Patent Application
20060241000
The present invention relates to hydrophilic polymers. More particularly, the present invention relates to a hydrophilic lubricous polymer blend that can form a hydrogel when cross-linked and placed into an aqueous environment and a method of making the same.
Water-sensitive hydrophilic polymers are commonly used in the manufacture of various personal care and medical devices. The water-sensitive polymers function to provide lubricity to the device when it becomes wetted with an aqueous solution such as water or a body fluid. The water-sensitive polymers may be used in conjunction with water-insoluble polymers that function to provide the appropriate structural characteristics and mechanical integrity to the device for its intended use. Typical medical devices that can benefit from lubricious properties include, for example, catheters, guide wires, endotracheal tubes and implants.
Patents have reported coating medical devices with water-soluble polymers that are hydrophilic. Such hydrophilic coatings have also been referred to as lubricous or “slippery”coatings. Typically, the hydrophilic polymer is dissolved in a suitable solvent and then applied to the desired medical device. The solvent is then evaporated to yield the coating. Oven drying may be utilized to remove the solvents. When the hydrophilic material is coated on the surface utilizing solvents in a wet method the polymer is usually formed as a fairly thin layer. The hydrophilic coating may break down or be removed upon prolonged turbulent flow, mechanical abrasion or soaking. Other drawbacks to the solution coating and curing process approach may include solution pot life, coating thickness control, and durability. See, for example, U.S. Pat. Nos. 4,119,094, 5,077,352 and 5,091,205, and EP Patent Nos. 0 106 004 B1 and 0 166 998 B1.
U.S. Pat. No. 5,061,424 discloses a method for preparing a shaped medical device provided with a lubricous coating. A coating composition comprising a blend of polyurethane and polyvinylpyrrolidone and polyethylene glycol is co-extruded with a substrate polymer to give a shaped medical device having a layer of the coating composition that then becomes lubricous when contacted with water.
U.S. Pat. No. 5,041,100 discloses a method for coating a substrate with a solution of polyethylene oxide and polyurethane. The polyethylene oxide is mixed with the polyurethane. The blend is then formed into a solution and then applied to medical device and dried to form a coating.
U.S. Pat. Nos. 5,113,585 and 5,454,164 report polymer blends for utilization in shaving systems. The polymer blends taught in these patents are specifically designed to abrade off with use in order to provide for skin lubrication. Accordingly, there is a need in the art for improved lubricious polymer m
aterials for incorporation into medical devices.
The present invention includes a blend of two or more polymer materials including a water insoluble polymer and a hydrophilic water-soluble polymer, the polymer blend is a finely dispersed blend that provides a lubricious surface.
One embodiment includes a method of forming a lubricious polymer that includes drying a polyethylene oxide of a molecular weight between about 200,000 and about 7,000,000, drying a polyether block amide, adding the polyethylene oxide into a first feeder and the polyether block amide into a second feeder, the first and second feeders controlled by a feeder control and situated to feed the polymers into a compounding extruder, melt mixing the polymers with a low shear/low energy screw into a generally uniform blend, extruding the blend through a forming die to form a strand, cooling the strand, and pelletizing the strand.
Another embodiment includes a lubricous polymer that includes a finely dispersed blend of a polyethylene oxide with a molecular weight of between about 200,000 and about 7,000,000 and a polyether block amide, the blend including up to about 60% by weight of the polyethylene oxide.
Another embodiment includes a lubricous polymer blend including a substantially uniform polymer blend of a polyethylene oxide with a molecular weight of between about 200,000 and 7,000,000 and a polyether block amide, the blend including up to 60% by weight of the polyethylene oxide.
Still another embodiment includes a lubricous polymer with a finely dispersed blend of a polyethylene oxide with a molecular weight of between about 200,000 and about 7,000,000 and a polyurethane, the blend including up to about 60% by weight of the polyethylene oxide.
While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. The present invention is capable of modifications in various obvious aspects, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.
The present invention is a formulation for and method of making a lubricious hydrophilic polymer blend and medical devices incorporating the same. The lubricious hydrophilic polymer blend may be referred to as a “polyblend,”a “hydrophilic polyblend,”or a “lubricious polymer.”In addition, the polyblend may be referred to as a hydrogel after cross-linking and exposure to a suitable aqueous solvent. A hydrogel is a colloidal gel in which the particles are dispersed in an aqueous solvent but only loses little or none of its structure to the solution.
The lubricious hydrophilic polyblend includes a lubricious water soluble polymer and an insoluble polymer. The two polymers are melt mixed and solidified to form a finely dispersed polyblend. The present invention polyblend can be utilized to provide a lubricious coating on a medical device formed by extruding, co-extruding, injection molding, or die forming, or, in further embodiments, the polyblend can be directly coated on a medical device. Embodiments of the coating formed using the lubricious hydrophilic polyblend of the present invention may be more robust and allow for superior permanence compared to previously taught lubricious coatings. As may be appreciated, the lubricious hydrophilic polyblend may be formed with or on any type of underlying structural article or framework to impart the desired lubricious properties to the final product.
Medical devices such as guidewires, catheters, sheaths, tubes, etc. that incorporate the present invention polyblend may help to reduce damage to the body during insertion because the lubricious surface will exert reduced frictional forces. Such medical devices may also help to reduce blood clotting as well. The materials of the present invention, therefore, help to prevent the devices from locking up or sticking during delivery procedures. In addition, the lubricious polyblend is not released or abraded away during use because the lubricious polymer is captured in the structural (or matrix) polymer.
The selection of the lubricious water-soluble polymer may depend on a number of factors. The lubricious polymer is partially miscible in the structural polymer but not completely miscible. When the lubricious polymer is only partially miscible rather than completely miscible the final lubricious hydrophilic polyblend will retain pockets of lubricious material dispersed throughout the polyblend. The lubricious polymer may also have a lower melting point and therefore a lower viscosity at a given temperature than the structural polymer. The lower viscosity lubricious polymer is more likely to migrate towards the outer surface of the polyblend. A lubricious hydrophilic material may be able to absorb many times its own weight in water.
In addition, the molecular weight may affect the lubricity of the final compound and so may be a factor in polymer selection. Extrusion grade resins may be of a higher molecular weight and therefore have more melt strength and will have more easily processed melt flow properties.
A lubricious hydrophilic polymer includes polyethylene oxide (PEO). Other lubricious materials may also be incorporated, such as polypropylene oxide (PPO), polyethylvinylalcohol (EVOH), polyethylvinylacetate (EVA), polyvinylpyrolidone (PVP), and other water-soluble lubricious polymers known to those skilled in the art may also be incorporated.
Structural polymers may include polyamides, polyurethanes, polyesters, olefin derived copolymers, polyethylene, high-density polyethylene (HDPE), natural and synthetic rubbers, styrenics, thermoplastic elastomers, and other specialty polymers. Polyamides may include homopolymers and copolymers like Nylon® 12 and 11, Pebax®, and Vestamid® resins. Nylon® 11 and Nylon® 12 copolymers may range in shore hardness from about 80D to 25D. Pebax is a polyether block amide manufactured by Arkema, Philadelphia, Pa. and is available in a variety of durometers. Polyurethanes may include polyesterurethanes and polyetherurethanes, like Pellethane® or Texin. One structural polymer may include polyetherurethane with a shore hardness from about 75D to 90D. Polyesters may include polyethylene terephthalate, polybutylene terephthalate, and co-polyesters like Hytrel® and Arnitel®. Rubbers may include silicone or Santoprene®. Thermoplastic elastomers may include commercially available materials like Kraton®.
In certain embodiments the structural polymer may be cross-linked by a predetermined amount to control the hydration rates and the swell of the polyblend. In further embodiments stabilizers may be included in the hydrophilic polymer blend, such as, for example, Irganox B225 or 1098. The polymer blend may also be formulated to include other advantageous materials, such as stabilizers, drugs, mixing aids, flow aids, plasticizers, heat stabilizers, antimicrobial agents, etc. In further embodiments, other anti-oxidants or other types of additives may also be utilized.
One hydrophilic polyblend of the present invention may include about 30 to about 60% PEO by weight. The polyblend may furthermore contain 35-50%, 40-50% PEO, or, particularly, about 40% PEO. The PEO is preferably greater than 100,000 MW. The PEO may include a molecular weight of about 200,000 to about 7,000,000, more particularly about 500,000 to 2,000,000, or, more particularly, about 1,000,000. In still further embodiments, the polyblend may be diluted during the extrusion or other medical device forming process to form materials with a lower weight percent of the hydrophilic polymer.
A PEO with a molecular weight of 7,000,000(Dow WSR 303) was selected as the hydrophilic polymer and Pebax 72D was selected for the structural polymer. The final hydrophilic polymer blend included PEO at 40% by weight.
The polyether block amide was first dried at 170° F. for four hours. The PEO was dried at 60° C. in a vacuum oven (<25 mbar) for four hours. The drying time in the present example and all of the examples below can be for about the listed time or longer. The polymer materials were then separately loaded into two feeders controlled by a feeder control for addition to the compounding extruder. The compounding extruder was a Werner and Pfliedere ZSK30 co-rotating twin screw extruder. The extruder was equipped with a low shear/low energy screw that included two mixing zones, one dispersive and one distributive, each with six elements. The aspect ratio of the selected screw was 30:1 length:diameter and included modular conveying and mixing elements.
The PEO feeder was set at 70 grams/minute and the Pebax feeder was set at 93 grams/minute. The mixing barrel included four heat zones. The various heat zones and the screw type and rate allowed the material to be mixed and homogenized before it was passed through the die. The temperature zones of the barrel ranged from 320 to 375° F. The extruder response had a drive torque of 72% and the extruder output was 22 pounds per hour. The die temperature was set at 375° F. and the die pressure response at 350 psi. The die temperature zone and pressure can be controlled to insure a desired strand viscosity. The extensional viscosity (i.e., melt strength) of the material when it passed through the die was adjusted so that the produced polyblend strand maintained its shape until it was properly cooled.
In the present embodiments a die with four holes of 0.180″inch diameter was utilized to form the polyblend into four concurrent strands. The extruded polyblend strands were then drawn out and cooled on the chill roller. Each strand was drawn to 0.100″before being pelletized. A cooled water/glycol solution (1:1) chilled each roller but in the present embodiment no water touched the hydrophilic polyblend during the cooling process. The chill rolls utilized were Davis Standard laboratory grade three-roll stack sheet extrusion rollers. The pelletizer was a Gala strand pelletizer.
Once the molten strands were solidified the polymer blend was chopped/cut into pellets by the pelletizer set at 210 rpm.
A PEO with a molecular weight of 7,000,000 was utilized as the hydrophilic polymer and Pebax 72D was selected as the structural polymer. The final hydrophilic polymer blend included PEO at 40% by weight.
The next example utilized a PEO with a molecular weight of 7,000,000 and Pebax 72D. The final hydrophilic polymer blend included PEO at 60% by weight
A PEO with a molecular weight of 1,000,000 (Dow WSRN12) was utilized as the hydrophilic polymer and Pebax 72D was the structural polymer. The final hydrophilic polymer blend included PEO at 40% by weight.
A PEO with a molecular weight of 200,000 (Dow WSRN80) was mixed with Pebax 72D. The final hydrophilic polymer blend included PEO at 40% by weight.
The hydrophilic polymer was a PEO with a molecular weight of 1,000,000 and the structural polymer was Pebax 72D. The final hydrophilic polymer blend included PEO at 40% by weight.
A PEO of with a molecular weight of 7,000,000 was mixed with HDPE as the structural polymer. The HDPE was a Quantum HDPE 6007 (0.6 MFI) (Phillips Slurry process). The final hydrophilic polymer blend included PEO at 35% by weight. Only the PEO was dried as the HDPE is hydrophobic. The PEO was dried under a vacuum to approximately 0.03 weight percent water.
A PEO with a molecular weight of 7,000,000 was mixed with Pebax 72D. The final hydrophilic polymer blend included PEO at 35% by weight. Both materials were dried under a vacuum to approximately 0.03 weight percent water.
In the ninth example a PEO with a molecular weight of 7,000,000 was utilized as the hydrophilic polymer and HDPE was the structural polymer. The final hydrophilic polymer blend included PEO at 40% by weight. The PEO was dried under a vacuum to approximately 0.03 weight percent water. The produced strands were cooled by conventional means, which included running the strands through a water bath at approximately room temperature and then pelletized.
A PEO with a molecular weight of 7,000,000 was utilized as the hydrophilic polymer and Pebax 72D was the structural polymer. The final hydrophilic polymer blend included PEO at 40% by weight. The produced strands were cooled by running on a conveyor belt cooled with an air conditioner and then pelletized.
The hydrophilic polyblend was formed utilizing 20% by weight PEO, with a molecular weight of 7,000,000, with 80% by weight Pellethane 90A. The two polymers were first mixed together with about 2% by weight triallyl triazine trione (Aldrich Chemical Co., Milwaukee, Wis.) and about 0.2% by weight Irganox 1098. The materials were added to the extruder through one feeder.
The miscibility characteristics of PEO in Pebax versus PVP in Pebax was compared. A polyblend of 40% PEO (WSRN12K, 1,000,000 MW)/60% Pebax 72D with 0.2 pphr (parts per hundred resin) Irganox B225 was formulated to compare with a polyblend of 40% PVP (K-90, 900,000-1,700,000 MW)/60% Pebax 72D with 0.2 pphr Irganox B225. After creation of each polyblend the material was extruded into a cylinder and cross-sectioned. The samples were placed in water at room temperature for 8 hours to dissolve the hydrophilic phase. Each sample was then dehydrated for eight hours in a vacuum oven and gold coated for viewing under a scanning electron microscope.
Each of the co-extruded PEO and PVP polyblends were also tested for suitability in a medical device. The PVP polyblend displayed brittle characteristics and could only be elongated less than 5%. The brittleness of the compound rendered it unacceptable for medical device applications. Moreover, upon hydration in 37° C. water the co-extruded PVP became only moderately lubricious to the hand.
In comparison, the PEO polyblend rendered a tough compound with high strength. The PEO polyblend was tested and showed elongation values greater than 80%. The tough properties of the PEO polyblend also made it useful for medical device applications. Moreover, upon hydration in 37° C. water the PEO polyblend became very lubricious to the hand. PEO polyblends, therefore, are superior to PVP polyblends for medical device lubricating applications.
Medical Devices Formed from the Polyblend
The inner layer 12 forms a lubricious surface when exposed to blood or other suitable polar liquids, such as water. The lubricious surface may reduce the drag friction experienced by a lead or stent when passed through the tube. In addition, the lubricious surface may reduce drag friction when incorporated as part of a telescoping dual catheter arrangement. In this telescoping embodiment, the lubricious layer may be included on the inside of the outer guide, the outside of the inner guide, or both.
In further embodiments, the inner layer 12 (or other medical device formed utilizing the lubricious polymer blend) may be electron beam cross-linked with, for example, a 10 kEV electron beam. Such an electron beam may be at a variety of strengths, such as at 5 or 10 Mrad, and may be applied once, twice, or more than twice. Utilizing such an electron beam is known in the art for sterilizing catheters and also for helping to secure the layers of the catheter together. Cross-linking the inner layer 12 improves the retention rate of the PEO when a stent or other device is passed through the lumen of the catheter. Such cross-linking may also improve the retention rate of the lubricious surface on the outside of the catheter. Cross-linking may furthermore reduce the swell rate.
The cross-linking of the PEO polyblend may form a cross-linked polymer matrix (an interpenetrating cross-linked network) that is water swellable. Such a material may form a hydrogel when hydrated. During hydration the hydrogel will not dissolve in the aqueous solution but will become water swollen and lubricious. Determining the right amount of cross-linking energy to expose the PEO polyblend to may be determined by minimizing the amount of free PEO that dissolves during hydration. This amount may be determined by the sol point or weight loss of the hydrogel after cross-linking, hydration, and drying. As may be appreciated, various structural polymer materials may be more or less susceptible to cross-linking in this manner. In addition, other agents may be added to the polyblend to improve the cross-linking and to affect the resultant structure.
In one example, a two-layer catheter liner (tube) was formed by co-extrusion using the 40% PEO (1 million MW)/Pebax 72D polyblend as an inner layer with Nylon 12 as the outer layer. The PEO polyblend inner layer was approximately 0.002 inch thick. The swell characteristics of the liner was then determined by soaking in a water bath at 37° C. and measuring at certain time intervals. As can be seen from
In still another embodiment illustrated in
As illustrated in
As may be appreciated, in further embodiments the lubricious polyblend of the present invention may be utilized with any type of medical device known to those in the art that benefits from a lubricious layer.
In another embodiment, a 20% PEO-PU polyblend (Pellethane® 90AE) material was formed. The material was then extruded to form a tube and cross-linked by exposure to an electron beam at 5 and 10 Mrads. As illustrated in
In further embodiments, the tubing formed from any of the previously described mixtures may be melted and utilized to directly coat a guidewire using a process such as is disclosed in U.S. Pat. No. 6,695,915, which is incorporated by reference for all that it teaches and discloses. Such a guidewire may be lubricous when exposed to blood during insertion and therefore be more easily inserted further into the vasculature. Moreover, the reduced swelling may aid in vasculature insertion. The lubricious hydrophilic polyblend may also be coated on the guidewire by other methods known to those in the art, such as dipping the guidewire directly into a melt pool of the hydrophilic polymer blend or by any other method known to those in the art. Various characteristics of the guidewire may make the polyblend may influence adhesion on to the guidewire. In further embodiments, pre-coatings or other pre-treatments may be applied to the guidewire before coating with the polyblend. Moreover, cross-linking the material coated on the guidewire may reduce swelling and improve retention of the lubricious material.
Other intravenous devices for which the present invention polyblend may impart desirable lubricious properties may include 1) a guiding catheter shaft using the hydrophilic compound as the inner layer; 2) a polymer shunt or stent delivery device where the hydrophilic compound is the inner layer and is impregnated with an anti-coagulant agent to prevent clotting, cholesterol or other blood component build up in the arteries; 3) an implantable device (lead) outer or inner layer; and 4) a lead electrode coating.
Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present invention. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.
