创制人工熊胆——平衡医药需求和动物福利的创新路径

李勇, 黄宇虹, 冯楠, 张和平, 屈晶, 马双刚, 刘云宝, 李江, 徐少锋, 王玲, 张咪, 蔡杰, 王伟平, 冯茹, 于航, 于博, 梁待亮, 秦和平, 罗素芗, 李艳芬, 李美凤, 王瑞华, 马辰, 王琰, 岑小波, 徐孝先, 张伯礼, 王晓良, 庾石山

工程（英文） ›› 2024, Vol. 38 ›› Issue (7) : 100-112.

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工程（英文） ›› 2024, Vol. 38 ›› Issue (7) : 100-112. DOI: 10.1016/j.eng.2023.09.017
研究论文
Article

创制人工熊胆——平衡医药需求和动物福利的创新路径

作者信息 +

Artificial Bear Bile: A Novel Approach to Balancing Medical Requirements and Animal Welfare

Author information +
History +

摘要

熊胆自古以来一直是中医药中珍贵且有效的药材，已有超过13个世纪的使用历史。然而，目前通过养熊活体取胆汁的做法因其对动物福利的不良影响而广受批评。在这里，我们提出了一种创制人工熊胆（ABB）的新方法，使之可以作为天然熊胆的高质量和可持续代用品。通过涉及资源、化学、生物学、医学、药理学和中医等多个领域的合作研究，解决了创造熊胆代用品的科学挑战。建立了一套全面的功效评估系统，弥合了传统功效描述与现代医学术语的壁垒，使得对治疗成分进行系统筛选成为可能。通过化学合成和酶工程技术的应用，我们的研究实现了对熊胆药效成分的环境友好型大规模生产，并对ABB配方进行了优化和重组。由此产生的ABB不仅在成分上与天然熊胆非常接近，而且具有产品质量稳定、原料可获性高以及不依赖濒危或野生资源等优势。全面的临床前功效评估已经证明ABB与市售的引流熊胆在治疗效果上相当。此外，临床前毒理学评估和I期临床试验显示ABB的安全性与引流熊胆相当。这种创新的策略可以作为开发其他濒危中药代用品的新的研究范式，从而为濒危药材可持续利用提供了新的方向。

Abstract

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 centuries. However, the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare. Here, we present a new approach for creating artificial bear bile (ABB) as a high-quality and sustainable alternative to natural bear bile. This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields, including resources, chemistry, biology, medicine, pharmacology, and TCM. A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established, allowing for the systematic screening of therapeutic constituents. Through the utilization of chemical synthesis and enzyme engineering technologies, our research has achieved the environmentally friendly, large-scale production of bear bile therapeutic compounds, as well as the optimization and recomposition of ABB formulations. The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality, availability of raw materials, and independence from threatened or wild resources. Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile (DBB). Furthermore, preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB. This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs, thereby strengthening the integrity and sustainability of TCM.

关键词

人工熊胆 / 化学成分 / 配方优化 / 药效一致性 / 临床前毒理学评估

Keywords

Artificial bear bile / Chemical profile / Formula optimization / Pharmacodynamic consistency / Preclinical toxicological assessment

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李勇, 黄宇虹, 冯楠. 创制人工熊胆——在医药需求和动物福利之间实现平衡的创新路径. Engineering. 2024, 38(7): 100-112 https://doi.org/10.1016/j.eng.2023.09.017

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