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Description  |
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CROSS-REFERENCES TO RELATED APPLICATIONS
The present application is directed to enhancing the aqueous solution of a
polysaccharide, such as hyaluronic acid and its salts, chondroitin
sulfate, agarose and the like. The enhanced solution provides uniform
wetting over the surface of an anchor film applied to plastics.
BACKGROUND OF THE INVENTION
(1) Field of the Invention
Hydrophilic coating of plastics, particularly a polysaccharide solution
which is enhanced by the addition of albumin to provide improved wetting
characteristics.
(2) Description of the Prior Art
Being separately submitted.
SUMMARY OF THE INVENTION
According to the present invention, aqueous solutions of polysaccharides
from the group comprising hyaluronic acid and its salts, chondroitin
sulfate, agarose and the like, are enhanced by the addition of albumin to
thoroughly wet the hydrophobic surface of a plastic, as well as an anchor
film which may be applied to the plastic.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Aqueous solutions of polysaccharides such as hyaluronic acid and its salts,
chondroitin sulfate, agarose, and the like, are well-known for their
viscous, slippery, lubricious nature which is responsible for their
utility in the body of man and other animals.
Various inventors have incorporated polysaccharides into compositions
intended for use as body implants or prostheses, for the purpose of
improving comfort of the wearer. Such compositions are heterogeneous,
polyphasic and opaque, because the polysaccharides are basically insoluble
and incompatible with the load-bearing components of a part such as an
implant or prosthesis. Such discontinuous dispersions may nevertheless be
of value for a limited period of time, as the polysaccharide is leached to
the surface of the part by aqueous body fluids and there acts to lubricate
the surface until it is carried away by body fluids. Eventually, of
course, the reservoir of polysaccharide is depleted, and its beneficial
effect on comfortable operation of the part is no longer exerted.
In some cases, inventors of such compositions have provided crosslinking of
the polysaccharide, so that it is not leached away and lost. In those
cases, however, it is obvious that the insolubilized polysaccharide in
reserve deposits below the surface of the part can no longer be leached to
the surface and might better not be present at all. Thus, the crosslinked
polysaccharide that happens to be at the surface of the part is not
providing a continuous, lubricating film, but on the contrary acts
relatively inefficiently, as small slippery spots here and there on the
surface of the part.
As described in the aforementioned copending application, applicants have
grafted continuous insolubilized films of polysaccharides onto the surface
of rigid materials, such as plastics and metals, so that formed parts are
endowed with excellent lubrication when wet. Furthermore, since the
continuous surface coating is grafted and crosslinked, the lubricating
effect is permanent and cannot be washed away. Still further, when the
underlying plastic body is transparent, the continuous surface coating is
also transparent and of excellent optical quality, so that lubricious
contact lenses and intraocular lenses can be fabricated in this manner
without harmful effects on the optical quality of the device.
According to application Ser. No. 643,598, the most useful procedure for
preparing such coated objects is first to apply an anchor coat on the
formed object of interest. This anchor coat will be of such composition as
to adhere strongly to the underlying body, with the appropriate degree of
flexibility to tolerate bending and twisting without failure, and to
provide reactive groups which will allow for chemical grafting to the
polysaccharide coat later applied. Such anchor coats may, for example, be
acrylic copolymers containing a multitude of hydroxyl, carboxyl, epoxy,
amino, or other functional groups for later reaction with appropriate
grafting agents.
However, when one attempts to prepare such articles, he encounters in many
cases certain natural obstacles that operate against and prevent
realization of the desired uniform coating. The first barrier is the
peculiar solubility of hyaluronic acid, of its salts, and of most other
polysaccharides of interest; i.e., the choice of solvents is limited
almost exclusively to water. With aqueous solutions of sodium or potassium
hyaluronate, viscosities are appropriate for conventional coating
processes when the solute concentration is in the range of 0.5 to 1.5%.
The corresponding viscosity is obtained with chondroitin sulfate at a
concentration of 5 to 20% in water.
When such solutions are applied to the surface of the anchor coat, the
second barrier is encountered: the aqueous solution does not wet the
hydrophobic surface, and the solution crawls into strings and isolated
droplets and pools. A useful, fully continuous, transparent film does not
form.
Applicants add small amounts of purified albumin, from about 0.1% to
several percent by weight of the polysaccharide, and so cause the aqueous
solution to flow uniformly over the surface of the anchor film, when
applied by conventional coating techniques, to produce useful, continuous,
transparent coatings or films. With appropriate grafting reagents, these
coatings or films can be anchored to the underlying anchor coat and become
permanent hydrophilic surfaces of great utility.
The albumin may be derived from any of a wide variety of plant and animal
tissues and fluids, but perhaps most often from the blood serum of
animals. The isolation and purification procedures used in isolating the
albumin from other proteins and lipids will determine the degree of purity
of the albumin produced, even to the extent that pure, crystalline product
can be obtained. According to the present invention, most conventional
grades of albumin are effective in achieving the flow and film uniformity
desired in this invention. However, other considerations may determine the
degree of purity to be preferred. For example, in the case of implanting a
coated medical device in the human body, it may be prudent to use a grade
of albumin that will not cause undesired immunological reactions. Methods
of isolating and purifying albumins have been detailed in the chemical
literature (e.g., E. J. Cohn, et al., J. Am. Chem. Soc., Vol. 68, pp.
459-475, 1968; ibid., Vol. 69, pp. 1753-1761, 1969; R. F. Chen, J. Biol.
Chem., Vol. 242, pp. 173-180, 1967).
The following examples are intended to illustrate, but not to limit the
invention.
EXAMPLE 1
A solution acrylic polymer comprising 7.5 mole-percent hydroxyethyl
methacrylate was applied at a wet thickness of approximately 3 mils to the
clean surface of a panel of polymethyl methacrylate. It was dried at a
temperature of 65 degrees Centigrade and at 20 inches of vacuum, for 25
minutes. When the panel had cooled to room temperature, an 0.5% aqueous
solution of "ultrapure" sodium hyaluronate (MedChem Products, Inc.) was
applied as a second coat intended to have 3 mils wet thickness also.
However, immediately after application, the wet film crawled and gathered
into strings and droplets scattered over the anchor coat. When the film
applicator was drawn over this surface a second time, the dispersed
solution was pulled together again to some degree, but it quickly crawled
again and was unable to form a continuous coating. When placed in the oven
at 65 degrees and 20 inches of vacuum for two hours, the final panel
showed a webbed pattern corresponding to the conformation of the wet
surface. The surface was not optically uniform, and the ability of the
surface to shed water appeared to be the same as that of a panel coated
only with the anchor coat.
EXAMPLE 2
Nine Plexiglas panels were coated with the same acrylic anchor coat as in
Example 1 and cured in the same manner. Onto one was then applied 3 mils
of the same hyaluronate solution as that described in Example 1, and onto
the other eight was applied the same hyaluronate solution containing one
of the following levels of bovine albumin (crystallized and lyophilized,
essentially free of fatty acids): 0.05%, 0.1%, 0.25%, 0.5%, 1.5%, 5%, 10%,
and 25%. The top coats containing 0% and 0.05% albumin crawled and
gathered into strings and droplets; all other panels had continuous
coatings with optical clarity and uniformity.
EXAMPLE 3
Example 2 was repeated in every respect, except that the polysaccharide was
chondroitin sulfate (7.5% solution in water). Again, the top coats
containing 0% and 0.05% (w/w on chondroitin sulfate) of albumin crawled
and gathered, but those containing higher levels of albumin were smooth
and uniform both before and after curing.
EXAMPLE 4
Two Plexiglas panels coated with the anchor coat and dried as in Example 1,
were coated with 1% aqueous solutions of potassium hyaluronate isolated
from submerged culture in "pure" form. The nominal 6-mil top-coat or film
on the first panel (contaning 0.% albumin) crawled and gathered and
produced a non-uniform coating of no value.
In the second panel, the aqueous solution applied as a topcoat contained
0.5% (w/w on hyaluronate) of the bovine albumin described in Example 1;
the applied top-coat did not crawl, but formed a smooth, uniform, clear
and transparent film with good lubricity and non-beading behavoir when
wetted.
EXAMPLE 5
Portions of 1% aqueous solution of potassium hyaluronate from human
umbilical cord (Sigma Chemical Company Grade III-P) were treated with
0.5%, 1.0% and 5% (w/w on hyaluronate) of chicken egg albumin
(crystallized and lyophilized; essentially salt-free: Sigma Chemical
Company Grade VI). All mixtures produced smooth, uniform top-coats when
knifed over the anchor coat described in Example 1.
EXAMPLE 6
An aqueous solution was prepared containing 0.5% of "pure" sodium
hyaluronate (MedChem Products, Inc.) and 0.5% (w/w on hyaluronate) of
human albumin (crystallized and lyophilized; essentially globulin-free.
When this solution was knifed onto the anchor coat described in Example 1
at a setting of 10 mils, a smooth, uniform, colorless, clear film was
obtained both before and after curing.
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