Study On The Safety Evaluation And Quality Standard Of Ivermectin Microemulsion

The ivermectin microemulsion with new efficient broad-spectrum and low toxicity can be used in many animals for endoparasite and ectoparasite. It is composed of nanoemulsion which as a carrier system and more than 80% water. The safety evaluation of injection, the content determination methods of ivermectin, stability test and injection,s sterility test were carried out in this dissertation.1. The safety evaluation of the ivermectin microemulsion injection include allergy test, haemolytic test, the muscle stimulation test, pyrogen test, acute toxicity test by intraperitoneal injection, and subchronic toxicity test. The results showed that the allergic reaction of ivermectin microemulsion injection on rat and guinea pig were negative and it had no sensitization. No hemolysis of rabbit red blood cells and the agglutination reaction were observed. There was no significant stimulation to muscle. The pyrogen test of Ivermectin microemulsion was negative and its pyrogen accords with the standard limitation. The LD50 of ivermectin microemulsion by intraperitoneal injection in rats was 3.8256g/kg, and 95% confidence limit was 3.4639 g/kg~4.2251 g/kg. The LD50 of ivermectin microemulsion by intraperitoneal injection in mice was 3.2200g/kg, and 95% confidence limit was(1.8197~5.6979).It is higher than ivermectin injection(24.2493 mg/kg) according to XUXia. Subchronic toxicity test showed that the weight, haematological index and biochemical criterion of rats in variety dose have no significant difference compared with normal group. It indicated that ivermectin microemulsion injection had no evident toxic and side effects on rats for long period and can be administered in clinic. All results proved that ivermectin microemulsion is safe and reliable based on the animal experiments.2. The content determination methods of ivermectin in the ivermectin microemulsion injection were established by High Performance Liquid Chromatography(HPLC). Hypersil ODS2 coloum(5um,4.6mm x 250mm) was used. A mobile phase composed of methanol, acetonitrile and water(35:65:5,v/v)at a flow rate of 1m L·min-1. The ultraviolet detector was set at 244 nm and coloum temperature was 30℃. The sample size was 10 μl. The content of ivermectin in three lots nolve compound injection was 94%~100% of labeled amount. The methods with accuracy, reliability, improved selectivity, and convenience could be employed to determine the content of ivermectin in the ivermectin microemulsion injection.3. The stability tests of novel compound ivermectin microemulsion injection included high temperature, high humidity test, strong illumination test and accelerated test. The results showed that the contents of ivermectin did not have significant changes among the tests. The rubble plug could be used in the preparation because of no obvious effect on the content change whether the samples were upright, upside down or flat place. So the preparation is conformed to store and transport.4. To study sterility test and the validation for sterility test of ivermectin microemulsion and to establish a method of sterility test for ivermectin microemulsion injection. Use this method of sterility test of ivermectin microemulsion for three lots nolve compound injection. The results showed that the positive control bacterias were growing good wihin 24 h. The negative control bacterias and three lots nolve compound injection were sterile. It indicated that sterility test results meet the requirements.