Alkalinizing Water-Soluble Local Anesthetic Solutions by Addition of Cyclodextrin
Alkalinizing Water-Soluble Local Anesthetic Solutions by Addition of Cyclodextrin
复制标题
添加环糊精碱化水溶性局部麻醉溶液
DOI：
10.1136/rapm-00115550-199823020-00011
复制
发表时间：
1997
影响因子：
5.1
通讯作者：
Y. Hiji
中科院分区：
文献类型：
--
作者：
M. Miyoshi;T. Imoto;Y. Hiji
背景与目的使用碳酸氢钠对局麻药进行碱化以提高其疗效，存在一些缺点，包括溶液的稳定性降低。本研究旨在评价环糊精(CDS)在接近生理pH且无沉淀的条件下改善局麻药溶液的溶解度和稳定性的有效性。方法通过目测混浊度或沉淀物的形成，并在620 nm处记录吸光度，考察局麻药在生理盐水中的溶解度。利用与包合物形成有关的药物的光谱变化，用分光光度法研究了麻醉剂与CD的相互作用。结果环糊精改善了四种局麻药(丁卡因、丁卡因、布比卡因和利多卡因)的溶解度和稳定性。在中性pH区，疏水性较强的地布卡因和丁卡因对CDS的影响更为明显。不同麻醉剂的有效CD类型不同，部分取决于与局麻药形成包合物的倾向。在中性条件下，CDS增溶的局麻药溶液保持透明72小时以上，无明显沉淀或混浊。结论加入Cd可提高局麻药的溶解度，这可能是由于Cd与局麻药形成包合物所致。这种碱化水溶性麻醉液的新制剂可能在临床上有实际应用价值，尽管这有待进一步研究。
Background and objectives The use of sodium bicarbonate for alkalinization of local anesthetics to improve their efficacy has some disadvantages including decreased stability of the solutions. The present study was performed to evaluate usefulness of cyclodextrins (CDs) in improving the solubility and stability of local anesthetic solutions at near physiologic pH without precipitation. Methods Solubility of local anesthetics with or without CDs in physiologic saline was investigated by monitoring cloudiness or precipitate formation visually and by recording absorbance at 620 nm. Interaction of anesthetic and CD was also studied spectrophotometrically using spectral change of the drugs associated with the inclusion complex formation. Results Cyclodextrins improved the solubility and stability of the four local anesthetics studied (dibucaine, tetracaine, bupivacaine, and lidocaine). In the neutral pH region, the effects of the CDs were more significant with dibucaine and tetracaine, which are more hydrophobic than the other two. A type of effective CD was different for each anesthetic depending partly on the tendency to form inclusion complex with local anesthetic. The local anesthetic solutions solubilized by CDs were found to remain clear for more than 72 hours without any visible precipitation or turbidity at neutral pHs. Conclusions The improved solubility of local anesthetics by adding CD may be caused by inclusion complex formation of CD with local anesthetics. This new preparation for the alkalinized water-soluble anesthetic solutions may be useful for practical application in the clinical setting, although this awaits further study.