Asbell P A, Epstein S P, Wallace J A, Epstein D, Stewart C C, Burger R M
Department of Ophthalmology, Mount Sinai Medical Center, New York, New York, USA.
Cornea. 1998 Sep;17(5):550-7. doi: 10.1097/00003226-199809000-00014.
A new class of antiviral agent, cobalt chelates (the CTC series), was evaluated for treating epithelial herpetic keratitis, consequent stromal disease being the major infectious cause of blindness in industrial nations.
Effects of CTC complexes were monitored in cell cultures and in a rabbit eye model, either infected with herpes simplex virus type 1 (HSV-1) or uninfected. Several antiviral concentrations of CTC complexes nontoxic to Vero cells were administered to rabbit eyes with HSV-1-induced keratitis. Corneal surface virus titers were measured, and corneal lesions of epithelial keratitis were monitored by slit-lamp microscopy and scored. Recovery rates and incidence were compared in eyes treated with CTC complexes, placebo, or clinically formulated trifluorothymidine (Viroptic), using nonparametric statistics.
All CTC complexes inhibited HSV-1 replication in vitro, CTC-96 being best. CTC-96, CTC-23, and CTC-67 eliminated (<1 plaque-forming unit[pfu]) corneal surface HSV-1 (otherwise >10(5) pfu) in order of descending potency, but CTC-82 was ineffective. CTC-96 (either 5 microg/ml six times daily or 10 microg/ml five times daily) accelerated herpetic dendritic keratitis recovery better than or the same as trifluorothymidine (10 mg/ml nine times daily). CTC complexes were nontoxic to Vero cells continuously exposed to < or =25 microg/ml; 50 microg/ml of CTC 96 nine times daily did not irritate uninfected rabbit eyes.
Topical CTC-96 applications were at least as effective as Viroptic in diminishing disease signs and corneal surface virus at concentrations less than one-thousandth that of Viroptic.
评估一类新型抗病毒药物——钴螯合物（CTC系列）治疗上皮性疱疹性角膜炎的效果，继发性基质疾病是工业化国家失明的主要感染原因。
在细胞培养物和兔眼模型中监测CTC复合物的效果，兔眼模型分为感染单纯疱疹病毒1型（HSV-1）和未感染两组。将几种对Vero细胞无毒的抗病毒浓度的CTC复合物施用于患有HSV-1诱导性角膜炎的兔眼。测量角膜表面病毒滴度，通过裂隙灯显微镜检查监测上皮性角膜炎的角膜病变并进行评分。使用非参数统计方法比较用CTC复合物、安慰剂或临床配方的三氟胸腺嘧啶（Viroptic）治疗的眼睛的恢复率和发病率。
所有CTC复合物在体外均抑制HSV-1复制，其中CTC-96效果最佳。CTC-96、CTC-23和CTC-67按效力递减顺序消除了（<1个空斑形成单位[pfu]）角膜表面的HSV-1（否则>10⁵ pfu），但CTC-82无效。CTC-96（每日6次，每次5微克/毫升或每日5次，每次10微克/毫升）比三氟胸腺嘧啶（每日9次，每次10毫克/毫升）更好或同样加速了疱疹性树枝状角膜炎的恢复。持续暴露于≤25微克/毫升的CTC复合物对Vero细胞无毒；每日9次，每次50微克/毫升的CTC 96不会刺激未感染的兔眼。
局部应用CTC-96在减轻疾病体征和角膜表面病毒方面至少与Viroptic一样有效，其浓度不到Viroptic的千分之一。
