| Cyclolab Ltd filed a patent application (US20220282001) on cyclodextrin containing physical mixtures and inclusion complexes that show improved protein stabilizing effect. In an attempt to provide efficient stabilization for proteins, both in physical and chemical sense, it was found that the parenterally applicable cyclodextrins, such as hydroxypropylated-alpha-beta- and gamma-cyclodextrins showed stabilizing effect. The probable mechanism of this effect is based on the complex formation between lipophilic domains of the proteins (inclusion of the aromatic amino acid residues) and cyclodextrins. However, it was surprisingly found that if natural lipophiles that are known to form stable inclusion complexes with cyclodextrins, were combined with CDs, the protein stabilizing potency of these cyclodextrin-lipid complexes was higher than that achieved by the empty cyclodextrins. This positive effect was not expected, since in case of these lipid-cyclodextrin complexes, the cavities of cyclodextrins were already occupied by respective lipophiles. It is thought that the complexation-dissociation equilibrium in aqueous solutions was responsible for the enhanced protein stabilization provided by lipid-CD complexes. Similar enhancement of the prevention of protein aggregation was found when ionic cyclodextrin derivatives (such as carboxyalkyl-, sulfoalkyl-, quaternary amino- etc. CDs), were combined with an oppositely charged, water-soluble small ionic compound, (e.g. nicotinamide, L-carnitine, spermine, creatinine, nucleosides and their phosphate esters). |
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