Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1988-01-27
1990-10-16
Griffin, Ronald W.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 2, 536 21, 536 47, 536 63, 536 55, 536 80, 536 98, 536106, 536112, 527300, 527301, C08B 3700, C08B 3708
Patent
active
049636669
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a chemically crosslinked material of polysaccharides which contain carboxyl groups. The process for producing this material provides a possibility of varying, within a wide range, the degradability of this material under physiological conditions.
Insoluble polymeric materials of varying degradability in physiological environments are useful for a broad spectrum of medical applications; for instance they may be employed for surgical implants, e.g. in order to prevent tissue adhesion, or for wound dressing bandages or for slow release depots of drugs.
A method commonly employed for producing insoluble polymeric materials involves covalent crosslinking of soluble polymers with bifunctional or polyfunctional reagents. Crosslinking of polysaccharides is often performed by reacting the hydroxyl groups of the polysaccharides in an alkaline aqueous solution with bi- or polyfunctional epoxides to thus bind the polysaccharide chains to one another via ether bonds, with concomitant formation of a gel. The ether bonds however are not degradable at a physiological pH; such a gel material therefore may prove to be very stable to degradation. An example of such an ether-bonded gel is given in Swedish patent application 8403090-7 which describes the use of a non-degradable crosslinked gel of hyaluronic acid as a vitreous humor substitute.
A process for producing degradable polysaccharide gels is described in Swedish patent application 8403817-3 according to which carboxyl groups of the polysaccharides are crosslinked with di- or polyfunctional epoxides by means of acid catalysis, whereby an insoluble gel is formed. In this case the bonds produced are ester bonds which in contrast to ether bonds are degradable in physiological environments; degradation times of such gels will typically be about 2 to 3 days.
The aforesaid gels, i.e. those produced under acid catalysis conditions and those produced under alkaline catalysis conditions, are manufactured and used in a swollen state; but the Swedish patent application SE 8501022-1 describes also methods for drying hyaluronic acid gels to thus obtain products of improved mechanical stability.
Dry films of hyaluronic acid are also known from the German patent application DE 3434082 which contains examples according to which hyaluronic acid and crosslinking agent are dried to form an insoluble product.
Although the method of SE 840317-3 allows for some variation in the degradation time of the resultant gel it will nevertheless be desirable to have a possibility of varying the degradation time within a wider range, and in a controllable manner.
We have now surprisingly found a novel method for producing gels of crosslinked polysaccharides by which it becomes possible inter alia to combine the aforesaid methods for acid- and base-catalyzed crosslinking so as to produce novel gel materials of controllable degradability. The present novel process moreover enables the crosslinking reaction to be carried out also with a low content of the activating reagent required for the crosslinking; this means that only very small amounts of residual reagent or degradation products thereof can potentially be released from the gel.
Such leakage from the gel may occur if the gel is used for a long period of time or in the course of controlled degradation, and is a factor to be taken into consideration in accordance with the particular environmental conditions in the practical use of the gel.
The principle of the manufacturing process is as follows: The polysaccharide containing carboxyl groups is at first reacted with a bi- or polyfunctional epoxide. This reaction may be performed in an alkaline, acidic or neutral medium and consists in a so-called epoxy-activation of the polysaccharide. The conditions chosen are such that no gel formation takes place in this stage; instead, the polysaccharide in this stage is still to be soluble. Next follows removal of excess epoxide i.e. of reagent that has not bound to the polysaccharide. Thereafter the polysaccharide is dried at a
REFERENCES:
patent: 3042667 (1962-07-01), Flodin et al.
patent: 3420788 (1969-01-01), Solms
patent: 4002173 (1977-01-01), Manning et al.
patent: 4076930 (1978-02-01), Ellingboe et al.
patent: 4370476 (1983-01-01), Usher et al.
patent: 4535152 (1985-08-01), Szejtli et al.
patent: 4713448 (1987-12-01), Balazs et al.
patent: 4716224 (1987-12-01), Sakurai et al.
patent: 4794177 (1988-12-01), Peska et al.
patent: 4814437 (1989-03-01), deBelder et al.
Griffin Ronald W.
Pharmacia AB
Philpitt Fred
LandOfFree
Material of polysaccharides containing carboxyl groups, and a pr does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Material of polysaccharides containing carboxyl groups, and a pr, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Material of polysaccharides containing carboxyl groups, and a pr will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-850655