Low Cost Production of the Malaria Drug Artemether

疟疾药物蒿甲醚的低成本生产

• 批准号: 7339512
• 负责人: BROOKS MICHAEL HYBERTSON
• 金额: $ 9.93万
• 依托单位: AEROPHASE, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7339512
• 关键词: Africa; Age-Years; Am 80; Antimalarials; Artemisia; Artemisia annua; Artemisinins; Biological; Capital; Carbon Dioxide; Chemicals; Child; Chinese People; Collection; Combined Modality Therapy; Communities; Condition; Cost Analysis; Country; Crude Extracts; Culicidae; Dental; Development; Drug resistance; Economics; Employee Strikes; Equipment; Goals; Half-Life; Health; Incidence; Left; Life; Link; Liquid substance; Location; Malaria; Medical; Medical Surveillance; Medicine; Melanocytic nevus; Methods; Methyl Ethers; Mole the mammal; NIH Program Announcements; Nature; Numbers; Parasites; Pharmaceutical Preparations; Phase; Plant Leaves; Plants; Population; Process; Production; Public Health; Purpose; Reaction; Recycling; Reporting; Research; Resources; Risk; Scheme; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solubility; Solvents; Staging; Standards of Weights and Measures; Stream; Supercritical Fluid Extraction; System; Technology; Temperature; Time; Transportation; Work; World Health; World Health Organization; artemether; artemisic acid; artemisin; artemisinine; base; benflumetol; chemical reaction; cost; design; improved; innovation; interest; killings; manufacturing process; member; novel; novel strategies; petroleum ether; pressure; programs; prototype; research and development

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.

描述（由申请人提供）：疟疾每年使1亿多人患病。绝大多数受害者生活在流行的热带国家。20世纪40年代的积极灭蚊计划基本上结束了美国当地获得性疟疾的发病率，但死灰复燃仍然是一个风险，因此监测和研究对美国公共卫生利益以及全球健康利益仍然至关重要。在过去十年中，基于从青蒿中提取的中药成分青蒿素（青蒿素），开发了新的高效抗疟疗法。世卫组织批准的治疗采取所谓的青蒿素联合疗法的形式，其中青蒿素衍生物，最常见的是蒿甲醚，与半衰期较长的抗疟药如苯芴醇相结合，以消除寄生虫并降低它们产生抗药性的风险。主要的问题是成本。疟疾患者通常是全球社会中最贫穷的成员，而蒿甲醚的生产成本并不便宜。幸运的是，Aerophase开发了一种简化的提取/反应/分离方案，预计将降低蒿甲醚生产的总成本。第一步，青蒿叶的超临界二氧化碳萃取，已知以高产率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，也同样是公认的。第三步，蒿甲醚产品的超临界流体萃取，以前没有报道过，但基于蒿甲醚的高度亲脂性，预期效果非常好。此外，我们预计结合这些步骤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工艺，降低以蒿甲醚为基础的抗疟产品的成本。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）确定在超临界二氧化碳条件下青蒿素转化为蒿甲醚的反应条件，2）确定蒿甲醚产品分离的超临界二氧化碳条件，3）证明我们可以设计和制造一个先进的原型，结合萃取，反应和分离步骤。这个多阶段SBIR项目的总体目标是开发、验证和商业化一种新的、更具成本效益的蒿甲醚生产方法，该方法在经济的过程中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，每年使1亿多人患病，其中100多万人死亡。不幸的是，疟疾通常袭击最无力支付药品的人群。该项目旨在开发、验证和商业化一种新的、更便宜的方法，从甜蒿植物中生产高效的疟疾药物蒿甲醚。