Coating processes – Medical or dental purpose product; parts; subcombinations;... – Implantable permanent prosthesis
Reexamination Certificate
1998-11-12
2001-02-13
Nakarani, D. S. (Department: 1773)
Coating processes
Medical or dental purpose product; parts; subcombinations;...
Implantable permanent prosthesis
C427S002300, C427S002310, C427S333000, C428S333000, C428S426000, C428S447000, C428S457000, C428S522000, C606S076000, C606S077000, C623S001460
Reexamination Certificate
active
06187369
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to the field of treating substrates to make them exceptionally hydrophilic and lubricious. The substrates so treated are intended especially for use in devices which are implanted in the body, but can be used in other applications.
It is important that any artificial device, which is implanted in the body, be biocompatible, highly lubricious, and wettable. Examples of devices which are permanently implanted include, but are not limited to, stents, intraocular lenses, and artificial pacemakers. Examples of devices which are temporarily implanted include, but are not limited to, contact lenses, vascular catheters and guidewires, and vascular introducers.
Coatings which increase the wettability of an underlying substrate are also useful in fields outside of medicine. For example, divers' goggles and masks, and eyeglasses used in water sports, are advantageously treated to make them more hydrophilic. As the objects become more hydrophilic, the contact angle, defined as the angle between the surface of the object and a tangent to the surface of a bead of water resting on the object, becomes relatively low. Divers' goggles or masks, when so treated, show minimal fogging in humid conditions. Eyeglasses so treated tend to provide undistorted vision, even when wet with water spray or snow.
Various means of imparting lubricity and wettability to surfaces have been proposed. Water-soluble polymers such as polyvinyl pyrrolidone and crosslinkable copolymers of N-vinyl pyrrolidone have found limited use as hydrophilic coatings, but these coatings have not been fully satisfactory, from the perspective of performance and durability.
Much attention has been given to ways of using the polysaccharides such as hyaluronic acid, heparin, and chondroitin sulfate, as components of coatings with good lubricity and wettability. U.S. Pat. Nos. 4,801,475 and 5,023,114, the disclosures of which are hereby incorporated by reference herein, disclose the application of such mucopolysaccharides as top coats grafted onto base coats with good adhesion and modulus matched to that of the substrate.
In the so-called “Carmeda” process, a polyamine such as polyethylenimine (PEI) is deposited on the substrate and a fragment of heparin carefully isolated to contain the antithrombotic active center, and terminated with an aldehyde group, is anchored on the substrate by formation of a Schiff base. Schiff bases can readily revert to the original aldehyde and amine, and the composition may be stabilized finally by chemical reduction.
U.S. Pat. Nos. 5,336,518 and 5,356,433, the disclosures of which are also incorporated by reference herein, show the attachment of heparin or other mucopolysaccharide to amine-functionalized surfaces of metals such as those used in the construction of stents, by use of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (EDC) or other carbodiimide. However, it has been shown (see Prestwick et al, Bioconjugate Chemistry, 1991, Vol. 2, pages 232-241) that under very similar conditions, none of the expected intermolecular coupling of hyaluronic acid with the amine occurs, but rather, hyaluronate-acylureas are produced. In a study of the attempted attachment of hyaluronic acid and chondroitin sulfate to amine-functionalized polystyrene, it has been speculated (see Hildreth et al, Anal. Biochem., 1996, Vol. 233, pages 216-220) that the much higher viscosity of hyaluronic solutions may be responsible for lower rates of attachment than with chondroitin sulfate solutions.
The use of hyaluronic acid, coupled to amine-functionalized surfaces, has several disadvantages. The attachment of hyaluronic acid is subject to variable results and low yields, and the high cost of suitable grades of hyaluronic acid limits its practical use to a few applications. The effective cost of hyaluronic acid is increased by the fact that solutions of polysaccharides have only short life before being attacked by microorganisms. A further problem with polysaccharide coatings is that they cannot be sterilized by gamma-radiation or by an electron beam without a serious loss in lubricity.
Other water-soluble polymers of very high molecular weight and viscosity, such as carboxymethyl cellulose and hydroxypropyl methyl cellulose, have also been used as components of hydrophilic coatings. A major disadvantage of these materials is that their high molecular weight makes their viscosity high. To counteract the high viscosity, one must reduce the concentration of the materials, but doing so may lead to the formation of unacceptably thin coatings on the substrate.
The present invention provides a simple, economical, and effective method of providing a hydrophilic and lubricious coating on a substrate. In the present invention, a substrate is coated with an inexpensive material of low molecular weight, but the resulting coating is at least as lubricious, hydrophilic, and durable as coatings formed with more expensive materials of high molecular weight.
SUMMARY OF THE INVENTION
The present invention includes a method of imparting lubricity and wettability to a substrate. The method comprises the principal steps of treating the substrate so that the substrate becomes amine-functionalized, and chemically joining an aldonic acid to amine groups on the substrate.
In the preferred embodiment, the chemical joining is performed by mixing aldonic acid with a coupling agent, which can be a water-soluble carbodiimide, such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The pH of the mixture is adjusted until the pH stabilizes. Then the mixture is brought into contact with the substrate, at room temperature. Components of the aldonic acid and the coupling agent react with the amine groups on the substrate, such that the substrate becomes coated with aldonic acid amide. The components which do not form part of the aldonic acid amide can be washed away and discarded.
The substrate is preferably amine-functionalized by exposing the substrate to a plasma, so as to activate its surface, and then exposing the substrate to a material containing amine groups, such as polyethylenimine (PEI). The substrate can be pre-treated with a highly adherent material, such as acrylic acid polymers or copolymers, to promote the adherence of the amine groups to the substrate.
The invention also includes a substrate which has been treated according to the method described above. The substrate can be metal, glass, plastic, rubber, or other material.
The invention is especially useful in forming coatings of objects that are intended to be temporarily or permanently implanted in the human body. The invention is not limited to such uses, however.
The invention therefore has the primary object of providing a method of imparting a highly lubricious and wettable coating to a substrate.
The invention has the further object of providing a method as described above, wherein the method uses materials of relatively low molecular weight.
The invention has the further object of improving the lubricity and wettability of hydrophilic coatings applied to various kinds of substrates.
The invention has the further object of reducing the cost of providing a lubricious and wettable coating.
The invention has the further object of enhancing the performance of various objects which are temporarily or permanently implanted into the human body.
The invention has the further object of providing a coated substrate having the desirable properties described above.
REFERENCES:
patent: 5409696 (1995-04-01), Narayanan et al.
“Chemical Modification of Hyaluronic Acid by Carbodiimides”, Kuo et al,Bioconjugate Chem.'91, vol. 2, pp. 232-241.
“Assess. of Cell Binding to Hyaluronic Acid in a Solid-Phase Assay”, Lee Guo et al,Anal. Biochem., '96, vol. 233, pp. 216-220.
Biocoat Incorporated
Eilberg William H.
Nakarani D. S.
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