Solid substrate coated with an aminopolysaccharide

Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Processes of preparing a desired or intentional composition...

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604266, 21050024, 427 224, 427 227, 427 231, 427 21, 427339, 4274197, 4284111, 428421, 428422, 4284231, 4284234, 4284253, 428426, 428436, 428447, 428448, 428457, 428458, A61L 3300, C08J 704

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active

056681933

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to solid substrates, the surfaces of which have been modified to introduce reactive groups of a hydrophilic nature thereon. The invention also covers a method for preparing such solid substrates.


BACKGROUND OF THE INVENTION

In medicinal technology, such .as technology involving medicinal equipment such as devices for implantation or apparatus exposed to living tissue, it is often desirable to make the exposed surfaces compatible with the environment. This is often done by immobilizing biologically active compounds onto the exposed surfaces. This is usually made in two steps, viz. a first step of activating the surface in question and a second step of coupling the biologically active compound to the activated surface.
In the first step residing in activation which frequently takes place by the treatment using a polymeric compound, the introduced reactive and functional groups should be attached to the substrate by strong binding thereto. In the second step residing in the coupling the binding shall also be as strong as possible. However, the biological activity of the immobilized substance must not be impaired.
As examples of techniques for the immobilization of a biologically active compound onto the surface of for example hospital equipment are the immobilization of glycoseaminoglycans (GAGs) on intraocular eye lenses, certain wound dressings, orthopedic implants etc. Such immobilization of GAGs is usually performed in two steps, namely pretreatment of the surface to make it more reactive and/or hydrophilic, and immobilization of the molecule by ionic or covalent binding. In such pretreatment procedure a reagent or primer containing reactive amino functions is adhered to the surface. This reagent can be further stabilized by the addition of a crosslinking agent, usually by a functional organic substance.


BACKGROUND ART

The primers and crosslinkers hitherto used are usually prepared from materials of a non-biological origin and are of a non-biodegradable type. Examples of reagents are polyethylen imine and tridodecylmethylammonium chloride. Further details on this immobilization techniques are found in Hoffman J. Larm O. and Sholander S., A new method for covalent coupling of heparin and other glycosaminoglycans to substances containing primary amino groups, Carbohydrate Research (1983) 117, 328; Larm O., Larsson R. and Olsson P., A new non-thrombogenic surface prepared by selective covalent binding of heparin via a modified reducing terminal residue, Biomaterials, Medical Devices and Artificial Organs (1983) 11, 161.
The present invention has for a main object to provide new techniques for modifying surfaces to enable the introduction of reactive groups of a hydrophilic nature on such surfaces.
Another object of the invention is to provide new techniques for performing such modification using substances that are of a biological origin and also are of a biodegradable type.
Yet another object of the invention is to introduce reactive amino and/or hydroxyl groups suitable for covalent binding of biologically active substances to the surfaces involved.
Still another object of the invention is to provide new techniques enabling modification of surfaces to make said surfaces more hydrophilic by the introduction of functional groups that can be used for covalent coupling of biologically active substances to such surfaces.


SUMMARY OF THE INVENTION

Accordingly, the present invention provides a solid substrate, the surface of which has been modified to introduce reactive groups of a hydrophilic nature thereon. The modification of the surface is provided by a primer comprising a first polysaccharide containing as reactive groups amino and hydroxyl groups. Thus, it has been surprisingly found that such first polysaccharide can be effectively attached to the surface of solid substrates, and a particularly preferred embodiment of the invention is constituted by said first polysaccharide being chitosan.
Chitosan consists of 1,4-.beta.-bound D-glucosamine units. The

REFERENCES:
patent: 4326532 (1982-04-01), Hammar
patent: 4419444 (1983-12-01), Quash
patent: 4876126 (1989-10-01), Takemura et al.
"A Method for Covalent Coupling of Heparin and Other Glycosaminoglycans to Substances Containing Primary Amino Groups", James Hoffman et al., Carbohydrate Research, 117, (1983),, pp. 328-331.
"A New Non-Thrombogenic Surface Prepared by Selective Covalent Binding of Heparin Via a Modified Reducing Terminal Residue", Olle Larm et al., Biomaterials, Medical Devices and Artificial Organs, 11(2&3), pp. 161-173 (1983).

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