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
1991-10-07
1993-11-23
Wityshyn, Michael G.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Scleroproteins, e.g., fibroin, elastin, silk, etc.
530333, C08H 106, A61L 2700
Patent
active
052645517
DESCRIPTION:
BRIEF SUMMARY
The present invention essentially relates to a process for cross-linking of collagen by diphenylphosphorylazide, the cross-linked collagen thus obtained as well as the collagen-based biomaterials thus cross-linked.
It is known that collagen constitutes one third of the proteins in the living being. Its low immunogenicity, its effect on cell development and its high mechanical properties make it definitely advantageous as a raw material for biomaterials. However, when it is implanted, it suffers a more or less rapid degradation depending on the form that it takes (solutions, sponges, films or native tissues), on the implantation site and on the animal species. Said collagen degradation is sometimes desirable (healing dressings), sometimes inconvenient, (bioprosthestic valves, vascular prosthese, etc.).
On the other hand, collagen degradation is a normal process which is part of the growth, of the development and of the renewing of the connective tissues. It is also an integral part of the healing process. Said collagen degradation is caused by a certain number of enzymes, particularly the collagenases which are responsible for the initial attack on the native collagen with the neutral pH. They are said to cleave the three peptide chains simultaneously. The cleavage takes place between the GLY-LEU or GLY-ILE residues. However, It is at present admitted that such degradation requires the cooperative effects of a number of enzymes among which the stromelysin, the gelatinases.
The great advantage, when collagen is used as biomaterial, is to be able to modulate the biodegradability of the collagen depending on the proposed use. Said biodegradability can be modulated in at least two ways which consist either in the addition of enzyme inhibitors (such as .alpha.-2-macroglobulin or .beta.-1-anticollagenase), or in the introduction of chemical cross-linking bonds between the collagen molecules. This second method is the most widely because being more efficient as regards the resistance to enzyme degradation. The cross-linking bonds may be obtained either by physical methods which have the advantage of not introducing any chemical agent in the tissue, but which have proved to be rather inefficient, or by chemical methods which are efficient but leave traces of cross-linking agent in the tissue. Thus, glutaraldehyde (abbreviated to GTA) is the cross-linking agent most widely used, unfortunately it has the property of polymerizing when in solution. This is how, during cross-linking of the collagen, there is formation of GTA polymers, which, with time, will salt out GTA monomers (which latter are cytotoxic at concentrations higher than 10-25 ppm) into the surrounding tissues, while making the collagen lose part of its biological properties for which it had been chosen.
In order to avoid using glutaraldehyde, the present inventors has already proposed, in document FR-A-8710317, a process for cross-linking of collagen by the introduction of the azide groups on the carboxyl groups of the side chains of collagen. In this document, the cross-linking was performed by esterifying the collagen carboxylic groups, after what the esters were successively converted into hydrazides, and then into acylazides. Finally, the acylazides reacted in basic medium with the amino functions of the side chains of the collagen in order to give peptide-type bonds. Said process, although very innovating, has the disadvantage of taking a long time since the cross-linking of the collagen takes 8 days and is unpractical to use on an industrial scale.
The present inventors have continued their research with a view to simplifying the cross-linking method without introducing a cross-linking agent in the finished material and while obtaining a degree of collagen cross-linking equivalent to that obtained with the process described in document FR-A-8710317.
Thus, it is the object of the present invention to solve the new technical problem consisting in providing a process for cross-linking collagen which is simplified while not introducing a cross-linking
REFERENCES:
patent: 3873509 (1975-03-01), Mequro
patent: 4755593 (1988-07-01), Laurea
Huc Alain
Menasche Philippe
Petite Herve
Bioetica
Touzeau P. Lynn
Wityshyn Michael G.
LandOfFree
Process for cross-linking of collagen by diphenylphosphorylazide does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for cross-linking of collagen by diphenylphosphorylazide, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for cross-linking of collagen by diphenylphosphorylazide will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1850107