Coating processes – With post-treatment of coating or coating material – Heating or drying
Reexamination Certificate
2000-11-09
2002-05-14
Cameron, Erma (Department: 1762)
Coating processes
With post-treatment of coating or coating material
Heating or drying
C427S002240, C623S926000
Reexamination Certificate
active
06387450
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a lubricious, biocompatible, biomimetic coating composition, which may be applied to a substrate in one step, comprising hyaluronic acid or a salt thereof, a blocked polyisocyanate, and a solvent, particularly water. The invention also relates to a method for producing the lubricious, biocompatible, biomimetic coating.
BACKGROUND OF THE INVENTION
It has long been known that hydrophilic coatings with low friction (coefficient of friction of 0.3 or less) are useful for a variety of medical devices such as catheters, catheter introducers and the like. When low friction surfaces are used, the devices, upon introduction into the body, slide easily within arteries, veins, cannula and other passageways and body orifices. There have been a wide variety of methods used to provide the surfaces desired. In some cases the material of the catheter or medical device is formed of a material having inherently good anti-friction properties, such as poly(tetrafluoroethylene) or other plastics. However, in many cases the selection of materials does not provide the properties desired in conjunction with other desirable properties for the particular medical device.
Prior art hydrophilic coatings typically rely on a two step, two coating process, usually involving a primer coat of isocyanate or isocyanate/polymer blend which is dried, followed by a second coat containing at least one hydrophilic polymer such as polyvinyl pyrrolidone or poly(ethylene oxide). The two coatings, one superimposed on the other, are then baked to effect a cure. This forms an interpolymer complex or a network including the hydrophilic polymer.
Prior patents have suggested applying solutions of polyvinylpyrrolidone with isocyanate and/or polyurethane in multi-step operations. These coatings often lack good durability. For example, U.S. Pat. No. 4,585,666 issued to Lambert discloses medical devices having hydrophilic coatings formed from an isocyanate layer overcoated with a polyvinylpyrrolidone layer. However, the multistep procedure makes it difficult to tailor the properties and values of the final coatings.
U.S. Pat. No. 5,356,433, Rowland et al., describes a two step method for preparing metal surfaces of medical devices with enhanced biocompatability properties. The method includes covalently linking an organosilane compound having amine reactive sites with the metallic surface of the medical device. A biologically active agent is covalently linked to the organosilane compound.
U.S. Pat. No. 5,607,475, Cahalan et al., discloses a two step method for preparing a metal or glass surface of a medical device with improved biocompatibility. The method includes applying to the surface of a medical device a silane compound having a pendant vinyl functionality such that the silane adheres to the surface. A graft polymer is then formed on the surface with vinylsilane such that the pendant vinyl functionality of the vinylsilane is incorporated into the graft polymer by covalent bonding with the polymer. Biomolecules are then covalently bonded to the graft polymer.
U.S. Pat. No. 5,037,677, Halpern et al., describes a two step method of interlaminar grafting of coatings upon an object, such as a plastic medical device, in order to bond sodium hyaluronate to the surface of the object. The method includes coating the object with an anchor coat containing an acrylic polymer having a grafting functionality in a solvent. The grafting functionality may be an isocyanate group. The object is then coated with an aqueous solution containing sodium hyaluronate. The coatings are heated and the grafting functionality in the anchor coat reacts with the sodium hyaluronate to form covalent bonds resulting in interlaminar grafting. The isocyanate groups, however, easily react with atmospheric moisture thereby becoming less available or unavailable for reaction with the sodium hyaluronate resulting in a poor coating.
There are several disadvantages to the two step process. First, the exact ratio of primer material to the hydrophilic polymer is difficult to control, as it depends on the amounts of primer and hydrophilic polymer which happen to be deposited by the wet film during the respective coating steps. Second, the primer may begin to redissolve in the second coating solution, causing some loss of primer and further resulting in difficulty in controlling the primer/hydrophilic polymer ratio. Third, since the hydrophilic polymer is not covalently bonded to the substrate, it may bond to other materials in the area, leading the coating to lose its desired properties. Fourth, additional facilities, time, and cost are needed for coating with a two step process, as is compared to a one step process.
The present invention provides a coating having hyaluronic acid which may be applied in a single step, alleviates the need for a primer or coupling agent, and can be applied on various substrates, including, but not limited to, metals and plastics.
Hyaluronic acid is a biopolymer which is present in the human body in body fluids, joints, and mucous membranes. The biological functions of hyaluronic acid include protection, lubrication and separation of cells, regulation of transport of molecules and cell metabolites, and maintenance of the structural integrity of connective tissues and fluid retention intercellular matrix.
SUMMARY OF THE INVENTION
The present invention provides a coating composition comprising hyaluronic acid or a salt thereof and a blocked polyisocyanate in a solvent comprising water.
According to another embodiment of the present invention, an article is provided comprising a substrate to which a coating composition comprising hyaluronic acid or a salt thereof and a blocked polyisocyanate in a solvent comprising water, is applied.
According to yet another embodiment of the invention, a method of preparing a coating on a substrate to be coated comprises forming a mixture of hyaluronic acid or a salt thereof and a blocked polyisocyanate in a solvent comprising water; applying the mixture to the substrate; and curing the mixture on the substrate to form the coating.
These and other features and objects of the invention are more fully appreciated from the following detailed description of a preferred embodiment of the invention.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
According to the present invention, a coating is formed from the reaction on a substrate to be coated of a mixture comprising hyaluronic acid or a salt thereof and a blocked polyisocyanate in a solvent. The solvent comprises water and, optionally, a water miscible cosolvent. The resulting coating is highly lubricious and thromboresistant.
The coating composition is prepared by weighing the appropriate quantities of hyaluronic acid or salt thereof, blocked polyisocyanate, and solvent into an appropriate mixing vessel. Additional solvents may be added to adjust the viscosity of the mixture. Solids contents in a range of from about 0.1 to about 25% and viscosities in the range of 50 cps to 500 cps are preferred. This solution is mixed well and then applied to an appropriate substrate, such as catheter tubes, medical tubing introducers, polymer coated medical wires, stents, guide wires, and dilatation balloons, by conventional coating application methods. Such methods include, but are not limited to, dipping, spraying, wiping, painting, and the like.
After applying the coating solution, the solvent is preferably allowed to evaporate from the coated substrate, such as by exposure to ambient conditions for at least 5 minutes.
The coating is subsequently cured. The cure time, temperature, and humidity vary with the choice of hyaluronic acid or salt thereof, blocked polyisocyanate, solvent, and the composition of the substrate. The ratio of ingredients in the coating mixture also affects the physical properties of the overall coating. The amount of sodium hyaluronate controls the lubricity of the coating. The amount of blocked polyisocyanate controls the flexibility of the coating.
Cure temperatures may range from about 120° C. to
Hudson John A.
Shah Chirag B.
Tedeschi Eugene
Cameron Erma
Medtronic AVE Inc.
Sterne Kessler Goldstein & Fox P.L.L.C.
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