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Application of dopamine receptor D1 agonist to preparation of lung injury treatment medicine

A treatment drug, dopamine technology, applied in the field of pharmacy, can solve the problems of inhomogeneity, insufficient alveolar opening, and increase the poor prognosis of ARDS patients

Inactive Publication Date: 2017-12-01
江来 +10
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, in the support measures for patients with acute respiratory distress syndrome (ARDS), the most widely used strategy is the "low tidal volume protective lung ventilation" strategy. However, most patients with ARDS have significantly reduced lung volume and uneven In severe cases, only 20% to 30% of the alveoli can participate in ventilation. At this time, even if a small tidal volume is given, it will still lead to hyperventilation of local lung tissue and insufficient opening of some alveoli. The periodic opening and closing of terminal small airways and some lung units can also generate shear stress between dilated and consolidated alveoli, eventually leading to mechanical ventilation-induced lung injury
[0004] On the one hand, the mechanical stimulation of VILI will further aggravate the pulmonary lesions of critically ill patients; Poor prognosis of patients with ARDS

Method used

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  • Application of dopamine receptor D1 agonist to preparation of lung injury treatment medicine
  • Application of dopamine receptor D1 agonist to preparation of lung injury treatment medicine
  • Application of dopamine receptor D1 agonist to preparation of lung injury treatment medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Study on the protective effect of dopamine (DA) on mechanical injury-induced lung injury.

[0066] This example studies the role of dopamine in the treatment of lung injury.

[0067] Specifically, the role of dopamine in alleviating mechanical ventilation-induced endothelial barrier disruption was investigated.

[0068] The mice were divided into four groups, namely: control group A, ventilation group a, control group B, and ventilation group b, with 7 mice in each group, among which, the mice in control group A were injected with normal saline (physiological saline) first. The injection dose of saline was 50 mg / kg), and then the mice were anesthetized, the trachea was incised, and the intubation was inserted for natural respiration; the mice in ventilation group a were first injected with normal saline (physiological intubation method). The injection dose of saline was 50 mg / kg), and then after the mice were anesthetized, the trachea was incised by the visual intubati...

Embodiment 2

[0077] To study the effect of small interfering RNA (siRNA) of dopamine receptor-encoding gene on the effect of dopamine on the protection of mechanical ventilation-induced endothelial barrier disruption.

[0078] In this example, the effect of siRNA of dopamine receptor-encoding gene on the effect of dopamine in alleviating mechanical ventilation-induced lung injury was investigated.

[0079] The siRNA fragments used to knock down DRD1 expression and the control siRNA fragments were synthesized by Shanghai Gema Pharmaceutical Technology Co., Ltd. The siRNA sequence of DRD1 is: siDRD1:5'-GGGAGACUAAAGUCCUGAA-3' (SEQ ID NO. 1).

[0080] The siRNA sequence of DRD2 is: siDRD2:5'-GGCCAUGCCUAUGUUGUAU-3' (SEQ ID NO. 2).

[0081] The negative control siRNA is a scrambled siRNA without a specific target sequence:

[0082] Negative control: 5'-UUCUCCGAACGUGUCACGUTT-3' (SEQ ID NO. 3).

[0083] The mice were divided into six groups, namely control group A, control group B, D1 group A, ...

Embodiment 3

[0099] Example 3 investigates the protective effect of dopamine receptor D1 agonists on lung injury.

[0100] In this example, the effect of dopamine receptor agonists in mitigating mechanical ventilation-induced endothelial barrier disruption was investigated.

[0101] In this example, the dopamine receptor D1 agonist used is SKF-38393, and the molecular formula of SKF-38393 is C 16 H 17 NO 2 , the structural formula is

[0102] The dopamine D2 receptor agonist used in this example is quinpirole, and the molecular formula of quinpirole is C 13 H 21 N 3 , the structural formula is

[0103] In this example, the mice were divided into four groups, namely control group A, control group B, group D1 and group D2, with 7 mice in each group.

[0104] The mice in the control group A were injected with normal saline (the injection dose of normal saline was 50 mg / kg), and then the mice were anesthetized.

[0105] The mice in the control group B were first injected with physi...

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Abstract

The invention relates to the field of pharmacy, and particularly discloses an application of a dopamine receptor D1 agonist to preparation of a lung injury treatment medicine, the lung injury treatment medicine and a lung injury treatment method. A novel treatment or prevention medicine is provided for lung injury and can be used for preventing and treating lung injury in the mechanical ventilation process of critical patients.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to the use of a dopamine receptor D1 agonist in preparing a medicine for treating lung injury. Background technique [0002] Lung injury, mainly refers to the damage of lung tissue. Including: severe chest trauma, inhalation of substances harmful to the lungs (toxic gas, stomach contents, seawater, etc.), severe lung infection and other injury factors caused by lung tissue damage, resulting in damage to the structural integrity of the lungs or disfunction. A common type of lung injury is Ventilator-induced lung injury (VILI). [0003] Mechanical ventilation is an important means of life support during surgery. However, with the rapid development of emergency medicine and critical care medicine, mechanical ventilation has become an indispensable technical means in the rescue and treatment of various critical illnesses. It has an irreplaceable position in the respiratory support treatment o...

Claims

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Application Information

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IPC IPC(8): A61K31/55A61K31/137A61P11/00
CPCA61K31/55A61K31/137
Inventor 江来朱晓燕刘宇健毛燕飞王艳董文文张云倩吕洲李思源徐敦凤徐楚帆
Owner 江来
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