Study Of Carbamide Peroxide And Sodium Chloride For Injection

OBJECTIVETo prepare a convenient, rapid and preservation hypertonic-hyperoxia intravenous preparation—carbamide peroxide and sodium chloride for injection, which can be used to improve the oxygen content in the patients'body, expand blood volume rapidly and is suitable to be used in field first aid and pre-hospital care.METHODSResearch work in this study mainly include the optimization of the preparation and formulation of carbamide peroxide and sodium chloride for injection, investigation of the physical and chemical properties of the preparation, inspections of stability, safty and pharmacodynamics, et al.1.Based on crude drugs'physical and chemical properties and optimization of preparative method, the designed formulation is carbamide peroxide:sodium chloride (w.w=1:6.6) and produced with axenic distribution.2. According to the requirements of injection in Chinese Pharmacopoeia (2005 edition), the key inspection items were investiged including description, identification, pH value, clarity, osmotic pressure and moisture content and content determination, et al. Iodometry and argentometry were used to determine the contents of hydrogen peroxide and sodium chloride.3.According to the method in Chinese Pharmacopoeia(2005) appendix XIX C, the stability of c arbamide peroxide and sodium chloride for injection were studied, including stress testing, accelerated testing and long-term testing with description, content, pH, clarity, osmotic pressure and moisture content as the key inspection items. The influences of temperature, humidity and light on the character of the preparation were studied.4. The allergy test,venors stimulation test and hemolysis test were done to evaluate the safety of carbamide peroxide and sodium chloride for injection by macroscopic observation and pathological examination.5. The rabbits model of hemorrhagic shock was established to observe the effect of carbamide peroxide and sodium chloride for injection on the blood gases and hemorheology and to evaluate this preparation in the early stage after hemorrhagic shock.24 healthy rabbits were bled to a mean arterial pressure of 45 mmHg and then randomized into three treatment groups:those treated with 7.5% sodium chloride group(6mL·kg-1, n=8, HS), carbamide peroxid for injection (6mL·kg-1, n=8, NCP) and carbamide peroxide and sodium chloride for injection group (6mL·kg-1, n=8, HCP). The rabbits model of hemorrhagic shock was made by the method of fixed pressure. Blood samples were taken for blood gas analysis at six time points:before shock,60min after shock, 10min after treatment,30min after treatment,60min after treatment and 120min after treatment.RESULTS1. The preparation is white crystalline powder, dissolved in water easily, clear and colorless after redissolved. pH is about 3.89 and osmotic pressure is around 2575 mOsmol. The contents of H2O2 and NaCl are between 30.0% to 36.0% and 95.0% to 105.0% of labelled amounts, respectively.2. The results indicated that Carbamide peroxide and sodium chloride for injection is sensitive to temperature and light. The optimum condition for the storage of the preparation was under airtight condition protected from light,2-8℃. The storage period is set to one years temporarily.3. No haemolysis and agglutination were observed. The hemolytic test showed that it had no hemolyzation and aggregation. The vascular stimulation test showed it had little congestion, but no evidences of abnormity.4. The results indicated rabbits in the HS groups had significantly higher mean arterial presssure than the other two groups in short time. NPS groups maintained or improved rabbits'arterial oxygen saturation (SaO2) and arterial oxygen pressure(PaO2). HPS groups unified the above two superiorities which can treat hypoxemia more effectually.CONCLUSIONSThe produced carbamide peroxide and sodium chloride for injection has a resonable and workable technology, a controllable and stable quality and is safe and efficient in preclinical study. The study provides good proof for the studing of preparations combining the oxygen therapy wih intravenous transfusion and provides the way of thinking for development of new pharmaceutical preparations.