Influence of pH on the effect of pilocarpine on aqueous dynamics.
Influence of pH on the effect of pilocarpine on aqueous dynamics.
复制标题
pH 对毛果芸香碱对水动力学影响的影响。
DOI：
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发表时间：
1968
影响因子：
4.1
通讯作者：
J. Cowle
中科院分区：
文献类型：
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作者：
ON Aqueous DYNAMICSt;R. Anderson;J. Cowle
匹洛卡品滴眼液通常配用在酸性溶液中，以防止灭菌和储存过程中生物碱的明显降解。然而，这样的溶液被认为比部分中和的溶液引起更大的刺激。鉴于此，Riegelman和Vaughan（1958）建议，患者可能更喜欢缓冲到pH为6.8的匹罗卡品溶液，尽管这些溶液不太稳定，需要经常更新。如果过度流泪导致的稀释和药物损失减少，缓冲到接近中性的溶液可能也会更有活性，也因为更多的药物会以不带电的游离碱的形式存在，这有利于通过角膜运输到作用部位。以前试图证明在酸性较弱的溶液中活性增加的尝试都是不确定的（Floyd, Kronfeld, and McDonald, 1953； Riegelman和Vaughan， 1958）。在目前的研究中，一种类似于Kronfeld（1964）的单滴技术已被用于患者中，通过pH为4和pH为65的匹洛卡品溶液和pH为4的反式异构体异匹洛卡品溶液的张力图来检查剂量-反应关系。方法用Wojciechowski和Ecanow（1961）的方法制备盐酸异哌嗪。该化合物和盐酸匹洛卡品（BDH）用于制备含有0.002%硝酸苯汞的0.5%、10%、20%、40%和8%的溶液。这些溶液的pH值约为4。另一系列相同浓度的匹罗卡品溶液中含有足够的硼砂，使pH值增加到65。5%、10%和20%的溶液通过加入氯化钠进行调整，使其与泪液等渗。溶液通过膜过滤消毒，缓冲溶液每隔一周更新一次，酸性溶液大约每月更新一次。
PILOCARPINE eye-drops are usually dispensed in acid solution to prevent appreciable degradation of the alkaloid during sterilization and storage. However, such solutions are considered to cause greater irritation than partly neutralized solutions. On account of this Riegelman and Vaughan (1958) have suggested that pilocarpine solutions buffered to pH 6 8 may be preferred by patients, even though these solutions are less stable and need to be renewed frequently. Solutions buffered to near-neutrality might be expected also to be more active if dilution and loss of drug from excessive lacrimation were reduced, and also because more drug would be present as uncharged free base which would favour transport through the cornea to the site of action. Previous attempts t'o demonstrate increased activity in less acid solutions have been inconclusive (Floyd, Kronfeld, and McDonald, 1953; Riegelman and Vaughan, 1958). In the present investigation a single-drop technique similar to that of Kronfeld (1964) has been used in patients to examine the dose-response relationships by tonography with pilocarpine solutions at pH 4 and pH 6 5 and with solutions of the trans-isomer isopilocarpine at pH 4. Methods Test Solutions Isopilocarpine hydrochloride was prepared by the method of Wojciechowski and Ecanow (1961). This compound and pilocarpine hydrochloride (BDH) were used to prepare 0.5, 1 0, 2 0, 4 0, and 8-0 per cent. solutions containing 0 002 per cent. phenylmercuric nitrate. These solutions had a pH value of about 4. Another series of pilocarpine solutions of the same concentrations was prepared containing sufficient borax to increase the pH to 6 5. The 0 5, 1 0, and 2 0 per cent. solutions were adjusted by the addition of sodium chloride to render them isotonic with tear fluid. Solutions were sterilized by membrane filtration and renewed at intervals of one week for the buffered solutions and about monthly for the acidic solutions.