The Preparation Of Flurbiprofen-chitosan Hydrogel In Situ And Study On Intrawound Analgesia Effect Afterincisional Administration To Rats

【Objective】⑴T o prepare injectable flurbiprofen–chitosan(FP-CS) Hydrogel(short name:gel) in situ,and inspect the sol-gel transition behavior and the capability of drug loading;⑵To evaluate the effect of analgesia by calculating the cumulative pain scores (CPS) after the Brennan's incision pain model established in rats.【Methods】⑴Developed Ultraviolet spectrophotometry content te-st of FP and determined the standard curve,the average recovery rate and RSD;⑵M ixed CS acetic solution and NaHCO3 solution togeth-er under certain condition; dispersed FP powder into above mixture at designed amount ,then got injectable CS or FP-CS hydrogel in situ which loaded FP at theoretical con-centration of 0mg?ml-1,1mg?ml-1,3mg?ml-1,5mg?ml-1 respectively,and numbered 0,1,2,3 for the corresponging gel.⑶The pH--meter is applied to investigate the pH value of both sol and gel. The drug loading,drug loading efficiency and RSD in gel are determined by UV. The gelati-on time is determined by the up-down vial method;⑷48rats weighing 200g±16g are randomly divided into 6 groups (n=8 each)and named group A(controlledA),group B(controlled B),group C,group D,group E and group F correspondingly. By the Brennan's method,every rat underwent operation for the incision pain model. While the operation finished, the 6 groups are respectively received physiological saline,gel 0,FP powder,gel 1,gel 2,gel 3.(each group is given FP powder or FP in gel at the dose of 10 mg/kg). The CPS are calculated at 2 hour before operation and at 2h,4h,6h,12hour,24h,48h,60h,72h,96h after operation.【Results】⑴The content test system of FP is accomplished by Ultraviolet spectrophotometry method.FP showed the peak of UV absorption at the wave length of 247 nm,the standard curves of FP is linear over the range of 1.0-10.0ug/ml,and the equation of standard curves is C=12.4825A-0.1631,R=0.9999; The average recovery rate is 99.15±0.69%;RSD is 0.4566%within a day and RSD=0.72%interday;⑵The prepration of FP-CS gel is accomplished The gel shows higher pH value than that of the corresponding sol, the gelation time is 30-40min at 37OC in vitro test;⑶the drug loading efficiency of 1-3 gelation is97.95±0.73%,96.64±0.74 %,94.98±1.57% respectively; RSD is0.44%,0.35%,0.15%within a day and 0.88%,0.71%,0.39% interday;⑷48case of rats incision pain model are finished. The CPS increased (P<0.05) after the incision pain model established compared to that before, the difference had st-atistics significance;During the whole postoperative period, the CPS of controlled group A and B had sustained the same high value; Within the first 6h, the CPS of group C is lower than group A and B (P<0.05), and showed the same level of groupE and F(P>0.05); after6h, the CPS increased to parar-ell group A and B, there is non-statistics significance (P>0.05); Within 72h, each of group D,E,F had lower value compare to controlled group A and B in CPS, and among the former three groups,both of group E and F, of which the CPS showed no difference to each other (P>0.05), but are higher than group D(P<0.05); after72h,the CPS of group D,E,F increased to reach the controlled group,there are non-statistics significance (P>0.05).【Conclusion】⑴The average recovery rate and RSD of FP suggested the good recurrence,the method of FP content analysis by UV is simple and effective;⑵The products showed sol-gel transition in vitro test,and could make most amount of given FP enclosed in gel frame.⑶FP–CS injectable gel exhibited the analgesia effect by intrawound adminstrationg.The time of analgesia sus-tained proximately 72h.⑷The both of FP-CS hydrogel loading 3mg?ml-1 and 5mg?ml-1 of FP worked the same effect as FP powder,which were stronger than the gel loading 1mg?ml-1 of FP.