Plasticized hydrophilic glasses for improved stabilization...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 9/00 (2006.01) C12N 1/04 (2006.01) C12N 9/02 (2006.01) C12N 9/08 (2006.01) C12N 9/52 (2006.01) C12N 9/58 (2006.01) C12N 9/60 (2006.01) C12N 9/64 (2006.01) C12N 9/96 (2006.01)

Patent

CA 2458794

The stabilization of biomaterials such as proteins in a nominally dry, hydrophilic glassy matrix is vastly improved by the addition of an appropriate amount of a small-molecule pasticizer such as a glycol or DMSO to the formulation, while maintaining a glass transition temperature (Tg) that is above the storage temperature. By plasticizing the glasses, their ability to preserve proteins is improved by as much as 100 times over the unplasticized glass at room temperature. The plasticizer confers the greatest beneficial effect when it is dynamically coupled into the bulk glass, and this coupling occurs over a fairly narrow range of plasticizer concentration. Methods are described in which a small-molecule plasticizer can be incorporated into a glass made of much larger molecules (e.g. a polymeric glass), with desired dynamic coupling, via a molecule that is believed to act as a dynamic linker. Protein preservation data was obtained from two enzymes, horseradish peroxidase (HRP) and alcohol dehydrogenase (ADH).

On améliore considérablement la stabilisation de matières biologiques telles que les protéines dans une matrice vitreuse, hydrophile, essentiellement sèche en ajoutant à la préparation une quantité appropriée d'un plastifiant à petites molécule, tel que le glycol ou le DMSO, et en maintenant la température de transition vitreuse (Tg) au-dessus de la température de stockage. De plus, en plastifiant le verre, on multiplie par au moins 100 sa capacité à préserver les protéines à température ambiante par rapport au verre non plastifié. Par ailleurs, on tire le maximum d'avantages du plastifiant lorsqu'il est couplé de façon dynamique au verre en vrac, ce couplage se produisant dans une plage relativement étroite de concentration de plastifiant. L'invention concerne également des procédés dans lesquels un plastifiant à petites molécules peut être incorporé à un verre constitué de molécules beaucoup plus grandes (par ex. un verre polymère), selon le couplage dynamique souhaité, via une molécule censée agir comme un liant dynamique. Deux enzymes, la peroxydase du raifort (HRP) et l'alcool déshydrogénase (ADH) permettent d'obtenir les données de préservation des protéines.

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