Conjugate, its preparation and use and a substrate prepared with

Details Conjugate, its preparation and use and a substrate prepared with Conjugate, its preparation and use and a substrate prepared with

1994-03-25

1996-06-25

Robinson, Douglas W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

514 55, 514 56, 514822, 536 20, 536 21, 536 187, 536124, 424422, 424423, 424427, A61K 31725, A61L 3300

Patent

active

055299865

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to a novel biologically active conjugate based upon sulphated glycosaminoglycan, a process of preparing the conjugate, a substrate whose surface has been prepared with such a conjugate, and a process of surface-preparation using the conjugate.
Sulphated glycosaminoglycans is the common name of a number of endogenous sulphated mucopolysaccharides, such as e.g. heparin, heparan sulphate, dermatan sulphate and chondroitin sulphate, which exhibit a number of different biological properties. While the invention relates to sulphated glycosaminoglycans generally, it will, however, in the following to a great extent be described with regard to the glycosaminoglycan that has so far found the greatest medical use, viz. heparin.
Heparin occurs naturally complex-bound to protein in various mammalian tissues, such as the intestine, liver and lung, as well as in mast cells, and has then a molecular weight which may extend up to 100,000, while commercially available preparations have a molecular weight varying between about 6,000 and 20,000 depending on the source and the determination method. It consists of alternating glucuronic acid and glucosamine units, and the anticoagulating effect has been shown to be linked to a specific pentasaccharide unit of the molecule which has antithrombin-binding properties.
Due to its anti-coagulating properties, heparin, which is usually prepared from intestinal mucosa from pig, has found use as an agent for dissolving thromboses, but perhaps above all for preventing the formation thereof. The latter is the case for inter alia procedures in, for example, the treatment of renal disease, open cardiac surgery and intensive care, which procedures involve treating the patient's blood in a circulating system outside the body, so-called extra-corporeal circulation (e.g. artificial kidneys, heart-lung machines, oxygenators), where the blood will get in contact with various materials foreign to the body.
To eliminate the clotting ability of the blood in such systems, and thereby avoid clogging by blood clots, high doses of heparin must be added to the blood. Due to the accompanying substantially increased risk of bleeding, which in the worst case may lead to life-threatening conditions, efforts have for a long time past aimed at trying to instead achieve the desired coagulation preventing effect by modifying the body-foreign material with which the blood will get in contact by surface-binding heparin thereto. Decisive factors which have stimulated this development are that the structure-activity relation of heparin has been elucidated, and that a heparin-like activity has been detected on the natural vascular wall. Thus, during the last few years several reports on successful extra-corporeal treatment with systems provided with surface-bound heparin have been published.
The surface-modification with heparin has, however, not been restricted the above mentioned contexts with extra-corporeal blood circulation, but has also come to be regarded as a more general solution to the problem of achieving biocompatibility of various devices within medical care which get in contact with blood and other body tissues. For example, surface-heparinization has also been used to improve the biocompatibility of intraocular lenses.
The hitherto used technical solutions to the problem of immobilizing heparin may be divided into two main principles, ionically and covalently bound heparin, which will be described in more detail in the following. To accomplish a surface which exhibits the desired biocompatibility based on immobilized heparin, it is important that heparin is immobilized such that its biological activity is maintained. As mentioned in the introductory part, the biological activity of heparin resides in a specific antithrombin-binding pentasaccharide structure which must remain intact after the immobilization on the surface to be capable of interacting with the constituents of the blood. In the majority of scientific articles and patents related to immobilization of heparin,

REFERENCES:
patent: 3810781 (1974-05-01), Eriksson et al.
patent: 4118485 (1978-10-01), Eriksson et al.
patent: 4239664 (1980-12-01), Teng et al.
patent: 4415490 (1983-11-01), Joh
patent: 4613665 (1986-09-01), Larm
patent: 4923980 (1990-05-01), Blomberg
Larm., Larson, Olsson. "A New Non-thrombogenic surface prepared by Selective Covalent Binding of Heparin via a Modified Reducing Terminal Residue." Marcel Dekker, Inc. 1984.

Affiliated with

Also associated with

Rating

Conjugate, its preparation and use and a substrate prepared with does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Conjugate, its preparation and use and a substrate prepared with, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Conjugate, its preparation and use and a substrate prepared with will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2188899