Preparation And Quality Evaluation Of Puerarin Lipid Microsphere Injection

Puerarin is an isoflavone compound extracted from the dried roots of the legume Pueraria lobata.Modern studies have shown that it has a significant therapeutic effect on cardiovascular and cerebrovascular diseases.Puerarin injection is more clinically used.Puerarin injection is too fast to release the drug,irritating,and adverse reactions occur from time to time;and low solubility,it is often necessary to add a co-solvent(propylene glycol).Studies have shown that the addition of propylene glycol can aggravate the adverse reactions of puerarin hemolysis.In view of the problems of puerarin injection,a safer drug delivery system is needed to avoid similar problems.This subject tried to prepare puerarin in the form of phospholipid complex into puerarin lipid microsphere injections,and to investigate the physical and chemical properties and stability of the prepared lipid microspheres,and to conduct pharmacokinetics and pharmacodynamics in rats.Scientific evaluation,in order to try to obtain a new way of puerarin-puerarin lipid microsphere injection,to better meet the needs of clinical safe medication.The pre-prescription research of the drug is the key to the success of the drug preparation.The in vitro analysis and detection method of puerarin was established by high performance liquid chromatography,and the apparent solubility of puerarin in buffers with different p H values and the oil and water in the n-octanol/water system were determined.Partition coefficient and solubility under different ratios of long-chain fatty acid glycerides(LCT)for injection and medium-chain fatty acid glycerides(MCT)for injection.The results show that puerarin is not highly soluble in water and oil.Stability experiments indicate that puerarin is unstable under strong light and high temperature.The formulation optimization of puerarin lipid microspheres used single factor investigation and star point design-curved surface effect method,and the preparation process was optimized by single factor investigation method.The optimized prescription of puerarin lipid microspheres is: egg yolk lecithin 1.40 g in puerarin phospholipid complex,pluronic 188 0.20 g,LCT 3.00 g,MCT 17.00 g,Tween 80 0.15 g,sodium oleate 0.05g;preparation The process is: the colostrum oil phase and the water phase are mixed at 70°C and then prepared in a high-pressure homogenizer at13000r/min for 10 minutes.The colostrum is homogenized 8 times under a pressure of 70 MPa in the high-pressure homogenizer to obtain a stable final product.milk.Transmission electron microscope was used to observe the appearance of puerarin lipid microspheres,and the particle size,particle size distribution andζ-potential of puerarin lipid microspheres were measured with a nanoparticle sizer.The drug loading of puerarin lipid microspheres was measured by high performance liquid chromatography,and the encapsulation efficiency was measured by Sephadex G-50(Sephadex G-50)microcolumn centrifugation method.The particle size of the puerarin lipid microspheres was measured to be 242.0nm,PDI was 0.130,ζ-potential was-33.1m V,encapsulation efficiency was 93.00%,and drug loading was 5.00mg/ml.The stability of puerarin lipid microspheres is mainly investigated by centrifugal acceleration test,freezing-heating cycle test and long-term stability.The results show that the puerarin lipid microsphere injection can remain stable for a long time.The PH value,the viscosity after dilution,the osmolality and other indicators of the puerarin lipid microspheres all meet the basic requirements of the Pharmacopoeia for injection emulsions.Taking puerarin injection as a reference preparation,puerarin lipid microspheres were used in rats to evaluate the pharmacokinetics and pharmacodynamics.Pharmacokinetic studies have shown that puerarin lipid microsphere injection can significantly improve the bioavailability,half-life and peak plasma concentration of puerarin.Pharmacodynamics Establish a rat model of focal cerebral ischemia-reperfusion injury(MCAO)by means of suture method.Evaluation indicators include neurological deficit score,percentage of cerebral infarction,water content of brain tissue,and inflammatory factors in brain homogenate And the influence level of intercellular adhesion molecule(ICAM-1)to investigate the protective effect of focal cerebral ischemia-reperfusion injury in rats.The results show that puerarin lipid microsphere injection has a protective effect on cerebral ischemia-reperfusion injury in rats.Conclusion: Under the optimized prescription ratio,the puerarin lipid microsphere injection prepared by the two-step high-pressure homogenization method has stable properties,and all indicators meet the basic requirements of the pharmacopoeia for injection emulsion.Pharmacokinetic experiments showed that the half-life,peak concentration and bioavailability of puerarin lipid microsphere injection in rats were significantly higher than puerarin injection.Pharmacodynamic experiments have proved that puerarin lipid microsphere injection has a better protective effect on the damage caused by MCAO in rats.It can be seen that,as a new drug delivery system for puerarin,puerarin lipid microsphere injection is worthy of further study to prepare for better clinical services.