Pharmaceutical composition for acute respiratory distress syndrome as well as preparation method and application of pharmaceutical composition

Abstract

The invention discloses a pharmaceutical composition for treating acute respiratory distress syndrome caused by pathogenic heat, turbid phlegm, blood stasis in lung and obstruction of viscera, which comprises an oral traditional Chinese medicine composition I and an enema traditional Chinese medicine composition II, the traditional Chinese medicine composition I comprises 8-30 parts by weight of American ginseng, 7-26 parts by weight of radix curcumae, 8-30 parts by weight of angelica sinensis, 10-40 parts by weight of gypsum, 8-30 parts by weight of thunberg fritillary bulb, 5-20 parts by weight of almond, 8-30 parts by weight of white mulberry root-bark, 5-20 parts by weight of rheum officinale, 5-20 parts by weight of mirabilite, 5-20 parts by weight of immature bitter orange and 5-20 parts by weight of mangnolia officinalis; the traditional Chinese medicine composition II comprises 8-30 parts by weight of Chinese angelica, 5-20 parts by weight of peach kernel, 8-30 parts by weight of thunberg fritillary bulb, 8-30 parts by weight of radish seed, 7-26 parts by weight of rheum officinale, 5-20 parts by weight of mirabilite, 5-20 parts by weight of immature bitter orange and 5-20 parts by weight of mangnolia officinalis. The invention also provides medical application of the pharmaceutical composition.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This patent application claims the priority benefit of the Chinese invention patent application with application number CN202311089155.2 filed on August 28, 2023, the entire contents of which are hereby incorporated by reference. Technical Field

[0003] The invention belongs to the field of traditional Chinese medicine, and specifically relates to a pharmaceutical composition for acute respiratory distress syndrome and a preparation method and application thereof. Background Art

[0004] Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse inflammatory alveolar and pulmonary capillary damage and rapid onset of hypoxemia. It is one of the most common clinical syndromes in critically ill patients with a high mortality rate. It has been nearly 60 years since ARDS was first proposed in 1967. Although the understanding of ARDS has been continuously deepened, the diagnosis and treatment of ARDS patients in the clinic have always faced huge challenges and almost reached a bottleneck due to the different causes, genetic backgrounds, and different inflammatory and immune response mechanisms of ARDS patients.

[0005] In recent years, with the substantial increase in the number of influenza cases and the widespread infection of new respiratory viruses, the number of patients with the disease outcome pattern of "lung infection-severe pneumonia-ARDS" has also been increasing year by year. Such patients often have high fever, cough, asthma, dyspnea, and bluish lips. In clinical practice, Chinese medicine compositions that clear away heat and detoxify, resolve phlegm and remove dampness are often used. For example, the Chinese invention patent with publication number CN101564459A (publication date October 28, 2009) discloses a Chinese medicine composition for treating upper respiratory tract infection, which is composed of Forsythia suspensa, honeysuckle, Radix Isatidis, Rhubarb, Patchouli, Rhizoma Cyrthospermi, Rhodiola rosea, Ephedra, Apricot kernel, Houttuynia cordata, Licorice, Gypsum, etc. Another example is the PCT patent application with publication number WO2021 / 179828A1 (published on September 16, 2021), which discloses a pharmaceutical composition for treating acute lung injury, which is made of ephedra, gypsum, forsythia, scutellaria, mulberry bark, bitter almond, peucedanum, pinellia, tangerine peel, fritillaria, burdock fruit, honeysuckle, rhubarb, platycodon and licorice. Although many similar Chinese medicine compositions have appeared in the prior art, ARDS still seriously threatens people's lives and safety, and its treatment needs are far from being met. Summary of the invention

[0006] In view of the deficiencies of the prior art, the present invention provides a pharmaceutical composition mainly used for treating acute respiratory distress syndrome with phlegm and blood stasis, as well as a preparation method and medical use thereof. The pharmaceutical composition is particularly suitable for acute respiratory distress syndrome in which pathogenic heat, phlegm, blood stasis in the lungs, obstruction of visceral qi, cough, wheezing, dyspnea, bluish lips, constipation, etc. are the main symptoms after bacterial or viral infection of the lungs, but in fact, the vital energy has been damaged. The pharmaceutical composition provided by the present invention focuses on strengthening the vital energy and eliminating the pathogenic heat, treating both the symptoms and the root cause, and can effectively cut off the further development of the pathogenic heat in the lungs and promote recovery from the disease.

[0007] In order to achieve the above technical effects, the present invention adopts the following technical solutions:

[0008] A pharmaceutical composition for acute respiratory distress syndrome characterized by pathogenic heat, phlegm, turbidity, blood stasis in the lungs and obstruction of internal qi, comprising an oral Chinese medicine composition I; the Chinese medicine composition I comprises the following medicinal materials in parts by weight:

[0009] 8-30 parts by weight of American ginseng, 7-26 parts by weight of turmeric, 8-30 parts by weight of angelica, 10-40 parts by weight of gypsum, 8-30 parts by weight of Fritillaria thunbergii, 5-20 parts by weight of apricot kernel, 8-30 parts by weight of mulberry bark, 5-20 parts by weight of rhubarb, 5-20 parts by weight of sodium sulfate, 5-20 parts by weight of immature bitter orange, and 5-20 parts by weight of Magnolia officinalis.

[0010] Preferably, the Chinese medicine composition I comprises the following medicinal materials in parts by weight:

[0011] 10-20 parts by weight of American ginseng, 9-20 parts by weight of turmeric, 10-20 parts by weight of angelica, 15-30 parts by weight of gypsum, 10-20 parts by weight of Fritillaria thunbergii, 8-15 parts by weight of apricot kernel, 10-20 parts by weight of mulberry bark, 8-15 parts by weight of rhubarb, 8-15 parts by weight of sodium sulfate, 8-15 parts by weight of immature bitter orange, and 8-15 parts by weight of Magnolia officinalis.

[0012] More preferably, the weight portions of American ginseng and Chinese angelica are the same.

[0013] More preferably, the weight portions of rhubarb, sodium sulfate, immature bitter orange and magnolia bark are the same.

[0014] As a preferred embodiment, the present invention provides an oral Chinese medicine composition I for acute respiratory distress syndrome with pathogenic heat, phlegm, blood stasis in the lungs and obstruction of internal organs, comprising the following medicinal materials in parts by weight:

[0015] 15 parts by weight of American ginseng, 13 parts by weight of turmeric, 15 parts by weight of angelica, 20 parts by weight of gypsum, 15 parts by weight of thunbergii bulbs, 10 parts by weight of apricot kernels, 15 parts by weight of mulberry bark, 10 parts by weight of rhubarb, 10 parts by weight of sodium sulfate, 10 parts by weight of immature bitter orange, and 10 parts by weight of Magnolia officinalis.

[0016] The above-mentioned pharmaceutical composition for acute respiratory distress syndrome with pathogenic heat, phlegm, blood stasis in the lungs and obstruction of internal organs also includes a Chinese medicine composition II for enema; the Chinese medicine composition II includes the following medicinal materials in parts by weight:

[0017] 8-30 parts by weight of angelica sinensis, 5-20 parts by weight of peach kernel, 8-30 parts by weight of thunbergia thunbergii, 8-30 parts by weight of radish seeds, 7-26 parts by weight of rhubarb, 5-20 parts by weight of sodium sulfate, 5-20 parts by weight of immature bitter orange, and 5-20 parts by weight of magnolia bark.

[0018] Preferably, the Chinese medicine composition II comprises the following medicinal materials in parts by weight:

[0019] 10-20 parts by weight of angelica sinensis, 8-15 parts by weight of peach kernel, 10-20 parts by weight of Fritillaria thunbergii, 10-20 parts by weight of radish seeds, 9-20 parts by weight of rhubarb, 8-15 parts by weight of sodium sulfate, 8-15 parts by weight of immature bitter orange, and 8-15 parts by weight of Magnolia officinalis.

[0020] Also preferably, the weight portions of the Glauber's Salt, Fructus Aurantii Immaturus and Cortex Magnoliae Officinalis are the same.

[0021] As a preferred embodiment, the present invention provides a Chinese medicine composition II for enema for acute respiratory distress syndrome with pathogenic heat, phlegm, blood stasis in the lungs and obstruction of internal organs, comprising the following medicinal materials in parts by weight:

[0022] 15 parts by weight of Chinese angelica, 10 parts by weight of peach kernel, 15 parts by weight of thunbergii bulb, 15 parts by weight of radish seed, 13 parts by weight of rhubarb, 10 parts by weight of sodium sulfate, 10 parts by weight of immature bitter orange, and 10 parts by weight of magnolia bark.

[0023] Preferably, in the Chinese medicine composition I and the Chinese medicine composition II, the rhubarb is selected from raw rhubarb, wine rhubarb or cooked rhubarb.

[0024] In the above Chinese medicine composition I and Chinese medicine composition II, the selection of rhubarb is determined according to the patient's condition. If the patient has been ill for a long time and his vital energy is weak, wine rhubarb or cooked rhubarb with slow laxative effect can be used; otherwise, raw rhubarb can be used.

[0025] The present invention also provides a medicine; the medicine is a clinically acceptable preparation made from the above-mentioned pharmaceutical composition and pharmaceutically acceptable auxiliary materials.

[0026] Preferably, the above-mentioned pharmaceutical composition further comprises pharmaceutically acceptable excipients.

[0027] The pharmaceutically acceptable excipients of the present invention are selected from (1) solvents, such as distilled water, ethanol, etc.; (2) diluents, such as starch, powdered sugar, dextrin, lactose, pregelatinized starch, microcrystalline cellulose, inorganic calcium salts (such as calcium sulfate, calcium hydrogen phosphate, medicinal calcium carbonate, etc.), mannitol, etc., vegetable oils, polyethylene glycol, etc.; (3) binders, such as distilled water, ethanol, starch slurry, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose and ethyl cellulose, hydroxypropyl methylcellulose, etc.; (4) disintegrants, such as dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, etc.; or (5) lubricants, such as magnesium stearate, micropowdered silica gel, talc, hydrogenated vegetable oil, polyethylene glycols, magnesium lauryl sulfate, etc.

[0028] Preferably, the drug comprises at least item 1) of the following two items:

[0029] 1) An oral preparation prepared from the Chinese medicine composition I, wherein the Chinese medicine composition I is as defined above;

[0030] 2) An enema prepared from the Chinese medicine composition II, wherein the Chinese medicine composition II is as defined above.

[0031] Another object of the present invention is to provide a method for preparing the drug, comprising preparing the traditional Chinese medicine composition I into an oral preparation.

[0032] Preferably, the oral preparation is a decoction, and the preparation method comprises the following steps:

[0033] A. preparing the medicinal materials according to the composition of the aforementioned Chinese medicine composition I;

[0034] B. decoct American ginseng with water to obtain American ginseng decoction; set aside;

[0035] C. decocting turmeric, angelica, gypsum, fritillaria thunbergii, apricot kernel, mulberry bark, immature bitter orange, magnolia bark and rhubarb twice with water, wherein gypsum is decocted first and rhubarb is added later, and the filtrates are combined to obtain a decoction of medicinal materials;

[0036] D. Combine the American ginseng decoction and the medicinal material decoction, mix them evenly, divide them into several portions, and concentrate them if necessary; divide the mirabilite into the same number of portions, and take 1 portion of mirabilite and 1 portion of the medicinal material decoction at the same time.

[0037] Preferably, the preparation method further comprises preparing the Chinese medicine composition II into an enema.

[0038] Preferably, the method for preparing the enema comprises the following steps:

[0039] (1) preparing various medicinal materials according to the composition of the Chinese medicine composition II;

[0040] (2) Decoction each herbal medicine except for Glauber's salt twice with water, with rhubarb added last, and combine the filtrates to obtain a herbal medicine decoction, which can be concentrated if necessary;

[0041] (3) Add Glauber's salt to every 400 ml of the medicinal material decoction, and stir until the Glauber's salt is dissolved.

[0042] When the above-mentioned Chinese medicine composition I is prepared as a decoction, and when the Chinese medicine composition II is prepared as an enema, those skilled in the art can determine the amount of water and the decoction time for decocting the medicinal materials according to the dosage and usage and the routine of the art. Generally, 2-10 times the total weight of the medicinal materials are added each time, and after boiling over high heat, decocting is continued over low heat for 20 minutes to 1 hour; preferably, before decocting after adding water, the medicinal materials are soaked for 20 minutes to 1 hour. The "gypsum first decoction" means that the gypsum is first decocted with water alone for 20-30 minutes, and then other medicinal materials (except the medicinal materials added later) are added and decocted together. The "rhubarb added later" means that rhubarb is added 5-6 minutes before the end of decoction and boiled together with other medicinal materials.

[0043] As an optional embodiment, the preparation method may also include preparing the oral preparation and / or enema using Chinese medicine formula granules, comprising the following steps:

[0044] A. taking a corresponding amount of Chinese medicine formula granules according to the composition of the Chinese medicine composition I or the Chinese medicine composition II;

[0045] B. Mix the Chinese medicine granules, add appropriate amount of water, and stir until completely dissolved.

[0046] In addition, another object of the present invention is to provide the use of the above-mentioned pharmaceutical composition, the above-mentioned drug, or the drug directly obtained according to the above-mentioned preparation method in the preparation of a drug for treating acute respiratory distress syndrome caused by pathogenic heat, phlegm, blood stasis in the lungs and obstruction of visceral qi, with symptoms such as cough and asthma, difficulty breathing, blue lips and constipation.

[0047] Preferably, the acute respiratory distress syndrome of pathogenic heat, phlegm, turbidity and blood stasis in the lungs and obstruction of visceral qi also includes fever.

[0048] Preferably, the oral preparation prepared from Chinese medicine composition I is first administered to a subject in need; if no stool is discharged or the above symptoms are not relieved within 1-2 days, an enema prepared from Chinese medicine composition II is added, and enema is performed every other day until stool is discharged or the above symptoms are relieved.

[0049] The above-mentioned medicine for treating acute respiratory distress syndrome with pathogenic heat, phlegm, blood stasis in the lungs and obstruction of visceral qi, and the subjects of administration are preferably humans. When administered to a person in need, the daily dosage of the Chinese medicine composition I is converted into the total weight of all medicinal materials, which is 74-286g, preferably 104-205g, and more preferably 143g; when the condition is critical, four times a day, frequent nasogastric feeding or oral administration; when the condition is stable, twice a day, nasogastric feeding or oral administration. When administered to a person in need, the daily dosage of the Chinese medicine composition II is converted into the total weight of all medicinal materials, which is 51-190g, preferably 71-140g, and more preferably 98g, once every other day, by enema.

[0050] Lung infection caused by bacteria or viruses activates multiple inflammatory and immune responses, and the lung qi is not in good condition. The lung's main function of spreading and descending is disordered, causing poor circulation of body fluid and blood, and the accumulation of body fluid into phlegm, which further hinders the circulation of qi and blood, and blood stagnation. Phlegm and blood stasis in the lungs, which become heat over time, and then form pathogenic heat, phlegm, and blood stasis in the lungs. The lungs and large intestine are exterior and interior, and the lung qi cannot spread and descend, which affects the large intestine's transmission of waste downward and causes constipation and obstruction of visceral qi, which in turn affects the function of spreading and descending of lung qi, and aggravates the accumulation of pathogenic heat, phlegm, and blood stasis in the lungs. "Where evil gathers, its qi must be weak." As lung disease lasts for a long time, it further depletes the body's positive qi. At this time, although the patient's condition is critical and mainly manifested as a positive syndrome, in fact, the positive qi has been damaged. If the qi is not replenished and the positive qi is not strengthened in time, the pathogenic evil will quickly enter the body, causing the condition to worsen, and hypoxemia is difficult to correct, causing the patient to fall into a critical state. Therefore, the pharmaceutical composition of the present invention is based on the principle of invigorating qi and strengthening the body, and treating phlegm and blood stasis at the same time, and provides a Chinese medicine composition I for oral administration and a Chinese medicine composition II for enema that matches it. In the Chinese medicine composition I, American ginseng and Chinese angelica are used to invigorate qi, nourish blood and strengthen the body, gypsum, curcuma, Fritillaria thunbergii, apricot, and white mulberry bark are used to clear away heat and resolve phlegm, regulate qi and relieve cough, and rhubarb, sodium sulfate, immature bitter orange and magnolia bark are used to clear the bowels and relieve heat, wherein Chinese angelica, curcuma, and rhubarb are used to promote blood circulation, remove blood stasis and dredge collaterals, and all medicines are used together to strengthen the body and eliminate evil, treat both the symptoms and the root causes, and promote recovery from the disease. If after administering the above-mentioned Chinese medicine composition I, it is still seen that the intestinal qi is blocked and the stool is constipated, the Chinese medicine composition II is added to nourish blood and moisten the intestines, remove phlegm and blood stasis, and clear the intestinal qi, and enema is performed every other day until the stool is discharged and the intestinal qi is unobstructed, then it is discontinued.

[0051] The weight parts of each medicinal material described in this specification represent the relative dosage ratio between the medicinal materials, rather than the actual weight of the medicinal materials. According to the actual application scenario, 1 weight part can be any weight such as 1g, 50g, 100g, 500g, 1kg, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] The present invention is further described below in conjunction with the accompanying drawings.

[0053] Figure 1The bar graph shows the survival rate of mouse alveolar macrophages MH-S treated with different drugs for 48 hours in Experimental Example 1, wherein the abscissa is the drug concentration and the ordinate is the absorbance value of the cell culture fluid at 450nm. In the figure, *P<0.05, **P<0.01, vs. blank control group (drug concentration 0mg / ml group).

[0054] Figure 2 The bar graph shows the IC values ​​of different drugs for inhibiting the growth of MH-S cells in Experimental Example 1. 50 value.

[0055] Figure 3 The bar graph shows the effects of different drugs on the secretion of inflammatory factor TNF-α by LPS-induced MH-S cells in Experimental Example 1. In the figure, "*" indicates that the difference between the groups is P < 0.05, and "**" indicates that the difference between the groups is P < 0.01.

[0056] Figure 4 The bar graph shows the effects of different drugs on the secretion of inflammatory factor IL-1β by LPS-induced MH-S cells in Experimental Example 1. In the figure, "*" indicates that the difference between the groups is P < 0.05, and "**" indicates that the difference between the groups is P < 0.01.

[0057] Figure 5 The bar graph shows the effects of different drugs on the secretion of inflammatory factor IL-6 by LPS-induced MH-S cells in Experimental Example 1. In the figure, "*" indicates that the difference between the groups is P < 0.05, and "**" indicates that the difference between the groups is P < 0.01.

[0058] Figure 6 The photograph shows the immunofluorescence staining results in Experimental Example 1, in which the blue fluorescence is the Hoechst staining of the cell nucleus, the green fluorescence is the CD86 protein staining, and the red fluorescence is the CD206 protein staining.

[0059] Figure 7 The bar graph shows the survival rate of mouse alveolar macrophages MH-S treated with different drugs for 48 hours in Experimental Example 2, wherein the abscissa is the drug concentration and the ordinate is the absorbance value of the cell culture fluid at 450nm. In the figure, *P<0.05, **P<0.01, vs. blank control group (drug concentration 0mg / ml group).

[0060] Figure 8 The bar graph shows the IC values ​​of different drugs for inhibiting the growth of MH-S cells in Experiment 2. 50 value.

[0061] Fig. 9The bar graph shows the effects of different drugs on the secretion of inflammatory factor TNF-α by LPS-induced MH-S cells in Experimental Example 2. In the figure, "*" indicates that the difference between the groups is P < 0.05, and "**" indicates that the difference between the groups is P < 0.01.

[0062] Fig.10 The bar graph shows the effects of different drugs on the secretion of inflammatory factor IL-1β by LPS-induced MH-S cells in Experimental Example 2. In the figure, "*" indicates the difference between the groups P < 0.05, and "**" indicates the difference between the groups P < 0.01. .

[0063] Fig.11 The bar graph shows the effects of different drugs on the secretion of inflammatory factor IL-6 by LPS-induced MH-S cells in Experimental Example 2. In the figure, "*" indicates that the difference between the groups is P < 0.05, and "**" indicates that the difference between the groups is P < 0.01.

[0064] Fig.12 The bar graph shows the total protein concentration in the bronchoalveolar lavage fluid (BALF) of each group of mice in Experimental Example 2.

[0065] Fig.13 The bar graph shows the number of cells in the bronchoalveolar lavage fluid (BALF) of mice in each group in Experimental Example 2.

[0066] Fig.14 The bar graph shows the concentration of inflammatory factor TNF-α in the bronchoalveolar lavage fluid (BALF) of mice in each group in Experimental Example 2.

[0067] Fig.15 The bar graph shows the concentration of inflammatory factor IL-1β in the bronchoalveolar lavage fluid (BALF) of mice in each group in Experimental Example 2.

[0068] Fig.16 The bar graph shows the concentration of inflammatory factor IL-6 in the bronchoalveolar lavage fluid (BALF) of mice in each group in Experimental Example 2.

[0069] Fig.17 Shown are the H&E staining results of lung tissue sections of mice in each group in Experimental Example 2.

[0070] Fig.18 The bar graph shows the lung injury scores of mice in each group in Experimental Example 2.

[0071] Fig.19 The bar graph shows the lung wet / dry weight ratio of each group of mice in Experimental Example 2.

[0072] Figure 12-19Medium, *P<0.05, **P<0.01, ***P<0.001, ****P≤0.0001, vs. ARDS group; #P<0.05, ##P<0.01, vs. ARDS+Ningfei Decoction medium dose group (26.2 g / kg). DETAILED DESCRIPTION

[0073] The present invention is described below with reference to specific examples. It will be appreciated by those skilled in the art that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention in any way.

[0074] The experimental methods in the following examples are conventional methods unless otherwise specified. The medicinal materials, reagents, etc. used in the following examples are commercially available products unless otherwise specified.

[0075] Example 1 A Chinese medicine composition I and a decoction prepared therefrom

[0076] The Chinese medicine composition I described in this embodiment is composed of the following medicinal materials:

[0077] American ginseng 15g, turmeric 13g, angelica 15g, gypsum 20g, Fritillaria thunbergii 15g, apricot kernel 10g, mulberry bark 15g, rhubarb 10g, sodium sulfate 10g, immature bitter orange 10g, Magnolia officinalis 10g.

[0078] The decoction is prepared by the following method:

[0079] A. Weigh each medicinal material;

[0080] B. Soak American ginseng in about 150 ml of water for 20 minutes to 1 hour, then boil and simmer for about 2 hours to obtain American ginseng decoction, set aside;

[0081] C. Mix turmeric, angelica, Fritillaria thunbergii, apricot kernel, white mulberry bark, immature bitter orange and Magnolia officinalis, and soak them in about 700 ml of water for 20 minutes to 1 hour; first decoct gypsum with about 150 ml of water for 20-30 minutes; then add the soaked turmeric, angelica, Fritillaria thunbergii, apricot kernel, white mulberry bark, immature bitter orange and Magnolia officinalis together with the extract, boil over high heat, then simmer for 20 minutes to 30 minutes over low heat, add rhubarb 5 minutes before the end of heating, and filter while hot. Add about 350 ml of water to the residue, decoct for 15 minutes to 20 minutes, filter while hot, and combine the filtrate to obtain a medicinal decoction;

[0082] D. Combine the American ginseng decoction and the medicinal material decoction, mix evenly, concentrate if necessary to make the total volume of the medicinal solution about 400 ml, and divide it into 2 parts; divide the mirabilite into 2 parts, and take 1 part of mirabilite and 1 part of the medicinal solution at the same time.

[0083] Dosage and Administration: When the condition is critical, take it four times a day, frequently by nasogastric feeding or orally; when the condition is stable, take it twice a day, by nasogastric feeding or orally.

[0084] Example 2 A Chinese medicine composition I and a decoction prepared therefrom

[0085] The Chinese medicine composition I described in this embodiment is composed of the following medicinal materials:

[0086] American ginseng 8g, turmeric 7g, angelica 8g, gypsum 10g, thunbergia 8g, apricot 5g, mulberry bark 8g, rhubarb 5g, mirabilite 5g, aurantium immaturum 5g, and magnolia officinalis 5g.

[0087] The decoction was prepared by the same method and steps as in Example 1, except that:

[0088] B. The amount of water used for decoction of American ginseng is about 100ml;

[0089] C. First decoct the raw gypsum with about 70ml of water, soak the turmeric, angelica, Fritillaria thunbergii, apricot kernel, mulberry bark, immature bitter orange and Magnolia officinalis with about 350ml of water, and then decoct them with the raw gypsum; add about 200ml of water for the second decoction.

[0090] Dosage and usage: Same as Example 1.

[0091] Example 3 A Chinese medicine composition I and a decoction prepared therefrom

[0092] The Chinese medicine composition I described in this embodiment is composed of the following medicinal materials:

[0093] 30g American ginseng, 26g Curcuma, 30g Chinese angelica, 40g gypsum, 30g Fritillaria thunbergii, 20g apricot kernel, 30g mulberry bark, 20g rhubarb, 20g Glauber's salt, 20g Citrus aurantium, 20g Magnolia officinalis.

[0094] The decoction was prepared by the same method and steps as in Example 1, except that:

[0095] B. The amount of water used for decoction of American ginseng is 300ml;

[0096] C. First decoct the raw gypsum with about 300ml of water, soak the turmeric, angelica, Fritillaria thunbergii, apricot kernel, mulberry bark, immature bitter orange and Magnolia officinalis with about 1400ml of water, and then decoct with the raw gypsum; add about 700ml of water for the second decoction.

[0097] Dosage and usage: Same as Example 1.

[0098] Example 4 A Chinese medicine composition I and a decoction prepared therefrom

[0099] The Chinese medicine composition I described in this embodiment is composed of the following medicinal materials:

[0100] American ginseng 10g, turmeric 9g, angelica 10g, gypsum 15g, Fritillaria thunbergii 10g, apricot kernel 8g, mulberry bark 10g, rhubarb 8g, sodium sulfate 8g, immature bitter orange 8g, Magnolia officinalis 8g.

[0101] The decoction was prepared by the same method and steps as in Example 1, except that:

[0102] B. The amount of water used for decoction of American ginseng is about 200ml;

[0103] C. Gypsum is first decocted with about 100 ml of water, and Curcuma, Angelica, Fritillaria, Apricot, Morus alba, Citrus aurantium and Magnolia officinalis are first soaked with about 500 ml of water, and then decocted with the gypsum; about 250 ml of water is added for the second decoction. Dosage and usage: Same as in Example 1.

[0104] Example 5 A Chinese medicine composition I and a decoction prepared therefrom

[0105] The Chinese medicine composition I described in this embodiment is composed of the following medicinal materials:

[0106] 20g American ginseng, 20g Curcuma, 20g Angelica sinensis, 30g Gypsum, 20g Fritillaria thunbergii, 15g Apricot, 20g Morus alba, 15g Rhubarb, 15g Sodium Sulfate, 15g Citrus aurantium, 15g Magnolia officinalis.

[0107] The decoction was prepared by the same method and steps as in Example 1, except that:

[0108] B. The amount of water used for decoction of American ginseng is about 200ml;

[0109] C. First decoct the raw gypsum with about 200ml of water, soak the turmeric, angelica, Fritillaria thunbergii, apricot, mulberry bark, immature bitter orange and Magnolia officinalis with about 1000ml of water, and then decoct with the raw gypsum; add about 500ml of water for the second decoction.

[0110] Dosage and usage: Same as Example 1.

[0111] Example 6 A Chinese medicine composition II and a decoction prepared therefrom

[0112] The Chinese medicine composition II described in this embodiment is composed of the following medicinal materials:

[0113] Angelica 15g, peach kernel 10g, Fritillaria thunbergii 15g, radish seed 15g, rhubarb 13g, Glauber's salt 10g, Citrus aurantium 10g, Magnolia officinalis 10g.

[0114] Prepare enema by the following method:

[0115] (1) Weigh each medicinal material;

[0116] (2) Mix angelica sinensis, peach kernel, Fritillaria thunbergii, radish seed, mirabilite, immature bitter orange and Magnolia officinalis, add about 600 ml of water and soak for 20 minutes to 1 hour, boil over high heat and then simmer for 20 to 30 minutes over low heat, add rhubarb 5 minutes before the end of heating and decoct together, filter while hot; add about 250 ml of water to the residue and decoct for 15 to 20 minutes, filter while hot, combine the filtrate, and obtain a decoction of medicinal materials; if necessary, concentrate the volume of the decoction to about 200 ml;

[0117] (3) Add Glauber's salt to the medicinal solution and stir until the Glauber's salt dissolves.

[0118] Dosage and Usage: Enema, once every other day, 200ml each time, stop using when stool is discharged.

[0119] Example 7 A Chinese medicine composition II and a decoction prepared therefrom

[0120] The Chinese medicine composition II described in this embodiment is composed of the following medicinal materials:

[0121] Angelica 8g, peach kernel 5g, Fritillaria thunbergii 8g, radish seed 8g, rhubarb 7g, Glauber's salt 5g, Citrus aurantium 5g, Magnolia officinalis 5g.

[0122] An enema was prepared according to the same method and steps as in Example 6, except that about 300 ml of water was used for soaking and decocting after the herbs were mixed, and about 150 ml of water was used for the second decoction.

[0123] Dosage and usage: Same as Example 6.

[0124] Example 8 A Chinese medicine composition II and a decoction prepared therefrom

[0125] The Chinese medicine composition II described in this embodiment is composed of the following medicinal materials:

[0126] Angelica 30g, peach kernel 20g, Fritillaria thunbergii 30g, radish seed 30g, rhubarb 26g, Glauber's salt 20g, Citrus aurantium 20g, Magnolia officinalis 20g.

[0127] An enema was prepared according to the same method and steps as in Example 6, except that about 1300 ml of water was used for soaking and decocting after the herbs were mixed, and about 500 ml of water was used for the second decoction.

[0128] Dosage and usage: Same as Example 6.

[0129] Example 9 A Chinese medicine composition II and a decoction prepared therefrom

[0130] The Chinese medicine composition II described in this embodiment is composed of the following medicinal materials:

[0131] Angelica 10g, peach kernel 8g, Fritillaria thunbergii 10g, radish seed 10g, rhubarb 9g, Glauber's salt 8g, Citrus aurantium 8g, Magnolia officinalis 8g.

[0132] An enema was prepared according to the same method and steps as in Example 6, except that about 500 ml of water was used for soaking and decocting after the herbs were mixed, and about 200 ml of water was used for the second decoction.

[0133] Dosage and usage: Same as Example 6.

[0134] Example 10 A Chinese medicine composition II and a decoction prepared therefrom

[0135] The Chinese medicine composition II described in this embodiment is composed of the following medicinal materials:

[0136] Angelica 20g, peach kernel 15g, Fritillaria thunbergii 20g, radish seed 20g, rhubarb 20g, Glauber's salt 15g, Citrus aurantium 15g, Magnolia officinalis 15g.

[0137] An enema was prepared according to the same method and steps as in Example 6, except that about 900 ml of water was used for soaking and decocting after the herbs were mixed, and about 400 ml of water was used for the second decoction.

[0138] Dosage and usage: Same as Example 6.

[0139] Embodiment 11 A medicine for treating acute respiratory distress syndrome caused by pathogenic heat, phlegm, blood stasis in the lungs and obstruction of visceral qi

[0140] The medicine of this embodiment is composed of a decoction selected from any one of embodiments 1-5 and an enema selected from any one of embodiments 6-10. The decoction is taken four times a day by frequent nasogastric feeding or oral administration when the patient is in critical condition, and twice a day by nasogastric feeding or oral administration when the patient is in stable condition. Enema is taken every other day and is discontinued when the stool is discharged.

[0141] Test Example 1 In vitro pharmacodynamics test I

[0142] 1. Materials

[0143] 1.1 Tested Chinese medicine composition

[0144] Ningfei Decoction low-dose composition 1: American ginseng 8g, turmeric 7g, angelica 8g, gypsum 10g, thunbergia 8g, apricot 5g, mulberry bark 8g, rhubarb 5g, mirabilite 5g, immature bitter orange 5g, magnolia bark 5g;

[0145] Ningfei Decoction low-dose composition 2: American ginseng 10g, turmeric 9g, angelica 10g, gypsum 15g, fritillaria thunbergii 10g, apricot kernel 8g, mulberry bark 10g, rhubarb 8g, sodium sulfate 8g, immature bitter orange 8g, Magnolia officinalis 8g;

[0146] Ningfei Decoction medium dose composition: American ginseng 15g, turmeric 13g, angelica 15g, gypsum 20g, thunbergia 15g, apricot 10g, mulberry bark 15g, rhubarb 10g, mirabilite 10g, immature bitter orange 10g, magnolia bark 10g;

[0147] Ningfei Decoction high-dose composition 1: American ginseng 20g, turmeric 18g, angelica 20g, gypsum 30g, thunbergia 20g, apricot 15g, mulberry bark 20g, rhubarb 15g, mirabilite 15g, immature bitter orange 15g, magnolia bark 15g;

[0148] Ningfei Decoction high-dose composition 2: American ginseng 30g, turmeric 26g, angelica 30g, gypsum 40g, thunbergia thunbergii 30g, apricot kernel 20g, mulberry bark 30g, rhubarb 20g, mirabilite 20g, immature bitter orange 20g, magnolia bark 20g;

[0149] Composition of enema prescription: 15g of angelica sinensis, 10g of peach kernel, 15g of Fritillaria thunbergii, 15g of radish seed, 13g of rhubarb, 10g of Glauber's salt, 10g of Citrus aurantium, and 10g of Magnolia officinalis.

[0150] The medicinal materials were purchased from the Chinese medicine pharmacies of Shanghai Longhua Hospital and Shanghai Shuguang Hospital.

[0151] 1.2 Cells and reagents

[0152] Mouse alveolar macrophage MH-S (BES-M027) was purchased from Shanghai BIOESN Biotechnology Co., Ltd. RPMI1640 medium (11875119), superior fetal bovine serum (FBS.10099158), 0.25% trypsin (25200114), and sterile phosphate buffer (Dulbecco's phosphate-buffered saline, dPBS.14040133) were purchased from Thermo Scientific, USA. CCK-8 cell proliferation and toxicity detection kit (CA1201) was purchased from Beijing Solebao Biotechnology Co., Ltd. TNF-α, IL-1β and IL-6 ELISA detection kits (BMS607-3, BMS6002-2 and KMC0061) were purchased from Invitrogen, USA. Dexamethasone (D4902) and bacterial lipopolysaccharide (LPS) were purchased from Sigma, USA. The primary and secondary antibodies were from Abcam, UK.

[0153] 1.3 Instruments

[0154] The microplate reader (Varioskan LUX model) was produced by Thermo Fisher, USA. The CO2 incubator (MCO-18M model) was produced by Sanyo, Japan. The microscope (IX-70) was produced by Olympus, Japan.

[0155] 2 Methods

[0156] 2.1 Drug preparation

[0157] According to the prescription, each medicinal material was weighed, mixed and crushed, and then decocted with water at a 10-fold mass-to-volume ratio, and rhubarb was added later; decocted twice, the decoctions were combined, and extracts were obtained after low-temperature freeze-drying and stored at -20°C. Before the experiment, an appropriate amount of extract was dissolved with dPBS, added with culture medium to dilute to the corresponding concentration (converted to the amount of crude drug), and filtered through a 0.22μm sterilizing filter membrane for use in the experiment. In addition, the extract of the Ningfei Decoction medium-dose composition and the extract of the enema prescription composition were mixed in proportion, dissolved with dPBS, so that the concentrations of the two extracts were equal in terms of crude drug amount, and then the culture medium was added to dilute until the total concentration reached the specified concentration (converted to the amount of crude drug).

[0158] 2.2 Drug toxicity test

[0159] The experimental groups are as follows:

[0160] 1) Ningfei decoction medium dose treatment group;

[0161] 2) enema prescription composition treatment group;

[0162] 3) Ningfei Decoction + Enema Formula Treatment Group: Ningfei Decoction medium dose composition + Enema Formula composition.

[0163] The final concentrations of the above groups were 0, 0.1, 0.2, 0.5, 1, 2, 5 and 10 mg / ml respectively.

[0164] MH-S cells were cultured in RPMI1640 medium containing 10% FBS at 37°C and 5% CO2. MH-S cells in the logarithmic phase were cultured at 5×10 4 The cells were inoculated at a density of cells / well in a 96-well culture plate and cultured overnight under normal conditions. The cell medium was replaced with fresh RPMI1640 medium containing 10% FBS, and drugs were added according to the final concentration, and cultured under normal conditions for 48 hours. The cell proliferation activity was then detected by the CCK-8 method: 10 μl of CCK-8 reagent solution was added to the culture medium of each well, incubated in an incubator at 37°C for 2 hours, and the absorbance (OD value) of each well was measured using a microplate reader, with a detection wavelength of 450 nm. According to the experimental design and the standard curve, the cell viability or cell proliferation rate of each group was calculated. At the same time, the drug concentration and cell inhibition rate curve was calculated and fitted with an equation, and then the IC of each group of drugs was calculated based on the fitted equation.50 value(half maximal inhibitoryconcentration).

[0165] 2.3 Detection of inflammatory factor content

[0166] Experimental groups:

[0167] 1) Blank control group (control);

[0168] 2) LPS group:

[0169] 3) Vehicle group: equal volume of dPBS;

[0170] 4) Dexamethasone group: positive control, 100 μg / ml;

[0171] 5) Ningfei Decoction low-dose group 1: Ningfei Decoction low-dose composition 1, 0.5 mg / ml;

[0172] 6) Ningfei Decoction low-dose group 2: Ningfei Decoction low-dose composition 2, 0.67 mg / ml;

[0173] 7) Ningfei Decoction medium dose group: Ningfei Decoction medium dose composition, 1.0 mg / ml;

[0174] 8) Ningfei Decoction high-dose group 1: Ningfei Decoction high-dose composition 1, 1.5 mg / ml;

[0175] 9) Ningfei Decoction high-dose group 2: Ningfei Decoction high-dose composition 2, 2.0 mg / ml;

[0176] 10) Enema group: enema, 1.0 mg / ml;

[0177] 11) Ningfei Decoction + Enema Formula Group: Ningfei Decoction medium-dose composition + enema formula, 2 mg / ml (equivalent to the concentrations of the Ningfei Decoction medium-dose composition and enema formula being 1 mg / ml respectively).

[0178] MH-S cells in logarithmic phase were cultured at a rate of 5×10 4Cells were inoculated into 96-well culture plates at a density of 100 / well and cultured overnight under normal conditions. The cells were replaced with fresh RPMI1640 medium containing 10% FBS, and drugs were added at the same time. The cells were cultured under normal conditions for 1 hour, and then LPS was added to the culture medium at a concentration of 1μg / ml, and then cultured under normal conditions for 48 hours. The cell supernatant was collected and centrifuged at 4°C for 10-15 minutes to remove cell debris, and the supernatant was taken for ELISA detection. A 96-well ELISA plate pre-coated with specific antibodies was used, and standards and samples to be tested (i.e., cell supernatants) were added to each well of the plate. The concentration of the standards was usually a known series of gradients. Three parallel wells were usually set for each sample, and the plates were incubated at room temperature for 1 hour. After removing the liquid in the wells, HRP-labeled detection antibodies were added, and the plates were incubated at room temperature again for 1 hour. The ELISA plate was washed 3 times with plate washing solution to remove unbound detection antibodies. Substrate solution was added to each well and reacted at 37°C for 15 minutes. When the color reaction reached the expected intensity, the stop solution was added. The absorbance (OD value) of each well was measured at 450 nm using an enzyme reader, and the concentration of inflammatory factors (TNF-α, IL-1β and IL-6) in the test samples was calculated using a standard curve.

[0179] 2.4 Immunofluorescence staining

[0180] MH-S cells in logarithmic phase were counted as 1×10 5 Cells were seeded in 6-well culture plates at a density of 100 / well and cultured overnight under normal conditions. The cells were replaced with fresh RPMI1640 medium containing 10% FBS, and drugs were added at a final concentration of 1 mg / ml. After 1 hour of normal culture, LPS was added to the culture medium at a concentration of 1 μg / ml, and cultured under normal conditions for 72 hours. Cells were fixed with 4% paraformaldehyde for 20 minutes, and washed with dPBS buffer 3 times for 5 minutes each time to remove excess fixative. Cells were treated with 0.1%-0.5% Triton X-100 for 5 minutes, and then washed with dPBS 3 times for 5 minutes each time. Cells were incubated in a blocking solution containing 5-10% BSA for 30 minutes. Cells were washed with dPBS 3 times for 5 minutes each time. Primary antibodies (CD206 and CD208) diluted 1:200 were added to the cells, incubated at room temperature for 2 hours, and then washed with dPBS 3 times for 5 minutes each time. Add fluorescently labeled secondary antibodies (labeled with FITC and Alexa Fluor, respectively) that match the primary antibody, incubate at room temperature in the dark for 45 minutes, then wash the cells 3-5 times with dPBS for 5 minutes each time. Add Hoechst stain, incubate in the dark for 5 minutes, and wash the cells 3 times with dPBS for 5 minutes each time. Mount the coverslip on a slide with anti-fluorescence quenching mounting medium, and seal the slide for microscopic examination.

[0181] 2.5 Statistics

[0182] The quantitative data were processed by SPSS17.0 software. The data with non-normal or unequal variance were analyzed by nonparametric test. P<0.05 indicated that the difference was statistically significant, and P<0.01 indicated that the difference was statistically significant.

[0183] 3. Results

[0184] 3.1 Effects of Ningfei Decoction and Enema on the Survival Rate of MH-S Cells

[0185] When the medium dose of Ningfei Decoction was 5 mg / ml, the enema formula was 2 mg / ml, and the Ningfei Decoction + enema formula was 2 mg / ml, the cell activity of mouse alveolar macrophages MH-S was treated for 48 hours, and there was a statistically significant difference between the cell activity of the blank control group and that of the control group (P < 0.05, P < 0.01); Figure 1 .

[0186] MH-S cells were treated with the medium-dose composition of Ningfei Decoction, enema prescription and Ningfei Decoction + enema prescription (0, 0.1, 0.2, 0.5, 1.2, 5 and 10 mg / ml) at gradient concentrations for 48 hours, and the IC of each drug on cell growth inhibition was calculated. 50 They are: 6.39mg / ml, 4.89mg / ml and 2.89mg / ml, see Figure 2 3.2 Effects of LPS on TNF-α, IL-6 and IL-1β levels in MH-S cell culture medium

[0187] The results are shown in Tables 1-3 and Figure 3-5 .

[0188] The data in Table 1-3 and Figure 3-5 The results showed that compared with the blank control group, the levels of inflammatory factors TNF-α, IL-1β and IL-6 in the cell supernatant of the LPS group were significantly increased (all P < 0.01), indicating that the modeling was successful; compared with the LPS group, the levels of various inflammatory factors in the cell supernatant of the dexamethasone group were extremely significantly reduced. Compared with the LPS group:

[0189] (1) The levels of inflammatory factors in the cell supernatant of each dose group of Ningfei Decoction were reduced, and the effect was concentration-dependent; among them, the differences between the medium dose group, high dose group 1 and high dose group 2 were statistically significant;

[0190] (2) There was no significant change in the levels of inflammatory factors in the cell supernatant of the enema group;

[0191] (3) The levels of inflammatory factors in the cell supernatant of the Ningfei Decoction + Enema Formula group were significantly reduced, and the inhibitory effect on IL-1β was better than that of the Ningfei Decoction medium-dose combination (1 mg / ml) or Enema Formula (1 mg / ml) alone. The inhibitory effect on TNF-α and IL-1β was equivalent to that of dexamethasone 100 μg / ml, while the inhibitory effect on IL-6 was significantly better than that of dexamethasone.

[0192] Table 1 Levels of inflammatory factor TNF-α in the cell supernatant of each group (n=3)

[0193]

[0194] Table 2 Levels of inflammatory factor IL-1β in the cell supernatant of each group (n=3)

[0195]

[0196] Table 3 Levels of IL-6, an inflammatory factor, in the cell supernatant of each group (n=3)

[0197]

[0198] 3.3 Effects on M1 and M2 polarization of macrophages

[0199] Results Figure 6 .

[0200] Figure 6 The immunofluorescence staining results showed that the expression of M1 polarization marker CD68 was significantly enhanced, while the expression of M2 polarization marker CD206 was significantly reduced in MH-S cells induced by 1 μg / ml LPS for 72 hours compared with the blank control group. The staining results also showed that compared with the LPS group, 1 mg / ml Ningfei Decoction treatment could significantly weaken the above effects of LPS. Therefore, Ningfei Decoction can significantly inhibit the M1 polarization of macrophages and promote M2 polarization.

[0201] 4. Conclusion

[0202] The medium-dose composition of Ningfei Decoction, high-dose composition 1 and high-dose composition 2 can significantly reduce the LPS-induced inflammatory response of MH-8 cells, reduce the levels of TNF-α, IL-6 and IL-1β in the cell culture fluid, inhibit cell M1 polarization and promote M2 polarization. The enema formula has no anti-inflammatory effect on cells when treated alone, but it can exert a very significant anti-inflammatory effect when used in combination with the medium-dose composition of Ningfei Decoction, which is better than dexamethasone 100 μg / ml.

[0203] Test Example 2 In vitro pharmacodynamics test II

[0204] 1. Materials

[0205] 1.1 Tested Chinese medicine composition:

[0206] 1) Ningfei Decoction low-dose composition 1: American ginseng 4g, turmeric 3g, angelica 4g, gypsum 5g, thunbergia 4g, apricot 2g, mulberry bark 4g, rhubarb 2g, mirabilite 2g, immature bitter orange 2g, magnolia bark 2g;

[0207] 2) Ningfei Decoction low-dose composition 2: American ginseng 8g, turmeric 7g, angelica 8g, gypsum 10g, thunbergia 8g, apricot 5g, mulberry bark 8g, rhubarb 5g, sodium sulfate 5g, immature bitter orange 5g, Magnolia officinalis 5g;

[0208] 3) Ningfei Decoction medium dose composition: American ginseng 15g, turmeric 13g, angelica 15g, gypsum 20g, thunbergia 15g, apricot 10g, mulberry bark 15g, rhubarb 10g, sodium sulfate 10g, immature bitter orange 10g, Magnolia officinalis 10g;

[0209] 4) Ningfei Decoction high-dose composition 1: American ginseng 30g, turmeric 26g, angelica 30g, gypsum 40g, thunbergia thunbergii 30g, apricot kernel 20g, mulberry bark 30g, rhubarb 20g, sodium sulfate 20g, immature bitter orange 20g, Magnolia officinalis 20g;

[0210] 5) Ningfei Decoction high-dose composition 2: American ginseng 45g, turmeric 39g, angelica 45g, gypsum 60g, thunbergia 45g, apricot kernel 30g, mulberry bark 45g, rhubarb 30g, sodium sulfate 30g, immature bitter orange 30g, Magnolia officinalis 30g;

[0211] 6) Ningfei decoction without rhubarb composition: American ginseng 15g, turmeric 13g, angelica 15g, gypsum 20g, fritillaria thunbergii 15g, apricot kernel 10g, mulberry bark 15g, sodium sulfate 10g, immature bitter orange 10g, Magnolia officinalis 10g;

[0212] 7) Composition of enema prescription: 15g of Chinese angelica, 10g of peach kernel, 15g of Fritillaria thunbergii, 15g of radish seed, 13g of rhubarb, 10g of sodium sulfate, 10g of immature bitter orange, and 10g of Magnolia officinalis.

[0213] The medicinal materials were purchased from the Chinese medicine pharmacies of Shanghai Longhua Hospital and Shanghai Shuguang Hospital.

[0214] 1.2 Cells and reagents

[0215] Same as “1.2” of “Test Example 1”.

[0216] 1.3 Instruments

[0217] Same as “1.3” of “Test Example 1”.

[0218] 2 Methods

[0219] 2.1 Drug preparation

[0220] The operation is the same as "2.1" of "Test Example 1".

[0221] 2.2 Drug toxicity test

[0222] The experimental groups are as follows:

[0223] 1) Ningfei Decoction medium-dose treatment group;

[0224] 2) Ningfei decoction without rhubarb treatment group;

[0225] 3) enema prescription treatment group;

[0226] 4) Ningfei Decoction + enema treatment group.

[0227] The final concentrations of the above groups were 0, 0.1, 0.2, 0.5, 1, 2, 5 and 10 mg / ml respectively.

[0228] The experimental operation is the same as "2.2" of "Test Example 1".

[0229] 2.3 Detection of inflammatory factor content

[0230] Experimental groups:

[0231] 1) Blank control group;

[0232] 2) LPS group;

[0233] 3) Solvent group: equal volume of dPBS;

[0234] 4) Dexamethasone group: positive control group, dexamethasone 100 μg / ml;

[0235] 5) Ningfei Decoction low-dose group 1: Ningfei Decoction low-dose composition 1, 0.5 mg / ml;

[0236] 6) Ningfei Decoction low-dose group 2: Ningfei Decoction low-dose composition 2, 0.67 mg / ml;

[0237] 7) Ningfei Decoction medium dose group: Ningfei Decoction medium dose composition, 1.0 mg / ml;

[0238] 8) Ningfei Decoction high-dose group 1: Ningfei Decoction high-dose composition 1, 1.5 mg / ml;

[0239] 9) Ningfei Decoction high-dose group 2: Ningfei Decoction high-dose composition 2, 2.0 mg / ml;

[0240] 10) Ningfei decoction without rhubarb group: Ningfei decoction without rhubarb combination, 1.0 mg / ml;

[0241] 11) Enema formula: Enema formula composition, 1.0 mg / ml;

[0242] 12) Ningfei Decoction + Enema Formula: 2.0 mg / ml (equivalent to the medium-dose composition of Ningfei Decoction 1.0 mg / ml + enema formula 1.0 mg / ml).

[0243] The experimental operation is the same as "2.3" of "Test Example 1".

[0244] 2.3 Statistics

[0245] Same as “2.5” in “Test Example 1”.

[0246] 3. Results

[0247] 3.1 Effect on MH-S cell survival rate

[0248] The MH-S cells of mouse alveolar macrophages were treated with the medium-dose Ningfei Decoction composition, the Ningfei Decoction without rhubarb composition, the enema formula and the Ningfei Decoction + enema formula for 48 hours. The cell activity was statistically different from that of the blank control group at the concentrations of 5 mg / ml, 0.5 mg / ml, 2 mg / ml and 2 mg / ml (P < 0.05, P < 0.01). Figure 7 .

[0249] MH-S cells were treated with the medium-dose Ningfei Decoction composition, the Ningfei Decoction without rhubarb composition, the enema recipe and the Ningfei Decoction + enema recipe (0, 0.1, 0.2, 0.5, 1.2, 5 and 10 mg / ml) at gradient concentrations for 48 hours, and the IC values ​​of each drug on cell growth inhibition were calculated. 50 They are: 6.20, 6.31, 4.89 and 2.89 mg / ml, see Figure 8 .

[0250] 3.2 Effects of LPS on TNF-α, IL-6 and IL-1β levels in MH-S cell culture medium

[0251] The results are shown in Tables 4-6 and Figure 9-11 .

[0252] The data in Table 4-6 and Figure 9-11 The results showed that compared with the blank control group, the levels of inflammatory factors TNF-α, IL-1β and IL-6 in the cell supernatant of the LPS group were significantly increased (all P < 0.01), indicating that the modeling was successful. Compared with the LPS group, the levels of inflammatory factors in the cell supernatant of the positive control dexamethasone group were significantly reduced, and the difference was statistically significant.

[0253] Compared with the LPS group:

[0254] (1) Although the levels of inflammatory factors in the cell supernatant of Ningfei Decoction low-dose group 1 (0.5 mg / ml) and Ningfei Decoction low-dose group 2 (0.67 mg / ml) were reduced, the difference was not statistically significant;

[0255] (2) The levels of various inflammatory factors in the cell supernatants of the Ningfei Decoction medium-dose group (1.0 mg / ml), Ningfei Decoction high-dose group 1 (1.5 mg / ml) and Ningfei Decoction high-dose group 2 (2.0 mg / ml) were significantly reduced (P < 0.05, or P < 0.01); however, there was no significant difference in the levels of various inflammatory factors in the cell supernatants of the Ningfei Decoction high-dose group 1 (1.5 mg / ml) and Ningfei Decoction high-dose group 2 (2.0 mg / ml);

[0256] (3) In the cell supernatant of the Ningfei Decoction without rhubarb group (1.0 mg / ml), the content of TNF-α was significantly reduced, and the levels of IL-6 and IL-1β decreased, but the difference was not statistically significant; and the levels of TNF-α and IL-1β were significantly higher than those of the medium-dose combination of Ningfei Decoction (P < 0.05);

[0257] (4) The levels of inflammatory factors in the cell supernatant of the enema group (1.0 mg / ml) were significantly reduced (P < 0.05), but the degree of decrease was not as high as that of the medium-dose Ningfei Decoction group, and the TNF-α levels were significantly higher than those of the medium-dose Ningfei Decoction group;

[0258] (5) The levels of inflammatory factors in the cell supernatant of the Ningfei Decoction + Enema group were significantly reduced, and the inhibitory effect on TNF-α was significantly better than that of the Ningfei Decoction medium-dose group; the levels of various inflammatory factors were significantly lower than those of the enema (1.0 mg / ml) alone treatment group; the inhibitory effect of the Ningfei Decoction + Enema group on various inflammatory factors was equivalent to that of dexamethasone 100 μg / ml.

[0259] Table 4 Levels of inflammatory factor TNF-α in the cell supernatant of each group (n=3)

[0260]

[0261] Table 5 Levels of inflammatory factor IL-1β in the cell supernatant of each group (n=3)

[0262]

[0263]

[0264] Table 6 Levels of inflammatory factor IL-6 in the cell supernatant of each group (n=3)

[0265]

[0266] 4. Conclusion

[0267] Ningfei Decoction low-dose composition 1 has no effect on inhibiting inflammation; low-dose composition 2 has a certain in vitro anti-inflammatory effect. Ningfei Decoction medium-dose composition, Ningfei Decoction high-dose composition 1 and Ningfei Decoction high-dose composition 2 can significantly reduce LPS-induced MH-8 cell inflammatory response and reduce the levels of TNF-α, IL-6 and IL-1β in cell culture fluid, but the inhibitory effect of Ningfei Decoction high-dose composition 1 and Ningfei Decoction high-dose composition 2 is not significantly different. The inflammatory inhibitory effect of the Ningfei Decoction minus rhubarb composition is significantly reduced. The combination of enema prescription and Ningfei Decoction can exert a very significant anti-inflammatory effect, which is equivalent to dexamethasone 100μg / ml.

[0268] Test Example 3 In vivo pharmacodynamics study

[0269] 1. Materials

[0270] 1.1 Drugs under investigation

[0271] 1) Ningfei Decoction: American ginseng 15g, turmeric 13g, angelica 15g, gypsum 20g, thunbergia 15g, apricot 10g, mulberry bark 15g, rhubarb 10g, sodium sulfate 10g, immature bitter orange 10g, magnolia bark 10g; total 143g.

[0272] The Ningfei Decoction test drug was prepared according to the following steps:

[0273] ①Weigh each medicinal material;

[0274] ② Soak American ginseng in about 150 ml of water for 30 minutes, then boil and simmer for about 2 hours to obtain American ginseng decoction, set aside;

[0275] ③ Mix turmeric, angelica, thunbergii, apricot, mulberry bark, immature bitter orange and magnolia bark, and soak them in about 700 ml of water for 30 minutes; first decoct gypsum with about 150 ml of water for 20 minutes; then add the soaked turmeric, angelica, thunbergii, apricot, mulberry bark, immature bitter orange and magnolia bark together with the extract, boil over high heat, then simmer for 20 minutes, add rhubarb 5 minutes before the end of heating, and filter while hot. Add about 350 ml of water to the residue, decoct for 20 minutes, filter while hot, and combine the filtrate to obtain a medicinal decoction;

[0276] ④ Combine the American ginseng decoction and the medicinal material decoction and mix them evenly;

[0277] ⑤ Freeze-dry in vacuum, dilute with appropriate amount of physiological saline to the specified concentration (calculated according to the amount of raw medicine) before use. 2) Enema recipe: 15g of Angelica sinensis, 10g of peach kernel, 15g of Fritillaria thunbergii, 15g of Radish Seed, 13g of Rhubarb, 10g of Sodium Sulfate, 10g of Citrus aurantium, 10g of Magnolia officinalis; a total of 98g.

[0278] Prepare the enema test drug according to the following steps:

[0279] ①Weigh each medicinal material;

[0280] ② Mix angelica sinensis, peach kernel, Fritillaria thunbergii, radish seed, mirabilite, immature bitter orange and Magnolia officinalis, add about 600 ml of water and soak for 30 minutes, boil over high heat and then simmer for 20 minutes over low heat, add rhubarb 5 minutes before the end of heating and decoct together, filter while hot; add about 250 ml of water to the residue and decoct for 20 minutes, filter while hot, combine the filtrate to obtain a medicinal decoction;

[0281] ③ Add Glauber's salt to the liquid medicine and stir until the Glauber's salt dissolves;

[0282] ④ Vacuum freeze-drying, dilute with appropriate amount of physiological saline before use (calculated according to the amount of crude drug).

[0283] The medicinal materials were purchased from the Chinese medicine pharmacies of Shanghai Longhua Hospital and Shanghai Shuguang Hospital.

[0284] 1.2 Animals and reagents

[0285] 77 8-week-old C57 mice (male, 20 ± 2 g) were purchased from Changzhou Cavens Laboratory Animal Co., Ltd., production license number SCXK (Su) 2021-0013. Protein primary and secondary antibodies were all products of Abcam, UK. TNF-α, IL-1β and IL-6 ELISA detection kits (BMS607-3, BMS6002-2 and KMC0061) were purchased from Invitrogen, USA. Dexamethasone (D4902) and bacterial lipopolysaccharide (LPS) were purchased from Sigma, USA. Myeloperoxidase (MPO) colorimetric activity detection kit was purchased from Wuhan Aimejie Company (K744-100). Hematoxylin-eosin (HE) stain was purchased from Beijing Solebao Company.

[0286] 1.3 Instruments

[0287] The microplate reader (Varioskan LUX model) was a product of Thermo Fisher, USA. The CO2 incubator (MCO-18M model) was a product of Sanyo, Japan. The microscope (IX-70) was produced by Olympus, Japan. The semi-automatic rotary slicer (HistoCore MULTICUT) was purchased from Leica, Germany.

[0288] 2 Methods

[0289] 2.1 Drug dosage setting:

[0290] Based on the standard of human body weight of 60kg and mouse body weight of 20g±2g, the dosage of each group was calculated in terms of crude drug amount:

[0291] Ningfei Decoction medium dose group (original dose group): 26.2 g / kg;

[0292] Ningfei decoction low-dose group: 13.1 g / kg;

[0293] Ningfei decoction high-dose group: 52.4 g / kg;

[0294] Enema soup group: 18.0g / kg.

[0295] 2.2 Grouping

[0296] (1) Sham group: the same volume of distilled water was given by gavage and enema;

[0297] (2) ARDS group: the same volume of distilled water was given by gavage and enema;

[0298] (3) ARDS + Ningfei Decoction low-dose group: 13.1 g crude drug / kg each time, intragastrically;

[0299] (4) ARDS + Ningfei Decoction medium-dose group: 26.2 g crude drug / kg each time, intragastrically;

[0300] (5) ARDS + Ningfei Decoction high-dose group: 52.4 g crude drug / kg each time, intragastrically;

[0301] (6) ARDS + Ningfei Decoction + Enema Group: Ningfei Decoction 26.2 g crude drug / kg per oral administration, Enema 18.0 g crude drug / kg per oral administration;

[0302] (7) ARDS+dexamethasone group: 2.0 mg / kg each time, positive control, intraperitoneal injection.

[0303] 2.3 Modeling

[0304] (1) Preparation of LPS solution

[0305] LPS powder was dissolved in sterile saline at a concentration of 5 mg / ml and then sterilized by filtration through a 0.22 μm filter membrane.

[0306] (2) Anesthesia of mice

[0307] Place the mouse in an anesthesia box and anesthetize it with isoflurane inhalation. After confirming that the mouse is completely unresponsive (foot pinch pain response disappears), proceed to the next step.

[0308] (3) Intratracheal instillation of LPS

[0309] Fix the mouse on the operating table in a supine position with the head slightly tilted back to expose the airway. Use a mouse-specific mouth brace or micro-stent to gently open the mouse's mouth and expose the throat. Use a small syringe or microtitrator with a curved needle to insert the trachea through the mouth and slowly inject the preset dose (10 mg / kg) of LPS solution into the trachea. Immediately after the instillation, gently massage the mouse's chest to help LPS be evenly distributed in the lungs.

[0310] (4) Postoperative care

[0311] Place the mouse in a warm environment and closely observe its awakening and breathing. After awakening, return the mouse to a clean home cage and continue to monitor its vital signs and behavioral changes.

[0312] 2.4 Medication and material collection

[0313] Six hours after modeling, the mice were given Ningfei Decoction once by oral gavage according to the dosage, and 12 hours later, they were given enema once according to the dosage; the Sham group and the ARDS group were given the same volume of normal saline in the same way; the dexamethasone group was injected intraperitoneally once 6 hours after modeling.

[0314] Eight mice were randomly selected from the surviving mice in each group 24 hours after modeling. The anesthetized mice were intubated for alveolar lavage, and the alveolar lavage fluid (BALF) was collected for the detection of total soluble protein concentration and cell count. The content of inflammatory factors (TNF-α, IL-1β and IL-6) in BALF was also detected by ELISA. The mice were then killed, and the intact lungs were removed for H&E staining and injury scoring.

[0315] 2.3 H&E staining and injury scoring of lung tissue

[0316] Lung tissue was taken for H&E staining to evaluate lung tissue damage and inflammatory response. The specific method was referred to the literature (Rui Gong, et al. Integrative proteomic profiling of lung tissues and blood in acute respiratory distress syndrome. Front Immunol. 2023: 14: 1158951) and slightly improved: the mouse lung tissue was fixed in 4% paraformaldehyde for 24 hours, then embedded in wax and sliced ​​at 4 μm. Hematoxylin and Eosin (H&E) were used to stain the lung tissue sections. H&E-stained lung tissue sections were observed under a microscope to evaluate the structural changes of the lung tissue, focusing on pathological features such as inflammatory cell infiltration, alveolar wall thickening, hemorrhage, and interstitial edema.

[0317] The specific rules for scoring lung tissue damage are as follows: (1) Scoring indicators: ① Inflammatory cell infiltration. ② Alveolar structural destruction. ③ Hemorrhage and fibrosis. ④ Pulmonary edema. (2) Scoring method: The scores of various pathological indicators are usually divided into 0-4 points, where 0 indicates no damage and 4 indicates the most severe damage. (3) Scoring criteria: 0 points, no damage; 1 point, mild damage, a small amount of inflammatory cell infiltration, mild alveolar wall thickening; 2 points, moderate damage, moderate amount of inflammatory cell infiltration, obvious alveolar wall thickening and partial hemorrhage; 3 points, severe damage, a large amount of inflammatory cell infiltration, severe alveolar wall thickening, and extensive hemorrhage; 4 points, extremely severe damage, large area of ​​alveolar collapse, hemorrhage and severe fibrosis.

[0318] 2.4 Determination of total lung wet-to-dry ratio

[0319] The mouse lung tissue was taken, and the moisture and part of the blood in the right upper lobe of the lung tissue were removed and weighed, which was recorded as the wet weight; then it was placed in a 60°C constant temperature oven to dry until constant weight was weighed, which was recorded as the dry weight, and the wet / dry weight ratio was calculated.

[0320] 2.5 Statistics

[0321] Same as “2.5” in “Test Example 1”.

[0322] 3. Results

[0323] 3.1 Effects on total protein concentration, cell number, TNF-α level, and IL-1β level in BALF of ARDS mice

[0324] The results are shown in Tables 7-11 and Figure 12-16 .

[0325] Table 7 Total protein concentration in BALF of mice in each group (n=8)

[0326]

[0327] Table 8 Number of cells in BALF of mice in each group (n=8)

[0328]

[0329] Table 9 TNF-α content in BALF of mice in each group (n=8)

[0330]

[0331] Table 10 IL-1β content in BALF of mice in each group (n=8)

[0332]

[0333] Table 11 IL-6 content in BALF of mice in each group (n=8)

[0334]

[0335] Table 7-11 and Figure 12-16 Shows:

[0336] 1) Compared with the Sham group, the total protein concentration, cell number, TNF-α level, IL-1β level and IL-6 level in BALF of ARDS mice were significantly increased (P < 0.0001), indicating that the model was successfully established. Compared with the ARDS group, dexamethasone treatment could significantly inhibit the increase of the above four indicators in BALF of ARDS mice.

[0337] 2) High-dose treatment with Ningfei Decoction could significantly reduce the above five indexes in BALF of ARDS mice (P<0.05 or P<0.01), while medium-dose treatment could only significantly reduce the number of cells and IL-6 level in BALF of ARDS mice (P<0.05); the effect of Ningfei Decoction was concentration gradient-dependent to a certain extent;

[0338] 3) Compared with the ARDS group, Ningfei Decoction + enema treatment could significantly reduce the total protein concentration, cell number, TNF-α, IL-1β and IL-6 levels in the BALF of ARDS mice (P < 0.01 or P < 0.001); and the inhibitory effect was better than that of the Ningfei Decoction medium-dose alone treatment group, and even better than that of the high-dose alone treatment group.

[0339] 3.2 H&E staining of lung tissue sections and lung injury scoring results

[0340] H&E staining results of lung tissue sections are shown in Fig.17 The lung injury scores of mice in each group are shown in Table 12 and Fig.18 .

[0341] Table 12 Lung injury scores of mice in each group (n=8)

[0342]

[0343] Table 12 and Fig.17 , Fig.18 The results showed that compared with the Sham group, the ARDS mice had destroyed alveolar structure, thickened lung septa, and a large number of inflammatory cells infiltrated, and the lung injury score of the mice was significantly increased (P < 0.0001). Compared with the ARDS group, the lung tissue structure of the mice in the dexamethasone group tended to be normal, with clear alveolar structure, thin alveolar wall, no obvious inflammatory cell infiltration in the alveolar wall and interstitium, and the tissue injury score was also significantly reduced (P < 0.0001).

[0344] Compared with the ARDS group, all doses of Ningfei Decoction could reduce the inflammatory infiltration and damage of lung tissue in ARDS mice, and its effect was related to the concentration gradient. Among them, the difference in the high-dose group was statistically significant (P < 0.01).

[0345] Compared with the ARDS group, Ningfei Decoction + enema treatment could significantly improve the lung tissue damage of ARDS mice (P < 0.001), and the inhibitory effect was significantly better than that of the medium-dose Ningfei Decoction alone treatment group.

[0346] 3.3 Mouse lung wet-to-dry weight ratio

[0347] The results are shown in Table 13 and Fig.19 .

[0348] Table 13 Lung wet / dry weight ratio of mice in each group (n=8)

[0349]

[0350] The wet / dry weight ratio of the lung is a direct indicator of pulmonary edema and a sensitive indicator of the severity of lung injury. Compared with the Sham group, the wet / dry weight ratio of the lung in the ARDS group was significantly increased (P≤0.0001), indicating that the model was successfully established and the lung injury of mice was severe. Compared with the ARDS group, dexamethasone could significantly reduce the wet / dry weight ratio of the lung in ARDS mice (P<0.001).

[0351] Compared with the ARDS group, the lung wet / dry weight ratio of each dose group of Ningfei Decoction was reduced, and the effect of reducing the lung wet / dry weight ratio in the medium and high dose groups was significant (P < 0.05 or P < 0.01), which was statistically significant.

[0352] Compared with the ARDS group, Ningfei Decoction + Enema could significantly reduce the lung wet / dry weight ratio of ARDS mice (P < 0.001), and the effect was significantly better than the medium dose of Ningfei Decoction alone (P < 0.05).

[0353] 4 Conclusion

[0354] Intratracheal instillation of LPS in mice can cause acute lung injury and respiratory distress in mice, which is manifested by increased levels of pulmonary inflammatory factors, increased total protein and cell counts in lung lavage fluid, and increased lung wet / dry weight ratio. Each dose group of Ningfei Decoction can improve various abnormal indicators of ARDS mice, and the effect is concentration gradient-related. The difference between the medium and high dose groups and the model group is statistically significant. Compared with the treatment of Ningfei Decoction alone, the oral administration of Ningfei Decoction combined with rectal enema has a significantly enhanced therapeutic effect on ARDS. The oral and enema Chinese medicine composition of the present invention has a synergistic effect on the therapeutic effect of ARDS.

[0355] In summary, the present invention provides a Chinese medicine composition I and a Chinese medicine composition II for acute respiratory distress syndrome (ARDS). In particular, oral administration of Chinese medicine composition I combined with enema of Chinese medicine composition II has a significant synergistic therapeutic effect on inhibiting lung inflammation, and can provide a new treatment option for clinical treatment of ARDS and saving patients' lives.

Claims

1. A pharmaceutical composition for treating acute respiratory distress syndrome characterized by pathogenic heat, phlegm, blood stasis in the lungs and obstruction of internal qi, comprising an oral Chinese medicine composition I; the Chinese medicine composition I comprises the following medicinal materials in parts by weight: 8-30 parts by weight of American ginseng, 7-26 parts by weight of turmeric, 8-30 parts by weight of angelica, 10-40 parts by weight of gypsum, 8-30 parts by weight of Fritillaria thunbergii, 5-20 parts by weight of apricot kernel, 8-30 parts by weight of mulberry bark, 5-20 parts by weight of rhubarb, 5-20 parts by weight of sodium sulfate, 5-20 parts by weight of immature bitter orange, 5-20 parts by weight of Magnolia officinalis; Preferably, the Chinese medicine composition I comprises the following medicinal materials in parts by weight: 10-20 parts by weight of American ginseng, 9-20 parts by weight of turmeric, 10-20 parts by weight of angelica, 15-30 parts by weight of gypsum, 10-20 parts by weight of Fritillaria thunbergii, 8-15 parts by weight of apricot kernel, 10-20 parts by weight of mulberry bark, 8-15 parts by weight of rhubarb, 8-15 parts by weight of sodium sulfate, 8-15 parts by weight of immature bitter orange, and 8-15 parts by weight of Magnolia officinalis.

2. The pharmaceutical composition according to claim 1, characterized in that The Chinese medicine composition I comprises the following medicinal materials in parts by weight: 15 parts by weight of American ginseng, 13 parts by weight of turmeric, 15 parts by weight of angelica, 20 parts by weight of gypsum, 15 parts by weight of thunbergii bulbs, 10 parts by weight of apricot kernels, 15 parts by weight of mulberry bark, 10 parts by weight of rhubarb, 10 parts by weight of sodium sulfate, 10 parts by weight of immature bitter orange, and 10 parts by weight of Magnolia officinalis.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that It also includes a Chinese medicine composition II for enema; the Chinese medicine composition II includes the following medicinal materials in parts by weight: 8-30 parts by weight of Chinese angelica, 5-20 parts by weight of peach kernel, 8-30 parts by weight of thunbergia thunbergii, 8-30 parts by weight of radish seeds, 7-26 parts by weight of rhubarb, 5-20 parts by weight of sodium sulfate, 5-20 parts by weight of immature bitter orange, 5-20 parts by weight of magnolia bark; Preferably, the Chinese medicine composition II comprises the following medicinal materials in parts by weight: 10-20 parts by weight of angelica sinensis, 8-15 parts by weight of peach kernel, 10-20 parts by weight of Fritillaria thunbergii, 10-20 parts by weight of radish seeds, 9-20 parts by weight of rhubarb, 8-15 parts by weight of sodium sulfate, 8-15 parts by weight of immature bitter orange, and 8-15 parts by weight of Magnolia officinalis.

4. The pharmaceutical composition according to claim 3, characterized in that The Chinese medicine composition II comprises the following medicinal materials in parts by weight: 15 parts by weight of Chinese angelica, 10 parts by weight of peach kernel, 15 parts by weight of thunbergii bulb, 15 parts by weight of radish seed, 13 parts by weight of rhubarb, 10 parts by weight of sodium sulfate, 10 parts by weight of immature bitter orange, and 10 parts by weight of magnolia bark.

5. The pharmaceutical composition according to any one of claims 1 to 4, characterized in that In the Chinese medicine composition I and the Chinese medicine composition II, the rhubarb is selected from raw rhubarb, wine rhubarb or cooked rhubarb.

6. A drug; the drug is a clinically acceptable preparation made from the pharmaceutical composition according to any one of claims 1 to 5 and pharmaceutically acceptable excipients; Preferably, the drug comprises at least item 1) of the following two items: 1) An oral preparation prepared from a Chinese medicine composition I, wherein the Chinese medicine composition I is as defined in claim 1 or 2; 2) An enema prepared from the Chinese medicine composition II, wherein the Chinese medicine composition II is as defined in claim 3 or 4.

7. A method for preparing the drug according to claim 6, comprising preparing the Chinese medicine composition I into an oral preparation, wherein the Chinese medicine composition I is as defined in claim 1 or 2; Preferably, the oral preparation is a decoction, and the preparation method comprises the following steps: A. preparing various medicinal materials according to the composition of the Chinese medicine composition I; B. decoct American ginseng with water to obtain American ginseng decoction; set aside; C. decocting turmeric, angelica, gypsum, fritillaria thunbergii, apricot kernel, mulberry bark, immature bitter orange, magnolia bark and rhubarb twice with water, wherein gypsum is decocted first and rhubarb is added later, and the filtrates are combined to obtain a decoction of medicinal materials; D. Combine the American ginseng decoction and the medicinal material decoction, mix evenly, concentrate if necessary, and divide into several portions; divide the mirabilite into the same number of portions, and take 1 portion of mirabilite and 1 portion of the medicinal solution at the same time.

8. The preparation method according to claim 7, characterized in that: It also includes preparing the Chinese medicine composition II into an enema, wherein the Chinese medicine composition II is as defined in claim 3 or 4; Preferably, the method for preparing the enema comprises the following steps: (1) preparing various medicinal materials according to the composition of the Chinese medicine composition II; (2) decoct each medicinal material except for Glauber's salt twice with water, add rhubarb last, combine the filtrates, and concentrate if necessary to obtain a decoction of the medicinal materials; (3) When using, add the sodium sulfate to the decoction of the medicinal materials and stir until the sodium sulfate is dissolved.

9. The preparation method according to claim 7 or 8, characterized in that The oral preparation or the enema is prepared by using Chinese medicine formula granules, comprising the following steps: A. taking a corresponding amount of Chinese medicine formula granules according to the composition of the Chinese medicine composition I or the Chinese medicine composition II; B. Mix the Chinese medicine formula granules, add appropriate amount of water, and stir until completely dissolved.

10. Use of the pharmaceutical composition according to any one of claims 1 to 5, the drug according to claim 6, or the drug directly obtained by the preparation method according to any one of claims 7 to 9 in the preparation of a drug for treating acute respiratory distress syndrome caused by pathogenic heat, phlegm, blood stasis in the lungs and obstruction of visceral qi, with symptoms of cough, asthma, dyspnea, bluish lips, and constipation; Preferably, the acute respiratory distress syndrome of pathogenic heat, phlegm, turbidity and blood stasis in the lungs and obstruction of visceral qi also includes fever.

11. The use according to claim 10, characterized in that: First, the oral preparation prepared from Chinese medicine composition I is given to the subject in need; if no stool is discharged or the symptoms are not relieved within 1-2 days, the enema prepared from Chinese medicine composition II is added, and enema is performed every other day until stool is discharged or the symptoms are relieved.

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