CA2007884C - Hydrophilic lubricious coatings - Google Patents
Hydrophilic lubricious coatingsInfo
- Publication number
- CA2007884C CA2007884C CA002007884A CA2007884A CA2007884C CA 2007884 C CA2007884 C CA 2007884C CA 002007884 A CA002007884 A CA 002007884A CA 2007884 A CA2007884 A CA 2007884A CA 2007884 C CA2007884 C CA 2007884C
- Authority
- CA
- Canada
- Prior art keywords
- solvent
- poly
- polyisocyanate
- polymer
- coated substrate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
- B05D5/04—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain a surface receptive to ink or other liquid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D3/00—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
- B05D3/10—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by other chemical means
- B05D3/101—Pretreatment of polymeric substrate
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/62—Polymers of compounds having carbon-to-carbon double bonds
- C08G18/6216—Polymers of alpha-beta ethylenically unsaturated carboxylic acids or of derivatives thereof
- C08G18/625—Polymers of alpha-beta ethylenically unsaturated carboxylic acids; hydrolyzed polymers of esters of these acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/703—Isocyanates or isothiocyanates transformed in a latent form by physical means
- C08G18/705—Dispersions of isocyanates or isothiocyanates in a liquid medium
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/04—Coating
- C08J7/042—Coating with two or more layers, where at least one layer of a composition contains a polymer binder
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/04—Coating
- C08J7/0427—Coating with only one layer of a composition containing a polymer binder
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/04—Coating
- C08J7/043—Improving the adhesiveness of the coatings per se, e.g. forming primers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/04—Coating
- C08J7/046—Forming abrasion-resistant coatings; Forming surface-hardening coatings
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/04—Coating
- C08J7/056—Forming hydrophilic coatings
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/04—Coating
- C08J7/06—Coating with compositions not containing macromolecular substances
- C08J7/065—Low-molecular-weight organic substances, e.g. absorption of additives in the surface of the article
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D2201/00—Polymeric substrate or laminate
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D3/00—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
- B05D3/10—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by other chemical means
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
- B05D5/08—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain an anti-friction or anti-adhesive surface
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2375/00—Characterised by the use of polyureas or polyurethanes; Derivatives of such polymers
- C08J2375/04—Polyurethanes
- C08J2375/12—Polyurethanes from compounds containing nitrogen and active hydrogen, the nitrogen atom not being part of an isocyanate group
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2433/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
- C08J2433/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
- C08J2433/06—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing only carbon, hydrogen, and oxygen, the oxygen atom being present only as part of the carboxyl radical
- C08J2433/08—Homopolymers or copolymers of acrylic acid esters
Abstract
IMPROVED HYDROPHILIC LUBRICIOUS COATINGS
ABSTRACT OF THE DISCLOSURE
A new method is provided to impart a hydrophilic lubricious coating onto articles such as medical devices. A device, for example a catheter, is first contacted with a polyisocyanate solution, to provide coupling, then contacted with a poly-carboxylic acid) solution to give a coating, and is then finally oven dried. These coatings have lubricity that only becomes manifest upon exposure to water or body fluids, and moreover, are also long lasting and have good abrasion resistance. This combination of properties is not available from other currently used or proposed coatings such as Teflon?.
ABSTRACT OF THE DISCLOSURE
A new method is provided to impart a hydrophilic lubricious coating onto articles such as medical devices. A device, for example a catheter, is first contacted with a polyisocyanate solution, to provide coupling, then contacted with a poly-carboxylic acid) solution to give a coating, and is then finally oven dried. These coatings have lubricity that only becomes manifest upon exposure to water or body fluids, and moreover, are also long lasting and have good abrasion resistance. This combination of properties is not available from other currently used or proposed coatings such as Teflon?.
Description
20~788~ ~
INPROVED HYDROPHI~.IC LUBRICIOUS COATINGS
BA~RGRO~ND OF ~ INV~NTIO~
(1) FI~LD OF T~ INVENTIOW :;:
This invention relate~ i~ general to coated sub~trate~. In one a~pect, thi~ in~e~tion i8 directed ~:
to medical device~ and other sub~trate~ ha~i~g `:
improved lubriciouB coatin~3. I~ a further a~ect, thi~ invention ~rovide~ medic~l de~ice~, ~uch a~ -catheter~, guide wire~ and the like, which when dry exhibit little or no lubricity but when moi3tened, ~05~e~3 a lubricity which aid~ in movin~ the devices ;~
within the body with ea~e and little di~comfort. In another a~ect, this invention i~ directed to a ~roce~ for the ~reparation of the coated medical de~ice~ which are usaful in the diagno~i3 or treatment of variou~ condition~ in the human body.
INPROVED HYDROPHI~.IC LUBRICIOUS COATINGS
BA~RGRO~ND OF ~ INV~NTIO~
(1) FI~LD OF T~ INVENTIOW :;:
This invention relate~ i~ general to coated sub~trate~. In one a~pect, thi~ in~e~tion i8 directed ~:
to medical device~ and other sub~trate~ ha~i~g `:
improved lubriciouB coatin~3. I~ a further a~ect, thi~ invention ~rovide~ medic~l de~ice~, ~uch a~ -catheter~, guide wire~ and the like, which when dry exhibit little or no lubricity but when moi3tened, ~05~e~3 a lubricity which aid~ in movin~ the devices ;~
within the body with ea~e and little di~comfort. In another a~ect, this invention i~ directed to a ~roce~ for the ~reparation of the coated medical de~ice~ which are usaful in the diagno~i3 or treatment of variou~ condition~ in the human body.
(2) D~SCRIPTION OF TH~ RE~ATED ART
Catheter~ which are u~ed ~ur~ically ~or insertion through blood vessels, urethrea, or body conduit~, and guide wire~ u~d with catheter~ for ~io~sy, balloon angio~la~ty and other medical ~i ~rocedure~ require a low-friction ~urface for ~re~enting `in~ury !to~ or inflamm tion o~, mUCOU
membrane~ and oth~r body ti~ue~
One cla~s o$ conventional catheter~ i~ made of low-friction m~terial~ ~uch as Teflon~, ~olyeth~lene or D-16094-1-C ~
788~L
other materials coated with a layer of Teflon or silicone. There are two shortcomings of these ~ -catheters: First, they are not sufficiently slippery ` ~ ~;
for the intended surglcal purposes mentioned above.
Second, they are difficult to handle and store because their surfaces are slippery at all times. ;
Another class of conventional catheters is rendered lubricious by coating with a layer of silicone fluid, glycerin, or olive oil. These materials are unsatisfactory because the low molecular weight additives tend to run off ~uickly. Thus, they lose the initial lubricity rather rapidly.
A~other class of conventional surface treatment involves the deposition of poly(vinyl pyrrolidone) in the presence of a polyisocyanate. This type of coating while lubricious initially lacks abrasion resistance, and is therefore easily removed from the surface of the medtcal devtces. An improved version of this technique was described by R. A. Winn in V. S.
Patent 4,373,009, where an active hydrogen containing vinyl pyrrolidone copolymer was used instead to result in a better bonding tc the substrate. The "monome~s containing active hydrogen" were needed according to Winn "to form a covalent bond between the coupling coating and the hydrophilic copolymer". These copolymers, however, were of unknown quality ~n terms of purity, toxicity, or not of sufficiently high molecular weight needed for this application. Both the availab:Llity and usefulness of these copolymers 30 are highly questionable.
In U.S. Patent ~,119,094, a substrate such as a 2~5~1788~
tube or catheter is disclosed having a hydrophillc coating which exhibits a low coefficient of friction.
The substrate is coated with a poly(vinyl pyrrol-idone)-polyurethane interpolymer. A polyisocyanate and a polyurethane mixture is applied to a substrate and after drying, a poly(vinyl pyrrolidone) in solution is applied.
U.S. Patent 4,589,873, issued on May 20, 1986 to A. Schwartz et al and discloses a method of applying a 10 hydrophilic coating to a polymeric substrate. The coating consists of poly(vinyl pyrrolidone) which is applied to the substrate in a solvent followed by drying.
W.S. Creasy et al were granted U. S. Patent 4,642,267 on February 10, 1987 which discloses and claims a hydrophilic polymer blend. The blend is comprised of a thermoplastic polyurethane havlng no reactive isocyanate groups and a hydroph~lic poly(N-vinyl lactam) such as poly(vinyl pyrrolidone). The blend can contain additional polymeric components such as homopolymers or copolymers of monomers including ;
vinyl chloride, acrylic acid, vinyl alcohol and the like.
A process for coating a polymer surface with a hydrophilic coating is also disclosed in U.S. Patent 4,666,437. A sol~ution of a compound containing at least two unreacted isocyanate groups per molecule is appl~ed to the polymer surface and the ~olvent evaporated. Thereafter, a solution of poly(vinyl pyrrolidone) i5 applled to the treated surface and the coated cured.
Accordi.ng to European patent application 0166998, .
2 ~ ~ 7 8 ~
N. Takamura de3cribed lubriciou~ coatin~ derived ~rom either a cellulo3ic ~olymer, a maleic anhydride pol~mer, a ~olyacrylamide or a ~ater-~oluble nylon which were convalen~ly bonded to a medic~l in~trument ~ub~trate. The ~ub~trate contained reactive ~unctional ~roup3 ~uch a3 aldehydea, e~oxy, i~ocyanate or amino ~rou~s. The re~erence indicate~ that the water soluble ~olymerR are non-cro~linked and contain hydro~hilic grou~s such a~ -0~, -C0NH2, -COOH, -NY2, -C00~, -S03-, and -MR3, R being alkyl or hydrogen.
However, a cellulo~ic ~olymer i~ undesirable becau~e it mu~t be ~rotected a~ain~t microbe attack.
Coatin~ made from a maleic a~hydride ~olymer must ~o through a tedious ~o~t tr,satment with water before developing lubricity, while water-~oluble nylon~ may have questionable ~tability.
It ha~ now unexpectedly and ~ur~ri~in~ly been ~ound that hi~h molecular weight carboxylic acid-containing ~olymer or their partially neutralized ~alt~, can be strongly bonded to a ~ubstrate, such a~
a catheter, u~ing a ~olyisocyanate reagent and at the ~ame tlme ~rovide~ a hydro~hilic lubriciou~ coatin~
Thus, the need for either an interpenetratin~ network containing poly(vinyl ~yrrolidone) and ~olyurethane or ~ ~ -a co~olymer containin~ both non-active hydro~en units and active-hydro~n unit~ can be avoided.
Furthermore, there is no ~eed for any ~o~t hydroly~
treatment in the invention. ~nlike a malaic anhyd~id~s ~olymer, the coa~ing devlslo~ lubricity in~tantly u~on eXpo~ure to an aqueou~ ~luid. Poly- -~
(acrylic acid~), 8uch a~ the Carbo~ol~ manu~actured ~':-.
16094-1-C ~ `
~788(~
by B.F. goodrich, are ideally suited for the intended medical applications, and also have sufficiently high molecular weights necessary for achieving both good hydrophilic lubricity and abrasion resistance.
Accordingly, one or more of the following objects will be achieved by the practice of this invention.
It is an object of this invention to provide medical and other devices which when dry do not exhibit a slipp~ry surface, but when contacted with a fluid such 10 as water, become very lubricious. Another ob;ect of this invention is to provide medical and other devices which are easily handled without fear of slipping, but when moistened or contacted with body fluids instantly become very lubricious. A further object of this 15 invention is to provide medical devices having a ;
coating of a poly~carboxylic acid) and a polyisocyanate which when dried can be handled with ease, but when moistened, become very slippery. A
still further ob;ect of this invention is to provide processes for the preparation of the coated medical and other substrates. Another object is to provide medical and other devices and instruments which have a coating of a material which becomes lubricious upon exposure to body fluids. These and other objects will readily become apparent to those skilled in the art in the light of the teachings herein set forth.
SUMMAR~ OF THE INVENTION
~ n its broad aspect, this invention is directed to coated substrates having a lubricious coating which 30 becomes slippery only upon exposure to an aqueous ~- ~
fluid. The invention is also directed to a method for ~ ~`
:: ' D-16094-1 ~
: 2(~7138a~
coating the devices and substrates as well as to the coated articles themselves.
One or more polyi~ocyanates ~s ap~ ~ a substrate such as a medical device. The co~.~ct time may vary fro~ a few seconds to an hour or mo~e depending upon the material of construction of the medical device and the polyisocyanat~ Pmployed. The primer coated medical device can be ~rled ~n an oven for removal D~ ~ny solvent and then ~ carboxylic acid-containing polymerlc top coat applied directly to the polyisocyanate coated device. The coa~ed medical device is then dried to complete the coat~g process.
The finished medical device has normal feel and handlin~ characteristics when dry. Upon exposure to body fluids, however, it becomes lubricious instantly.
DETAILED DESCRIPTION OF THE INVENTION
The hydrophilic lubricious coating of this invention is prepared ~y fir~t contacting ~ sub~trate or medical device, such as a catheter, with a polyisocyanate such as a toluene diisocyanate in a liquid medium. The liquid medium can be removed by drying or the the cathet~r ~an ~e ~treated directly wlth a high molecular weight poly(carboxylic acid) in a liquid medium. After drying in an ovem~ a non- ~ ;
tacky, easy-to-handle, and uniformly coate~ ~atheter is obtained. The surface of the rèsultant catheter becomes lubricious ins~ntly ~p~ ~e~posure to an aqueous solution or body fluids.
In addition to a quick initial lubricity, the ~ -~
hydrophilic lubrlcious coa~ing oE ~his lnventio~ is resistant to abrasion. Consequently, a catheter ;~ ~
.
Z~
coated in accordance with the teachings of thls invention will retain a lubricious surface for a long duration which is often required during the course of a surgical procedure.
Unlike catheters made of or coated with Teflon or sillcones, catheters coated in accordance with the present invention are non slippery when dry but become instantly slippery when wet. As a result, medical devices coated with the hydrophilic lubriclous coatings of this invention are easier to handle and store.
The term "bath" as employed throughout the specification and appended claims is meant to include not only solutions of the indicated organic compounds, but dispersions and emulsions.
Application of the coatings from the bath can be effected by a variety of methods and includes, but is not llmited to, dipp~hg, spraying, electrical deposition, painting and the like. Optionally, the coated substrate can be further treated with an aqueous bath to partially or totally neutralize the free acid. In those instances wherein the substrate is subjected to high temperatures, such as tn thermoforming processes, the treatment with the 25 aqueous bath to effect neutralization or part~al ~ ~ ;
neutralization is desired.
As indicated above, the hydrophilic lubricious coating of this invention is comprised of at least two components; a polyisocyanate primer and a water~
soluble or water dispersible polymer topcoatO They are normally applied in two separate coating steps.
~ ' Z~7138~
However, if desired, the drying step after application of the polyisocyanate coating can be omitted and drying effected after application of the top coat.
The solvents useful for applying the polyisocyanates include methyl ethyl ketone, ethyl acetate, ethyl lactate, chloroform, trichloroethylene, dichloromethane, hexane, heptane, toluene, their mixtures with mineral oil~ or other suitable organic solvents which do not react with isocyanates under the coating conditions. The preferred solvent is methyl ethyl ketone.
Alternatively, the polyisocyanates can be dispersed in a solvent/non-solvent mixture to form a dispersion or emulsified to form an oil-in-water emulsion. When an emulsion is used, the reactive isocyanate groups need to be protected by suitable chemical groups known to those skilled in the art.
A wide variety of polyi~ocyan~tes can be employed in preparing the coatings of the present invention and include, but are not limited to, toluene-2,3-diisocyanate, toluene-2,6-diisocyanate, commercial mixtures of toluene-2,4- and 2,6-diisocyanates, 4,4'-diphenylmethane diisocyanate, cyclohexylene-1,4-diiisocyanate, m-phenylene diisocyanate, 3,3~diphenyl-25 4-biphenylene diisocyanate, 4,4-biphenyl ~;
diisocyanate, l,6-hexamethylene diisocyanate, 1,5 naphthalene diisocyanate, cumene-2,3-diisocyanate, 2,4-diisocyallatodiphenylether, 5,6-dimethyl-1.3 phenylenediisocyanate, 2,4-dimethyl-1,3-phenylenedii~ocyanate, 2,~-dimethyl-1,3 phenylenedii~ocyanate, 4,4-diisocyanatodiphenylether, 9,10-anthracene dilsocyanate, 2,4-diisocyanatotoluene, ~ ~ ) 2(~88~
g 1,4-anthracene diisocyanate, 2,4,6-toluene l -triisocyanate, isophorone diisocyanate, and p,p',p"- ~
triphenylmethane triisocyanate, and the like. Equally ~ -u~eful are isocyanate end-capped prepolymers and adducts, isocyanate end-capped polyfunctional aromatic adducts, isocyanate end-capped polyfunctional aliphatic adduct and two component systems such as end capped aliphatic polyester polyol and aliphatic polyol compound, and their mixtures with different 10 polyisocyanates as d~scribed above.
Illustrative of isocyanate end-capped adducts are the reaction products of 2,4-tolylene dilsocyanate, 4,4'-diphenylmethane diisocyanate, polymethylenepolyphenyl isocyanate, or 1,5-naphthylene dlisocyanate, with 1,2-polypropylene glycol, polytetramethylene ether glycol, 1,4-butanediol, 1,4-butylene glycol, 1,3-butylene glycol, poly~1,4-oxybutylene) glycol, caprolactone, adip~c acid esters, phthalic anhydride, ethylene glycol, diethylene `~
glycol, and the like.
The polymers suitable for use in forming the top coatings of the present invention are carboxylic acid-containing polymers. The polymer can be a free acid or partially neutralized as 25 represented by the following formula: -Z n H. m p 2~a7ss~l - ~o -where n = 0-0.95 mole fracl:ion of ~eutralize~ acid moietie~;
m - 0.05-1.0 mole raction of acid moietie~ with the ~roviso that n+m = 1;
X1,X2,X3 are each a hydro~en atom or a Yuitable mono~alent organic radical, such a3 lower al~yl or cycloalkyl or aryl of u~ to 8 carbon atom~, and wherein the X grou~ are ~uch that the ~ol~mer remain~
water ~oluble;
0 Y iB either a sin~le bond or any suitable di~alent organic radical, ~uch aQ a hydrocarbon grou~ ~ :
of u~ to 8 carbon atom~, provided it does not ~ -ad~er~ely af~ect the ~olubility of the ~olymer; Z i~
either a metallic ion or a ~uitable ammonium ion;
a~d ~ i~ a very largo number ~uch that the ~olymer ha~ a molecular weight between about 200,000 and about 5,000,000. :
Even thou~h all ~oly(carboxylic acid) homopolymers can be u~e~ul to different de~ree~, the high molecular wei~ht ~olymer~ are more de~irable. : -The u~e~ul molecular weight~ ran~e from 200,000 to .~
about 5,000,000. Re~resentative carboxylic acid . ~:
containi~ homo~olymer~ include, but are not li~ited to, ~oly~acrylic acid), ~oly(methacrylic acid), ; ~:
poly(i~ocrotonic acid), and the like, the ! ' ..
~oly(carboxylic acid) of this inventio~ can be either linear or ~artia~ly cro~-linked ~uch that it would ;
~orm either a ~olution or a colloidal d~ r~ion in ;:~
the coating medium. The ~re~erred ~oly(car~oxylic acid) ~o:Lymer i3 a ~oly(acrylic acid) ha~ing a ' '~
: .
200788~
molecular weight of ~xom abou~ 200,000 to about 5,000,000. Particularly ~xeferred ~oly(carboxyl~c acid) ~olymerR include ~oly(acrylic acid) ~olymers having mole~ular wei~hts oi from about 1,000,000 to about 3,000,000.
Olefinic a~id~ ~uch a~ acrylic acid can be co~olymarized with one or more of other unisaturated monomer~ to ~roduce copolymers containing carboxylic acid moieties. Examplary co~olymer~ include Carboset~ and Surlyn~ produeed by B.F. Goodrich and DuPo~t re~ectively. Co~olymer~ containing water-ini~oluble unit~ a~ well ais ~arboxylic acid unit3 ~an be mixed with the homopolymer~ if 80 de~ired, a~ long a~ they are com~atible.
Polyiam~holytes which conta~n one or more ~oly-meri~ acids mentioned above may be al~o useful for the ~ur~ose of this invention as lon~ as the basic moiety i~ a tertiary amine.
~ny organic solvents or mixed solvents for the ~oly(carboxylic acid) polymers used in thi~ invention may be em~loyed for making ths to~coat ~olution ~ro~ided that they are not reactive with the ~olyisocyanate~. Bxem~L3ry ~ol~entis or sol~ent m~xture~ include acetonitrile, ac~tonitrile-DMF ~,N-aimethyl formam~de (DNF), acetyl acetone, acrylonitrile, benzonitrile, diethyl a~etiamide, di~thyl formamide,i diethylformamide-DMF, dimet~yl acetamide, l,~-d~oxane, di~ro~yl sulfone, DMF-acetone, DNF-toluene, DMS0 (dimethyl sulfoxlde), DMS0-DMF, ethyl formamide, N-methyl-2-~yroolidone, nitrobenæene, nitrobenzene-DNF, ~henyla~etate, pro~ionitrile, ~ ~
~` ~'''~'' ~ ~ ) 2~7138~
styrene, and the like. The dissolution of poly(carboxylic acid) polymers in many of the above-mentioned sol~ents may be enhance by the additlon of suitable amines. The preferr~ed solvent is dimethyl formamide.
To prepare a seed-free poly(carboxylic acid) solution, it is advantageous to add a small amount of `
surfactant in the solvent before mixing with the ~ ~;
polymer. Any soluble surfactant or a mixture of ~-surfactants in the above-mentioned solvents may be useful. The preferred surfactants are soluble non-ionic surfactants such as polyoxyethylene sorbitan fatty acid esters, polyoxyethylene acids, polyoxyethylene alcohols, fluorinated alkyl esters, fluorinated alkoxylates and their mixtures.
Due to the high molecular weight of the poly(carboxylic acld) polymers preferred for use in the present invention, their solution viscosities may be too high to ~e suitable for some coating processes. ~ ~`
It is advantages in these instances to convert the polymer solution to a colloidal dispersion by mixing with one or more non-solvents. Exemplary non-solvents lnclude tertiary alcohols, ketones, aliphatic ethers, allphatic and aromatic hydrocarbons. The preferred non-solvents are acetone, methyethylketone (MEK~ and tertiary butyl alcohol.
Alternatively, the poly(carboxylic acid) may be emulsified to a water-in-oil emulsion. an example for forming such a water-in-oil emulsion is descrlbed ln my earller IJnlted States Patent No. 4,618,647.
'~ ~" . `~.L) 2(~)788~
For some applications it might be desirable to incorporate one or more add~tives in the coatings particularly the top coating. For example, some catheters are comprised of a thermoplastic rubber and it is preferred that the primer coating contaln a plasticizer to minimiæe loss of flexibility due to the coating operation. A wide variety of plasticizers can be employed such as the esters of fatty acids, mineral~ `
oil or silicone oil. The plasticizer must, of course, 10 be compatible with the components of the coatings and have no undersirable biological properties which would limit their use.
Other additives can be employed in the coat~nys `
ln addition to the surfactants such as, stabilizers, 15 antioxidants, antimicrobial agents, colorants, biological components and the like. ~or example, in catheters which are inserted into blood vessels, lt may be des~rable to have contained in the coating an ~`
antithrombogenic agent such as heparin, to avoid blood clot formation during the surgical procedure. The antithrombogenic agent can be used either as an `
additive or as a chemically bonded moiety of the polytcarboxylic acid) polymer.
The techniques employed in coat~ng the substrates and devices are not neces~arily critical and any coating processes suitable for making thin coatings may be utilized. For operations -~
where the ~;helf-life of the coating solutions ls not a :
D-16094-1 ~
7~
crltical issue, a single solution system containing a blend of both polyisocyanate and poly(carboxyl~c acid) may be used in a single coat operation.
In practice it has ~een found that excellent ;~
lubricity and abrasion resist:ance properties are obta~ned when the total thickness of the primer and top coating applied to the substrates in accordance with the teachings of this invention is from the sub-micron range to a few microns The concentration of the isocyanate and the carboxylic acid-containing polymer in the respective coating solutions can vary depending upon the particular components employed, their solubility as well as other considerations. In general the polyisocyanate component in the primer coating is contained in the coating solvent in an amount of at least about 0~1~ by weight. If the polyisocyanate is in li~uid form, it can be employed without a solvent.
However, in practice, it is preferred to employ the polyisocyanate in a solvent in a con~entration of from about 0.5 to about 20% by weight, and more preferably from about 1 to about 5% by weight.
The amount of the poly(carboxylic acid) component employed in the solvent will be controlled by the -viscosity of the medium. Most any concentration can .
be used as long as it is high enough ~o permit the preparation of a satisfactory coating, and yet is low enough so that the solution is not too viscous.
Concentrations of from about 0.1 to about 10% by we~ght are preferred with a concentration within the range of about 0.5 to about 2% by weight the most 7l3~4 preferred. In practice, the stoichiometry ls such that the molar ratio of carboxylic acid groups to isocyanate groups is in excess and will generally be at least about 1:1.
Although the drying temperatures and times are not necessarily critical, it has been found that the coated substrate can be dried at temperatures of from about 20 to about 150C and more preferably from about 50 to about 100C. Drying periods can range from a few secon~s to 60 minutes or more.
Many types of catheters need to be thermoformed to specific shapes for their intended applications.
Depending on the temperature and length of time of the thermoforming process many coated catheters may lose their hydrophilic lubricity during the thermoforming process. The degree of lubricity loss depends on the severity of the thermoformlng conditions.
Thus, when the temperatures are sufficlently high lubricity may be decreased due to the cyclization of -adjacent acid groups. Accordingly, it is preferred to neutrall2e or partially neutralize the acid groups to prevent such cyclization. The description of treatment of the acid groups by sodium phosphates and preferred formulations are set forth ln the example~
The hydrophilic lubricious coatings of this inve~tion are useful in coating medical devices, where a slippery exterior and/or interior, are necessary or desirable to minimize injury to tissues and to aid in man~pulation of the devices during surgical procedures. Examplary medical devices include catheters, needles, guide wires, prophylactic devices, ~ a~ ~
`: ` 2~)7~
_ 16 -delivery systems, filters, sheaths, and other accessories ~mpolyed in medical diagnosties, draninage, dilatation occlusion, vena cava and the like. While the invention iS particularly applicable to medical devlces, it can also be used to coat a variety of other substrates. for instance, the coatings can be applied to condoms, skis, toboggans, and those instances wherein a lubricious surface is desired.
In the examples which follow, certain abbreviations have been employed to define the various polyisocyanates and poly(carboxylic acids). All of the compounds are readily available from commercial sources.
PolYisocyanate Composition A- 1,6-diisocyanatohexane B- 2,4-toluene diisocyanate D- An isocyanate end-capped aliphatlc prepolymer having an average NCO
equivalent weight of 350 and a solution viscoslty of about 1,000 eps at 25C.
E- An aromatic lsocyanate end-capped pre-polymer average NCO equivalent weight 182.
Poly(carboxyl`ic acid ~ Composition L- A poly(acrylic acid) partially cross-linked homopolymer having a -molecular w~ight of about 3,000,000.
M- A USP grade poly(acrylie aeid) partially eross-linked homopolymer having a molecular we~ght of about 3,000,000. ~1 ~
"
D-~6094-1 - , ' "';
, , , -2(~788a~
- 17 - ~
.
N- A poly(acryllc acid) homopolymer havlng a ~ ~
molecular weight of about 1,250,009. ~ -The following examples are illustrative of the invention:
Exam~le 1 A nylon 6 coupon was compression molded from Capron 8000 (Allied Chemicalsl. The coupon was first dipped into a 1% solution of 1,6-diisocyanatohexane (A) in methyl ethyl ketone (MEK) for one hour. The ;
coupon was subsequently removed from the MEK bath and dried in a 60C air oven for 30 minutes. The dried coupon was then dipped in a 1% solution of -~
polytacrylic acid) ~L) in dimethylsulfoxlde ~DMSO) for one second. It was redried at 60C air oven for 30 minutes. ~he finished coating was smooth, non-tacky, as well as easy to handle. It became instantly slippery upon exposure to water.
Example 2 The coated nylon 6 coupon was soaked in a water bath for three hours at room temperature~ The soaked coupon retained a high degree of lubricity. T~is experiment shows that the poly(acrylic acid) coatlng was held tightly onto the nylon 6 substrate and was not leached out during the soaklng.
Example 3 A nylon 11 coupon was compression molded from RISAN BESNO-~45344. The coupon was treated according to the same procedure described in Example 1. The finished c:oating on the nylon 11 coupon became lubricious lnstantly upon exposure to water.
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.
21~78~
- 18 ~
Example 4 -The coated nylon 11 coupon was soaked in a water bath for three hours at room temperature. The soaked nylon 11 coupon remained to be highly lubriclous.
This experiment illustrates that the poly(acrylic acid) coating was not dissolved away during the soaking.
Example 5 Example 1 was repeated with the exception that N,N-dimethyl formamide (DMF) was substituted for DMS0 as the solvent for the poly(acrylic acid). A very lubricious coating was obtained when exposed to water.
Example 6 Example 5 was repeated with the exception that the concentration of the poly(acrylic acid) was 0.5 instead of 1~. The finished coating was slightly more smooth and become lubrlcious upon exposure to water.
~xample 7 Example 6 was repeated with the exception that (1) an 0.2% poly(acryllc acid) solution was used and ~2) the acid polymer was partially neutalized by adding 5~% stoichiometric amount of triethylamine. A
smooth coating was obtained which became lubrlclous upon exposure to water.
-; ~' 'ExamPle 8 A nylon 11 coupon was compression molded from bismuth carbonate fllled nylon 11 pellets. The coupon was coatecl in a 1% solutlon of toluene 2,4-diisocyanate ~B) in MEK ~or one hourO After drying ln ~:, . . -.
.
! ' 2~7~
an air o~en at 60C for 30 minute~; the cou~on wa~
di~ed in a 1% ~olution o~ ~oly(acrylic acid) (~) in dimethylformanide (DMF). ~ter redrying at 60C for 30 minute3, a smooth coati~g wa$ obtained. The ~-~
5 ~urface of the cou~on beca~e lubricious in~tantly u~on ex~o$urs to water.
Exam~le 9 ~ ~urgical catheter made o~ bismuth carbonate filled nylon 11 was coated by the ~ama ~rocedure aB
10 describ~d in ~xam~le 8 with the exce~tion that ~oly(acrylic) acid (M) was sub3tituted for (L). The ~inished catheter had a continuous, 3mooth coating which became very lubricious u~on exposurQ to water.
~xam~le 10 (a) ~xam~le 9 wa~ re~eated with the excep~ion that a 1% ~olution of a vinyl methyl ether-maleic anhydrido) co~olymer (GA~TR~Z-an 169TM produced by GAF) in M~K wa~ ~ubqtituted for the ~oly(acrylic acid) solution a~ the ~o~coat. The fre~hly ~re~ared coating showed no lubricity u~on exposure to water.
I~ became lubricious, however, after o~ernight ~oaking in a water bath. Thi~ example illustrates a deficiency of the ~rior technique aescribed in Euro~ean ~atent a~lication 0166998.
(b) A nylon 11 catheter was coated by di~ing in a 1% DM~ 301ution of ~olyi~ocyanate (B) for 1 hour after which it wa~ dried at 60C for one hour.
The catheter was then di~d in a 1% DNF solution of ~olyvinyl hydro~hthalate for 1 second and dried 30 minutes at 60C. U~on di~ing in water there wa~ ~o de~elo~ment of a lubricious coating. -,.
Example 11 Example 9 was repeated with the exception that 1,6-diisocyanatohexane (A) was substituted for toluene 2,4-diisocyanate (B) in the primer solution. A smooth coating was obtained which became slippery instantly upon exposure to water.
Example 12 Example 9 was repeated with the exception that an isocyanate end capped polyfunctional aliphatic adduct (D) was substituted for toluene diisocyanate. The isoeyanate solution was made of 2.03 grams of (~) and 150 grams of MEK which corresponded to an 0.8%
solids solution. The finished coating was continuous and smooth, which developed lubricity immediately upon exposure to water.
Example 13 Example 12 was repeated with the exception that an ~ethylene-vinyl acetate) copolymer catheter was substituted for the nylon 11 catheter. The coat~d 20 catheter showed no discoloration and was smooth. It developed lubricity instantly upon exposure to water. ;
Example 14 A section of the coated catheter prepared in example 12 was examined for lubric~ty retention in a 25 saline solution (0.5% NaCl). The following observations were noted and are set forth in Table I ;
below:
; TABLE I
Soaking time, hours_ Observation 1/6 remained lubricious 1/2 remained lubriclous 1 remained lubrlcious ~` -24 remained lubricious ;~
After redrying at 60C normal feel -~
Exposed to saline again ~emained lubricious D-16094-1 .
2(3~78~34 1 ~
, - 21 ~
These results demonstrate that the hydrophllic lubricious coating of this invention is resistant to saline.
Example 15 Two coated nylon 11 catheters, one taken from example 9 and the other from example 12, were immersed in a hot water bath at 70C and examined for any loss of lubricity. The results obtained are set forth in Table II below:
TABLE II
Time in 70C Bath, hours Observation 0 lubricious 1 lubricious 2 lubricious .
15 3 lubricious 4 lubrlcious It is evident from the above data that the coating of the present inventlon demonstrated a good retention of lubricity in hot water at 70C.
20Example 16 :
This example illustrates a preferred method for making a uniform low-viscosity solution (or colloidal dispersion) of poly(acrylic acid) (M) in DMF or similar solvents. Such a solution is easier to 25 handle, filters more rapidly and results in a more :.
uniform coating. -~
A total of 180 grams of DMF and 0.09 grams of Tween 80 lpoly(oxyethylene) t20) Sorbitan monooleate, :~
a non-inoi~- surfactan~ supplied by ICI~ were placed in - .:~:
30 a 500 ml beaker. The mlxture was blended ~or 5 `
minutes using an air-driven Cowless mixer.
` . D-16094-1 ;,,. 20~788~1 - 2:2 -Thereafter, 1.8 gram of (~) wa~ s~rinkled into the liquid while undes mixing. The mixing was continued for a total o~ 15 minute A highly uniform, gel-~eed~-free ~olution (colloidal dis~eraion) was ob~ained, the finished ~olution exhibited a Brookfield vi~co~ity (Model ~VT, 6 RPM at 25C) of 55 C~8. The di~olution ~roce~s wa3 much more time-consuming without the ~ur~actant, and the fini~hed ~olution ty~ically exhibited a vi~co~ity of about 100 c~
Rxam~le 17 ~xam~le 16 wa~ re~eated with the exce~tion that BRIJ 98TM ~olyoxyethylene (20) oleylether, a non- -ionic ~urfactant ~roduced by ICI] wa~ 3ubstituted for ~he ~ween 80~. A uniform gel-seed-free 301ution 1~ ~colloldal dis~er~ion) was obtained. The solution ~iltered through a 16 micron ~ilter with ea~e. The ~inished solution exhibited a Brookfield vi~cosity of 4 5 a~
~xamDle 18 -~xample 17 wa~ re~eated with the exce~tion that NYRJ 53T~ (~olyoxyethylene ( 50 ) ~tearate, a non-ionic ~urfactant ~roduced by ICI) was substituted for BRIJ
98. A u~i~orm, gel-seed-free solution (colloidal dis~er~ion~ was obtained. The ~olution filtered 25 through a 16 micron filter with ease. The finished ;
solution exhibited a Brookfie}d viscosity of 45 c~
(Model ~TV, 6 rm~ at 25C).
~xam~le 19 A tainle~s ~teal guide wire made by ~edi-tech was coated with a ~rimer ~olution compo~ed of 1%
~olyisocyanate (D~ in N~R and a to~coat ~olution com~o~ed of 1% ~oly(acr~lic acid) (M) and 0.05% of ~, ~ D-16094-1-C
.~ .
.
( ~ 8~
MYRJ 53 ~surfactant) in DMF. The drying cycles used for the two coats were 30 minutes at 70C and 30 minutes at 60C, respectively. The finished stainless steel guide wire showed a lubricious surface upon exposure to water.
Example 20 A bismuth carbonate filled nylon 11 catheter was first " , dipped in a 1% tolylene-2,4-dlioscyanate solution in MEK for one hour. The catheter was removed from the bath and dried in an air oven at 90C for 30 minutes.
It was dipped-coated in a poly(acrylic acid) (M) bath having a formulation identical to that of example 18 for 1 second. The catheter was redried at 90C for 30 minutes. The finished coating was very lubricious and showed a high degree of abrasion resistance.
Example 21 ' A nylon 11 catheter was coated by first treating `
in a primer solution containing 0.54 and 0.5~ of polyiscyanate (D) and tolylene 2,4-diisocyanate, ~
20 respectively. The catheter was dried at 85C for 30 ,~' minutes and subsequently dipped in a 1~ poly(acrylic acid) (L) solution for one second. It was then ;~ , redried at 85C for 30 minutes. The finished catheter was smooth, and showed a high degree of lubrlcity upon 25 exposure to water. The hydrophilic lubricious coating '~
on this catheter was resistant to abras,ion, and , , reta$ned much of its initial lubricity after rubbing with a wet tissue ten times.
Example 22 ~ , A nylon 11 catheter was coated according to the same procedure desc'ribed ln example 21 with the - 2~ _ exception that the ratio of tolylene 2,4-dilsocyanate to ~D) was changed from 0.5/O.S to 0.75/0.25. The finished catheter was very lubricious upon exposure to water. It exhibited good abrasion resistance as measured by th~ rub test described in example 21.
Example 23 A catheter was coated according to the procedure of example 22 with the exception that the drying temperature was 60 instead of 85C. The flnished catheter was very lubricious upon exposure to water.
Example 24 A double-coatlng procedure is illustrated in this example. Five pieces of nylon 11 catheters were first soaked in a 1% tolylene 2,4-diisocyanate solution in MEK for one hour. After 30 minutes dryLng in an air oven at 85C., they were dipped-coated in a 1%
poly~acrylic acid) (M) bath for one second. They were redried at 85C for 30 minutes. The above coating procedure was repeated once more with the exception that the dipping time in the primer solution was shortened from one hour to 10 minutes for the second coating. The finished catheters were very ~;
slippery upon exposure to water.
Example 25 A low viscosity, uniform colloidal dispersion of polytacrylic àc~d) (N~ [a high molecular weight linear poly~acrylLc acid) was prepared by the following procedure~ Ten grams of (N) were added under mlxing with a Cowless air mixer to a 601ution containing 0.5 grams of MYRJ 53 surfactant and 659.7 grams of DMF. A
D-16094-1 - ~
' ' ~ ' . ) 2(3~7B8~
~ 25 -viscous ~olution was obtained ln about 15 minutes.
Thereafter, 32.98 grams of MEK were added into the solution under mixing to yield a slightly cloudy colloidal dispersion. The colloidal dispersion possessed a Brookfield visco~;ity (Model LVT, 6 rpm at 25C) of 162cps. Without MEK, a 1% (N) in DMF would produce a viscosity of 2,300 cps~
Example 26 A nylon 11 catheter was coated using the procedure 10 described in example 21 with the exception that the primer solution was a 1% tolylene 2,4-diisocyanate solution in MEK and the top coat solution was a 1%
poly(acrylic acid) (N) in DMF prepared in accordance with example 24. The finished coating was very smooth and became lubricious instantly upon exposure to water.
Example 27 A bismuth carbonate filled nylon 11 catheter waq coated with a hydrophilic lubricious coating by the following procedure:
(1) Dipped in an 14 tolylene 2,4-diisocyanate solution in MEK for one hour.
(2) Dried in an air oven at 85C for 30 minutes n (3) Dipped in a 1~ poly(acrylic acid) (~L) solution for one second.
Catheter~ which are u~ed ~ur~ically ~or insertion through blood vessels, urethrea, or body conduit~, and guide wire~ u~d with catheter~ for ~io~sy, balloon angio~la~ty and other medical ~i ~rocedure~ require a low-friction ~urface for ~re~enting `in~ury !to~ or inflamm tion o~, mUCOU
membrane~ and oth~r body ti~ue~
One cla~s o$ conventional catheter~ i~ made of low-friction m~terial~ ~uch as Teflon~, ~olyeth~lene or D-16094-1-C ~
788~L
other materials coated with a layer of Teflon or silicone. There are two shortcomings of these ~ -catheters: First, they are not sufficiently slippery ` ~ ~;
for the intended surglcal purposes mentioned above.
Second, they are difficult to handle and store because their surfaces are slippery at all times. ;
Another class of conventional catheters is rendered lubricious by coating with a layer of silicone fluid, glycerin, or olive oil. These materials are unsatisfactory because the low molecular weight additives tend to run off ~uickly. Thus, they lose the initial lubricity rather rapidly.
A~other class of conventional surface treatment involves the deposition of poly(vinyl pyrrolidone) in the presence of a polyisocyanate. This type of coating while lubricious initially lacks abrasion resistance, and is therefore easily removed from the surface of the medtcal devtces. An improved version of this technique was described by R. A. Winn in V. S.
Patent 4,373,009, where an active hydrogen containing vinyl pyrrolidone copolymer was used instead to result in a better bonding tc the substrate. The "monome~s containing active hydrogen" were needed according to Winn "to form a covalent bond between the coupling coating and the hydrophilic copolymer". These copolymers, however, were of unknown quality ~n terms of purity, toxicity, or not of sufficiently high molecular weight needed for this application. Both the availab:Llity and usefulness of these copolymers 30 are highly questionable.
In U.S. Patent ~,119,094, a substrate such as a 2~5~1788~
tube or catheter is disclosed having a hydrophillc coating which exhibits a low coefficient of friction.
The substrate is coated with a poly(vinyl pyrrol-idone)-polyurethane interpolymer. A polyisocyanate and a polyurethane mixture is applied to a substrate and after drying, a poly(vinyl pyrrolidone) in solution is applied.
U.S. Patent 4,589,873, issued on May 20, 1986 to A. Schwartz et al and discloses a method of applying a 10 hydrophilic coating to a polymeric substrate. The coating consists of poly(vinyl pyrrolidone) which is applied to the substrate in a solvent followed by drying.
W.S. Creasy et al were granted U. S. Patent 4,642,267 on February 10, 1987 which discloses and claims a hydrophilic polymer blend. The blend is comprised of a thermoplastic polyurethane havlng no reactive isocyanate groups and a hydroph~lic poly(N-vinyl lactam) such as poly(vinyl pyrrolidone). The blend can contain additional polymeric components such as homopolymers or copolymers of monomers including ;
vinyl chloride, acrylic acid, vinyl alcohol and the like.
A process for coating a polymer surface with a hydrophilic coating is also disclosed in U.S. Patent 4,666,437. A sol~ution of a compound containing at least two unreacted isocyanate groups per molecule is appl~ed to the polymer surface and the ~olvent evaporated. Thereafter, a solution of poly(vinyl pyrrolidone) i5 applled to the treated surface and the coated cured.
Accordi.ng to European patent application 0166998, .
2 ~ ~ 7 8 ~
N. Takamura de3cribed lubriciou~ coatin~ derived ~rom either a cellulo3ic ~olymer, a maleic anhydride pol~mer, a ~olyacrylamide or a ~ater-~oluble nylon which were convalen~ly bonded to a medic~l in~trument ~ub~trate. The ~ub~trate contained reactive ~unctional ~roup3 ~uch a3 aldehydea, e~oxy, i~ocyanate or amino ~rou~s. The re~erence indicate~ that the water soluble ~olymerR are non-cro~linked and contain hydro~hilic grou~s such a~ -0~, -C0NH2, -COOH, -NY2, -C00~, -S03-, and -MR3, R being alkyl or hydrogen.
However, a cellulo~ic ~olymer i~ undesirable becau~e it mu~t be ~rotected a~ain~t microbe attack.
Coatin~ made from a maleic a~hydride ~olymer must ~o through a tedious ~o~t tr,satment with water before developing lubricity, while water-~oluble nylon~ may have questionable ~tability.
It ha~ now unexpectedly and ~ur~ri~in~ly been ~ound that hi~h molecular weight carboxylic acid-containing ~olymer or their partially neutralized ~alt~, can be strongly bonded to a ~ubstrate, such a~
a catheter, u~ing a ~olyisocyanate reagent and at the ~ame tlme ~rovide~ a hydro~hilic lubriciou~ coatin~
Thus, the need for either an interpenetratin~ network containing poly(vinyl ~yrrolidone) and ~olyurethane or ~ ~ -a co~olymer containin~ both non-active hydro~en units and active-hydro~n unit~ can be avoided.
Furthermore, there is no ~eed for any ~o~t hydroly~
treatment in the invention. ~nlike a malaic anhyd~id~s ~olymer, the coa~ing devlslo~ lubricity in~tantly u~on eXpo~ure to an aqueou~ ~luid. Poly- -~
(acrylic acid~), 8uch a~ the Carbo~ol~ manu~actured ~':-.
16094-1-C ~ `
~788(~
by B.F. goodrich, are ideally suited for the intended medical applications, and also have sufficiently high molecular weights necessary for achieving both good hydrophilic lubricity and abrasion resistance.
Accordingly, one or more of the following objects will be achieved by the practice of this invention.
It is an object of this invention to provide medical and other devices which when dry do not exhibit a slipp~ry surface, but when contacted with a fluid such 10 as water, become very lubricious. Another ob;ect of this invention is to provide medical and other devices which are easily handled without fear of slipping, but when moistened or contacted with body fluids instantly become very lubricious. A further object of this 15 invention is to provide medical devices having a ;
coating of a poly~carboxylic acid) and a polyisocyanate which when dried can be handled with ease, but when moistened, become very slippery. A
still further ob;ect of this invention is to provide processes for the preparation of the coated medical and other substrates. Another object is to provide medical and other devices and instruments which have a coating of a material which becomes lubricious upon exposure to body fluids. These and other objects will readily become apparent to those skilled in the art in the light of the teachings herein set forth.
SUMMAR~ OF THE INVENTION
~ n its broad aspect, this invention is directed to coated substrates having a lubricious coating which 30 becomes slippery only upon exposure to an aqueous ~- ~
fluid. The invention is also directed to a method for ~ ~`
:: ' D-16094-1 ~
: 2(~7138a~
coating the devices and substrates as well as to the coated articles themselves.
One or more polyi~ocyanates ~s ap~ ~ a substrate such as a medical device. The co~.~ct time may vary fro~ a few seconds to an hour or mo~e depending upon the material of construction of the medical device and the polyisocyanat~ Pmployed. The primer coated medical device can be ~rled ~n an oven for removal D~ ~ny solvent and then ~ carboxylic acid-containing polymerlc top coat applied directly to the polyisocyanate coated device. The coa~ed medical device is then dried to complete the coat~g process.
The finished medical device has normal feel and handlin~ characteristics when dry. Upon exposure to body fluids, however, it becomes lubricious instantly.
DETAILED DESCRIPTION OF THE INVENTION
The hydrophilic lubricious coating of this invention is prepared ~y fir~t contacting ~ sub~trate or medical device, such as a catheter, with a polyisocyanate such as a toluene diisocyanate in a liquid medium. The liquid medium can be removed by drying or the the cathet~r ~an ~e ~treated directly wlth a high molecular weight poly(carboxylic acid) in a liquid medium. After drying in an ovem~ a non- ~ ;
tacky, easy-to-handle, and uniformly coate~ ~atheter is obtained. The surface of the rèsultant catheter becomes lubricious ins~ntly ~p~ ~e~posure to an aqueous solution or body fluids.
In addition to a quick initial lubricity, the ~ -~
hydrophilic lubrlcious coa~ing oE ~his lnventio~ is resistant to abrasion. Consequently, a catheter ;~ ~
.
Z~
coated in accordance with the teachings of thls invention will retain a lubricious surface for a long duration which is often required during the course of a surgical procedure.
Unlike catheters made of or coated with Teflon or sillcones, catheters coated in accordance with the present invention are non slippery when dry but become instantly slippery when wet. As a result, medical devices coated with the hydrophilic lubriclous coatings of this invention are easier to handle and store.
The term "bath" as employed throughout the specification and appended claims is meant to include not only solutions of the indicated organic compounds, but dispersions and emulsions.
Application of the coatings from the bath can be effected by a variety of methods and includes, but is not llmited to, dipp~hg, spraying, electrical deposition, painting and the like. Optionally, the coated substrate can be further treated with an aqueous bath to partially or totally neutralize the free acid. In those instances wherein the substrate is subjected to high temperatures, such as tn thermoforming processes, the treatment with the 25 aqueous bath to effect neutralization or part~al ~ ~ ;
neutralization is desired.
As indicated above, the hydrophilic lubricious coating of this invention is comprised of at least two components; a polyisocyanate primer and a water~
soluble or water dispersible polymer topcoatO They are normally applied in two separate coating steps.
~ ' Z~7138~
However, if desired, the drying step after application of the polyisocyanate coating can be omitted and drying effected after application of the top coat.
The solvents useful for applying the polyisocyanates include methyl ethyl ketone, ethyl acetate, ethyl lactate, chloroform, trichloroethylene, dichloromethane, hexane, heptane, toluene, their mixtures with mineral oil~ or other suitable organic solvents which do not react with isocyanates under the coating conditions. The preferred solvent is methyl ethyl ketone.
Alternatively, the polyisocyanates can be dispersed in a solvent/non-solvent mixture to form a dispersion or emulsified to form an oil-in-water emulsion. When an emulsion is used, the reactive isocyanate groups need to be protected by suitable chemical groups known to those skilled in the art.
A wide variety of polyi~ocyan~tes can be employed in preparing the coatings of the present invention and include, but are not limited to, toluene-2,3-diisocyanate, toluene-2,6-diisocyanate, commercial mixtures of toluene-2,4- and 2,6-diisocyanates, 4,4'-diphenylmethane diisocyanate, cyclohexylene-1,4-diiisocyanate, m-phenylene diisocyanate, 3,3~diphenyl-25 4-biphenylene diisocyanate, 4,4-biphenyl ~;
diisocyanate, l,6-hexamethylene diisocyanate, 1,5 naphthalene diisocyanate, cumene-2,3-diisocyanate, 2,4-diisocyallatodiphenylether, 5,6-dimethyl-1.3 phenylenediisocyanate, 2,4-dimethyl-1,3-phenylenedii~ocyanate, 2,~-dimethyl-1,3 phenylenedii~ocyanate, 4,4-diisocyanatodiphenylether, 9,10-anthracene dilsocyanate, 2,4-diisocyanatotoluene, ~ ~ ) 2(~88~
g 1,4-anthracene diisocyanate, 2,4,6-toluene l -triisocyanate, isophorone diisocyanate, and p,p',p"- ~
triphenylmethane triisocyanate, and the like. Equally ~ -u~eful are isocyanate end-capped prepolymers and adducts, isocyanate end-capped polyfunctional aromatic adducts, isocyanate end-capped polyfunctional aliphatic adduct and two component systems such as end capped aliphatic polyester polyol and aliphatic polyol compound, and their mixtures with different 10 polyisocyanates as d~scribed above.
Illustrative of isocyanate end-capped adducts are the reaction products of 2,4-tolylene dilsocyanate, 4,4'-diphenylmethane diisocyanate, polymethylenepolyphenyl isocyanate, or 1,5-naphthylene dlisocyanate, with 1,2-polypropylene glycol, polytetramethylene ether glycol, 1,4-butanediol, 1,4-butylene glycol, 1,3-butylene glycol, poly~1,4-oxybutylene) glycol, caprolactone, adip~c acid esters, phthalic anhydride, ethylene glycol, diethylene `~
glycol, and the like.
The polymers suitable for use in forming the top coatings of the present invention are carboxylic acid-containing polymers. The polymer can be a free acid or partially neutralized as 25 represented by the following formula: -Z n H. m p 2~a7ss~l - ~o -where n = 0-0.95 mole fracl:ion of ~eutralize~ acid moietie~;
m - 0.05-1.0 mole raction of acid moietie~ with the ~roviso that n+m = 1;
X1,X2,X3 are each a hydro~en atom or a Yuitable mono~alent organic radical, such a3 lower al~yl or cycloalkyl or aryl of u~ to 8 carbon atom~, and wherein the X grou~ are ~uch that the ~ol~mer remain~
water ~oluble;
0 Y iB either a sin~le bond or any suitable di~alent organic radical, ~uch aQ a hydrocarbon grou~ ~ :
of u~ to 8 carbon atom~, provided it does not ~ -ad~er~ely af~ect the ~olubility of the ~olymer; Z i~
either a metallic ion or a ~uitable ammonium ion;
a~d ~ i~ a very largo number ~uch that the ~olymer ha~ a molecular weight between about 200,000 and about 5,000,000. :
Even thou~h all ~oly(carboxylic acid) homopolymers can be u~e~ul to different de~ree~, the high molecular wei~ht ~olymer~ are more de~irable. : -The u~e~ul molecular weight~ ran~e from 200,000 to .~
about 5,000,000. Re~resentative carboxylic acid . ~:
containi~ homo~olymer~ include, but are not li~ited to, ~oly~acrylic acid), ~oly(methacrylic acid), ; ~:
poly(i~ocrotonic acid), and the like, the ! ' ..
~oly(carboxylic acid) of this inventio~ can be either linear or ~artia~ly cro~-linked ~uch that it would ;
~orm either a ~olution or a colloidal d~ r~ion in ;:~
the coating medium. The ~re~erred ~oly(car~oxylic acid) ~o:Lymer i3 a ~oly(acrylic acid) ha~ing a ' '~
: .
200788~
molecular weight of ~xom abou~ 200,000 to about 5,000,000. Particularly ~xeferred ~oly(carboxyl~c acid) ~olymerR include ~oly(acrylic acid) ~olymers having mole~ular wei~hts oi from about 1,000,000 to about 3,000,000.
Olefinic a~id~ ~uch a~ acrylic acid can be co~olymarized with one or more of other unisaturated monomer~ to ~roduce copolymers containing carboxylic acid moieties. Examplary co~olymer~ include Carboset~ and Surlyn~ produeed by B.F. Goodrich and DuPo~t re~ectively. Co~olymer~ containing water-ini~oluble unit~ a~ well ais ~arboxylic acid unit3 ~an be mixed with the homopolymer~ if 80 de~ired, a~ long a~ they are com~atible.
Polyiam~holytes which conta~n one or more ~oly-meri~ acids mentioned above may be al~o useful for the ~ur~ose of this invention as lon~ as the basic moiety i~ a tertiary amine.
~ny organic solvents or mixed solvents for the ~oly(carboxylic acid) polymers used in thi~ invention may be em~loyed for making ths to~coat ~olution ~ro~ided that they are not reactive with the ~olyisocyanate~. Bxem~L3ry ~ol~entis or sol~ent m~xture~ include acetonitrile, ac~tonitrile-DMF ~,N-aimethyl formam~de (DNF), acetyl acetone, acrylonitrile, benzonitrile, diethyl a~etiamide, di~thyl formamide,i diethylformamide-DMF, dimet~yl acetamide, l,~-d~oxane, di~ro~yl sulfone, DMF-acetone, DNF-toluene, DMS0 (dimethyl sulfoxlde), DMS0-DMF, ethyl formamide, N-methyl-2-~yroolidone, nitrobenæene, nitrobenzene-DNF, ~henyla~etate, pro~ionitrile, ~ ~
~` ~'''~'' ~ ~ ) 2~7138~
styrene, and the like. The dissolution of poly(carboxylic acid) polymers in many of the above-mentioned sol~ents may be enhance by the additlon of suitable amines. The preferr~ed solvent is dimethyl formamide.
To prepare a seed-free poly(carboxylic acid) solution, it is advantageous to add a small amount of `
surfactant in the solvent before mixing with the ~ ~;
polymer. Any soluble surfactant or a mixture of ~-surfactants in the above-mentioned solvents may be useful. The preferred surfactants are soluble non-ionic surfactants such as polyoxyethylene sorbitan fatty acid esters, polyoxyethylene acids, polyoxyethylene alcohols, fluorinated alkyl esters, fluorinated alkoxylates and their mixtures.
Due to the high molecular weight of the poly(carboxylic acld) polymers preferred for use in the present invention, their solution viscosities may be too high to ~e suitable for some coating processes. ~ ~`
It is advantages in these instances to convert the polymer solution to a colloidal dispersion by mixing with one or more non-solvents. Exemplary non-solvents lnclude tertiary alcohols, ketones, aliphatic ethers, allphatic and aromatic hydrocarbons. The preferred non-solvents are acetone, methyethylketone (MEK~ and tertiary butyl alcohol.
Alternatively, the poly(carboxylic acid) may be emulsified to a water-in-oil emulsion. an example for forming such a water-in-oil emulsion is descrlbed ln my earller IJnlted States Patent No. 4,618,647.
'~ ~" . `~.L) 2(~)788~
For some applications it might be desirable to incorporate one or more add~tives in the coatings particularly the top coating. For example, some catheters are comprised of a thermoplastic rubber and it is preferred that the primer coating contaln a plasticizer to minimiæe loss of flexibility due to the coating operation. A wide variety of plasticizers can be employed such as the esters of fatty acids, mineral~ `
oil or silicone oil. The plasticizer must, of course, 10 be compatible with the components of the coatings and have no undersirable biological properties which would limit their use.
Other additives can be employed in the coat~nys `
ln addition to the surfactants such as, stabilizers, 15 antioxidants, antimicrobial agents, colorants, biological components and the like. ~or example, in catheters which are inserted into blood vessels, lt may be des~rable to have contained in the coating an ~`
antithrombogenic agent such as heparin, to avoid blood clot formation during the surgical procedure. The antithrombogenic agent can be used either as an `
additive or as a chemically bonded moiety of the polytcarboxylic acid) polymer.
The techniques employed in coat~ng the substrates and devices are not neces~arily critical and any coating processes suitable for making thin coatings may be utilized. For operations -~
where the ~;helf-life of the coating solutions ls not a :
D-16094-1 ~
7~
crltical issue, a single solution system containing a blend of both polyisocyanate and poly(carboxyl~c acid) may be used in a single coat operation.
In practice it has ~een found that excellent ;~
lubricity and abrasion resist:ance properties are obta~ned when the total thickness of the primer and top coating applied to the substrates in accordance with the teachings of this invention is from the sub-micron range to a few microns The concentration of the isocyanate and the carboxylic acid-containing polymer in the respective coating solutions can vary depending upon the particular components employed, their solubility as well as other considerations. In general the polyisocyanate component in the primer coating is contained in the coating solvent in an amount of at least about 0~1~ by weight. If the polyisocyanate is in li~uid form, it can be employed without a solvent.
However, in practice, it is preferred to employ the polyisocyanate in a solvent in a con~entration of from about 0.5 to about 20% by weight, and more preferably from about 1 to about 5% by weight.
The amount of the poly(carboxylic acid) component employed in the solvent will be controlled by the -viscosity of the medium. Most any concentration can .
be used as long as it is high enough ~o permit the preparation of a satisfactory coating, and yet is low enough so that the solution is not too viscous.
Concentrations of from about 0.1 to about 10% by we~ght are preferred with a concentration within the range of about 0.5 to about 2% by weight the most 7l3~4 preferred. In practice, the stoichiometry ls such that the molar ratio of carboxylic acid groups to isocyanate groups is in excess and will generally be at least about 1:1.
Although the drying temperatures and times are not necessarily critical, it has been found that the coated substrate can be dried at temperatures of from about 20 to about 150C and more preferably from about 50 to about 100C. Drying periods can range from a few secon~s to 60 minutes or more.
Many types of catheters need to be thermoformed to specific shapes for their intended applications.
Depending on the temperature and length of time of the thermoforming process many coated catheters may lose their hydrophilic lubricity during the thermoforming process. The degree of lubricity loss depends on the severity of the thermoformlng conditions.
Thus, when the temperatures are sufficlently high lubricity may be decreased due to the cyclization of -adjacent acid groups. Accordingly, it is preferred to neutrall2e or partially neutralize the acid groups to prevent such cyclization. The description of treatment of the acid groups by sodium phosphates and preferred formulations are set forth ln the example~
The hydrophilic lubricious coatings of this inve~tion are useful in coating medical devices, where a slippery exterior and/or interior, are necessary or desirable to minimize injury to tissues and to aid in man~pulation of the devices during surgical procedures. Examplary medical devices include catheters, needles, guide wires, prophylactic devices, ~ a~ ~
`: ` 2~)7~
_ 16 -delivery systems, filters, sheaths, and other accessories ~mpolyed in medical diagnosties, draninage, dilatation occlusion, vena cava and the like. While the invention iS particularly applicable to medical devlces, it can also be used to coat a variety of other substrates. for instance, the coatings can be applied to condoms, skis, toboggans, and those instances wherein a lubricious surface is desired.
In the examples which follow, certain abbreviations have been employed to define the various polyisocyanates and poly(carboxylic acids). All of the compounds are readily available from commercial sources.
PolYisocyanate Composition A- 1,6-diisocyanatohexane B- 2,4-toluene diisocyanate D- An isocyanate end-capped aliphatlc prepolymer having an average NCO
equivalent weight of 350 and a solution viscoslty of about 1,000 eps at 25C.
E- An aromatic lsocyanate end-capped pre-polymer average NCO equivalent weight 182.
Poly(carboxyl`ic acid ~ Composition L- A poly(acrylic acid) partially cross-linked homopolymer having a -molecular w~ight of about 3,000,000.
M- A USP grade poly(acrylie aeid) partially eross-linked homopolymer having a molecular we~ght of about 3,000,000. ~1 ~
"
D-~6094-1 - , ' "';
, , , -2(~788a~
- 17 - ~
.
N- A poly(acryllc acid) homopolymer havlng a ~ ~
molecular weight of about 1,250,009. ~ -The following examples are illustrative of the invention:
Exam~le 1 A nylon 6 coupon was compression molded from Capron 8000 (Allied Chemicalsl. The coupon was first dipped into a 1% solution of 1,6-diisocyanatohexane (A) in methyl ethyl ketone (MEK) for one hour. The ;
coupon was subsequently removed from the MEK bath and dried in a 60C air oven for 30 minutes. The dried coupon was then dipped in a 1% solution of -~
polytacrylic acid) ~L) in dimethylsulfoxlde ~DMSO) for one second. It was redried at 60C air oven for 30 minutes. ~he finished coating was smooth, non-tacky, as well as easy to handle. It became instantly slippery upon exposure to water.
Example 2 The coated nylon 6 coupon was soaked in a water bath for three hours at room temperature~ The soaked coupon retained a high degree of lubricity. T~is experiment shows that the poly(acrylic acid) coatlng was held tightly onto the nylon 6 substrate and was not leached out during the soaklng.
Example 3 A nylon 11 coupon was compression molded from RISAN BESNO-~45344. The coupon was treated according to the same procedure described in Example 1. The finished c:oating on the nylon 11 coupon became lubricious lnstantly upon exposure to water.
"'"', "~;:'~""''`.
.
21~78~
- 18 ~
Example 4 -The coated nylon 11 coupon was soaked in a water bath for three hours at room temperature. The soaked nylon 11 coupon remained to be highly lubriclous.
This experiment illustrates that the poly(acrylic acid) coating was not dissolved away during the soaking.
Example 5 Example 1 was repeated with the exception that N,N-dimethyl formamide (DMF) was substituted for DMS0 as the solvent for the poly(acrylic acid). A very lubricious coating was obtained when exposed to water.
Example 6 Example 5 was repeated with the exception that the concentration of the poly(acrylic acid) was 0.5 instead of 1~. The finished coating was slightly more smooth and become lubrlcious upon exposure to water.
~xample 7 Example 6 was repeated with the exception that (1) an 0.2% poly(acryllc acid) solution was used and ~2) the acid polymer was partially neutalized by adding 5~% stoichiometric amount of triethylamine. A
smooth coating was obtained which became lubrlclous upon exposure to water.
-; ~' 'ExamPle 8 A nylon 11 coupon was compression molded from bismuth carbonate fllled nylon 11 pellets. The coupon was coatecl in a 1% solutlon of toluene 2,4-diisocyanate ~B) in MEK ~or one hourO After drying ln ~:, . . -.
.
! ' 2~7~
an air o~en at 60C for 30 minute~; the cou~on wa~
di~ed in a 1% ~olution o~ ~oly(acrylic acid) (~) in dimethylformanide (DMF). ~ter redrying at 60C for 30 minute3, a smooth coati~g wa$ obtained. The ~-~
5 ~urface of the cou~on beca~e lubricious in~tantly u~on ex~o$urs to water.
Exam~le 9 ~ ~urgical catheter made o~ bismuth carbonate filled nylon 11 was coated by the ~ama ~rocedure aB
10 describ~d in ~xam~le 8 with the exce~tion that ~oly(acrylic) acid (M) was sub3tituted for (L). The ~inished catheter had a continuous, 3mooth coating which became very lubricious u~on exposurQ to water.
~xam~le 10 (a) ~xam~le 9 wa~ re~eated with the excep~ion that a 1% ~olution of a vinyl methyl ether-maleic anhydrido) co~olymer (GA~TR~Z-an 169TM produced by GAF) in M~K wa~ ~ubqtituted for the ~oly(acrylic acid) solution a~ the ~o~coat. The fre~hly ~re~ared coating showed no lubricity u~on exposure to water.
I~ became lubricious, however, after o~ernight ~oaking in a water bath. Thi~ example illustrates a deficiency of the ~rior technique aescribed in Euro~ean ~atent a~lication 0166998.
(b) A nylon 11 catheter was coated by di~ing in a 1% DM~ 301ution of ~olyi~ocyanate (B) for 1 hour after which it wa~ dried at 60C for one hour.
The catheter was then di~d in a 1% DNF solution of ~olyvinyl hydro~hthalate for 1 second and dried 30 minutes at 60C. U~on di~ing in water there wa~ ~o de~elo~ment of a lubricious coating. -,.
Example 11 Example 9 was repeated with the exception that 1,6-diisocyanatohexane (A) was substituted for toluene 2,4-diisocyanate (B) in the primer solution. A smooth coating was obtained which became slippery instantly upon exposure to water.
Example 12 Example 9 was repeated with the exception that an isocyanate end capped polyfunctional aliphatic adduct (D) was substituted for toluene diisocyanate. The isoeyanate solution was made of 2.03 grams of (~) and 150 grams of MEK which corresponded to an 0.8%
solids solution. The finished coating was continuous and smooth, which developed lubricity immediately upon exposure to water.
Example 13 Example 12 was repeated with the exception that an ~ethylene-vinyl acetate) copolymer catheter was substituted for the nylon 11 catheter. The coat~d 20 catheter showed no discoloration and was smooth. It developed lubricity instantly upon exposure to water. ;
Example 14 A section of the coated catheter prepared in example 12 was examined for lubric~ty retention in a 25 saline solution (0.5% NaCl). The following observations were noted and are set forth in Table I ;
below:
; TABLE I
Soaking time, hours_ Observation 1/6 remained lubricious 1/2 remained lubriclous 1 remained lubrlcious ~` -24 remained lubricious ;~
After redrying at 60C normal feel -~
Exposed to saline again ~emained lubricious D-16094-1 .
2(3~78~34 1 ~
, - 21 ~
These results demonstrate that the hydrophllic lubricious coating of this invention is resistant to saline.
Example 15 Two coated nylon 11 catheters, one taken from example 9 and the other from example 12, were immersed in a hot water bath at 70C and examined for any loss of lubricity. The results obtained are set forth in Table II below:
TABLE II
Time in 70C Bath, hours Observation 0 lubricious 1 lubricious 2 lubricious .
15 3 lubricious 4 lubrlcious It is evident from the above data that the coating of the present inventlon demonstrated a good retention of lubricity in hot water at 70C.
20Example 16 :
This example illustrates a preferred method for making a uniform low-viscosity solution (or colloidal dispersion) of poly(acrylic acid) (M) in DMF or similar solvents. Such a solution is easier to 25 handle, filters more rapidly and results in a more :.
uniform coating. -~
A total of 180 grams of DMF and 0.09 grams of Tween 80 lpoly(oxyethylene) t20) Sorbitan monooleate, :~
a non-inoi~- surfactan~ supplied by ICI~ were placed in - .:~:
30 a 500 ml beaker. The mlxture was blended ~or 5 `
minutes using an air-driven Cowless mixer.
` . D-16094-1 ;,,. 20~788~1 - 2:2 -Thereafter, 1.8 gram of (~) wa~ s~rinkled into the liquid while undes mixing. The mixing was continued for a total o~ 15 minute A highly uniform, gel-~eed~-free ~olution (colloidal dis~eraion) was ob~ained, the finished ~olution exhibited a Brookfield vi~co~ity (Model ~VT, 6 RPM at 25C) of 55 C~8. The di~olution ~roce~s wa3 much more time-consuming without the ~ur~actant, and the fini~hed ~olution ty~ically exhibited a vi~co~ity of about 100 c~
Rxam~le 17 ~xam~le 16 wa~ re~eated with the exce~tion that BRIJ 98TM ~olyoxyethylene (20) oleylether, a non- -ionic ~urfactant ~roduced by ICI] wa~ 3ubstituted for ~he ~ween 80~. A uniform gel-seed-free 301ution 1~ ~colloldal dis~er~ion) was obtained. The solution ~iltered through a 16 micron ~ilter with ea~e. The ~inished solution exhibited a Brookfield vi~cosity of 4 5 a~
~xamDle 18 -~xample 17 wa~ re~eated with the exce~tion that NYRJ 53T~ (~olyoxyethylene ( 50 ) ~tearate, a non-ionic ~urfactant ~roduced by ICI) was substituted for BRIJ
98. A u~i~orm, gel-seed-free solution (colloidal dis~er~ion~ was obtained. The ~olution filtered 25 through a 16 micron filter with ease. The finished ;
solution exhibited a Brookfie}d viscosity of 45 c~
(Model ~TV, 6 rm~ at 25C).
~xam~le 19 A tainle~s ~teal guide wire made by ~edi-tech was coated with a ~rimer ~olution compo~ed of 1%
~olyisocyanate (D~ in N~R and a to~coat ~olution com~o~ed of 1% ~oly(acr~lic acid) (M) and 0.05% of ~, ~ D-16094-1-C
.~ .
.
( ~ 8~
MYRJ 53 ~surfactant) in DMF. The drying cycles used for the two coats were 30 minutes at 70C and 30 minutes at 60C, respectively. The finished stainless steel guide wire showed a lubricious surface upon exposure to water.
Example 20 A bismuth carbonate filled nylon 11 catheter was first " , dipped in a 1% tolylene-2,4-dlioscyanate solution in MEK for one hour. The catheter was removed from the bath and dried in an air oven at 90C for 30 minutes.
It was dipped-coated in a poly(acrylic acid) (M) bath having a formulation identical to that of example 18 for 1 second. The catheter was redried at 90C for 30 minutes. The finished coating was very lubricious and showed a high degree of abrasion resistance.
Example 21 ' A nylon 11 catheter was coated by first treating `
in a primer solution containing 0.54 and 0.5~ of polyiscyanate (D) and tolylene 2,4-diisocyanate, ~
20 respectively. The catheter was dried at 85C for 30 ,~' minutes and subsequently dipped in a 1~ poly(acrylic acid) (L) solution for one second. It was then ;~ , redried at 85C for 30 minutes. The finished catheter was smooth, and showed a high degree of lubrlcity upon 25 exposure to water. The hydrophilic lubricious coating '~
on this catheter was resistant to abras,ion, and , , reta$ned much of its initial lubricity after rubbing with a wet tissue ten times.
Example 22 ~ , A nylon 11 catheter was coated according to the same procedure desc'ribed ln example 21 with the - 2~ _ exception that the ratio of tolylene 2,4-dilsocyanate to ~D) was changed from 0.5/O.S to 0.75/0.25. The finished catheter was very lubricious upon exposure to water. It exhibited good abrasion resistance as measured by th~ rub test described in example 21.
Example 23 A catheter was coated according to the procedure of example 22 with the exception that the drying temperature was 60 instead of 85C. The flnished catheter was very lubricious upon exposure to water.
Example 24 A double-coatlng procedure is illustrated in this example. Five pieces of nylon 11 catheters were first soaked in a 1% tolylene 2,4-diisocyanate solution in MEK for one hour. After 30 minutes dryLng in an air oven at 85C., they were dipped-coated in a 1%
poly~acrylic acid) (M) bath for one second. They were redried at 85C for 30 minutes. The above coating procedure was repeated once more with the exception that the dipping time in the primer solution was shortened from one hour to 10 minutes for the second coating. The finished catheters were very ~;
slippery upon exposure to water.
Example 25 A low viscosity, uniform colloidal dispersion of polytacrylic àc~d) (N~ [a high molecular weight linear poly~acrylLc acid) was prepared by the following procedure~ Ten grams of (N) were added under mlxing with a Cowless air mixer to a 601ution containing 0.5 grams of MYRJ 53 surfactant and 659.7 grams of DMF. A
D-16094-1 - ~
' ' ~ ' . ) 2(3~7B8~
~ 25 -viscous ~olution was obtained ln about 15 minutes.
Thereafter, 32.98 grams of MEK were added into the solution under mixing to yield a slightly cloudy colloidal dispersion. The colloidal dispersion possessed a Brookfield visco~;ity (Model LVT, 6 rpm at 25C) of 162cps. Without MEK, a 1% (N) in DMF would produce a viscosity of 2,300 cps~
Example 26 A nylon 11 catheter was coated using the procedure 10 described in example 21 with the exception that the primer solution was a 1% tolylene 2,4-diisocyanate solution in MEK and the top coat solution was a 1%
poly(acrylic acid) (N) in DMF prepared in accordance with example 24. The finished coating was very smooth and became lubricious instantly upon exposure to water.
Example 27 A bismuth carbonate filled nylon 11 catheter waq coated with a hydrophilic lubricious coating by the following procedure:
(1) Dipped in an 14 tolylene 2,4-diisocyanate solution in MEK for one hour.
(2) Dried in an air oven at 85C for 30 minutes n (3) Dipped in a 1~ poly(acrylic acid) (~L) solution for one second.
(4) Dried in an air oven at 85C for 30 minutes.
~S) Repeated ~1) except for 10 minutes. ! ' (6) Repeated (2).
(7) Repeated (3).
(8) Repeated (4l.
The finished coating was smooth and ~ont~nuous. It D~16094-1 2~71 3~A
.. .
became very slippery instantly upon exposure to water and showed a good abrasion re!~lstance by the tlssue paper rub test.
Example ;28 S Example 27 was repeated with the exception that a nylvn 12 catheter was substituted for the nylon 1t catheter. The finished coating was lubricious and exhibited good abrasion re~istance.
Example 29 A catheter made of thermal plastic rubber Xraton was coated according to the following procedure:
(1) Dipped in a bath containing a primer solution of the following composition Tolylene diisocyanate 0.75%
Isocyanate (D) 0.25 Mineral Oil 15 for one minute duration.
(2) Dried in an air oven at 85C for 30 minutes.
(3) Dipped in a 1.5% poly(acrylic acid) (M), solution in DMF for one second.
(4) Dried in an air oven at 85C for 30 minutes.
The finished catheter xetained its flexibility, showed negligible shrin~age, and a smooth coating. The latter became very lubricious upon exposure to water and was resistant to abrasion. `
~ Example 30 A catheter made of poly~ethylene vinyl acetate~ `
was coated according to the following procedure: -~
(1) Dipped in a 1% isocyanate (D) solution ln MEK
for 30 minutes. - -~
~ J 2(~7~38fl~
.
(2) Dried at 60C for 30 minut~s;
(3) Dipped in a 1.5% poly(acrylic acid) (M) solution in DMF for one second.
(4) Dried at 60C for 30 minutes.
~S) Repeated ~1) except for 10 minutes. ! ' (6) Repeated (2).
(7) Repeated (3).
(8) Repeated (4l.
The finished coating was smooth and ~ont~nuous. It D~16094-1 2~71 3~A
.. .
became very slippery instantly upon exposure to water and showed a good abrasion re!~lstance by the tlssue paper rub test.
Example ;28 S Example 27 was repeated with the exception that a nylvn 12 catheter was substituted for the nylon 1t catheter. The finished coating was lubricious and exhibited good abrasion re~istance.
Example 29 A catheter made of thermal plastic rubber Xraton was coated according to the following procedure:
(1) Dipped in a bath containing a primer solution of the following composition Tolylene diisocyanate 0.75%
Isocyanate (D) 0.25 Mineral Oil 15 for one minute duration.
(2) Dried in an air oven at 85C for 30 minutes.
(3) Dipped in a 1.5% poly(acrylic acid) (M), solution in DMF for one second.
(4) Dried in an air oven at 85C for 30 minutes.
The finished catheter xetained its flexibility, showed negligible shrin~age, and a smooth coating. The latter became very lubricious upon exposure to water and was resistant to abrasion. `
~ Example 30 A catheter made of poly~ethylene vinyl acetate~ `
was coated according to the following procedure: -~
(1) Dipped in a 1% isocyanate (D) solution ln MEK
for 30 minutes. - -~
~ J 2(~7~38fl~
.
(2) Dried at 60C for 30 minut~s;
(3) Dipped in a 1.5% poly(acrylic acid) (M) solution in DMF for one second.
(4) Dried at 60C for 30 minutes.
(5) Repeated (1) but for 10 minutes. .
(6) Repeated (2).
(7) Repeated (3).
(8) repeated (4).
The finished catheter was very smooth and retalned its original whitish color. It became lubricious instantly upon exposure to water. The coatinq was practically unaffected after 10 rubs with a wet ;-tissue paper. ;
Example 31 A 6-inch tip of a guide catheter wire used in conjunction with a catheter was coated using the procedure described in the previous examples. The gulde wire was dipped ln a primer solution containing 1.0% isocyanate (D) in MEK and dried for 10 minutes at 85C. The wire was subsequently dipped in a 1.5 poly(acrylic acid) (M) solution in DMF for 1 second and redried~ The coated guide wire showed a good degree of lubricity and retained much of its initlal lubricity after rubbing with a wet tissue 4 times.
Example 32 Example 31 was repeated on the full length of the guide wire uslng a 7:3 DMF/MEK solvent ~or the poly(acrylic acid) and the sequence of coating was repeated a second ~ime. the coated guide wire 3~ axhibited a good degree of lubricity upon exposure to water.
{; 3 2~
Example 33 The full length of a nylon 11 catheter comprised of a polyether thermoplastic elastomer and fitted with a polyethylene terephthalate balloon was coated in a manner similar to the prececling examples. The catheter including the balloon were dipped in a primer solution containing 1% isocyanate (D) in MEK and dried for 30 mlnutes at 85C. The catheter with balloon were subsequently dipped in a 1.5% poly(acrylic acid~
(L) dispersion (7:3 DMF/MEK) for 1 second and dried.
The catheter showed very good lubricity upon exposure to water and retained much of initial lubricity after -~
rubbing ~ times with a wet tissue. `
Example 34 An experiment was conducted to demonstrate the preparation of catheters having hydrophilic lubricious coatings from a blend of a polyisocyanate and a carboxylic acid-co~aining polymer. A dispersion was psepared containinq 98 grams of poly(acrylic acid) ~M) , 0.3 gram of MYRJ53 surfactant, 157.5 grams of MEK, and 433.18 grams of DMF. This dispersion had a ~
Brookfield viscosity of 40 cps. Into 196.67 grams of ;A .,.,,~,',., this dlspersion was added 3.33 grams of isocyanate (D) and the blend stirred for 10 minutes. Two nylon 11 ;
catheters were dipped into this blend, the first for 1 minute and the second for 10 minutes. Both catheters ~ére dried for 30 minutes at 85C. Both catheters were not slippery when dry, but upon exposure to water, they exhibited good lubricity. The catheters also exhibited falrly good abrasion a~ter 9 and 12 rubs respectively ~y the t~ssue rub test.
~ - ) z~3~7~38~
- 29 ~
ExamPles 35-58 ~`
Additional experiments ~were conducted to evaluate various catheters coated in accordance with the present invention and whereim variations were made in coating compositions, solvents, number of coatings, drying times and the like. The pertinent data is set ~orth in Tables I-III below:
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ExamPle 59 A low viscosity, uniform colloidal dispersion of poly~acrylic acid) (N) was prepared by the following procedure: Into a 2-liter stainless steel reactor, equipped with a turbine agitator, condenser, thermometer, and an exterior heating bath, there was charged under agitation 487.17 grams of DMF
(Mallinckrodt), 252.7 grams of MEK (Mallinckrodt~, 234.3 grams of tertiary butyl alcohol (Arco), and 0.83 grams of MYRJ-53 (an ethoxylated steric acid produced by ICI). Once a uniform solution was obtalned, 25 gram~
of poly(acrylic acid) (N) powder were introduced by pouring directly into the reator, The reactor was heated to 50C and maintained at 50 + 2C ~or one hour while under agitation at 2000 rpm. Thereafter, the reactor was cooled to room temperature and the content was transferred into a Waring Blender for homongenization. The homogenizad product was filtered through a 10 micron polypropylene filter cartridge ! to ~ `
yleld a uniform colloidal dispersion. It showed the following viscosity properties:
Before homogenlzation Brookfleld viscosity 40 centlpoises Kinematic viscosity 17.3 centistokes After homogenization Brookfield vis~osity 7 censtpoises Kinematic viscosity 8.7 centistokes ExamPle 60 r A prLmer solution was prepared by ffllxing ~0.91 parts of N~EK (Mallinckrodt), 15.47 parts of m~neral oil (Mal$ncrodt), 3.6 parts of polyisocyanate E and D- l 6 0 9 4 -1 f ) 20~1381 ,--, . . .
0.02 parts of FLUORAD 431 ( a surfactant produced by 3M) to yield a mobil, clear liquid. ~he solution contained 0.844 by weight of isocyanate groups.
Example 61 This example illustrates the preparation of a sodium phosphate solution for the acid neutalization of the poly(carboxylic acid) coating of this invention.
An 0.1 N sodium phosphate solution was prepared by dissolvlng 13.8 grams of the reagent (Matheson, Coleman ~ Bell) into one liter of distilled water.
Separately, an O.lN disodium phosphate solution was made by mixing 7.1 grams of the reagent (Matheson, Coleman & Bell) into one liter of distiled water.
Into a one liter beaker containing about 660 ml of the 0.1N disodium phosphate solution, there was added under mixing a sufficient amount of the O.lN sodium phosphat~ solution ~ntil pH reached 7.
Example 62 A plasticized styrene-butadiene catheter was -coated according to the following process to yield durable lubricious coating of this invention.
A 15 inch long, catheter was dipped for 1 minute in a stalnless steel bath contalning the primer of -~
25 Example 60. The coated catheter was air dried briefly -~
and followed by baking in a forced air oven at 85C
for 30 minutes. Thle primed cathatar was dipped quickly ln a topcoat bath containing the polyacrylic ~`
acid colloidal dispersion of Example 59. following a br1eP air--drying the wet cathe er was dried ln the ovsn at 8'iC for 60 minutes.
.,1 ~ . . , , : , 2~7~34 A uniform coating was produced, which became lubricious instantly upon exposure to water. The coating exhibited a good adhesion to the catheter.
Example 63 This example illustrates the utillty of post neutralization ~or preserving hydroph~lic lubrlcity of the coated catheter during a thermoforming process.
A plasticized polystyrene-butadiene catheter coated ~ccording to Example 62 was dlpped in a bath containing the sodium phosphate solution of Example 61. The treated catheter was air dried for one hour.
thereafter the catheter was shaped and heated in that shape at 1200C for 90 minutes. The finished shaped catheter became lubricious instantly upon exposure to water.
Example 64 The thermoforming treatment of Example 63 was repeated without first dipping ln the sodium phosphate solution. The finished stem was no longer lubriclous ;;~
upon exposure to water.
Example 65 Thls example lllustrates the preparative -~
procedure ~or producing a top coat solution containing a poly~methacrylic acid) polymer.
Into a one-liter size Pyrex glass reactor equipped with a turbine agitator, a thermometer, a condenser, an èxternal heating bath and an addition ;~
funnel there was charged 312 grams of DMF~ 120 grams of t-butyl ~lcohol, 158.7 grams of MEK, 0.3 grams of MYRJ-53 ~urfactant and 9 grams of poly(methacrylic acld) (Polysciences). The mlxture was heated to 50C.
D-1~094-1 . ': ' '~
:~
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~ ,.,,~
while under vigorous mixing. After 1 hour mlxing, a uniform solution was obtained. The solut~on was cooled to room temperature and its solution viscosity measured with a Brookfleld Model LVT Viscometer. The value was 5 centipoises.
Example 66 The same thermoplastic rubber catheter used in Example 43 was coated with the polylsocyanate primer (E) and the poly~methacrylic acid) top coat solution prepared in Example 65 according to the following procedure:
1. One minute dip in the primer solutlon.
2. One minute air dry and followed by a 30 minute bake in a 85C forced-air oven.
3. One second dip in the poly(methacrylic acid) top coat solution.
4. One minute air dxaln and followed by a 60 minute bake ln a 85C forced-Alr oven.
The finished catheter was lubricious upon contacting with water. , Exam~e 67 Example 66 was repeated with the exceptlon that a ~`
Nylon 11 catheter was used instead of the thermoplastic rubber catheter. The coated catheter was lubricious upon contact with water.
Example 68 This example illustrates the utllity of a spray coating process for producing the lubriclous coatlng of the invention.
a group of four thermoplastic rubber catheters were cut to a length of 18 inches and mounted on steel .'"'-',., '`''''"
D-16094~
- ( ~ 2(3~8~34 mandrels. The latter were mounted on a steel stand inside a ventilated hood. Thle polyisocyanate primer ~E) was sprayed onto the catheters using an air-spray gun(the Devilbiss Co., Toledo, Ohio, Type JGA-502).
After a 30 minute baking at 85C in a forced-air oven, the primed catheters were sprayed with a coat of poly(methacrylic acid) top coat (N). After a 60 -~
minute baking, a fairly s~ooth coating was obtained.
the coated catheters became lubricious immediately upon exposure to water.
Although the invention has been illustrated by the preceding examples r it is not to be construed as being limited to the materials employed therein, but rather; the invention relates to the generic area as herein before disclosed. Various modifications and embodiments thereof can be made without departlng from the spirit or scope thereof. ;~;
" .,:
,: :. ;,, D-16~94-1 ,: .
::
The finished catheter was very smooth and retalned its original whitish color. It became lubricious instantly upon exposure to water. The coatinq was practically unaffected after 10 rubs with a wet ;-tissue paper. ;
Example 31 A 6-inch tip of a guide catheter wire used in conjunction with a catheter was coated using the procedure described in the previous examples. The gulde wire was dipped ln a primer solution containing 1.0% isocyanate (D) in MEK and dried for 10 minutes at 85C. The wire was subsequently dipped in a 1.5 poly(acrylic acid) (M) solution in DMF for 1 second and redried~ The coated guide wire showed a good degree of lubricity and retained much of its initlal lubricity after rubbing with a wet tissue 4 times.
Example 32 Example 31 was repeated on the full length of the guide wire uslng a 7:3 DMF/MEK solvent ~or the poly(acrylic acid) and the sequence of coating was repeated a second ~ime. the coated guide wire 3~ axhibited a good degree of lubricity upon exposure to water.
{; 3 2~
Example 33 The full length of a nylon 11 catheter comprised of a polyether thermoplastic elastomer and fitted with a polyethylene terephthalate balloon was coated in a manner similar to the prececling examples. The catheter including the balloon were dipped in a primer solution containing 1% isocyanate (D) in MEK and dried for 30 mlnutes at 85C. The catheter with balloon were subsequently dipped in a 1.5% poly(acrylic acid~
(L) dispersion (7:3 DMF/MEK) for 1 second and dried.
The catheter showed very good lubricity upon exposure to water and retained much of initial lubricity after -~
rubbing ~ times with a wet tissue. `
Example 34 An experiment was conducted to demonstrate the preparation of catheters having hydrophilic lubricious coatings from a blend of a polyisocyanate and a carboxylic acid-co~aining polymer. A dispersion was psepared containinq 98 grams of poly(acrylic acid) ~M) , 0.3 gram of MYRJ53 surfactant, 157.5 grams of MEK, and 433.18 grams of DMF. This dispersion had a ~
Brookfield viscosity of 40 cps. Into 196.67 grams of ;A .,.,,~,',., this dlspersion was added 3.33 grams of isocyanate (D) and the blend stirred for 10 minutes. Two nylon 11 ;
catheters were dipped into this blend, the first for 1 minute and the second for 10 minutes. Both catheters ~ére dried for 30 minutes at 85C. Both catheters were not slippery when dry, but upon exposure to water, they exhibited good lubricity. The catheters also exhibited falrly good abrasion a~ter 9 and 12 rubs respectively ~y the t~ssue rub test.
~ - ) z~3~7~38~
- 29 ~
ExamPles 35-58 ~`
Additional experiments ~were conducted to evaluate various catheters coated in accordance with the present invention and whereim variations were made in coating compositions, solvents, number of coatings, drying times and the like. The pertinent data is set ~orth in Tables I-III below:
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~ : . ) 2(~78~3~
ExamPle 59 A low viscosity, uniform colloidal dispersion of poly~acrylic acid) (N) was prepared by the following procedure: Into a 2-liter stainless steel reactor, equipped with a turbine agitator, condenser, thermometer, and an exterior heating bath, there was charged under agitation 487.17 grams of DMF
(Mallinckrodt), 252.7 grams of MEK (Mallinckrodt~, 234.3 grams of tertiary butyl alcohol (Arco), and 0.83 grams of MYRJ-53 (an ethoxylated steric acid produced by ICI). Once a uniform solution was obtalned, 25 gram~
of poly(acrylic acid) (N) powder were introduced by pouring directly into the reator, The reactor was heated to 50C and maintained at 50 + 2C ~or one hour while under agitation at 2000 rpm. Thereafter, the reactor was cooled to room temperature and the content was transferred into a Waring Blender for homongenization. The homogenizad product was filtered through a 10 micron polypropylene filter cartridge ! to ~ `
yleld a uniform colloidal dispersion. It showed the following viscosity properties:
Before homogenlzation Brookfleld viscosity 40 centlpoises Kinematic viscosity 17.3 centistokes After homogenization Brookfield vis~osity 7 censtpoises Kinematic viscosity 8.7 centistokes ExamPle 60 r A prLmer solution was prepared by ffllxing ~0.91 parts of N~EK (Mallinckrodt), 15.47 parts of m~neral oil (Mal$ncrodt), 3.6 parts of polyisocyanate E and D- l 6 0 9 4 -1 f ) 20~1381 ,--, . . .
0.02 parts of FLUORAD 431 ( a surfactant produced by 3M) to yield a mobil, clear liquid. ~he solution contained 0.844 by weight of isocyanate groups.
Example 61 This example illustrates the preparation of a sodium phosphate solution for the acid neutalization of the poly(carboxylic acid) coating of this invention.
An 0.1 N sodium phosphate solution was prepared by dissolvlng 13.8 grams of the reagent (Matheson, Coleman ~ Bell) into one liter of distilled water.
Separately, an O.lN disodium phosphate solution was made by mixing 7.1 grams of the reagent (Matheson, Coleman & Bell) into one liter of distiled water.
Into a one liter beaker containing about 660 ml of the 0.1N disodium phosphate solution, there was added under mixing a sufficient amount of the O.lN sodium phosphat~ solution ~ntil pH reached 7.
Example 62 A plasticized styrene-butadiene catheter was -coated according to the following process to yield durable lubricious coating of this invention.
A 15 inch long, catheter was dipped for 1 minute in a stalnless steel bath contalning the primer of -~
25 Example 60. The coated catheter was air dried briefly -~
and followed by baking in a forced air oven at 85C
for 30 minutes. Thle primed cathatar was dipped quickly ln a topcoat bath containing the polyacrylic ~`
acid colloidal dispersion of Example 59. following a br1eP air--drying the wet cathe er was dried ln the ovsn at 8'iC for 60 minutes.
.,1 ~ . . , , : , 2~7~34 A uniform coating was produced, which became lubricious instantly upon exposure to water. The coating exhibited a good adhesion to the catheter.
Example 63 This example illustrates the utillty of post neutralization ~or preserving hydroph~lic lubrlcity of the coated catheter during a thermoforming process.
A plasticized polystyrene-butadiene catheter coated ~ccording to Example 62 was dlpped in a bath containing the sodium phosphate solution of Example 61. The treated catheter was air dried for one hour.
thereafter the catheter was shaped and heated in that shape at 1200C for 90 minutes. The finished shaped catheter became lubricious instantly upon exposure to water.
Example 64 The thermoforming treatment of Example 63 was repeated without first dipping ln the sodium phosphate solution. The finished stem was no longer lubriclous ;;~
upon exposure to water.
Example 65 Thls example lllustrates the preparative -~
procedure ~or producing a top coat solution containing a poly~methacrylic acid) polymer.
Into a one-liter size Pyrex glass reactor equipped with a turbine agitator, a thermometer, a condenser, an èxternal heating bath and an addition ;~
funnel there was charged 312 grams of DMF~ 120 grams of t-butyl ~lcohol, 158.7 grams of MEK, 0.3 grams of MYRJ-53 ~urfactant and 9 grams of poly(methacrylic acld) (Polysciences). The mlxture was heated to 50C.
D-1~094-1 . ': ' '~
:~
:- :
" ( '`-) Z(~)788~1L
~ ,.,,~
while under vigorous mixing. After 1 hour mlxing, a uniform solution was obtained. The solut~on was cooled to room temperature and its solution viscosity measured with a Brookfleld Model LVT Viscometer. The value was 5 centipoises.
Example 66 The same thermoplastic rubber catheter used in Example 43 was coated with the polylsocyanate primer (E) and the poly~methacrylic acid) top coat solution prepared in Example 65 according to the following procedure:
1. One minute dip in the primer solutlon.
2. One minute air dry and followed by a 30 minute bake in a 85C forced-air oven.
3. One second dip in the poly(methacrylic acid) top coat solution.
4. One minute air dxaln and followed by a 60 minute bake ln a 85C forced-Alr oven.
The finished catheter was lubricious upon contacting with water. , Exam~e 67 Example 66 was repeated with the exceptlon that a ~`
Nylon 11 catheter was used instead of the thermoplastic rubber catheter. The coated catheter was lubricious upon contact with water.
Example 68 This example illustrates the utllity of a spray coating process for producing the lubriclous coatlng of the invention.
a group of four thermoplastic rubber catheters were cut to a length of 18 inches and mounted on steel .'"'-',., '`''''"
D-16094~
- ( ~ 2(3~8~34 mandrels. The latter were mounted on a steel stand inside a ventilated hood. Thle polyisocyanate primer ~E) was sprayed onto the catheters using an air-spray gun(the Devilbiss Co., Toledo, Ohio, Type JGA-502).
After a 30 minute baking at 85C in a forced-air oven, the primed catheters were sprayed with a coat of poly(methacrylic acid) top coat (N). After a 60 -~
minute baking, a fairly s~ooth coating was obtained.
the coated catheters became lubricious immediately upon exposure to water.
Although the invention has been illustrated by the preceding examples r it is not to be construed as being limited to the materials employed therein, but rather; the invention relates to the generic area as herein before disclosed. Various modifications and embodiments thereof can be made without departlng from the spirit or scope thereof. ;~;
" .,:
,: :. ;,, D-16~94-1 ,: .
::
Claims (51)
1. A method of covering at least a portion of a substrate with a hydrophilic coating which coating exhibits good abrasion resistance and an increased lubricity when contacted with an aqueous-containing fluid, said method comporising the steps of:
(1) contacting said substrate with polyisocyanate contained in at least one first inert solvent to provide at least a partially coated substrate;
(2) contacting said coated substrate with a poly(acrylic acid) polymer of the formula:
where n=0-0.95 mole fraction of neutralized acid moities, m-0.05-1.0 mole fraction of acid moieties with the proviso that n+m=1, X1, X2, X3 are each a hydrogen atom or a monovalent organic radical, Y is a single bond or a divalent organic radical, z is a metallic ion or a tertiary ammonium ion, and p is a number such that the polymer has a molecular weight between about 200,000 and about 5,000,000 said poly(acrylic acid) polymer contained in at least one second solvent to provide a multiple coated substrate; and (3) thereafter drying said multiple coated substrate to provide a hydrophilic, lubricious coating which contains free carboxylic acid groups or partially neutralized carboxylic acid groups.
(1) contacting said substrate with polyisocyanate contained in at least one first inert solvent to provide at least a partially coated substrate;
(2) contacting said coated substrate with a poly(acrylic acid) polymer of the formula:
where n=0-0.95 mole fraction of neutralized acid moities, m-0.05-1.0 mole fraction of acid moieties with the proviso that n+m=1, X1, X2, X3 are each a hydrogen atom or a monovalent organic radical, Y is a single bond or a divalent organic radical, z is a metallic ion or a tertiary ammonium ion, and p is a number such that the polymer has a molecular weight between about 200,000 and about 5,000,000 said poly(acrylic acid) polymer contained in at least one second solvent to provide a multiple coated substrate; and (3) thereafter drying said multiple coated substrate to provide a hydrophilic, lubricious coating which contains free carboxylic acid groups or partially neutralized carboxylic acid groups.
2. The method of claim 1 wherein said substrate is a medical device.
3. The method of claim 2 wherein said medical device is a catheter.
4. The method of claim 1 wherein said substrate coated with said polyisocyanate is dried at a temperature of up to about 150°C. before step (2).
5. The method of claim 4 wherein said multiple coated substrate is dried at a temperature of from about 25° to about 150°C.
6. The method of claim 1 wherein said first solvent is methyl ethyl ketone.
7. The method of claim 1 wherein said first solvent is ethyl acetate.
8. The method of claim 1 wherein said first solvent is a mixture of at least two solvents.
9. The method of claim 8 wherein said mixture contains mineral oil
10. The method of claim 8 wherein said mixture contains at least one surfactant.
11. The method of claim 1 wherein said second solvent is at least one organic solvent inert to said poly(acrylic acid) polymer.
12. The method of claim 1 wherein said second solvent is dimethylformamide.
13. The method of claim 1 wherein said second solvent is dimethylsulfoxide.
14. The method of claim 1 wherein said second solvent is a mixture of dimethylformamide and methly ethyl ketone.
15. The method of claim 1 wherein said second solvent is a mixture of dimethylformamide, methyl ethyl ketone and t-butyl alcohol.
16. The method of claim 1 wherein said polyisocyanate is a diisocyanate.
17. The method of claim 16 wherein said diisocyanate is a mixture of toluene 2,4- and 2,6-diisocyanate.
18. The method of claim 16 wherein said diisocyanate is a diphenylmethane diisocyanate.
19. The method of claim 16 wherein said diisocyanate is an adduct of diphenylmethane diisocyanate and a polyol.
20. The method of claim 1 wherein said polyisocyanate is an isocyanate end-capped polyfunctional aliphatic adduct.
21. The method of claim 1 wherein said polyisocyanate is an isocyanate end-capped polyfunctional aromatic adduct.
22. The method of claim 1 wherein said coated substrate is thermoformed to different shapes.
23. The method of claim 22 wherein said coated substrate is first treated with an alkaline bath before thermoforming.
24. The method of claim 22 wherein said coated substrate is first treated with an alkali metal salt bath before thermoforming.
25. The method of claim 22 wherein said coated substrate is first treated with an alkali metal phosphate bath before thermoforming.
26. The method of claim 1 wherein said polyisocyanate is a reaction product of a polyfunctional isocyanate with an aliphatic polyester polyol.
27. The method of claim 1 wherein said polyisocyanate is a reaction product of a polyfunctional isocyanate with an aromatic polyester polyol.
28. The method of claim 1 wherein said polyisocyanate is a mixture of a diisocyanate and an isocyanate end-capped polyfunctional adduct.
29. The method of claim 1 wherein said poly(acrylic acid) polymer is a colloidal dispersion of a homopolymer.
30. The method of claim 1 wherein said poly(acrylic acid) polymer has a molecular weight of about 3,000,000.
31. The method of claim 1 wherein said poly(acrylic acid) polymer is a copolymer.
32. The method of claim 1 wherein said poly(acrylic acid) polymer is partially cross-linked, and contains at least some water insoluble units.
33. The method of claim 1 wherein said polyisocyanate is applied as a dispersion.
34. The method of claim 1 wherein said poly(siocyanate is applied as an oil-in-water emulsion.
35. The method of claim 1 wherein said poly(acrylic acid) polymer is applied as an emulsion.
36. The method of claim 1 wherein said poly(acrylic acid) polymer is applied as a dispersion.
37. A method of covering at least a portion of a substrate with a hydrophilic coating having good abrasion resistance, and which exhibits an increased lubricity when contacted with an aqueous-containing fluid, said method comprising the steps of:
(1) contacting said substrate with a polyisocyanate contained in at least one first inert organic solvent to provide at least a partially coated substrate;
(2) contacting said coated substrate with a poly(acrylic acid) polymer of the formula:
where a = 0-0.95 mole fraction of neutralized acid moities;
m = 0.05-1.0 mole fraction of acid moieties with the proviso that n+m = 1;
X1, X2, X3 are each a hydrogen atom or a monovalent organic radical;
Y is a single bond or a divalent organic radical;
Z is a metallic ion or a tertiary Ammonium ion; and p is a number such that the polymer has a molecular weight between about 200,000 and about 5,000,000;
said carboxylic acid-containing polymer contained in at least one second inert organic solvent to provide a multiple coated substrate; and (3) thereafter drying said multiple coated substrate to provide a hydrophilic, lubricious coating,
(1) contacting said substrate with a polyisocyanate contained in at least one first inert organic solvent to provide at least a partially coated substrate;
(2) contacting said coated substrate with a poly(acrylic acid) polymer of the formula:
where a = 0-0.95 mole fraction of neutralized acid moities;
m = 0.05-1.0 mole fraction of acid moieties with the proviso that n+m = 1;
X1, X2, X3 are each a hydrogen atom or a monovalent organic radical;
Y is a single bond or a divalent organic radical;
Z is a metallic ion or a tertiary Ammonium ion; and p is a number such that the polymer has a molecular weight between about 200,000 and about 5,000,000;
said carboxylic acid-containing polymer contained in at least one second inert organic solvent to provide a multiple coated substrate; and (3) thereafter drying said multiple coated substrate to provide a hydrophilic, lubricious coating,
38. The method of claim 37 wherein the first solvent is methyl ethyl ketone.
39. The method of claim 37 wherein the second solvent is dimethylfotmamide.
40. The method of claim 37 wherein said second solvent is a mixture of dimethylfoymamide and methyl ethyl ketone.
41. The method of claim 37 wherein said substrate coated with said polyisocyanate is dried at a temperature of up to about 150°C. before step (2).
42. The method of claim 37 wherein at least one of said first or second solvents contains a surfactant.
43. The method of claim 1 wherein at least one additive is incorporated into said coating.
44. The method of claim 37 wherein at least one additive is incorporated into said coating.
45. The method of claim 43 wherein the additive is an antithrombogenic.
46. The method of claim 43 wherein said additive is heparin.
47. A method of covering at least a portion of a substrate with a hydrophilic coating which coating exhibits good abrasion resistance and an increased lubricity when contacted with an aqueous-containing fluid, said method comprising the steps of:
(1) contacting said substrate with polyisocyanate contained in at least one first inert solvent to provide at least a partially coated substrate;
(2) drying said coated substrate to provide a primer coat of the polyisocyanate on the substrate;
(3) contacting said coated substrate with a poly(acrylic acid) polymer of the formula:
where n = 0-0.95 mole fraction of neutralized acid moieties, m = 0.05-1.0 mole fraction of acid moieties with the proviso that n + m = 1, X1, X2, X3 are each a hydrogen atom or a monovalent organic radical, Y is a single bond or a divalent organic radical, Z is a metallic ion or a tertiary ammonium ion, and p is a number such that the polymer has a molecular weight between about 200,000 and about 5,000,000, said poly(acrylic acid) polymer contained in at least one second solvent to provide a multiple coated substrate;
(4) thereafter drying said multiple coated substrate to provide a hydrophilic, lubricious coating which contains free carboxylic acid groups or partially neutralized carboxylic acid groups; and (5) optionally neutralizing the multiple coated substrate.
(1) contacting said substrate with polyisocyanate contained in at least one first inert solvent to provide at least a partially coated substrate;
(2) drying said coated substrate to provide a primer coat of the polyisocyanate on the substrate;
(3) contacting said coated substrate with a poly(acrylic acid) polymer of the formula:
where n = 0-0.95 mole fraction of neutralized acid moieties, m = 0.05-1.0 mole fraction of acid moieties with the proviso that n + m = 1, X1, X2, X3 are each a hydrogen atom or a monovalent organic radical, Y is a single bond or a divalent organic radical, Z is a metallic ion or a tertiary ammonium ion, and p is a number such that the polymer has a molecular weight between about 200,000 and about 5,000,000, said poly(acrylic acid) polymer contained in at least one second solvent to provide a multiple coated substrate;
(4) thereafter drying said multiple coated substrate to provide a hydrophilic, lubricious coating which contains free carboxylic acid groups or partially neutralized carboxylic acid groups; and (5) optionally neutralizing the multiple coated substrate.
48. The method of claim 47 wherein the polyisocyanate is diphenylmethane diisocyanate or an adduct thereof, wherein the first inert solvent is either methyl ethyl ketone or toluene, wherein the second inert solvent is a mixture of methyl ethyl ketone, dimethylformamide and t-butyl alcohol.
49. The method of claim 48 wherein the polyisocyanate is diphenylmethane diioacyanate or an adduct thereof in the first inert solvent is present in a concentration of from about 0.5 to about 20 percent by weight and the poly(acrylic acid) in the second inert solvent is present in a concentration of from about 0.1 to about 10 percent by weight.
50. The method of claim 49 wherein the in a concentration of from about 1 to about 5 percent by polyisocyanate is diphenylmethane diisocyanate or an adduct thereof in the first inert solvent is present solvent is present in a concentration of from about 0.5 to about 2 percent by weight.
51. The method of claim 47 wherein the polyisocyanate is a mixture of different polyisocyanates, wherein the first inert solvent is either methyl ethyl ketone or toluene, wherein the second inert solvent is a mixture of methyl ethyl ketone, dimethylformamide and t-butyl alcohol.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29733189A | 1989-01-17 | 1989-01-17 | |
| US297,331 | 1989-01-17 | ||
| US449,777 | 1989-12-22 | ||
| US07/449,777 US5091205A (en) | 1989-01-17 | 1989-12-22 | Hydrophilic lubricious coatings |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2007884A1 CA2007884A1 (en) | 1990-07-17 |
| CA2007884C true CA2007884C (en) | 1994-07-12 |
Family
ID=26970100
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002007884A Expired - Lifetime CA2007884C (en) | 1989-01-17 | 1990-01-16 | Hydrophilic lubricious coatings |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5091205A (en) |
| EP (1) | EP0379156B1 (en) |
| JP (1) | JPH0790040B2 (en) |
| AT (1) | ATE136565T1 (en) |
| CA (1) | CA2007884C (en) |
| DE (1) | DE69026396T2 (en) |
| ES (1) | ES2085290T3 (en) |
| GR (1) | GR3019636T3 (en) |
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1989
- 1989-12-22 US US07/449,777 patent/US5091205A/en not_active Expired - Lifetime
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- 1990-01-16 CA CA002007884A patent/CA2007884C/en not_active Expired - Lifetime
- 1990-01-16 DE DE69026396T patent/DE69026396T2/en not_active Expired - Lifetime
- 1990-01-16 JP JP2004672A patent/JPH0790040B2/en not_active Expired - Lifetime
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1996
- 1996-04-11 GR GR960400852T patent/GR3019636T3/en unknown
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| DE69026396T2 (en) | 1996-08-08 |
| CA2007884A1 (en) | 1990-07-17 |
| JPH0790040B2 (en) | 1995-10-04 |
| GR3019636T3 (en) | 1996-07-31 |
| US5091205A (en) | 1992-02-25 |
| ES2085290T3 (en) | 1996-06-01 |
| EP0379156A2 (en) | 1990-07-25 |
| DE69026396D1 (en) | 1996-05-15 |
| ATE136565T1 (en) | 1996-04-15 |
| JPH02277458A (en) | 1990-11-14 |
| EP0379156B1 (en) | 1996-04-10 |
| EP0379156A3 (en) | 1991-11-21 |
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