Low Cost Production of the Malaria Drug Artemether

描述(申请人提供)：每年有超过1亿人感染疟疾。绝大多数受害者生活在地方性热带国家。20世纪40年代积极的灭蚊计划基本上结束了美国本地获得的疟疾的发病率，但疟疾的卷土重来仍然存在风险，因此监测和研究对美国的公共卫生利益以及全球卫生利益仍然至关重要。在过去的十年里，基于从青蒿素(Artemisia Annua)中提取的中药成分青蒿素(青蒿素)，已经开发出了新的高效抗疟疾疗法。世卫组织批准的治疗方法是所谓的青蒿素联合疗法(ACT)，即将青蒿素衍生物(最常见的是蒿甲醚)与更长的半衰期抗疟疾药物(如鲁米芬)结合起来，以消除寄生虫并降低它们产生耐药性的风险。主要问题是成本。疟疾受害者通常是全球社会中最贫穷的成员之一，用目前的方法制造蒿甲醚并不便宜。幸运的是，Aerphase已经开发出一种简化的提取/反应/分离方案，预计将降低蒿甲醚生产的总体成本。第一步，超临界二氧化碳萃取青蒿叶，已知的是高产率地分离青蒿素和青蒿酸。第二步，将这些化合物化学转化为蒿甲醚，这一步也同样行之有效。第三步，超临界流体萃取蒿甲醚产品，以前没有报道过，但基于蒿甲醚高度亲油的性质，预计效果很好。此外，我们预计，将这些步骤结合起来将节省资本设备和能源成本。拟议工作的主要目的是开发一种降低以蒿甲醚为基础的抗疟疾产品成本的过程。这项核心技术还将商业化用于其他应用。第一阶段的具体目标是1)确定超临界二氧化碳下青蒿素转化为蒿甲醚的反应条件，2)确定分离蒿甲醚的超临界二氧化碳条件，3)展示我们可以设计和制造结合萃取、反应和分离步骤的先进原型。这个多阶段SBIR项目的总体目标是开发、验证一种新的、更具成本效益的蒿甲醚生产方法，并将其商业化，该方法以经济的方式利用超临界二氧化碳。 疟疾仍然是一个世界性的公共卫生问题，每年导致1亿多人患病，其中100多万人死亡。不幸的是，疟疾通常袭击那些最负担不起药品的人群。该项目寻求开发、验证和商业化一种新的、更便宜的方法，从甜艾草厂生产高效疟疾药物蒿甲醚。

DESCRIPTION (provided by applicant): Malaria sickens over 100 million people each year. The vast majority of the victims live in endemic, tropical countries. Aggressive mosquito eradication programs in the 1940s essentially ended the incidence of locally-acquired malaria in the US, but resurgence remains a risk, so surveillance and research remain vital to US public health interests, as well as to global health interests. In the past decade, new, highly-effective antimalarial therapies have been developed based on the Chinese medicine component Qinghaosu (artemisinin) - extracted from sweet wormword (Artemisia annua). The WHO-approved treatment takes the form of a so-called artemisinin combination therapy (ACT) in which an artemisinin derivative, most commonly artemether, is combined with a longer half-life antimalarial such as lumefantrine to eliminate the parasites and decrease the risk of them developing drug resistance. The main problem is cost. Malaria victims are usually among the poorest members of the global community, and artemether is not inexpensive to make by current methods. Fortunately, Aerophase has developed a streamlined extraction/reaction/separation scheme that is anticipated to reduce the overall cost of artemether production. The first step, supercritical carbon dioxide extraction of Artemisia annua leaves, is known to isolate artemisinin and artemisinic acid in high yield. The second step, chemical conversion of these compounds to artemether, is likewise well-established. The third step, supercritical fluid extraction of the artemether product, has not been reported before, but is anticipated to work very well based on the highly lipophilic nature of artemether. Further, we anticipate that combining these steps will save on capital equipment and energy costs. The primary purpose of the proposed work is to develop a process that reduces the cost of artemether-based antimalarial products. The core technology will also be commercialized for other applications. The specific aims in phase I are 1) determine reaction conditions for conversion of artemisinin to artemether under supercritical carbon dioxide, 2) determine supercritical carbon dioxide conditions for isolation of artemether product, and 3) demonstrate that we can design and fabricate an advanced prototype that combines the extraction, reaction, and separation steps. The overall goal of this multi-phase SBIR project is to develop, validate, and commercialize a new, more cost-effective method for artemether production that utilizes supercritical carbon dioxide in an economical process. Malaria continues to be a worldwide public health problem, sickening over 100 million people per year and killing over 1 million of them. Unfortunately, malaria usually strikes populations that are least able to afford medicines. This project seeks to develop, validate, and commercialize a new, cheaper method for producing the highly effective malaria drug artemether from the Sweet Wormwood plant.