壳聚糖包覆的硝酸毛果芸香碱眼用亚微乳的研究

本文设计了一种壳聚糖包覆的硝酸毛果芸香碱眼用亚微乳(chitosan-coated pilocarpine nitrate submicroemulsion,CS-PN/SE),旨在开发一种新型的具有黏膜黏附性的亚微乳眼部给药系统,以延长药物在眼表滞留时间,促进药物的眼部吸收。以中长链甘油三酯(medium chain triglycerides,MCT)为油相,Tween 80为主乳化剂,采用高速剪切工艺制备硝酸毛果芸香碱亚微乳(pilocarpine nitrate submicro emulsion,PN/SE),进一步采用孵育法制备CS-PN/SE,并利用星点设计-效应面优化法进行处方优化。对其粒径、zeta电位、包封率和微观形态进行表征,以新西兰白兔为动物模型,评价了CS-PN/SE在兔眼表滞留特性以及缩瞳作用。眼表滞留特性评价结果显示,与硝酸毛果芸香碱溶液剂组(pilocarpine nitrate solution,PNs)和PN/SE组相比,CS-PN/SE组在眼表的清除率下降,KCS-PN/SE为(0.006 4±0.000 3)min-1,平均驻留时间(mean residence tim...     

人工晶状体植入术中应用粘弹剂与缩瞳剂

目的观察粘弹剂与缩瞳剂对ECCE＋IOL术后角膜反应的影响。方法根据术中是否注入粘弹剂截囊以及是否使用缩瞳剂，术毕前是否冲吸，将100只眼分为6组，并将术后角膜的变化根据裂隙灯检查分为4级。结果经X2检验，用粘弹剂截囊与注水截囊两组间临床表现差异有显著性（P＜0．05），缩瞳后冲吸与未冲吸组之间均有显著差异，而未缩瞳组与缩瞳后冲吸组之间差异无显著性（P＞0．05）。结论应提倡注入粘弹剂截囊，使用毛果芸香碱缩瞳后应将其灌洗出前房。     

Indications for medical treatment of ocular hypertension and the initial use of pilocarpine

Ocular hypertension is defined. The decision to initiate treatment depends on the estimate of the benefit to injury ratio with a given treatment and the risk without treatment. Factors that determine our perception of the former are discussed. The key to the latter is the identification and evaluation of the ocular and systemic risk factors for the development of glaucomatous visual field loss. Discussion of these risk factors in the author's clinical practice is presented; overall, approximately 5% of his patients with ocular hypertension are treated. A review of his four-and-a-half year study on uniocular pilocarpine treatment in 59 ocular hypertensive patients is presented. The results suggest that one should be conservative in prescribing pilocarpine.     

卡巴考的合成及其缩瞳作用

采用一锅、两步连续反应的方法合成了卡巴考，其化学结构经红外光谱、核磁共振谱和元素分析证实．经兔眼前房注射实验表明，卡巴考为一快速缩瞳剂。     

匹罗卡品脂质体与凝胶缩瞳作用的实验研究

目的　研究 1%匹罗卡品脂质体与 4 %匹罗卡品凝胶对兔眼的缩瞳作用。方法　家兔 2 4只 ,随机分为 4组 ,每组 6只 ,按 1%匹罗卡品脂质体滴眼液 ,4 %匹罗卡品凝胶 ,1%匹罗卡品滴眼液 ,空白对照分为四组 ,给药后观察兔眼的刺激反映情况并间隔一定时间测量其瞳孔大小。结果　 4组兔眼滴药前瞳孔直径左右眼比较 ,差异无显著性 (P >0 .0 5 )。 1%匹罗卡品滴眼液组滴药后 0 .2 5h ,缩瞳作用最大 (P <0 .0 1) ,滴药后 1h瞳孔开始散大 ,滴药后 5h ,左右眼差异无显著性 (P >0 .0 5 ) ;1%匹罗卡品脂质体滴眼液组 ,滴药后 0 .5h缩瞳作用最大 (P <0 .0 1) ,滴药后 3h瞳孔开始散大 ,滴药后 7h ,左右眼差异无显著性 (P >0 .0 5 ) ;4 %匹罗卡品凝胶组 ,滴药后 0 .5h缩瞳作用最大 (P <0 .0 1) ,滴药后 4h瞳孔开始散大 ,滴药后 5h左右眼差异无显著性(P >0 .0 5 ) ;空白对照组在观察的 7h内左右眼差异无显著性 (P >0 .0 5 )。结论　 1%匹罗卡品脂质体滴眼液具有缓慢释药 ,延长作用时间的优点。其作用时间长于 4 %匹罗卡品凝胶。     

Angle block and pupil block—theories and mechanisms of angle-closure glaucoma

ABSTRACT Angle-closure glaucoma is caused by obstruction of the filtration angle by the root of the iris. For many years the obstruction was thought to result from the physical crowding of the angle by the iris when the pupil was dilated. However, since 1920 the pupil block-angle-closure hypothesis has been the subject of much research both in the aetiology of pupil block and its relief with the use of drugs.     

Ocular Absorption and Irritation of Pilocarpine Prodrug Is Modified with Buffer,Polymer, and Cyclodextrin in the Eyedrop

The influence of buffer, viscosity and cyclodextrin on the ocular absorption and irritation of a pilocarpine prodrug, O,O-dipropionyl-(1,4-xylylene) bispilocarpic acid diester, was studied in albino rabbits. The prodrug solutions, equivalent to 0.5% pilocarpine, were prepared in 0, 10, 20, 50, or 75 mM citrate buffer at pH 5.0. Viscosity of the solutions (20, 50 or 115 cP) was modified with hydroxypropyl methylcellulose. 2-hydroxypropyl--cyclodextrin (HPCD) was included at concentrations 5,10 and 15% (w/v). The formulations were compared to a commercial pilocarpine eyedrop (1.7%). Ocular irritation was graded in a double-masked experiment and miosis was used as a bioassay for pilocarpine delivery to the iris. The prodrug showed decreased peak and prolonged duration of miosis compared to pilocarpine, but it caused ocular irritation. Increasing buffer strength decreased and elevated viscosity intensified the miotic response and irritation by the pilocarpine prodrug. HPCD decreased both the ocular delivery of pilocarpine and the irritation by the pro-drug, but the net effect was positive. Thus, administering 1.0% of pilocarpine as a prodrug with 15% (w/v) HPCD, the irritation was at the same level with the commercial pilocarpine eyedrop, but the ocular delivery was substantially improved. In conclusion, the ocular delivery of the pilocarpine prodrug may be enhanced in relation to its local irritation by properly combining buffer, viscosity and HPCD.     

New Water-Soluble Pilocarpine Derivatives with Enhanced and Sustained Muscarinic Activity

The synthesis of an homologous series of new water-soluble derivatives of pilocarpine is described. The new compounds, referred to as soft quaternary salts, are water soluble by virtue of a cationic ammonium head and their lipophilicity can be modulated by manipulating the size and the nature of the substituent in the inactive portion of the molecule. The miotic activity of the compounds was evaluated after administration to normotensive New Zealand White rabbits. Changes in pupil size indicated a substantial cholinergic effect on the iridal sphincter musculature. The best candidate, compound 20, which has a 16-carbon side chain, was evaluated for reduction of the intraocular pressure in genetically glaucomatous Beagles. Compound 20 is superior to pilocarpine in both tests, with a potency 10 to 20 times that of the parent compound and a longer duration of action. It is suggested that the new compounds are pro-drug forms of pilocarpine which greatly enhance the corneal bio-availability of the parent compound.