Experimental Study On LNG Release And Cu²⁺ Concentration Of MAS-IUS In Simulated Uterine Cavity Fluid

Objective:To explore the releasing rule of levonorgestrel(LNG)and the existence form of Nano copper and determination of copper ion concentration in simulated uterine cavity fluid using "memory alloy silicone intrauterine sustained release system"(MAS-IUS)optimization(in constant temperature environment at 37℃),with a view to providing experimental data for continuous improvement of MAS-IUS and subsequent research.Methods:MAS-IUS optimization was prepared by adding 52 mg levonorgestrel standard in increments according to the standard IUS manufacturing process,using a Nano copper silica membrane thickness of 1 mm and a nano copper concentration of3 g/L in the membrane as loop parameters;MAS-IUS optimization pieces were put into 15 m L polypropylene tubes after extensive washing,respectively,and randomly divided into two groups with five samples in each group,the test group was added with 7.5 m L simulated uterine cavity fluid(completely flooded with MAS-IUS optimization pieces),the control group with 7.5 m L normal saline,the samples were placed in a 37℃ constant temperature water bath,and 1 m L of each sample solution was taken every 24 h,respectively,The remaining liquid was replaced with 7.5 m L of new simulated uterine cavity fluid or saline,respectively,after each fluid pick-up,for31 consecutive days,and the amount of LNG released from the sample solutions of the two groups was measured by a timed ultrahigh performance liquid-tandem mass spectrometry system;The copper ion reaction was measured by a chemical chromogenic method,and the copper ion content in simulated uterine cavity fluid was measured by UV spectrophotometer.Results:The MAS-IUS optima showed significant differences(P <0.001)in LNG release in simulated uterine fluid and saline at different time points,but not at adjacent time points(P< 0.05);LNG release patterns before and after 15 days were investigated using segmented linear regression,and the results showed that LNG release in the saline group before 15 days decreased significantly with time(P < 0.01),with the release model formula: LR(?g/24 h)= 2.550-0.058×T;In the saline group,LNG release did not change significantly over time after 15 days(P >0.05),and LNG release was almost constant with a mean release of 1.900±0.110(?g/24 h);In the simulated intrauterine fluid group LNG release 15 days earlier decreased significantly with time(P < 0.01)and the release model formula was: LR(?g/24 h)= 3.359-0.083×T;There was no significant difference(P >0.05)in the release volume over time in the simulated uterine fluid group after 15 days,while LNG release volume remained almost constant after 15 days,almost in accordance with the zero order release law,with a mean release volume of 2.440±0.110(?g/24 h)。The mean LNG release was significantly(P < 0.05)higher in the simulated intrauterine fluid group(2.560 ?g/24 h)than in the saline group(1.990 ?g/24 h).The copper ion concentration was measured to be 0.0176 g/L by chromogenic reaction,which proved to mimic the copper ion in the uterine cavity fluid.Conclusion: Theamount of LNG released before 15 days in simulated intrauterine fluid decreased gradually with time in MAS-IUS optimization,and was almost constant after 15 days,with a mean LNG release of 2.440±0.110(?g/24 h),which conformed to the zero order release law;MAS-IUS optimization released copper ions in simulated uterine cavity fluid,which existed as copper ions,and the copper ion concentration was 0.0176 g/L.