阅读说明：本技术 白鲜碱在制备用于舒张预收缩的气管平滑肌方面的药物中的应用 (Application of dictamnine in preparation of medicine for relaxing pre-contracted tracheal smooth muscle ) 是由 沈金花 韩淑慧 于 2019-12-31 设计创作，主要内容包括：本发明涉及医药技术技术领域,尤其涉及白鲜碱在制备用于舒张预收缩的气管平滑肌方面的药物中的应用,本发明发现了白鲜碱在舒张预刺激的气道平滑肌方面的作用机理,尤其是对高钾诱导和乙酰胆碱诱导的气道平滑肌的收缩具有舒张作用,也为开发白鲜碱舒张气管平滑肌用于制备治疗哮喘的药物提供了依据。(The invention relates to the technical field of medicines, in particular to application of dictamnine in preparation of a medicine for relaxing pre-contracted airway smooth muscle.)

1. Use of dictamnine in the manufacture of a medicament for relaxing pre-contracted tracheal smooth muscle.

2. Use of dictamnine in the manufacture of a medicament for relaxing pre-contracted airway smooth muscle according to claim 1, wherein: dictamnine achieves this application by relaxing the high potassium-induced contraction of airway smooth muscle.

3. Use of dictamnine in the manufacture of a medicament for relaxing pre-contracted airway smooth muscle according to claim 1, wherein: dictamnine achieves this application by relaxing acetylcholine-induced contraction of airway smooth muscle.

4. Use of dictamnine in the manufacture of a medicament for relaxing pre-contracted airway smooth muscle according to claims 1-3, wherein: the medicine is used for treating respiratory diseases such as asthma.

5. Use of dictamnine in the manufacture of a medicament for relaxing pre-contracted airway smooth muscle according to claims 1-3, wherein: the dosage forms of the medicine at least comprise capsules, tablets, oral preparations and microcapsule preparations.

6. Use of dictamnine in the manufacture of a medicament for relaxing pre-contracted airway smooth muscle according to claims 1-3, wherein: the administration modes of the medicine at least comprise injection, oral administration and subcutaneous administration.

Technical Field

The invention relates to the technical field of medicines, in particular to application of dictamnine in preparing a medicine for relaxing pre-contracted tracheal smooth muscle.

Background

Asthma is also called bronchial asthma, and is an airway inflammatory disease involving a plurality of inflammatory cells and cytokines such as eosinophil. The continuous contraction of airway smooth muscle and the increase of calcium sensitivity are one of the main symptoms of asthma and chronic obstructive pulmonary disease. Among the therapeutic agents for the above respiratory diseases, bronchodilatory drugs such as glucocorticoid are clinically common drugs. In recent years, various new therapies and medicines for treating asthma are continuously developed, but no effective medicine for completely curing asthma exists at present, so that the development of a small molecular compound capable of relaxing and pre-contracting tracheal smooth muscle as a new medicine for treating asthma is still required.

Dictamnine is a natural compound with a definite chemical structureCompound of formula C₁₂H₉NO₂It has effects in inhibiting platelet aggregation, relaxing blood vessel, lowering blood pressure, and resisting insect. Recent research shows that the dictamnine has cytotoxicity to human cervical cancer, colon cancer and oral cancer cells, but the dictamnine is never applied to the medicines for relaxing airway smooth muscle and treating asthma.

Disclosure of Invention

The invention discovers the action mechanism of the dictamnine in relaxing the pre-stimulated airway smooth muscle, makes a biological activity experiment, and provides a basis for developing the application of the dictamnine in relaxing the tracheal smooth muscle to prepare the medicine for treating asthma.

The technical scheme provided by the invention is the application of dictamnine in preparing the medicine for relaxing the pre-contracted tracheal smooth muscle.

Wherein the dictamnine achieves the use by relaxing high potassium-induced contraction of airway smooth muscle.

Wherein the use of dictamnine is achieved by relaxing acetylcholine-induced contraction of airway smooth muscle.

Moreover, the medicament is a medicament for treating respiratory diseases such as asthma.

Moreover, the dosage forms of the medicament at least comprise capsules, tablets, oral preparations and microcapsule preparations.

Furthermore, the administration modes of the drug at least include injection, oral administration and subcutaneous administration.

Compared with the prior art, the technical scheme has the beneficial effects that: according to the invention, through detecting the tension of isolated tracheal ring muscle of an experimental mouse, the dictamnine has a high-efficiency effect of relaxing tracheal smooth muscle, and is expected to be applied to relieving symptoms of airway spasm and airway obstruction when asthma patients attack. Provides a basis for developing the application of the dictamnine in relaxing the tracheal smooth muscle to prepare the medicine for treating asthma.

Drawings

FIG. 1 is a graph showing the vasodilatory effect of dictamnine on high potassium pre-contracted tracheal rings;

figure 2 is a graph of the vasodilatory effect of dictamnine on acetylcholine (ACh) preshrinked tracheal rings.

Detailed Description

The present invention will be described in detail with reference to the accompanying drawings and examples, and the present invention is not limited to the examples.

In vitro isolation of mouse trachea:

sacrifice male BABL/C mice for 6-8 weeks by cervical dislocation, place the mice on a dissecting plate with the abdomen facing up, cut open the chest to expose the cardiopulmonary tissue, remove the heart and then remove the entire tissue from the laryngeal prominence to the lung, immediately soak the removed tissue in pre-cooled PSS solution (NaCl 135mM, KCl 5mM, MgCl)₂1mM，CaCl₂2mM HEPES 10mM glucose10mM, NaOH to pH 7.4), and then transferred to a gel plate for further separation of the tracheal rings. Connective tissue around the periphery of the trachea and residual blood in the lumen were carefully removed under a stereomicroscope using a Venus scissors, and a main tracheal ring of about 5-7mm was isolated.

The tension detection method of the mouse airway smooth muscle comprises the following steps:

the trachea with proper length is inserted into two triangular rings, one is fixed, the other is connected with a tension transducer, the trachea is placed in a water bath containing 6mL of PSS solution, the temperature of the bath is 37 ℃, and oxygen is continuously introduced. Adjusting the preload to 300mg, changing the PSS solution every 15min and adjusting the preload again for 4 times of balancing, adding 80mmol/L KCl or 100 mu mol/L ACh to pre-stimulate the trachea after balancing for 60min, eluting to recover to the baseline after the trachea is fully contracted, and starting the experiment after the trachea has a rest for 30 min. Stimulation was performed again using 80mmol/L KCl or 100. mu. mol/L ACh, followed by addition of DMSO-solubilized dictamnine in a concentration gradient to see if it caused a pre-systolic tracheal ring to relax.

Experiment 1: relaxation of high potassium preshrinked tracheal rings by dictamnine

Contraction of myocytes and intracytoplasmic Ca²⁺The concentration is relevant. The use of 80mmol/L KCl induces the opening of voltage-dependent calcium ion channels (VDCCs) of tracheal smooth muscle cells, spasms tracheal smooth muscle, and abnormal contraction of the tracheal ring. As shown in FIG. 1, dictamnine inhibited this abnormal contraction dose-dependently, in 6 casesExperiments were performed to calculate, by nonlinear fitting, the dose-effect curve of dictamnine dilating high potassium pre-contracted trachea, with the maximum diastolic value of (93.72 ± 1.06)%, and the concentration (IC50) at which contraction is half inhibited of (51.6 ± 1.02)%. The dictamnine can relax high potassium to cause airway smooth muscle contraction, and the effect of the medicine is dose-dependent.

Experiment 2: relaxation of ACh preshrinked tracheal rings by dictamnine

Intracellular Ca²⁺Besides VDCCs, a plurality of ion channels are involved in the regulation. Acetylcholine (ACh) is a commonly used inducer in asthma studies and it activates voltage-dependent calcium channels (VDCCs) and nonselective cation channels (NSCCs). As shown in FIG. 2, abnormal trachea contraction caused by ACh can also be inhibited by dose-dependently by dictamnine, and the dose-effect curve of the pre-contracted trachea of the dictamnine by dilating ACh is obtained by nonlinear fitting through statistics of 6 experiments, wherein the maximum diastole value is (89.47 +/-3.17)%, and the concentration (IC50) when the contraction is inhibited by half is (190.11 +/-1.02)%. The dictamnine can relax ACh to cause airway smooth muscle contraction, and the effect of the medicine is dose-dependent.

In conclusion, the experiment shows that the dictamnine has the efficient effect of relaxing the airway smooth muscle, particularly has the effect of relaxing the contraction of the airway smooth muscle induced by high potassium and acetylcholine, and is expected to be applied to relieving the symptoms of airway spasm and airway obstruction during the attack of asthma patients.