舒巴坦和金刚烷胺盐中增加的热稳定性和保留的抗菌特性:朝向有效的抗菌抗病毒联合疗法†

Josephine Bicknell, Ivan Bondarenko, Alice Colatrella, Elani J. Cabrera-Vega, Jesus Daniel Loya, Delbert S. Botes, Jay L. Mellies and Gonzalo Campillo-Alvarado
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摘要

我们描述了由舒巴坦(SUL, β-内酰胺酶抑制剂)和金刚烷胺(AMNH,抗病毒药物)组成的多药盐的形成。对SUL·AMNH盐的理化研究表明,与原始起始材料相比,该盐的热稳定性有所提高。体外研究发现,在SUL·AMNH中形成盐不会破坏对模式生物大肠杆菌和表皮葡萄球菌的抗菌活性。据我们所知,我们展示了第一种β-内酰胺酶抑制剂-抗病毒盐,其中两种成分都已获得美国食品和药物管理局(FDA)的批准,以及第一种含有SUL的多组分固体。我们设想我们的策略可以启发设计用于抗菌联合治疗的多组分固体。
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Increased thermal stability and retained antibacterial properties in a sulbactam and amantadine salt: towards effective antibacterial–antiviral combination therapies†

We describe the formation of a multidrug salt comprising sulbactam (SUL, β-lactamase inhibitor) and amantadine (AMNH, antiviral). Physicochemical investigation of the SUL·AMNH salt revealed enhanced thermal stability compared to pristine starting materials. In vitro studies found that salt formation in SUL·AMNH does not disrupt antibacterial activity against model organisms Escherichia coli and Staphylococcus epidermidis. To our knowledge, we show the first β-lactamase inhibitor-antiviral salt where both components have been approved by the U.S. Food and Drug Administration (FDA), and the first multicomponent solid containing SUL. We envisage our strategy could inspire the design of multicomponent solids for antimicrobial combination therapies.

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