Misoprostol, a light yellow viscous liquid, can be miscible with ethanol, ether or chloroform, and is very difficult to dissolve in water or n-hexane. It is a derivative of prostaglandin E1, which has a strong effect of inhibiting gastric acid secretion and contractile effect on pregnant uterus. In addition, misoprostol has the pharmacological activity of e-prostaglandins, which can soften the cervix, enhance uterine tension and intrauterine pressure. At present, the sequential application of mifepristone to induce labor has become one of the main methods for mid-term induction of labor. It can better replace the surgical operations such as forceps curettage and amniocentesis. The success rate of abortion is about 96.1%. It is a safe and effective method for induction of labor. Misoprostol is the first clinical PGE (prostaglandin E) derivative, which has obvious curative effect on various ulcers (except duodenal ulcer). However, its price is relatively expensive. At present, it is generally used as a second-line drug for the treatment of ulcers, mainly for refractory ulcers or recurrent ulcers.
Artificial synthesis of misoprostol: take azelaic acid as raw material, react with diimidazolyl sulfoxide to produce imidazole acylation product, which has strong acylation activity. After reacting with monomethyl malonate, it is acidified and decarboxylated to produce 2-[8- (methoxycarbonyl) octyl] methyl acetate, then hydrolyzed and decarboxylated to produce 8-oxo decanoic acid, cyclized and decarboxylated with dimethyl oxalate to produce 3-substituted cyclopentatrione, One of the carbonyl groups was selectively hydrogenated to hydroxyl, and then reduced to 4-hydroxy-2- (methyl heptanate-7-yl) - 2,3-cyclopentenone after reaction with acetone acetal. Finally, misoprostol was obtained by reaction with organic aluminum reagent.
It is mainly used as the first chemically synthesized prostaglandin E1 anti ulcer drug. It has a strong effect on inhibiting gastric acid secretion and preventing ulcer formation. The gastric acid that can be inhibited includes basal gastric acid secretion and gastric acid secretion caused by histamine pentagastrin, food or coffee stimulation, and can also reduce gastric acid secretion at night. It is the first anti peptic ulcer drug used in clinic. It is superior to receptor antagonists in prolonging ulcer recurrence, but less effective in relieving peptic ulcer pain than Island receptor antagonists. For gastric and duodenal ulcers, especially for cases with low prostaglandin levels.
With regard to the pharmacological knowledge of misoprostol, prostaglandins and their derivatives are a class of anti peptic ulcer drugs that have been discovered in recent 20 years and have attracted increasing attention. This product is the first derivative of synthetic prostaglandin I to enter the clinic. It has been proved to have a strong effect on inhibiting gastric acid secretion in animals and humans. After administration, the gastric juice secretion and acid excretion caused by basal gastric acid, histamine, gastrin and food stimulation were significantly reduced, and the protease excretion was also reduced. However, the mechanism of action has not been elucidated yet, which may be related to the effect of adenylate cyclase activity on the cAMP level of parietal cells. Animal experiments have also proved that it can prevent the formation of ulcers. Therefore, it is considered that this product has strong cell protective effect in addition to inhibiting gastric acid secretion. In addition, this product also has the pharmacological activity of e-prostaglandins, which can soften the cervix, enhance uterine tension and intrauterine pressure. Sequential use with mifepristone can significantly increase and induce the frequency and amplitude of spontaneous uterine contraction in early pregnancy, which can be used to stop early pregnancy. Its adverse reactions were smaller than those of thioprostone and carboprost methyl ester, and it was easy to use. The oral absorption is good. After taking a single dose, Tmax is 0.5 hours and the elimination half-life is 20-40 minutes. The plasma protein binding rate was 80~90%. The drug concentration in liver, kidney, intestine, stomach and other tissues was higher than that in blood. After oral administration, about 75% of the product labeled with radioactive elements is excreted from urine, about 15% is excreted from feces, and 56% is excreted from urine within 8 hours.
Knowledge of pharmacokinetics: misoprostol is absorbed rapidly by oral administration, and can be completely absorbed after 1.5h. After 15 minutes of oral administration, the plasma active metabolite misoprostoic acid reached a peak. Single oral administration 200 μ g. The mean peak plasma concentration was 0.309 μ g/L。 The plasma protein binding rate of misoprostol was 80% ~ 90%. The drug concentration in liver, kidney, intestine, stomach and other tissues was higher than that in blood. The elimination half-life of misoprostol is 20 ~ 40min, and it is taken orally every 12 hours for 400 μ G misoprostol did not accumulate in vivo. About 75% of misoprostol was excreted in urine through the kidney and about 15% was excreted from the stool after oral administration; The excretion of urine within 8h was 56%.
Relevant experts have evaluated this product. Misoprostol is a derivative of prostaglandin E1, which has a strong effect on inhibiting gastric acid secretion and has a contractile effect on pregnant uterus. In addition, misoprostol has the pharmacological activity of e-prostaglandins, which can soften the cervix, enhance uterine tension and intrauterine pressure. At present, the sequential application of mifepristone to induce labor has become one of the main methods for mid-term induction of labor. It can better replace the surgical operations such as forceps curettage and amniocentesis. The success rate of abortion is about 96.1%. It is a safe and effective method for induction of labor. Misoprostol is the first clinical PGE (prostaglandin E) derivative, which has obvious curative effect on various ulcers (except duodenal ulcer). However, its price is relatively expensive. At present, it is generally used as a second-line drug for the treatment of ulcers, mainly for refractory ulcers or recurrent ulcers.