Lacey C J, Woodhall S, Qi Z, Sawant S, Cowen M, McCormack S, Jiang S
Centre for Immunology and Infection, Hull York Medical School, University of York, York, UK.
Int J STD AIDS. 2010 Oct;21(10):714-7. doi: 10.1258/ijsa.2010.010215.
We carried out a phase 1 trial of a candidate vaginal microbicide gel against HIV-1 and other sexually transmitted diseases, which contained cellulose acetate 1,2-benzenedicarboxylate (also known as cellulose acetate phthalate) in a glycerol-based vehicle. We had to terminate the study after five women had completed dosing, due to all women experiencing unacceptable vulvo-vaginal side-effects. Further investigations showed that the gel had a very high osmolality, which we believe led to excessive fluid transudation across the vaginal mucosa and acute mucosal dysfunction. We also showed that the rheology of the gel changed dramatically on fluid dilution. The osmolality and rheology of candidate microbicides and other genital mucosal products should therefore be analysed and considered at an early stage of product development.
我们开展了一项针对HIV-1及其他性传播疾病的候选阴道杀微生物剂凝胶的1期试验，该凝胶在甘油基载体中含有1,2-苯二甲酸醋酸纤维素（也称为邻苯二甲酸醋酸纤维素）。在五名女性完成给药后，我们不得不终止该研究，因为所有女性都出现了无法接受的外阴阴道副作用。进一步调查显示，该凝胶具有非常高的渗透压，我们认为这导致了阴道黏膜过多的液体渗出和急性黏膜功能障碍。我们还表明，凝胶在液体稀释后其流变学发生了显著变化。因此，在候选杀微生物剂和其他生殖器黏膜产品开发的早期阶段，就应该对其渗透压和流变学进行分析和考量。
