Removing Ammonia By Microemulsion-In Situ Gel For Preventing Hepatic Encephalopathy

The increase of blood ammonia is the main cause of Hepatic Encephalopathy(HE). Enema is the main clinical measure to eliminate ammonia in the colon to prevent HE; however,most patients won't suffer this inconvenient measure.The preparation of oral drug system improves the circumstances.Lactulose,which could be decomposed to acetic acid by enzymes in the colon to eliminate ammonia,and antibiotics,which could decrease the ammonia yield by making the physiology activity of enzymes down,but the ammoniaremoved efficiency of these two drugs is relatively low,also accompanying the side effect. Considering this situation,a new oral reagent was prepared to eliminate ammonia to prevent HE,by embedding acetic acid microemulsion in pH-sensitive in situ gel(sodium alginate) which could protect microemulsion from being destroyed in gastric and small intestine with different gelation in various pH environment and finally take acetic acid microemulsion to the colon,and this increased the efficiency of eliminating ammonia.Polydimethyl silicone oil(PDMS) which is not absorbed,degraded and is biocompatible with the body was considered as microemulsion oil phase,and by investigating its pseudo-ternary phase diagram,the more optimal preparation conditions of high water solubilization of microemulsion were determined that the Tween80 was as surfactant, ethylene glycol or 1,2-propadiol was as cosurfactant,the mass ratio between Tween80 and cosurfactant was 1:1,that of oil to Tween80 and cosurfactant was 2:1,and the acetic acid solution containing 0.01mol/L NaCl was as inner water phase of microemulsion.Under the above conditions,the water solubilization could be around 20%which achieved the drugloaded amount of acetic acid microemulsion.Adding more water into this microemulsion, there was no phase inversion of microemuslion from W/O to O/W which ensured no drug burst release of the system and this laid a basis for preparation of microemuslion-in situ gel.The new system of acetic acid microemulsion-in situ gel was prepared by dropping acetic acid microemulsion into sodium alginate solution,based on the pH-sensitivity of sodium alginate.The comparison of in vitro experiment between acetic acid microemulsion and acetic acid microemulsion-in situ gel showed that the sodium alginate gel could protect acetic acid microemulsion from being destroyed in gastric and small intestine,with the increased ammonia-removed efficiency from 39.24%of single microemuslion to 58.29%of microemulsion-in situ gel,and this ammonia-removed microemulsion-in situ gel could preserve for more than 130 days at room temperature.The optimal preparation conditions of such microemulsion-in situ gel were that the acetic acid microemulsion was embedded in the sodium alginate solution with volume ratio of 1:1,the acetic acid concentration was 30%～50%,and the sodium alginate concentration was 4%.The initial animal experiment showed that there was no difference between in vitro experiment and in vivo experiment with acetic acid microemulsion,and this microemulsion swelled into emulsion in rat's stomach,still being emulsion in small intestine and colon.The pH in rat's colon decreased from 7.9 to 7.5 and it showed acetic acid microemuslion could improve rat's colon environment to some extent.The animal experiment with microemulsion-in situ gel will be carried out.