摘要
目的:以猫豆为原料生产左旋多巴有很大的市场潜力。研究猫豆产业链一套支撑技术,为广西打造猫豆产业奠定坚实基础。
方法:通过对猫豆药材开展系列研究,包括猫豆的应用基础研究、猫豆药材种植技术研究、猫豆的应用研究、猫豆中左旋多巴提取工艺研究、猫豆中猫豆胍的研究、猫豆非左旋多巴组分研究、左旋多巴系列衍生物的研究、猫豆废料的再利用研究等,从而构建了猫豆产业链的一套完整的支撑技术。
结果:通过本文研究,掌握了猫豆种植丰产技术、高纯度左旋多巴高效提取技术、猫豆渣湿法保鲜技术,以左旋多巴为原料开展系列衍生物研究,获得盐酸左旋多巴甲酯、左旋多巴乙酯、左旋多巴正丙酯、左旋多巴异丙酯、盐酸左旋多巴正丁酯、盐酸左旋多巴异丁酯、盐酸左旋多巴正戊酯、盐酸左旋多巴异戊酯、盐酸左旋多巴正己酯、乙酰左旋多巴甲酯、乙酰左旋多巴乙酯、乙酰左旋多巴正丙酯、乙酰左旋多巴异丙酯、乙酰左旋多巴正丁酯、乙酰左旋多巴异丁酯、乙酰左旋多巴正戊酯、Boc左旋多巴等17个新药和化学中间体原料合成和纯化工艺,开展成药性研究,形成5个专利成果,其中治疗弱视的1类新药左旋多巴甲酯原料药及其制剂已进行产业化转化,拓展了左旋多巴的用途,提升猫豆产业链的盈利能力,全套技术应用于广西那坡制药有限公司,获得风险基金青睐,引入5000万元战略投资,改制为广西圣多宝制药有限公司,开展cGMP认证,成为全球最大的左旋多巴生产企业。
结论:形成的支撑技术有效支撑猫豆产业发展。
Objective: The production of L-dopa through chemical synthesis has been declining due to the cost, environmental pollution control and other reasons in foreign country. The supply of natural L-dopa in foreign country is mainly imported from China. We can see that the potential market of producing natural L-dopa from Maodou is very great. In order to set up supporting technologies for the development of industry of Maodou in Guangxi, we have done a series of investigation in Maodou.
Methods:In order to set up supporting technologies for the development of industry of Maodou in Guangxi, we have done a series of investigation in Maodou. These investigations focused on application of Maodou, technology of Maodou planting, extraction of L-dopa from Maodou, mucunaguanide in Maodou, non-levodopa components in Maodou, L-dopa derivatives, recycle of extraction waste of Maodou and so on.
Results: In this paper, we have developed a series of technology in high-yield planting of Maodou, efficient extraction of high purity of levodopa and wet-preservation of extraction waste of Maodou. We have synthesized, isolated and purified 17 new L-dopa derivatives. These are levodopa methyl ester hydrochloride、(3,4-dihydroxy-L-phenylalanine ethyl ester)、((S)-propyl 2-amino-3-(3,4-dihydroxyphenyl) propanoate)、((S)-isopropyl 2-amino-3-(3,4-dihydroxyphenyl)propanoate)、((S)-butyl -2-amino-3-(3,4- dihydroxyphenyl)propanoate hydrochloride)、((S)-iso -butyl 2-amino-3-(3,4-dihydroxyphenyl) propanoate hydrochloride)、((S)- pentyl 2-amino-3-(3,4-dihydroxyphenyl)propanoate hydrochloride)、((S) -isopentyl-2-amino-3-(3,4-dihydroxyphenyl)propanoate hydrochloride)、((S)-hexyl 2-amino-3-(3,4-dihydroxyphenyl)propanoate hydrochloride)、((S)-4-(2-acetamido-3-methoxy-3-oxopropyl)-1,2-phenylene diacetate)、 ((S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate)、((S)-4-(2-acetamido-3-oxy-3-propoxypropyl)-1, 2-phenylene diacetate)、((S)-4-(2-acetamido-3-isopropoxy-3-oxopropyl)-1,2-phenylene diaceta -te)、((S)-4-(2-acetami-do-3-butoxy-3-oxopropyl)-1, 2-phenylene diaceta -te)、((S)-4-(2-acetamido-3-isobutoxy-3-oxopropyl)-1, 2-phenylene diacet -ate)、((S)-4-(2-acetamido-3-oxo-3-(pentyloxy) propyl)-1, 2-phenylene diacetate) and ((S)-2-((tert-butoxycarbonyl)amino)-3-(3,4-dihydroxyph -enyl) propanoic acid) Charaterization and functional detection of all derivatives have been done. We found one derivative, levodopa methyl ester hydrochloride was useful in treatment of amblyopia. Translational research of Levodopa methyl ester hydrochloride is under going. This expands the use of levodopa, and enhance the profitability of industrial chain of Maodou. These technologies have been used in Guangxi Napo Pharma Co., Ltd.. We have founded a new company, Guangxi Sedopa Co., Ltd. on the base of Guangxi Banger Pharma Co., Ltd. with the strategy investment of 50 million yuan. We are applying certificate of cGMP. Our goal is to become the largest manufacturer of levodopa in the world.
Conclusions: The supporting technologies for the development of industry of Maodou in Guangxi expands the use of levodopa, and enhance the profitability of industrial chain of Maodou.
引文
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