Verma Richa, Akhtar Yumna, Singh Somnath
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University 68178, Omaha, Nebraska, NE. United States.
Recent Pat Drug Deliv Formul. 2017;11(2):114-123. doi: 10.2174/1872211311666170911160914.
Hydrogen sulfide (H2S) is a colorless gas with a characteristic smell of rotten eggs. Once only thought of as a toxic gas, evidence now shows that H2S plays major roles in pathological and physiological activities. These roles are being utilized to treat diseases and disorders ranging from hypertension, inflammation, edema, cardiovascular issues, chronic pain, cancer, and many more. Challenges facing the use of H2S currently involve achieving the optimum therapeutic concentrations, synthesizing chemically and physiologically stable donors, and developing clinically appropriate delivery systems.
We did an extensive literature search on therapeutic potentials and related issues of H2S which were presented in a systematic flow pattern in introduction. Patents accepted/filed on various aspects of hydrogen sulfide were searched using the United States Patent and Trademark Office database at http://patft.uspto.gov/ and google patents at https://patents.google.com/. The important search terms combined with H2S were therapeutic effect, pharmacological action, biochemistry, measurement, and delivery. We also incorporated our own experiences and publications while discussing the delivery approaches and associated challenges.
In the process, researchers have discovered novel techniques in preparing the noxious gas by discovering and synthesizing H2S donors and developing controlled and predictable delivery systems. Donors utilized thus far include derivatives of anti-inflammatory drugs like H2S -aspirin, Allium sativum extracts, inorganic salts, phosphorodithioate derivatives, and thioaminoacid derivatives. Use of controlled delivery systems for H2S is critical to maintain its physiological stability, optimum therapeutic window, increase patient compliance, and make it easier to manufacture and administer. Numerous patents overcoming the challenges of using H2S therapeutically with various donors and delivery mechanisms have been reviewed.
The scientific knowledge gained from the last decade researches has moved H2S from a foul smelling pungent gas to the status of a gasotransmitter with many potential therapeutic applications. However, developing a suitable donor and a delivery system using that donor for providing precise and sustained release of H2S for an extended period, is critically needed for any further development towards its translation into clinical practices.
硫化氢（H₂S）是一种无色气体，具有臭鸡蛋的特征气味。曾经它仅被视为一种有毒气体，但现在有证据表明，H₂S在病理和生理活动中发挥着重要作用。这些作用正被用于治疗从高血压、炎症、水肿、心血管问题、慢性疼痛、癌症等多种疾病和病症。目前使用H₂S面临的挑战包括实现最佳治疗浓度、合成化学和生理稳定的供体以及开发临床上合适的给药系统。
我们对H₂S的治疗潜力及相关问题进行了广泛的文献检索，这些内容在引言中以系统的流程模式呈现。使用美国专利商标局数据库（http://patft.uspto.gov/）和谷歌专利（https://patents.google.com/）搜索了关于硫化氢各个方面的已接受/已提交的专利。与H₂S相关的重要搜索词包括治疗效果、药理作用、生物化学、测量和给药。在讨论给药方法及相关挑战时，我们还融入了自己的经验和出版物。
在此过程中，研究人员通过发现和合成H₂S供体以及开发可控且可预测的给药系统，发现了制备这种有害气体的新技术。迄今为止使用过的供体包括H₂S -阿司匹林等抗炎药物的衍生物、大蒜提取物、无机盐、二硫代磷酸酯衍生物和硫代氨基酸衍生物。对H₂S使用可控给药系统对于维持其生理稳定性、最佳治疗窗口、提高患者依从性以及便于制造和给药至关重要。已对众多克服将H₂S与各种供体和给药机制用于治疗所面临挑战的专利进行了综述。
过去十年研究获得的科学知识已使H₂S从一种恶臭刺鼻的气体转变为具有许多潜在治疗应用的气体递质。然而，如果要进一步将其转化为临床实践，迫切需要开发一种合适的供体以及使用该供体的给药系统，以实现H₂S长时间的精确和持续释放。
