Compositions and Methods for Preservation of Materials in the Amorphous State

Patent metadata

Field	Value
Publication number	US-2016165879-A1
Application number	US-201514969624-A
Country	US
Kind code	A1
Filing date	Dec 15, 2015
Priority date	Dec 15, 2014
Publication date	Jun 16, 2016
Grant date	—

Abstract

The present disclosure provides methods and compositions including a sugar and a choline hydrogen phosphate salt for preservation and stabilization of materials in the amorphous state. The compositions and methods suppress the formation of crystals in materials in the amorphous state.

First claim

1 . A method for preservation of a biomaterial comprising:
combining the biomaterial with a preservative composition comprising a sugar or sugar alcohol and a salt comprising choline hydrogen phosphate (HPO 4 −2 ) to form a mixture; and converting the preservative composition within the biomaterial to an amorphous state.

2 . The method of claim 1 , wherein the sugar is selected from the group consisting of: sucrose, glucose, fructose, and trehalose.

3 . The method of claim 1 , wherein the sugar comprises trehalose.

4 . The method of claim 1 , wherein the biomaterial is selected from the group consisting of: living tissues, living cells, live viruses, peptides, nucleic acids, biomolecules, and combinations of these.

5 . The method of claim 1 , wherein converting the material to the amorphous state comprises processes selected from the group consisting of: cooling the material to a temperature less than the glass transition temperature of the composition, dehydration, or a combination of both cooling and dehydrating.

6 . The method of claim 5 , wherein the cooling or dehydration is selected from the group consisting of: freezing, freeze-drying, vitrification, cryopreservation, heat drying, microwave drying, lyophilization, use of a desiccant, air-flow drying, spin drying, spray drying, and combinations thereof.

7 . The method of claim 1 , wherein the preservative composition forms an amorphous state matrix around the biomaterial.

8 . The method of claim 1 , wherein the preservative composition suppresses crystal formation in the amorphous state preservative composition around biomaterial for a greater amount of time as compared to a biomaterial preserved with a comparative composition having the same formulation as the preservative composition except for having a greater amount of choline dihydrogen phosphate (H 2 PO 4 − ).

9 . The method of claim 1 , wherein the preservative composition has a salt:sugar ratio of about 0.1 to about 2.0.

10 . A method of suppressing crystallization of a composition in an amorphous state comprising a sugar or sugar alcohol comprising:
combining the sugar or sugar alcohol with a salt comprising choline hydrogen phosphate (HPO 4 −2 ) in an amount effective to increase the amount of time to formation of crystals in the composition when in the amorphous state as compared to a composition in the amorphous state made without the choline hydrogen phosphate.

11 . A preservative composition comprising:
a sugar or sugar alcohol and a salt comprising choline hydrogen phosphate (HPO 4 −2 ),
the composition having a salt:sugar ratio effective to suppress the formation of crystals in the composition in the amorphous state such that the amount of time to formation of crystals in the presence of moisture is increased over the amount of time to crystal formation in a comparative composition that is the same as the preservative composition except for having a greater amount of choline dihydrogen phosphate than the salt of the preservative composition.

12 . The preservative composition of claim 11 , wherein the salt:sugar ratio is about 0.2 or greater

13 . The preservative composition of claim 11 , wherein the salt:sugar ratio is about 0.5 or greater.

14 . The preservative composition of claim 11 , wherein the salt:sugar ratio is between about 0.1 and 2.0.

15 . The preservative composition of claim 11 , wherein the composition has a pH of about 7.0 or greater.

16 . The preservative composition of claim 11 , wherein the composition has a pH between about 7.0 and 10.0.

17 . The preservative composition of claim 11 , wherein the sugar is selected from the group consisting of: sucrose, glucose, fructose, and trehalose.

18 . The preservative composition of claim 11 , wherein the sugar comprises trehalose.

19 . The preservative composition of claim 11 , wherein the salt comprises about 60% or less wt percent choline dihydrogen phosphate.

20 . A composition comprising:
a living biomaterial, and a preservative composition comprising a sugar or sugar alcohol and a salt comprising choline hydrogen phosphate (HPO 4 −2 ), wherein the preservative composition is in an amorphous state and wherein the amount of time to formation of crystals in the presence of moisture is increased over the amount of time to crystal formation in a composition comprising the biomaterial without the preservative composition.

21 . The composition of claim 20 , wherein the pH is about 7.4 or greater and wherein the salt in the preservative composition comprises about 50% or less of choline dihydrogen phosphate.

22 . The composition of claim 20 , wherein the sugar is trehalose.

Assignees

• Univ North Carolina Charlotte

Inventors

• Elliott Gloria
• Bagheri Babak

Classifications

• C12N1/04

  Preserving or maintaining viable microorganisms (immobilised microorganisms C12N11/00) · CPC title

• A23B2/779

  Sugars; Derivatives thereof · CPC title

• A23B2/775

  Organic compounds containing phosphorus · CPC title

• A01N1/128 Primary

  Chemically defined matrices for immobilising, holding or storing living parts, e.g. alginate gels; Chemically altering living parts, e.g. by cross-linking · CPC title

• A61K47/186

  Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide · CPC title