不同配方哌仑西平滴眼液的兔角膜通透性的实验研究

目的探讨不同配方哌仑西平滴眼液的角膜通透性,为临床应用提供依据。方法配制2%哌仑西平滴眼液(单纯哌仑西平组)、2%哌仑西平+0.1%透明质酸钠滴眼液(透明质酸钠组)及2%哌仑西平+0.1%氮酮滴眼液(氮酮组)。将63只新西兰白兔分为3组,分别在各组兔双眼结膜囊内滴入上述眼液,滴眼6次,每次间隔5min。在最后1次滴眼后0.5、1·0、2·0、4·0、8·0、12·0、24·0h抽取前房水约0.2ml,使用高效液相色谱仪分析前房水中哌仑西平的浓度,并于每次滴眼前后和穿刺抽吸房水前用裂隙灯显微镜观察3组兔眼部的一般情况。结果最后1次滴眼后0.5、1·0、2·0、4·0h单纯哌仑西平组前房水中哌仑西平的浓度分别为(0.40±0.06)、(0.53±0.03)、(1.52±0.33)及(0.15±0.02)μg/ml,8·0h后高效液相色谱仪未能检测到哌仑西平。各时间点氮酮组和透明质酸钠组前房内哌仑西平浓度均明显高于单纯哌仑西平组(P<0.01),生物利用度分别约是其23·0倍和3.4倍。并且实验过程中各组兔眼部均无刺激症状。结论氮酮组的角膜通透性最好,透明质酸钠组次之,均显著高于单纯哌仑西平组,表明氮酮和透明质酸钠均可用于哌仑西平滴眼液中,为临床应用提供了新的思路。

Corneal permeability of topically applied pirenzepine solution

OBJECTIVE: To study the corneal permeability of three different pirenzepine eye-drop solutions and provide reference for further clinical use. METHODS: Sixty-three New Zealand white rabbits were divided into three groups. Each group of rabbits received 2% pirenzepine (pirenzepine group), 2% pirenzepine with 0.1% hyaluronic acid (hyaluronic acid group), or 2% pirenzepine with 0.1% azone (azone group). One drop eye-drops was applied to conjunctive sac every 5 min for six times. Aqueous samples were obtained from each group at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 24.0 h after the last drop, respectively. Concentration of pirenzepine in these samples was determined by the HPLC (high pressure liquid chromatography). Stimulation symptom of rabbit eyes was also observed. RESULTS: The concentrations of pirenzepine in aqueous humor were (0.40 +/- 0.06) microg/ml at 0.5 h, (0.53 +/- 0.03) microg/ml at 1.0 h, (1.52 +/- 0.33) microg/ml at 2.0 h and (0.15 +/- 0.02) microg/ml at 4.0 h in pirenzepine group. Aqueous humor concentration of pirenzepine in both 2% pirenzepine with 0.1% azone and 2% pirenzepine with 0.1% hyaluronic acid were significantly higher than that of single pirenzepine application, and their bioavailability in the groups with combinations of pirenzepine with 0.1% azone or 0.1% hyaluronic acid were 23.0 times and 3.4 times higher than that of single pirenzepine usage. No obvious irritate symptom was found in rabbit of all three groups after eye-drop applying. CONCLUSIONS: The combination application of pirenzepine with azone or hyaluronic acid has higher corneal permeability compared with pirenzepine alone. This result indicates that azone and hyaluronic acid could be used in pirenzepine eye-drop solution to increase corneal permeability.