冰片眼用的药效和机制研究
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摘要
冰片是一味常用中药,常在复方中与其他药物联用,用于促进吸收、增加药物的药效,穿透某些生物屏障。冰片作为眼科外用药历史悠久。冰片在中医眼科的应用与其通透的药性有关;同时冰片有轻度的镇痛抗炎作用,并能抑制杀灭一些有害细菌,这些药效在眼科得到充分的应用。
近年来研究表明冰片的促渗透作用与药物有关,并对冰片的促渗作用进行机制的探讨,认为冰片的作用与其开放细胞间隙有关,并可改善了角膜上皮细胞膜的流动性。
以往的冰片药效评价都是以所实验的药物为评价指标,缺乏横向比较的可能。为了对冰片的眼科促渗透效果有一系统了解,有必要建立一个通用的评价指标,系统的评价冰片的药效,并用于比较冰片剂型改良后的药效,也可以作为冰片衍生物药效的一个粗筛模型。
本课题在前期研究的基础上,改进建立了适合角膜的体外灌流装置和实验方法;用离体实验比较天然冰片(右旋龙脑)、异龙脑、水杨酸冰片酯促进荧光素钠透过角膜的效果;用离体实验考察天然冰片对普萘洛尔透过角膜的影响,探讨天然冰片促药物透过角膜的机制;通过离体实验考察了天然冰片与哌仑西平合用对后者的促通透作用,并用在体实验证实。
1.离体角膜灌流装置的改进
改良了角膜的体外灌流装置和建立相应的实验方法,采用荧光素钠作为作为统一的探针药物,测量给予不同浓度受试药后其在灌流接收池中的浓度变化,从而建立一个观察评价对冰片和其他促渗透剂的方法。
2.天然冰片开放角膜屏障的机制及药效
取新鲜无损新西兰兔角膜,分别损毁上皮层或内皮层,或采用从内侧灌流的方法,测量不同条件下荧光素钠透过量;兔角膜随机分为龙脑、异龙脑的高、中、低,溶剂对照组,和阳性对照组(氮酮)。置于体外灌流装置后,在给药池中加入不同浓度的药物和相同浓度的荧光素钠,在不同时点取接收池灌流液,以紫外分光光度法测量透过角膜的荧光素钠含量,评价药物的促通透效果。
结果表明,天然冰片开放角膜屏障作用部位可能在角膜的上皮细胞层,与内皮细胞层无关。龙脑、异龙脑不同浓度给药,其促荧光素钠渗透效果与浓度呈正相关,与溶剂组有显著差异,与异龙脑间无显著差异。
3.天然冰片对普萘洛尔透过角膜屏障的影响
采用盐酸普萘洛尔作为作为探针药物,以荧光分光光度法测量给予冰片后其在灌流接收池中的浓度变化,考察冰片是否对其能促渗透,并推测冰片的作用机制。
取新鲜无损新西兰兔角膜,在给药池中加入不同浓度的盐酸普萘洛尔,在不同时点取接收池灌流液,测量透过角膜的盐酸普萘洛尔含量,考察建立适宜的探针浓度;设立龙脑高、中、低、溶剂、空白对照组,放入体外灌流装置后在给药池中加入相应的药物和统一浓度的盐酸普萘洛尔,评价药物的促通透效果。
结果显示:不同浓度的冰片对盐酸普萘洛尔透过角膜有抑制作用,其抑制效果随浓度增加而加强,溶剂对照组对盐酸普萘洛尔透过也有抑制作用,高、中浓度组与溶剂对照组有显著差别。
4.水杨酸冰片酯对角膜通透性的影响
采用荧光素钠作为探针药物,评价冰片衍生物水杨酸冰片酯的促透过能力,并考察其作用物质,推测其机制。
取新鲜无损新西兰兔角膜,放入体外灌流装置后在给药池中加入不同浓度的水杨酸冰片酯和统一浓度的荧光素钠,在不同时点取接收池灌流液,以紫外分光光度法测量透过角膜的荧光素钠含量,评价药物的促通透效果。
水杨酸冰片酯促荧光素钠渗透效果中、低浓度与龙脑相似,高浓度略差,其药效与原型直接作用角膜有关。
5.天然冰片对派仑西平进入眼内的影响
采用冰片作为促渗透剂与哌仑西平合用,研制一种能用于临床的滴眼剂。在离体和在体两个层次与单方的哌仑西平滴眼液作了对比实验。
建立了哌仑西平的高效液相测量方法;取新鲜无损新西兰兔角膜,在给药池中加入含/不含冰片的盐酸哌仑西平滴眼液,在不同时点取接收池灌流液,测量透过角膜的盐酸哌仑西平含量;在活体新西兰兔一侧眼滴加含冰片哌仑西平滴眼液50μl,对测滴加等量哌仑西平滴眼液,每5min第一次,连续6次后过量戊巴比妥麻醉处死动物,摘取眼球,吸出房水,按部位解剖眼球,分别匀浆各部位,取上清液测量哌仑西平的含量。
结果证明冰片可以有效的提高哌仑西平在眼内各部位的浓度,以接收池和房水中药物累积浓度计,离体增加19倍,在体增加13.3倍,除视网膜和晶状体外,各部位的药物含量均有不同程度的增加。给予冰片后不仅透过角膜吸收的哌仑西平数量增加,其延续时间也延长。
从整个课题的研究结果,我们可以得到以下结论:
1.天然冰片(右旋龙脑)、异龙脑对于荧光素钠的角膜渗透有促进作用,强度与局部应用的浓度成正相关,其作用部位可能在角膜上皮细胞层。表明右旋龙脑、异龙脑能促进经细胞间隙转运的药物透过角膜。水杨酸冰片酯的促渗透效果与右旋龙脑相似。
2.天然冰片(右旋龙脑)可以抑制盐酸普萘洛尔透过角膜,作用与浓度成正相关。表明右旋龙脑对跨细胞转运的药物透过角膜有抑制作用。
3.天然冰片能促进哌仑西平进入眼内,并延长其滞留时间,增加其生物利用度。
通过本课题的研究,我们明确了冰片对于经细胞间隙转运药物透过角膜有促进作用,而对跨细胞转运药物透过角膜有抑制作用;比较了冰片衍生物水杨酸冰片酯的促渗透效果;验证了冰片哌仑西平滴眼液能促进哌仑西平进入眼内,改善哌仑西平的生物利用度。实验结果提示冰片与经细胞间隙转运的药物合用时会产生较好的促进作用,而对跨细胞转运的药物透过生物屏障则有消极的影响。实验结果对于临床联合用药有指导意义,可以采用监测荧光素钠透过率方法作为筛选促渗透剂的指标。
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 Chamber
A 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 Effect
Fresh 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 Barrier
Propranolole 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 Barrier
Fluorescein 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 Barrier
Borneol 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.
近年来研究表明冰片的促渗透作用与药物有关,并对冰片的促渗作用进行机制的探讨,认为冰片的作用与其开放细胞间隙有关,并可改善了角膜上皮细胞膜的流动性。
以往的冰片药效评价都是以所实验的药物为评价指标,缺乏横向比较的可能。为了对冰片的眼科促渗透效果有一系统了解,有必要建立一个通用的评价指标,系统的评价冰片的药效,并用于比较冰片剂型改良后的药效,也可以作为冰片衍生物药效的一个粗筛模型。
本课题在前期研究的基础上,改进建立了适合角膜的体外灌流装置和实验方法;用离体实验比较天然冰片(右旋龙脑)、异龙脑、水杨酸冰片酯促进荧光素钠透过角膜的效果;用离体实验考察天然冰片对普萘洛尔透过角膜的影响,探讨天然冰片促药物透过角膜的机制;通过离体实验考察了天然冰片与哌仑西平合用对后者的促通透作用,并用在体实验证实。
1.离体角膜灌流装置的改进
改良了角膜的体外灌流装置和建立相应的实验方法,采用荧光素钠作为作为统一的探针药物,测量给予不同浓度受试药后其在灌流接收池中的浓度变化,从而建立一个观察评价对冰片和其他促渗透剂的方法。
2.天然冰片开放角膜屏障的机制及药效
取新鲜无损新西兰兔角膜,分别损毁上皮层或内皮层,或采用从内侧灌流的方法,测量不同条件下荧光素钠透过量;兔角膜随机分为龙脑、异龙脑的高、中、低,溶剂对照组,和阳性对照组(氮酮)。置于体外灌流装置后,在给药池中加入不同浓度的药物和相同浓度的荧光素钠,在不同时点取接收池灌流液,以紫外分光光度法测量透过角膜的荧光素钠含量,评价药物的促通透效果。
结果表明,天然冰片开放角膜屏障作用部位可能在角膜的上皮细胞层,与内皮细胞层无关。龙脑、异龙脑不同浓度给药,其促荧光素钠渗透效果与浓度呈正相关,与溶剂组有显著差异,与异龙脑间无显著差异。
3.天然冰片对普萘洛尔透过角膜屏障的影响
采用盐酸普萘洛尔作为作为探针药物,以荧光分光光度法测量给予冰片后其在灌流接收池中的浓度变化,考察冰片是否对其能促渗透,并推测冰片的作用机制。
取新鲜无损新西兰兔角膜,在给药池中加入不同浓度的盐酸普萘洛尔,在不同时点取接收池灌流液,测量透过角膜的盐酸普萘洛尔含量,考察建立适宜的探针浓度;设立龙脑高、中、低、溶剂、空白对照组,放入体外灌流装置后在给药池中加入相应的药物和统一浓度的盐酸普萘洛尔,评价药物的促通透效果。
结果显示:不同浓度的冰片对盐酸普萘洛尔透过角膜有抑制作用,其抑制效果随浓度增加而加强,溶剂对照组对盐酸普萘洛尔透过也有抑制作用,高、中浓度组与溶剂对照组有显著差别。
4.水杨酸冰片酯对角膜通透性的影响
采用荧光素钠作为探针药物,评价冰片衍生物水杨酸冰片酯的促透过能力,并考察其作用物质,推测其机制。
取新鲜无损新西兰兔角膜,放入体外灌流装置后在给药池中加入不同浓度的水杨酸冰片酯和统一浓度的荧光素钠,在不同时点取接收池灌流液,以紫外分光光度法测量透过角膜的荧光素钠含量,评价药物的促通透效果。
水杨酸冰片酯促荧光素钠渗透效果中、低浓度与龙脑相似,高浓度略差,其药效与原型直接作用角膜有关。
5.天然冰片对派仑西平进入眼内的影响
采用冰片作为促渗透剂与哌仑西平合用,研制一种能用于临床的滴眼剂。在离体和在体两个层次与单方的哌仑西平滴眼液作了对比实验。
建立了哌仑西平的高效液相测量方法;取新鲜无损新西兰兔角膜,在给药池中加入含/不含冰片的盐酸哌仑西平滴眼液,在不同时点取接收池灌流液,测量透过角膜的盐酸哌仑西平含量;在活体新西兰兔一侧眼滴加含冰片哌仑西平滴眼液50μl,对测滴加等量哌仑西平滴眼液,每5min第一次,连续6次后过量戊巴比妥麻醉处死动物,摘取眼球,吸出房水,按部位解剖眼球,分别匀浆各部位,取上清液测量哌仑西平的含量。
结果证明冰片可以有效的提高哌仑西平在眼内各部位的浓度,以接收池和房水中药物累积浓度计,离体增加19倍,在体增加13.3倍,除视网膜和晶状体外,各部位的药物含量均有不同程度的增加。给予冰片后不仅透过角膜吸收的哌仑西平数量增加,其延续时间也延长。
从整个课题的研究结果,我们可以得到以下结论:
1.天然冰片(右旋龙脑)、异龙脑对于荧光素钠的角膜渗透有促进作用,强度与局部应用的浓度成正相关,其作用部位可能在角膜上皮细胞层。表明右旋龙脑、异龙脑能促进经细胞间隙转运的药物透过角膜。水杨酸冰片酯的促渗透效果与右旋龙脑相似。
2.天然冰片(右旋龙脑)可以抑制盐酸普萘洛尔透过角膜,作用与浓度成正相关。表明右旋龙脑对跨细胞转运的药物透过角膜有抑制作用。
3.天然冰片能促进哌仑西平进入眼内,并延长其滞留时间,增加其生物利用度。
通过本课题的研究,我们明确了冰片对于经细胞间隙转运药物透过角膜有促进作用,而对跨细胞转运药物透过角膜有抑制作用;比较了冰片衍生物水杨酸冰片酯的促渗透效果;验证了冰片哌仑西平滴眼液能促进哌仑西平进入眼内,改善哌仑西平的生物利用度。实验结果提示冰片与经细胞间隙转运的药物合用时会产生较好的促进作用,而对跨细胞转运的药物透过生物屏障则有消极的影响。实验结果对于临床联合用药有指导意义,可以采用监测荧光素钠透过率方法作为筛选促渗透剂的指标。
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 Chamber
A 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 Effect
Fresh 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 Barrier
Propranolole 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 Barrier
Fluorescein 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 Barrier
Borneol 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.
引文
[1]葆光道人.秘传眼科龙木论[M].北京:人民卫生出版社,1958.
[2]肖国士 眼科外用片脑的研究[J].贵阳中医学院学报1987,3:11-12
[3]陈艳明,王宁生.冰片对血脑屏障体外模型细胞问紧密连接和细胞吞饮囊泡的影响[J].中国中西医结合杂志,2004,24(7):632-634
[4]樊岚岚,唐由之,陆丽珠等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003,28(1):81-82
[5]赵威博士毕业论文[D].广州中医药大学2005届
[6]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[7]Urtti A.Challenges and obstacles of ocular pharmaeokineties and drag delivery [J].Adv Drug Del Rev,2006,58(11):1131-1135
[8]S.D.Klyce,C.E.Crosson,Transport processes across the rabbit corneal epithelium:a review,[J].Curr.Eye Res.1985,4(4):323-331
[9]A.J.Huang,S.C.Tseng,K.R.Kenyon,Paracellular permeability of corneal and conjunctival epithelia,[J].Invest.Ophthalmol.Vis.Sci.1989,30(4):684-9
[10]H.S.Huang,R.D.Schoenwald,J.L.Lach,Corneal penetration behavior of beta-blocking agents Ⅱ:assessment of barrier contributions[J].,J.Pharm.Sci.1983,72(11):1272-1279.
[11]R.D.Schoenwald,H.-S.Huang,Corneal penetration behaviour of beta-blocking agents Ⅰ:physicochemical factors,[J].J.Pharm.Sci.1983,72(11):1266-1272.
[12]Hornof M,Toropainen E,Urtti A.Cell culture models of the ocular barriers[J].Eur J Pharm Biopharm,2005,60(2):207-225
[13]K.M.Ha"ma"la"inen,K.Kananen,S.Auriola,K.Kontturi,A.Urtti,Characterization of paracellular and aqueous penetration routes in cornea,conjunctiva,and sclera,[J].Inve st.Ophthalmol.Vis.Sci.1997,38(3):627-634.
[14]J.J.Palmgre'n,E.Toropainen,S.Auriola,A.Urtti,Liquid chromatographic-electrospray ionization mass spectrometric analysis of neutral and charged polyethylene glycols,[J].J.Chromatogr.A 2002,976(1-2) 165-170.
[15]M.R.Prausnitz,J.S.Noonan,Permeability of cornea,sclera,and conjunctiva:a literature analysis for drug delivery to the eye,J.[J].Pharm.Sci.1998,87(12)1479-1488
[16]I.Ahmed,T.F.Patton,Importance of the noncorneal absorption route in topical ophthalmic drug delivery,[J].Invest.Ophthalmol.Vis.Sci.1985,26(4) 584-587.
[17]A.Urtti,L.Salminen,Minimizing systemic absorption of topically administered ophthalmic drugs,[J].Surv.Ophthalmol.1993,37(6) 435-456.
[18]Hosoya K,Lee VH,Kim KJ.Roles of the conjunctiva in ocular drug delivery:a review of conjunctival transport mechanisms and their regulation[J].Eur J Pharm Biopharm,2005,60(2):227-240
[19]李风鸣 眼科全书[M]北京人民卫生出版社 眼的生理生化,1996,257-287
[20]Bill A.The blood-aqueous Trans[J].Ophthalmol Soc U K.1986;105(Pt2):149-55
[21]J.M.Conrad,J.R.Robinson,Aqueous chamber drug distribution volume measurement in rabbits,[J].J.Pharm.Sci.1977,66(2) 219-224.
[22]S.Duvvufi,S.Majumdar,A.K.Mitra,Drug delivery to the retina:challenges and opportunities,[J].Expert Opin.Biol.Ther.2003,3(1) 45-56.
[23]J.G.Cunha-Vaz,The blood- ocular barriers:past,present,and future,[J].Doc.Ophthalmol.1997,93(1-2) 149-157
[24]P.A.Stewart,U.I.Tuor,Blood-eye barriers in the rat:correlation of ultrastructure with function,[J].J.Comp.Neurol.1994,340(4):566-576.
[25]R.H.Quinn,S.S.Miller,Ion transport mechanisms in native human retinal pigment epithelium,[J].Invest.Ophthalmol.Vis.Sci.1992,33 (13):3513-3527.
[26]Tso MO,Shih CY,McLean IW.Is there a bloo j-brain barrier at the optic—nerve head [J].Arch Ophthalmol.1975,93(9):815-25
[1]戴耀华等.长效利福平眼药膜的研制及其对沙眼的疗效[J].中华眼科杂志1986,22(2):102
[2]Oechsner M,Keipert S.Polyacrylic acid/polyvinylpyrrolidone bipolymeric systems.I.Rheological and mucoadhesive properties of formulationspotentially useful for the treatment of dry-eye-syndrome[J].Eur J Biopharm,1999,47(2):113-118
[3]El-Kamel AH.In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate.[J].Int J Pharm.2002,241(1):47-55.
[4]Kim EY,Gao ZG,Park JS,et al.rhEGF/HP-beta-CD complex in poloxamer gel for ophthalmic delivery.[J].Int J Pharm,2002,233(1-2):159-167.
[5]Gupta P,Vermani K,Garg S.Hydrogels:from controlled release to pH-responsive drug delivery.[J].Drug Discov Today,2002,7(10):569-579.
[6]Annouk Rozier,Claude Mazuel,Jeflh'ey Grove,Bernard Plazonnet.Functionality testing of gellan gum,a polymeric excipient material for ophthalmic dosage forms.[J].Int J Pharm,1997,153 (2):191-198
[7]Cohen S,Lobel E,Trevgoda A,et al.A novel in situ—forming ophthalmic drug delivery systems form alginates undergoing gelation in the eye.[J]Controlled Release,1997,44(2-3):201～208
[8]Paulsson M,HagerstromH,Edsman K.Rheological studies of the gelation of deacetylated gellan gum (Gelrite)in physiologial conditions [,J].Eur J Pharm Sci,1999,9(1):99～105
[9]Carlfors J,Edsman K,Petersson R,et al.Reheological evaluation of gelrite in situ gels for ophthalmic use [J].Eur J Pharmsci,1998,6(2):113～119
[10]Kaur IP,Smitha R.Penetration enhancers and ocular bioadhesives:two new avenues for ophthalmic drug delivery [J].Drug Devel Ind Pharm,2002,28 (4):353-369.
[11]Grass GM,Robisson JR.Mechanisms of corneal drug penetration I:in vivo and in vitro kinetics [J].J Pharm Sci,1988,77(1):3-14
[12]Rathore MS,Majumdar DK.Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin from aqueous drops [J].AAPS Pharm Sci Tech,2006,7(3):Article57,E12～17.
[13]Kaur IP,Singhm,Kanwarm.Formulation and evaluation of ophthalmic preparations of acetazolamide [J].Int J Pharm,2000,199 (2):119-127.
[14]Anderberg EK,Artursson P.Epithelial transport of drugs in cell cultureV Ⅲ:effects of sodium dodecyl sulfate on cellmem-brane and tight junction permeability in human intestinal epithelial (Caco-2)cells [J].J Pharm Sci,1993,82 (4):392-398.
[15]Grzeskow IAK E.Biopharmaceutical availability of sulphadicramide from ocular ointments in vitro [J].Eur J Pharm Sci,1998,6 (3):247-253.
[16]Hochman JH,Fix JA,Lecluyer EL.In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoyl carnitine [J].J Pharmacol Exp Ther,1994,269 (2):813-822
[17]Sasaki H,Igarashi Y,Nagano T,et al.Different effect of absorp tion p romoters on corneal are conjunctival penetration of ophthalmic beta-blockers [J].Pharm Res, 1995,12(8):1146-1162
[18]Durand Cavagna G,Duprat P,Molon N S,et al.Corneal endothelial changes with azone,a penetration enhancer[J].Lens Eye Toxic Res,1989,6(1-2):109-117.
[19]Kompella UB,Bandi N,Ayalasomayajula SP.Subconjunctival nano- and microparticles sustain retinal delivery of budesonide,a corticosteroid capable of inhibiting VEGF expression.[J].Invest Ophthalmol Vis Sci,2003,4(3):1192-1201.
[20]Assil KK,Hartzer M,Weinreb RN,et al.Liposome suppression of proliferative vitreorefinopathy.Rabbit model using an timetabolite encapsulated liposomes.[J].Invest Ophthalmol Vis Sci,1991,32(11):2891-2897.
[21]Cavalli R,Gasco MR,Chetoni P,et al Solid lipid nanoparticles(SLN)as ocular delivery system for tobramycin.[J].Int J Pharm,2002.238(1-2):241-245.
[22]李安良.生物利用度控制[M].第1版.北京:化学工业出版社,2004年,P146-171
[23]Mandell AI,Stentz F,Kitabchi AE Dipivalyl epinephrine:a new pro-drug in the treatment of glaucoma.[J]Ophthalmology.1978,85(3):268-75
[24]Miller-Meeks MJ,Farrell TA,Munden PM,Folk JC,Rao C,Schoenwald RD.Phenylephrine prodrug.Report of clinical[J]Ophthalmology.1991,98(2):222-6]
[25]Ranta VP,Urtti A.Transscleral drug delivery to the posterior eye:prospects of pharmaeokinetic modeling[J].Adv Drug Deliv Rev,2006,58(11):1164-118
[26]Bourges JL,Bloquel C,Th omas A,et al.Intraoeular implants for extended drug delivery:therapeutic applications[J].Adv Drug Deliv Rev,2006,58(11):1182-1202.
[27]Cheng L,Hostetler KY,Chaidhawangul S,et al.Treatment or prevention of herpes simplex virus retinitis with intravitreally injectable crystalline 1-O-hexa decylpropanediol-3-phosphoganciclovir[J].Inv Ophthal Sci,2003,121(1):57-61.
[28]Dhillon B,Kamal A,Leen C.Intravttrcal sustained-release ganctclovtr implantation to control cytomegalovirus retinitis in AIDS[J]J.Int J STD AIDS 1998;9(4):227-230.
[29]Tao W,Wen R,GoddardMB,et al.Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa [J].lnvest Ophthalmol Vis Sci,2002,43(10):3292-3298.
[1]林斌 冰片旋光性的研究[J].华西药学杂志1988,3(3):145-146
[2]王强 杨显荣 陈金泉.冰片的鉴定分析研究[J]中草药1994,25(5):241-244
[3]葆光道人.秘传眼科龙木论[M].北京:人民卫生出版社,1958
[4]傅仁宇.审视瑶函[M],新1版.上海:上海人民出版社,1959.
[5]肖国士 眼科外用片脑的研究[J].贵阳中医学院学报1987,3:11-12
[6]孙启明 冰片的药性问题及其反思[J]中成药1993,15(5):43
[7]姜道平 王树才 韩其江 李志民 董玉根 李长林 仙人掌冰片外敷治疗眼部带状疱疹[J]中医外治杂志1997,1:28
[8]谢培德 王宝琴 利眼膏中冰片的薄层鉴别与气相色谱测定[J]中国中药杂志1989,14(7):31-33
[9]周文袅,曾立威,周嵩煌,陆敏仪 两种气相色谱法测定珍珠明目滴眼液中冰片的含量[J]华西药学杂志2004,19(2):137-139
[10]孙晓萍,欧立娟,宓穗卿,王宁生 冰片抗炎镇痛作用的实验研究[J].中药新药与临床药理2007,18(05):353-355
[11]江光池,杨胜华,冯旭军 龙脑和异龙脑的抗炎作用[J].华西药学杂志1990,5(03):190-191
[12]牟家琬,杨胜华,孙玉梅,伍朝筼 龙脑与异龙脑的体外抗菌作用的研究[J].华西药学杂志1989,4(1):20-22
[13]樊岚岚,唐由之,陆丽珠等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003,28(1):81-82.
[14]王灿.冰片对中医眼科外用药促渗作用的研究[J].中国中医基础医学杂志,2002,8(6):46,54
[15]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[16]赵威 博士毕业论文[D]广州中医药大学2005届
[17]胡利民,屈菜芹,李怡岚,刘洋,孙玉敏,张伯礼 合成冰片和天然冰片的小鼠骨髓嗜多染红细胞微核试验[J].中草药,2005,36(4):571-572
[18]何庆 夏忠玉 冰片口服制剂安全性的实验研究[J].中国药师2006,9(5):419-421
[19]吴纯洁 黄勤挽 齐红艺 郭平 侯世祥 中药冰片眼部用药的局部毒性研究 [J].中国药学杂志,2005,40(22):1710-1713
[20]杨洪滨,寻延滨,张小宇,李志坚,崔欧,张立琼,崔浩 局部应用天然与合成冰片的眼刺激性与长期毒性[J].国际眼科杂志,2008,8(11):2228-2231
[21]王晖,许卫铭,王宗锐,等.薄荷醇与冰片的促透作用[J].中草药,1997,28(2):93-94
[22]周成萍,彭松,廖蔚珍,等.复方雷公藤涂剂透皮吸收的研究[J].中草药,1998;29(6):391-393。
[23]江光池 冯旭军 黄岚 杨正菀 杨胜华 龙脑和异龙脑对小鼠和家兔的药理作用[J].华西药学杂志1989,4(1):23-25
[24]潘嘉 邹文俊 刘洁 张白嘉 刘亚欧 潘晓鹃 川芎嗪、冰片对纤毛持续运动时间的影响[J].中药材2006,29(8):813-816
[25]潘嘉 张白嘉 喻舸 刘亚欧 邹文俊 潘晓鹃 川芎嗪和冰片对鼻腔生化指标及鼻黏膜形态的影响[J].华西药学杂志2006,21(3):234-237
[26]潘嘉 张白嘉 刘亚欧 邹文俊 潘晓鹃 川芎嗪冰片的溶血实验研究[J].中医药学刊2006,24(08):1442-1443
[27]廖艳 王雪 张立实 李冠民 张宝旭 溶血试验作为眼刺激试验替代方法的研究[J].现代预防医学2002年29(4):593-595
[28]王庆利,彭健眼刺激性试验的评价[J].中药新药与临床药理2005,16(4):301-304
[1]王志宣,姜典卓,张晓鹏,武凤兰 格尔德霉素滴眼液在离体兔眼角膜的吸收与扩散[J]沈阳药科大学学报2003,20(3):160-164
[2]卢荣枝,唐干益,宫琦 阿昔洛韦眼用凝胶在兔离体角膜中的渗透释药行为研究[J]中国药房2006,17(4):258-260
[3]张卫,钟华玉,唐瑞嫦,钟银送,杨彩群 氟啶酸眼用缓释凝胶的制备及释药研究[J]广东药学2005,15(4):28-30
[4]宋成君,刘志东,曹国良,温子一,李杰,潘卫三 渗透促进剂对葛根素角膜透过性的影响[J]沈阳药科大学学报2007,24(3):142-144
[5]M A Thiel,N Morlet,D Schulz,H F Edelhauser,J K Dart,D J Coster,K A Williams A simple corneal perfusion chamber for drug penetration and toxicity studies Br J Ophthalmol,2001;85(4):450-453
[6]Grass GM,Robinson JR Mechanisms of corneal drug penetration,Ⅰ:In vivo and in vitro kinetics.[J].J Pharm Sci.1988,77(1):3-14
[7]Richman JB,Tang-Liu DD.A corneal perfusion device for estimating ocular bioavailability in vitro.[J].J Pharm Sci 1990;79:153-7.
[8]Markuszewski R,Diehl H.The infrared spectra and structures of the three solid forms of fluorescein and related compounds.[J]Talanta 1980,27(11 Pt 2):937-46
[9]孙衍增 荧光素钠荧光寿命的测定[J]分析化学,2000,28(11):1413-1416
[10]魏刚,丁平田,赵会英,等.渗透促进剂对马来酸噻吗洛尔角膜透过性的影响(J}.中国药学杂志,2002,37(6):430-433
[11]Saettone MF,Chetoni P,Cerbai R,et al.Evaluation of ocular permeation enhancers:in vitro effects on corneal transport of four β-blockers,and in vitroPin vivo toxic activity[J].Int J Pharm,1996,142(2):103-113.
[12]谢立信 角膜内皮细胞活性的快速鉴定及其临床应用 眼科新进展1981,1(3):29-32
[13]谢立信 正常人角膜内皮细胞的内皮显微镜观察[J]中华眼科杂志1985:(6):354-357
[14]郑湖铃,陈家祺,刘华 两种角膜内皮细胞活性染色的应用比较[J]中国实用眼科杂志1995,13,(11):684-685
[15]不同染色剂对兔眼角膜内皮细胞影响的研究[J]眼科新进展2005,25(4):335-337
[16]Becket U;Ehrhardt C;Schneider M;Muys L;Gross D;Eschmann K;Schaefer UF;Lehr CM A comparative evaluation of corneal epithelial cell cultures for assessing ocular permeability.[J].Alternatives To Laboratory Animals 2008,36(1),33-44
[17]Johnny J.Yang,Kwang-Jin Kim,Vincent H.L.Lee Role of P-Glycoprotein in Restricting Propranolol Transport in Cultured Rabbit Conjunctival Epithelial Cell Layers[J].Pharmaceutical Research,2000,17(5):533-538
[18]David Maurice Characterization of Paracellular Penetration Routes [J]Invest Ophthalmol Vis Sci.1997,38(11):2177-2179
[19]Hamalainen KM,Kananen K,Auriola S,Kontturi K,Urtti A.Characterization of paracellular and aqueous penetration routes in cornea,conjunctiva,and sclera.[J].Invest Ophthalmol Vis Sci.1997;38:627-634
[20]Huang AJW,Tseng SCG,Kenyon KR.Paracellular permeability of corneal and conjunctival epithelia.[J].Invest Ophthalmol Vis Sci.1989;30:684-689
[21]Mishima S.Clinical investigations on the corneal endothelium[J].Am J Ophthalmol Am J Ophthalmol.1982,93(1):1-29
[1]肖国士 眼科外用片脑的研究[J].贵阳中医学院学报1987,3:11-12
[2]江光池,杨胜华,冯旭军 龙脑和异龙脑的抗炎作用[J].华西药学杂志1990,5(03):190-191
[3]孙晓萍,欧立娟,宓穗卿,王宁生 冰片抗炎镇痛作用的实验研究[J].中药新药与临床药理2007,18(05):353-355
[4]牟家琬,杨胜华,孙玉梅,伍朝筼 龙脑与异龙脑的体外抗菌作用的研究[J].华西药学杂志1989,4(1):20-22
[5]樊岚岚,唐由之,陆丽珠等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003,28(1):81-82.
[6]王灿.冰片对中医眼科外用药促渗作用的研究[J].中国中医基础医学杂志,2002,8(6):46,54
[7]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeabiJity of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[8]赵威 博士毕业论文[D].广州中医药大学2005届
[9]M A Thiel,N Morlet,D Schulz,H F Edelhauser,J K Dart,D J Coster,K A Williams A simple corneal perfusion chamber for drug penetration and toxicity studies[J].Br J Ophtalmol,2001;85:450-453
[10]Grass GM,Robinson JR Mechanisms of corneal drug penetration.Ⅰ:In vivo and in vitro kinetics.[J].J Pharm Sci.1988,77(1):3-14
[11]Richman JB,Tang-Liu DD.A corneal perfusion device for estimating ocular bioavailability in vitro.[J].J Pharm Sci 1990;79:153-7. 医学科学院学报1995,6(2):34-35
[13]陆敏仪,周嵩煜,李梅 珍珠明目滴眼液中冰片的含量测定[J]中药材2001,24(9):673-674
[14]黄天来,王宁生 复方丹参滴丸中冰片的生物体液的含量测定[J]中药新药与临床药理2001,12(5):354-358
[15]梁美蓉,张银卿,黄天来,等 气相色谱法测定大鼠脑组织中冰片含量[J]中药新药临床与临床药理通讯1991,2(1):34-37
[16]吴纯洁,黄勤挽,齐红艺,等.中药冰片眼部用药的局部毒性研究[J].中国药学杂志,2005:40(22):1710-1713
[17]许碧莲,王晖,许卫铭.冰片对盐酸川芎嗪促透作用的研究[J].中成药,2001:23(12):864-867.
[18]Tang-liu DD,Richman JB,Weinkanl RJ,et al.Elect of four penetration enhancers on comeal permeability of drugs in vitro.[J].J Pharm Sci.1994,83:85-90
[19]Newton C,Gebhardt BM,Kaufman HE.Topically applied cyclospofine in azone prolongs corneal allogrft survival.[J].Invest Ophthalmol Vis Sci.1988.29:208-215
[20]徐岩,陈祖基,宋洁贞,等.高效皮肤渗透促进剂-氮酮对角膜内皮的影响.[J]中华眼科杂志,1998,34:25-27
[21]Durand-Cavagna G.Duprat P,Molon-Noblot S,et al.Coneal endothelial changes with azone.a penetration enhancer.[J].Lens Eye Toxic Res.1989.6:109-117
[1]周红宇,王萍,林丹,等.冰片对卡马西平在家兔体内药代动力学的影响[J].中国药理学通报,2005;21(10):1263-1266.
[2]郑晓晖,赵欣,房敏峰,等.复方丹参方中使药冰片对君药丹参药代动力学的影响[J].西安交通大学学报(医学版),2007;28(2):170-173.
[3]王宁生,梁美蓉,刘启德,等.冰片“佐使则有功”之实验研究[J].中医杂志,1994;35(1):46-47.
[4]陈瑞玲,赵志刚,张星虎,等.冰片对丙戊酸钠透过血脑屏障的影响[J].中国康复理论与实践,2007;13(2):151-153.
[5]刘启德,梁美蓉,陈芝喜,等.冰片对庆大霉素透血脑屏障的影响[J].广州中医学院学报,1994;11(1):37-40.
[6]徐伟,王宗锐.薄荷醇及冰片对磺胺嘧啶和伊文思蓝在脑内分布的影响[J].中药药理与临床,1995;(6):31-33.
[7]肖玉强,张良玉,唐海涛,等.冰片促进砷剂透过血脑屏障实验研究[J].中华神经外科疾病研究杂志,2007;6(3):243-246.
[8]董先智,汤小爱,高秋华,等.冰片对顺铂透血脑屏障促进作用的研究[J].中国药学杂志,2002;37(4):275-277.
[9]王原,吴伟康,黄志宏,等.冰片在正常人皮肤增加曲安缩松的透皮生物利用度[J].中药药理与临床,1992;8(特辑):178.
[10]王晖,许卫铭.薄荷醇与冰片的促透作用[J].中草药,1997;28(2):93-94.
[11]朱健平,王宗锐,吴宋夏.龙脑促进药物经皮渗透作用的研究[J].中国药学杂志,1999;34(2):104-106.
[12]许碧莲,王晖,许卫铭.冰片对盐酸川芎嗪促透作用的研究[J].中成药,2001;23(12):864-867.
[13]宇克莉,孙建华,张世林,等.透皮吸收促进剂对柴胡解热方水提液体外透皮吸收的影响[J].山东医药,2005;45(5):16-17.
[14]胡利民,樊官伟,高秀梅,等.天然冰片、合成冰片对大鼠胃黏膜屏障影响的比较[J].天津中医学院学报,2005;24(3):123-125.
[15]吴寿荣,程刚,王琳,等.冰片对利福平大鼠小肠的吸收动力学影响[J].沈 阳药科大学学报,2003;20(4):245-248.
[16]樊岚岚,唐由之,陆丽珠,等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003;28(1):81-82.
[17]张瑞涛,王晖,陈丽,等.冰片滴鼻对豚鼠鼻粘膜血管和脑血管通透性的影响研究[J].中国药房,2005;16(17):1291-1293.
[18]陈新梅,朱家壁,孙卫东,等.冰片对人参皂苷Rgl鼻腔吸收的促进作用及鼻腔纤毛毒性研究[J].中国药学杂志,2006;41(4):261-264.
[19]吴庆知,高秋华,朱玉山,等.冰片对胰岛素透粘膜吸收的促进作用研究[J].华中科技大学学报,2001;29(增刊1):41-43.
[20]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[21]许卫华,王晖,许卫铭川芎嗪的鼻腔吸收及冰片的促进作用 中国临床药理学与治疗学2002,7(5):434-436)
[22]王晖,薛漫清 呋塞米的鼻腔吸收及薄荷醇的促进作用 中国临床药理学与治疗学2000,5(1):59-60
[23]Kwong EC,Shen DD.Versatile isocratic high-performance liquid chromatographic assay for propranolol and its basic,neutral and acidic metabolites in biological fluids.J Chromatogr.1987 Mar 6;414(2):365-79
[24]Lennernas H,Nylander S,Ungell AL.Jejunal permeabilityl:a comparison between the ussing chamber technique and the single-pass perfusion in humans[J].PharmRes,1997.14(5):667-671
[25]Siok Lam Lira and Lee.Yong Lim.Effects of citrus fruit juices on cytotoxicity and drug transport pathways of Caco-2 cell monolayers.International Journal of Pharmaceutics,2006,307(1):42-50
[26]马燕,李沛波,苏薇薇,陈大为 药理实验中Caco-2细胞模型建立的评价指标 中药材2006,29(9):946-948
[27]Rekhi GS,Jambhekar SS,Souney PF,Williams DA.A fluorimetric liquid chromatographic method for the determination of propranolol in human serum/plasma.J Pharm Biomed Anal.1995,13(12):1499-505
[28]谢红光 HPLC荧光检测普萘洛尔及其4羟化产物的方法述评[J]国外医 学:生理病理科学与临床分册1991,11(1):21-24
[29]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of bomeol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):783-788
[30]许卫华,王晖,许卫铭 川芎嗪的鼻腔吸收及冰片的促进作用 中国临床药理学与治疗学,2002,7(5):434-436
[31]平其能 孙国庆 普萘洛尔经皮吸收膜剂的研制:Ⅰ.促吸剂对普萘洛尔透皮速率的影响[J]中国药科大学学报,1990,21(2):81-83]
[32]苏景福 苑振亭 普萘洛尔透皮吸收的研究[J]中国医院药学杂志,1991,11(10):455-456
[33]樊岚岚,唐由之,卢景,陆丽珠,王丽霞 冰片对兔角膜上皮细胞膜促渗透作用的实验研究[J].中国中医眼科杂志,1998,8(2):67-69)
[34]Pham-Huy C,Sahui-Gnassi A,Saada V,Gramond JP,Galons H,Ellouk-Achard S,Levresse V,Fompeydie D,Claude JR.Microassay of propranolol enantiomers and conjugates in human plasma and urine by high-performance liquid chromatography after chiral derivatization for pharmacokinetic study.J Pharm Biomed Anal.1994,12(9):1189-98.
[35]曹雪玲 刘发现 金东日 王清珊 李熔一 手性固定相反相高效液相色谱法分析普萘洛尔对映体[J]分析试验室2007,26(z1):330-333
[36]王凌志,邱宗荫.RP-HPLC拆分普萘洛尔对映体的洗脱顺序及其荧光响应研究[J].色谱,1997,15(5):411-413
[1]梁美蓉,叶少梅,张银卿,等.冰片对兔、大鼠脑组织伊文氏蓝染色作用的观察[J].广州中医学院学报,1993;10(4):211-213.
[2]刘启德,梁美蓉,陈之喜,等.冰片对庆大霉素透血脑屏障的影响[J].广州中医学院学报,1994;11(1):38-40.
[3]王宁生,梁美蓉,刘启德,等.冰片“佐使则有功”之实验研究[J].中药研究,1994;35(1):46-47.
[4]贾钰铭,丁正,曾令源,等.冰片促进顺铂透过血脑屏障的实验研究[J].四川医学,2004;25(2):156-157.
[5]董先智,汤小爱,高秋华,等.冰片对顺铂透血脑屏障促进作用的研究[J].中 国药学杂志,2002;37(4):275-277.
[6]徐伟,王宗锐.薄荷醇及冰片对磺胺嘧啶和伊文氏蓝在脑中分布有影响[J].中药药理与临床,1995;11(6):31.
[7]黄萍,吴清和,荣向路,等.冰片与川芎配伍对脑缺血再灌注损伤的保护作用[J].广州中医药大学学报,2000;17(4):323-324.
[8]林咸明,陈华德,严建伟,等.穴位注射“冰片液”对血脑屏障通透性的影响[J].针刺研究,2003;28(2):99-101.
[9]王勇,张忠义,徐峰,等.冰片对川芎嗪血药浓度和在脑中分布的影响[J].药物研究,2006;15(1):30-31
[10]王涛 广州中医药大学2008届博士毕业论文
[11]陈艳明,王宁生.冰片对BBB体外模型细胞间紧密连接和细胞吞饮囊泡的影响[J].中国中西医结合杂志,2004;24(7):632-634.
[12]李伟荣,姚丽梅,宓穗卿,等.冰片对大鼠下丘脑组胺、5-羟色胺含量的影响[J].中药材,2004;27(12):937-939.
[13]赵保胜,宓穗卿,张银卿.冰片对大鼠脑血管内皮细胞ICAM-1表达量的影响[J].中药新药与临床药理,2001;12(2):88-90.
[14]樊岚岚,唐由之,卢景芬,等.冰片对兔角膜上皮细胞促渗透作用的实验研究[J].中国中医眼科杂志,1998;9(2):67-69.
[1]McBrien NA,Moghaddam HO,Reeder AP;Atropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism.Invest Ophthalmol Vis Sci.1993;34(1):205-15
[2]Rickers M,Schaeffel F.Dose-dependent effects of intravitreal pirenzepine on deprivation myopia and lens-induced refractive errors in chickens.Exp Eye Res.1995;61(4):509-16
[3]Cottriall CL,McBrien NA.The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew.Invest Ophthalmol Vis Sci.1996;37(7):1368-79
[4]Leech EM,Cottriall CL,McBrien NA.Pirenzepine prevents form deprivation myopia in a dose dependent manner.Ophthalmic Physiol Opt.1995;15(5):351-6.
[5]Truong HT,Cottriall CL,Gentle A,McBrien NA.Pirenzepine affects scleral metabolic changes in myopia through a non-toxic mechanism.Exp Eye Res. 2002;74(1):103-11
[6]Bartlett JD,Niemann K,Houde B,Allred T,Edmondson M J,Crockett RS.A tolerability study of pirenzepine ophthalmic gel in myopic children.J Ocul Pharmacol Ther.2003;19(3):271-9
[7]Tan DT,Lam DS,Chua WH,Shu-Ping DF,Crockett RS;.One-year multicenter,double-masked,placebo-controlled,parallel safety and efficacy study of 2%pirenzepine ophthalmic gel in children with myopia.Ophthalmology.2005;112(1):84-91
[8]McBrien NA,Jobling AI,Truong HT,Cottriall CL,Gentle A Expression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia..Mol Vis.2009;15:464-75
[9]McBrien NA,Annies R,Leech EM.Cottriall CL,Prevention of form-deprivation myopia with pirenzepine:a study of drug delivery and distribution.Ophthalmic Physiol Opt.1999;19(4):327-35
[10]王楷迪,张金嵩,闫磐石.不同配方哌仑西平滴眼液的兔角膜通透性的实验研究[J].中华眼科杂志2006:42(6):531-53
[11]李朋梅,涂家生,张明,庞卉,杨晓燕 盐酸哌仑西平在水溶液中的降解动力学[J]中国药科大学学报2005,36(3):220-224
[12]戴怡康,褚仁远.哌仑西平滴眼剂在兔房水中的药代动力学研究[J].眼视光学杂志2002;4(4):228-229
[13]乐琦骅 褚仁远 程能能 陈斌艳 哌仑西平滴眼剂的刺激性和致敏性研究中国眼耳鼻喉科杂志2005,5(5):281-283
[2]肖国士 眼科外用片脑的研究[J].贵阳中医学院学报1987,3:11-12
[3]陈艳明,王宁生.冰片对血脑屏障体外模型细胞问紧密连接和细胞吞饮囊泡的影响[J].中国中西医结合杂志,2004,24(7):632-634
[4]樊岚岚,唐由之,陆丽珠等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003,28(1):81-82
[5]赵威博士毕业论文[D].广州中医药大学2005届
[6]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[7]Urtti A.Challenges and obstacles of ocular pharmaeokineties and drag delivery [J].Adv Drug Del Rev,2006,58(11):1131-1135
[8]S.D.Klyce,C.E.Crosson,Transport processes across the rabbit corneal epithelium:a review,[J].Curr.Eye Res.1985,4(4):323-331
[9]A.J.Huang,S.C.Tseng,K.R.Kenyon,Paracellular permeability of corneal and conjunctival epithelia,[J].Invest.Ophthalmol.Vis.Sci.1989,30(4):684-9
[10]H.S.Huang,R.D.Schoenwald,J.L.Lach,Corneal penetration behavior of beta-blocking agents Ⅱ:assessment of barrier contributions[J].,J.Pharm.Sci.1983,72(11):1272-1279.
[11]R.D.Schoenwald,H.-S.Huang,Corneal penetration behaviour of beta-blocking agents Ⅰ:physicochemical factors,[J].J.Pharm.Sci.1983,72(11):1266-1272.
[12]Hornof M,Toropainen E,Urtti A.Cell culture models of the ocular barriers[J].Eur J Pharm Biopharm,2005,60(2):207-225
[13]K.M.Ha"ma"la"inen,K.Kananen,S.Auriola,K.Kontturi,A.Urtti,Characterization of paracellular and aqueous penetration routes in cornea,conjunctiva,and sclera,[J].Inve st.Ophthalmol.Vis.Sci.1997,38(3):627-634.
[14]J.J.Palmgre'n,E.Toropainen,S.Auriola,A.Urtti,Liquid chromatographic-electrospray ionization mass spectrometric analysis of neutral and charged polyethylene glycols,[J].J.Chromatogr.A 2002,976(1-2) 165-170.
[15]M.R.Prausnitz,J.S.Noonan,Permeability of cornea,sclera,and conjunctiva:a literature analysis for drug delivery to the eye,J.[J].Pharm.Sci.1998,87(12)1479-1488
[16]I.Ahmed,T.F.Patton,Importance of the noncorneal absorption route in topical ophthalmic drug delivery,[J].Invest.Ophthalmol.Vis.Sci.1985,26(4) 584-587.
[17]A.Urtti,L.Salminen,Minimizing systemic absorption of topically administered ophthalmic drugs,[J].Surv.Ophthalmol.1993,37(6) 435-456.
[18]Hosoya K,Lee VH,Kim KJ.Roles of the conjunctiva in ocular drug delivery:a review of conjunctival transport mechanisms and their regulation[J].Eur J Pharm Biopharm,2005,60(2):227-240
[19]李风鸣 眼科全书[M]北京人民卫生出版社 眼的生理生化,1996,257-287
[20]Bill A.The blood-aqueous Trans[J].Ophthalmol Soc U K.1986;105(Pt2):149-55
[21]J.M.Conrad,J.R.Robinson,Aqueous chamber drug distribution volume measurement in rabbits,[J].J.Pharm.Sci.1977,66(2) 219-224.
[22]S.Duvvufi,S.Majumdar,A.K.Mitra,Drug delivery to the retina:challenges and opportunities,[J].Expert Opin.Biol.Ther.2003,3(1) 45-56.
[23]J.G.Cunha-Vaz,The blood- ocular barriers:past,present,and future,[J].Doc.Ophthalmol.1997,93(1-2) 149-157
[24]P.A.Stewart,U.I.Tuor,Blood-eye barriers in the rat:correlation of ultrastructure with function,[J].J.Comp.Neurol.1994,340(4):566-576.
[25]R.H.Quinn,S.S.Miller,Ion transport mechanisms in native human retinal pigment epithelium,[J].Invest.Ophthalmol.Vis.Sci.1992,33 (13):3513-3527.
[26]Tso MO,Shih CY,McLean IW.Is there a bloo j-brain barrier at the optic—nerve head [J].Arch Ophthalmol.1975,93(9):815-25
[1]戴耀华等.长效利福平眼药膜的研制及其对沙眼的疗效[J].中华眼科杂志1986,22(2):102
[2]Oechsner M,Keipert S.Polyacrylic acid/polyvinylpyrrolidone bipolymeric systems.I.Rheological and mucoadhesive properties of formulationspotentially useful for the treatment of dry-eye-syndrome[J].Eur J Biopharm,1999,47(2):113-118
[3]El-Kamel AH.In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate.[J].Int J Pharm.2002,241(1):47-55.
[4]Kim EY,Gao ZG,Park JS,et al.rhEGF/HP-beta-CD complex in poloxamer gel for ophthalmic delivery.[J].Int J Pharm,2002,233(1-2):159-167.
[5]Gupta P,Vermani K,Garg S.Hydrogels:from controlled release to pH-responsive drug delivery.[J].Drug Discov Today,2002,7(10):569-579.
[6]Annouk Rozier,Claude Mazuel,Jeflh'ey Grove,Bernard Plazonnet.Functionality testing of gellan gum,a polymeric excipient material for ophthalmic dosage forms.[J].Int J Pharm,1997,153 (2):191-198
[7]Cohen S,Lobel E,Trevgoda A,et al.A novel in situ—forming ophthalmic drug delivery systems form alginates undergoing gelation in the eye.[J]Controlled Release,1997,44(2-3):201～208
[8]Paulsson M,HagerstromH,Edsman K.Rheological studies of the gelation of deacetylated gellan gum (Gelrite)in physiologial conditions [,J].Eur J Pharm Sci,1999,9(1):99～105
[9]Carlfors J,Edsman K,Petersson R,et al.Reheological evaluation of gelrite in situ gels for ophthalmic use [J].Eur J Pharmsci,1998,6(2):113～119
[10]Kaur IP,Smitha R.Penetration enhancers and ocular bioadhesives:two new avenues for ophthalmic drug delivery [J].Drug Devel Ind Pharm,2002,28 (4):353-369.
[11]Grass GM,Robisson JR.Mechanisms of corneal drug penetration I:in vivo and in vitro kinetics [J].J Pharm Sci,1988,77(1):3-14
[12]Rathore MS,Majumdar DK.Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin from aqueous drops [J].AAPS Pharm Sci Tech,2006,7(3):Article57,E12～17.
[13]Kaur IP,Singhm,Kanwarm.Formulation and evaluation of ophthalmic preparations of acetazolamide [J].Int J Pharm,2000,199 (2):119-127.
[14]Anderberg EK,Artursson P.Epithelial transport of drugs in cell cultureV Ⅲ:effects of sodium dodecyl sulfate on cellmem-brane and tight junction permeability in human intestinal epithelial (Caco-2)cells [J].J Pharm Sci,1993,82 (4):392-398.
[15]Grzeskow IAK E.Biopharmaceutical availability of sulphadicramide from ocular ointments in vitro [J].Eur J Pharm Sci,1998,6 (3):247-253.
[16]Hochman JH,Fix JA,Lecluyer EL.In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoyl carnitine [J].J Pharmacol Exp Ther,1994,269 (2):813-822
[17]Sasaki H,Igarashi Y,Nagano T,et al.Different effect of absorp tion p romoters on corneal are conjunctival penetration of ophthalmic beta-blockers [J].Pharm Res, 1995,12(8):1146-1162
[18]Durand Cavagna G,Duprat P,Molon N S,et al.Corneal endothelial changes with azone,a penetration enhancer[J].Lens Eye Toxic Res,1989,6(1-2):109-117.
[19]Kompella UB,Bandi N,Ayalasomayajula SP.Subconjunctival nano- and microparticles sustain retinal delivery of budesonide,a corticosteroid capable of inhibiting VEGF expression.[J].Invest Ophthalmol Vis Sci,2003,4(3):1192-1201.
[20]Assil KK,Hartzer M,Weinreb RN,et al.Liposome suppression of proliferative vitreorefinopathy.Rabbit model using an timetabolite encapsulated liposomes.[J].Invest Ophthalmol Vis Sci,1991,32(11):2891-2897.
[21]Cavalli R,Gasco MR,Chetoni P,et al Solid lipid nanoparticles(SLN)as ocular delivery system for tobramycin.[J].Int J Pharm,2002.238(1-2):241-245.
[22]李安良.生物利用度控制[M].第1版.北京:化学工业出版社,2004年,P146-171
[23]Mandell AI,Stentz F,Kitabchi AE Dipivalyl epinephrine:a new pro-drug in the treatment of glaucoma.[J]Ophthalmology.1978,85(3):268-75
[24]Miller-Meeks MJ,Farrell TA,Munden PM,Folk JC,Rao C,Schoenwald RD.Phenylephrine prodrug.Report of clinical[J]Ophthalmology.1991,98(2):222-6]
[25]Ranta VP,Urtti A.Transscleral drug delivery to the posterior eye:prospects of pharmaeokinetic modeling[J].Adv Drug Deliv Rev,2006,58(11):1164-118
[26]Bourges JL,Bloquel C,Th omas A,et al.Intraoeular implants for extended drug delivery:therapeutic applications[J].Adv Drug Deliv Rev,2006,58(11):1182-1202.
[27]Cheng L,Hostetler KY,Chaidhawangul S,et al.Treatment or prevention of herpes simplex virus retinitis with intravitreally injectable crystalline 1-O-hexa decylpropanediol-3-phosphoganciclovir[J].Inv Ophthal Sci,2003,121(1):57-61.
[28]Dhillon B,Kamal A,Leen C.Intravttrcal sustained-release ganctclovtr implantation to control cytomegalovirus retinitis in AIDS[J]J.Int J STD AIDS 1998;9(4):227-230.
[29]Tao W,Wen R,GoddardMB,et al.Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa [J].lnvest Ophthalmol Vis Sci,2002,43(10):3292-3298.
[1]林斌 冰片旋光性的研究[J].华西药学杂志1988,3(3):145-146
[2]王强 杨显荣 陈金泉.冰片的鉴定分析研究[J]中草药1994,25(5):241-244
[3]葆光道人.秘传眼科龙木论[M].北京:人民卫生出版社,1958
[4]傅仁宇.审视瑶函[M],新1版.上海:上海人民出版社,1959.
[5]肖国士 眼科外用片脑的研究[J].贵阳中医学院学报1987,3:11-12
[6]孙启明 冰片的药性问题及其反思[J]中成药1993,15(5):43
[7]姜道平 王树才 韩其江 李志民 董玉根 李长林 仙人掌冰片外敷治疗眼部带状疱疹[J]中医外治杂志1997,1:28
[8]谢培德 王宝琴 利眼膏中冰片的薄层鉴别与气相色谱测定[J]中国中药杂志1989,14(7):31-33
[9]周文袅,曾立威,周嵩煌,陆敏仪 两种气相色谱法测定珍珠明目滴眼液中冰片的含量[J]华西药学杂志2004,19(2):137-139
[10]孙晓萍,欧立娟,宓穗卿,王宁生 冰片抗炎镇痛作用的实验研究[J].中药新药与临床药理2007,18(05):353-355
[11]江光池,杨胜华,冯旭军 龙脑和异龙脑的抗炎作用[J].华西药学杂志1990,5(03):190-191
[12]牟家琬,杨胜华,孙玉梅,伍朝筼 龙脑与异龙脑的体外抗菌作用的研究[J].华西药学杂志1989,4(1):20-22
[13]樊岚岚,唐由之,陆丽珠等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003,28(1):81-82.
[14]王灿.冰片对中医眼科外用药促渗作用的研究[J].中国中医基础医学杂志,2002,8(6):46,54
[15]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[16]赵威 博士毕业论文[D]广州中医药大学2005届
[17]胡利民,屈菜芹,李怡岚,刘洋,孙玉敏,张伯礼 合成冰片和天然冰片的小鼠骨髓嗜多染红细胞微核试验[J].中草药,2005,36(4):571-572
[18]何庆 夏忠玉 冰片口服制剂安全性的实验研究[J].中国药师2006,9(5):419-421
[19]吴纯洁 黄勤挽 齐红艺 郭平 侯世祥 中药冰片眼部用药的局部毒性研究 [J].中国药学杂志,2005,40(22):1710-1713
[20]杨洪滨,寻延滨,张小宇,李志坚,崔欧,张立琼,崔浩 局部应用天然与合成冰片的眼刺激性与长期毒性[J].国际眼科杂志,2008,8(11):2228-2231
[21]王晖,许卫铭,王宗锐,等.薄荷醇与冰片的促透作用[J].中草药,1997,28(2):93-94
[22]周成萍,彭松,廖蔚珍,等.复方雷公藤涂剂透皮吸收的研究[J].中草药,1998;29(6):391-393。
[23]江光池 冯旭军 黄岚 杨正菀 杨胜华 龙脑和异龙脑对小鼠和家兔的药理作用[J].华西药学杂志1989,4(1):23-25
[24]潘嘉 邹文俊 刘洁 张白嘉 刘亚欧 潘晓鹃 川芎嗪、冰片对纤毛持续运动时间的影响[J].中药材2006,29(8):813-816
[25]潘嘉 张白嘉 喻舸 刘亚欧 邹文俊 潘晓鹃 川芎嗪和冰片对鼻腔生化指标及鼻黏膜形态的影响[J].华西药学杂志2006,21(3):234-237
[26]潘嘉 张白嘉 刘亚欧 邹文俊 潘晓鹃 川芎嗪冰片的溶血实验研究[J].中医药学刊2006,24(08):1442-1443
[27]廖艳 王雪 张立实 李冠民 张宝旭 溶血试验作为眼刺激试验替代方法的研究[J].现代预防医学2002年29(4):593-595
[28]王庆利,彭健眼刺激性试验的评价[J].中药新药与临床药理2005,16(4):301-304
[1]王志宣,姜典卓,张晓鹏,武凤兰 格尔德霉素滴眼液在离体兔眼角膜的吸收与扩散[J]沈阳药科大学学报2003,20(3):160-164
[2]卢荣枝,唐干益,宫琦 阿昔洛韦眼用凝胶在兔离体角膜中的渗透释药行为研究[J]中国药房2006,17(4):258-260
[3]张卫,钟华玉,唐瑞嫦,钟银送,杨彩群 氟啶酸眼用缓释凝胶的制备及释药研究[J]广东药学2005,15(4):28-30
[4]宋成君,刘志东,曹国良,温子一,李杰,潘卫三 渗透促进剂对葛根素角膜透过性的影响[J]沈阳药科大学学报2007,24(3):142-144
[5]M A Thiel,N Morlet,D Schulz,H F Edelhauser,J K Dart,D J Coster,K A Williams A simple corneal perfusion chamber for drug penetration and toxicity studies Br J Ophthalmol,2001;85(4):450-453
[6]Grass GM,Robinson JR Mechanisms of corneal drug penetration,Ⅰ:In vivo and in vitro kinetics.[J].J Pharm Sci.1988,77(1):3-14
[7]Richman JB,Tang-Liu DD.A corneal perfusion device for estimating ocular bioavailability in vitro.[J].J Pharm Sci 1990;79:153-7.
[8]Markuszewski R,Diehl H.The infrared spectra and structures of the three solid forms of fluorescein and related compounds.[J]Talanta 1980,27(11 Pt 2):937-46
[9]孙衍增 荧光素钠荧光寿命的测定[J]分析化学,2000,28(11):1413-1416
[10]魏刚,丁平田,赵会英,等.渗透促进剂对马来酸噻吗洛尔角膜透过性的影响(J}.中国药学杂志,2002,37(6):430-433
[11]Saettone MF,Chetoni P,Cerbai R,et al.Evaluation of ocular permeation enhancers:in vitro effects on corneal transport of four β-blockers,and in vitroPin vivo toxic activity[J].Int J Pharm,1996,142(2):103-113.
[12]谢立信 角膜内皮细胞活性的快速鉴定及其临床应用 眼科新进展1981,1(3):29-32
[13]谢立信 正常人角膜内皮细胞的内皮显微镜观察[J]中华眼科杂志1985:(6):354-357
[14]郑湖铃,陈家祺,刘华 两种角膜内皮细胞活性染色的应用比较[J]中国实用眼科杂志1995,13,(11):684-685
[15]不同染色剂对兔眼角膜内皮细胞影响的研究[J]眼科新进展2005,25(4):335-337
[16]Becket U;Ehrhardt C;Schneider M;Muys L;Gross D;Eschmann K;Schaefer UF;Lehr CM A comparative evaluation of corneal epithelial cell cultures for assessing ocular permeability.[J].Alternatives To Laboratory Animals 2008,36(1),33-44
[17]Johnny J.Yang,Kwang-Jin Kim,Vincent H.L.Lee Role of P-Glycoprotein in Restricting Propranolol Transport in Cultured Rabbit Conjunctival Epithelial Cell Layers[J].Pharmaceutical Research,2000,17(5):533-538
[18]David Maurice Characterization of Paracellular Penetration Routes [J]Invest Ophthalmol Vis Sci.1997,38(11):2177-2179
[19]Hamalainen KM,Kananen K,Auriola S,Kontturi K,Urtti A.Characterization of paracellular and aqueous penetration routes in cornea,conjunctiva,and sclera.[J].Invest Ophthalmol Vis Sci.1997;38:627-634
[20]Huang AJW,Tseng SCG,Kenyon KR.Paracellular permeability of corneal and conjunctival epithelia.[J].Invest Ophthalmol Vis Sci.1989;30:684-689
[21]Mishima S.Clinical investigations on the corneal endothelium[J].Am J Ophthalmol Am J Ophthalmol.1982,93(1):1-29
[1]肖国士 眼科外用片脑的研究[J].贵阳中医学院学报1987,3:11-12
[2]江光池,杨胜华,冯旭军 龙脑和异龙脑的抗炎作用[J].华西药学杂志1990,5(03):190-191
[3]孙晓萍,欧立娟,宓穗卿,王宁生 冰片抗炎镇痛作用的实验研究[J].中药新药与临床药理2007,18(05):353-355
[4]牟家琬,杨胜华,孙玉梅,伍朝筼 龙脑与异龙脑的体外抗菌作用的研究[J].华西药学杂志1989,4(1):20-22
[5]樊岚岚,唐由之,陆丽珠等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003,28(1):81-82.
[6]王灿.冰片对中医眼科外用药促渗作用的研究[J].中国中医基础医学杂志,2002,8(6):46,54
[7]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeabiJity of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[8]赵威 博士毕业论文[D].广州中医药大学2005届
[9]M A Thiel,N Morlet,D Schulz,H F Edelhauser,J K Dart,D J Coster,K A Williams A simple corneal perfusion chamber for drug penetration and toxicity studies[J].Br J Ophtalmol,2001;85:450-453
[10]Grass GM,Robinson JR Mechanisms of corneal drug penetration.Ⅰ:In vivo and in vitro kinetics.[J].J Pharm Sci.1988,77(1):3-14
[11]Richman JB,Tang-Liu DD.A corneal perfusion device for estimating ocular bioavailability in vitro.[J].J Pharm Sci 1990;79:153-7. 医学科学院学报1995,6(2):34-35
[13]陆敏仪,周嵩煜,李梅 珍珠明目滴眼液中冰片的含量测定[J]中药材2001,24(9):673-674
[14]黄天来,王宁生 复方丹参滴丸中冰片的生物体液的含量测定[J]中药新药与临床药理2001,12(5):354-358
[15]梁美蓉,张银卿,黄天来,等 气相色谱法测定大鼠脑组织中冰片含量[J]中药新药临床与临床药理通讯1991,2(1):34-37
[16]吴纯洁,黄勤挽,齐红艺,等.中药冰片眼部用药的局部毒性研究[J].中国药学杂志,2005:40(22):1710-1713
[17]许碧莲,王晖,许卫铭.冰片对盐酸川芎嗪促透作用的研究[J].中成药,2001:23(12):864-867.
[18]Tang-liu DD,Richman JB,Weinkanl RJ,et al.Elect of four penetration enhancers on comeal permeability of drugs in vitro.[J].J Pharm Sci.1994,83:85-90
[19]Newton C,Gebhardt BM,Kaufman HE.Topically applied cyclospofine in azone prolongs corneal allogrft survival.[J].Invest Ophthalmol Vis Sci.1988.29:208-215
[20]徐岩,陈祖基,宋洁贞,等.高效皮肤渗透促进剂-氮酮对角膜内皮的影响.[J]中华眼科杂志,1998,34:25-27
[21]Durand-Cavagna G.Duprat P,Molon-Noblot S,et al.Coneal endothelial changes with azone.a penetration enhancer.[J].Lens Eye Toxic Res.1989.6:109-117
[1]周红宇,王萍,林丹,等.冰片对卡马西平在家兔体内药代动力学的影响[J].中国药理学通报,2005;21(10):1263-1266.
[2]郑晓晖,赵欣,房敏峰,等.复方丹参方中使药冰片对君药丹参药代动力学的影响[J].西安交通大学学报(医学版),2007;28(2):170-173.
[3]王宁生,梁美蓉,刘启德,等.冰片“佐使则有功”之实验研究[J].中医杂志,1994;35(1):46-47.
[4]陈瑞玲,赵志刚,张星虎,等.冰片对丙戊酸钠透过血脑屏障的影响[J].中国康复理论与实践,2007;13(2):151-153.
[5]刘启德,梁美蓉,陈芝喜,等.冰片对庆大霉素透血脑屏障的影响[J].广州中医学院学报,1994;11(1):37-40.
[6]徐伟,王宗锐.薄荷醇及冰片对磺胺嘧啶和伊文思蓝在脑内分布的影响[J].中药药理与临床,1995;(6):31-33.
[7]肖玉强,张良玉,唐海涛,等.冰片促进砷剂透过血脑屏障实验研究[J].中华神经外科疾病研究杂志,2007;6(3):243-246.
[8]董先智,汤小爱,高秋华,等.冰片对顺铂透血脑屏障促进作用的研究[J].中国药学杂志,2002;37(4):275-277.
[9]王原,吴伟康,黄志宏,等.冰片在正常人皮肤增加曲安缩松的透皮生物利用度[J].中药药理与临床,1992;8(特辑):178.
[10]王晖,许卫铭.薄荷醇与冰片的促透作用[J].中草药,1997;28(2):93-94.
[11]朱健平,王宗锐,吴宋夏.龙脑促进药物经皮渗透作用的研究[J].中国药学杂志,1999;34(2):104-106.
[12]许碧莲,王晖,许卫铭.冰片对盐酸川芎嗪促透作用的研究[J].中成药,2001;23(12):864-867.
[13]宇克莉,孙建华,张世林,等.透皮吸收促进剂对柴胡解热方水提液体外透皮吸收的影响[J].山东医药,2005;45(5):16-17.
[14]胡利民,樊官伟,高秀梅,等.天然冰片、合成冰片对大鼠胃黏膜屏障影响的比较[J].天津中医学院学报,2005;24(3):123-125.
[15]吴寿荣,程刚,王琳,等.冰片对利福平大鼠小肠的吸收动力学影响[J].沈 阳药科大学学报,2003;20(4):245-248.
[16]樊岚岚,唐由之,陆丽珠,等.冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J].中国中药杂志,2003;28(1):81-82.
[17]张瑞涛,王晖,陈丽,等.冰片滴鼻对豚鼠鼻粘膜血管和脑血管通透性的影响研究[J].中国药房,2005;16(17):1291-1293.
[18]陈新梅,朱家壁,孙卫东,等.冰片对人参皂苷Rgl鼻腔吸收的促进作用及鼻腔纤毛毒性研究[J].中国药学杂志,2006;41(4):261-264.
[19]吴庆知,高秋华,朱玉山,等.冰片对胰岛素透粘膜吸收的促进作用研究[J].华中科技大学学报,2001;29(增刊1):41-43.
[20]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):.783-788
[21]许卫华,王晖,许卫铭川芎嗪的鼻腔吸收及冰片的促进作用 中国临床药理学与治疗学2002,7(5):434-436)
[22]王晖,薛漫清 呋塞米的鼻腔吸收及薄荷醇的促进作用 中国临床药理学与治疗学2000,5(1):59-60
[23]Kwong EC,Shen DD.Versatile isocratic high-performance liquid chromatographic assay for propranolol and its basic,neutral and acidic metabolites in biological fluids.J Chromatogr.1987 Mar 6;414(2):365-79
[24]Lennernas H,Nylander S,Ungell AL.Jejunal permeabilityl:a comparison between the ussing chamber technique and the single-pass perfusion in humans[J].PharmRes,1997.14(5):667-671
[25]Siok Lam Lira and Lee.Yong Lim.Effects of citrus fruit juices on cytotoxicity and drug transport pathways of Caco-2 cell monolayers.International Journal of Pharmaceutics,2006,307(1):42-50
[26]马燕,李沛波,苏薇薇,陈大为 药理实验中Caco-2细胞模型建立的评价指标 中药材2006,29(9):946-948
[27]Rekhi GS,Jambhekar SS,Souney PF,Williams DA.A fluorimetric liquid chromatographic method for the determination of propranolol in human serum/plasma.J Pharm Biomed Anal.1995,13(12):1499-505
[28]谢红光 HPLC荧光检测普萘洛尔及其4羟化产物的方法述评[J]国外医 学:生理病理科学与临床分册1991,11(1):21-24
[29]Wu CJ;Huang QW;Qi HY;Guo P Promoting effect of bomeol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.[J].Die Pharmazie 2006,61(9):783-788
[30]许卫华,王晖,许卫铭 川芎嗪的鼻腔吸收及冰片的促进作用 中国临床药理学与治疗学,2002,7(5):434-436
[31]平其能 孙国庆 普萘洛尔经皮吸收膜剂的研制:Ⅰ.促吸剂对普萘洛尔透皮速率的影响[J]中国药科大学学报,1990,21(2):81-83]
[32]苏景福 苑振亭 普萘洛尔透皮吸收的研究[J]中国医院药学杂志,1991,11(10):455-456
[33]樊岚岚,唐由之,卢景,陆丽珠,王丽霞 冰片对兔角膜上皮细胞膜促渗透作用的实验研究[J].中国中医眼科杂志,1998,8(2):67-69)
[34]Pham-Huy C,Sahui-Gnassi A,Saada V,Gramond JP,Galons H,Ellouk-Achard S,Levresse V,Fompeydie D,Claude JR.Microassay of propranolol enantiomers and conjugates in human plasma and urine by high-performance liquid chromatography after chiral derivatization for pharmacokinetic study.J Pharm Biomed Anal.1994,12(9):1189-98.
[35]曹雪玲 刘发现 金东日 王清珊 李熔一 手性固定相反相高效液相色谱法分析普萘洛尔对映体[J]分析试验室2007,26(z1):330-333
[36]王凌志,邱宗荫.RP-HPLC拆分普萘洛尔对映体的洗脱顺序及其荧光响应研究[J].色谱,1997,15(5):411-413
[1]梁美蓉,叶少梅,张银卿,等.冰片对兔、大鼠脑组织伊文氏蓝染色作用的观察[J].广州中医学院学报,1993;10(4):211-213.
[2]刘启德,梁美蓉,陈之喜,等.冰片对庆大霉素透血脑屏障的影响[J].广州中医学院学报,1994;11(1):38-40.
[3]王宁生,梁美蓉,刘启德,等.冰片“佐使则有功”之实验研究[J].中药研究,1994;35(1):46-47.
[4]贾钰铭,丁正,曾令源,等.冰片促进顺铂透过血脑屏障的实验研究[J].四川医学,2004;25(2):156-157.
[5]董先智,汤小爱,高秋华,等.冰片对顺铂透血脑屏障促进作用的研究[J].中 国药学杂志,2002;37(4):275-277.
[6]徐伟,王宗锐.薄荷醇及冰片对磺胺嘧啶和伊文氏蓝在脑中分布有影响[J].中药药理与临床,1995;11(6):31.
[7]黄萍,吴清和,荣向路,等.冰片与川芎配伍对脑缺血再灌注损伤的保护作用[J].广州中医药大学学报,2000;17(4):323-324.
[8]林咸明,陈华德,严建伟,等.穴位注射“冰片液”对血脑屏障通透性的影响[J].针刺研究,2003;28(2):99-101.
[9]王勇,张忠义,徐峰,等.冰片对川芎嗪血药浓度和在脑中分布的影响[J].药物研究,2006;15(1):30-31
[10]王涛 广州中医药大学2008届博士毕业论文
[11]陈艳明,王宁生.冰片对BBB体外模型细胞间紧密连接和细胞吞饮囊泡的影响[J].中国中西医结合杂志,2004;24(7):632-634.
[12]李伟荣,姚丽梅,宓穗卿,等.冰片对大鼠下丘脑组胺、5-羟色胺含量的影响[J].中药材,2004;27(12):937-939.
[13]赵保胜,宓穗卿,张银卿.冰片对大鼠脑血管内皮细胞ICAM-1表达量的影响[J].中药新药与临床药理,2001;12(2):88-90.
[14]樊岚岚,唐由之,卢景芬,等.冰片对兔角膜上皮细胞促渗透作用的实验研究[J].中国中医眼科杂志,1998;9(2):67-69.
[1]McBrien NA,Moghaddam HO,Reeder AP;Atropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism.Invest Ophthalmol Vis Sci.1993;34(1):205-15
[2]Rickers M,Schaeffel F.Dose-dependent effects of intravitreal pirenzepine on deprivation myopia and lens-induced refractive errors in chickens.Exp Eye Res.1995;61(4):509-16
[3]Cottriall CL,McBrien NA.The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew.Invest Ophthalmol Vis Sci.1996;37(7):1368-79
[4]Leech EM,Cottriall CL,McBrien NA.Pirenzepine prevents form deprivation myopia in a dose dependent manner.Ophthalmic Physiol Opt.1995;15(5):351-6.
[5]Truong HT,Cottriall CL,Gentle A,McBrien NA.Pirenzepine affects scleral metabolic changes in myopia through a non-toxic mechanism.Exp Eye Res. 2002;74(1):103-11
[6]Bartlett JD,Niemann K,Houde B,Allred T,Edmondson M J,Crockett RS.A tolerability study of pirenzepine ophthalmic gel in myopic children.J Ocul Pharmacol Ther.2003;19(3):271-9
[7]Tan DT,Lam DS,Chua WH,Shu-Ping DF,Crockett RS;.One-year multicenter,double-masked,placebo-controlled,parallel safety and efficacy study of 2%pirenzepine ophthalmic gel in children with myopia.Ophthalmology.2005;112(1):84-91
[8]McBrien NA,Jobling AI,Truong HT,Cottriall CL,Gentle A Expression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia..Mol Vis.2009;15:464-75
[9]McBrien NA,Annies R,Leech EM.Cottriall CL,Prevention of form-deprivation myopia with pirenzepine:a study of drug delivery and distribution.Ophthalmic Physiol Opt.1999;19(4):327-35
[10]王楷迪,张金嵩,闫磐石.不同配方哌仑西平滴眼液的兔角膜通透性的实验研究[J].中华眼科杂志2006:42(6):531-53
[11]李朋梅,涂家生,张明,庞卉,杨晓燕 盐酸哌仑西平在水溶液中的降解动力学[J]中国药科大学学报2005,36(3):220-224
[12]戴怡康,褚仁远.哌仑西平滴眼剂在兔房水中的药代动力学研究[J].眼视光学杂志2002;4(4):228-229
[13]乐琦骅 褚仁远 程能能 陈斌艳 哌仑西平滴眼剂的刺激性和致敏性研究中国眼耳鼻喉科杂志2005,5(5):281-283