Traditional Chinese medicine composition for treating acute respiratory distress syndrome and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating acute respiratory distress syndrome and a preparation and a preparation method thereof, and the traditional Chinese medicine composition is prepared from the following raw materials: 12-30g of ginseng, 6-30 parts of rheum officinale, 9-30 parts of salvia miltiorrhiza and 3-15 parts of semen lepidii. Pharmacological experiments prove that the traditional Chinese medicine composition can improve lung inflammation infiltration to different degrees, improve lung tissue structure disorder and relieve pulmonary edema, and the clinical death rate is remarkably reduced in clinical application; the prepared preparation, especially granules, can be stored for 36 months for a long time, and is suitable for further industrial mass production.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for acute respiratory distress syndrome and its preparation method. Background Technology

[0002] Traditional Chinese medicine formulas or prepared medicines with the effects of "detoxification, blood stasis removal, tonification, and diuresis" have significant therapeutic effects. Zou Qiao et al. proposed that the Qi-invigorating, blood-activating, and detoxifying formula has a protective effect on LPS-induced ARDS model mice, which may be related to the regulation of the expression levels of Cav-1 protein and inflammatory factors IL-12 and IL-13, which can reduce inflammatory response and lung injury. Liu Yuan et al. applied the blood-activating and detoxifying method to treat sepsis ARDS, which was beneficial to inflammatory markers, pulmonary capillary permeability index and extravascular lung water index, and could also reduce the 28-day mortality rate in the experimental group. Xuebijing injection, a traditional Chinese medicine injection with the effect of blood-activating and detoxifying, helps to improve lung function in ARDS patients, reduce the body's inflammatory response, and improve patients' hemodynamic parameters. Huang Mei et al. found that Qingfei Huatan Decoction can improve patients' lung compliance, improve patients' lung ventilation function, shorten the time of mechanical ventilation and ICU hospitalization, and also reduce patients' serum N-terminal pro-B-type natriuretic peptide and procalcitonin (PCT) levels. Zhang Shina used Shengxian Decoction with added ingredients to treat patients with acute respiratory distress syndrome and lung and kidney qi deficiency, which can effectively improve patients' inflammation, oxygenation and other indicators, reduce patients' mechanical ventilation time, and effectively improve patients' clinical symptoms.

[0003] In Western medicine, the current treatment for ARDS mainly focuses on lung-protective ventilation strategies and restrictive fluid management. Lung-protective ventilation strategies typically involve using small tidal volumes, appropriately high PEEP, prone positioning ventilation, and, when necessary, the use of neuromuscular blocking agents.

[0004] Studies show that the prevalence of mild, moderate, and severe ARDS is 30.0%, 46.6%, and 23.4%, respectively; the in-hospital mortality rate is 34.9% for mild ARDS, 40.3% for moderate ARDS, and 46.1% for severe ARDS. ARDS accounts for 10% of ICU inpatients and 23% of mechanically ventilated patients. Despite some progress in lung-protective ventilation strategies and prone positioning ventilation, the mortality rate for severe ARDS remains as high as 45%. ARDS is also a common complication of severe pneumonia, requiring intensive care unit treatment, where the mortality rate can reach 30%–70%. Furthermore, decreased immunity and antibiotic overuse leading to an increase in drug-resistant strains further increase the risk of poor prognosis. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by providing a traditional Chinese medicine composition for acute respiratory distress syndrome, its preparation method, and its application. The self-formulated prescription, Shenhuang Xiefei Decoction, or granules, can effectively improve the respiratory index, reduce pulmonary edema, and inhibit cell apoptosis and the release of inflammatory factors.

[0006] Specifically, the technical solution of the present invention is as follows:

[0007] The traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 12-30 parts ginseng, 6-30 parts rhubarb, 9-30 parts salvia miltiorrhiza, and 3-15 parts lepidium seed.

[0008] Furthermore, the traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 12-30 parts ginseng, 6-30 parts rhubarb, 9-30 parts salvia miltiorrhiza, 3-15 parts lepidium seed, and 14-28 parts pharmaceutically acceptable excipients.

[0009] The traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 21 parts ginseng, 18 parts rhubarb, 20 parts salvia miltiorrhiza, 9 parts lepidium seed, and 21 parts pharmaceutically acceptable excipients.

[0010] The traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 12 parts ginseng, 6 parts rhubarb, 9 parts salvia miltiorrhiza, 3 parts lepidium seed, and 14 parts pharmaceutically acceptable excipients.

[0011] The traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 30 parts ginseng, 30 parts rhubarb, 30 parts salvia miltiorrhiza, 15 parts lepidium seed, and 28 parts pharmaceutically acceptable excipients.

[0012] The traditional Chinese medicine composition for acute respiratory distress syndrome is available in any one of the following dosage forms: decoction, granules, tablets, capsules, mixture, syrup, or pills. Preferably, the dosage form of the traditional Chinese medicine composition is granules.

[0013] The granules are made from the following raw materials in parts by weight: 21 parts ginseng, 18 parts rhubarb, 20 parts salvia miltiorrhiza, 9 parts lepidium seed, 5 parts mannitol, 5 parts polyethylene glycol 2000, 1.5 parts menthol, and 9.5 parts dextrin.

[0014] The preparation method of the granules is as follows:

[0015] Preparation of fine powder of Ginseng and Astragalus Lung-Clearing Extract

[0016] 1) Slice rhubarb and salvia miltiorrhiza and set aside; grind ginseng into a fine powder under vacuum and set aside;

[0017] 2) Extract ginseng powder by reflux twice with 10-20g of 70% ethanol, 1.5-3 hours each time, and combine the two filtrates for later use;

[0018] 3) Boil Lepidium seeds in water to extract volatile oil inclusion complexes. The volatile oil is then refined into inclusion complexes using β-cyclodextrin. The residue and aqueous solution are kept for later use.

[0019] 4) In step 3), the Chinese herbal medicine residue and aqueous solution are decocted twice with rhubarb and danshen, each time for 0.5-1 hour, and the two decoctions are mixed.

[0020] 5) Combine the filtrate from step 2) and the liquid obtained in step 4), filter, concentrate to a clear paste with a relative density of 1.03-1.07, add ethanol, let stand overnight, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.12-1.18 to obtain a thick paste, vacuum dry at a vacuum degree of -0.08 to -0.10 MPa and a drying temperature of 55-65℃, and pulverize under vacuum through an 80-mesh sieve to obtain a fine powder for later use;

[0021] 6) Mix the inclusion complexes obtained in steps 5) and 1) with those obtained in step 3) to obtain the fine powder of Ginseng and Astragalus Extract for Lung Cleansing.

[0022] Preparation of Ginseng and Rhubarb Lung-Clearing Granules:

[0023] 1) Dissolve mannitol in water, add polyethylene glycol 2000 and menthol, and set aside.

[0024] 2) Add the fine powder of Ginseng and Huanglian Xiefei extract and dextrin to step 1), stir evenly, perform wet granulation, then dry, pulverize, and sieve to obtain Ginseng and Huanglian Xiefei granules.

[0025] The traditional Chinese medicine composition for acute respiratory distress syndrome has a ratio of mannitol: polyethylene glycol 2000: menthol of 3-7: 2-4: 1-2; more preferably, it has a ratio of mannitol: polyethylene glycol 2000: menthol of 5: 3: 1.5.

[0026] The traditional Chinese medicine composition for acute respiratory distress syndrome has an ethanol content of 60-70% in step 5) (tanshinone is reduced, and low-purity degradation is not significant); more preferably, the ethanol content in step 5) is 65%.

[0027] Furthermore, the method for preparing the granules is as follows:

[0028] Preparation of fine powder of Ginseng and Astragalus Lung-Clearing Extract

[0029] 1) Slice rhubarb and salvia miltiorrhiza and set aside; grind ginseng into a fine powder under vacuum and set aside;

[0030] 2) Extract ginseng powder twice by reflux with 15% ethanol (by weight), 2 hours each time. Combine the two filtrates and set aside.

[0031] 3) Boil Lepidium seeds in water to extract volatile oil inclusion complexes. The volatile oil is then refined into inclusion complexes using β-cyclodextrin. The residue and aqueous solution are kept for later use.

[0032] 4) In step 3), the Chinese herbal medicine residue and aqueous solution are decocted twice with rhubarb and danshen, each time for 45 minutes, and the two decoctions are mixed.

[0033] 5) Combine the filtrate from step 2) and the liquid obtained in step 4), filter, concentrate to a clear paste with a relative density of 1.05, add 65% ethanol, let stand overnight, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.15 to obtain a thick paste, vacuum dry at a vacuum degree of -0.08 MPa and a drying temperature of 60°C, and pulverize under vacuum through an 80-mesh sieve to obtain a fine powder for later use;

[0034] 6) Mix the inclusion complexes obtained in steps 5) and 1) with those obtained in step 3) to obtain the fine powder of Ginseng and Astragalus Extract for Lung Cleansing.

[0035] Preparation of Ginseng and Rhubarb Lung-Clearing Granules:

[0036] 1) Dissolve mannitol in an appropriate amount of water, add polyethylene glycol 2000 and menthol, and set aside. The ratio of mannitol: polyethylene glycol 2000: menthol is 5:3:1.5.

[0037] 2) Add the fine powder of Ginseng and Huanglian Xiefei extract and dextrin to step 1), stir evenly, perform wet granulation, then dry, pulverize, and sieve to obtain Ginseng and Huanglian Xiefei granules.

[0038] The use of the aforementioned traditional Chinese medicine composition in the preparation of drugs for the prevention or treatment of acute respiratory distress syndrome.

[0039] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0040] 1) Ginseng, sweet, slightly bitter, and slightly warm in nature, enters the lung, spleen, heart, and kidney meridians. It is a powerful tonic for vital energy, strengthening the spleen and benefiting the lungs. Acute respiratory distress syndrome often involves insufficient vital energy, and the disease location is in the lungs. Ancient books record that ginseng can replenish lung qi, relieve asthma, and unblock the meridians, improving symptoms of shortness of breath and lung qi deficiency. For example, the "Diannan Materia Medica" states that it "treats yin and yang deficiency and lung qi weakness." Experimental studies have also found that ginseng can reduce inflammatory responses. Rhubarb, bitter and cold in nature, enters the spleen, stomach, large intestine, liver, and pericardium meridians. It has the functions of purging accumulations, clearing heat and purging fire, cooling blood and detoxifying, and removing blood stasis and unblocking the meridians. Its main component, emodin, has anti-inflammatory and antioxidant properties, thus reducing lung damage. Salvia miltiorrhiza, bitter and slightly cold in nature, enters the heart and liver meridians, and has the effect of promoting blood circulation and removing blood stasis. It can dilate blood vessels, improve microcirculation, and also has a certain diuretic effect, reducing edema. It has a positive inotropic effect on the heart, increasing oxygen supply to the body and improving cell function. Lepidium apetalum, pungent, bitter, and very cold in nature, enters the lung and bladder meridians, and has the effects of purging lung heat, relieving asthma, promoting diuresis, and reducing edema. It can reduce pulmonary capillary leakage, alleviate pulmonary edema, improve oxygenation, and effectively reduce mortality. Lepidium apetalum and rhubarb are frequently used in combination. Lepidium apetalum specifically purges lung heat and relieves asthma; when combined with rhubarb, it can also purge lung heat, relieve asthma, and clear heat from the bowels.

[0041] 2) Network pharmacology revealed that IL-17 is one of the key pathways for the treatment of ARDS with Shenhuang Xiefei Decoction. Western blot analysis showed that the protein expression levels of IL-17 in each group were significantly reduced compared with the model group. The protein expression levels in the dexamethasone group and each dose group of Shenhuang Xiefei Decoction were reduced to varying degrees, with the high-dose group showing the most significant reduction. RT-qPCR analysis showed that the Shenhuang Xiefei Decoction group had significant effects on the IL-17 index, with the high-dose group showing the lowest expression level and the best effect. Microscopic observation of HE-stained sections of mouse lung tissue showed that the lung structure of the control group mice was clear, the alveolar structure was normal, and no obvious inflammatory cell infiltration was observed. The normal structure of the lung tissue in the model group was destroyed, with obvious inflammatory cell infiltration, obvious inflammatory exudation, and obvious pulmonary edema. The inflammatory infiltration in the dexamethasone group and the low, medium, and high dose groups of Shenhuang Xiefei Decoction showed varying degrees of improvement, the disordered lung tissue structure was improved, and the pulmonary edema was reduced.

[0042] 3) The wet / dry ratio of lung tissue showed a significant difference between the blank group and the model group (P<0.0001), and the positive control group, namely the dexamethasone group and the low, medium and high dose groups of Shenhuang Xiefei Decoction, also showed a significant difference from the model group (P<0.0001). The wet / dry ratio of the Shenhuang Xiefei Decoction group was significantly lower than that of the model group, and the dose dependence was not high.

[0043] 4) Enzyme-linked immunosorbent assay (ELISA) showed that the effects of Shenhuang Xiefei Decoction on inflammatory markers TGF-β1, TNF-α, IL-1β, and the anti-inflammatory marker IL-10 were as follows: For the inflammatory marker TGF-β1, compared with the model group, the low-dose group (P < 0.01) and the medium-dose group (P < 0.01) showed significant differences, while the high-dose group showed no statistically significant difference. For the inflammatory marker TNF-α, the low-dose group (P < 0.001), the medium-dose group (P < 0.001), and the high-dose group (P < 0.0001) all showed statistically significant differences compared with the model group. Similarly, the inflammatory marker IL-1β and the anti-inflammatory marker IL-10 also showed statistically significant differences compared with the model group. The herbal composition of this invention has significant effects, providing a convenient, effective, and non-toxic drug for the clinical treatment of cold-dampness obstruction type low back pain, and has high practical value.

[0044] 5) The traditional Chinese medicine composition of the present invention is prepared into traditional Chinese medicine granules. In the present invention, different preparation processes are used for different traditional Chinese medicines to ensure the activity and content of the effective ingredients. The water content of the final granules is less than 1.0%. After long-term experiments, the liquid after dissolution is clear and there is no turbidity. Attached Figure Description

[0045] Figure 1 Results of HE staining of mouse lung tissue sections under a microscope. In the control group, the lung structure was clear, the alveolar structure was normal, and no obvious inflammatory cell infiltration was observed. In the model group, the normal lung structure was disrupted, with obvious inflammatory cell infiltration, significant inflammatory exudation, and obvious pulmonary edema. In the dexamethasone group and the low, medium, and high dose groups of Shenhuang Xiefei Decoction, varying degrees of improvement in inflammatory infiltration, improvement in lung tissue structural disorder, and reduction in pulmonary edema were observed.

[0046] Figure 2 The wet / dry ratio of mouse lung tissue showed a significant difference between the blank group and the model group (P < 0.0001), and the positive control group, namely the dexamethasone group and the low, medium and high dose groups of Shenhuang Xiefei Decoction, also showed significant differences between the positive control group and the model group (P < 0.0001). The wet / dry ratio of the Shenhuang Xiefei Decoction group was significantly lower than that of the model group, and the dose dependence was not high.

[0047] Figure 3 The results showed that the Shenhuang Xiefei Decoction had the following effects on the inflammatory markers TGF-β1, TNF-α, IL-1β, and the anti-inflammatory marker IL-10: Regarding the inflammatory marker TGF-β1...

[0048] 1. Compared with the model group, the low-dose group (P<0.01) and medium-dose group (P<0.01) showed significant differences, while the high-dose group showed no statistically significant difference. The inflammatory marker TNF-α showed statistically significant differences compared with the model group in the low-dose group (P<0.001), medium-dose group (P<0.001), and high-dose group (P<0.0001). The inflammatory marker IL-1β and the anti-inflammatory marker IL-10 also showed statistically significant differences compared with the model group.

[0049] Figure 4 Western blot analysis in mice. The results showed that, compared with the model group, the protein expression levels of IL-17 in the dexamethasone group and the various dose groups of Shenhuang Xiefei Decoction were reduced to varying degrees, with the highest dose group showing the most significant reduction (P < 0.01).

[0050] Figure 5 RT-qPCR analysis in mice. The results showed that for the indicator IL-17, all dose groups of Shenhuang Xiefei Decoction had significant effects, with the highest dose group showing the lowest expression level and the best effect (P < 0.0001). Detailed Implementation

[0051] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention.

[0052] Example 1: Preparation of fine powder from Ginseng and Astragalus Extract for Lung Cleansing

[0053] Ginseng 12 parts, rhubarb 6 parts, salvia miltiorrhiza 9 parts, lepidium seed 3 parts

[0054] 1) Slice rhubarb and salvia miltiorrhiza and set aside; grind ginseng into a fine powder under vacuum and set aside;

[0055] 2) Extract ginseng powder by reflux twice with 10% ethanol (by weight), 1.5 hours each time. Combine the two filtrates and set aside.

[0056] 3) Boil Lepidium seeds in water to extract volatile oil inclusion complexes. The volatile oil is then refined into inclusion complexes using β-cyclodextrin. The residue and aqueous solution are kept for later use.

[0057] 4) In step 3), the Chinese herbal medicine residue and aqueous solution are decocted twice with rhubarb and danshen, each time for 0.5 hours, and the two decoctions are mixed.

[0058] 5) Combine the filtrate from step 2) and the liquid obtained in step 4), filter, concentrate to a clear paste with a relative density of 1.03, add ethanol to make the ethanol content 60%, let stand overnight, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.12 to obtain a thick paste, vacuum dry at a vacuum degree of -0.08 MPa and a drying temperature of 55°C, and pulverize under vacuum through an 80-mesh sieve to obtain a fine powder for later use;

[0059] 6) Mix the inclusion complexes obtained in steps 5) and 1) with those obtained in step 3) to obtain the fine powder of Ginseng and Astragalus Extract for Lung Relief.

[0060] Example 2: Preparation of fine powder from Ginseng and Astragalus Extract for Lung Cleansing

[0061] 30 parts ginseng, 30 parts rhubarb, 30 parts salvia miltiorrhiza, 15 parts lepidium seed.

[0062] 1) Slice rhubarb and salvia miltiorrhiza and set aside; grind ginseng into a fine powder under vacuum and set aside;

[0063] 2) Extract ginseng powder by reflux twice with 20g of 70% ethanol for 3 hours each time, combine the two filtrates and set aside.

[0064] 3) Boil Lepidium seeds in water to extract volatile oil inclusion complexes. The volatile oil is then refined into inclusion complexes using β-cyclodextrin. The residue and aqueous solution are kept for later use.

[0065] 4) In step 3), the Chinese herbal medicine residue and aqueous solution are decocted twice with rhubarb and danshen, each time for 1 hour, and the two decoctions are mixed.

[0066] 5) Combine the filtrate from step 2) and the liquid obtained in step 4), filter, concentrate to a clear paste with a relative density of 1.07, add ethanol to make the ethanol content 70%, let stand overnight, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.12-1.18 to obtain a thick paste, vacuum dry at a vacuum degree of -0.10 MPa and a drying temperature of 65°C, and pulverize under vacuum through an 80-mesh sieve to obtain a fine powder for later use.

[0067] 6) Mix the inclusion complexes obtained in steps 5) and 1) with those obtained in step 3) to obtain the fine powder of Ginseng and Astragalus Extract for Lung Relief.

[0068] Example 3: Preparation of fine powder from Ginseng and Astragalus Extract for Lung Cleansing

[0069] Ginseng 21 parts, rhubarb 18 parts, salvia miltiorrhiza 20 parts, lepidium seed 9 parts

[0070] 1) Slice rhubarb and salvia miltiorrhiza and set aside; grind ginseng into a fine powder under vacuum and set aside;

[0071] 2) Extract ginseng powder twice by reflux with 15% ethanol (by weight), 2 hours each time. Combine the two filtrates and set aside.

[0072] 3) Boil Lepidium seeds in water to extract volatile oil inclusion complexes. The volatile oil is then refined into inclusion complexes using β-cyclodextrin. The residue and aqueous solution are kept for later use.

[0073] 4) In step 3), the Chinese herbal medicine residue and aqueous solution are decocted twice with rhubarb and danshen, each time for 45 minutes, and the two decoctions are mixed.

[0074] 5) Combine the filtrate from step 2) and the liquid obtained in step 4), filter, concentrate to a clear paste with a relative density of 1.05, add ethanol to make the ethanol content 65%, let stand overnight, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.15 to obtain a thick paste, vacuum dry at a vacuum degree of -0.09 MPa and a drying temperature of 60°C, and pulverize under vacuum through an 80-mesh sieve to obtain a fine powder for later use;

[0075] 6) Mix the inclusion complexes obtained in steps 5) and 1) with those obtained in step 3) to obtain the fine powder of Ginseng and Astragalus Extract for Lung Relief.

[0076] Example 4: Preparation of Ginseng and Astragalus Lung-Clearing Granules

[0077] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0078] 1) Dissolve mannitol in an appropriate amount of water, add polyethylene glycol 2000 and menthol, and prepare the mixture for later use. The weight ratio of mannitol: polyethylene glycol 2000: menthol is 3:2:1; (the weight-volume ratio of the three substances to water (in g / mL) is 1:3).

[0079] 2) Add the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin is 1:9) to the mixture in step 1), stir evenly, and then perform wet granulation. After drying, pulverizing, and sieving, the granules of Ginseng and Astragalus Extract for Lung Cleansing are obtained. The ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing to the mixed solution is 1:5 by mass-volume ratio.

[0080] Example 5: Preparation of Ginseng and Astragalus Lung-Clearing Granules

[0081] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0082] 1) Dissolve mannitol in an appropriate amount of water, add polyethylene glycol 2000 and menthol, and prepare the mixture for later use. The weight ratio of mannitol: polyethylene glycol 2000: menthol is 7:4:2 (the weight volume ratio of the three substances to water (in g / mL) is 1:3).

[0083] 2) Add the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin is 1:9) to the mixture in step 1), stir evenly, and then perform wet granulation. After drying, pulverizing, and sieving, the granules of Ginseng and Astragalus Extract for Lung Cleansing are obtained. The ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing to the mixed solution is 1:5 by mass-volume ratio.

[0084] Example 7: Preparation of Ginseng and Astragalus Lung-Clearing Granules

[0085] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0086] 1) Dissolve mannitol in an appropriate amount of water, add polyethylene glycol 2000 and menthol, and prepare the mixture for later use. The weight ratio of mannitol: polyethylene glycol 2000: menthol is 5:3:1.5 (the weight volume ratio of the three substances to water (in g / mL) is 1:3).

[0087] 2) Add the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin is 1:9) to the mixture in step 1), stir evenly, perform wet granulation, then dry, pulverize, and sieve to obtain Ginseng and Astragalus Extract for Lung Cleansing granules. The ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing to the mixed solution is 1:5, calculated by mass-volume ratio (g / mL).

[0088] Comparative Example 1: Preparation of fine powder from Ginseng and Astragalus Extract for Lung Purification

[0089] Ginseng 21 parts, rhubarb 18 parts, salvia miltiorrhiza 20 parts, lepidium seed 9 parts

[0090] 2) Extract ginseng powder by reflux twice with 15% ethanol by weight, each time for 1.5-3 hours. Combine the two filtrates and set aside.

[0091] The other steps are the same as described in Example 3.

[0092] Comparative Example 2: Preparation of Fine Powder of Ginseng and Astragalus Extract for Lung Purification

[0093] Ginseng 21 parts, rhubarb 18 parts, salvia miltiorrhiza 20 parts, lepidium seed 9 parts

[0094] The above-mentioned Chinese medicinal materials were decocted twice with water, each time for 0.5 hours, and the two decoctions were mixed. The mixture was filtered and concentrated to a clear extract with a relative density of 1.03-1.07. Ethanol was added to make the alcohol content 65%, and the mixture was allowed to stand overnight. The mixture was then filtered, and the ethanol was recovered under reduced pressure and concentrated to a relative density of 1.15 to obtain a thick extract. The extract was then vacuum dried at a vacuum degree of -0.09 MPa and a drying temperature of 60°C. The extract was then pulverized under vacuum and passed through an 80-mesh sieve to obtain a fine powder.

[0095] Comparative Example 3: Preparation of Ginseng and Codonopsis Lung-Clearing Granules

[0096] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0097] Add the fine powder of Ginseng and Astragalus Extract and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract to dextrin is 1:9), stir evenly, perform wet granulation, then dry, pulverize, and sieve to obtain Ginseng and Astragalus Extract granules.

[0098] Comparative Example 4: Preparation of Ginseng and Codonopsis Lung-Clearing Granules

[0099] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0100] The ingredients of ginseng and astragalus lung-clearing extract powder, mannitol, dextrin, menthol, and polyethylene glycol 2000 (the weight ratio of ginseng and astragalus lung-clearing extract powder to dextrin is 1:1:9:1:0.5) are mixed evenly and then wet-granulated. After drying, pulverizing, and sieving, ginseng and astragalus lung-clearing granules are obtained.

[0101] Comparative Example 5: Preparation of Ginseng and Astragalus Lung-Clearing Granules

[0102] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0103] 1) Dissolve mannitol in an appropriate amount of water, add polyethylene glycol 2000, and prepare the mixture for later use. The weight ratio of mannitol: polyethylene glycol 2000: menthol is 5:3 (the weight-volume ratio of the two substances to water (in g / mL) is 1:3).

[0104] 2) Add the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin is 1:9) to the mixture in step 1), stir evenly, and then perform wet granulation. After drying, pulverizing, and sieving, the granules of Ginseng and Astragalus Extract for Lung Cleansing are obtained. The ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing to the mixed solution is 1:5 by mass-volume ratio.

[0105] Comparative Example 6: Preparation of Ginseng and Codonopsis Lung-Clearing Granules

[0106] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0107] 1) Dissolve mannitol in an appropriate amount of water, add menthol, and prepare the mixture for later use. The weight ratio of mannitol: polyethylene glycol 2000: menthol is 5:1.5 (the weight-volume ratio of the two substances to water (in g / mL) is 1:3).

[0108] 2) Add the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin is 1:9) to the mixture in step 1), stir evenly, perform wet granulation, then dry, pulverize, and sieve to obtain Ginseng and Astragalus Extract for Lung Cleansing granules. The ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing to the mixed solution is 1:5, calculated by mass-volume ratio (g / mL).

[0109] Comparative Example 7: Preparation of Ginseng and Codonopsis Lung-Clearing Granules

[0110] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0111] 1) Dissolve mannitol in an appropriate amount of water, add polyethylene glycol 2000 and menthol, and prepare the mixture for later use. The weight ratio of mannitol: polyethylene glycol 2000: menthol is 2:5:3 (the weight volume ratio of the three substances to water (in g / mL) is 1:3).

[0112] 2) Add the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin is 1:9) to the mixture in step 1), stir evenly, and then perform wet granulation. After drying, pulverizing, and sieving, the granules of Ginseng and Astragalus Extract for Lung Cleansing are obtained. The ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing to the mixed solution is 1:5 by mass-volume ratio.

[0113] Comparative Example 8: Preparation of Ginseng and Codonopsis Lung-Clearing Granules

[0114] The fine powder of the ginseng and rhubarb lung-clearing extract prepared in Example 3.

[0115] 1) Dissolve sucrose in an appropriate amount of water, add calcium stearate and menthol, and prepare the mixture for later use. The weight ratio of mannitol: calcium stearate: menthol is 5:3:1.5 (the weight volume ratio of the three substances to water (in g / mL) is 1:3).

[0116] 2) Add the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin (the weight ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing and dextrin is 1:9) to the mixture in step 1), stir evenly, and then perform wet granulation. After drying, pulverizing, and sieving, the granules of Ginseng and Astragalus Extract for Lung Cleansing are obtained. The ratio of the fine powder of Ginseng and Astragalus Extract for Lung Cleansing to the mixed solution is 1:5 by mass-volume ratio.

[0117] Example 1: Therapeutic effect of the traditional Chinese medicine composition of the present invention

[0118] 1. Experimental Methods

[0119] Grouping and Model Establishment: Sixty BALB / c mice, weighing 18-22g, were provided with free access to food and water, and the room temperature was maintained at 20-25℃. After passing quarantine for 7 days, 10 mice were randomly selected as the blank control group (BL), and the remaining mice were used for model establishment. All animal experimental procedures were strictly performed in accordance with the principles of the Declaration of Helsinki under the approval of the Experimental Animal Committee of Tianjin Haihe Hospital. BALB / c mice were injected 6mg / kg of lipopolysaccharide (dissolved in 0.9% sodium chloride solution) into their nasal cavity. The mice were kept upright to allow the lipopolysaccharide to enter the lungs. After 24 hours, if the mice exhibited respiratory distress, wheezing, and significantly reduced lung function, the model was considered successfully established. The mice were randomly divided into a model group (DEX), a dexamethasone group (DEX), a low-dose group (SH-LD), a medium-dose group (SH-MD), and a high-dose group (SH-HD). The dexamethasone group was administered via gavage daily (5 mg / kg); the low-dose group received 5.157 g / kg, the medium-dose group received 10.313 g / kg, and the high-dose group received 15.47 g / kg; the model group and the control group received an equal volume of 0.9% saline solution, administered via gavage for 7 consecutive days. The low-dose, medium-dose, and high-dose decoctions were prepared according to the formula in Example 3 of this invention. The specific preparation method was as follows: rhubarb and salvia miltiorrhiza were sliced ​​and set aside; ginseng was ground into a fine powder under vacuum and set aside; ginseng, rhubarb, lepidium apetalum, and salvia miltiorrhiza seeds were decocted twice with water, 45 minutes each time, and the two decoctions were mixed to obtain the final product.

[0120] 2. Indicator Observation

[0121] 2.1 Pathological damage observation

[0122] Mouse lung tissue was fixed with 4% paraformaldehyde and embedded in paraffin. After sectioning, it was stained with hematoxylin-eosin (HE) and Masson's stain, and lung tissue damage was observed under a microscope at 400x magnification.

[0123] 2.2 Lung tissue wet / dry ratio

[0124] Take mouse lung tissue, remove water and some blood from the upper lobe of the right lung, weigh it and record it as wet weight; then dry it in a 60℃ constant temperature oven until constant weight, weigh it and record it as dry weight, and calculate the wet / dry weight ratio.

[0125] 2.3 Enzyme-linked immunosorbent assay (ELISA)

[0126] Serum IL-1β, IL-10, TNF-β1 and TNF-α levels were measured according to the kit instructions.

[0127] 2.4 Western Blot Analysis

[0128] To detect IL-17 protein expression in lung tissue using a horizontal method, total protein was extracted from lung tissue using RIPA reagent, and protein concentration was determined and quantified using a BCA kit. After gel preparation, sample loading, electrophoresis, membrane transfer, and membrane excision, protein bands were blocked with blocking buffer for 1 hour, incubated with primary and secondary antibodies, and then exposed to light for analysis of band grayscale values.

[0129] 2.5 RT-qPCR analysis

[0130] Lung tissue was collected and SparkZol reagent was added to extract total RNA. The RNA was then reverse transcribed into cDNA according to the reverse transcription kit instructions (primer sequences are shown in Table 1). Real-time quantitative PCR was then performed for detection. The relative mRNA expression level of the IL-17 gene was calculated using the 2-ΔΔCT method.

[0131] Table 1

[0132]

[0133] 3. Statistical Analysis

[0134] Data processing was performed using GraphpadPrism 7.0 software, and the measurement data was... This indicates that one-way ANOVA was used for comparisons among multiple groups, and pairwise comparisons between groups were performed using SNK-q, with P < 0.05 considered statistically significant.

[0135] 4. Results Analysis

[0136] 2.1 Results of HE staining of mouse lung tissue sections under a microscope

[0137] Figure 1 Results of HE staining of mouse lung tissue sections under a microscope. In the control group, the lung structure of mice was clear, the alveolar structure was normal, and no obvious inflammatory cell infiltration was observed. In the model group, the normal structure of the lung tissue was disrupted, with obvious inflammatory cell infiltration, significant inflammatory exudation, and obvious pulmonary edema. In the dexamethasone group and the low, medium, and high dose groups of Shenhuang Xiefei Decoction, varying degrees of improvement in inflammatory infiltration, improvement in lung tissue structural disorder, and reduction in pulmonary edema were observed.

[0138] 2.2 Wet / dry ratio of mouse lung tissue

[0139] Figure 2 It can be seen that the wet / dry ratio of mouse lung tissue was significantly different between the blank group and the model group (P<0.0001), and the positive control group, namely the dexamethasone group and the low, medium and high dose groups of Shenhuang Xiefei Decoction, were also significantly different from the model group (P<0.0001). The wet / dry ratio of the Shenhuang Xiefei Decoction group was significantly lower than that of the model group, and the dose dependence was not high.

[0140] 2.3 Mouse enzyme-linked immunosorbent assay (ELISA) detection

[0141] Figure 3 The results showed that the Shenhuang Xiefei Decoction had the following effects on the inflammatory markers TGF-β1, TNF-α, IL-1β, and the anti-inflammatory marker IL-10: Regarding the inflammatory marker TGF-β1...

[0142] 1. Compared with the model group, the low-dose group (P<0.01) and medium-dose group (P<0.01) showed significant differences, while the high-dose group showed no statistically significant difference. The inflammatory marker TNF-α showed statistically significant differences compared with the model group in the low-dose group (P<0.001), medium-dose group (P<0.001), and high-dose group (P<0.0001). The inflammatory marker IL-1β and the anti-inflammatory marker IL-10 also showed statistically significant differences compared with the model group.

[0143] 2.4 Mouse Western Blot Analysis

[0144] Figure 4 Western blot analysis in mice. The results showed that, compared with the model group, the protein expression levels of IL-17 in the dexamethasone group and the various dose groups of Shenhuang Xiefei Decoction were reduced to varying degrees, with the highest dose group showing the most significant reduction (P < 0.01).

[0145] 2.5 Mouse RT-qPCR Analysis

[0146] Figure 5 RT-qPCR analysis in mice. The results showed that for the indicator IL-17, all dose groups of Shenhuang Xiefei Decoction had significant effects, with the highest dose group showing the lowest expression level and the best effect (P < 0.0001).

[0147] Verification Example 2: Granule Quality Testing Method

[0148] Soluble particles: Take 10g of the test sample, add 200mL of hot water, stir for 5 minutes, and observe immediately. The soluble particles should dissolve completely or leave only slight turbidity.

[0149] Moisture content determination method: Determined according to General Chapter 0832 of the Chinese Pharmacopoeia 2025. Take 2-5 g of the test sample and spread it evenly in a flat weighing bottle dried to constant weight, with a thickness not exceeding 5 mm (10 mm for loose samples). Accurately weigh the sample. Open the bottle cap and dry at 100-105℃ for 5 hours. Close the cap, transfer the bottle to a desiccator, and cool for 30 minutes. Accurately weigh the sample again. Dry at the same temperature for another hour, cool, and weigh. Continue drying until the difference between two consecutive weighings does not exceed 5 mg. Calculate the moisture content (%) of the test sample based on the weight loss.

[0150] Long-term testing: Place the product at a temperature of 25℃±2℃ and a relative humidity of 60%±10% for 36 months, and then conduct performance testing.

[0151] Table 2. Granule quality testing methods from different embodiments.

[0152]

[0153] Table 3 Tanshinone IIA and Tanshinone B in different examples

[0154]

[0155] Verification Example 3: Detection of Tanshinone and Tanshinone B in Granules

[0156] [Content Determination] Tanshinones were determined by high performance liquid chromatography (General Rule 0512).

[0157] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; acetonitrile was used as mobile phase A, and 0.02% phosphoric acid solution was used as mobile phase B, with gradient elution performed according to the specifications in the table below; the column temperature was 20℃; and the detection wavelength was 270nm. See Table 3 for details.

[0158] Table 3

[0159]

[0160] Preparation of reference solution: Take an appropriate amount of tanshinone IIIA reference standard, accurately weigh it, place it in a brown volumetric flask, and add methanol to prepare a solution containing 20 μg per 1 mL.

[0161] Preparation of the test solution: Accurately weigh approximately 0.3 g of the powder (passed through a No. 3 sieve), place it in a stoppered conical flask, accurately add 50 mL of methanol, seal tightly, weigh, sonicate (140 W, 42 kHz) for 30 minutes, cool, weigh again, replenish the lost weight with methanol, shake well, filter, and collect the filtrate. Assay: Accurately inject 10 μl each of the reference solution and the test solution into the liquid chromatograph for determination.

[0162] Using tanshinone IIA as a reference and its corresponding peak as the S peak, calculate the relative retention times of cryptotanshinone and tanshinone I. The relative retention times should be within ±5% of the specified value. The relative retention times and correction factors are shown in Table 4 below.

[0163] Table 4

[0164]

[0165] Using the peak area of ​​tanshinone IIA as a control, the contents of cryptotanshinone, tanshinone I, and tanshinone IIA were calculated by multiplying by a correction factor.

[0166] Tanshinone B was determined by high performance liquid chromatography (General Rule 0512).

[0167] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; acetonitrile-0.1% phosphoric acid solution (22:78) was used as the mobile phase; the column temperature was 20℃; the flow rate was 1.2 mL per minute; and the detection wavelength was 286 nm.

[0168] Preparation of reference solution: Take an appropriate amount of salvianolic acid B reference standard, accurately weigh it, and add it to a methanol-water (8:2) mixed solution to prepare a solution containing 0.10 mg per 1 mL.

[0169] Preparation of the test solution: Accurately weigh approximately 0.15 g of the powder (passed through a No. 3 sieve), place it in a stoppered conical flask, accurately add 50 mL of a methanol-water (8:2) mixture, seal tightly, weigh, sonicate (140 W, 42 kHz) for 30 minutes, cool, weigh again, replenish the lost weight with the methanol-water (8:2) mixture, shake well, filter, accurately measure 5 mL of the filtrate, transfer to a 10 mL volumetric flask, dilute to the mark with the methanol-water (8:2) mixture, shake well, filter, and collect the filtrate. The present invention has been described in detail above with general descriptions and specific embodiments. However, modifications or improvements can be made to the present invention, which are obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A traditional Chinese medicine composition for acute respiratory distress syndrome, characterized in that, The traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 12-30 parts ginseng, 6-30 parts rhubarb, 9-30 parts salvia miltiorrhiza, and 3-15 parts lepidium seed.

2. The traditional Chinese medicine composition for acute respiratory distress syndrome according to claim 1, characterized in that, The aforementioned combination of traditional Chinese medicines and pharmaceutically acceptable excipients are used to prepare a formulation.

3. The traditional Chinese medicine composition for acute respiratory distress syndrome according to claim 2, characterized in that, The traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 12-30 parts ginseng, 6-30 parts rhubarb, 9-30 parts salvia miltiorrhiza, 3-15 parts lepidium seed, and 14-28 parts pharmaceutically acceptable excipients.

4. The traditional Chinese medicine composition for acute respiratory distress syndrome according to claim 3, characterized in that, The traditional Chinese medicine composition for acute respiratory distress syndrome is made from the following raw materials in parts by weight: 30 parts ginseng, 30 parts rhubarb, 30 parts salvia miltiorrhiza, 15 parts lepidium seed and 28 parts pharmaceutically acceptable excipients; or 12 parts ginseng, 6 parts rhubarb, 9 parts salvia miltiorrhiza, 3 parts lepidium seed and 14 parts pharmaceutically acceptable excipients; or 21 parts ginseng, 18 parts rhubarb, 20 parts salvia miltiorrhiza, 9 parts lepidium seed and 21 parts pharmaceutically acceptable excipients.

5. The traditional Chinese medicine composition for acute respiratory distress syndrome according to any one of claims 1-4, characterized in that, The dosage form of the traditional Chinese medicine composition is any one of decoction, granules, tablets, capsules, mixture, syrup or pills, preferably, the dosage form of the traditional Chinese medicine composition is granules.

6. The traditional Chinese medicine composition for acute respiratory distress syndrome according to claim 5, characterized in that, The granules are made from the following raw materials in parts by weight: 21 parts ginseng, 18 parts rhubarb, 20 parts salvia miltiorrhiza, 9 parts lepidium seed, 5 parts mannitol, 5 parts polyethylene glycol 2000, 1.5 parts menthol and 9.5 parts dextrin.

7. The traditional Chinese medicine composition for acute respiratory distress syndrome according to claim 5, characterized in that, The preparation method of the granules is as follows: Preparation of fine powder of Ginseng and Astragalus Lung-Clearing Extract 1) Slice rhubarb and salvia miltiorrhiza and set aside; grind ginseng into a fine powder under vacuum and set aside; 2) Extract ginseng powder twice by reflux with 10-20g of 70% ethanol, 1.5-3 hours each time, and combine the two filtrates for later use; 3) Boil Lepidium seeds in water to extract volatile oil inclusion complexes. The volatile oil is then refined into inclusion complexes using β-cyclodextrin. The residue and aqueous solution are kept for later use. 4) In step 3), the Chinese herbal medicine residue and aqueous solution are decocted twice with rhubarb and danshen, each time for 0.5-1 hour, and the two decoctions are mixed. 5) Combine the filtrate from step 2) and the liquid obtained in step 4), filter, concentrate to a clear paste with a relative density of 1.03-1.07, add ethanol, let stand overnight, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.12-1.18 to obtain a thick paste, vacuum dry at a vacuum degree of -0.08~-0.10 MPa and a drying temperature of 55-65℃, and pulverize under vacuum through an 80-mesh sieve to obtain a fine powder for later use; 6) Mix the inclusion complexes obtained in steps 5) and 1) with those obtained in step 3) to obtain the fine powder of Ginseng and Astragalus Extract for Lung Cleansing; Preparation of Ginseng and Rhubarb Lung-Clearing Granules: 1) Dissolve mannitol in water, add polyethylene glycol 2000 and menthol, and set aside. 2) Add the fine powder of Ginseng and Huanglian Xiefei extract and dextrin to step 1), stir evenly, perform wet granulation, then dry, pulverize, and sieve to obtain Ginseng and Huanglian Xiefei granules.

8. The traditional Chinese medicine composition for acute respiratory distress syndrome according to claim 5, characterized in that, Mannitol: polyethylene glycol 2000: menthol = 3-7: 2-4: 1-2; more preferably, mannitol: polyethylene glycol 2000: menthol = 5: 3: 1.5; the ethanol content of step 5) is 60-70%; more preferably, the ethanol content of step 5) is 65%.

9. The traditional Chinese medicine composition for acute respiratory distress syndrome according to claim 5, characterized in that, The preparation method of the granules is as follows: Preparation of fine powder of Ginseng and Astragalus Lung-Clearing Extract 1) Slice rhubarb and salvia miltiorrhiza and set aside; grind ginseng into a fine powder under vacuum and set aside; 2) Extract ginseng powder by reflux twice with 15% ethanol (by weight), 2 hours each time. Combine the two filtrates and set aside. 3) Boil Lepidium seeds in water to extract volatile oil inclusion complexes. The volatile oil is then refined into inclusion complexes using β-cyclodextrin. The residue and aqueous solution are kept for later use. 4) In step 3), the Chinese herbal medicine residue and aqueous solution are decocted twice with rhubarb and danshen, each time for 45 minutes, and the two decoctions are mixed. 5) Combine the filtrate from step 2) and the liquid obtained in step 4), filter, concentrate to a clear paste with a relative density of 1.05, add 65% ethanol, let stand overnight, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.15 to obtain a thick paste, vacuum dry at a vacuum degree of -0.08 MPa and a drying temperature of 60°C, and pulverize under vacuum through an 80-mesh sieve to obtain a fine powder for later use; 6) Mix the inclusion complexes obtained in steps 5) and 1) with those obtained in step 3) to obtain the fine powder of Ginseng and Astragalus Extract for Lung Cleansing; Preparation of Ginseng and Rhubarb Lung-Clearing Granules: 1) Dissolve mannitol in an appropriate amount of water, add polyethylene glycol 2000 and menthol, and set aside. The ratio of mannitol: polyethylene glycol 2000: menthol is 5:3:1.

5. 2) Add the fine powder of Ginseng and Huanglian Xiefei extract and dextrin to step 1), stir evenly, perform wet granulation, then dry, pulverize, and sieve to obtain Ginseng and Huanglian Xiefei granules.

10. Use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for the prevention or treatment of acute respiratory distress syndrome.

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