparations leads to increased pathogen resistance, and most compositions lack the regulatory effect on the body's immune function, which can easily cause the side effect of "bitter and cold damaging the body's resistance". Therefore, there is an urgent need to develop a traditional Chinese medicine composition that is simple in formulation, has controllable quality, high extraction efficiency, and combines heat-clearing and detoxifying functions with immune regulation, and to optimize existing preparation processes to reduce energy consumption and component loss. This is an urgent need to solve the problem of heat toxicity prevention and treatment in clinical and aquaculture fields. Summary of the Invention

[0004] To address the technical problems mentioned in the background section, this application provides a pharmaceutical composition with heat-clearing and detoxifying effects, its preparation method, and its application.

[0005] This application provides a pharmaceutical composition with heat-clearing and detoxifying effects, using the following technical solution:

[0006] A pharmaceutical composition with heat-clearing and detoxifying effects 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.

[0007] Preferably, the fermented Chinese herbal medicine components include: Astragalus membranaceus, Poria cocos, Dioscorea opposita, and Glycyrrhiza uralensis.

[0008] Preferably, the decoction of Chinese medicinal herbs includes: houttuynia cordata, isatis root, scutellaria baicalensis, and dandelion.

[0009] Preferably, the preparation method of the fermented traditional Chinese medicine component includes the following preparation steps;

[0010] 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.

[0011] Step 2: Inoculate the fermentation substrate with compound fermentation bacteria, seal and ferment for 48-60 hours to obtain the fermented material;

[0012] 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.

[0013] Preferably, the mass ratio of Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in step 1 is 20-30:15-25:15-25:5-15.

[0014] Preferably, the inoculation amount of the compound fermentation strain in step 2 is 3-5% of the mass of the fermentation substrate.

[0015] Preferably, the compound fermentation strain in step 2 consists of Aspergillus niger, Candida utilis, and Lactobacillus plantarum with an effective viable count ratio of 10-12:4-6:2-3.

[0016] Preferably, the preparation method of the decoction components includes the following preparation steps:

[0017] 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.

[0018] Preferably, the mass ratio of Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis and Taraxacum mongolicum is 30-45:25-35:20-30:15-25.

[0019] This application also provides a method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects, using the following technical solution:

[0020] 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.

[0021] Preferably, 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.

[0022] In summary, this application has the following beneficial effects:

[0023] The fermentation components of this application contain Astragalus membranaceus (for tonifying Qi and raising Yang), Poria cocos (for strengthening the spleen and promoting diuresis), Dioscorea opposita (for tonifying the spleen and nourishing the stomach), and Glycyrrhiza uralensis (for harmonizing the other herbs). All four are tonifying Chinese herbs; fermentation enhances the dissolution and absorption of their active ingredients, thus better exerting their "strengthening the body's resistance" effect and laying the foundation for the body to resist external pathogens. The decoction components contain Houttuynia cordata (for clearing heat and detoxifying), Isatis indigotica (for cooling the blood and relieving sore throat), Scutellaria baicalensis (for clearing heat and drying dampness), and Taraxacum mongolicum (for reducing swelling and dissipating nodules). All four are heat-clearing Chinese herbs; decoction fully extracts their water-soluble heat-clearing and detoxifying components, achieving the "eliminating pathogens" effect. This division of "fermentation of the strengthening components + decoction of the pathogen-eliminating components," along with precise matching of processes according to the characteristics of the medicinal materials, maximizes the retention of effective components and achieves synergistic effects. Astragalus, Poria, and two other herbs are rich in macromolecules such as starch and polysaccharides. During fermentation, the hydrolytic enzymes secreted by the microorganisms can break them down into smaller active molecules, significantly increasing the dissolution rate of effective components compared to direct decoction. This process also converts glycyrrhizic acid and other substances into milder components, balancing the warming and tonifying properties and preventing damage to the spleen and stomach during heat-clearing. Houttuynia cordata, Isatis indigotica, and two other herbs have mostly water-soluble heat-clearing components, and Houttuynia cordata contains volatile decanoyl acetaldehyde. Ultrasonic-decoction synergistic extraction utilizes the ultrasonic "cavitation effect" to disrupt cell walls, while low-temperature decoction significantly reduces the dissolution of impurities such as tannins compared to simple decoction, improving component purity. These two processes respectively activate the "strengthening" effect of warming and tonifying herbs and the "eliminating pathogens" effect of heat-clearing herbs, creating a synergistic effect of "clearing heat without harming the body's vital energy," ensuring both the efficacy and safety of heat-clearing and detoxifying.

[0024] This application utilizes the synergistic fermentation of three microbial species: Aspergillus niger, Candida utilis, and Lactobacillus plantarum. Through functional complementarity, a complete fermentation chain is constructed, overcoming the efficiency limitations of single-species fermentation and achieving a dual upgrade in efficacy and safety. It is particularly suitable for processing warming and tonifying medicinal materials such as Astragalus membranaceus and Poria cocos. From the perspective of component transformation, Aspergillus niger secretes amylase and cellulase, which can break down the starch and cellulose in the medicinal materials into small-molecule sugars. These small-molecule sugars can then serve as a carbon source for Candida utilis, promoting the synthesis of new substances such as bioactive peptides and B vitamins, thus enhancing the "strengthening" effect of Astragalus membranaceus. Simultaneously, the lactic acid produced by Lactobacillus plantarum regulates the pH of the fermentation system, not only activating the enzyme activity of Aspergillus niger and accelerating the decomposition of macromolecules, but also preventing the growth of other microorganisms and solving the problem of easy contamination in single-species fermentation. Ultimately, this results in a higher dissolution rate of the effective components of the medicinal materials compared to single-species fermentation. From the perspective of efficacy and safety, the synergistic effect of these three components can balance the properties of mild tonic herbs: *Lactobacillus plantarum* can reduce the trace amounts of irritating substances produced during fermentation, thus reducing gastrointestinal discomfort after consumption; the metabolites of *Candida utilis* can also synergize with the active ingredients decomposed by *Aspergillus niger*, enhancing anti-inflammatory and immunomodulatory effects and avoiding the problem of single-strain fermentation resulting in limited efficacy. Furthermore, synergistic fermentation reduces batch-to-batch variations, and repeated steaming and air-drying removes trace impurities produced during fermentation, while simultaneously stabilizing the components and providing a more reliable raw material guarantee for subsequent drug preparation. Detailed Implementation

[0025] The present application will be further described in detail below with reference to the embodiments.

[0026] The Aspergillus niger (product number: B94857), Candida utilis (product number: B81627), and Lactobacillus plantarum (product number: B94828) used in the embodiments and comparative examples of this application were all purchased from Ningbo Mingzhou Biotechnology Co., Ltd.

[0027] Examples 1-3 provide a pharmaceutical composition with heat-clearing and detoxifying effects, its preparation method, and its application.

[0028] Example 1

[0029] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 5:10.

[0030] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0031] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 20:15:15:5, then pulverize and pass through a 60-mesh sieve to obtain fermentation raw materials. Add 5 times the amount of purified water to the fermentation raw materials and stir at a stirring speed of 200 rpm for 20 minutes. After stirring evenly, the fermentation substrate is obtained.

[0032] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 32°C for 48 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 10:4:2.

[0033] Step 3: After boiling the fermented material, steam it for 20 minutes, air-dry it until the moisture content is 30%, repeat the steaming-air-drying process twice, dry it at 40℃ until the moisture content is 5%, pulverize it through a 40-mesh sieve, and obtain the fermented Chinese medicine components.

[0034] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0035] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 30:25:20:15, pulverized, and passed through a 40-mesh sieve to obtain the decoction raw material. Ten times the volume of purified water was added to the decoction raw material, and after soaking for 20 minutes, it was extracted twice by ultrasound-decoction synergistic extraction. The ultrasound power was 300W, the ultrasound frequency was 40kHz, the decoction temperature was 60℃, and the extraction time was 40 minutes each time. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.15 to obtain the decoction Chinese medicine components.

[0036] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0037] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 50 rpm for 20 minutes. After stirring evenly, 12% of dextrin by weight is added to form a soft material, which is then shaped and dried at 60°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0038] Example 2

[0039] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 7:11.

[0040] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0041] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 25:20:20:10, then pulverize and pass through a 70-mesh sieve to obtain fermentation raw materials. Add 7 times the amount of purified water to the fermentation raw materials and stir at 300 rpm for 25 minutes. After stirring evenly, the fermentation substrate is obtained.

[0042] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 34℃ for 54 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 4% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 11:5:2.5.

[0043] Step 3: After boiling the fermented material, steam it for 25 minutes, and air-dry it until the moisture content is 35%. Repeat the steaming-air-drying process 3 times, dry it at 50℃ until the moisture content is 3%, and pulverize it through a 50-mesh sieve to obtain the fermented Chinese medicine components.

[0044] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0045] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 38:30:25:20 and then pulverized through a 50-mesh sieve to obtain the decoction raw material. 12 times the volume of purified water was added to the decoction raw material and soaked for 25 minutes. Then, ultrasonic-decoction synergistic extraction was performed 3 times, with an ultrasonic power of 350W, an ultrasonic frequency of 50kHz, a decoction temperature of 65℃, and a duration of 45 minutes each time. The extracts were combined and concentrated under reduced pressure to a relative density of 1.21 to obtain the decoction Chinese herbal components.

[0046] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0047] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 80 rpm for 25 minutes. After stirring evenly, corn starch accounting for 13% of the total weight is added to form a soft material. Then, it is shaped and dried at 62°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0048] Example 3

[0049] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 8:12.

[0050] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0051] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 30:25:25:15, then pulverize and pass through an 80-mesh sieve to obtain fermentation raw materials. Add 8 times the amount of purified water to the fermentation raw materials and stir at a stirring speed of 400 rpm for 30 minutes. After stirring evenly, the fermentation substrate is obtained.

[0052] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 35°C for 60 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 5% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger, Candida utilis, and Lactobacillus plantarum with an effective viable count ratio of 12:6:3.

[0053] Step 3: After boiling the fermented material, steam it for 30 minutes, air-dry it until the moisture content is 40%, repeat the steaming-air-drying process 3 times, dry it at 60℃ until the moisture content is 4%, and pulverize it through a 60-mesh sieve to obtain the fermented Chinese medicine components.

[0054] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0055] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 45:35:30:25, pulverized, and passed through a 60-mesh sieve to obtain the decoction raw material. 15 times the volume of purified water was added to the decoction raw material, and after soaking for 30 minutes, it was extracted three times using a combination of ultrasound and decoction. The ultrasound power was 400W, the ultrasound frequency was 60kHz, the decoction temperature was 70℃, and each extraction lasted for 50 minutes. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.25 to obtain the decoction Chinese medicine components.

[0056] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0057] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 100 rpm for 30 minutes. After stirring evenly, dextrin accounting for 14% of the total weight is added to form a soft material, which is then shaped and dried at 65°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0058] Comparative Example 1

[0059] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 5:10.

[0060] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0061] Step 1: Mix houttuynia cordata, isatis root, scutellaria baicalensis and dandelion in a mass ratio of 30:25:20:15, then pulverize and pass through a 60-mesh sieve to obtain fermentation raw material. Add 5 times the amount of purified water to the fermentation raw material and stir at a stirring speed of 200 rpm for 20 minutes. After stirring evenly, the fermentation substrate is obtained.

[0062] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 32°C for 48 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 10:4:2.

[0063] Step 3: After boiling the fermented material, steam it for 20 minutes, air-dry it until the moisture content is 30%, repeat the steaming-air-drying process twice, dry it at 40℃ until the moisture content is 5%, pulverize it through a 40-mesh sieve, and obtain the fermented Chinese medicine components.

[0064] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0065] Astragalus membranaceus, Poria cocos, Dioscorea opposita, and Glycyrrhiza uralensis were mixed in a mass ratio of 20:15:15:5 and then pulverized through a 40-mesh sieve to obtain the decoction raw material. Ten times the volume of purified water was added to the decoction raw material, and after soaking for 20 minutes, it was extracted twice by ultrasound-decoction synergistic extraction. The ultrasound power was 300W, the ultrasound frequency was 40kHz, the decoction temperature was 60℃, and the extraction time was 40 minutes each time. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.15 to obtain the decoction Chinese medicine components.

[0066] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0067] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 50 rpm for 20 minutes. After stirring evenly, 12% of dextrin by weight is added to form a soft material, which is then shaped and dried at 60°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0068] Comparative Example 2

[0069] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 5:10.

[0070] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0071] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 20:15:15:5, then pulverize and pass through a 60-mesh sieve to obtain fermentation raw materials. Add 5 times the amount of purified water to the fermentation raw materials and stir at a stirring speed of 200 rpm for 20 minutes. After stirring evenly, the fermentation substrate is obtained.

[0072] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 32°C for 48 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain consists of Candida utilis and Lactobacillus plantarum with an effective live bacteria ratio of 4:2.

[0073] Step 3: After boiling the fermented material, steam it for 20 minutes, air-dry it until the moisture content is 30%, repeat the steaming-air-drying process twice, dry it at 40℃ until the moisture content is 5%, pulverize it through a 40-mesh sieve, and obtain the fermented Chinese medicine components.

[0074] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0075] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 30:25:20:15, pulverized, and passed through a 40-mesh sieve to obtain the decoction raw material. Ten times the volume of purified water was added to the decoction raw material, and after soaking for 20 minutes, it was extracted twice by ultrasound-decoction synergistic extraction. The ultrasound power was 300W, the ultrasound frequency was 40kHz, the decoction temperature was 60℃, and the extraction time was 40 minutes each time. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.15 to obtain the decoction Chinese medicine components.

[0076] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0077] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 50 rpm for 20 minutes. After stirring evenly, 12% of dextrin by weight is added to form a soft material, which is then shaped and dried at 60°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0078] Comparative Example 3

[0079] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 5:10.

[0080] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0081] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 20:15:15:5, then pulverize and pass through a 60-mesh sieve to obtain fermentation raw materials. Add 5 times the amount of purified water to the fermentation raw materials and stir at a stirring speed of 200 rpm for 20 minutes. After stirring evenly, the fermentation substrate is obtained.

[0082] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 32°C for 48 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger and Lactobacillus plantarum with an effective viable count ratio of 10:2.

[0083] Step 3: After boiling the fermented material, steam it for 20 minutes, air-dry it until the moisture content is 30%, repeat the steaming-air-drying process twice, dry it at 40℃ until the moisture content is 5%, pulverize it through a 40-mesh sieve, and obtain the fermented Chinese medicine components.

[0084] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0085] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 30:25:20:15, pulverized, and passed through a 40-mesh sieve to obtain the decoction raw material. Ten times the volume of purified water was added to the decoction raw material, and after soaking for 20 minutes, it was extracted twice by ultrasound-decoction synergistic extraction. The ultrasound power was 300W, the ultrasound frequency was 40kHz, the decoction temperature was 60℃, and the extraction time was 40 minutes each time. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.15 to obtain the decoction Chinese medicine components.

[0086] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0087] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 50 rpm for 20 minutes. After stirring evenly, 12% of dextrin by weight is added to form a soft material, which is then shaped and dried at 60°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0088] Comparative Example 4

[0089] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 5:10.

[0090] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0091] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 20:15:15:5, then pulverize and pass through a 60-mesh sieve to obtain fermentation raw materials. Add 5 times the amount of purified water to the fermentation raw materials and stir at a stirring speed of 200 rpm for 20 minutes. After stirring evenly, the fermentation substrate is obtained.

[0092] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 32°C for 48 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger and Candida utilis with an effective viable cell ratio of 10:4.

[0093] Step 3: After boiling the fermented material, steam it for 20 minutes, air-dry it until the moisture content is 30%, repeat the steaming-air-drying process twice, dry it at 40℃ until the moisture content is 5%, pulverize it through a 40-mesh sieve, and obtain the fermented Chinese medicine components.

[0094] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0095] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 30:25:20:15, pulverized, and passed through a 40-mesh sieve to obtain the decoction raw material. Ten times the volume of purified water was added to the decoction raw material, and after soaking for 20 minutes, it was extracted twice by ultrasound-decoction synergistic extraction. The ultrasound power was 300W, the ultrasound frequency was 40kHz, the decoction temperature was 60℃, and the extraction time was 40 minutes each time. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.15 to obtain the decoction Chinese medicine components.

[0096] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0097] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 50 rpm for 20 minutes. After stirring evenly, 12% of dextrin by weight is added to form a soft material, which is then shaped and dried at 60°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0098] Comparative Example 5

[0099] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 5:10.

[0100] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0101] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 20:15:15:5, then pulverize and pass through a 60-mesh sieve to obtain fermentation raw materials. Add 5 times the amount of purified water to the fermentation raw materials and stir at a stirring speed of 200 rpm for 20 minutes. After stirring evenly, the fermentation substrate is obtained.

[0102] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 32°C for 48 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 10:4:2.

[0103] Step 3: After boiling the fermented material, steam it for 20 minutes, air-dry it until the moisture content is 30%, dry it at 40℃ until the moisture content is 5%, and then pulverize it through a 40-mesh sieve to obtain the fermented Chinese medicine components.

[0104] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0105] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 30:25:20:15, pulverized, and passed through a 40-mesh sieve to obtain the decoction raw material. Ten times the volume of purified water was added to the decoction raw material, and after soaking for 20 minutes, it was extracted twice by ultrasound-decoction synergistic extraction. The ultrasound power was 300W, the ultrasound frequency was 40kHz, the decoction temperature was 60℃, and the extraction time was 40 minutes each time. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.15 to obtain the decoction Chinese medicine components.

[0106] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0107] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 50 rpm for 20 minutes. After stirring evenly, 12% of dextrin by weight is added to form a soft material, which is then shaped and dried at 60°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0108] Comparative Example 6

[0109] A pharmaceutical composition with heat-clearing and detoxifying effects includes fermented Chinese herbal medicine components and decocted Chinese herbal medicine components; the mass ratio of fermented Chinese herbal medicine components to decocted Chinese herbal medicine components is 10:5.

[0110] The preparation method of fermented traditional Chinese medicine components includes the following preparation steps:

[0111] Step 1: Mix Astragalus membranaceus, Poria cocos, Dioscorea opposita and Glycyrrhiza uralensis in a mass ratio of 20:15:15:5, then pulverize and pass through a 60-mesh sieve to obtain fermentation raw materials. Add 5 times the amount of purified water to the fermentation raw materials and stir at a stirring speed of 200 rpm for 20 minutes. After stirring evenly, the fermentation substrate is obtained.

[0112] Step 2: Inoculate the fermentation substrate with a compound fermentation strain and ferment in a sealed container at 32°C for 48 hours to obtain the fermented material. The inoculation amount of the compound fermentation strain is 3% of the mass of the fermentation substrate. The compound fermentation strain consists of Aspergillus niger, Candida utilis and Lactobacillus plantarum with an effective viable count ratio of 10:4:2.

[0113] Step 3: After boiling the fermented material, steam it for 20 minutes, air-dry it until the moisture content is 30%, repeat the steaming-air-drying process twice, dry it at 40℃ until the moisture content is 5%, pulverize it through a 40-mesh sieve, and obtain the fermented Chinese medicine components.

[0114] The preparation method of the decoction components of traditional Chinese medicine includes the following preparation steps:

[0115] Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis, and Taraxacum mongolicum were mixed in a mass ratio of 30:25:20:15, pulverized, and passed through a 40-mesh sieve to obtain the decoction raw material. Ten times the volume of purified water was added to the decoction raw material, and after soaking for 20 minutes, it was extracted twice by ultrasound-decoction synergistic extraction. The ultrasound power was 300W, the ultrasound frequency was 40kHz, the decoction temperature was 60℃, and the extraction time was 40 minutes each time. The extracts were combined, and the combined extracts were concentrated under reduced pressure to a relative density of 1.15 to obtain the decoction Chinese medicine components.

[0116] A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects includes the following preparation steps:

[0117] Fermented Chinese herbal medicine components are added to decocted Chinese herbal medicine components, and stirred at 50 rpm for 20 minutes. After stirring evenly, 12% of dextrin by weight is added to form a soft material, which is then shaped and dried at 60°C to obtain a drug composition with heat-clearing and detoxifying effects.

[0118] Performance testing

[0119] The heat-clearing efficacy of the pharmaceutical compositions with heat-clearing and detoxifying effects prepared in Examples 1-3 and Comparative Examples 1-6 of this application was tested, as follows:

[0120] Experimental animals: Select healthy white rabbits weighing 5-6 catties, regardless of sex, and ensure they are free of disease and in good spirits before the experiment;

[0121] Test samples: the drug compositions with heat-clearing and detoxifying effects prepared in Examples 1-3 and Comparative Examples 1-6, and compound honeysuckle granules (the drug compositions with heat-clearing and detoxifying effects prepared in Examples 1-3 and Comparative Examples 1-6 and compound honeysuckle granules were all prepared as 0.5 g / mL gavage solutions).

[0122] Reagents and instruments: bacterial endotoxins, physiological saline, disposable syringes, electronic thermometers, electronic balances, timers, etc.; among which, bacterial endotoxins must meet pharmaceutical standards, and physiological saline should be prepared and used immediately.

[0123] III. Experimental Methods: Animal Screening and Adaptation Experiments: Before the experiment, large-eared white rabbits were placed in a breeding room with an ambient temperature of 22-25℃ and a relative humidity of 50-60% for 7 days to acclimatize, with free access to food and water. One day before the experiment, 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 that the daily temperature fluctuation did not exceed 0.4℃. Rabbits meeting the criteria were selected for use. On the day of the fever model establishment experiment, the basal body temperature (T0) of each rabbit before modeling was measured first. Subsequently, bacterial endotoxin saline solution was injected into the ear vein of the large-eared white rabbits at a dose of 1mL / kg. After injection, body temperature changes were continuously observed, and the body temperature was measured again after 1 hour (denoted as T1). Rabbits with a body temperature rise exceeding 0.5℃ (i.e., T1-T0>0.5℃) were selected as qualified fever model animals. Grouping and drug administration: The qualified fever model rabbits were randomly divided into 11 groups, with 12 rabbits in each group, half male and half female. The specific grouping is as follows: The blank control group was not given any drug and was given an equal volume of physiological saline by gavage; the positive control group was given commercially available compound honeysuckle granules by gavage; the groups of Examples 1-3 and Comparative Examples 1-6 were given the drug composition with heat-clearing and detoxifying effects prepared in Examples 1-3 and Comparative Examples 1-6 by gavage. Body temperature monitoring: After drug administration, body temperature changes were continuously observed and recorded every 1 hour for 3 consecutive hours. Compared with the blank control group, *p<0.05. When measuring body temperature, the operation method was fixed to ensure good contact between the thermometer and the rabbit's anus, and the measurement time was not less than 1 minute each time to ensure data accuracy.

[0124] The test results are shown in Table 1.

[0125] Table 1. The heat-clearing and detoxifying effects of the pharmaceutical compositions prepared in Examples 1-3 and Comparative Examples 1-6.

[0126]

[0127] As shown in Table 1, the pharmaceutical composition prepared in this application has significant advantages. In terms of process, it combines fermentation with ultrasound-decoction synergistic extraction. Fermentation decomposes large molecules of traditional Chinese medicine, enhancing the dissolution of active ingredients, while ultrasound strengthens extraction efficiency, balancing component retention and extraction effect. In terms of efficacy, experiments have verified its excellent heat-clearing effect. In terms of practicality, it exhibits good quality stability and a guaranteed shelf life. The addition of excipients to create a soft material ensures good formability and convenient administration, guaranteeing both efficacy and improved user experience, resulting in significant overall advantages.

[0128] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

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; 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. 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; In step 2, the inoculation amount of the compound fermentation strain is 3-5% of the mass of the fermentation substrate; 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. 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 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. The mass ratio of Houttuynia cordata, Isatis indigotica, Scutellaria baicalensis and Taraxacum mongolicum is 30-45:25-35:20-30:15-25.

2. A method for preparing a pharmaceutical composition with heat-clearing and detoxifying effects as described in claim 1, 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.

3. The method for preparing the pharmaceutical composition with heat-clearing and detoxifying effects according to claim 2, 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.

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