Crosslinking of biopolymers in a semi-solid state
The present invention relates to methods of providing biocompatible/biodegradable hydrogels obtained by crosslinking of biopolymers (for example polysaccharides or proteins) in the semi-solid (modelling-clay like) state at water content below 70% by weight. The resulting materials can be applied in medicine, pharmacy and/or in cosmetics.
1. A method of producing a cross-linked biopolymer, comprising:
providing a polymer or a plurality of polymers as a powder;
mixing the polymer or the plurality of polymers with a crosslinker and an aqueous solution at a water content below 70 weight % to form a homogenous semi-solid, paste-like mass;
moulding the semi-solid, paste-like mass; and
performing a cross-linking reaction to obtain a solid body.
2. The method of claim 1 , further comprising micronizing the solid body to obtain microparticles.
3. The method of claim 1 , further comprising washing the solid body.
4. The method of claim 1 , wherein the mixing is carried out at ambient temperature.
5. The method of claim 1 , wherein the cross-linking reaction is carried out at higher temperatures compared to ambient temperature.
6. The method of claim 1 , wherein the mixing is carried out at lower temperatures compared to ambient temperature.
7. The method of claim 1 , further comprising adding one or more active ingredients before the crosslinking reaction.
8. A method of producing a cross-linked biopolymer, comprising:
mixing a biopolymer with an aqueous solution at a water content below 70 weight % to form a semi-solid mass;
placing the semi-solid mass into a crosslinker solution; and
performing a crosslinking reaction to form a crosslinked biopolymer matrix.
9. The method of claim 8 , further comprising adding one or more active ingredients before performing the crosslinking reaction.
10. The method of claim 8 , wherein the biopolymer comprises hyaluronic acid.
11. The method of claim 1 , comprising mixing the polymer or the plurality of polymers with a crosslinker to form a mixed powder, and then hydrating the mixed powder with the aqueous solution.
12. The method of claim 1 , wherein at least one of the polymers or the plurality of polymers is hyaluronic acid.
13. The method of claim 1 , wherein moulding comprises pressing the semi-solid, paste-like mass into a mould, and crosslinking is performed under continuous pressure.
14. The method of claim 1 , wherein mixing comprises grinding in a grinding mill.
15. The method of claim 14 , wherein mixing further comprises using an extruder.
16. The method of claim 1 , comprising mixing the polymer or the plurality of polymers with a crosslinker and an aqueous solution at a water content of 50 weight % or lower.