Method for Preparing a Sterile Hydrogel Comprising a Cross-Linked or Non-Crosslinked Polysaccharide or a Mixture Thereof
AssigneeTeoxane
InventorsRomain BRUSINI, Camille VANTOU, Killian FLEGEAU, Laura Jing JING, Jimmy FAIVRE, François BOURDON
Life of this patent
Estimating the term…
Abstract
The present invention concerns a sterile hydrogel comprising a cross-linked polysaccharide, a non-cross-linked polysaccharide or a mixture thereof, in particular comprising a cross-linked hyaluronic acid, a non-cross-linked hyaluronic acid or a mixture thereof, and further comprising zinc and citrate ions, as well as a method for preparing same.
Claims20
A method for preparing a sterile hydrogel comprising a cross-linked polysaccharide, a non-cross-linked polysaccharide, or a mixture thereof, and further comprising zinc ions, the method comprising the following steps:
- (1) preparing a hydrogel comprising a cross-linked polysaccharide, a non-cross-linked polysaccharide, or a mixture thereof, the hydrogel preparation comprising the following steps:
- contacting the cross-linked polysaccharide, non-cross-linked polysaccharide or mixture thereof with a physiological saline solution, comprising phosphate or carbonate or sulfate salts or mixtures thereof,
- adding citrate ions to the cross-linked polysaccharide, non-cross-linked polysaccharide or mixture thereof in a quantity sufficient to obtain a citrate ion concentration of at least 0.1 mM in the hydrogel,
- adding zinc ions to the cross-linked polysaccharide, non-cross-linked polysaccharide or mixture thereof in a quantity sufficient to obtain a zinc ion concentration of at most 20 mM in the hydrogel,
- the addition of citrate ions and zinc ions being carried out in a molar ratio of [citrate ions]/[zinc ions] ranging from 1 to 20, and
- provided that the addition of zinc ions is not carried out before the addition of citrate ions when contact with the physiological saline solution, is carried out before the addition of citrate ions,
- (2) sterilizing, the hydrogel obtained at the end of step (1) to obtain a sterile hydrogel comprising a cross-linked polysaccharide, a non-cross-linked polysaccharide or a mixture thereof and further comprising zinc ions.
A method for preparing a sterile hydrogel comprising a cross-linked polysaccharide, and further comprising zinc ions, the method comprising the following steps:
- (0) preparing a cross-linked polysaccharide from a cross-linking reaction medium comprising one or more polysaccharides, one or more cross-linking agents, a solvent and zinc ions in a quantity permitting the preparation of a hydrogel comprising at most 20 mM zinc ions;
- (1) preparing a hydrogel from the cross-linked polysaccharide obtained at the end of step (0), the preparation of the hydrogel comprising a step of contacting the cross-linked polysaccharide with a physiological saline solution comprising phosphate or carbonate or sulfate salts or mixtures thereof;
- (2) sterilizing, the hydrogel obtained at the end of step (1) to obtain a sterile hydrogel;
- wherein:
- the cross-linking reaction medium further comprises citrate ions in a quantity sufficient to obtain a concentration of citrate ions of at least 0.1 mM in the hydrogel, the molar ratio of [citrate ions present in the reaction medium]/[zinc ions present in the reaction medium] ranging from 1 to 20;
- or
- step (1) also comprises, before the step of contacting the cross-linked polysaccharide with the physiological saline solution a step of adding citrate ions in a quantity sufficient to obtain a concentration of citrate ions of at least 0.1 mM in the hydrogel, the molar ratio of [added citrate ions]/[zinc ions present in the reaction medium] ranging from 1 to 20;
- or
- the physiological saline solution buffered further comprises citrate ions in a quantity sufficient to obtain a concentration of citrate ions of at least 0.1 mM in the hydrogel, the molar ratio of [citrate ions present in the physiological saline solution]/[zinc ions present in the reaction medium] ranging from 1 to 20.
A method for preparing a sterile hydrogel comprising a cross-linked polysaccharide and further comprising zinc ions, the method comprising the following steps:
- (0′) preparing a cross-linking reaction medium comprising:
- one or more polysaccharides,
- one or more cross-linking agents,
- citrate ions in a quantity sufficient to obtain a citrate ion concentration of at least 0.1 mM in the hydrogel,
- zinc ions in a quantity allowing the preparation of a hydrogel comprising at most 20 mM zinc ions, and
- a physiological saline solution comprising phosphate or carbonate or sulfate salts or mixtures thereof;
- the molar ratio of [citrate ions present in the reaction medium]/[zinc ions present in the reaction medium] ranging from 1 to 20,
- the reaction medium being prepared by addition of citrate ions before any contact of zinc ions with the physiological saline solution;
- (0) preparing a cross-linked polysaccharide from the reaction medium obtained at the end of step (0′);
- (1) preparing a hydrogel from the cross-linked polysaccharide obtained at the end of step (0) saccharide;
- (2) sterilizing the hydrogel obtained at the end of step (1) to obtain a sterile hydrogel.
A method for protecting a hydrogel comprising a cross-linked polysaccharide, a non-cross-linked polysaccharide or a mixture thereof, and additionally zinc ions, from degradation of its rheological properties during sterilization by addition of citrate ions in the hydrogel.
A method for preserving the stability over time of the rheological properties of a hydrogel comprising a cross-linked polysaccharide, a non-cross-linked polysaccharide or a mixture thereof, and additionally zinc ions by addition of citrate ions in the hydrogel.
A method for protecting a hydrogel comprising a cross-linked and/or non-cross-linked polysaccharide from degradation of its rheological properties during sterilization by addition of a solution comprising citrate ions and zinc ions in the hydrogel.
A method for preserving the stability over time of a hydrogel comprising a cross-linked polysaccharide, a non-cross-linked polysaccharide or a mixture thereof by addition of a solution comprising citrate ions and zinc ions in the hydrogel.
Dependencies are inferred from the claim text.