May 16, 2019
Lappaconitine is a diterpenoid alkaloid isolated from the genus Ranunculaceae. It is chemically known as (1α,14α,16β)-20-B. Base-1,14,16-trimethoxyoxatol-4,8,9-triol 4-[2-(acetylamino)benzoate hydrobromide monohydrate. It is the first non-addictive analgesic drug in China. It has the functions of analgesia, antipyretic, swelling and local anesthesia, and has no addiction and accumulation. Its analgesic effect is stronger than that of indomethacin and weaker than morphine.
1. Analgesic effect
Peritoneal injection of lappaconitine hydrobromide can significantly alleviate the thermal pain sensation in rats with chronic constrictive injury (CCL), achieve analgesic treatment effect, and have no obvious toxicity.
2. Anti-inflammatory effect
Lappaconitine has obvious inhibitory effects on xylene-induced swelling of mouse ear shell, arthritic foot swelling in rats and agar granuloma hyperplasia in rats. It indicates that lappaconitine has anti-acute and chronic inflammatory effects. This effect provides a theoretical basis for the treatment of pain and redness caused by rheumatoid arthritis and rheumatoid arthritis.
3. Anti-tumor effect
The inhibitory rate of lappaconitine on mouse liver cancer was 11.20% to 53.08%, and the tumor inhibition rate to mouse S180 was 29.81%-53.%. It indicated that hydrouric acid and lappaconitine had certain anti-mouse liver cancer S180 effect, and had no obvious effect on the body weight of mice.
4. Anti-arrhythmia effect
Lappaconitine can increase the arrhythmia threshold of aconitine induced by rats, and can significantly improve myocardial ischemic arrhythmia in dogs, thereby reducing the incidence of arrhythmia, the mechanism may be Block the sodium ion channel.
Pharmacokinetics [Pharmacokinetics] The plasma elimination half-life (tl/2), clearance rate CL and apparent volume of distribution V of lappaconitine hydrobromide were not significantly different at high, medium and low doses, ie The pharmacokinetic parameters of the drug did not substantially change with dose changes, manifested as linear kinetic behavior. The drug-time process in the body conforms to the two-compartment open model, which absorbs faster and eliminates moderate speed.
[Distribution] It is widely distributed in mouse tissues and binds to tissue proteins, resulting in lower drug concentrations in plasma.
[Metabolism] There are 10 metabolites in the metabolism of lappaconitine in rats. Metabolites include hydroxylated metabolites, O-demethyl metabolites, N-deacetylated metabolites, O-desmethyl N-deacetylated metabolites, double O-desmethyl N-desylation Metabolites, ester hydrolysis metabolites. The main metabolic pathways of lappaconitine in rats are hydroxylation, O-demethylation, N-deacetylation and ester hydrolysis. These metabolic pathways may also cross, producing secondary metabolites.
The roots of Gaowutou roots are pulverized→added to the extraction tank and soaked in ethanol for 1 hour, heated to reflux for 3 hours and 3 times→concentrated, acidified with 2% hydrochloric acid, filtered by suction → alkalized with ammonia to PH 9-10, stirred and precipitated, filtered → The precipitate is dissolved with chloroform → water is added to the process, and the mixture is allowed to stand for stratification. The mixture is stirred and dehydrated by adding anhydrous potassium carbonate, and the mixture is dehydrated to a paste form → dissolved in ethanol, and ethanol is recovered until crystallization is carried out to obtain lappaconitine.