Degradation-stabilised, biocompatible collagen matrices
The present invention relates to degradation-stabilized, biocompatible collagen matrices which are distinguished in particular by the fact that they contain soluble collagen and peptide constituents, to processes for the preparation of such collagen matrices, which processes include in particular chemical crosslinking with an epoxy-functional crosslinking agent, and to the use of the collagen matrices according to the invention as a cosmetic or pharmaceutical agent, in particular for topical use, and as a wound treatment agent, as an implant or as a haemostatic agent in humans or animals, and as a scaffold for cell population in the biotechnology, basic research and tissue engineering field.
1. Process for the preparation of crosslinked collagen matrices, comprising the steps:
a) preparing an aqueous collagen suspension,
b) adjusting the pH value of the collagen suspension from step a) to pH<4,
c) optionally adding at least one of structure-forming agents, active ingredients and auxiliary substances,
d) adding an epoxy-functional crosslinking agent in an amount of not more than 50 wt. % based on the dry mass of the collagen suspension from step a), the order of steps c) and d) being variable,
e) freezing the collagen mixture obtainable from step d),
f) freeze-drying of the frozen mixture from step e) at a freeze-drying temperature<100° C.,
g) adjusting the freeze-dried crosslinked collagen material so obtained to a moisture content of from 3 to 25 wt. %, based on the end product, and
h) optionally converting the materials obtainable from step g) into a desired form to afford formed materials, and
i) at least one of sterilizing and processing the formed materials.
2. The process according to claim 1 , wherein the collagen suspension from step a) comprises native acid-insoluble collagen in the form of fibres and fibrils.
3. The process according to claim 1 , wherein the collagen suspension comprises acid-soluble collagen and peptide constituents and/or wherein in step c) structure-forming agents or active ingredients from the group of the matrix proteins, extracellular matrix constituents, proteinogenic active ingredients and soluble protein or peptide constituents are added.
4. The process according to claim 1 , wherein the epoxy-functional crosslinking agent is a diepoxide.
5. The process according to claim 1 , wherein the freezing according to step e) is carried out within 24 hours of the preparation of the collagen mixture from step d).
6. The process according to claim 4 , wherein the diepoxide is 1,4-butanediol diglycidyl ether.
7. The process according to claim 1 , wherein the epoxy-functional crosslinking agent is added in an amount of not more than 20 wt. %, based on the dry mass of the collagen suspension from step a).
8. The process according to claim 1 , wherein the epoxy-functional crosslinking agent is added in an amount of not more than 10 wt. %, based on the dry mass of the collagen suspension from step a).