Design,preparation And Properties Of Two Novel Pyraloxime Methylchloride Delayed Release Systems

Chemical warfare agent is a chemical substance that posses a great threat to the environment and human life safety.The direct application of chemical warfare agent antidote has many drawbacks,such as cumbersome application,multiple application of small amount,and no specific targeting.It is of great significance to research and develop a suitable carrier of chemical warfare agent antidote to prepare a suitable drug-loading system for the smooth progress of the integration of chemical warfare agents.In this thesis,drug-loaded composites were prepared using mesoporous molecular sieve MCM-41 and a bio-based metal organic framework compound bio-MOF-1.The two drug-loaded materials were characterized by infrared spectroscopy(IR),N2 adsorption-desorption(BET)and X-ray powder diffraction(XRD).The drug loading rate and encapsulation efficiency as well as its release performance in a suitable buffer solution were examined.The main findings of the paper are as follows:(1)The chemical warfare agent antidote pyraloxime methylchloride(2PAM)is introduced into the pores of the silica-based mesoporous material MCM-41 by simple stirring,and the inhibitor of silanol and acetylcholinesterase(AChE)on the surface of MCM-41 is passed.The ethoxy group on the surface of the pyridinium derivative is dehydrated and the other end of the derivative is combined with the active site anion and cation of AChE to block the direct release of chloropHospHonium,thereby encapsulating the chloropHospHonium in MCM-41.(2PAM@MCM-41)-P1-AChE composite drug-loading material was prepared.The structure of the drug-loaded material was characterized by infrared,x-ray diffraction and transmission electron microscopy.At the same time,it can be concluded that the drug loading rate reached 22.1%by the method of measuring the ultraviolet absorption value of the drug in the solution before and after the weight loss method(TGA)and the drug loading.When the composite material encounters the G-type neurochemical warfare agent DFP,the hydroxyl group on the active site of AChE on the surface of the material can be combined with the P-F bond of DFP,and the binding force is strong,resulting in AChE from MCM-41.The surface is detached,the material pores are opened,and the pyraloxime is released,thereby achieving the targeting and controlled release of the neurotoxic agent antidote.Tris-HCl(trishydroxymethylaminomethane)solution and deionized water were used as buffer solutions for drug release.The in vitro release kinetics monitoring was carried out by visible light-ultraviolet spectropHotometry,and the efficiency of release of(2PAM@MCM-41)-P1-AChE drug-loaded material after exposure to organopHospHorus poisoning agent was obtained.The results showed that the drug release rate increased rapidly within 20 min,and then the release rate gradually slowed down and became flat after 60 min.At room temperature and 5 mg of composite material,the release rate of pyraloxime can reach 93.4%within 90 min,and the minimum detection limit is 0.25 ppm.It is suitable for various neurological factors such as DFP and DMNP.The chemical warfare agent has a targeting effect,and the surface-grafted acetylcholinesterase can specifically bind to the neurobiopHospHate poisoning agent,so that the pyraloxime can be targeted for high-efficiency release.The composite drug-loading material is expected to be a multifunctional chemical sustained-release drug release material for degrading chemical poisoning agents and treating poisoning agents.(2)The method of vigorously stirring and solvent exchange was used to introduce methylchloride(2PAM)with neurochemical chemical warfare agent into the bio-MOF-1 channel of adenine as ligand.The composite drug-loading material bio-MOF-1@2PAM with anion-cation exchange characteristics was characterized,and its related pores and surface structures were characterized by IR,P-XRD,SEM,BET and other characterization methods.The thermogravimetric method(TGA),(C,H,N)elemental analysis before and after drug loading and the UV absorption value of chlorhexidine in the solution before and after drug loading were quantified,within 2-3 days of drug soaking.The drug loading rate reached 20.8%.At the same time,the simulated body fluid and deionized water were used as buffers for drug release,and the in vitro release kinetics monitoring was carried out by visible light-ultraviolet spectropHotometry.The drug release properties of the composite drug-loaded materials were investigated.The results showed that the drug release showed a controlled release profile,and the release rate of the drug in the buffer was faster than that in the control group,indicating that the presence of cations in the simulated body fluid could further trigger the release of the drug.Within 48 hours,it was observed that the release of chlorhexidine was rapidly released within 10 h and a slow release began at 10 h to 50 h.The maximum drug release rate of chlorhexidine was 88.5%at room temperature and 15 mg of composite.The drug-loading material can spontaneously perform the anion-cation exchange process in the simulated body fluid simulating the human body environment,and this characteristic can control the slow release of the drug.Therefore,the composite drug-loading material bio-MOF-1@2PAM synthesized herein can As a drug in the late stage of neurochemical chemical warfare poisoning,it maintains the long-term blood concentration of chlorhexidine in the human body,and continuously removes the poison in the body without causing side effects.