WO2007018618A1

WO2007018618A1 - Improved hydrophilic coating method and article

Info

Publication number: WO2007018618A1
Application number: PCT/US2006/011016
Authority: WO
Inventors: Thomas H. Gilman
Original assignee: Hollister Incorporated
Priority date: 2005-07-27
Filing date: 2006-03-27
Publication date: 2007-02-15

Abstract

A method of forming a hydrophilic coating of polyvinylpyrrolidone or a substrate using a solvent mixture of nitroethane and a ketone.

Description

IMPROVED HYDROPHILIC COATING METHOD AND ARTICLE

Background and Summary of the Invention

[0001] United States Patents 4,585,666 and 4,666,437 disclose a method for forming on a polymeric substrate a hydrophilic coating that becomes lubricious when wetted with a water-based liquid. The coating is formed by applying to the substrate a compound that has at least two unreacted isocyanate groups per molecule, then evaporating the methylene chloride solvent, and then applying a solution of polyvinylpyrrolidone to the treated substrate surface and again evaporating the methylene chloride solvent. The coating is then cured with moist heat to polymerize the isocyanate into a polyurea that serves to anchor the polyvinylpyrrolidone on the substrate.

[0002] While methylene chloride is disclosed as the preferred solvent for both coating steps, the use of methylene chloride is not free of problems. Methylene chloride has a very low boiling point (40.1 degrees C.) which makes for fast evaporation and results in a process that is difficult to control, being affected dramatically by small changes in temperature, air movements, relative humidity and the like. Methylene chloride is also recognized as presenting biocompatibility issues. It is a known human carcinogen and has been listed in terms of its tolerable intake level at 0.2 mg/day (California Proposition 65 list).

[0003] The concern involves not only the manufacturing environment but also the conditions of product use. The need to provide a lubricious surface for a substrate is particularly evident in the medical field where the use of medical articles, such as urinary and vascular catheters, benefits greatly if such articles have lubricious coatings that facilitate the medical procedures and reduce patient discomfort and potential injury. However, if there is any risk that a patient might be exposed to even trace amounts of methylene chloride, then the disadvantages posed by that risk might be far greater than the benefits derived from the use of such a solvent system. [0004] Despite these and other shortcomings, the art has so far failed to identify other solvents as effective as methylene chloride for dissolving isocyanates and polyvinylpyrrolidones and, in addition, for swelling the surface of a polymeric substrate to promote a secure attachment of a highly lubricious hydrophilic coating. In some applications, it also desirable for the coating to have an adequate "open time" for a user. The term "open time" is used here to mean the length of time a hydrated coating will remain lubricious in a drying environment, it being understood that such a coating loses its lubricity as it dries.

[0005] In the prior published patent art, other solvents have been suggested for use, such as ethylacetate, acetone, chloroform, methyl ethyl ketone, ethylene dichloride and 1 ,2 trans dichloroethylene. However, in practice PVP is not sufficiently soluble in ethylacetate, acetone, or methyl ethyl ketone. The chlorinated solvents will have similar biocompatibility issues as methylene chloride, and again they are not as effective as solvents. For further information concerning the state of the art, reference may also be had to the following United States patents: 6,629,961 ; 4,487,808; 4,906,237; 4,459,317; 5,077,352.

[0006] This invention concerns the discovery that a solvent mixture of nitroethane and a ketone is highly effective in dissolving polyvinylpyrrolidone and also swelling the surface of a polymeric substrate such as polyvinylchloride and, in addition, avoiding or greatly reducing the biocompatibility problems associated with the use of methylene chloride. Using the method of this invention, a substrate, particularly one for medical applications, such as a urinary catheter, may be provided with a highly lubricious hydrophilic polyvinylpyrrolidone-based coating that is well anchored to the substrate. Further, the method provides a means to make coatings having sufficient thickness and stability to offer extended open time following hydration. The invention includes the further discovery that such a coating is achieved only at relatively high polyvinylpyrrolidone concentrations and at a narrow range of selected nitroethane and methyl ethyl ketone ratios.

Detailed Description of Preferred Embodiments

[0007] The technical approach of using PVP as a hydrophilic polymer to form the basis of a hydrophilic coating, and polymerizing a multifunctional isocyante in the presence of PVP and in the presence of a solvent-swollen substrate, provides a very effective, well anchored, lubricous hydrophilic coating. In considering solvents for use in applying such a coating system, one would like to choose solvents that are not very low in boiling point, as is the case for methylene chloride (41C), nor very high, like the commonly used N-Methyl 2 pyrollidone (212C). The very low boiling point of methylene chloride causes some process control difficulties, and very high boiling solvents like N-Methyl 2 pyrollidone are difficult to remove from the product prior to use. Another consideration is that ideal boiling point solvents such as methanol or ethanol cannot be used, because they will react with the isocyanate and prevent its polymerization. To avoid this issue, one needs to choose an aprotic solvent. Nitroethane is a somewhat unique aprotic solvent with a relatively attractive boiling point (114 degrees C), that effectively dissolves polyvinylpyrrolidone (PVP). However, nitroethane lacks the ability to appreciably swell the surface of a polymeric substrate such as polyvinylchloride (PVC). However, by blending nitroethane and a ketone, for example methyl ethyl ketone, in carefully selected proportions, a solvent mixture is provided that may be easily and safely handled in production and is highly effective in the coating method of this invention, resulting in a stable hydrophilic coating that becomes lubricious when wetted with a water-based liquid. In certain proportions, we have found that a methyl ethyl ketone-nitroethane system is also capable of making coatings sufficiently thick to provide extended open time when used on medical products such as catheters.

[0008] While PVC is mentioned as a suitable substrate, the coating may be applied to the surfaces of articles made from any of a number of different polymers such as latex rubber and other rubbers, other vinyl polymers, polyesters and polyacrylates. PVC is identified here because it is commonly used for making catheters which are required to be relatively soft, flexible and non-irritating to body tissues, and PVC is relatively inexpensive.

[0009] The first step in the method of this invention comprises applying to the substrate surface a first solution of a multifunctional isocyanate dissolved in a ketone, for example methyl ethyl ketone. More specifically, the compound must contain at least two unreacted isocyanate groups per molecule. Suitable isocyanate containing compounds known in the art are 4,4'-diphenylmethane diisocyanate, 2,4-toluene diisocyanate, a pentamer of hexamethylene diisocyanate and toluene diisocyanate trimerized hexamethylene diisocyanate biuret.

[0010] The isocyanate solultion may advantageously contain between 0.5 to 10%, preferably 1 to 6%, (weight/volume) of isocyanate compound and may be applied by dipping or spraying or the like, followed by evaporating at least some of the methyl ethyl ketone solvent, preferably by air drying. Thereafter, the surface is again coated, this time with a second solution of PVP dissolved in a solvent mixture of nitroethane and the ketone, and allowed to dry. Finally, the substrate with its first and second coatings is exposed to moist heat (usually ambient air at 50 to 100 degrees C.) for an interval of 5 to 40 minutes. In such curing step, the isocyanate groups react with water to yield a polyurea/PVP interpolymer that anchors the PVP to the substrate.

[0011] In accordance with the teachings of the prior art, the PVP should have a mean molecular weight of between 10⁴ and 10⁷, preferably about 10⁵. In the prior art teachings, the maximum PVP concentration is generally considered to be 10% and is preferably 6% to 8% (weight/volume, i.e. kg/I). Here, however, to obtain the most functional coatings, the concentration should exceed 10%, and will then yield the most effective type of coating only if the proportions of nitroethane and the ketone in the solvent mixture are carefully controlled. It has been found that a solvent mixture containing about 65% to 85% (weight/volume) nitroethane and about 15% to 35% (weight/volume) methyl ethyl ketone is effective. A solvent mixture of about 75% nitroethane and 25% methyl ethyl ketone is believed particularly effective.

[0012] By way of comparative examples, a 50:50 ratio of nitroethane and methyl ethyl ketone, when used with PVP at a concentration of 6% (a concentration notably used when methylene chloride is the solvent), results in cured coatings that are highly lubricious and are well anchored to a PVC substrate. These coatings are very functional for certain applications, for example peripheral intravenous catheters. However, these coatings are too thin to have the open time demanded for some applications, for example, single use intermittent urinary catheters. When PVP concentrations higher than 6% are used, a 50:50 ratio for the solvent mixture results in coatings that are unstable and slide off of the substrate before the solvent mixture has evaporated, leading to even thinner and less acceptable coatings.

[0013] The surprising aspects of this invention become particularly apparent If a comparison is made with a method involving the same constituents where the solvent mixture is changed to 75:25. Again, the coating exhibits the same instability problem found with a 50:50 ratio, the material sliding off of a substrate leaving a coating that is unacceptably thin even when the PVP concentration is increased to 10%. However, surprisingly, with the same substrate and a solvent ratio of 75:25, excellent results are obtained when the PVP concentration is elevated to 12% weight/volume (the solvent mixture then constituting 88% weight/volume). Such coating is found to be highly stable and of a thickness sufficient to produce extended open times upon hydration.

[0014] The biocompatibility profile for a solvent system of this invention is superior to that of the solvent system commonly used in the prior art, namely, methylene chloride. North American Scientific Associates (NAMSA) is widely respected as a biocompatibility testing house and has assessed what it deems to be tolerable intake levels for nitroethane and methyl ethyl ketone in humans. Such levels are based on NAMSA's review of existing toxicology literature on these solvents. For nitroethane, the tolerable intake level is found to be more than 70 mg/day and for methyl ethyl ketone it is more than 0.5 grams/day (both for a 70 kg person).

[0015] In contrast, the tolerable intake level for methylene chloride has been set by the State of California (which deems methylene chloride to be a human carcinogen) at 0.2 mg/day. So, compared to nitroethane (the more restricted solvent of our two-solvent mixture), the intake level for methylene chloride used in prior art coatings is at least 350 times lower (less tolerable) than the solvent system of this invention.

[0016] While in the foregoing I have disclosed the invention in considerable detail for purposes of illustration, it will be understood by those skilled in the art that many of the details may be varied without departing from the spirit and scope of the invention.

Claims

Claims:

1. A method of forming on a polymeric substrate a hydrophilic polyvinylpyrrolidone coating that becomes lubricious when wetted with a water-based liquid, comprising the steps of applying to the surface of the substrate a first solution of a multifunctional isocyanate dissolved in a ketone to form a first coating on said substrate; drying said first coating; then applying to said coated substrate a second solution of polyvinylpyrrolidone dissolved in a solvent mixture of nitroethane and a ketone to form a second coating on said substrate; then exposing said substrate with said first and second coatings to moist heat at a temperature and for a time sufficient to polymerize said isocyanate into a polyurea serving to anchor the polyvinylpyrrolidone polymer on said substrate; the concentration of said PVP and the ratio of said nitroethane and methyl ethyl ketone of said solvent mixture being selected to produce a stable hydrophilic coating of suitable thickness on said substrate.

2. The method of claim 1 where the ketone is methylethylketone.

3. The method of claims 1 Or 2 in which the concentration of said polyvinylpyrrolidone in said second solution exceeds 10% by weight/volume.

4. The method of claim 3 in which said concentration of said polyvinylpyrrolidone in said second solution falls within the range of about 11 % to 15% by weight volume.

5. The method of claim 4 in which said concentration of said polyvinylpyrrolidone in said second solution is about 12% by weight volume.

6. The method of claims 2, 3, 4 or 5 in which said solvent mixture of said second solution comprises about 65% to 85% nitroethane and about 15% to 35% methyl ethyl ketone, by weight volume.

7. The method of claim 6 in which said solvent mixture comprises about 75% nitroethane and 25% methyl ethyl ketone, by weight/volume.

8. The method of any of the foregoing claims in which said polymeric substrate is selected from the group consisting of vinyl polymers, polyesters, polyacrylates and rubber, including latex rubber.

9. The method of claim 8 in which said polymeric substrate is polyvinylchloride.

10. A polymeric substrate having a polyvinylpyrrolidone coating formed in accordance with any of claims 1-9.

11. The polymeric substrate of claim 10 in which said substrate is in the form of a medical article.

12. The polymeric substrate of claim 11 in which said medical article is a catheter.

13. The polymeric substrate of claim 12 in which said catheter is a urinary catheter.