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首页> 外文期刊>Bioprocess and Biosystems Engineering >A novel one-pot de-blocking and conjugation reaction step leads to process intensification in the manufacture of PEGylated insulin IN-105
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A novel one-pot de-blocking and conjugation reaction step leads to process intensification in the manufacture of PEGylated insulin IN-105

机译：新颖的一锅解封和共轭反应步骤导致制造聚乙二醇化胰岛素IN-105的过程更加激烈

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摘要

Bio-catalytic in vitro multistep reactions can be combined in a single step in one pot by optimizing multistep reactions under identical reaction condition. Using this analogy, the process of making PEGylated insulin, IN-105, was simplified. Instead of taking the purified active insulin bulk powder as the starting material for the conjugation step, an insulin process intermediate, partially purified insulin ester, was taken as starting material. Process intensification (PI) was established by performing a novel deblocking (de-esterification) of the partially purified insulin ester and conjugation at B-29 Lys residue of B chain with a short-chain methoxy polyethylene glycol (mPEG) in a single-pot reactor. The chromatographic profile at the end of the reaction was found similar irrespective of whether both the reactions were performed sequentially or simultaneously. The conjugated product of interest, IN-105 (conjugation at LysB_(29)), was purified from the heterogeneous mixture of conjugated products. The new manufacturing process was deduced to be more simplified and economical in making the insulin conjugates as several downstream purification steps could be circumvented. The physico-chemical characteristics of IN-105 manufactured through this economic process was found to be indifferent from the product formed through the traditional process where the conjugation starting material was purified from bulk insulin.
机译：通过在相同反应条件下优化多步反应，生物催化体外多步反应可以在一个罐中一步完成。使用这种类比，简化了制备聚乙二醇化胰岛素IN-105的过程。代替将纯化的活性胰岛素本体粉末作为缀合步骤的起始原料，将胰岛素工艺中间体，部分纯化的胰岛素酯作为起始原料。通过在单罐中对短链甲氧基聚乙二醇（mPEG）进行部分纯化的胰岛素酯的新型解封闭（去酯化）并在B链的B-29 Lys残基处缀合来建立过程强化（PI）反应堆。无论反应是顺序进行还是同时进行，都发现反应结束时的色谱图相似。从共轭产物的异质混合物中纯化目标共轭产物IN-105（在LysB_（29）处缀合）。由于可以绕开几个下游纯化步骤，因此推论出新的制造工艺在制造胰岛素偶联物方面更加简化和经济。发现通过这种经济方法制造的IN-105的理化特性与通过传统方法形成的产品没有什么区别，在传统方法中，结合原料是从大量胰岛素中纯化得到的。

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