Effect Of Borneol As Ocular Penetrant And Its Mechanism

Borneol is a common traditional Chinese medicine and few alone used in clinical therapy.It is often combined with other Chinese medicines to treating many kinds of diseases in the compound prescription.It is used to promote other drugs' absorption, enhance their effects and help them pentrate the barrier.It is a long history for borneol as a external used ocular drug in China.The permeating property of borneol benefits its using on ophthalmology of TCM.Borneol has a low-grade analgesia and antiinflammatory effect. Besides these,it can inhabit some malignant bacteria.All these effects are used sufficiently at ophthalmology.Some studies show the effect of borneol changed with its partner,and its mechanism has been studied this year.The effect was presumed with its opening the paracellular gap and improving the flowability of corneal epithelium membranes.The evaluation of drug action were studied with the combined drug,which lead a deficiency of comparing with other drug.It is necessary to set up a public index to compare borneol's drug action with others or its improved dosage form.It can be used as a coarse screen model of derivate of borneol too.The study invested the promotive effect of borneol in vitro and in vivo based on the previous studies.Different qualitative drugs were used as probes to presume the penetrant mechanism of borneol.The difference of drug action were studied among d-borneol,d-isoborneol and borneol salicylate.The promotive effect of bomeol to pirenzepin was proved,which founded the next study for clinic use.1.The Improvement of Corneal Diffusion ChamberA better corneal diffusion chamber was developed and method was set up.Fluorescein sodium was used as a common probe.The concentrations of fluorescein sodium in the perfusion chamber were measured at different dosage of borneol,and the dose-effect relationship was described which was used to observe and evaluate among bomeol and other penetrants.2.Mechanism of Borneol on Opening Corneal Barrier and Its EffectFresh and harmless corneas of Newzealand rabbit were destructed in epithelium or endothelium,or perfused from the inside of cornea.The concentration of fluorescein sodium was measured.Cornea were divided to different groups randomly.The groups included high,middle,low concentration of borneol,isoborneol,azone and solvent control group. Different concentration drugs and fluorescein sodium at a constancy concentration were added in administer chamber,the perfusate were collected at designed time.The concentration of fluorescein sodium was measured with ultraviolet spectrophotometry,and the effects of penetrants were evaluated.The results showed the possible site of action of borneol is the corneal epithelium,it has no relationship with endothelium.The effects of borneol and isoborneol promoting fluorescein sodium permeation were paralleled with their concentrations.The results increased significantly compared with solvent control group and showed no significant deviation to isoborneol.3.Effect of Borneol on Propranolol Penetrateing Corneal BarrierPropranolole hydrochloride was used as a common probe.The concentration of propranolole hydrochloride in the perfusion chamber was measured with fluorospectrophotometry at different dosage of borneol.The effect of penetrant was inspected and the mechanism of which was presumed.Fresh and harmless corneas of Newzealand rabbit were tested with different concentration of propranolole hydrochloride.The perfusate were collected at designed time and the concentration of propranolole hydrochloride in perfusate were measured.The suitable concentration of propranolole hydrochloride was selected as the concentration of probe.The high,middle,low concentration of borneol,solvent control and blank group were set.Different concentration borneol and fluorescein sodium at a constancy concentration were added in concentrationadminister chamber,and the effects of penetrants were evaluated.The results showed a depressant effect of borneol on propranolole hydrochloride permeation.The results depressed significantly at high and middle concentration compared with solvent control group and showed a negative correlation of borneol concentration.The solvent control group showed a depressant effect too.4.Effect of borneol salicylate on Corneal BarrierFluorescein sodium was used as a probe to evaluated permeation effect of borneol salicylate -a Borneol derivate.The material included was inspected and the mechanism of which was presumed.Fresh and harmless corneas of Newzealand rabbit were tested.Different concentration borneol derivate and fluorescein sodium at a constancy concentration were added in administer chamber,the perfusate were collected at designed time.The concentration of fluorescein sodium was measured with ultraviolet spectrophotometry,and the effects of penetrants were evaluated.The results showed a similar effect with borneol at middle and low concentration group and low at high concentration group.The effect was related with prototype of borneol salicylate.4.Influence of Borneol on Pirenzepine Penetrateing Corneal BarrierBorneol was combined with pirenzepine hydrochloride as a penetrant to produce a gutta for clinic.The complex gutta was tested compare with single pirenzepine hydrochloride gutta in vitro and in vivo.A HPLC method to calculate pirenzepine hydrochloride concentration.Fresh and harmless corneas of Newzealand rabbit were tested.Pirenzepine gutta with/without borneol were added in administer chamber,the perfusate were collected at designed time.The concentration of pirenzepine hydrochloride was measured with HPLC system.The alive Newzealand rabbit were droped with complex gutta 50μl per 5 min at one side saccus conjunctivae and the other side with single pirenzepine hydrochloride gutta.The rabbits were anaesthesia and sacrifaced with a over load pentobarbite after 6 droped gutta.The eyeballs were selected and aqueous humor was collected.The eyeballs were dissected refer to position,and homogenated.The clear supernatant of homogenate or perfusate was used to measured pirenzepine hydrochloride concentration with HPLC system.The results showed borneol can elevate pirenzepine concentration effectively at most regional of eyeball.The accumulation concentration in receive chamber was rasied to 19 times and 13.3 times at aqueous humor.Content of pirenzepine at most position increased at different level except retina and crystalline lens.The duration of pirenzepine in eyeball was prolonged as the content was raised.So,the following conclusions could be draw from the findings of the whole issue researches:1.Borneol and isoborneol can promote the corneal permeation of fluorescein sodium, the effect correlated with the concentration of local application positively.The possible site of action of borneol is the corneal epithelium.Borneol and isoborneol can promote those drug' s permeation,which cross cornea via passive paracellular permeation.Borneol salicylate has(?) similar effect with borneol.2.A depressant effect of borneol was observed on propranolole hydrochloride permeation,the effect correlated with the concentration of local application positively. Borneol inhibit those drug' s permeation,which cross cornea via transcellular.3.Borneol can promote pirenzepine's permeation of cornea and prolong the resistance time.The bioavailability of pirenzepine was increased.In conclusion,it is clear that borneol can promote those drug' s permeation,which cross cornea via passive paracellular permeation,Borneol inhibit those drug' s permeation, which cross cornea via transcellular.The penetrant effect of borneol derivate- borneol salicylate,was compaired with borneol and isoborneol.It is peoved that borneol can promote pirenzepine's permeation of cornea and increased.its bioavailability.The results hint that borneol can promote the drugs crossed cornea via passive paracellular permeation and inhibit the drugs crossed cornea via transcellular method The experiment offered a method to screen penetrant,the results could be a guide to clinical compound prescription.