WO2014052283A1

WO2014052283A1 - Polyether-polyamide plastics for surgical applications

Info

Publication number: WO2014052283A1
Application number: PCT/US2013/061336
Authority: WO
Inventors: Robert M. Braun; Orlando Manuel CABARCOS
Original assignee: Bausch & Lomb Incorporated
Priority date: 2012-09-25
Filing date: 2013-09-24
Publication date: 2014-04-03

Abstract

A Pebax substrate prepared by a process comprising: providing Pebax resin and removing oligomers from the Pebax resin by sonicating the Pebax resin in the presence of an organic solvent to provide clean Pebax resin substantially free of labile oligomer; and forming a Pebax substrate with the clean Pebax resin. The Pebax substrate can be in the form of an inserter tip used in conjunction with an intraocular lens inserter.

Description

POL YETHER-POLY AMIDE PLASTICS FOR SURGICAL APPLICATIONS

[0001] The present invention relates to polyether block polyamide plastics and chemical or physical treatments of the plastics for surgical applications. The invention also relates to a method of coating inserter tips used in the delivery of intraocular lenses.

BACKGROUND OF THE INVENTION

[0002] Devices used in medical or surgical applications, particularly disposable devices, are typically molded from plastics. Catheters and guide wires which are used for insertion through blood vessels, urethra or other body conduits require low-friction surfaces for preventing injury or inflammation of mucous membranes and for facilitating surgical procedures. To render the device more slippery, the device surfaces are often coated with low- friction materials such as Teflon® or a lubricating agent can be applied to the device such as a viscoelastic polymer.

[0003] Nearly all intraocular lenses (IO Ls) implanted today include a deformable, discus-like, polymeric optic that functions much like a natural lens. Implantation of an IOL into the eye involves making a surgical incision in the eye as small as possible (1.8 to 2.6 mm) to reduce trauma and speed healing. Unlike their long ago predecessors, deformable IOLs of today are rolled into tubes or folded into various configurations, all of which present a substantially reduced profile for insertion into an eye. To assist the surgeon in folding the lens into a preferred arrangement for implantation of an intraocular lens, insertion devices have been created. In one instance, the IOL is first folded into a shape resembling a taco shell and then is pushed through an insertion cartridge or "insertion tip" whereby it is progressively rolled or compressed into a tubular shape and readily inserted into an eye through a very small incision. Following release of the folded IOL into the lens capsule, the IOL unfolds and assume its original uncompressed shape. The surgeon may make minor positional adjustments to the IOL as needed. It is desirable that an IOL be released from the tip of the IOL inserter in an undamaged condition and in a predictable orientation. Should an IOL be damaged or released from the inserter in an incorrect orientation, a surgeon may need to remove the IOL. [0004] A problem arises, however, as the surgeon demands even smaller incision sizes and/or the design complexities of the IOL inhibits an efficient folding of the lens. For instance, the material from which the inserter body or tip is made, for example, polypropylene and the like polymeric materials, may not be compatible or suitable for passing a tightly folded IOL through an inserter tip of sufficient size to fit within the incision. An inserter tip can be made of a polymeric material that has insufficient lubricity to facilitate the passage of a tightly folded and compressed IOL completely through the tip without physical damage to the IOL. With the demand for ever decreasing incision sizes there will be an increase in frictional forces between the folded IOL and the polymeric or 'plastic" substrate of the insertion tip as the IOL travels through the tip. This friction too often could result in damage to the IOL, even to the point of having the IOL become stuck in the tip.

[0005] One approach to enhancing the lubricity of an inserter tip is to temporarily coat the folded IOL with viscoelastic agents such as hyaluronic acid or HPMC. Another approach is to attach a coating to an interior surface of the inserter tip to facilitate the passing of the IOL through the tip. U.S. Patent No. 5,716,364 is said to describe a lubricity enhancing component at an interior surface of the inserter tip following plasma treatment. The plasma-exposed interior surface is said to have an enhanced ability to physically secure or bond the lubricity enhancing component relative to a substantially identical interior surface that is not plasma-exposed. In particular, the '364 Patent describes and provides examples of IOL inserters that have been subjected to both a thermal process of "blooming", i.e., a known process in which a hydrophilic or lubricant additive in a molded hydrophobic polymer migrates to the surface, and a known plasma surface treatment.

[0006] It would be advantageous to provide an IOL inserter tip with an enhanced lubricity profile such that incision sizes as small as 2.2 mm can be used during surgical procedures. Also, lubricious coatings that exhibit prolonged shelf-stability, are stable under sterilization conditions and show little or no transfer of the coating to the IOL during delivery would provide a significant technical improvement in ocular cataract surgery.

[0007] Prior art references have chemically linked a hydrophilic polymer to a more durable undercoat to improve the physical integrity of a hydrophilic coating. See, Gould in U.S. Pat. No. 4,810,543 and Kliment in U.S. Pat. No. 4,729,914. Baker (U.S. Pat. No. 4,980,231) and Markel (U.S. Pat. No. 4,943,460) describe the coupling of a

polyvinylpyrrolidone polymer with an undercoating of an acid functional or anhydride functional material. The prior art also has attempted to improve wet strength and coating durability while retaining slip by physically blending or co-extruding the hydrophilic polymer with a co-material having greater physical integrity. See, Creasy in U.S. Pat. Nos. 4,642,267 and 4,847,324, in which a polyurethane or a polyvinyl butyral is blended with a poly(N-vinyl lactam). Other references disclose the preparation of interpolymers. See, Micklus (U.S. Pat. Nos. 4, 100,309 and 4,1 19,094) which report an association between polyurethane and polyvinylpyrrolidone polymers. Whitborne in U.S. Pat. No. 5,001,009 describes hydrophilic coatings including a polyolefin such as polyvinylpyrrolidone and a water-insoluble stabilizing polymer such as cellulose ester. The two polymers can be applied in separate layers or may be premixed and applied in a single step. Other attempts in the prior art to improve the performance of hydrophilic coatings include use of modified polyurethanes, which possess short hydrophilic segments. See, Teffenhart in U.S. Pat. No. 4,789,720, in which a hydrophilic polyurethane is prepared having polyethylene glycol and polypropylene glycol segments.

SUMMARY OF THE INVENTION

[0008] The invention is directed to a Pebax substrate with a hydrophilic coating prepared by a process comprising: providing a Pebax substrate and removing oligomers of Pebax at or near the surface of the Pebax substrate by sonicating the Pebax substrate in the presence of an organic solvent to provide a surface cleaned Pebax substrate; and forming a hydrophilic coating on the surface cleaned Pebax substrate.

[0009] The invention is also directed to an inserter for delivery of an intraocular lens that includes an inserter tip that comprises a Pebax substrate with a hydrophilic coating. The Pebax substrate is prepared by a process comprising: providing a Pebax substrate and removing oligomers of Pebax at or near the surface of the Pebax substrate by sonicating the Pebax substrate in the presence of an organic solvent to provide a surface cleaned Pebax substrate; and forming a hydrophilic coating on the surface cleaned Pebax substrate. [0010] The invention is also directed to an inserter for delivery of an intraocular lens that includes an inserter tip molded from Pebax and having an internal surface coating with a percent gradient of from 5% to 35%.

[0011] The invention is also directed to an inserter tip with a hydrophilic coating prepared by a process comprising contacting an internal surface of an inserter tip with a coating composition; and distributing the coating composition along the length of the interior surface by applying a centrifugal shear force to the contacted internal surface of the tip. The hydrophilic coating will have a gradient thickness with the coating at the proximal end of the tip that is greater than the thickness of the tip at the opposite distal end, i.e., the end of the tip that is inserted into the surgical incision.

BRIEF DESCRIPTION OF DRAWING

[0012] FIG. 1 is a photograph of an enVista +23.5 diopter lens delivered from a sonicated tip and a control tip.

[0013] FIG. 2 is a plot indicating the dimensional thickness of coating along a tapered inserter tip.

[0014] FIG. 3 is an illustration of an ILID having an inserter tip with a coated internal surface.

DETAILED DESCRIPTION OF THE INVENTION

[0015] In one embodiment, the invention is directed to a durable, hydrophilic coating on polyether block polyamide, hereafter, "Pebax", substrates for use in articles such as medical devices. The coating provides lubricous properties to the substrate when wetted. The medical device can be a catheter, an arterial catheter, a short-term central venous catheter, a long-term central venous catheter, a peripheral venous catheter, a vascular port catheter, a dialysis device, a guide wire, an introducer, an arteriovenous shunt, a hydrocephalus shunt, a biliary stent, a coronary stent, a urological stent, a vascular stent, an endotracheal tube, each of which includes a Pebax substrate to which a hydrophilic coating is applied. In particular, the medical device is an intraocular lens insertion device. [0016] As used herein an "intraocular lens insertion device" (ILID) refers to a device designed to facilitate the insertion of a folded IOL through a small incision in an eye after which the lens unfolds to become an artificial lens replacing the diseased natural lens. Virtually all ILIDs comprise an inserter tip, the portion of the device that actually enters the eye and through which the IOL is inserted into the space previously occupied by the natural lens. The inserter tip may be integral with the body of the ILID or it may be separable from the main body of the ILID. Either type of inserter tip is amenable to the coating methods described. If the inserter tip is integral to the body of the ILID, then the end of the ILID that comprises the inserter tip will be subject to the described coating method of this invention. If the inserter tip is separable from the body of the ILID, then it may be disconnected, separately subjected to the described coating method, and then reassembled with the body of the ILID.

[0017] As used herein, "tip," or "insertion tip," are used interchangeably to refer to the narrowed portion of an ILID that comes in contact with the IOL just prior to the release of the IOL into an eye of a patient. Accordingly, it is an aspect of this invention to lubricate the interior portions of the insertion tip that will come in contact with an IOL and thereby to reduce friction between the tip's polymeric substrate and the IOL. The term "tapered tip" means an inserter tip with a tapered configuration and having a proximal end of the tip, i.e., the end of the tapered tip with a wider opening, and an opposite distal end, i.e., the end of the tip that is inserted into the surgical incision.

[0018] As used herein, "hydrophilic coating" is a relatively thin film coating of 1 to

10 microns that is positioned on a polymeric substrate. In the wetted state, the hydrophilic coating lowers the coefficient of friction of the polymeric substrate relative to a non-coated substrate made of the same polymeric material and similarly configured. The coefficient of friction is measured using IOL delivery force measurements well known to those in the art of designing ILIDs.

[0019] As used herein a "polymeric primer" refers to a polymer or blend of polymers that exhibit good adhesion characteristics with regard to a polymeric substrate and good adhesion characteristics with regard to the lubricious top layer polymer coat. Thus, a primer layer serves as an adhesion-enhancing intermediary between the substrate and the lubricious top layer. In some instances, the primer is a copolymer in which at least one of the constitutional monomer units is compatible with the substrate.

[0020] The coating can have a dual role: provide a lubricous coating as well as improve the integrity of the surface of a substrate, particularly a Pebax substrate.

Applicants have discovered that some hydrophilic coatings when applied to a Pebax substrate fail with respect to the later functional role. For example, Applicants have a particular interest to deliver intraocular lenses with an inserter device without delivering component portions of the coating or the Pebax substrate, that is, the Applicants have an interest to deliver lenses with little or no component debris. During attempts by Applicant to test deliver hydrophobic intraocular lenses with some commercially available inserter devices with Pebax tips into buffered saline solution, Applicants have also observed microscopic particles. These particles are believed to be chemical components of the Pebax substrate tip, i.e., small oligomers present in the Pebax which come to the surface during an ethanol wash step of the molded tip prior to the coating step. Applicants have found, however, that the number of particles eluted with the delivery of a lens can be abated by removing the particles prior to the coating of Pebax inserter tip.

[0021] In many instances, the hydrophilic coating is directly applied to the Pebax substrate to provide a robust and durable coating. In other instances, the hydrophilic coating includes more than one layer, i.e., at least one layer in addition to the external (top) layer, in which the layers are sequentially applied to the Pebax substrate to form the coating. For example, if the coating includes a primer layer and a top layer, the primer layer is applied to the substrate and dried, and optionally cured; the top layer is then applied to the primer layer. In some instances, the coating can also include an intermediate layer that is positioned between the primer layer and the top layer. The intermediate layer can be used to improve upon the robustness or lubricity of the coating.

[0022] A robust coating is important for positioning intraocular lenses in the eye to minimize the amount of coating that can flake off the inserter tip and come in contact with ocular fluids or tissues. The coating should remain adhered to the Pebax substrate when subjected to the compression forces of dispensing an intraocular lens through an inserter tip with an orifice of 2.4 mm or less. As stated, a primer (pre-coat) layer can be used to further improve the adhesion of the bonding and/or lubricious coating layers to the Pebax substrate.

[0023] The organic coating components are usually applied to the substrate using well known methods in the art. Typically, a solvent is used to dissolve the coating components, and a coating solution is applied to the Pebax substrate. A number of solvents useful for applying the hydrophilic coating to a Pebax substrate include alcohols (e.g., ethanol, iso-propanol, n-butyl alcohol, i-butyl alcohol, t-butyl alcohol, and the like). These solvents and others cause different degrees of swelling of the Pebax substrate, and can have varying effects on the integrity of the Pebax substrate with respect to particle release. The duration and temperature of solvent evaporation may be selected to achieve stability of the coating layer and to achieve a bond between the Pebax surface and the coating.

[0024] A two-part coating procedure is exemplified as follows. A primer layer is applied to a Pebax inserter tip by any means known in the art. The simplest and currently preferred means is simply to submerge the insertion tip in an organic or alcohol solution of the primary polymer. The submerged tip is then removed from the solution of primer and dried under mild conditions such as ambient temperature or at 35° C. Another means is to simply pass a solution comprising a primer through the inserter tip. Applicants have found it advantageous to place the previously primed tips in cylindrical centrifuge vessels, followed by a brief centrifuge cycle to coat the interior surface of the tip and minimize agglomeration of the coating. Once the primer layer has been dried, it is cured at a higher temperature, that is, from about 30° C. to about 80° C. The exact time to cure is easily optimized by those skilled in the art based on the curing temperature. The cured primed insertion tip is then contacted with a lubricious polymer that is dissolved in a suitable solvent. The solvent is selected such that it is capable of dissolving the lubricious polymer and is compatible with the primer layer to create a robust coating having a robust and lubricious top layer.

[0025] A top coating layer for use in coating an article comprises one or more hydrophilic polymers. The hydrophilic polymer may be any polymer which swells in the presence of water to provide a "slippery" or lubricous surface. Exemplary hydrophilic polymers include, but are not limited to, poly( -vinyl lactams), such as

polyvinylpyrrolidone) (PVP) and the like, polyurethanes, polyacrylamides, polyalkylene glycols polyacrylic acids, such as acrylic and methacrylic acids and the like, polyvinyl alcohols, and polyvinyl ethers and the like. The hydrophilic polymer can be of any molecular weight, but it preferably has an average molecular weight in the range of about 50,000 to 500,000. By way of example, a commercially available polyurethane can be prepared by condensation in the presence of organic acid to provide a polyurethane with a desired number of acid functional pendant groups.

[0026] In some embodiments, the lubricious polymer is considered a hydrogel polymer. When hydrated and placed in an aqueous environment, such as that inside the cornea, the high water content of the hydrogel provides a very lubricious surface for the passage of the intraocular lens. Many of the polymers mentioned above are either inherently hydrogels or can be rendered hydrogel-like by light cross-linking. Techniques for making hydrogel polymer coatings are well-known to those skilled in the art.

[0027] In another embodiment, a lubricious coating that is deposited on a Pebax substrate is prepared from an aqueous mixture of a hydrophilic polymer and a supporting polymer having functional groups capable of undergoing crosslinking reactions. The supporting polymer and hydrophilic polymer are well blended and form an association complex in the aqueous-based medium. The association of the two polymer types may be preserved and maintained by crosslinking the functional moieties of the supporting polymer to form a three dimensional polymer network. The three dimensional network entrains, entraps and otherwise immobilizes the hydrophilic polymer within the coating to minimize its loss to the environment when wet, without interfering with the hydrophilic properties of the hydrophilic polymer.

[0028] As above, the hydrophilic polymer can be any polymer which swells in the presence of water to provide a "slippery" or lubricous surface. Exemplary hydrophilic polymers include, but are not limited to, poly( -vinyl lactams), such as

polyvinylpyrrolidone) (PVP) and the like, poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO), polyacrylamides, polyacrylic acids, such as acrylic and methacrylic acids and the like, polyvinyl alcohols, and polyvinyl ethers and the like. The hydrophilic polymer may be of any molecular weight, but it preferably has an average molecular weight in the range of about 50,000 to 1,000,000. It is contemplated that for hydrophilic polymers of lower molecular weights, e.g., less than about 250,000, the crosslink density of the supporting polymer can be adjusted upward.

[0029] The supporting polymer is selected for its ability to positively interact with the lubricious hydrophilic polymer to form an association complex, for its durability and for its ability to form a three-dimensional polymer network. A hydrophilic polymer typically possesses a high ionic content, typically by way of polar bonds, which promotes the polymer's affinity for water. Thus, association complexes are favored when the supporting polymer contains a complementary ionic content. Suitable supporting polymers include, but are not limited to, polyacrylates and polymethacrylates, polyurethanes, polyethylene or polypropylene copolymers, polyvinyl chloride, epoxides, polyamides, polyesters, alkyd or copolymers with rubbers, siloxanes or other polymers.

[0030] The supporting polymer may be a homopolymer or copolymers or blends. In one embodiment, the supporting polymer can be a copolymer of ethylene and acrylic acid. While not required of the invention, it is contemplated that supporting polymers possessing some degree of branching may be preferred, because such branching will serve to further minimize the disassociation and/or leaching of the hydrophilic polymer from the resultant hydrophilic coating.

[0031] The supporting polymer possesses a plurality of functional moieties which are capable of participating in a crosslink reaction. In addition, the functional moieties should be stable in the aqueous environment of the coating composition. The functional moieties may be located along the supporting polymer backbone or they may be located as groups pendant to the supporting polymer backbone. Suitable functional moieties include, but are not limited to, amino, hydroxyl, amido, carboxylic acid and derivatives thereof, sulfhydryl (SH), unsaturated carbon and heteroatom bonds. The functional moiety is incorporated into the supporting polymer in an amount which will provide, under the appropriate curing conditions, the desired crosslink density in the hydrophilic coating. The amount of functional moiety in the supporting polymer is designated by equivalent weight (eq. wt), which is defined as the weight of supporting polymer per one equivalent of functional group in the polymer. Thus, the lower the number, the greater the level of functional moiety in the supporting polymer. For example, it has been generally observed in a polyacrylate supporting polymer/PEO or PVP hydrophilic polymer coating composition in which a polyfunctional aziridine is used as the crosslink agent that an equivalent weight of about 1 100 is insufficient to provide a durable lubricous coating. In contrast, a similar coating composition having an equivalent weight of about 200-375 satisfactorily immobilizes the hydrophilic polymer to provide a durable hydrophilic coating, even when aged up to one year.

[0032] The supporting polymer may be an oligomer or polymer having an average molecular weight in the range of 30,000 to 400,000. Note that when an epoxy is used as the supporting polymer, the molecular weight may be considerably less than that stated. Epoxy oligomers are cured in situ in the presence of amines to provide the high molecular weight supporting polymers. Likewise, isocyanates dispersible in water may allow for similar reactions with active hydrogen containing compounds.

[0033] Polymers have several advantages over the use of monomers. First, it avoids toxic monomers which must be rigorously removed before subsequent use in medical applications. Second, it allows preparation of water-based formulations because the polymer is either soluble in water or may be prepared as a water-based emulsion or dispersion. In addition, there is less control over the nature of the polymer, e.g., molecular weight, degree of branching, etc. before blending and crosslinking.

[0034] In one embodiment, a commercially available polyurethane is prepared by condensation in the presence of organic acid to provide a polyurethane with a desired number of acid functional pendant groups. The supporting polymer may be ethylene copolymerized with acrylic acid (or other unsaturated organic acid) to provide a poly(ethylene-co-acrylate). The copolymer is selected to have the appropriate

apportionment of the two component polymer so as to provide the desired level of pendant acid functional groups.

[0035] The coating composition may additionally include a crosslink agent.

Suitable crosslink agent include, but are not limited to, polyfunctional aziridines, polyfunctional carbodiimides and polyfunctional epoxides. In some embodiments, where the crosslink agent is quite reactive to the functional groups of the supporting polymer, it should be added to the coating composition just before the coating operation. In other embodiments, where the crosslink agent is not very reactive, the crosslinking reaction may require initiation by some external trigger such as heat, irradiation, etc. In these instances, the crosslinking agent may be added to the coating composition and stored together.

[0036] Once applied, the hydrophilic coating may be "locked" in place by crosslinking of the supporting polymer to form a three-dimensional network. The crosslink reaction may occur before, during or after the drying step, but most typically occurs during or after the drying step. Crosslink density in the product hydrophilic coating will vary significantly with the nature of the supporting polymer and the crosslink agent, as well as the conditions and duration of curing. Crosslink density may be in the range of 100-1000 g/equivalent crosslink. This figure will be modified in the manner discussed above for the equivalent weight of functional moiety.

Cleaning of Pebax tip with commercially applied coating

[0037] Applicants sought a method to pre-clean Pebax substrates beyond a typical ethanol wash or soak because elongated particles were observed as a cloudy mass under magnification in test saline solution following delivery of an intraocular lens into a saline solution using a 2.2 mm Pebax inserter tip coated with a hydrophilic coating. The hydrophilic coating was coated by an outside vendor. The particles, approximately about one micron in width and 10 to 75 microns in length were identified using IR spectroscopy as nylon 12, one of the primary components of the Pebax substrate. The ethanol wash was not sufficient to remove stray or loose Pebax oligomers at or near the internal surface of the tips.

[0038] To reduce the number of elongated polyamide crystalline particles observed in the test saline solution during delivery of a hydrophobic enVista intraocular lens from Bausch + Lomb, a sonicated ethanol rinse step was introduced into the manufacturing process and investigated. The tips are placed in a sonication unit reservoir with

ethanol/isopropanol (95/5); between 2 to 10 mL of solution per tip), and sonicated for seven minutes at 50° C. It is understood by a person of skill that the temperature of the solution and sonication time can vary - with lower temperatures requiring longer sonication times. The sonicated tips were then shipped to the commercial supplier for coating. To determine the efficacy of the sonication step, enVista intraocular lenses were delivered using sonicated, coated tips and compared to control deliveries using non- sonicated, coated tips. In comparison to the control deliveries, the lenses delivered with the sonicated tips are dramatically cleaner and do not generate the cloudy, wispy particle plumes that are characteristic of the presence of elongated polyamide crystalline particles.

[0039] A photograph of an enVista +23.5 diopter lens delivered from a sonicated tip and a control tip is depicted in FIG. 1. The lens on the left was delivered using a sonicated tip while the lens on the right was delivered using a non-sonicated tip. As demonstrated by FIG. 1, the sonicated tip delivery is dramatically cleaner and has less cloudy, wispy particle plumes that accompany the lens delivery. The cloudy, wispy plumes observed are characteristic of the presence of elongated polyamide crystalline particles and are entrained within the viscoelastic, which is also used to facilitate passage of the lens through the inerter tip.

[0040] The experiment in the preceding paragraph was repeated with enVista +32.0 diopter lenses, and this time an effort was undertaken to actually count the number of emitted particles of Pebax (nylon) particles. The test indicated that there is a 97% reduction in the number of elongated particles using the sonicated inserter tips. On average, the sonicated tips generate ~44 elongated particles in contrast to the -1500 elongated particles observed in coated tips that were not sonicated prior to coating.

EXAMPLES

[0041] Example 1. Twelve inserter tips molded from Pebax resin are placed in a

200 ml glass beaker containing 100 ml of 95/5 ethanol/isopropanol. A Teflon-coated bar magnet is placed in the alcohol solution and the solution is stirred in a sonication bath at 50° C for seven (7) minutes. Alternatively, the sonication step can be conducted at room temperature for about thirty (30) minutes. The tips are removed from the solution and placed on a Teflon sheet and dried in an oven at 60° C for 6 hours. The tips are allowed to come to room temperature. A Hydromed® D640 resin polymer, obtained from

AdvanSource Biomaterials, is a commercially available PEG-polyurethane copolymer that is dissolved in ethanol/water (95/5) at a solid concentration of 5 wt.%. The polymer solution is drawn into inserter tips with a pipette and released. The coated inserter tips are placed in a centrifuge vial tip side (distal end) down (about 6 to a vial) and spun at 2000 RPM for about one minute. The tips are placed in an 80° C oven for one hour, and then sterilized with ethylene oxide. [0042] Delivery force measurements were conducted with inserter tips coated from the supplier and two inserter tips prepared in accordance with the coating procedure of Example 1. The Example 1 tips had a slightly less delivery force, but more importantly, there was little or no particulates transferred to the lens. In other words, there were no wispy, cloudy plumes observed when a lens is delivered into a saline solution. See, FIG. 1.

[0043] In addition, the use of a centrifuge in the coating process is believed to provide a novel coating configuration to the tip. Spinning the tapered tips with the narrow distal end down provides a tapered coating to the tips. As indicated by the data of FIG. 2 the thickness of the coating varies along the length of the tip. The coating at the proximal end has a thickness of about 1.6 microns, the coating at the midpoint of the tip is about 1.5 microns, and the thickness of the coating at the distal end is about 1.4 microns.

[0044] The thickness of the coating along the length of a tip can be described by the following formula

percent gradient = thickness at proximal end - thickness at distal end x 100

thickness at proximal end

[0045] Under the spin conditions of Example 1 the coating has a percent gradient of 12.5%.

[0046] It is understood by one of ordinary skill in the art that the percent gradient of an inserter tip coating can be influenced by spin rate. Accordingly, a coating described herein can have a percent gradient from about 5% to about 35%, or from 5% to about 25%, or from 5% to about 20%.

[0047] It is also understood by one of ordinary skill in the art that the use of a centrifuge is one of many processes that can be used to distribute a coating on a Pebax substrate, and particularly a coating on an inserter tip, by applying a shear force to the coated substrate.

[0048] Example 2. The same procedure as that described in Example 1 is followed using 0.2% Hydroslip™ C as the polymer coating layer instead of Hydromed®D640. [0049] Example 3. The same procedure as that described in Example 1 is followed using 1.0% polyvinylpyrrolidone (PVP-C15) as the polymer coating layer. The PVP-C15 was dissolved in 50:50 isopropanol:THF.

[0050] Example 4. The same procedure as that described in Example 1 is followed using 0.5% polyhydroxyethylmethacrylate (MW 5000) dissolved in 70:30

ethanokchloroform as the polymer coating layer.

[0051] Example 5. Twelve inserter tips molded from Pebax resin are placed in a

200 ml glass beaker containing 100 ml of ethanol. A Teflon-coated bar magnet was placed in the solution and the solution was stirred using a magnetic stirrer for 30 minutes at room temperature to remove surface contaminants. The tips are removed from the ethanol, placed on a Teflon sheet and dried in an oven at 60° C for 6 hours. The tips are allowed to come to room temperature. A primer polymer layer is deposited on the ethanol cleaned tips, Unistole P-401 used as received from Mitsui Chemicals (8% solids) is drawn into inserter tips with a pipette and released. The coated inserter tips are placed in a centrifuge vial (about 6 to a vial) and spun at 2000 RPM for about one minute. An intermediate layer, AdvanceSource Biomaterials 10% bonding agent using the same pipette and centrifuge above is then applied to the primed tips. Lastly, a top layer is applied using the

Hydromed® D640 resin polymer of Example 1. Again, the polymer solution is drawn into inserter tips with a pipette and released. The coated inserter tips are placed in a centrifuge vial (about 6 to a vial) and spun at 2000 RPM for about one minute. The tips are placed in an 80° C oven for one hour, and then sterilized with ethylene oxide.

[0052] Example 6. The same procedure as that described in Example 5 is followed using 0.2% Hydroslip™ C as the polymer coating layer instead of Hydromed®D640.

[0053] Example 7. The same procedure as that described in Example 5 is followed using 1.0% poly(vinylpyrrolidone) (PVP-C15) as the polymer coating layer. The PVP-C15 was dissolved in 50:50 isopropanokTHF.

[0054] Example 8. The same procedure as that described in Example 5 is followed using 0.5% polyhydroxyethylmethacrylate (MW 5000) dissolved in 70:30

ethanokchloroform as the polymer coating layer. [0055] Example 9. This example describes the preparation of a variety of polyacrylate-poly(vinylpyrrolidone) coating using melamine formaldehyde as a crosslink agent. An aqueous coating composition is prepared using polyacrylates having various equivalent weights of acid moieties. To a solution containing polyacrylate is added PVP Povidone K-90 (poly(vinylpyrrolidone), MW 1,000,000, ISP Chemical) in a 3/1 ratio to obtain a composition having a total of 10 wt % solids. A melamine formaldehyde crosslink agent (hexamethoxy melamine/formaldehyde, Cymel 303, Cytec Corp.) at 2.0 times the stoichiometric level (relative to eq. wt. acid) is added. The stoichiometric calculations were based upon a functionality of three rather than six for the hexamethoxymelamine, assuming that steric hindrance and lack of availability of reactive acid functionalities for all crosslink functional sites would prevent all six sites from reacting. The coating is cured at 160°F for 30 minutes.

[0056] Example 10. This example describes the preparation of a variety of epoxide/polyethylene oxide coating compositions using a polyamine as crosslink agent. To a solution containing a polyamine is added Polyox WSR-205 (polyethylene oxide, MW 600,000, Union Carbide) in to obtain a composition having a total of 10 wt % solids. A hydrophilic coating is prepared by adding an epoxy crosslink agent (Waterpoxy 1401, Hankel Corp.) at 1.0 times the stoichiometric level (relative to eq. wt. functionality of the polyamine). The coating is cured at 160°F for 30 minutes.

[0057] With reference to FIG. 3, there is illustrated an exemplary ILID that includes a cartridge 12 having a body portion 14 and n inserter tip 16. The cartridge 12, particularly the body portion 14 and the inserter tip 16, define an internal surface 18 that defines a lumen 20 extending along a length of the cartridge 12, the body portion 14 and the inserter tip 16. At least a portion of an internal surface 18 is covered by a coating 22 described herein. The inserter tip 16 is typically configured to fit into an incision in an eye to aid in the delivery an IOL through the tip 16 into the eye. As can be seen, the tip 16 has an inner diameter (ID) and an outer diameter (OD) taken perpendicular to an axis 24 extending along a length of the tip.

Claims

We Claim:

1. A Pebax substrate prepared by a process comprising:

providing Pebax resin and removing oligomers from the Pebax resin by sonicating the Pebax resin in the presence of an organic solvent to provide clean Pebax resin substantially free of labile oligomer; and

forming a Pebax substrate with the clean Pebax resin.

2. The Pebax substrate of claim 1 wherein the organic solvent is selected from the group consisting of an alcohol, an ether and tetrahydrofuran.

3. The Pebax substrate of claim 1 wherein the organic solvent includes Ci-C₃alcohol.

4. The Pebax substrate of any one of claims 1 to 3 molded in the form of an intraocular lens (10 L) inserter tip.

5. The Pebax substrate of claim 4 further comprising coating an internal surface of the molded IOL inserter tip, the coating comprising a layer comprising a polyurethane polymer or a copolymer thereof, or a poly(vinylpyrrolidone) polymer or a copolymer thereof.

6. The Pebax substrate of claim 5 wherein the coating further comprises a crosslink agent.

7. The Pebax substrate of claims 5 or 6 wherein forming the coating comprises contacting the Pebax substrate with a coating composition and distributing the coating composition on the Pebax substrate by applying a shear force to the coated substrate.

8. The Pebax substrate of claim 7 wherein the distributing of the coating composition includes centrifugation of the coated Pebax substrate.

9. An inserter for delivery of an intraocular lens comprising an inserter tip that comprises a Pebax substrate molded from clean Pebax resin, wherein the Pebax substrate is prepared by a process comprising:

forming the inserter tip with the clean Pebax resin.

10. The inserter of claim 9 wherein the inserter tip is a tapered tip having an internal surface coating with a percent gradient of from 5% to 35%.

11. The inserter of claim 10 wherein the internal surface coating comprises a layer comprising a polyurethane polymer or a copolymer thereof, or a

polyvinylpyrrolidone) polymer or a copolymer thereof.

12. The inserter of claims 10 or 1 1 wherein the internal surface coating has a percent gradient of from 5% to 20%.

13. The inserter of claims 9 or 10 wherein the internal surface coating comprises a primary layer positioned between a Pebax internal surface and a top layer coat, wherein the top layer coat is a polyurethane polymer or a copolymer thereof, or a polyvinylpyrrolidone) polymer or a copolymer thereof.

14. An inserter tip prepared by a process comprising:

contacting an internal surface of an inserter tip with a coating composition; and distributing the coating composition along the length of the interior surface by applying a centrifugal shear force to the contacted internal surface of the tip.

15. The inserter tip of claim 15 wherein the coating composition comprises a polyurethane polymer or a copolymer thereof, or a poly(vinylpyrrolidone) polymer or a copolymer thereof.

16. The inserter tip of claim 15 comprising a coating having a gradient thickness along the length of the interior surface with the thickness of the coating at the proximal end of the tip being greater than the thickness of the coating at the opposite distal end of the tip.

17. The inserter tip of claim 17 wherein the gradient thickness of the coating comprises a percent gradient of from 5% to 35%.

18. The inserter tip of claim 15 molded from Pebax or polypropylene.