Chondroitin sulfate/sodium hyaluronate

Invasive fungal infections (IFIs) are a serious infectious disease worldwide, characterized by high mortality and morbidity. Azole drugs are the most commonly used drugs for the treatment of invasive fungal infections. However, because azole drugs can easily interact with human CYPs metabolic enzymes, the risk of drug-to-drug interaction is high when multiple drugs are used together with azole drugs in clinic. As the problem of fungal drug resistance is becoming increasingly serious, there is an urgent need to develop new CYP51 inhibitors. The successful marketing of Oteseconazole has brought the development of azole drugs into a new era. Compound A33, previously discovered by our group, showed excellent antifungal activity against a variety of pathogenic and drug-resistant fungi. Nevertheless, owing to its structural characteristics, it showed poor selectivity for the human CYPs family and extremely poor metabolic stability. To address the above problem, inspired by the reduced CYP inhibition observed in Oteseconazole, we replaced its triazole group with tetrazole and attempted deuteration strategies and carbonyl introduction to block the metabolic site. This modification led to the synthesis of compounds V01-V24, in which V23 showed broad-spectrum activity and resistance characteristics, especially against Aspergillus fumigatum (MIC₈₀ = 1 μg/mL), which had no inhibitory activity for many azole drugs. Compared to A33, the introduction of the tetrazole structure reduced its inhibitory activity against the human CYPs family. Furthermore, V23 could prevent fungal phase transformation and biofilm formation, resulting in satisfactory fungicidal activity. V23 showed negligible toxicity toward SH-SY5Y and HUVEC cells, and in vivo pharmacodynamic studies have shown that V23 has significant in vivo antifungal activity. In conclusion, the discovery of compound V23 is a successful exploration of a new tetrazole CYP51 inhibitor for the treatment of invasive fungal infections.

The one significant complication of viscoelastic materials is that they may cause postoperative intraocular pressure rise. We investigated the rate and ease of removal of various viscoelastics using the Miyake video technique. Five viscoelastics were investigated: sodium hyaluronate (Healon), Healon GV, chondroitin sulfatesodium hyaluronate (Viscoat), hydroxypropylmethylcellulose (Occucoat), and polyacrylamide (Orcolon). The viscoelastics were dyed with fluorescein and, after filling the capsular bag with a viscoelastic material, a posterior chamber intraocular lens (IOL) was implanted. The viscoelastic was then aspirated using an automated irrigation/aspiration device. Healon and Healon GV were completely removed within 20 to 25 seconds. Viscoat adhered to the lens capsule and to the posterior surface of the IOL and cooplete removal required approximately 3.5 minutes. Most Occucoat and Orcolon was aspirated within one minute; however, removal was completed only after three minutes. Removal of Healon and Healon GV was faster and more complete than removal of the other viscoelastics. Whether a small amount of viscoelastic left in the eye or trapped behind the IOL optic has any clinical significance has to be studied.