Application of Yangxue Oral Liquid in preparation of drugs for improving blood oxygen saturation

Abstract

The present application belongs to the technical field of medicine preparation, and relates to application of a blood-nourishing oral liquid in preparation of medicine for improving blood oxygen saturation. The blood-nourishing oral liquid can improve blood oxygen saturation, improve hypoxemia, improve lung function, and has a preventive and / or therapeutic effect on lung injury, especially acute lung injury.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine preparation, and particularly relates to application of a blood-nourishing oral liquid in preparation of a medicine for improving blood oxygen saturation. BACKGROUND

[0002] Acute lung injury (ALI) is caused by damage to alveolar epithelial cells and capillary endothelial cells due to direct and indirect injury factors, resulting in diffuse pulmonary interstitial and alveolar edema, and leading to acute hypoxic respiratory insufficiency. The pathological and physiological characteristics are reduced lung volume, reduced lung compliance, and imbalance of ventilation / blood flow ratio, and the clinical manifestations are progressive hypoxemia and respiratory distress, and the lung imaging shows non-uniform exudative lesions.

[0003] Acute lung injury is an exudative lesion, and treatment methods can be selected from traditional Chinese medicine treatment, western medicine treatment and hyperbaric oxygen treatment.

[0004] Western medicine treatment:

[0005] The most common treatment method for acute lung injury is to use adrenal cortex hormone for treatment. However, the side effects of adrenal cortex hormone are also obvious, mainly promoting protein decomposition and inhibiting protein synthesis, producing negative nitrogen balance; increasing calcium and phosphorus metabolism, and having an anti-vitamin D effect, so as to affect calcium absorption; long-term use can also inhibit the activity of bone cells, causing bone formation disorders, leading to osteoporosis, and even causing bone fracture. In addition, adrenal cortex hormone has an anti-growth hormone effect, which can inhibit bone growth and protein synthesis.

[0006] In addition, acute lung injury can also be treated by licorice tablets, ambroxol and the like.

[0007] Licorice tablets, as a common traditional Chinese medicine, can timely relieve the symptoms of dyspnea, chest tightness and shortness of breath of patients; however, licorice tablets contain opiate components, are easy to be addictive, and are not suitable for long-term use.

[0008] Ambroxol: in the case of excessive sputum or with purulent sputum, some expectorant drugs such as ambroxol can be used for treatment, which can effectively improve the phenomenon of excessive sputum, cough and asthma of patients. However, ambroxol can easily cause adverse reactions such as nausea, vomiting, diarrhea, abdominal pain and skin rash.

[0009] At present, there is still a lack of acute lung injury treatment drugs with small side effects. SUMMARY

[0010] The application aims to provide an application of the blood-nourishing oral liquid in the preparation of a medicine for improving blood oxygen saturation.

[0011] The application provides the application of the blood-nourishing oral liquid in the preparation of a medicine for improving blood oxygen saturation.

[0012] The application also provides the application of the blood-nourishing oral liquid in the preparation of a medicine for improving hypoxemia.

[0013] The application also provides the application of the blood-nourishing oral liquid in the preparation of a medicine for improving lung function.

[0014] The application also provides the application of the blood-nourishing oral liquid in the preparation of a medicine for preventing and / or treating lung injury.

[0015] Preferably, the lung injury includes acute lung injury.

[0016] The application also provides the application of the blood-nourishing oral liquid in the preparation of a medicine for treating inflammation.

[0017] The application provides the application of the blood-nourishing oral liquid in the preparation of a medicine for improving blood oxygen saturation. BRIEF DESCRIPTION OF DRAWINGS

[0018] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments will be briefly introduced as follows. Obviously, the drawings in the following description only constitute some embodiments of the present application, and other drawings can be obtained by those skilled in the art without any creative effort on the basis of these drawings.

[0019] Figure 1 The content of the inflammatory factor interleukin-1 of cells before and after the test medicine provided by the present application is determined.

[0020] Figure 2 The content of the inflammatory factor interleukin-6 of cells before and after the test medicine provided by the present application is determined.

[0021] Figure 3 The content of the inflammatory factor tumor necrosis factor alpha (TNF-α) of cells before and after the test medicine provided by the present application is determined. DETAILED DESCRIPTION

[0022] The application provides the application of the blood-nourishing oral liquid in the preparation of a medicine for improving blood oxygen saturation.

[0023] The application also provides the use of the blood-nourishing oral liquid in the preparation of a medicine for improving hypoxemia.

[0024] The application also provides the use of the blood-nourishing oral liquid in the preparation of a medicine for improving lung function. The blood gas analysis test results show that the blood-nourishing oral liquid can effectively improve the hypoxemia index, increase the blood oxygen saturation, and improve the lung function.

[0025] The application also provides the use of the blood-nourishing oral liquid in the preparation of a medicine for preventing and / or treating lung injury. In the application, the lung injury includes acute lung injury. The blood gas analysis and the lung tissue wet / dry weight ratio detection results show that the blood-nourishing oral liquid can effectively reduce the lung tissue injury of the ALI model mice, and the blood-nourishing oral liquid has a preventive and / or therapeutic effect on acute lung injury.

[0026] The application also provides the use of the blood-nourishing oral liquid in the preparation of a medicine for treating inflammation. With the increase of the dose of the blood-nourishing oral liquid, the IL-1β content, the IL-6 content, and the tumor necrosis factor alpha (TNF-α) content are reduced, which shows that the blood-nourishing oral liquid can effectively reduce the inflammatory reaction, thereby improving the acute lung injury.

[0027] In the application, the preparation raw materials of the blood-nourishing oral liquid preferably include soap ash, sea buckthorn, hawthorn, jujube, and auxiliary materials.

[0028] In the application, the auxiliary materials preferably include sucrose, vitamin C, sodium benzoate, and citric acid.

[0029] The application does not have special limitations on the source of the blood-nourishing oral liquid. The blood-nourishing oral liquid in the application can be a commercially available product, such as the 12 bottles / box blood-nourishing oral liquid sold by Hubei Phoenix White Cloud Mountain Pharmaceutical Co., Ltd. In the application, the preparation raw materials of the blood-nourishing oral liquid preferably include the following components by weight: soap ash 5.3 parts, sea buckthorn 200 parts, hawthorn 100 parts, jujube 100 parts, vitamin C 5 parts, sucrose 200 parts, and sodium benzoate 2 parts, and the pH value is adjusted to 2.5-4.0 by citric acid.

[0030] In order to further illustrate the application, the use of the blood-nourishing oral liquid provided by the application in the preparation of a medicine for increasing blood oxygen saturation is described in detail below in combination with the accompanying drawings and examples, but they should not be understood as limiting the protection scope of the application.

[0031] Example 1

[0032] 50 C57BL / 6 mice were randomly divided into 5 groups: control (CON) group, model (LPS) group, low-dose Yangxue oral liquid group (200 mg / Kg), medium-dose Yangxue oral liquid group (400 mg / Kg) and high-dose Yangxue oral liquid group (600 mg / Kg), 10 in each group. The clinical equivalent dose of Yangxue oral liquid (purchased from Hubei Phoenix Baiyun Mountain Pharmaceutical Co., Ltd.) was 200-400 mg / Kg.

[0033] Preparation of acute lung injury (ALI) mouse model and administration: LPS was prepared into 0.5 g / L and 2 g / L solutions (solvent: normal saline) before the experiment. Each animal was intraperitoneally injected with LPS (2 mg / Kg) for the first time and tracheally instilled with LPS (4 mg / Kg) for the second time. After instillation, the animal was immediately straightened and rotated left and right for modeling. The control group of mice was intraperitoneally injected with the same volume of normal saline as the model group for the first time, and tracheally instilled with the same volume of normal saline as the model group for the second time. The Yangxue oral liquid groups of various doses were intraperitoneally injected with Yangxue oral liquid 30 min before the first intraperitoneal injection of LPS and 30 min after the second tracheal instillation of LPS. The control group and the model group of mice were given the same volume of normal saline as the Yangxue oral liquid groups of various doses at the same time.

[0034] Measurement of hemodynamics

[0035] Right common carotid artery cannulation method for arterial blood gas analysis: The mice were intraperitoneally injected with 20% urethane aqueous solution (1 ml / 100 g), and the limbs were fixed on the wooden board in a supine position with adhesive tape. After the skin was disinfected with alcohol, the skin was cut about 1.5 cm from the top to the bottom along the median line of the neck. The connective tissue between the sternothyroid muscle and the sternothyroid muscle was separated with tissue forceps along the anterior margin of the sternothyroid muscle. The pulsating common carotid artery can be seen on the right deep side of the trachea. The accompanying nerve was separated with a glass needle. A common carotid artery about 1.5 cm long was separated along the direction of the blood vessel. The distal end was ligated with silk thread, and the proximal end was clamped with an artery clamp and threaded with a silk thread. The mouse board was moved to the dissection microscope. A "V" shape was cut with a microscissors near the distal end of the artery, about 1 / 2 of the diameter of the artery, at an angle of about 30-40 degrees with the long axis of the blood vessel. The left hand held a microforceps to lift the incision, and the right hand held a pre-vacuum arterial blood collection device that had been heparinized. The PE microcatheter was inserted into the artery and fixed with the standby silk thread. The arterial clamp was loosened, the pre-vacuum arterial blood collection set was closed (OFF) to the position of a 5 ml syringe, 0.1-0.2 ml of arterial blood was immediately aspirated with a 1 ml syringe, the closed valve (OFF) was turned to the microcatheter position again, the 1 ml syringe was removed, and the blood gas analyzer was immediately detected.

[0036] Heart rate and peripheral blood oxygen saturation (SpO2) were measured using PhysioSuite (Kent Scientific) at baseline and at the end of the experiment. The animals in each treatment group were read at 24 h after the second intratracheal instillation of LPS, and the average values were analyzed.

[0037] The diagnostic criteria of ALI is to evaluate the degree of hypoxemia by arterial blood gas analysis to determine the ratio of arterial oxygen partial pressure (PaO2) to inhaled oxygen concentration percentage (FiO2) (PaO2 / FiO2). The ALI animal model of the present application is constructed without ventilator support, and the present application mainly uses significant and sustained SpO2 decrease and PaO2 / FiO2 ratio to measure the degree of hypoxemia. The SpO2 and PaO2 / FiO2 decrease of the control group and model group mice are compared, and the general state of the mice such as spirit and fur color, whether there is dyspnea, skin cyanosis and other conditions are observed to evaluate whether the modeling is successful.

[0038] The results are shown in Tables 1 and 2.

[0039] Table 1 Blood gas analysis results

[0040]

[0041]

[0042]

[0043] Table 2 Blood gas analysis results (average)

[0044]

[0045] Detection index explanation:

[0046] Blood oxygen partial pressure (PaO2): to determine whether the body is hypoxic and its degree. When the arterial oxygen partial pressure is lower than the lowest value in the normal range, it is called hypoxemia.

[0047] Carbon dioxide partial pressure (PaCO2): when PaCO2>6.0kPa, it is hypercapnia, indicating that the lung ventilation is insufficient, which can cause respiratory acidosis or respiratory failure; when PCO2<4.67kPa, it is hypocapnia, indicating that the lung ventilation is excessive, which can cause respiratory alkalosis.

[0048] Oxygenation index (PaO2 / FiO2): is an indicator for detecting whether oxygen can be effectively transmitted from the airway to the blood during patient breathing. A high ratio indicates better oxygen diffusion in the patient's lungs. A low ratio indicates severe lung function impairment.

[0049] Arterial oxygen saturation (SaO2): reflects whether the body is hypoxic and the degree of hypoxia, but its sensitivity to reflect hypoxia is insufficient.

[0050] Conclusion: Through the blood gas analysis of the acute lung injury (ALI) model mouse test group, the partial pressure of oxygen (PaO2), oxygenation index (PaO2 / FiO2), and blood oxygen saturation (SaO2) index of the low-dose, medium-dose, and high-dose groups of Yangxue Oral Liquid increased with the increase of the dose, showing a dose-effect relationship; the high value of the partial pressure of carbon dioxide (PaCO2) is an important indicator for detecting ALI, and the test showed that PaCO2 decreased with the increase of the dose; Conclusion: Yangxue Oral Liquid can effectively improve the indicators of hypoxemia, increase the blood oxygen saturation, and improve the lung function.

[0051] After blood gas analysis, 25 mice were selected for the detection of the wet-to-dry weight ratio (W / D) of lung tissue.

[0052] The surface water of the lung tissue was gently absorbed with filter paper, and the wet weight was accurately weighed. The lung tissue was baked in a 70℃ air-drying oven for 48h until the weight was constant. The wet and dry weights were accurately weighed, and the W / D was calculated according to the formula. The results are shown in Table 3.

[0053] Table 3 Results of lung tissue wet-to-dry weight ratio detection

[0054]

[0055]

[0056] Through the acute lung injury (ALI) mouse model detection, the wet-to-dry weight ratio of lung tissue decreased with the increase of the dose of Yangxue Oral Liquid. The wet-to-dry weight ratio of lung tissue is an indicator for evaluating the severity of ALI. The greater the wet-to-dry weight ratio, the more severe the pulmonary edema, and the more severe the ALI. Preliminary analysis results show that through the acute lung injury (ALI) mouse model group detection, the mean value of wet-to-dry weight ratio is 6.340; the mean values of the low-dose, medium-dose, and high-dose Yangxue Oral Liquid groups are 5.416, 5.318, and 5.170, respectively. This indicates that the wet-to-dry weight ratio of lung tissue in the test group decreases with the increase of the dose of Yangxue Oral Liquid, showing a dose-effect relationship. The results show that Yangxue Oral Liquid can effectively reduce the lung tissue damage of ALI model mice.

[0057] In addition, 25 mice were detected for the content of IL-1, IL-6, and TNF-α in lung tissue by ELISA kit

[0058] Take lung tissue, add tissue protein extractant, and homogenize thoroughly in an automatic homogenizer. Centrifuge at 3000 r / min for 20 min. According to the ELISA kit method, set up blank control wells and standard wells in the test, and use the instructions to standardize sample addition. Finally, detect the absorbance at 450 nm, and according to the absorbance value and the corresponding concentration value of the standard, prepare a standard curve. According to the standard curve, calculate the concentration value of the sample to be tested IL-1, IL-6 and TNF-α. Proinflammatory cytokines (IL-1, IL-6 and TNF-α) have a wide range of biological activities and help to coordinate the body's response to infection.

[0059] IL-1 cytokine has two types of IL-1α and IL-1β, and inflammation often occurs with the secretion of a large amount of IL-1β. The secretion of IL-1β is an important influencing factor for the onset of inflammation in some diseases, therefore, the monitoring of IL-1β level plays a crucial role in the prevention and treatment of inflammatory diseases. The higher the IL-1β content, the more severe the inflammatory reaction; the lower the IL-1β content, the less severe the inflammatory reaction. The detection of IL-1β content decreases with the increase of the dose in the present application, indicating that the blood-nourishing oral liquid can effectively reduce the inflammatory reaction, thereby improving the state of acute lung injury.

[0060] IL-6, i.e. interleukin-6, is a common inflammation indicator. If interleukin-6 increases in the examination, it indicates that the patient has an infection. The higher the IL-6 content, the more severe the inflammatory reaction; the lower the IL-6 content, the less severe the inflammatory reaction. The detection of IL-6 content decreases with the increase of the dose in the present application, indicating that the blood-nourishing oral liquid can effectively reduce the inflammatory reaction, thereby improving the state of acute lung injury.

[0061] Tumor necrosis factor alpha (TNF-α) is a cytokine secreted by macrophages that can directly kill tumor cells without obvious toxicity to normal cells, and is one of the strongest biological active factors found so far. TNF-α not only plays a role in tumors and viral infections, but also is related to chronic inflammation and autoimmune diseases. The higher the TNF-α content, the more severe the inflammatory reaction; the lower the TNF-α content, the less severe the inflammatory reaction. The detection of TNF-α content decreases with the increase of the dose in the present application, indicating that the blood-nourishing oral liquid can effectively reduce the inflammatory reaction, thereby improving the state of acute lung injury.

[0062] Although the above embodiments make a detailed description of the present application, it is only a part of the embodiments of the present application, but not all the embodiments, and other embodiments can be obtained according to the present embodiments without creativity, which are within the protection scope of the present application.

Claims

1. The application of Yangxue oral liquid in the preparation of drugs for preventing and / or treating acute lung injury; the Yangxue oral liquid is made of the following components by weight: soap 5.3 parts, sand 200 parts, hawthorn 100 parts, 100 parts of Chinese date, vitamin C 5 parts, sucrose 200 parts and sodium benzoate 2 parts, and citric acid is used to adjust the pH value to 2.5~4.

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2. Use according to claim 1, characterized in that, The prevention and / or treatment of acute lung injury is to improve the indicators of hypoxemia, increase the oxygen saturation, improve the lung function and reduce the inflammatory response.

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