Study On Anti-lung Cancer Targeting Drug ZP-1 Lyophilized Powder For Injection

Current treatment technique for lung cancer is molecular targeted therapy, research and development of a new anti-lung cancer targeting drug,which has curative effect, low toxicity and the proprietary intellectual property rights,has the vital significance.Our group research and development anti-lung cancer targeting drug ZP-1 which guarantees the inhibitory effect of Platinum compounds for lung cancer, also reduces the side effects f Platinum compounds and prolongs survival. But the experimental result indicated that ZP-1 has thermal instability and also is unstable in the water, so should not be used as water injection. In order to solve this problem, improve the stability of ZP-1, this topic uses the vacuum freezing drying method, through screening prescription and optimized preparation progress,to be developed as a powder for injection. Not only causes the product by solid state form storing, moreover avoids the high temperature and high pressure of sterilization measures, thus effectively improving the quality of products. This topic consists of the following four parts: 1. Preformulation study of anti-lung cancer targeting drug ZP-1 lyophilized powder for injectionThis chapter has established the content determination of ZP-1 through high performance liquid chromatography(HPLC) method, chromatographic conditions: chromatographiccolumn:Waters Xbridge C18(4.6mm×150mm,3.5 μm);Mobile phase:0.1% trifluoroacetic acid/water-0.1% trifluoroacetic acid/acetonitrile(volume r a t i o 9 7 : 3); F l o w r a t e : 1 m L / m i n; d e t e c t i o n w a v e l e n g t h : 2 1 5 n m; c o l u m n temperature:25℃;sample quantity:20μL.And has conducted the preliminary investigation for stability of ZP-1 under this chromatograph condition, finally indicated, ZP-1 to the high temperature, the humidity and the illumination is unstable, preserves 6 month stabilities under 25℃ and 4℃ the condition to be good. 2. The preparation of anti-lung cancer targeting drug ZP-1 lyophilized powder for injectionTake the product characteristics, solubility, clarity, moisture as index, through excipient compatibility test and single factor sthdy, finally indicated that using mannitol as excipient, amount is 8(w/v), 0.9% NS as solvent; And through inspects ZP-1 under the dissimilar condition stability and freeze-drying curve screening, has determined the preparation progress. Finally, the product meet the requirements. 3. Quality research of anti-lung cancer targeting drug ZP-1 lyophilized powder for injectionThis chapter has established the partial quality control index. The product is white foam lumps, the moisture content does not surpass 2%, the bacterium endotoxin limit is 2.5 EU/mg, after the dissolution obtains colorless and clarifing solution, p H5.5-6.0, the content is determined by high performance liquid chromatography, ZP- 1 should be labeled content of 90.0%-110.0%. 4. The preliminary stability of anti-lung cancer targeting drug ZP-1 lyophilized powder for injectionThis chapter examines the preliminary stability of ZP-1 lyophilized powder.the, mainly influencing factors of products test, accelerated test and long-term test.The results show that ZP-1 lyophilized powder is placed under the condition of 25 ℃ and 4℃ for 3 months is stable, the test is still continue.