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）：疟疾每年有超过1亿人患病。绝大多数受害者生活在流行的热带国家。 1940年代，积极进取的消除蚊子根本结束了美国当地疟疾的发病率，但复兴仍然是一种风险，因此监视和研究对美国的公共卫生利益以及全球健康利益仍然至关重要。在过去的十年中，基于中药成分青闻（Artemisinin）开发了新的，高效的抗疟疾疗法 - 从Sweet Wormword（Artemisia annua）中提取。 WHO批准的治疗采取了所谓的青蒿素联合疗法（ACT）的形式，其中青蒿素衍生物（最常见的是小节）与更长的半寿命抗疟药结合在一起，例如Lumefantrine，以消除寄生虫并降低产生耐药性的风险。主要问题是成本。疟疾受害者通常是全球社区中最贫穷的成员之一，而通过目前的方法，Artementh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，该方案预计可以降低肉细胞计生产的总成本。第一步，众所周知，甲莫西西亚叶叶的超临界二氧化碳提取可以分离青蒿素和artemisinic酸。第二步，这些化合物将这些化合物的化学转化为artemether，同样是公认的。以前尚未报道第三步，是丁香产物的超临界流体提取，但预计基于高亲脂性的性质，可以很好地发挥作用。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个降低基于artemether的抗疟药成本的过程。核心技术还将用于其他应用程序。第一阶段中的具体目的是1）确定在超临界二氧化碳下将青蒿素转化为art骨的反应条件，2）确定超临界二氧化碳条件以隔离小臂产品，3）证明我们可以设计和制造一种与提取，反应，反应和分离步骤结合的先进原型。这个多相SBIR项目的总体目标是开发，验证和商业化一种新的，更具成本效益的方法，用于在经济过程中利用超临界二氧化碳。 疟疾仍然是一个全球的公共卫生问题，每年令人病性超过1亿人，造成超过100万人的杀害。不幸的是，疟疾通常会罢工人群，这些人群无法负担药物。该项目旨在开发，验证和商业化一种新的，更便宜的方法，用于从甜虫木植物中产生高效的疟疾药物。