Process for the coating of objects with hyaluronic acid, derivat

Coating processes – Direct application of electrical – magnetic – wave – or... – Pretreatment of substrate or post-treatment of coated substrate

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427387, 427409, 4274121, B05D 306

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061299561

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BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention concerns processes of coating the outer surfaces of objects with hyaluronic acid and its derivatives or other natural or semisynthetic polymers for applications in the fields of surgery, health care and diagnostics. According to this process it is possible to bind the polymer in a stable manner to the surfaces of objects made of a wide range of materials. Surfaces treated by the processes described in the present invention are characterized by a high degree of wettability and slipperiness in an aqueous environment, and improved properties in interactions with biological phases. For example, they are able to inhibit the adhesion of cells or bacteria present in the biological fluids.


BACKGROUND OF THE INVENTION

Hyaluronic acid is a natural mucopolysaccharide present at varying concentrations in practically all tissues. As any expert in the art knows, aqueous solutions of hyaluronic acid or of the salts or derivatives thereof, or of polysaccharides in general, are characterized by notable viscosity, slipperiness, and ability to reduce friction, a characteristic which is at the basis of the presence and function of polysaccharides of the same family as hyaluronic acid in the bodies of humans and other animals (Michels R. G. et al., "Sodium hyaluronate in anterior and posterior segment surgery". Physicochemical and Pharmacological Characteristics of Hyaluronic Acid, 1-15, 1989)
Because of these qualities, polysaccharides of the same family as hyaluronic acid (both natural polysaccharides and those obtained by chemical synthesis on natural compounds) have been widely researched. In particular, great effort has been put into identifying methods by which thin layers of hyaluronic acid (Hyalectin fraction, as described in European patent No. 0138572) or the derivatives thereof (U.S. Pat. No. 4,851,521) can be permanently fixed to the surface of other materials. The aim of this research was to create objects with improved surface properties, while maintaining the overall characteristics of the material of which they are made (said material will hereafter be referred to as the substrate). In particular, because of their high degree of hydrophilia, hyaluronic acid and the derivatives thereof are especially suitable for making objects whose use requires that their surfaces resist adhesion to the cell species present in the tissues or biological fluids. Such surfaces are of particular interest in applications wherein adhesion between materials and cells can cause damage to biological tissues (Kaufman, H. E. et al., Science, 189, 525, 1977).
Modification of the surfaces of materials with hyaluronic acid or the derivatives thereof has proved difficult for many researchers. One of the first things one notices is that hyaluronic acid solutions have a rather high surface tension, the same as or slightly less than that of water (F. H. Silver et al., Journal of Applied Biomaterials, 5, 89, 1994). It is well known that to obtain a homogeneous coating by the application of a solution, the applied material must have a surface tension which is lower than that of the substrate in order to obtain complete, even coverage. Moreover, almost all polymer materials which can be used as substrates present a surface tension which is lower than that of water, a characteristic which prevents the formation of a thin layer of hyaluronic acid covering the substrate evenly (Garbassi F. et al., "Polymer Surfaces, from Physics to Technology", Wiley, Chichester, 304, 1994).
It should be noted that hyaluronic acid is water soluble, so any objects obtained by simply coating them with a layer of hyaluronic acid solution instantly lose their coating on contact with aqueous solutions, including biological fluids. Hyaluronic acid derivatives, even those which are not water soluble, are in any case extremely hydrophilic and have a strong tendency to swell in the presence of water or aqueous solutions (H. N. Joshi and E. M. Topp, International Journ. of Pharm. 80 (1992) 213-225). In aqueous environments, this

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JP 59183762 Sep. 25, 1993-Abstract.

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