Synthesis and use of heptakis(2,6-di-O-methyl)-beta-cyclodextrin related to therapeutic applications: Patent and literature review.

The heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB), a methylated beta-cyclodextrin isomer has gained special interest due to its outstanding properties including high solubility and excellent solubilizing effect. It was found to enhance the pertussis toxin production in 1980s and has been used as an auxiliary material in manufacturing acellular pertussis vaccine since then. This vaccine applied world-wide against whooping cough has maintained the demand for DIMEB. In the meantime, further applications were discovered in other biotechnologies, drug delivery and tissue imaging. The high potential in the use as a therapeutic agent was also studied by several research groups. The increasing amount of knowledge concerning DIMEB calls for a systematic review. In this work we give the background based on the scientific literature and patents on the synthesis, effect and mechanism of action of this special cyclodextrin derivative. In relation to its applications, also, suitable analytical methods are enumerated to distinguish various methylated species of beta-cyclodextrins. Industrially produced DIMEB is a mixture of methylated cyclodextrin isomers containing at least 40 % of the specific single isomer heptakis(2,6-di-O-methyl)-beta-cyclodextrin. It was proved that this special methylation pattern has several advantages over the other methylated beta-cyclodextrin isomers including enhanced solubilizing and stabilizing effect, increased catalytic activity in various biotechnologies and special cellular effects with a potential in the therapy of various diseases.