Application of vanoxaline dihydrochloride in preparation of chronic obstructive pulmonary disease resisting medicine
By using vanosin dihydrochloride in anti-Chronic obstructive pulmonary disease drugs, the impaired lung function and inflammatory factors are reduced, and the problem of poor effectiveness of existing treatment methods is solved, and effective for chronic obstructive pulmonary disease is achieved. treat.
Patent Information
- Application Number
- CN202411267949.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-05
- Publication Date
- 2024-12-13
AI Technical Summary
The existing treatment methods for anti-COPD are not effective, especially with the long-term use of antibiotics and hormones, the therapeutic effect is reduced, and new therapeutic drugs are needed.
Varnoslin dihydrochloride is used as the active ingredient for anti-Chronic obstructive pulmonary disease drugs. By reducing the lung end-expiratory pause time, 50% expiratory flow rate and airway stenosis index, the maximum expiratory volume of the lungs is increased and the alveolar volume is reduced. Levels of interleukin 6 and tumor necrosis factor alpha.
Varnoslin dihydrochloride significantly improved the lung function of the mouse model of chronic obstructive pulmonary disease, reduced the level of inflammatory factors, and demonstrated effective therapeutic effects on chronic obstructive pulmonary disease.
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of vanoxerine dihydrochloride in the preparation of anti-chronic obstructive pulmonary disease drugs. Background Art
[0002] Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease. Together with cardiovascular disease, diabetes, and tumors, it constitutes the world's four major chronic diseases. The global prevalence rate is 9-10%, and it has become the third leading cause of death in the world. COPD is characterized by persistent low-grade lung inflammation and airflow obstruction. Due to severe air pollution in recent years, workers are often exposed to toxic gases or smoke. It is expected that the incidence and mortality of COPD will continue to increase gradually in the next few decades. Although the treatment of chronic obstructive pulmonary disease (COPD) has improved in the past two decades, modern medicine mainly divides its treatment into non-drug treatments such as oxygen therapy and smoking cessation; drug treatment mainly includes drugs that promote bronchial dilation, antibacterial drugs, and hormone drugs, which are not ideal, and with the long-term use of antibiotics, hormones, etc., the treatment effect is reduced. Therefore, it is necessary to develop new therapeutic drugs. Summary of the invention
[0003] In view of the above problems, the present invention provides the use of vanoxerine dihydrochloride in the preparation of anti-chronic obstructive pulmonary disease drugs.
[0004] In order to achieve the purpose of the present invention, the following technical means are specifically adopted:
[0005] Application of vanoxerine dihydrochloride in the preparation of medicines for treating chronic obstructive pulmonary disease.
[0006] Vanoxerine dihydrochloride can reduce the end-expiratory pause time, 50% expiratory flow rate and airway stenosis index, and increase the maximum expiratory volume of the lung. Vanoxerine dihydrochloride can reduce the levels of interleukin-6 and tumor necrosis factor-α in the alveoli.
[0007] A drug for treating chronic obstructive pulmonary disease, characterized in that the active ingredient comprises vanoxerine dihydrochloride. The dosage form of the drug is any pharmaceutically acceptable dosage form. The drug also comprises pharmaceutically acceptable pharmaceutical excipients. The pharmaceutical excipients are any one of carriers, diluents, excipients, fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH regulators, antioxidants, antibacterial agents, and buffers, or a combination of at least two of them.
[0008] Beneficial Effects
[0009] Beneficial effects of the present invention:
[0010] The present invention finds that vanoxerine dihydrochloride is expected to be used as an anti-chronic obstructive pulmonary disease active ingredient in the research and development of related drugs or the diagnosis or treatment of diseases. DETAILED DESCRIPTION
[0011] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0012] Example 1
[0013] 1. Modeling and drug administration of COPD mouse model
[0014] C57BL / 6 male mice were randomly divided into 5 groups according to body weight, including blank group, model group, azithromycin positive administration group, and vanoxerine dihydrochloride low and high groups, with 10 mice in each group. Except for the blank group, the mice in the other groups were placed in a homemade fumigation box, and the smoke of a cigarette was extracted and placed in the fumigation box for 30 minutes, 6 days a week for a total of 16 weeks. On the first and seventh days of the first week of fumigation, lipopolysaccharide (10μg / mouse) was dripped into the nose, and on the seventh day of the rest of the week, lipopolysaccharide (10μg / mouse) was dripped into the nose to model chronic obstructive pulmonary disease in mice. From the 13th week of modeling, the corresponding drugs were given for intervention for 4 weeks, once a day, and the volume of oral administration was 10mL / kg, the dosage of azithromycin was 2.5mg / kg, and the dosage of vanoxerine dihydrochloride was 10mg / kg and 20mg / kg.
[0015] 2. Pulmonary function test
[0016] After all the administration was completed, the lung function of each group of mice was measured. After the mice were anesthetized, the trachea was separated and exposed, an incision was made in the mouse throat with surgical scissors, and the breathing connector was quickly inserted into the trachea, and then connected to the lung function tester. After the mice's breathing stabilized, the changes in lung function-related parameters were measured and recorded. The main lung function parameters measured were: 50% expiratory flow rate (EF50), maximum inspiratory volume (PIF), end-expiratory pause (EEP), maximum expiratory volume (PEF) and airway stenosis index (Penh).
[0017] The experimental results are shown in Table 1. As can be seen from the experimental results in Table 1, the model group mice showed statistical differences in lung function test parameters EF50, EEP, PEF and Penh compared with the blank group mice, indicating that the lung function of the model group mice was significantly damaged and the model was successfully established. The positive drug and low and high doses of vanoxerine dihydrochloride can significantly reverse the above problems, showing statistical differences, indicating that vanoxerine dihydrochloride can improve the lung function of model mice.
[0018] Table 1 Pulmonary function test results
[0019] index Blank Group Model Group Azithromycin Vanoxerine dihydrochloride Vanoxerine dihydrochloride EF50(ml / s) <![CDATA[11.45±0.28 ### ]]> 13.75±0.14 <![CDATA[12.95±0.30 # ]]> <![CDATA[13.08±0.25 # ]]> <![CDATA[12.63±0.27 ## ]]> PIF(ml / s) 10.44±0.31 10.11±0.21 10.35±0.29 9.97±0.097 10.33±0.21 EEP(s) <![CDATA[0.17±0.012 # ]]> 0.20±0.011 <![CDATA[0.18±0.0069 # ]]> 0.18±0.0084 <![CDATA[0.17±0.0088 # ]]> PEF(ml / s) <![CDATA[14.90±0.16 ### ]]> 13.14±0.25 <![CDATA[14.35±0.37 ## ]]> <![CDATA[13.96:±0.28 # ]]> <![CDATA[14.53±0.25 ## ]]> Penh <![CDATA[5.01±0.16 ### ]]> 6.94±0.11 <![CDATA[5.98±0.13 ### ]]> <![CDATA[6.24±0.19 ## ]]> <![CDATA[5.82±0.15 ### ]]>
[0020] Note: Compared with the model group, #P<0.05, ##P<0.01, ###P<0.001
[0021] 3. Determination of inflammatory factors in bronchoalveolar lavage fluid
[0022] After the mice were anesthetized, 1 mL of phosphate buffer was injected into the lungs of mice in each group, and the phosphate buffer lavage fluid was slowly aspirated. This process was repeated three times and centrifuged. The supernatant was taken and the contents of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined using ELISA kits.
[0023] The experimental results are shown in Table 2. As can be seen from the experimental results in Table 2, the levels of IL-6 and TNF-α in the alveolar lavage fluid of the model group mice showed statistical differences compared with the blank group mice, indicating that inflammation occurred in the lungs of the model group mice and the model was successfully established. The positive drug and low and high doses of vanoxerine dihydrochloride can significantly reverse the above problems, showing statistical differences, indicating that vanoxerine dihydrochloride can reduce inflammation in the lungs of model mice.
[0024] Table 2 Results of determination of inflammatory factors in bronchoalveolar lavage fluid
[0025] index Blank Group Model Group Azithromycin Vanoxerine dihydrochloride Vanoxerine dihydrochloride IL-6 (pg / mL) <![CDATA[38.9±3.3 ### ]]> 85.1±7.8 <![CDATA[59.3±4.4 ## ]]> <![CDATA[69.0±5.4 # ]]> <![CDATA[55.6±4.9 ## ]]> TNF-α(pg / mL) <![CDATA[106.2±8.6 ### ]]> 313.8±25 <![CDATA[167.3±14 ### ]]> <![CDATA[208.7±21 ## ]]> <![CDATA[163.3±9.8 ### ]]>
[0026] Note: Compared with the model group, #P<0.05, ##P<0.01, ###P<0.001
[0027] The above experimental results show that vanoxerine dihydrochloride can improve the lung function of model mice, reduce inflammation in the lungs of model mice, and demonstrate a therapeutic effect on chronic obstructive pulmonary disease.
[0028] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims
1. Use of vanoxerine dihydrochloride in the preparation of drugs for treating chronic obstructive pulmonary disease.
2. The use according to claim 1, characterized in that: The vanoxerine dihydrochloride can reduce the end-expiratory pause time, 50% expiratory flow rate and airway stenosis index, and increase the maximum expiratory volume of the lung.
3. The use according to claim 1, characterized in that: The vanoxerine dihydrochloride can reduce the levels of interleukin-6 and tumor necrosis factor-α in the alveoli.
4. A drug for treating chronic obstructive pulmonary disease, characterized in that: The active ingredient includes vanoxerine dihydrochloride.
5. The anti-chronic obstructive pulmonary disease drug according to claim 4, characterized in that: The dosage form of the drug is any pharmaceutically acceptable dosage form.
6. The anti-chronic obstructive pulmonary disease drug according to claim 4, characterized in that: The drug also includes pharmaceutically acceptable excipients.
7. The drug for treating chronic obstructive pulmonary disease according to claim 4, characterized in that: The pharmaceutical excipients are any one of carriers, diluents, excipients, fillers, adhesives, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH regulators, antioxidants, antibacterial agents, and buffers, or a combination of at least two of them.