Application of traditional Chinese medicine composition in preparation of medicine for treating or preventing respiratory failure

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating or preventing respiratory failure. The traditional Chinese medicine composition comprises 1-3 parts of honey-fried ephedra, 1-10 parts of semen armeniacae amarae, 1-6 parts of platycodon grandiflorum, 1-6 parts of radix peucedani, 1-6 parts of thunberg fritillary bulb, 1-6 parts of radix stemonae, 1-3 parts of oroxylum indicum, 1-10 parts of radix glehniae and 1-3 parts of liquorice. The composition disclosed by the invention can be used for effectively relieving severe dysfunction of lung ventilation or ventilation and improving effective gas exchange, and can be used for treating or preventing respiratory failure.

Description

Technical Field

[0001] The present invention relates to the field of disease treatment drugs, and more specifically, to the use of a traditional Chinese medicine composition in preparing drugs for treating or preventing respiratory failure NOS dysfunction. Background Art

[0002] Respiratory failure NOS is a condition in which oxygen in the blood drops to dangerous levels or carbon dioxide rises to dangerous levels. The main manifestations are that the oxygen level in the blood becomes too low (hypoxic respiratory failure) and the carbon dioxide level in the blood becomes too high (hypercapnic respiratory failure). Sometimes patients have both low oxygen levels and high carbon dioxide levels. Patients usually have severe shortness of breath. Low blood oxygen levels can cause shortness of breath. People with light skin will have bluish skin (cyanosis), and people with dark skin will have gray or white mouths, around eyes, and nails. Low oxygen levels, high carbon dioxide levels, and increased blood acidity cause confusion and drowsiness. Due to abnormal lung function, the brain and heart malfunction, leading to drowsiness (sometimes even loss of consciousness) and abnormal heart rhythm (arrhythmia), both of which can lead to death. Respiratory failure dysfunction can be caused by lung disease or as a complication of various diseases. It must be treated promptly, otherwise it can be life-threatening. Acute respiratory failure (ARF) is a clinical syndrome of a series of physiological dysfunctions caused by severe ventilation or gas exchange disorders caused by primary or secondary lesions of the respiratory system, which makes the body unable to maintain adequate gas exchange under normal atmospheric pressure, leading to severe hypoxia or combined with carbon dioxide retention. The causes of acute respiratory failure are mainly divided into three categories: airway obstructive diseases, lung parenchymal lesions and respiratory pump abnormalities.

[0003] Respiratory failure NOS dysfunction often requires meticulous treatment to correct respiratory function and protect the patient's life safety. Traditional Chinese medicine often has the function of regulating the body's qi and blood, yin and yang, and internal organs. It can help adjust the body's internal environment, improve the body's resistance and self-healing ability, and thus promote recovery. Many herbs in traditional Chinese medicine have sedative, expectorant, and cough-relieving effects, which can help relieve symptoms such as dyspnea and chest tightness, and improve the patient's comfort. Traditional Chinese medicine can also regulate the function of the human immune system, enhance the body's resistance, help prevent and reduce the inflammatory response caused by respiratory infections, and reduce the risk of worsening of the disease. Summary of the invention

[0004] The present invention aims to propose a use of a Chinese medicine composition in the preparation of a drug for treating or preventing respiratory failure NOS dysfunction, wherein the Chinese medicine composition comprises, by weight ratio: 1-3 parts of honey-fried ephedra, 1-10 parts of bitter almonds, 1-6 parts of platycodon grandiflorum, 1-6 parts of peucedanum, 1-6 parts of thunbergii, 1-6 parts of stemon, 1-3 parts of oroxylum, 1-10 parts of northern adenophora, and 1-3 parts of liquorice. The respiratory failure NOS is acute respiratory failure, preferably airway obstructive disease, lung parenchyma lesions or respiratory pump abnormalities.

[0005] Furthermore, the Chinese medicine composition includes: 1-1.5 parts of honey-roasted ephedra, 2-4 parts of bitter almonds, 1-3 parts of platycodon, 1-3 parts of peucedanum, 1-3 parts of thunbergii, 1-3 parts of stemona, 1-1.5 parts of oroxylum, 2-4 parts of northern adenophora, and 1-1.5 parts of liquorice.

[0006] Furthermore, the Chinese medicine composition includes: 1-1.5 parts of honey-roasted ephedra, 3-4 parts of bitter almonds, 1.5-2 parts of platycodon, 1.5-2 parts of peucedanum, 1.5-2 parts of thunbergii, 1.5-2 parts of stemona, 1-1.5 parts of oroxylum, 3-4 parts of northern adenophora, and 1-1.5 parts of liquorice.

[0007] Optionally, the Chinese medicine composition includes: 1 part of honey-roasted ephedra, 3.33 parts of bitter almonds, 2 parts of platycodon, 2 parts of peucedanum, 2 parts of thunbergii, 2 parts of stemona, 1 part of oroxylum, 3.33 parts of northern adenophora, and 1 part of licorice.

[0008] Among them, the raw materials used in the present invention can be directly ground into powder, or they can be extracts prepared by conventional means in the art; the composition can be directly ground into powder by traditional methods, or it can be an extract prepared by conventional means, so as to be made into different dosage forms, obtain better therapeutic effects and be more conducive to the preparation of modern drug dosage forms.

[0009] Specifically, the drug for treating or preventing NOS dysfunction in respiratory failure provided by the present invention is in an optional preparation form.

[0010] Furthermore, the preparation forms include tablets, capsules, pills, powders, granules, and pellets.

[0011] Preferably, the preparation method of the Chinese medicine composition as described above may include the following steps: adding 4-8 times the amount of 50%-80% ethanol to the four raw materials of honey-roasted ephedra, peucedanum, fritillaria thunbergii and stemonae, refluxing for 1-3 hours, filtering, and concentrating the filtrate under reduced pressure to obtain a clear paste; heating Platycodon grandiflorum, Glehnia littoralis, Oroxylum indica and Glycyrrhiza uralensis with water to boil, then adding bitter almonds and boiling, filtering, and concentrating the filtrate under reduced pressure to obtain a clear paste; combining the above two clear pastes and drying.

[0012] Furthermore, the preparation method of the Chinese medicine composition as described above may include the following steps: adding 6 times of 70% ethanol to ephedra, peucedanum, thunbergii and radix stemonae, refluxing for 2 hours, filtering, adding 4 times of 70% ethanol to the residues, refluxing for 2 hours, filtering, combining the filtrate, and concentrating under reduced pressure film to a relative density of 1.07 to obtain an alcohol-extracted clear paste; adding 10 times of water to bitter almond, northern adenophora, platycodon, licorice and oroxylum, boiling them and then adding bitter almond, boiling for 1.5 hours, filtering, adding 8 times of water to the residues, boiling for 1.5 hours, filtering, combining the filtrate, and concentrating under reduced pressure film to a relative density of 1.09 to obtain a water-extracted clear paste; combining the clear pastes, mixing them evenly, and drying.

[0013] The present invention also provides a method for preparing the aforementioned granules, which can be optionally: the dry powder prepared by any of the above composition preparation methods is mixed with 37%-41% dextrin and 1% aspartame, and dry granulated to obtain the granules.

[0014] The present invention also proposes the use of the Chinese medicine composition as described above in the preparation of a drug for treating or preventing lung injury, wherein the Chinese medicine composition comprises: 1-3 parts of honey-fried ephedra, 1-10 parts of bitter almonds, 1-6 parts of platycodon, 1-6 parts of peucedanum, 1-6 parts of thunbergii, 1-6 parts of stemon, 1-3 parts of oroxylum, 1-10 parts of northern adenophora, and 1-3 parts of liquorice. The lung injury may be acute lung injury. The lung injury is caused by the imbalance of the body's inflammatory response and oxidative stress or acute lung injury.

[0015] Furthermore, the Chinese medicine composition includes: 1-1.5 parts of honey-roasted ephedra, 2-4 parts of bitter almonds, 1-3 parts of platycodon, 1-3 parts of peucedanum, 1-3 parts of thunbergii, 1-3 parts of stemona, 1-1.5 parts of oroxylum, 2-4 parts of northern adenophora, and 1-1.5 parts of liquorice.

[0016] Furthermore, the Chinese medicine composition includes: 1-1.5 parts of honey-roasted ephedra, 3-4 parts of bitter almonds, 1.5-2 parts of platycodon, 1.5-2 parts of peucedanum, 1.5-2 parts of thunbergii, 1.5-2 parts of stemona, 1-1.5 parts of oroxylum, 3-4 parts of northern adenophora, and 1-1.5 parts of liquorice.

[0017] Optionally, the Chinese medicine composition includes: 1 part of honey-roasted ephedra, 3.33 parts of bitter almonds, 2 parts of platycodon, 2 parts of peucedanum, 2 parts of thunbergii, 2 parts of stemona, 1 part of oroxylum, 3.33 parts of northern adenophora, and 1 part of licorice.

[0018] The composition of the present invention can effectively alleviate severe disorders of pulmonary ventilation or gas exchange function, enhance effective gas exchange, reduce hypoxia with (or without) carbon dioxide retention, reduce the accumulation of peroxidation product malondialdehyde (MDA), and reduce cell death; reduce the content of nitric oxide synthase (iNOS), reduce the production of nitric oxide (NO), and alleviate the degree of tissue damage; increase the expression of IL-10 factor, inhibit the release of pro-inflammatory factors, and reduce the content of myeloperoxidase (MPO), and alleviate inflammatory response. DETAILED DESCRIPTION

[0019] Respiratory failure is a clinical syndrome characterized by hypoxia with (or without) carbon dioxide retention due to impaired ventilation and gas exchange function of the lungs after respiratory insufficiency enters the decompensation stage. There are many causes of acute respiratory failure, but the main causes are severe pneumonia and lung injury. Therefore, replicating the pathological model of acute respiratory failure by inducing lung injury in experimental animals is a common method to study the pathogenesis of respiratory failure. The main cause of lung injury is the imbalance of the body's inflammatory response and oxidative stress. The inflammatory response involves the activation of inflammatory cells and the release of inflammatory cytokines, which can cause lung injury and further acute hypoxic respiratory insufficiency or acute respiratory failure. When the body is adversely stimulated, the oxidation and antioxidant processes become unbalanced, leading to the accumulation of peroxidation products such as malondialdehyde (MDA), which leads to cell death. Inducible nitric oxide synthase (iNOS) produced by macrophages is considered to be an intracellular messenger for the development of inflammation. Its high level catalyzes the massive production of nitric oxide (NO), which in turn aggravates the degree of tissue damage. At the same time, the body will initiate an anti-inflammatory response, and the expression of the anti-inflammatory factor IL-10 increases to inhibit the release of pro-inflammatory factors. Myeloperoxidase (MPO), as a member of the heme peroxidase superfamily, also indicates excessive inflammatory response. Therefore, acute respiratory failure can be improved by inhibiting inflammatory response and oxidative stress to alleviate lung damage.

[0020] The present invention aims to provide a Chinese medicine composition for use in preparing a medicine for treating or preventing respiratory failure NOS. The following will be described in detail in conjunction with the contents of the experimental examples.

[0021] It is particularly important to point out that similar substitutions and modifications made to the present invention are obvious to those skilled in the art, and they are all considered to be included in the present invention. Relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments.

[0022] If no specific conditions are specified in the present invention, all experiments were carried out under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used without specifying the manufacturer are conventional products that can be purchased commercially.

[0023] Example 1. Preparation of Chinese medicine compound granules

[0024] Raw materials: 100g of honey-roasted ephedra, 333g of bitter almond, 200g of platycodon, 200g of peucedanum, 200g of thunbergii, 200g of stemona, 100g of oroxylum, 333g of northern adenophora, and 100g of licorice.

[0025] Add 6 times of 70% ethanol to the medicinal materials (cooked pieces) such as ephedra, peucedanum, thunbergii and radix stemonae, reflux for 2 hours, filter, add 4 times of 70% ethanol to the medicinal residue, reflux for 2 hours, filter, combine the filtrate, and concentrate by vacuum film to a relative density of 1.07 (60°C) to obtain an alcohol-extracted clear paste, which is set aside for use. Add 10 times of water to the five medicinal materials (cooked pieces) such as bitter almond, northern adenophora, platycodon, licorice and oroxylum, boiled and added, boiled for 1.5 hours, filtered, add 8 times of water to the medicinal residue, boiled for 1.5 hours, filtered, combined the filtrate, and concentrated by vacuum film to a relative density of 1.09 (60°C) to obtain a water-extracted clear paste. Combine the clear pastes, mix well, spray dry, and obtain dry powder. Dextrin (37% to 41% of the theoretical yield of particles) and aspartame (1% of the theoretical yield of particles) were added to the dry powder, mixed evenly, dry granulated, and packaged with aluminum foil (4.0 g per bag) to obtain 1000 g of Chinese medicine composition granules.

[0026] Example 2 Effects on LPS-induced Acute Respiratory Failure in Wistar Rats

[0027] Animals: Wistar rats, SPF grade, male, 6-8 weeks old, weighing 160-180 g, 60 in total, purchased from Sibeifu (Beijing) Biotechnology Co., Ltd.

[0028] Drug: Dexamethasone acetate tablets (batch number 2101142) Anhui Golden Sun Biochemical Pharmaceutical Co., Ltd.

[0029] Test drug: Chinese medicine composition granules, provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd. Drug dosage: The daily dosage for humans is 52.99 g of crude drug, the clinical dosage for adults (calculated as 70 kg) is 0.76 g of crude drug / kg, and the equivalent dosage for rats is calculated to be 4.69 g of crude drug / kg. This dosage is set as the medium dosage, and the low, medium, and high dosage groups are set according to the dosage ratio of 0.5:1:2, with dosages of 2.345, 4.69, and 9.38 g of crude drug / kg, respectively, which are equivalent to 3.085, 6.17, and 12.34 times the clinical dosage, respectively.

[0030] Reagents: Lipopolysaccharide (LPS): SIGMA, extracted from Escherichia coli O55:B5, batch number O00135218; dexamethasone acetate tablets Anhui Golden Sun Biochemical Pharmaceutical Co., Ltd., batch number 2101142; MDA kit No. S0131S, purchased from Beyotime Biotechnology Co., Ltd.; IL-10 kit No. 69-30495, iNOS kit No. 69-30327, MPO kit No. 69-30257, all purchased from Wuhan Merck Biotechnology Co., Ltd.

[0031] Instruments: MULITSKAN Sky microplate reader (Thermo Fisher Scientific, USA), MINIP-2500 microplate centrifuge, MINI-4K microcentrifuge (Hangzhou Miou Instrument Co., Ltd.), 5418R low-temperature high-speed centrifuge (Eppendorf, Germany), Nano-100 micro-spectrophotometer (Hangzhou Aosheng Instrument Co., Ltd.).

[0032] Experimental methods

[0033] 60 Wistar rats were randomly divided into 6 groups, 10 rats in each group, namely blank group, model group, positive control group, and low, medium and high dose groups of Chinese medicine composition granules. Except for the blank group and the model group, which were given the same volume of pure water, the other groups were continuously gavaged for 14 days, twice a day. The model was established by exposed intratracheal instillation. 0.5h after the last administration, the hair on the neck of the rat was shaved, and the neck area was disinfected with iodine. The midline of the rat's neck was incised to expose the trachea, and a sterilized intravenous indwelling needle was inserted into the trachea. Then, the rat's body position was tilted 60°, and the drug was slowly administered into the trachea with a microsyringe for 1 minute. After the drip, the rat was rotated upright to evenly distribute the drug solution in both lungs. Finally, the wound was sutured and disinfected. Except for the blank group, which was intratracheally instilled with sterile PBS at the same dose as the model group, the other groups were instilled with 5mg / kg LPS to replicate the acute respiratory failure model by inducing lung injury. After the modeling is completed, the rats have obvious breathing sounds and a small amount of secretions flow out of their mouths and noses, indicating that the drug has entered the trachea, and the modeling can be preliminarily determined to be successful.

[0034] Detection indicators: ① 6 hours after modeling, the rats were anesthetized with 10% chloral hydrate 0.35g / kg, 1ml of abdominal aortic blood was drawn into an anticoagulant tube, and the arterial oxygen partial pressure (PO2) and carbon dioxide partial pressure (PCO2) of the blood were detected as soon as possible using an automatic blood gas analyzer. ② The left lung lobe was lavaged with 1mL of normal saline, repeated 3 times, and the alveolar lavage fluid (BALF) was collected. The ELISA was used to detect the content of IL-10 and iNOS in the alveolar lavage fluid according to the steps in the kit instructions. ③ The right lung tissue of the rat was taken, and cold normal saline was used as the homogenization medium to prepare lung tissue homogenate, and the MDA and MPO contents were detected according to the kit instructions.

[0035] The results showed that compared with the blank group, the PO2 value in the model group decreased (P<0.01) and the PCO2 value increased (P<0.01). Compared with the model group, the PO2 value in the high-dose group increased significantly (P<0.01), and the PCO2 values ​​in the medium- and high-dose groups decreased significantly (P<0.05 or P<0.01). See Table 1.

[0036] Compared with the blank group, the levels of iNOS and IL-10 in the model group were significantly increased (P<0.01). Compared with the model group, the levels of iNOS in the medium and high dose groups were significantly decreased (P<0.01), and the levels of IL-10 in the low, medium and high dose groups were significantly increased (P<0.05 or P<0.01). See Table 2.

[0037] After LPS modeling, the levels of MDA and MPO in the model group increased significantly (P<0.01); compared with the model group, the levels of MDA in the low, medium and high dose groups decreased significantly (P<0.05 or P<0.01), and the MPO activity in the medium and high dose groups decreased significantly (P<0.01). See Table 3.

[0038] The above results suggest that the Chinese medicine composition granules can significantly increase the PO2 value in arterial blood, reduce the PCO2 value, and effectively improve the ventilation and ventilation dysfunction of the lungs. In addition, the Chinese medicine composition granules can reduce the expression level of iNOS in rat BALF, increase the expression level of IL-10 in rat BALF, and significantly reduce the MDA content and MPO activity, and alleviate acute respiratory failure induced by lung injury by inhibiting inflammatory response and oxidative stress. Therefore, the Chinese medicine composition granules have a certain therapeutic effect on acute respiratory failure.

[0039] Table 1 Effects on rat arterial blood PO2 and PCO2

[0040]

[0041] Note: Compared with the blank control group, * P<0.05, ** P<0.01. Compared with the model group # P<0.05, ## P<0.01.

[0042] Table 2 Effects on the levels of inflammatory factors in rat BALF (n=10)

[0043]

[0044] Note: Compared with the blank control group, * P<0.05, ** P<0.01. Compared with the model group# P<0.05, ## P<0.01.

[0045] Table 3 Effects on oxidative stress factors in rat lung tissue (n=10)

[0046]

[0047] Note: Compared with the blank control group, * P<0.05, ** P<0.01. Compared with the model group # P<0.05, ## P<0.01.

[0048] The above is only an exemplary description of the implementation mode of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for treating or preventing respiratory failure NOS; characterized in that: The traditional Chinese medicine composition comprises: 1-3 parts of honey-fried ephedra, 1-10 parts of bitter almond, 1-6 parts of platycodon, 1-6 parts of peucedanum, 1-6 parts of thunbergii, 1-6 parts of stemona, 1-3 parts of oroxylum, 1-10 parts of northern adenophora, and 1-3 parts of liquorice.

2. The use according to claim 1, characterized in that The traditional Chinese medicine composition comprises: 1-1.5 parts of honey-fried ephedra, 2-4 parts of bitter almonds, 1-3 parts of platycodon, 1-3 parts of peucedanum, 1-3 parts of thunbergii, 1-3 parts of stemona, 1-1.5 parts of oroxylum, 2-4 parts of northern adenophora, and 1-1.5 parts of liquorice.

3. The use according to claim 1, characterized in that The Chinese medicine composition comprises: 1 part of honey-roasted ephedra, 3.33 parts of bitter almonds, 2 parts of platycodon, 2 parts of peucedanum, 2 parts of thunbergii bulbs, 2 parts of stemona, 1 part of oroxylum bungeana, 3.33 parts of northern adenophora, and 1 part of liquorice.

4. The use according to any one of claims 1 to 3, characterized in that: The drug for treating or preventing respiratory failure (NOS) is in an optional preparation form.

5. The use according to any one of claims 1 to 3, characterized in that: The respiratory failure NOS is acute respiratory failure, preferably airway obstructive disease, lung parenchymal lesions or respiratory pump abnormalities.

6. The use according to any one of claims 1 to 3, characterized in that: The preparation forms include tablets, capsules, pills, powders, granules and drop pills.

7. A use according to claim 6, characterized in that The preparation of the Chinese medicine composition comprises the following steps: Take four raw materials of honey-roasted ephedra, peucedanum, thunbergii and radix stemonae, add 4-8 times amount of 50%-80% ethanol, reflux for 1-3 hours, filter, and concentrate the filtrate under reduced pressure to obtain a clear paste; heat Platycodon grandiflorum, Glehnia littoralis, Oroxylum indica and licorice with water, then add bitter almonds and boil, filter, and concentrate the filtrate under reduced pressure to obtain a clear paste; combine the above two clear pastes, mix well and dry.

8. The use according to claim 7, characterized in that: The preparation of the traditional Chinese medicine composition comprises: adding 6 times of 70% ethanol to ephedra, peucedanum chinense, fritillaria thunbergii and stemonae, refluxing for 2 hours, filtering, adding 4 times of 70% ethanol to the residues, refluxing for 2 hours, filtering, combining the filtrate, concentrating under reduced pressure film to a relative density of 1.07, and obtaining an alcohol-extracted clear paste; adding 10 times of water to bitter almond, northern adenophora, platycodon, licorice and oroxylum, wherein the bitter almond is boiled and then added, boiling for 1.5 hours, filtering, adding 8 times of water to the residues, boiling for 1.5 hours, filtering, combining the filtrate, concentrating under reduced pressure film to a relative density of 1.09, and obtaining a water-extracted clear paste; combining the clear pastes, mixing evenly, and drying.

9. Use of a Chinese medicine composition in the preparation of a drug for treating or preventing lung injury, characterized in that: The traditional Chinese medicine composition comprises: 1-3 parts of honey-fried ephedra, 1-10 parts of bitter almond, 1-6 parts of platycodon, 1-6 parts of peucedanum, 1-6 parts of thunbergii, 1-6 parts of stemona, 1-3 parts of oroxylum, 1-10 parts of northern adenophora, and 1-3 parts of liquorice.

Images