Mesylate Ropivacaine Injection Experiments

Ropivacaine is a long-acting amino amide class of local anesthetics, developed by Astra Pain Control AB, Sweden . The data concerning the physiochemical and clinical features of ropivacaine has been collected before it is testified and determined . And evaluate the biopharmaceutical and pHarmacokinetical properties. On this basis and through certain important biopharmaceutical and pharmacokinetical methods ,a new drug project is put forward o The old prescription is optimized by substituting methanesulfonic acid for hydrochloric acid. According to the requirements of the 4th type new drug development a pHarmaceutical and pharmacodynamical research has been done.1 pharmacy part(study of the technology of preparation of inj ection)1. 1 Use qualified raw material to optimize the prescription of ropivacaine methanesulfonic acid injection to make sure a safe, valid ,stable and economical prescription constituents.1. 2 Check the craft process and its external color ,pH value, clearness degree, germfree checking, content, stability respectively. By increasing the liquid solubility, stability, clearness degree determine the most appropriate pH value and the technology of preparation of the injection.1. 3 Check its stability against light and heat and test its content and pH value. The result is no obvious change. The temporarily determined term of validity is 2 years. The injection conforms to the requirements of 20 CPS. It lays the foundation for further pharmacodynamical and clinical research.2 pharmacodynamical check(pharmacological and toxicological research) Abide by the items of requirements of the 4th new drug development, and complete the experiments on documents of no.12,13,14,and 16.2. 1 major pharmacodynamical experimentsRopivacaine methanesulfonic acid injection into the inside of skin can repress the sharp pain reaction of guinea pig. The injection into the off-body sciatic nerve of frogs can repress the contraction of musculus gastrocnemius caused by electric stimulation and it can repress the range of electric potential of bigrats' off-body sciatic nerve. The injection into hard membrane vertebra ofdomestic rabbits can repress the changes of respirator}' range and frequencycaused by the electric stimulation on the skin of legs. It indicates thatropivacaine methanesulfonic acid and ropivacaine HCL are similar intake-effect-time,duration and action strength.2. 2 general pharmacologic experimentsThe injection on the muscle of cats make a tendency of decreasing of theirblood pressure ,heart rate, and respiratory frequency. While the bloodpressure ,heart rate, respiratory frequency and depth as well as the QRSx S-TNT wave make no obvious difference between those without the injection andreference group. The small dosage does not affect the rats' activities ,whilelarge dosage can decrease their activities after 10 minutes and recover 60minutes later.2. 3 acute toxicological experimentsRopivacaine methanesulfonic acid injection into the vein of rats, the LDso is22.4mg / kg (19.3-26.lmg / kg); into the skin ,the LD50 is 108.7mg/kg (93.8-126.3mg/kg)o While ropivacaine HCL injection into the vein of rats, theLD50 is 21.6mg/kg(19.6-23.7mg/kg); into the skin, the LD50 is 101.4mg / kg(95.0-107.4mg/kg)c2. 4 safety experimentsThe local stimulation experiments, allergy experiments and hemolysisexperiments indicate: the injection has no obvious irritant reaction , noobvious allergic reaction, and no hemolysis or coagulation. In conclusion, thedesign and development of ropivacaine methanesulfonic acid injection hasachieved preliminary success.