Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Scleroproteins – e.g. – fibroin – elastin – silk – etc.
Patent
1995-06-16
1998-06-09
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Scleroproteins, e.g., fibroin, elastin, silk, etc.
530402, 530408, 530410, 424443, 424444, 424445, 424484, 602 42, 602 43, 602 48, 602 50, A61K 3817, A61K 970, C07K 1300
Patent
active
057635790
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to new collagen derivatives, in particular which can be cross-linked and which are capable of being used, especially in the preparation of biomaterials, from which products, which are applicable especially in medicine and more particularly in surgery or cosmetics, can be obtained.
Among these products, there may be mentioned artificial tissues or organs such as artificial skin, bone, ligament, cardiovascular or intraocular prostheses or implants and the like, or alternatively bioencapsulation systems (implants, microspheres and microcapsules) which permit the controlled release of active ingredients in vivo.
As example, there may also be mentioned medical accessories such as suture threads or coatings for the biocompatibilization of implantable medical items.
The invention also relates to processes for producing these new collagen derivatives as well as new intermediate products which are involved in the abovementioned process and, finally, the cross-linked collagen derived from the cross-linkable collagen which is among the new collagen derivatives conforming to the invention.
The field of the invention is that of biocompatible materials based on collagen, which are useful as raw material for the production of items intended to be placed in contact with or implanted in the human or animal body and which are capable of becoming perfectly assimilated into the biological materials, especially from the mechanical point of view, so as to be able to replace them.
Collagen is a known protein which is present at all levels of the organization of the connective tissues: it is the principle protein of the skin and the connective tissue. By nature, it has biochemical and physico-chemical characteristics which are relatively quite suitable for uses as biomaterials.
For the purposes of the resent invention, the term collagen designates any peptide of collagenic nature, such as collagen, denatured collagen and gelatin.
PRIOR ART
Various qualities of collagen of animal or human origin are currently marketed world-wide, essentially for the elaboration of biomaterials or cosmetic products.
In the applications which are currently widespread, the properties of the various qualities available are sufficient.
Thus, among these collagens, there are excellent supports for cell adhesion, multiplication and growth, which are valued for the production of cell culture media.
Advantage is also taken of their hydrophilicity, their low immunogenicity, their high resistance to proteolysis and their hemostatic character.
The mechanical properties of native collagens are acceptable for a number of uses.
Nevertheless, it has to be recognized that, in the field of implantable medical items such as implants and prostheses, the native collagens on the market suffer major defects with respect to their mechanical resistance and their resistance to proteolysis.
Indeed, the introduction of these foreign bodies, which implants and prostheses represent, into a living organism induces rejection phenomena which result especially in inflammatory reactions causing, inter alia, the production of collagenase, which hydrolyzes collagen. This results, at the very least, in an alteration of the mechanical behavior of the collagen-based transplant.
It is known that cross-linking makes it possible to improve the mechanical properties of collagen. It confers a very high tensile strength, tear strength and resistance to enzymatic degradation on the collagen fibers by virtue of the numerous covalent bonds which it creates between the collagen chains.
On the basis of this scientific knowledge, numerous studies have been undertaken in order to develop the possibilities of artificial cross-linking of collagen.
Three main types of techniques for cross-linking this protein thus emerged.
The first type of technique is cross-linking by means of a bridging agent in which the exogenous molecules, which are most often bifunctional, react in order to allow the formation of bonds. The reagents most frequently used are:
Mono
REFERENCES:
patent: 3111512 (1963-11-01), Benesch et al.
patent: 4294241 (1981-10-01), Miyata
patent: 4407787 (1983-10-01), Steinberger
patent: 5219895 (1993-06-01), Kelman et al.
patent: 5412076 (1995-05-01), Gagnieu
Gagnieu Christian
Nicolas Florence
Soula Gerard
Flamel Technologies
Mohamed Abdel A.
Tsang Cecilia J.
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