Application of small molecules in prevention and treatment of acute and chronic bronchitis
By using a pharmaceutical composition containing N-dodecylmethylamine, the problem of the lack of specific drugs for chronic bronchitis has been solved, significantly improving cough symptoms in both acute and chronic bronchitis and providing a simple and effective treatment option.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- LANZHOU UNIV
- Filing Date
- 2024-11-18
- Publication Date
- 2026-05-19
AI Technical Summary
There are currently no effective drugs to cure chronic bronchitis, and the treatment of acute bronchitis has limited effectiveness and is prone to drug resistance.
A pharmaceutical composition of N-dodecylmethylamine or its pharmaceutically acceptable salt or active ingredient, administered via double-distilled water suspension, is used to prepare a drug for treating bronchitis, including dosage forms such as injections, tablets, capsules, granules, sustained-release preparations, and pills.
It significantly prolonged the cough latency time and significantly reduced the number of coughs in mice with acute and chronic bronchitis, providing a new and simple treatment option for bronchitis.
Smart Images
Figure CN122056856A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedicine, specifically to the application of a small molecule in the prevention and treatment of acute and chronic bronchitis. Background Technology
[0002] Bronchitis is a common respiratory disease caused by non-specific inflammation of the trachea, bronchial mucosa, and surrounding tissues due to infectious or non-infectious factors. Bronchitis can be divided into acute bronchitis (AB) and chronic bronchitis (CB). Acute bronchitis is an acute inflammation of the bronchial mucosa, primarily caused by chemical or physical irritants, microbial infections, and allergic reactions. It has a rapid onset, often without obvious symptoms in the early stages. Some patients may experience cough and sputum production; as the inflammation spreads, the cough worsens, sputum production increases, and lung ventilation and gas exchange function decline. Chronic bronchitis, on the other hand, is a chronic inflammatory disease caused by excessive mucus production and secretion, leading to small airway obstruction, epithelial remodeling, and changes in airway surface tension, resulting in cough, sputum production, and wheezing. Chronic bronchitis is prone to recurrence and is difficult to cure, leading to critical conditions such as emphysema, respiratory insufficiency, and respiratory failure, posing a serious threat to health. This disease has a wide incidence rate, with a global adult prevalence of approximately 3.4% to 22%, and this rate continues to rise. Chronic airway inflammation and hypersecretion of airway mucus are the basic pathological processes of chronic bronchitis, and the two influence and interact with each other. When the airway encounters inflammatory pathogenic factors such as excessive smoking, infection, and air pollutants, it releases pro-inflammatory mediators such as interleukins IL-6, IL-1β, and tumor necrosis factor-α (TNF-α), inducing excessive metaplasia of airway epithelial mucous glands and goblet cells, resulting in hypersecretion of mucin. This leads to excessive mucus production in the airway mucosa, obstructing the airway and promoting the development of chronic bronchitis.
[0003] Currently, clinical treatment for bronchitis primarily focuses on controlling infection, suppressing cough and expectoration, and relieving bronchospasm, often using antibiotics, expectorants, bronchodilators, and corticosteroids. In addition, physical therapy (including airway cleaning, airway dilation, and breathing exercises) and behavioral therapy (including smoking cessation, increased exercise, and maintaining a healthy diet) play a positive role in treating acute bronchitis exacerbations. However, due to the complex causes of chronic bronchitis, there is currently no specific cure, and the long treatment duration of chronic bronchitis easily leads to drug resistance.
[0004] In response to the aforementioned technical problems, the inventors unexpectedly discovered during their research that N-dodecylmethylamine has a good therapeutic effect on bronchitis. It can not only treat acute bronchitis but also has a significant therapeutic effect on chronic bronchitis, showing broad prospects for clinical application. Summary of the Invention
[0005] The object of this invention is to provide the use of N-dodecylmethylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as an active ingredient, in the preparation of medicaments for the prevention and / or treatment of bronchitis, characterized in that the N-dodecylmethylamine has the structural formula shown in Formula (I):
[0006]
[0007] Preferably, the bronchitis is acute bronchitis or chronic bronchitis.
[0008] Preferably, the N-dodecylmethylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof with the active ingredient, is formulated into a pharmaceutically acceptable dosage form by adding pharmaceutically acceptable excipients.
[0009] Preferably, the dosage forms include injections, tablets, capsules, granules, suspensions, sustained-release formulations, and pills.
[0010] A second object of the present invention is to provide a pharmaceutical composition for treating bronchitis, said pharmaceutical composition comprising N-dodecylmethylamine and excipients.
[0011] The beneficial effects of this invention are as follows: This invention provides the use of N-dodecylmethylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as an active ingredient in the preparation of drugs for the prevention and / or treatment of bronchitis. The N-dodecylmethylamine can significantly prolong the cough latency time in mice with acute or chronic bronchitis and significantly reduce the number of coughs in mice with acute or chronic bronchitis, indicating that the small molecule described in this invention can be used as a drug for the treatment or relief of acute or chronic bronchitis, providing a new option for the clinical treatment of bronchitis. Furthermore, this invention uses double-distilled water suspension of the small molecule for administration, a simple and rapid method that achieves significant effects. Attached Figure Description
[0012] Figure 1 The effect of N-dodecylmethylamine on cough latency time in mice with acute bronchitis;
[0013] Figure 2 The effect of N-dodecylmethylamine on the number of coughs in mice with acute bronchitis;
[0014] Figure 3 To investigate the effect of ammonia nebulization modeling on cough latency in mice;
[0015] Figure 4 To investigate the effect of ammonia atomization on the number of coughs in mice;
[0016] Figure 5 The effect of N-dodecylmethylamine on cough latency in mice with chronic bronchitis;
[0017] Figure 6 The effect of N-dodecylmethylamine on the number of coughs in mice with chronic bronchitis; Detailed Implementation
[0018] To make the objectives, technical solutions, and advantages of this invention clearer, the following detailed description of the invention through specific embodiments is provided. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Unless otherwise specified, the experimental methods in the following embodiments are conventional experimental methods. Unless otherwise specified, the reagents and materials used in the following embodiments are commercially available.
[0019] The reagents and instruments used in the following examples are shown in Table 1 below:
[0020] Table 1 Experimental Reagents and Instruments
[0021]
[0022] Example 1: The therapeutic effect of N-dodecylmethylamine on acute bronchitis
[0023] 1. Grouping and administration of SPF-grade Kunming mice with acute bronchitis
[0024] 1.1 Grouping
[0025] Thirteen 6-8 week old SPF-grade male Kunming mice weighing 18-22g were randomly divided into three groups according to their body weight: a model control group (n=5), an administration group (n=4, N(10mg / kg)), and an administration group (n=4, N(100mg / kg)).
[0026] 1.2 Administration
[0027] The model control group was administered normal saline by gavage at a dose of 0.1 ml / 10 g daily; the treatment group (N (10 mg / kg)) was administered a suspension of N-dodecylmethylamine and double-distilled water by gavage at a dose of 0.1 ml / 10 g; the treatment group (N (100 mg / kg)) was administered a suspension of N (100 mg / kg) by gavage at a dose of 0.1 ml / 10 g. All three groups were administered gavage once a day for 7 consecutive days.
[0028] 2. Detection methods and indicators
[0029] 2.1 Ammonia-induced coughing method in mice
[0030] One hour after the end of gavage administration on the seventh day, each group of mice was placed in a nebulizer and sprayed with 25%-28% ammonia water for 30 seconds. The time of the first cough (cough latency) and the number of coughs within 2 minutes and 30 seconds were measured and recorded for each mouse. 3. Data processing
[0031] Statistical analysis was performed using Graphpad Prism 8.3.0 software. One-way ANOVA and t-tests were used for pairwise comparisons between groups. A p-value < 0.05 was considered statistically significant.
[0032] 4. Experimental Results
[0033] The effect of N-dodecylmethylamine on cough latency time in mice with acute bronchitis, such as Figure 1 As shown, compared with the model control group, N-dodecylmethylamine at a dose of 10 mg / kg significantly prolonged the cough latency time in mice with acute bronchitis, while at a dose of 100 mg / kg, there was no significant change in cough latency time.
[0034] The effect of N-dodecylmethylamine on the number of coughs in mice with acute bronchitis, as follows: Figure 2 As shown, compared with the model control group, the number of coughs was significantly reduced when N-dodecylmethylamine was administered at doses of 10 mg / kg or 100 mg / kg, but the effect was more significant at a dose of 10 mg / kg. In summary, this indicates that the small molecule N-dodecylmethylamine described in this invention has a significant effect on the prevention and treatment of acute bronchitis, and the effect is more significant at a dose of 10 mg / kg.
[0035] Example 2: The therapeutic effect of N-dodecylmethylamine on chronic bronchitis
[0036] 1. Establishment and grouping of a BALB / c mouse model of chronic bronchitis
[0037] 1.1 Model Establishment
[0038] Twenty-five healthy male BALB / c mice aged 6-8 weeks and weighing 18-22g were randomly divided into two groups according to their weight: a blank control group of 6 mice and a model group of 19 mice. The 19 mice in the model group were induced to develop a model by ammonia atomization.
[0039] 1.2 Ammonia water atomization molding
[0040] The model was established using ammonia water (concentration 25%-28%) stimulation method (5 times a day, 30 seconds each time, with an interval of 1 hour and 30 minutes between each time, and the atomization degree was weak); during the modeling period of the model group, the blank control group mice were treated in the same way as the model group, but without ammonia water stimulation.
[0041] 1.3 Detection Model
[0042] After 30 days of continuous modeling, mice in the model group exhibited symptoms such as difficulty breathing, coughing, nose scratching, huddling together, squinting, lethargy, weight loss or slow weight gain, reduced food and water intake, and dull fur. The blank control group and the model group were then placed in a nebulizer and sprayed with 25%–28% ammonia solution for 30 seconds. The time to the first cough (cough latency) and the number of coughs within 2 minutes and 30 seconds were measured and recorded. Coughing was defined as severe abdominal muscle contraction, mouth opening, and, in severe cases, a coughing sound. Statistical analysis was performed using Graphpadprism 8.3.0 after all experiments were completed. Mice were provided with ample food and water during the experiment.
[0043] like Figure 3 and Figure 4 As shown, compared with the blank control group, the cough latency time and cough frequency of mice in the model group were significantly different (P<0.05), which can be considered as the stable chronic bronchitis model and the modeling was successful.
[0044] 2. Grouping
[0045] When the cough latency time and cough frequency of mice in the model group were significantly different from those in the blank control group (P < 0.05), the model was considered to have been successfully established. A total of 19 mice were successfully modeled and divided into 3 groups as follows:
[0046] a. The model group (CB) consisted of 6 animals. After successful modeling, the animals were given 0.1 ml / 10 g of physiological saline by gavage daily.
[0047] b. The low-dose administration group (CB+N(10mg / kg)) consisted of 7 animals. After successful modeling, they were given a daily oral gavage dose of 0.1ml / 10g of a suspension of 10mg / kg N-dodecylmethylamine and double-distilled water.
[0048] c. Six animals in the high-dose administration group (CB+N(20mg / kg)) were given a suspension of 20mg / kg N-dodecylmethylamine and double-distilled water by gavage at a volume of 0.1ml / 10g per day after successful modeling.
[0049] d. Six animals were placed in the blank control group and administered physiological saline by gavage at a dose of 0.1 ml / 10 g daily.
[0050] 3. Ammonia-induced coughing method in mice
[0051] After 14 days of continuous oral administration, each group of mice was placed in a nebulizer and sprayed with 25%-28% ammonia water for 30 seconds. The time of the first cough (cough latency) and the number of coughs within 2 minutes and 30 seconds were detected and counted.
[0052] 4. Data Processing
[0053] Statistical analysis was performed using Graphpad Prism 8.3.0 software. One-way ANOVA and t-tests were used for pairwise comparisons between groups. A p-value < 0.05 was considered statistically significant.
[0054] 5. Experimental Results
[0055] The effect of N-dodecylmethylamine on cough latency time in mice with chronic bronchitis, such as Figure 5 As shown, compared with the blank control group, the cough latency time of mice in the model group without drug treatment was significantly shortened, while there was no significant change in the 10mg / kg and 20mg / kg drug treatment groups.
[0056] The effect of N-dodecylmethylamine on the number of coughs in mice with chronic bronchitis, as follows: Figure 6 As shown, compared with the blank control group, the number of coughs in the model group without drug treatment was significantly increased, while the number of coughs in the drug-treated group was significantly reduced, but the effect was more significant when the drug dose was 10 mg / kg.
[0057] In summary, this invention provides the use of N-dodecylmethylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as an active ingredient, in the preparation of drugs for the prevention and / or treatment of bronchitis. The N-dodecylmethylamine significantly prolongs the cough latency time in mice with acute or chronic bronchitis and significantly reduces the number of coughs in mice with acute or chronic bronchitis, indicating that the small molecule described in this invention can serve as a drug for treating or alleviating acute or chronic bronchitis, providing a new option for clinical treatment of bronchitis. Furthermore, this invention uses double-distilled water suspension for drug administration, a simple and rapid method that achieves significant effects.
Claims
1. The use of N-dodecylmethylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as an active ingredient, in the preparation of a medicament for the prevention and / or treatment of bronchitis, characterized in that, The N-dodecylmethylamine has the structural formula shown in formula (Ⅰ):
2. The application as described in claim 1, characterized in that, The bronchitis mentioned refers to either acute or chronic bronchitis.
3. The application as described in claim 1 or 2, characterized in that, The N-dodecylmethylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof containing an active ingredient, is formulated into a pharmaceutically acceptable dosage form by adding pharmaceutically acceptable excipients.
4. The application as described in claim 3, characterized in that, The dosage forms include injections, tablets, capsules, granules, suspensions, sustained-release formulations, and pills.
5. A pharmaceutical composition for treating bronchitis, characterized in that, The pharmaceutical composition comprises N-dodecylmethylamine and excipients.