熊去氧胆酸（UDCA）合成方法研究进展
摘要：熊去氧胆酸是用于治疗人体胆固醇结石药物的主要成分，对于肝胆疾病的治疗具有十分高效的作用。其作用主要机理包括：影响胆汁酸池的成分，作为细胞保护剂，免疫调节物质和亲水性胆汁酸；熊去氧胆酸还可通过将胆脂中的一些胆固醇含量降低和抑制肠道内对胆固醇的吸收，使胆固醇分泌入胆汁减少，从而显著降低胆汁中胆固醇饱和度；此外，鉴于熊去氧胆酸对血清胆固醇、甘油三酯均有明显的降低作用，近年来熊去氧胆酸已成为防治高脂血症的有效基础治疗药。然而，原始的熊去氧胆酸提取方法是从熊胆中提取原料，这一种方法的原料来源是非常有限的。因此， 开发UDCA新的合成方法是一个重要课题。本文综述了目前熊去氧胆酸合成的一些方法，包括：1.以动物体内的胆酸类物质作为原料；2.以非胆酸甾体作为原料；3.以异构体鹅去氧胆酸的合成；4.微生物催化法；5.酶催化法。与化学催化相比，生物酶催化合成UDCA具有专一性与高效性等优势，但在目前国内外的研究中，酶催化的转化效率仍是一大问题。本文试图通过比较，为合成方法的改进提供一些思路和参考。
关键词：UDCA ; 药用价值; 化学合成; 酶; 生物转化
Research progress in synthesis of ursodeoxycholic acid (UDCA)
Abstract:Ursodeoxycholic acid (URSOdeoxycholic acid) is the main ingredient in the treatment of cholesterol stones, which is highly effective in the treatment of hepatobiliary diseases. The main mechanisms of its action include affecting the constituents of bile acid pools, acting as cell protectants, immunomodulators and hydrophilic bile acids. Ursodeoxycholic acid can also significantly reduce the cholesterol saturation in bile by reducing the cholesterol content in bile fat and inhibiting the absorption of cholesterol in the intestinal tract. In addition, ursodeoxycholic acid (URSOdeoxycholic acid) has significantly reduced serum cholesterol and triglyceride, so ursodeoxycholic acid has become an effective basic treatment for hyperlipidemia in recent years. However, the original ursodeoxycholic acid extraction method is to extract raw materials from bear bile, this method of raw materials is very limited. Therefore, using new methods to synthesize UDCA has become our most important goal at present. This article mainly introduces some methods of chemical synthesis of ursus deoxycholic acid, including: 1. Cholic acids in animals as raw materials; 2. Non-cholic steroids were used as raw materials; 3. Synthesis of andeoxycholic acid with isomer. Compared with chemical catalysis, biological enzyme catalysis has the advantages of specificity and high efficiency in UDCA synthesis. However, the conversion efficiency of enzyme catalysis is still a major problem in current research at home and abroad. Therefore, some ideas and references are provided for the improvement of their synthesis methods through comparison.
Key words: UDCA; Medicinal value; Chemical synthesis; Enzyme; biocatalysis
熊去氧胆酸是一种有机化合物，外观呈白色粉末，无臭，味苦，它的化学名称为3a,7-二羟基-5-胆甾烷-24-酸，纯白色粉末，分子式为C24H40O4，相对分子质量392.56。熊去氧胆酸作为熊胆的主要成分广泛应用于临床，《中国药典》2015（第二部）将熊去氧胆酸归类为胆石溶解药，制成片剂服用。
熊去氧胆酸的药用价值
熊去氧胆酸 Ursodeoxycholic acid( UDCA),熊胆粉的主要活性成分是熊去氧胆酸,它实际应用于临床医学，用于去除或者减少人体中的胆固醇结石。其作用主要机理包括影响胆汁酸池的成分，作为细胞保护剂，免疫调节物质和亲水性胆汁酸。熊去氧胆酸呈弱酸性，在人体内可以快速扩散并且吸收，非常适合作为药物。此外，熊去氧胆酸还可通过将胆脂中的一些胆固醇含量降低和抑制肠道内对胆固醇的吸收，使胆固醇分泌入胆汁减少，从而显著降低胆汁中胆固醇饱和度。大量的临床研究证实UDCA具有保护细胞、抗氧化、免疫调节和对一些胆结石和胆汁淤积性肝硬化等疾病确有治疗作用。伴随着现代科学对细胞凋亡和对熊去氧胆酸抗凋亡机制的研究逐渐深入, 也可以使其对细胞保护作用的研究进一步扩展。
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