Use of aminoadamantane nitrate esters or pharmaceutically acceptable salts thereof in the prevention and/or treatment of lung diseases

A technology for adamantane nitrate and lung diseases, applied in organic chemistry, active ingredients of esters, respiratory diseases, etc., can solve problems such as excessive speed, proarrhythmia, body tremors, etc., to improve pulmonary circulation and expand lungs blood vessels, improving the effect of pulmonary hypertension

Active Publication Date: 2019-01-11
FOSHAN MAGPIE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] However, there are some adverse effects of existing drugs for the treatment of lung diseases: (1) β2 receptor agonists: in sensitive patients, stimulation of β2 adrenergic receptors can lead to sinus tachycardia at rest, with potential proarrhythmic effect
For some elderly patients receiving high doses of β2-agonists, regardless of the route of administration, severe body tremors will have a great impact

Method used

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  • Use of aminoadamantane nitrate esters or pharmaceutically acceptable salts thereof in the prevention and/or treatment of lung diseases
  • Use of aminoadamantane nitrate esters or pharmaceutically acceptable salts thereof in the prevention and/or treatment of lung diseases
  • Use of aminoadamantane nitrate esters or pharmaceutically acceptable salts thereof in the prevention and/or treatment of lung diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1. The effect of MN-08 on the ratio of wet weight to dry weight of lung tissue.

[0066] After 1 hour and 6 hours on the day of modeling, the mice were given anesthesia treatment with 4% chloral hydrate after 12 hours of LPS administration. After taking blood from the orbit, fix the patient on the operating table in a supine position, cut off the skin from above the perineum through the abdomen until the neck fully exposes the abdomen and chest, and cut the abdominal muscles and peritoneum through a large cross incision to expose the abdominal cavity. Cut from the diaphragm surface of the liver and the diaphragm into the chest cavity, cut the diaphragm along the radian of the thorax on both sides, and cut upward from both sides of the chest to the neck, remove the entire sternum and chest wall of the front chest, and fully expose the lungs, heart, and neck trachea And the left and right main bronchi, be careful not to damage the trachea and lungs. Take the lung...

Embodiment 2

[0068] Example 2. Effect of MN-08 on neutrophils in bronchoalveolar lavage fluid and total protein in bronchoalveolar lavage fluid.

[0069] After the mice were modeled and administered, lung tissue was collected, and a trocar was inserted into the left lung tissue through the neck trachea, and the trachea and trocar were tied with silk thread through the tracheoesophageal space to fix and seal them. The right main bronchus was clamped with a vascular clip, and 0.3mL of PBS buffer solution was injected into a 1mL empty needle connected to the trocar. The left lung was seen to swell, and the left lung was withdrawn slowly, repeated 3 times, and the liquid was recovered. Centrifuge at 1500rpm at 4°C for 10min. The supernatant was taken and stored at -80°C for the determination of protein and cytokines in the lavage fluid, and the cell pellet was used for cell counting and determination. Resuspend the bronchoalveolar lavage fluid precipitate in pre-cooled PBS, add 20mL of BALF s...

Embodiment 3

[0072] Example 3, the effect of MN-08 on the permeability index of lung tissue.

[0073] After the mice were modeled and administered, the ratio of BALF supernatant protein content to plasma protein content was used to express the lung permeability index (LPI), and the protein content was measured with BCA, ie LPI=BALF protein content / plasma protein content. Increased values ​​indicate increased pulmonary capillary permeability. For the experimental procedure, see Example 2 BCA Protein Quantitative Determination of BALF Protein and Plasma Protein Concentration.

[0074] The result is as image 3 As shown, MN-08 treatment can reduce the increase of LPS-induced lung tissue permeability index (LPI) value in model group mice.

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Abstract

An aminoadamantane nitrate compound represented by formula (I) or a pharmaceutically acceptable salt thereof is disclosed for use in preparing a drug for preventing and / or treating lung diseases. Theaminoadamantane nitrate compound represented by the formula (I) or pharmaceutically acceptable salts thereof can both inhibit NMDA receptor over-activation by non-competitive binding to NMDA receptorchannels and inhibit NMDA receptor over-activation by non-competitive binding, Play anti-inflammatory and antioxidant role, but also targeted pulmonary vascular NMDA receptor release of nitric oxide,dilate pulmonary blood vessels, improve pulmonary circulation and reduce pulmonary hypertension. As such, these compounds can be used as drug for that prevention and / or treatment of lung diseases, including acute lung injury, asthma and chronic obstructive pulmonary disease, and can be combined with existing drugs to form various dosage forms with available drug carriers.

Description

technical field [0001] The invention belongs to the technical field of medicines, and particularly relates to the application of aminoadamantane nitrate ester compounds or pharmaceutically acceptable salts thereof in the preparation of medicines for preventing and / or treating lung diseases. Background technique [0002] Lung diseases, especially acute lung injury, asthma and chronic obstructive pulmonary disease, have always been diseases with high morbidity and high mortality. With the acceleration of urbanization in recent years, the air quality has become increasingly worrying. The incidence of disease has also increased, and the disease itself has seriously affected the quality of life of patients, and the medical burden brought to the society has become heavier and heavier. The research and development of drugs for the treatment of lung diseases has thus become a new hot spot and is widely favored by people. Pay attention to. [0003] (1) Acute lung injury [0004] Ac...

Claims

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Application Information

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IPC IPC(8): A61K31/21C07C219/24A61P11/00A61P11/06A61P29/00
CPCA61P11/00A61P11/06A61P29/00A61K31/21C07C219/24C07C2603/74
Inventor 刘伟王玉强徐立朋张在军孙业伟张高小
Owner FOSHAN MAGPIE PHARM CO LTD
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