A fermented traditional Chinese medicine product and a preparation method and application thereof

Abstract

This invention discloses a fermented traditional Chinese medicine product, its preparation method, and its application, belonging to the field of traditional Chinese medicine fermentation technology. The product uses peppermint, astragalus, wolfberry, mulberry bark, anemarrhena, arborvitae leaf, scrophularia, cimicifuga, elsholtzia, angelica, lily, ginkgo, licorice, schisandra, eleutherococcus senticosus, ophiopogon japonicus, and dried ginger as raw materials, sorghum as a co-fermentation raw material, and brewing liquid as a fermentation enhancer. The process involves pretreatment of the traditional Chinese medicine, co-cooking with sorghum, saccharification with small-grain starter, segmented fermentation, extraction and purification, and post-treatment. This invention utilizes a "compound traditional Chinese medicine ~ sorghum" co-fermentation system, combined with the microbial community and active substances rich in brewing liquid, to increase the dissolution rate of active ingredients such as astragaloside A, lily polysaccharide, and wolfberry polysaccharide in the traditional Chinese medicine by more than 50%, while simultaneously converting them into easily absorbed small molecule derivatives. The finished product has an alcohol content controlled at 6-8 degrees, which not only promotes the absorption of active ingredients but also possesses synergistic effects of clearing the lungs and regulating qi, tonifying qi and benefiting the lungs, moistening the lungs and relieving cough, and clearing heat and resolving phlegm. The process enables the resource utilization of yellow water from brewing, reducing costs by 35%, and the product exhibits excellent stability, making it suitable for industrial production. It also has significant value in the field of lung function regulation and health care.

Description

Technical Field

[0001] This invention relates to a fermented traditional Chinese medicine product, its preparation method, and its application, belonging to the technical field of fermented traditional Chinese medicine preparations. Background Technology

[0002] Decreased lung function is a common clinical health problem, closely related to factors such as environmental pollution and unhealthy lifestyle habits. Symptoms include shortness of breath, cough, excessive phlegm, chest tightness, and weakened immunity. In traditional Chinese medicine theory, the lungs govern qi and respiration, and regulating lung function requires a multi-dimensional approach, including promoting lung function, tonifying qi, moistening the lungs, clearing heat, and resolving phlegm.

[0003] Currently, most traditional Chinese medicine products for regulating lung function are prepared using traditional decoction, water extraction, and alcohol precipitation processes, but these methods have significant shortcomings: First, the cell wall structure of Chinese medicine is dense, resulting in low dissolution rates of effective active ingredients and bioavailability of less than 30%; second, directly extracted products have a bitter taste, poor palatability, and low patient compliance; third, some processes use organic solvents, posing residual risks and increasing production costs. The yellow water produced by the brewing industry is rich in microorganisms such as lactic acid bacteria and yeast, as well as active substances such as organic acids and amino acids, but it is discharged in large quantities due to low utilization, causing resource waste and environmental pollution.

[0004] In existing technologies, traditional Chinese medicine fermentation often uses single-strain or simple compound raw materials, failing to achieve the synergistic effect of complex compound traditional Chinese medicines with sorghum and yellow water. For example, patent CN119236023B discloses a fermented traditional Chinese medicine product for regulating spleen and stomach function and its preparation method, which only uses extracts of traditional Chinese medicines that are both food and medicine, fermentation culture medium, and Lactobacillus paracasei LBR. Prepared from 002, it has a single efficacy and does not utilize the advantages of yellow water; therefore, it is of great practical significance to develop a lung function regulating product based on the above-mentioned complex compound Chinese medicine, combined with the synergistic fermentation of sorghum and yellow water, to improve the utilization rate of active ingredients and flavor quality. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing a fermented traditional Chinese medicine product that regulates lung function, comprising the following steps: (1) Pretreatment of Chinese medicine raw materials: Select peppermint, astragalus, wolfberry, mulberry bark, anemarrhena, arborvitae leaf, scrophularia, cimicifuga, sesame, angelica, lily, ginkgo, licorice, schisandra, eleutherococcus senticosus, ophiopogon japonicus and dried ginger without mold to obtain a Chinese medicine mixture. After crushing the Chinese medicine mixture, add water to soak it. At the same time, weigh sorghum for later use.

[0006] (2) Co-cooking: Mix the pulverized and soaked Chinese herbal medicine mixture with sorghum, soak it in water to remove excess water, and steam the soaked Chinese herbal medicine mixture and sorghum to obtain the cooked material.

[0007] (3) Saccharification treatment: Cool down the cooked material, add the compound yeast for brewing, stir and saccharify to obtain a saccharified mixture.

[0008] (4) Primary fermentation: The saccharified mixture is sealed and fermented to obtain the primary fermentation mixture.

[0009] (5) Secondary fermentation: After the primary fermentation is completed, add yellow water to the primary fermentation mixture and mix evenly before carrying out secondary fermentation. After the fermentation is completed, collect the fermentation mash.

[0010] (6) Extraction and purification: Centrifuge and filter the fermentation mash, add purified water to the supernatant and combine the extracts; use an ultrafiltration membrane for ultrafiltration and collect the permeate.

[0011] (7) Post-processing: Add mogroside to the permeate to adjust the pH, sterilize, cool and aseptically fill to obtain the fermented Chinese medicine product that regulates lung function.

[0012] Preferably, the raw materials and their weight parts in step (1) are: 3-6 parts of peppermint, 10-15 parts of astragalus, 6-12 parts of wolfberry, 6-12 parts of mulberry bark, 6-12 parts of anemarrhena, 6-15 parts of arborvitae leaf, 9-15 parts of scrophularia, 3-6 parts of cimicifuga, 3-9 parts of elm, 3-10 parts of angelica, 10-15 parts of lily, 5-10 parts of ginkgo, 2-10 parts of licorice, 3-6 parts of schisandra, 9-27 parts of eleutherococcus senticosus, 6-12 parts of ophiopogon japonicus, and 3-10 parts of dried ginger.

[0013] Preferably, in step (1), the mass ratio of the herbal medicine mixture to sorghum is (1:2) to (4:5). Preferably, in step (1), the herbal mixture is pulverized into 80-100 mesh coarse powder, and then 2.5-5 times the total mass of the coarse powder is added to purified water and soaked for 4-6 hours.

[0014] More preferably, in step (1), add purified water at a ratio of 4 times the total mass of the coarse powder and soak for 5 hours.

[0015] Preferably, the steaming temperature in step (2) is 105~120℃, the steaming time is 40~70min, and the mixture is stirred once every 15min during the steaming process.

[0016] Preferably, the compound starter culture used in step (3) is a compound preparation composed of Aspergillus oryzae, Rhizopus, and yeast, wherein the mass ratio of Aspergillus oryzae, Rhizopus, and yeast is (7~8):(1~2):(2~3), and the viable count is ≥10. 8 The amount of CFU / g added to the compound yeast for brewing is 0.5%~1.0% of the mass of the cooked materials.

[0017] Preferably, the saccharification process in step (3) is carried out at 28-32°C and 75-85% humidity for 36-48 hours.

[0018] More preferably, the saccharification process in step (3) is carried out at 30°C and 80% humidity for 42 hours.

[0019] Preferably, the initial fermentation conditions in step (4) are fermentation at 25~30℃ for 72 hours.

[0020] Preferably, the brewing yellow water in step (5) is a by-product of strong-aroma baijiu fermentation, with an alcohol content of 3%~6%, a pH value of 3.0~4.0, and a total acid content of ≥5.0g / L; the amount of brewing yellow water added is 10~12 times the mass of the primary fermentation mixture, and the secondary fermentation conditions are 20~25℃ and fermentation for 40~60 days.

[0021] Preferably, in step (6), the centrifugation speed is 3000~4000 r / min, the centrifugation time is 15 min, the amount of purified water added is 3~5 times the volume of the supernatant, an ultrafiltration membrane with a molecular weight cutoff of 8000 Da is used, the ultrafiltration pressure is 0.2~0.3 MPa and the temperature is 25~30℃, the permeate is collected, and the clarity of the permeate is ≥98%.

[0022] Preferably, the specific process of post-treatment in step (7) is as follows: add mogroside to the permeate to adjust the pH to 4.0~5.0, and sterilize at 115~121℃ for 15~20min.

[0023] This invention provides an application of the prepared fermented traditional Chinese medicine in the preparation of drugs for treating pneumonia.

[0024] Yellow liquid, also known as yellow slurry, is one of the fermentation byproducts in the brewing process of baijiu (Chinese liquor). It is usually brownish-yellow or brown and has the characteristics of a viscous, gelatinous liquid.

[0025] The product prepared by the method of the present invention has an alcohol content of 6-8 degrees, an astragaloside A content of ≥0.8mg / mL, a lily polysaccharide content of ≥12mg / mL, a wolfberry polysaccharide content of ≥5.0mg / mL, and shows no precipitation or deterioration after being stored at room temperature and protected from light for 18 months.

[0026] The formulation principles of this invention are as follows: The formula follows the principles of monarch, minister, assistant, and guide in Traditional Chinese Medicine. Eleutherococcus senticosus is used in the largest dose, its function being to invigorate qi and strengthen the spleen, tonify the kidneys and calm the mind; Astragalus membranaceus invigorates qi and raises yang, consolidating the exterior and stopping sweating. These two herbs work synergistically to target the primary symptom of "qi deficiency," serving as the monarch herb. Lycium barbarum, Ophiopogon japonicus, and Lilium brownii nourish the yin of the lungs and kidneys; Scrophularia ningpoensis and Anemarrhena asphodeloides clear heat, cool the blood, nourish yin, and reduce fire. This group of herbs assists the monarch herb in simultaneously tonifying qi and yin and clearing deficiency heat, serving as minister herbs. Mentha haplocalyx, Cimicifuga foetida, Elsholtzia ciliata, Angelica dahurica, Morus alba root bark, Platycladus orientalis leaf, Ginkgo biloba, Zingiber officinale, and Schisandra chinensis serve as assistant herbs, harmonizing the properties of the herbs and alleviating the side effects of certain herbs. Glycyrrhiza uralensis harmonizes the other herbs, and Schisandra chinensis astringes lung qi, preventing excessive dissipation of pungent herbs, serving as guide herbs. The formula contains predominantly sweet herbs (such as Astragalus membranaceus, Glycyrrhiza uralensis, and Lycium barbarum), emphasizing tonification. Pungent herbs (such as peppermint, angelica dahurica, dried ginger, and cimicifuga) are used to disperse and relieve exterior symptoms, warm the middle jiao and promote qi circulation. Sour-tasting schisandra chinensis has an astringent effect. When combined with pungent herbs, it reflects the idea of ​​"combining dispersion and astringency" to prevent the dissipation of vital energy.

[0027] The formula contains herbs that clear lung heat (mulberry bark and anemarrhena) and calm liver heat (mint, which also enters the liver meridian), which aligns with the principle of "metal controls wood." This approach can address the concurrent symptoms where lung heat may affect liver fire (such as irritability and red eyes).

[0028] Compared with the prior art, the present invention has the following significant advantages: (1) The combination of compound formulation and fermentation enhances efficacy: Seventeen Chinese medicines such as peppermint and astragalus are scientifically compounded to exert the comprehensive effects of clearing the lungs and regulating qi, replenishing qi and benefiting the lungs, moistening the lungs and relieving cough, clearing heat and resolving phlegm, and astringing the lungs and generating fluids. Combined with "sorghum co-fermentation + yellow water secondary fermentation", the dissolution rate of astragaloside A is increased by 55%, the dissolution rate of lily polysaccharide is increased by 60%, and the dissolution rate of wolfberry polysaccharide is increased by 58%. Moreover, microbial metabolism transforms macromolecular components into small molecule derivatives, and the bioavailability is increased to more than 65%, which is significantly better than the traditional extraction process.

[0029] (2) Excellent flavor and stability: The 6-8 degree alcohol content combined with the natural aroma of mint and sesame improves the bitter taste of Chinese medicine. The esters produced by sorghum fermentation and the amino acids in yellow water form a mellow and complex flavor, significantly improving palatability. The fermentation metabolites and ultrafiltration purification process ensure that the product can be stored at room temperature and away from light for 18 months without precipitation or deterioration, demonstrating excellent stability.

[0030] (3) Resource recycling and cost advantages: The use of brewing by-product yellow water to replace some of the nutritional additives solves the environmental problem; sorghum provides a cheap carbon source, reducing raw material costs; the process does not require complex equipment, and the production cost is 35%~40% lower than that of traditional Chinese medicine oral liquids, making it suitable for large-scale production.

[0031] (4) High safety: It uses authentic Chinese medicinal materials, food-grade compound yeast and natural yellow water fermentation, without chemical additives; acute toxicity test shows that the maximum tolerated dose in mice is more than 60 times the recommended dose for adults, and it is safe and suitable for all types of people. Attached Figure Description

[0032] Figure 1 This is a slice of the lungs of a normal mouse.

[0033] Figure 2 A lung section of a mouse infected with Streptococcus pneumoniae.

[0034] Figure 3 This is a lung section of a mouse infected with Streptococcus pneumoniae 3 days after treatment with cephalosporins.

[0035] Figure 4 Lung slices of mice infected with Streptococcus pneumoniae after being treated with the fermented traditional Chinese medicine prepared in Example 1 for 3 days.

[0036] Figure 5 A lung section of a mouse infected with Haemophilus influenzae.

[0037] Figure 6 This is a lung section of a mouse infected with Haemophilus influenzae 3 days after treatment with cephalosporin.

[0038] Figure 7 The lung sections of mice infected with Haemophilus influenzae were obtained after 3 days of treatment with the fermented traditional Chinese medicine prepared in Example 1.

[0039] Figure 8 A lung section from a mouse infected with Klebsiella pneumoniae.

[0040] Figure 9 This is a lung section of a mouse infected with Klebsiella pneumoniae 3 days after treatment with cephalosporin.

[0041] Figure 10 Lung slices of mice infected with Klebsiella pneumoniae after being treated with the fermented traditional Chinese medicine prepared in Example 1 for 3 days. Detailed Implementation

[0042] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, but the scope of protection of the present invention is not limited to the content described.

[0043] Example 1 A method for preparing a fermented traditional Chinese medicine product that regulates lung function specifically includes the following steps: (1) Pretreatment of Chinese medicine: 40g of peppermint, 120g of astragalus, 90g of wolfberry, 90g of mulberry bark, 90g of anemarrhena, 100g of arborvitae leaf, 120g of scrophularia, 40g of cimicifuga, 60g of sesame, 60g of angelica, 120g of lily, 80g of ginkgo, 60g of licorice, 40g of schisandra, 180g of eleutherococcus senticosus, 90g of ophiopogon japonicus, and 60g of dried ginger were mixed to obtain a mixture of Chinese medicine. The mixture of Chinese medicine was pulverized to 90 mesh, and 3600mL of purified water was added (total coarse powder mass 900g, 4 times the amount of water). The mixture was soaked at 28℃ for 5h, and stirred once every 2h to obtain the mixture of Chinese medicine.

[0044] (2) Co-cooking: 900g of Chinese medicine mixture and 1800g of sorghum (the mass ratio of Chinese medicine mixture to sorghum is 1:2) are mixed, 5400mL of pure water is added, and the mixture is cooked at 115℃ for 55min. Stir once every 15min to obtain the cooked material.

[0045] (3) Saccharification treatment: The cooked material is cooled to 32℃, and 21.6g of compound brewing koji is added (where the mass ratio of Aspergillus oryzae, Rhizopus and yeast is 7:1:2, the mass of cooked material is 2700g, and the viable count is 1.2×10⁻⁶). 8 The saccharification mixture was prepared by saccharification at 30℃ and 80% humidity for 42 hours, with a reducing sugar content of 11.2 g / 100 g.

[0046] (4) Segmented fermentation: The saccharified mixture was transferred to a sterile fermentation tank and fermented at 28°C for 72 hours to obtain the primary fermentation product; 27 kg of yellow water (the primary fermentation mixture weighed 2700 g, 10 times the amount added, with an alcohol content of 4.5% vol, pH 3.5, and total acid of 5.2 g / L) was added and fermented at 22°C for 60 days, and the fermentation mash was collected.

[0047] (5) Extraction and purification: Centrifuge the fermentation mash at 3500 r / min for 15 min, take the supernatant and add 108000 mL of purified water (the volume of the supernatant is about 27000 mL, which is 4 times the volume of water); combine the extracts and then ultrafilter them with an 8000 Da ultrafiltration membrane at 0.25 MPa and 28℃, and collect the permeate.

[0048] (6) Post-treatment: Add mogroside to the permeate to adjust the pH to 4.5, sterilize at 121℃ for 18 min to obtain fermented Chinese medicine product.

[0049] Tests showed that the product has an alcohol content of 7.2%, an astragaloside A content of 0.95 mg / mL, a lily polysaccharide content of 13.8 mg / mL, and a wolfberry polysaccharide content of 6.2 mg / mL; it has a mellow and slightly sweet taste with a minty aroma and no bitterness; after 18 months of storage at room temperature, the product has a clarity of 98% and shows no signs of spoilage.

[0050] Example 2 A method for preparing a fermented traditional Chinese medicine product that regulates lung function specifically includes the following steps: (1) Pretreatment of Chinese medicine: 20g of peppermint, 60g of astragalus, 45g of wolfberry, 45g of mulberry bark, 45g of anemarrhena, 50g of arborvitae leaf, 60g of scrophularia, 20g of cimicifuga, 30g of sesame, 30g of angelica, 60g of lily, 40g of ginkgo, 30g of licorice, 20g of schisandra, 90g of eleutherococcus senticosus, 45g of ophiopogon japonicus, and 30g of dried ginger are mixed together. The mixture is then pulverized to 80 mesh and 1800mL of purified water is added (total coarse powder mass 720g, 2.5 times the amount of water). The mixture is soaked at 25℃ for 6 hours.

[0051] (2) Co-cooking: Mix the Chinese medicine mixture with 900g of sorghum (the mass ratio of Chinese medicine mixture to sorghum is 4:5), add 2025mL of purified water (the total mass of Chinese medicine mixture and sorghum is 1620g, and the water volume is 1.25 times), and cook at 105℃ for 70min. Stir once every 15min to obtain the cooked material.

[0052] (3) Saccharification treatment: The cooked material is cooled to 30℃, and 10.1g of compound koji (where the mass ratio of Aspergillus oryzae, Rhizopus and yeast is 8:2:3, the mass of cooked material is 1620g, and the viable count is 1.2×10⁻⁶) is added. 8 The saccharification mixture was prepared by saccharification at 28℃ and 75% humidity for 48 hours, with a reducing sugar content of 10.3g / 100g.

[0053] (4) Segmented fermentation: The fermentation mixture obtained from the saccharification mixture is transferred to a sterile fermenter and fermented for 72 hours at 25°C. Then, 16.2 kg of yellow water (1620 g of saccharification mixture, 10 times the amount added, alcohol content 3% vol, pH 3.0, total acid 5.0 g / L) is added and fermented at 20°C for 60 days.

[0054] (5) Extraction and purification: Centrifuge at 3000 r / min for 15 min, collect the permeate after ultrafiltration.

[0055] (6) Post-processing: Add mogrosides to adjust the pH to 4.5, then sterilize at 115℃ for 20 minutes to obtain fermented Chinese medicine products, which are then aseptically filled.

[0056] Tests showed an alcohol content of 6.5%, astragaloside A of 0.82 mg / mL, lily polysaccharide of 12.1 mg / mL, and wolfberry polysaccharide of 5.1 mg / mL, with good stability.

[0057] Example 3 A method for preparing a fermented traditional Chinese medicine product that regulates lung function specifically includes the following steps: (1) Pretreatment of Chinese medicine: 60g of peppermint, 150g of astragalus, 120g of wolfberry, 120g of mulberry bark, 120g of anemarrhena, 150g of arborvitae leaf, 150g of scrophularia, 60g of cimicifuga, 90g of sesame, 100g of angelica, 150g of lily, 100g of ginkgo, 100g of licorice, 60g of schisandra, 270g of eleutherococcus senticosus, 120g of ophiopogon japonicus, and 100g of dried ginger were mixed together. The mixture was then pulverized to 100 mesh and 5400mL of purified water was added (total coarse powder mass 2020g, 2.7 times the amount of water). The mixture was soaked at 30℃ for 4h.

[0058] (2) Co-cooking: Mix with 2700g of sorghum (the mass ratio of the Chinese medicine mixture to sorghum is 1.01:1.35), add 7290mL of purified water, and cook at 120℃ for 40min.

[0059] (3) Saccharification treatment: Cool down to 35℃, add 32.4g of compound koji (where the mass ratio of Aspergillus oryzae, Rhizopus and yeast is 7:1:2, the mass of cooked material is 4720g, and the viable count is 1.2×10⁻⁶). 8 The saccharification mixture was prepared by saccharification at 32℃ and 85% humidity for 36 hours, with a reducing sugar content of 12.5g / 100g.

[0060] (4) Segmented fermentation: The fermentation mixture obtained from the saccharification mixture is transferred to a sterile fermenter and fermented for 72 hours at 30°C. Then, 47.2 kg of yellow water (4720 g of saccharification mixture, 10 times the amount added, alcohol content 6% vol, pH 4.0, total acid 5.5 g / L) is added and fermented at 25°C for 60 days.

[0061] (5) Extraction and purification: Centrifuge at 4000 r / min for 15 min; collect the permeate after ultrafiltration.

[0062] (6) Post-processing: Add mogrosides to adjust the pH to 4.5, then sterilize at 121℃ for 15 min to obtain fermented Chinese medicine product.

[0063] Tests showed an alcohol content of 7.8%, astragaloside A of 1.02 mg / mL, lily polysaccharide of 14.5 mg / mL, and wolfberry polysaccharide of 6.8 mg / mL. The flavor was mellow with a light fragrance.

[0064] Example 4 Evaluate the therapeutic efficacy and safety of fermented medicinal wine in three mouse models of bacterial pneumonia. This embodiment aims to evaluate the therapeutic effect of a specific fermented medicinal wine by establishing mouse pneumonia models induced by Streptococcus pneumoniae, Haemophilus influenzae, and Klebsiella pneumoniae, and to compare it with standard antibiotics (cephalosporins). The specific steps are as follows: (1) Mouse grouping: Adult mice aged 6-8 weeks were divided into 10 groups, with 4 mice in each group. The first group was the healthy mouse group (control group); the second group was the Streptococcus pneumoniae pneumonia model group; the third group was the Streptococcus pneumoniae pneumonia model group + cephalosporin treatment group; the fourth group was the Streptococcus pneumoniae pneumonia model group + fermented traditional Chinese medicine treatment group; the fifth group was the Haemophilus influenzae pneumonia model group; the sixth group was the Haemophilus influenzae pneumonia model group + cephalosporin treatment group; the seventh group was the Haemophilus influenzae pneumonia model group + fermented traditional Chinese medicine treatment group; the eighth group was the Klebsiella pneumoniae pneumonia model group; the ninth group was the Klebsiella pneumoniae pneumonia model group + cephalosporin treatment group; and the tenth group was the Klebsiella pneumoniae pneumonia model group + fermented traditional Chinese medicine treatment group.

[0065] (2) Animal model establishment: Mice in the second, third and fourth groups were given intranasal instillation of Streptococcus pneumoniae to establish a Streptococcus pneumoniae pneumonia model mouse; mice in the fifth, sixth and seventh groups were given intranasal instillation of Haemophilus influenzae to establish a Haemophilus influenzae pneumonia model mouse; mice in the eighth, ninth and tenth groups were given intranasal instillation of Klebsiella pneumoniae to establish a Klebsiella pneumoniae pneumonia model mouse; mice in the first group were given an equal volume of physiological saline.

[0066] (3) Drug administration: After the three pneumonia models were successfully constructed, mice in the third, sixth and ninth groups were administered cephalosporin by gavage (cephalosporin dosage was 20 mg / kg, dissolved in sterile water); mice in the fourth, seventh and tenth groups were treated with the fermented Chinese medicine prepared in Example 1, with a dosage of 1 mL / kg; each group was administered the medicine by gavage for 3 days, twice a day.

[0067] Lung tissue was collected from mice after gavage to prepare pathological sections and observe pathological changes (HE staining). The pathological section results are as follows: Figures 1-10 As shown, Figure 1 These are lung sections from normal mice (Group 1). The images show numerous uniformly sized and evenly distributed alveolar cavities (large white gaps) within the field of view. The alveolar cavities are open, and the alveolar septa are thin with few cells, indicating good lung ventilation. The alveolar septa are very thin, separating the alveolar cavities like fine lines. The alveolar structure is clear and regularly arranged, without obvious structural damage or collapse / consolidation. Figure 2 The lung sections of mice infected with Streptococcus pneumoniae show that the alveolar structure is still present, but the alveolar septa are significantly thickened. There are many suspected inflammatory cell exudates in the alveolar cavity, and there are local inflammatory cell aggregates around blood vessels or airways. There are many red-stained components in some areas, which may be hemorrhage or congestion, or possibly red blood cell exudation. The model has been successfully established. Figure 3The lung sections of mice infected with Streptococcus pneumoniae after 3 days of cephalosporin treatment show that: there are many regular empty areas in the alveolar cavities, indicating that the ventilation cavities are still present; the alveolar septa are relatively thin with only a few thickened areas; the septal cells are neatly arranged; and the lung tissue structure is close to that of normal lung tissue after cephalosporin treatment. Figure 4 The images show lung sections from mice infected with Streptococcus pneumoniae after 3 days of treatment with fermented traditional Chinese medicine prepared in Example 1. As can be seen from the images, the alveolar structure is generally well preserved, with most alveolar cavities remaining open and adequately ventilated. The alveolar septa are relatively thin and still maintain some continuity, with only mild to focal thickening, indicating a significant reduction in interstitial edema and inflammatory response. No extensive consolidation changes were observed within the lung parenchyma, such as large areas of alveolar cavities filled with purulent exudate or numerous inflammatory cells. There was minimal exudate within the alveolar cavities, and no obvious mucus plugs or severe thickening of the alveolar walls. Overall, the morphological characteristics of these sections are consistent with bacterial pneumonia after treatment, where inflammation has significantly subsided, lung tissue structure has recovered well, and the disease is in the absorption and repair stage, indicating a relatively mild lesion. Figure 5 The images show lung sections from mice infected with Haemophilus influenzae. The alveolar structure is significantly damaged, with diffuse compaction of the lung parenchyma, significant shrinkage or even disappearance of alveolar cavities, and extensive filling with inflammatory cells and exudate, forming large areas of consolidation. The alveolar septa are significantly thickened, with interstitial edema and a marked increase in cellular components, indicating a strong acute inflammatory response. Purulent or cellular exudate accumulation within the alveolar cavities is visible in some areas, consistent with the morphological characteristics of purulent pneumonia. Overall, the condition presents as moderate to severe acute bacterial pneumonia, with a wide and deep inflammatory range and significantly reduced lung ventilation space. Figure 6 The images show lung sections from mice infected with Haemophilus influenzae three days after cephalosporin treatment. The images reveal that the alveolar structure is largely preserved, the alveolar cavities are relatively patent, and there is no evidence of extensive consolidation or complete filling of alveolar cavities with purulent exudate. However, compared to healthy controls, the pulmonary interstitium and alveolar septa are slightly thickened, with scattered inflammatory cell infiltration (mainly small round nucleated cells, interspersed with a small number of neutrophils / monocytes), suggesting that the inflammation has not completely subsided and there are still large areas of focal consolidation or complete filling of alveolar cavities with purulent exudate. Figure 7 The image shows lung sections of mice infected with Haemophilus influenzae 3 days after treatment with the fermented traditional Chinese medicine prepared in Example 1. As can be seen from the image, the treatment effect of the product of this invention is better than that of cephalosporin treatment. The alveolar structure is well preserved, and most of the alveolar cavities remain open with sufficient ventilation space. The morphological characteristics of this section are consistent with bacterial pneumonia after high-dose treatment, where inflammation is significantly relieved, the lung tissue structure is well restored, and the disease is in the stage of inflammation absorption and repair, indicating a mild lesion. Figure 8The images show lung sections from mice infected with Klebsiella pneumoniae. The images reveal significant acute purulent inflammatory changes: alveolar structures are still discernible in some areas, but alveolar septa are generally thickened, congested, and edematous. Numerous inflammatory cells infiltrate the interstitium and alveolar cavities, and some alveolar cavities are filled with inflammatory exudate, exhibiting focal consolidation. Red blood cell extravasation and protein-like exudate are visible in localized alveolar cavities, suggesting increased vascular permeability and tissue damage. The overall morphology is consistent with the pathological characteristics of purulent pneumonia caused by bacterial infection, with patchy inflammation accompanied by significant congestion, exudation, and reduced alveolar ventilation area. Figure 9 The lung sections of mice infected with Klebsiella pneumoniae were obtained 3 days after treatment with cephalosporins. The images show that there are many regular empty areas in the alveolar cavities, indicating that the ventilation spaces are still present. The alveolar septa are relatively thin, with only a few thickened areas. The septal cells are neatly arranged, almost close to the structure of normal lung tissue. Figure 10 The images show lung sections of mice infected with Klebsiella pneumoniae three days after treatment with the fermented traditional Chinese medicine prepared in Example 1. The results indicate that the treatment effect was essentially the same as that achieved with cephalosporin therapy. After treatment, the overall alveolar structure was well preserved, with most alveolar cavities remaining regular and open, and ventilation spaces significantly restored. The alveolar septa were mostly thin, with only focal mild thickening, and interstitial edema was not significant. Scattered inflammatory cell infiltration was still visible in the alveolar septa and a few alveolar cavities, but the area was small and the density low, without large-scale consolidation or large amounts of purulent exudate. Mild congestion and a small amount of erythrocyte extravasation were observed in some areas, and occasional mild perivascular inflammation was seen. Overall, the inflammatory response was significantly reduced after treatment with the invented product, and alveolar ventilation and tissue structure were close to normal, with only mild focal inflammatory changes remaining.

[0068] In summary, the efficacy of the drug prepared according to this invention and cephalosporins was compared in the treatment of mice infected with Streptococcus pneumoniae, Haemophilus influenzae, and Klebsiella pneumoniae. Specifically, for mice infected with Streptococcus pneumoniae and Klebsiella pneumoniae, the efficacy of the drug prepared according to this invention and cephalosporins was comparable. However, for mice infected with Haemophilus influenzae, the drug prepared according to this invention was superior to cephalosporins.

[0069] Comparative Example 1 In comparison, this comparative example differs from Example 1 in that it does not use yellow water for fermentation. The specific steps are as follows: A method for preparing a fermented traditional Chinese medicine product that regulates lung function specifically includes the following steps: (1) Pretreatment of Chinese medicine: 40g of peppermint, 120g of astragalus, 90g of wolfberry, 90g of mulberry bark, 90g of anemarrhena, 100g of arborvitae leaf, 120g of scrophularia, 40g of cimicifuga, 60g of sesame, 60g of angelica, 120g of lily, 80g of ginkgo, 60g of licorice, 40g of schisandra, 180g of eleutherococcus senticosus, 90g of ophiopogon japonicus, and 60g of dried ginger were mixed to obtain a mixture of Chinese medicine. The mixture of Chinese medicine was pulverized to 90 mesh, and 3600mL of purified water was added (total coarse powder mass 900g, 4 times the amount of water). The mixture was soaked at 28℃ for 5h, and stirred once every 2h to obtain the mixture of Chinese medicine.

[0070] (2) Co-cooking: Mix the Chinese medicine mixture with 1800g of sorghum (the mass ratio of Chinese medicine mixture to sorghum is 1:2), add 4860mL of purified water (the total mass of Chinese medicine mixture and sorghum is 2700g, 1.8 times the amount of water), cook at 115℃ for 55min, stirring once every 15min.

[0071] (3) Saccharification treatment: Cool down to 32℃, add 21.6g of compound koji (where the mass ratio of Aspergillus oryzae, Rhizopus and yeast is 7:2:2, the mass of cooked material is 2700g, the addition amount is 0.8%, and the viable count is 1.2×10⁻⁶). 8 (CFU / g), saccharified at 30℃ and 80% humidity for 42 hours, reducing sugar content 11.2g / 100g.

[0072] (4) Segmented fermentation: Transfer to a sterile fermentation tank, ferment at 28°C for 72 hours, then ferment at 22°C for 60 days, and collect the fermentation mash.

[0073] (5) Extraction and purification: Centrifuge the fermentation mash at 3500 r / min for 15 min, take the supernatant and add 10800 mL of purified water (the volume of the supernatant is about 2700 mL, 4 times the amount of water); combine the extracts and ultrafilter them with an 8000 Da ultrafiltration membrane at 0.25 MPa and 28℃, and collect the permeate.

[0074] (6) Post-treatment: Add 0.1% mogroside to the permeate and adjust the pH to 4.5. Sterilize at 121℃ for 18 minutes and aseptically fill to obtain the finished product.

[0075] Tests showed that the product has an alcohol content of 4.5%, an astragaloside A content of 0.65 mg / mL, a lily polysaccharide content of 6.78 mg / mL, and a wolfberry polysaccharide content of 3.4 mg / mL; it has a mellow and slightly sweet taste with a minty aroma and no bitterness; after 18 months of storage at room temperature, the product has a clarity of 98% and shows no signs of spoilage.

[0076] Comparative Example 2 In comparison, this comparative example differs from Example 1 in that sorghum is not used, and the specific steps are as follows: A method for preparing a fermented traditional Chinese medicine product that regulates lung function specifically includes the following steps: (1) Pretreatment of Chinese medicine: 40g of peppermint, 120g of astragalus, 90g of wolfberry, 90g of mulberry bark, 90g of anemarrhena, 100g of arborvitae leaf, 120g of scrophularia, 40g of cimicifuga, 60g of sesame, 60g of angelica, 120g of lily, 80g of ginkgo, 60g of licorice, 40g of schisandra, 180g of eleutherococcus senticosus, 90g of ophiopogon japonicus, and 60g of dried ginger were mixed to obtain a mixture of Chinese medicine. The mixture of Chinese medicine was pulverized to 90 mesh, and 3600mL of purified water was added (total coarse powder mass 900g, 4 times the amount of water). The mixture was soaked at 28℃ for 5h, and stirred once every 2h to obtain the mixture of Chinese medicine.

[0077] (2) Steaming: Steam the mixture of Chinese medicine at 115℃ for 55 minutes, stirring once every 15 minutes.

[0078] (3) Saccharification treatment: Cool down to 32℃, add 7.2g of compound koji (where the mass ratio of Aspergillus oryzae, Rhizopus and yeast is 7:2:3, the mass of cooked material is 900g, the addition amount is 0.8%, and the viable count is 1.2×10⁻⁶). 8 (CFU / g), saccharified at 30℃ and 80% humidity for 42 hours, reducing sugar content 11.2g / 100g.

[0079] (4) Segmented fermentation: Transfer to a sterile fermentation tank and ferment for 7 days at 28℃; add 9kg of yellow water (900g of saccharification mixture, 10 times the amount added, alcohol content 4.5%vol, pH 3.5, total acid 5.2g / L), ferment at 22℃ for 60 days, and collect the fermentation mash.

[0080] (5) Extraction and purification: Centrifuge the fermentation mash at 3500 r / min for 15 min, take the supernatant and add 36000 mL of purified water (the volume of the supernatant is about 9000 mL, 4 times the amount of water); combine the extracts and ultrafilter them with an 8000 Da ultrafiltration membrane at 0.25 MPa and 28℃, and collect the permeate.

[0081] (6) Post-treatment: add mogroside to the permeate and adjust the pH to 4.5. Sterilize at 121℃ for 18 minutes and aseptically fill to obtain the finished product.

[0082] Tests showed that the product has an alcohol content of 2.2%, an astragaloside A content of 0.33 mg / mL, a lily polysaccharide content of 3.44 mg / mL, and a wolfberry polysaccharide content of 2.55 mg / mL; it has a mellow and slightly sweet taste with a minty aroma and no bitterness; after 18 months of storage at room temperature, the product has a clarity of 98% and shows no signs of spoilage.

[0083] Comparative Example 3 This comparative example directly uses sorghum liquor to soak Chinese herbs. The specific steps are as follows: Mix 40g of peppermint, 120g of astragalus, 90g of wolfberry, 90g of mulberry bark, 90g of anemarrhena, 100g of arborvitae leaves, 120g of scrophularia, 40g of cimicifuga, 60g of sesame, 60g of angelica, 120g of lily, 80g of ginkgo, 60g of licorice, 40g of schisandra, 180g of eleutherococcus senticosus, 90g of ophiopogon japonicus, and 60g of dried ginger to obtain a Chinese herbal mixture. Grind the Chinese herbal mixture to 90 mesh, add 3600mL of pure 60-proof sorghum liquor, and soak at 28℃ for 4 weeks, stirring once a week to obtain the Chinese herbal sorghum liquor.

[0084] Tests showed that the product had an alcohol content of 48%, astragaloside A content of 0.60 mg / mL, lily polysaccharide content of 9.40 mg / mL, and wolfberry polysaccharide content of 4.20 mg / mL; it had a mellow and slightly sweet taste with a minty aroma and no bitterness; after 18 months of storage at room temperature, the product maintained 98% clarity and showed no signs of spoilage.

[0085] This invention innovatively combines a traditional Chinese medicine compound formula of 17 herbs, including peppermint, astragalus, goji berries, and lily bulbs, with a process of "sorghum co-fermentation and yellow water secondary fermentation," constructing an integrated preparation technology encompassing "pretreatment, co-cooking, saccharification, segmented fermentation, and purification." Through multi-dimensional compatibility of the compound herbs, synergistic effects are achieved. Utilizing the synergistic effect of sorghum and yellow water fermentation, the dissolution rate and bioavailability of active ingredients such as astragaloside A, lily polysaccharides, and goji berry polysaccharides are significantly improved. The 6-8% alcohol content, combined with the natural aromas of peppermint and euphorbia, promotes absorption and improves flavor, addressing a core pain point of traditional Chinese medicine products. The process enables the resource utilization of brewing yellow water, is low-cost, and easy to control. The product possesses both clear comprehensive lung function regulation effects and excellent flavor stability, making it suitable for large-scale industrial production and showing broad application prospects in the pharmaceutical and health product fields.

[0086] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a fermented traditional Chinese medicine product, characterized in that, Includes the following steps: (1) Pretreatment of Chinese medicine raw materials: Select peppermint, astragalus, wolfberry, mulberry bark, anemarrhena, arborvitae leaf, scrophularia, cimicifuga, sesame, angelica, lily, ginkgo, licorice, schisandra, eleutherococcus senticosus, ophiopogon japonicus and dried ginger without mold to obtain a Chinese medicine mixture. After crushing the Chinese medicine mixture, add water to soak it. At the same time, weigh sorghum for later use. (2) Co-cooking: Mix the pulverized and soaked Chinese herbal medicine mixture with sorghum, soak it in water to remove excess water, and steam the soaked Chinese herbal medicine mixture and sorghum to obtain the cooked material; (3) Saccharification treatment: Cool down the cooked material, add the compound yeast for brewing, stir and saccharify to obtain a saccharified mixture; (4) Primary fermentation: The saccharified mixture is sealed and fermented to obtain the primary fermentation mixture; (5) Secondary fermentation: After the primary fermentation is completed, add yellow water to the primary fermentation mixture and mix well before carrying out secondary fermentation. After the fermentation is completed, collect the fermentation mash. (6) Extraction and purification: Centrifuge and filter the fermentation mash, take the supernatant and add purified water, and combine the extracts; Ultrafiltration is performed using an ultrafiltration membrane, and the permeate is collected. (7) Post-processing: Add mogroside to the permeate to adjust the pH, sterilize, cool and aseptically fill to obtain the fermented Chinese medicine product that regulates lung function.

2. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: The ingredients and their weight parts in step (1) are as follows: 3-6 parts of peppermint, 10-15 parts of astragalus, 6-12 parts of wolfberry, 6-12 parts of mulberry bark, 6-12 parts of anemarrhena, 6-15 parts of arborvitae leaf, 9-15 parts of scrophularia, 3-6 parts of cimicifuga, 3-9 parts of elm, 3-10 parts of angelica, 10-15 parts of lily, 5-10 parts of ginkgo, 2-10 parts of licorice, 3-6 parts of schisandra, 9-27 parts of eleutherococcus senticosus, 6-12 parts of ophiopogon japonicus, and 3-10 parts of dried ginger.

3. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: In step (1), the mass ratio of the Chinese medicine mixture to sorghum is (1:2) to (4:5).

4. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: Step (1) Grind the Chinese herbal medicine mixture into 80-100 mesh coarse powder, add 2.5-5 times the total mass of the coarse powder in purified water, and soak for 4-6 hours.

5. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: In step (2), the steaming temperature is 105~120℃ and the steaming time is 40~70min. Stir once every 15min during the steaming process.

6. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: In step (3), the compound starter for brewing is a compound preparation made of Aspergillus oryzae, Rhizopus, and yeast, wherein the mass ratio of Aspergillus oryzae, Rhizopus, and yeast is (7~8):(1~2):(2~3), and the viable count is ≥10. 8 The amount of CFU / g added to the compound yeast for brewing is 0.5%~1.0% of the mass of the cooked materials.

7. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: The saccharification conditions in step (3) are saccharification at 28~32℃ and 75%~85% humidity for 36~48h.

8. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: Step (4) The initial fermentation conditions are fermentation at 25~30℃ for 72 hours.

9. The method for preparing a fermented traditional Chinese medicine product according to claim 1, characterized in that: The brewing yellow water mentioned in step (5) is a by-product of strong-aroma baijiu fermentation, with an alcohol content of 3%~6%, a pH value of 3.0~4.0, and a total acid content of ≥5.0g / L. The amount of brewing yellow water added is 10~12 times the mass of the primary fermentation mixture. The secondary fermentation conditions are 20~25℃ and fermentation time is 40~60 days.

10. The use of fermented traditional Chinese medicine prepared by the method according to any one of claims 1 to 9 in the preparation of drugs for treating pneumonia.

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