Research Of Palonosetron Hydrochloride Injection

Palonosetron Hydrochloride, commercially named Aloxi, chemically called 2-[1-Azabicyclo[2,2,2]oct-3(S)-yl]-2,3,3a(S),4,5,6-hexahydro-lH-benz[de]isoqui nolin-1-one hydrochloride. It is a high effective, high elective and high emulative 5-hydroxytepatmin3(5-HT3) antagonist, developed by Helsinn Healthcare Corp. in Swizerland. This drug is used to prevent the emesis which is caused by chemical therapy in the beginning course and to treat the cute and delayed naused and vomiting in the repetitive period of treatment. It is the only drug that can act on delayed naused and vomiting and the fourth 5-HT3 antagonist approved by FDA, now it has been included in the nation cancer combination net of USA, so it brings great convenience to the cancer patient. On the 25th of july in 2003, this drug was faced to the market in America and Japan as injection and oral dosage. In China, QILU Pharmaceutical Comp has studyed this drug since 2002, and till 2008, the Comp obtained the production lot of this drug and began to produce palonosetron hydrochloride injection. According to the articles and patents nationally, the present research is still concentrated on the study of injection, mainly about the improvement of formula to raise its stability.The content of this text is distributed into seven parts:1):Overview of current research status at home and abroad antiemetic, and 5-HT3 receptor antagonist palonosetron discovery and development were reviewed for the study after the theoretical basis. 2):References and franchised palonosetron hydrochloride synthetic route to reform, be of high purity raw material medicine, in accordance with the Pharmacopoeia of the need to examine their conduct, and to study its physical and chemical properties and stability, for the selection and quality of prescription analysis of the basis.3):establish of the analysis methods of palonosetron hydrochloride in vitro including determination of content and related sustances and isomers.4):research of the improvement of palonosetron hydrochloride formula and preparetion. Through a series of single factors and the L9 (3)4 orthogonal design test, optimization formulation and preparation process, the optimal prescription is:dose of palonosetron hydrochloride at 0.25mg/5mL,0.9% sodium chloride as isotonic regulator, calcium disodium 0.05% as the metal ion complexing agent, and citrate-sodium hydroxide buffer pH3.5-4.0 in regulating the composition; the optimal preparation technique:accessories in accordance with the prescribed amount of mixing, dissolved in water for injection in prescription volume, accessories and the main drug in accordance with the prescribed amount of mixing, dissolved in water for injection prescription volume, ultrafiltration 30min,then filter by 0.22μm membrane,5mL/branch filling, sealing,121℃15min sterilization.5):accordiong to the optimal preparation process, enlarge the best formula, carry out factors experiment, isothermal heating experiments and long-term stability eperiments, the result is that the fomula is very stable. 6):safety evaluation of palonosetron hydrochloride injection by hemolysis in vitro, vascular irritation, acute toxicity and long-term toxicity test. The outcome is satisfaction to us:the dosage would not induce hemolysis or stimulatory, and the toxicity of this drug is also extremely weak. In one world finally, the best formula and preparation of palonosetron hydrochloride is safe and stable.7):carry out the pharmacokinetic study of the products on rabbits to explore the in vivo drug concentration curve, and provide a basis for clinical...