环孢素超细溶液加压计量吸入器在COVID-19患者治疗中的潜在应用

Touraj Ehtezazi
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摘要

导语:当病毒到达肺泡水平时,严重的COVID-19呼吸道问题就开始了,II型细胞被感染并死亡。因此,肺泡水平的病毒抑制有助于预防这些呼吸道并发症。方法:通过文献检索,收集可用于新冠肺炎治疗的小分子化合物的理化性质。选择熔点低的化合物以及可溶于乙醇、氢键给体和受体的化合物。结果:有几种具有良好理化性质的严重急性呼吸综合征冠状病毒抑制剂,适合作为超细加压计量吸入器(pMDI)。霉酚酸、debio25和环孢素A是这些化合物的主要候选者。环孢素A(以下简称环孢素)是一种有效的SARS-CoV-2抑制剂,已被用于治疗COVID-19患者,显示出提高生存率。此外,吸入治疗雾化环孢素是耐受的,用于肺移植患者。最后,将环孢素配制成超细pMDI溶液。尽管大多数国家已开始疫苗治疗,但具有非免疫活性的吸入疗法可最大限度地减少疾病的传播,并可用于对疫苗犹豫不决的个体。结论:应研究环孢素或debio25超细pMDI制剂用于COVID-19吸入治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Potential Use of Cyclosporine Ultrafine Solution Pressurised Metered- Dose Inhaler in the Treatment of COVID-19 Patients.

Introduction: Serious COVID-19 respiratory problems start when the virus reaches the alveolar level, where type II cells get infected and die. Therefore, virus inhibition at the alveolar level would help preventing these respiratory complications.

Method: A literature search was conducted to collect physicochemical properties of small molecule compounds that could be used for the COVID-19 treatment. Compounds with low melting points were selected along with those soluble in ethanol, hydrogen-bond donors, and acceptors.

Results: There are severe acute respiratory syndrome coronavirus inhibitors with physicochemical properties suitable for the formulation as an ultrafine pressurised metered-dose inhaler (pMDI). Mycophenolic acid, Debio 025, and cyclosporine A are prime candidates among these compounds. Cyclosporine A (hereafter cyclosporine) is a potent SARS-CoV-2 inhibitor, and it has been used for the treatment of COVID-19 patients, demonstrating an improved survival rate. Also, inhalation therapy of nebulised cyclosporine was tolerated, which was used for patients with lung transplants. Finally, cyclosporine has been formulated as a solution ultrafine pMDI. Although vaccine therapy has started in most countries, inhalation therapies with non-immunological activities could minimise the spread of the disease and be used in vaccine-hesitant individuals.

Conclusion: Ultrafine pMDI formulation of cyclosporine or Debio 025 should be investigated for the inhalation therapy of COVID-19.

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