45 years ago, Szejtli et al. reported on the synthesis of heptakis(2,6-di-O-methyl)-beta-cyclodextrin using dimethyl sulfate as alkylating agent in a solution of beta-cyclodextrin prepared with 1: 1 DMSO- DMF mixture containing equal amount of BaO and Ba(OH)2 8H2O [1]. CycloLab Ltd still found novelty in their follow-up, revised technology based on Szejtli’s work and recently new patent applications related to synthesis of heptakis(2,6-di-O-alkyl)-beta-cyclodextrin have been published, signaling continued research and development in the field of pharmaceutical formulations and delivery systems.
1. Chinese Patent Application: CN120239712A
Title: PROCESS FOR THE SYNTHESIS OF SELECTIVELY ALKYLATED CYCLODEXTRINS
Publication Date: July 1, 2025
Applicant: CycloLab Cyclodextrin R&D Laboratory Ltd.
2. International Patent Application: WO2024057083A1
Title: PROCESS FOR THE SYNTHESIS OF SELECTIVELY ALKYLATED CYCLODEXTRINS
Publication Date: March 21, 2024
Applicant: CycloLab Cyclodextrin R&D Laboratory Ltd.
Key Highlights:
- Novelty: Process for selective partial alkylation in the 2 and 6 positions of cyclodextrins performed with Cl -4 alkyl halogenides in a single step.
- Inventiveness: The advantage of the novel process is that the resulting product contains low amount of residual impurities (i.e. barium catalyst and residual alkylating agent) due to the suitable selection of precipitating solvents. Barium level is maximized in 30 ppm related to the most critical pharmaceutical products as referenced in document ICH guideline Q3 page 26 (28 March 2019).
- Potential Benefits: Low nitrosamine impurity.
For more detailed patent information, you can view the full applications on Espacenet:
[1] Szejtli, J., Liptak, A., Jodal, I., Fügedi, P., Nanasi, P., Neszmelyi, A. Die Starke 32 165-169 (1980)
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