Heat-sterilized formulation comprising chitosan and process of preparation thereof
The present invention relates to a heat-sterilized aqueous composition comprising a solubilized chitosan and glycerol. It also relates to a process of preparation of the same, as well as the use thereof, including compositions useful for the prevention and treatment of dry eye syndrome and arthritic diseases or disorders.
1. A process for preparing a heat-sterilized aqueous composition comprising solubilized chitosan and glycerol, wherein said composition is a clear and viscous solution, at a pH between 6 and 7.5, wherein said process comprises the following steps:
(i) solubilizing chitosan having an average molecular weight ranging from about 10 kDa to about 250 kDa and a degree of deacetylation higher than 60% in an aqueous solution of a weak acid comprising a carboxylic group, wherein the molar ratio between the carboxyl group (—COOH) of said weak acid and the amine group (—NH 2 ) of said chitosan is between 1:0.9 and 1:1.1;
(ii) adding glycerol;
(iii) adjusting the pH to a pH between 6 and 7.5 by addition of an aqueous solution of weak base; and
(iv) steam sterilizing;
thereby forming a heat-sterilized composition comprising solubilized chitosan and glycerol that is a clear and viscous solution at a pH between 6 and 7.5.
2. The process according to claim 1 , wherein said weak acid is lactic acid.
3. The process according to claim 1 , wherein the weak base is selected from sodium succinate and potassium sorbate.
4. The process according to claim 1 , wherein:
in step (i), said chitosan is present at a concentration between 0.05 and 3% (w/w), and said weak acid is lactic acid present at a concentration between 0.12 and 0.22% (w/w),
in step (ii), said glycerol is present at a concentration between 0.4 and 1% (w/w), and
in step (iii), said weak base is sodium succinate present at a concentration between 1.0 and 1.7% (w/w).
5. The process according to claim 1 , wherein said chitosan of step (i) has an average Molecular Weight (MW) ranging from about 150 to about 180 kDa and a degree of deacetylation (DD) between 60% (mol) and 75% (mol).
6. The process according to claim 1 , wherein said chitosan of step (i) is a chitosan of fungal origin.
7. The process according to claim 1 , wherein the chitosan is solubilized under step (i) in an aqueous solution of weak acid further comprising a solubilized pullulan.
8. The process according to claim 1 , wherein the molar ratio between the carboxyl group (—COOH) of said weak acid and the amine group (—NH 2 ) of said chitosan is between 1:1 or 1:1.05.