Bromocarbanine compound and its preparation method and application
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A technology of bromocribanine and compound, applied in the field of medicine, can solve the problems of difficulty in finding antiarrhythmic drugs, hypothyroidism or hyperthyroidism, lung damage, adverse reactions and the like
Active Publication Date: 2018-08-10
YUNNAN UNIV OF TRADITIONAL CHINESE MEDICINE
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Problems solved by technology
The reports about the antiarrhythmic effect of 3-bromocarbanine and 10,11-bromocarbanine have not been reported before the completion of the present invention
[0005] 3-Bromocrebanine (3-Bromocrebanine) and 10,11-Bromocrebanine (10,11-Dibromocrebanine) are synthesized from Crebanine (Crebanine). see related reports
[0006] Most commonly used antiarrhythmic drugs on the market are accompanied by adverse reactions that cannot be ignored. For example, lidocaine often manifests as dizziness, paresthesia, confusion and other nervous system adverse reactions, while amiodarone has hypothyroidism or hyperthyroidism, and lung damage. If the dose of verapamil is improperly adjusted, there will also be adverse reactions in cardiovascular, neurological, endocrine and other aspects, and it is difficult to find ideal antiarrhythmic drugs in all aspects simply from natural products.
How to overcome the problem of adverse reactions of antiarrhythmic drugs in the prior art is an urgent problem to be solved at present
Method used
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Embodiment 1
[0084] Step (1), under ice-bath condition, add trifluoroacetic acid to make grambanine dissolve completely in grambanine; Then slowly add N-bromosuccinimide, N-bromosuccinimide The addition time of the solution was more than 10 minutes; after the addition, the ice bath was removed, and the reaction solution was stirred at room temperature for 11 hours, and then rotary evaporated to remove the solvent trifluoroacetic acid to obtain a concentrate;
[0085] The mass volume ratio of kebanine to trifluoroacetic acid is 0.2:4.9; the molar ratio of kebanine to N-bromosuccinimide is 1:1.1;
[0086] Step (2), add water that is 9.5 times of the volume of trifluoroacetic acid in the concentrate that step (1) obtains, then use saturated Na 2 CO 3 The aqueous solution was adjusted to pH 8, followed by CH 2 Cl 2 Perform the extraction, extracting 2 times, each extraction of CH 2 Cl 2 The amount used is one-fifth of the volume of water, and the organic layers are combined;
[0087] Ste...
Embodiment 2
[0113] An antiarrhythmic drug, comprising the following components in parts by weight: 250 parts of bromocarbanine compounds, 60 parts of powdered sugar, and 5 parts of dextrin; the bromocarbanine compounds are 3 parts - Bromocarbanine or 10,11-bromocarbanine and pharmaceutically acceptable salts thereof. The bromocarbanine compound is 10,11-bromocarbanine.
[0114] The preparation method is the same as in Example 1.
Embodiment 3
[0116] An antiarrhythmic drug, comprising the following components in parts by weight: 120 parts of bromocarbanine compounds, 90 parts of powdered sugar, and 10 parts of dextrin; the bromocarbanine compounds are 3 parts - Bromocarbanine or 10,11-bromocarbanine and pharmaceutically acceptable salts thereof.
[0117] The bromocarbanine compound is a pharmaceutically acceptable salt of 3-bromocarbanine.
[0118] The preparation method is the same as in Example 1.
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Abstract
The invention relates to a brominated crebanine compound and preparation method and an application thereof, which belongs to the technical field of medicine. The invention firstly discloses the synthesis of 3-brominated crebanine and 10, 11-brominated crebanine, through research on effect of chloroform for inducing mice arrhythmia, the research shows that the 3-brominated crebanine and 10, 11-brominated crebanine can antagonize the chloroform-induced ventricular fibrillation, so that the 3-brominated crebanine and 10, 11-brominated crebanine have anti-arrhythmia effect through preliminary determination; the barium chloride-induced rat ventricular rhythm tests confirm that the 3-brominated crebanine and 10, 11-brominated crebanine have good anti-arrhythmia effect, acute toxicity of two brominated crebanine compounds is lower than that of crebanine, LD50 is 65.15+ / -1.132 mg / kg of 3-brominated crebanine and 59.62+ / -2.610 mg / kg of 10,11-brominated crebanine respectively, and a good base can be established for further deep researches.
Description
technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to bromocarbanine compounds and their preparation methods and applications. Background technique [0002] Cardiac arrhythmia refers to abnormalities in the frequency, rhythm, origin, conduction velocity, or sequence of cardiac impulses. Arrhythmia is an important group of diseases in cardiovascular diseases. It can occur alone or accompany other cardiovascular diseases. Its prognosis is related to the etiology, inducement, evolution trend of arrhythmia, and whether it leads to severe hemodynamic disturbance. It can occur suddenly and cause sudden death, or it can continue to involve the heart and cause it to fail. Although there are radiofrequency ablation and other treatment methods, antiarrhythmic drugs are still the main treatment method or an essential part of it. For a long time, people have been unremittingly committed to the research and development of antiarrhy...
Claims
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