CA1206668A - Polymer surfaces for blood-contacting surfaces of a biomedical device, and methods for forming - Google Patents
Polymer surfaces for blood-contacting surfaces of a biomedical device, and methods for formingInfo
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- CA1206668A CA1206668A CA000371214A CA371214A CA1206668A CA 1206668 A CA1206668 A CA 1206668A CA 000371214 A CA000371214 A CA 000371214A CA 371214 A CA371214 A CA 371214A CA 1206668 A CA1206668 A CA 1206668A
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L83/00—Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
- C08L83/10—Block- or graft-copolymers containing polysiloxane sequences
- C08L83/12—Block- or graft-copolymers containing polysiloxane sequences containing polyether sequences
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/062—Mixtures of macromolecular compounds
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/068—Use of macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- 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
- C08G18/08—Processes
- C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
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- 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
- C08G18/61—Polysiloxanes
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- 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
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/42—Block-or graft-polymers containing polysiloxane sequences
- C08G77/452—Block-or graft-polymers containing polysiloxane sequences containing nitrogen-containing sequences
- C08G77/455—Block-or graft-polymers containing polysiloxane sequences containing nitrogen-containing sequences containing polyamide, polyesteramide or polyimide sequences
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- 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
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/42—Block-or graft-polymers containing polysiloxane sequences
- C08G77/458—Block-or graft-polymers containing polysiloxane sequences containing polyurethane sequences
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- 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
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/42—Block-or graft-polymers containing polysiloxane sequences
- C08G77/46—Block-or graft-polymers containing polysiloxane sequences containing polyether sequences
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L75/00—Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
- C08L75/04—Polyurethanes
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Abstract
POLYMER SURFACES FOR BLOOD-CONTACTING SURFACES
OF A BIOMEDICAL DEVICE, AND METHODS FOR FORMING
Abstract of the Invention A polymer admixture is formed from at least 95 volume % of a base polymer and less than 5 volume % of a polymer additive including at least first and second different homopolymer chains in graft or block copolymer form. The first chains are characterized by a low critical surface tension but with a tendency to exudate while the second ones lower this tendency. This polymer mixture is formed into the exposed blood-contacting surface of a biomedical device.
A preferred additive is a block copolymer of (a) polydialkyl-siloxanes and (b) a polyurethane.
OF A BIOMEDICAL DEVICE, AND METHODS FOR FORMING
Abstract of the Invention A polymer admixture is formed from at least 95 volume % of a base polymer and less than 5 volume % of a polymer additive including at least first and second different homopolymer chains in graft or block copolymer form. The first chains are characterized by a low critical surface tension but with a tendency to exudate while the second ones lower this tendency. This polymer mixture is formed into the exposed blood-contacting surface of a biomedical device.
A preferred additive is a block copolymer of (a) polydialkyl-siloxanes and (b) a polyurethane.
Description
~L2~ i6~
POLYMER SURFACES FOR BLOOD-CONTACTING SUR~ACES
OF A BIOMEDICAL DEVICE, AND METHODS FOR EOR~IING
. Background of the Invention One widely accepted hypothesis regarding blood compaki-bility is that it is maximized within a narrow range of surface free energies which give rise to favorable inter-actions with plasma proteins. A common measurement of surface free energies is by Zisman~s critical ~urface tension tYC)~ The optimum value has been found empir-ically to lie wi~hin the range of a y~ equal to about 20 to 30 dyne/cm., see, e.gO, R.A. Baeir, Ann. N.Y, Acad.
Sci. 17t 283 (1977) Common polymers te.9~ polyurethane) which provide the desired physical properties for the blood contact surfaces of biomedical devices often do not fall within this range of critical ~urface tensions.
Polysiloxanes are known to have a particularly low critical surface tension value and have been suggested for incorpo-ration into polyurethanes to improve the surf ace character-iStiC5 of such materials. However, polysiloxane by itself is known to have a tendency to exudate rom the polyurethane base polymer as illustrated in Reischl et al~, UOS. Patent 3,243,475.
Polysiloxane-polyurethane block copolymers have been suggested for use to modify the surface characteristics of blood contact surfaces of devices of biomedical devices as illustrated in Nyilas U.S. Patent 3,562,352. The technique disclosed for such use includes fabricating the entire blood contact devices from such block copolymers or coating such devices with the copolymers. The block copolymers themselves have poor structural characteristics due to a ~igh proportion of polysiloxane. On the other hand, the coated materials are particularly expensive to form as they are not processable by thermoplastic methods such as injection molding and extru~ion. The manufacture of tubing, catheters and other blood-contacting disposable devices from such materials is particularly expensive due to ~5 the necessity of employing solution fabrication techniques.
Certain experimental work has been published relating to the blending of block copolymers of polydimethylsiloxane with homopolymers of higher critical surface tensions. These materials are known to produce films with high siloxane surface concentrations. See, for example, D.G Legrand and R.L.Gaines, Jr., Polym Prepr. 11, 442 (l970); D.W. Dwight et al., Polym. Prepr. 20, (1), 702 (1979); and J.J. O'Malley, Polym Prepr. 18 (1977). However, all of these references describe the polymer blends in terms of scientific experi-ments without suggestion that the material would have any advantage for use in any biomedical application.
Summary of the Invention and Objects It is an object of the invention to provide a new form of polymer of low surface free energy for use as ~he surface of a blood-contacting medical device which is of low cost, is readily processed, and which is characterized by excellent engineering properties. Further objects and features of the invention will be apparent from the following description of its preferred embodiments.
In accordance with the above objects, a new technique has been provided for forming the exposed blood-contacting surface of a biomedical device or componen-t. In one embodiment, a minor amount of a polymer additive is dispersed through the base polymer while both are fluid -to form a polymer admixture. The polymer additive includes at least two different homopolymer chains, which in a preferred embodiment may be in a graft or a block copolymer form. One of the chains is of low surface free energy (e.g., a polysiloxane~, while the other chain is characterized by an ability to reduce the tendency of this material to exudate from the base polymer. In a preferred embodi-ment the base polymer and second component of the polymer additive are of the same material (e.g., polyurethane). The polymer additive serves to reduce -the critical surface tension of the base polymer to render it blood compatible.
In one aspect, the invention provides a blood-compatible polymer admixture comprising at least 95 volume % of a base polymer and no greater than 5 volume % of a polymer additive comprising a copolymer of a ~irst homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a Yc less than said base polymer and said polymer admixture being characterized by Yc between about 10 and 35 dyne/cm.
In another aspect, the inventi~n provides a blood-compatible polymer additive solid at 37C comprising a block polymer including a sequence of block segments represented by the formula [A][B][C], in which A is a poly(dialkylsiloxane), B is a hard block polymer segment with a crys-talline melting point above 37C or a glass transi-tion temperature above 37C, and C
is a hydrophilic polymer selected from the group consisting of polyethylene oxide and polyethylene oxide-copolypropylene oxide.
In a further aspect, the invention provides a biomedical device, or component thereof, having a blood-compatible, blood-contacting surface, the said surface formed of a polymer admixture comprising at least 95 volume % of a base polymer and no greater than 5 volume % of a polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being dispersed throughout said base polymer and being characterized by a Yc less than said base polymer, said polymer admixture being characterized by a Yc between about 10 and 35 dyne/cm.
In a further aspect, the invention provides a method of forming a polymer admixture of low surface free energy from a base polymer and polymer additive comprising the s-teps of (a) thoroughly dispersing no greater than about 5 volume %
of a polymer addltive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive compris-ing a copolymer of a first homopolymer chain component chemically bonded to at least a second homopolymer chain compQnent of a different type than said first component, said polymer additive being characterized by a y less than said base polymer and said - 3a -~2ai6~i68 polymer admixture being characterized by a ~c between about 10 and 35 dyne/cm; and (b) solidifying said polymer admixture.
In yet a further aspect, the invention provides, in a method of forming the exposed blood-contacting surface of a biomedical device, or components thereof, the steps of (a) thoroughly dispersing no yreater than about 5 volume %
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a ~c less than said base polymer and said polymer admixture being characterized by a ~c between about 10 and 35 dyne/cm.; and (b) solidifying said polymer admixture and forming it into the blood-contacting surface of a biomedical device or component thereof.
The invention also provides a method of forming a polymer of low surface free energy comprising the steps of (a) reacting about 0.0002 to 2 volume % of a homopolymer additive with at least 98 volume % of a base polymer, while said homopolymer additive and base polymer are in fluid form to form a fluid polymer admixture of at least 95 volume % pure base polymer and, thoroughly dispersed in said base polymer, no greater than 5 volume % of a copolymer of said base polymer and said nomo-polymer additive, and 3b -~,...
~2iC~6~6~
(b) solidifying said polymer admixture, said homopolymer additive being characterized by a ~ less than said base polymer and said polymer admixture being characterized by a ~ between about 10 and 35 dyne/cm.
In yet a further aspec-t, the invention provides, in a method of forming a polymer admixture of iow surface free energy from a base polymer and polymer additive wherein said base polymer includes end groups capable of hydrogen bonding or reacting with protein, the steps of (a) fractionating a base polymer to remove a lower molecular weight fraction to reduce the Yc of the remaining base polymer, (h) thoroughly dispersing no greater than about 5 volume %
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a ~ less than said base polymer and said polymer admixture being characterized by a ~c between about 10 and 35 dyne/cm.; and (c) solidifying said polymer admixture.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
One major feature of the presen-t invention is to provide a technique for lowering the surface free energy of a ~ood structural polymer to convert a su~face formed from such material from one which is blood incompatible to one which is hl~od .;?~ _ 3c compatible. As used herein, the term "base polymer" will refer to the polymer whose surface characteristics is so modified.
Typical base polymers whose surfaces may be improved by the present technique include polyurethanes, polysulfones, poly-carbonates, polyesters, polyethylene, polypropylene, polystyrene poly(acrylonitrile-butadiene-styrene), polybutadiene, polyisoprene, styrene-butadiene-styrene block copolymers, styrene-isoprene-styrene block copolymers, poly-~-methylpen-tene, polyisobutylene, - 3d -polymethyl-methacrylate, polyvinylacetate, polyacrylo-nitrile, polyvinyl chloride, polyethylene terephthalate, cellulose and its esters and derivatives, and the like.
The base polymer is of a type capable of being formed into a sel~-supporting structural body, a self-supporting film, or deposited as a coating onto a self-supporting body. The end use of the final product is the surface of a biomedical d~vice or component.
Another characteri~tic of the base polymer is that it includes a critical surface tension (Yc) in excess of that desirable for a blood contact surface and in excess of the polymer additive to be described below which reduce5 its ~c value. As defined herein, Yc measurements -are performed by the direct method using a contact angle meter of the Kernco or Rame-Hart type and a series of seven solvents according to the Zisman procedure as set forth in A.W. Adamson, Physical Chemistry for Surfaces 339-357, 351-~3d Ed.). Measurements are made at room temperature usingadvancing angles on solvent cast films annealed at 60C for four hours. The mean contact angles are fitted to a Zisman plot using a linear regression calcula~or program.
.
In accordance with the present invention, a base polymer of the foregoing type is mixed with a polymer additive as set out below to lower its surface free energy. The polymer additive with a substantially lower Yc value than that of the base polymer is thoroughly dispersed into ~he base polymer while in fluid form to form a fluid polymer admix-ture. Thereafter, the polymer admixture is solidified and formed into the blood contacting surface of a biomedical device or component. A suitable broad range of surface free energies of the polymer admixture is from 10 ~o 35 dyne/cm.
while a preferred range is from 20 to 30 dyne/cm. An optimum range is 20-25 dyne/cm.
The polymer additive includes at least two different homopolymer chain components of different functional characteristics. One homopolymer chain, herein the "first component", has a relatively low Yc value, less than that of both the base polymer and the second component and causes reduction in the Yc f the polymer admixture as set out below. Such material typically has a tendency to exudate from the base polymer in admixture.
To prevent exudation, at least a second homopolymer chain, herein the ~second component~, is chemically bonded to the first component in the polymer additive to lower this tendency to exuâate~ The second componen~ may be selected from the group of nhard block~ polymer segments useful in the preparation of thermoplastic block copolymers as set out in A. Noshay and J.E. McGrath, Block Copolymers Overview and Critical Survey ~Academic Press 1977). For biomedical applications, the hard blocks are characterized by a crystal line melting point greater than about 37C and/or a glass transition temperature also greater ~han about 37C. This second component has a higher surface free energy than the first one. For compatibility, the second component is preferably formed of a polymer sf the same type as the base copolymer.
It has been found that the homopolymer component of the additive with the lowest y~ value controls the Yc value of the entire polymer additive. Thus, for example, if the first component has a Yc value of 25 and the second component a Yc value of 35, the total Yc f the annealed additive i5 approxima~ely 25.
Suitable homopolymers for the first component are those with a Yc val~e in the desired range to lower the value of the base pol~mer to that desired for blood compatibilitY-Thus, it is preferable that such first component be charac-terized by a ~ value les~ than 30 dyne~cm. One particularly effec~ive homopolymer for this purpoe $s a polydimethylsiloxane with a Y~ on ~he order of 22 dynefcm. Techniques for ~orming siloxane copolymers for use in the presen~ invention are known, e.g., as described in WO Noll, ChemistrY and Technolo~y of Silicones ~Academic Press, 196B). Suitable first component homopolymer include other polydialkylsiloxanes, polyfluoroalkyl alkylsiloxanes, polyal~ylene oxides, polyolefins, polydienes and polyfluoro-carbon~O
Where the polymer admixture of the present invention is Eormed by mixi~g a preormed polymer additive o.~ the foregoing type wit~ base polymer, ~ueh polymer addi~ive~
~ui~ably f~rmed of block copolymers of alterna~ing ~irst and seeond ~omponents interlinked by chemi~al bonds in accordance with known techniquesO For example~ ~uch block copolymerQ may be ~ormed in accordance with th2 foregoing Noshay and McGrat~ publi~ation. A suitable number of repea~ing units of each homopolymer of the first component is that ~ufficient to retain the y~ value of the homopoly-mer a~ evidenced by re~ntion of approximately the same glass tran ition temperature as its pure homopolymer.
Typically, ~his number is on the order o~ 5 to 10 units or more. Similarly, there should be a sufficie~t number of repeating unit~ ~f the ~econd component in a segment so that the polymer additive i~ ~olid 3~ ro~m ~emperature.
The preparation of bloc~ cop~lymers t~r multipolymers) may be performed by ~everal proeedures which ~if~er in the degree to which the ~truc~cure of the resulting produet may be de~ined.
One proced~re ~nvolves ~he coupling of two (~r more~
preformed blocks which are prepared in E;eparate reactic~ns prior to 1:he coupling reactionl This procedure involves a ~3 ~7 very well def ined ~tructure ~f ~he ~oupling re~ction pre-cludes l~ke blo6}c~ ~rom reactin~ witl themselves but only -3110ws diss~milar blocics ~o ~ouple to one another.
5 A ~lightly le~s well deined Etruc~cure result~ ~f the two pre~ormed block~ posse~ the abili~y (via the coupling reaction) to react ~ith hemselve~ as well a~ w~th the di~similar block. .
10 An even le~s well defined ~ru~ture results when ~ single (or more ) pre ormed Iblodc i~ soupled with a ~econd block ~rea~ed during tbe ¢:oupling reaction. In ~his case the ~ ni ~ial leng~ch o~ the pre~ormed block i~ lcnown ~by v~rtue of 'che ~eparate reaetion u~ed ~o prep~re it) bu~ ~he ~equen~e distr~bution of the copoly~Der i~ not known ~xactly since . both ~oupling ~nd ~bain growth ~8 possible in the reaction.
wh~ch produces the ~e~ond blocl;. 8uitable ~ethods of forming the e ~nd other ~uch copolymer~ for u~e ln the presen~ inven~isn ~re ~et out ~n ~he ~rementione~ Noshay and Mc~rath publ~stiDn.
~n~ unigue ~peci~ic ~dmixture ~o~ording to the present ~n-~ention include~ ~ blGck or gr~f~ copolymer of poly~dial~yl--~iloxane); fipeci~ic~lly poly(di~ethyl6iloxane), ~ the ~is6t componen~ ~nd p~lyurethane ~s ~he ~eco~d componentO As u ed here~n, the ~erm ~polyuretha~e~ encompasse~ polyetherureD
~haneurea~p~lye her urethan~sO p~lye ter urethan2s, or any ~u of the other ~nown polyure~hane~, e.g., a~ ~et forth ~
Nyilas ~.S. Patent 3,562~352 ~Col. 2, line 66-Col~ 3, line 37). This ~opolymer may ~ blended wi~h ~ny base p~l~mer of de~ired phy ~eal propert~e~ It ~ paxticularly effec~ive ~or ~ w~th the ~ame type of ba e pol~mer ~ the ~econd ~omponent t~ pr~v~de ~mpr~ved ~mpatibilityD
35 If desired, thre~ or more type~ o~ pol~mer chains may be employed ~n s2guence ~o long ~6 ~t leas~ one t~pe ha~ a l~w ~2~ i8 Y~ value~ An excellent terpolymer additive includes a block copolymer seyment o the first and ~econd components.
The second component is linked to a segment formed of specîfically either polyethylene oxide or polyethylene oxid~-copolypropylene oxide, herein the ~hydrophilic com-ponen~, In this instance, ~he ~econd componPnt is a hard block with a crystaIline melting point above 37C or a glass transition teMperature above 37DCo In a terpolymer sf this type, the second component link~ the first component and the hydrophilic component. In one excellent terpolymer, the first component i~ a poly(dialkylsiloxane~, the second component ~s any of a broad group including polyure~hane ~r polyureaure~hane, ~nd ~he hydrophili~ componen~ is either polyethylene oxide ~r polyethylene oxide-copolypropylene oxideO This ~erpolymer provides unexpec~edly ~uperior improv~ment in blood compatibility for a base polymer of the de~ired structural characteristics, ~uch ~ a hard polymer o~ ~he same type as the second component~ .
Other forms of iinked first ~nd ~econd homopolymer~ are of the graft copoly~e~etype~ Either the first ~r ~econd copolymer may ~ved ~ the ~ubstrate upon which the pendant chains of the other ~ype of ~omopolymer are grafted.
Th~ mode of ~orming graft copolymer~ i~ well known to those skilled in the polymer field. For example, see pp. 13-23 of the aforementioned Noshay ~nd ~cGr~th publi~ation. The third mechanism in Table ~-1 illustrates a bac~bon~ structure suitable for grafting a hydroxyalkyl-terminated polydimethyl-siloxane (e.g.~ through a urethane linkage using a diisocyanate`
The ratio of first and ~econd components ~n the polymer ~dditive ~ay vary to a con idera~le extent ~ long as there is sufficient ~mount of first component to reduce the ~c value ~nd sufficient amount of ~econd homopolymer to prevent ~udation of ~he polymer ~dditive. It ~s preferable 6~
_9_ that the polymer additive include at least about 20 volume ~ of the first component. A suitable ratio is from 20 to 80 volume ~ of the first type of component and about 20 to 80 volume ~ of the second type of polymer component.
The total amount of polymer additive required to reduce the Yc value of the base polymer to that desired for the polymer admixture is very low. For example, it has been found that less than 5 volume % and preferably less than 1 to 2 volume % of total polymer additive for silicone as the first component performs this function even though the first component typically comprises about half or less of the polymer additi~e~ A suitable ratio of polymer additive to ~ base ~ ~ on the order of 0.00002 to 2 volume % polymer additive based on the total polymer admixture. Experimental results have indicated that even though the polymer additive is initially ~ixed in bulk into the base polymer, it migrates to the surface to form an exceptionally thin (monomolecular) film which provides the desired surface characteristics.
23 Sufficient polymer additive should be included to provide this uniform layer. The presence of an adequate amount of polymer additive is hown by a dramatic drop in the ~c value of the polymer admixture to approximately that of the first component~ While the required amount varies from system to ~ystem, it is generally less than 1 volume % of the first component based on the total polymer admixture.
It is advantageous to use such low amounts of polymer additive as large amounts of the first component can be detrimental to the physical properties of the polymer admixture.
It has been found that the required minimum amount of polymer additive m2y be 2p?ro~ C~ by 2 ~.n~ cs~ o tne film thickness of a polymer additive monolayer and the ~urface area to bulk volume ratio of the fabrica~ed material.
This is based on the simplifying assumption that prior to surface saturation, essentially all of the polymer additive migrates to the surface. By simple calculationO this minimum amount may b precalculated based on this knowledge~
A number of techniques may be employed for mixing the polymer additive with the base polymer in accordance with the present inventi~n. I~ one technique, both the base polymer and polymer additive are thermoplastic and are melted at elevated temperatures to perform the mixing.
Thereafter, the polymer is solidified by cooling. If desired, the bulk polymer may be simultaneously processed into he desired final form. Alternatively, the material may be solidified for subsequent formation of the material into the desired form by thermoplasti~ methods such as injection molding and extrusion.
Another technique for mixinq of the polymer additive and base polymer is by dissolving both of them in solvent and thereafter evaporating the solvent to form the solid product of he present invention. This product may also be sub~equently processed by thermoplastic techniques if desired.
A third technique for forming the polymer admixture of the -present invention is to polymerize in place with a vast excess (e.gO~ at lea~t 95 volume %) of base polymer and a minor amount (e.g., no greater than 5 volume ~3 of a homo- -polymer additive of the first component type ~et out aboYe.
For example, low molecular weight polydimethylsiloxane having hydroxypropyl end groups is substituted for a small amount of polyetherglycol in the synthesis ~f a typical polyether urethane. Bere the reaction produ~t can contain enough silicone~ polyurethane block copolymer to provide the desired surface characteristics. The conc~ntration of the polymer additive would be o low that the great majority (e.g., at least 95 volume %) ~f the base polymer would not be linked to the addi~ive polymer.
.
~he polymer additive o ~he present invention ~ust be ~horoughly dispersed in the base polymerO ~or this pur- .
pose, it is preferable that the polymer additive be thermo- .
plastic~ soluble in organic solvents, and relatively S unc~osslinked.
For ~oslt biomedical applications, ~he base polymer~ o the present in~en~ion sh~uld be thermoplas'c~c ~o thak they may be readlly proces~ed as desired" ~oweve~, ~here are certain ~ppl~cation~ in wh~ch ~h~ polymers may be fabricated while 1uid and therea~ter solidified ~n ~he form of ~he fabricated part whi~h cannot ~gain be placed into ~che fluid ~osm. For example, ~uch base polymer ~nay compri~e her~o-set'cing sy~tems whicb are cured or vulcanized immediately following disper~ion o$ the polymer addit~ve. Such sy~tems may include ~wo componerlt polyurethanes or epoxy re~in ~y~tems .
One advantageous ~ystem an accordance with the present
POLYMER SURFACES FOR BLOOD-CONTACTING SUR~ACES
OF A BIOMEDICAL DEVICE, AND METHODS FOR EOR~IING
. Background of the Invention One widely accepted hypothesis regarding blood compaki-bility is that it is maximized within a narrow range of surface free energies which give rise to favorable inter-actions with plasma proteins. A common measurement of surface free energies is by Zisman~s critical ~urface tension tYC)~ The optimum value has been found empir-ically to lie wi~hin the range of a y~ equal to about 20 to 30 dyne/cm., see, e.gO, R.A. Baeir, Ann. N.Y, Acad.
Sci. 17t 283 (1977) Common polymers te.9~ polyurethane) which provide the desired physical properties for the blood contact surfaces of biomedical devices often do not fall within this range of critical ~urface tensions.
Polysiloxanes are known to have a particularly low critical surface tension value and have been suggested for incorpo-ration into polyurethanes to improve the surf ace character-iStiC5 of such materials. However, polysiloxane by itself is known to have a tendency to exudate rom the polyurethane base polymer as illustrated in Reischl et al~, UOS. Patent 3,243,475.
Polysiloxane-polyurethane block copolymers have been suggested for use to modify the surface characteristics of blood contact surfaces of devices of biomedical devices as illustrated in Nyilas U.S. Patent 3,562,352. The technique disclosed for such use includes fabricating the entire blood contact devices from such block copolymers or coating such devices with the copolymers. The block copolymers themselves have poor structural characteristics due to a ~igh proportion of polysiloxane. On the other hand, the coated materials are particularly expensive to form as they are not processable by thermoplastic methods such as injection molding and extru~ion. The manufacture of tubing, catheters and other blood-contacting disposable devices from such materials is particularly expensive due to ~5 the necessity of employing solution fabrication techniques.
Certain experimental work has been published relating to the blending of block copolymers of polydimethylsiloxane with homopolymers of higher critical surface tensions. These materials are known to produce films with high siloxane surface concentrations. See, for example, D.G Legrand and R.L.Gaines, Jr., Polym Prepr. 11, 442 (l970); D.W. Dwight et al., Polym. Prepr. 20, (1), 702 (1979); and J.J. O'Malley, Polym Prepr. 18 (1977). However, all of these references describe the polymer blends in terms of scientific experi-ments without suggestion that the material would have any advantage for use in any biomedical application.
Summary of the Invention and Objects It is an object of the invention to provide a new form of polymer of low surface free energy for use as ~he surface of a blood-contacting medical device which is of low cost, is readily processed, and which is characterized by excellent engineering properties. Further objects and features of the invention will be apparent from the following description of its preferred embodiments.
In accordance with the above objects, a new technique has been provided for forming the exposed blood-contacting surface of a biomedical device or componen-t. In one embodiment, a minor amount of a polymer additive is dispersed through the base polymer while both are fluid -to form a polymer admixture. The polymer additive includes at least two different homopolymer chains, which in a preferred embodiment may be in a graft or a block copolymer form. One of the chains is of low surface free energy (e.g., a polysiloxane~, while the other chain is characterized by an ability to reduce the tendency of this material to exudate from the base polymer. In a preferred embodi-ment the base polymer and second component of the polymer additive are of the same material (e.g., polyurethane). The polymer additive serves to reduce -the critical surface tension of the base polymer to render it blood compatible.
In one aspect, the invention provides a blood-compatible polymer admixture comprising at least 95 volume % of a base polymer and no greater than 5 volume % of a polymer additive comprising a copolymer of a ~irst homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a Yc less than said base polymer and said polymer admixture being characterized by Yc between about 10 and 35 dyne/cm.
In another aspect, the inventi~n provides a blood-compatible polymer additive solid at 37C comprising a block polymer including a sequence of block segments represented by the formula [A][B][C], in which A is a poly(dialkylsiloxane), B is a hard block polymer segment with a crys-talline melting point above 37C or a glass transi-tion temperature above 37C, and C
is a hydrophilic polymer selected from the group consisting of polyethylene oxide and polyethylene oxide-copolypropylene oxide.
In a further aspect, the invention provides a biomedical device, or component thereof, having a blood-compatible, blood-contacting surface, the said surface formed of a polymer admixture comprising at least 95 volume % of a base polymer and no greater than 5 volume % of a polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being dispersed throughout said base polymer and being characterized by a Yc less than said base polymer, said polymer admixture being characterized by a Yc between about 10 and 35 dyne/cm.
In a further aspect, the invention provides a method of forming a polymer admixture of low surface free energy from a base polymer and polymer additive comprising the s-teps of (a) thoroughly dispersing no greater than about 5 volume %
of a polymer addltive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive compris-ing a copolymer of a first homopolymer chain component chemically bonded to at least a second homopolymer chain compQnent of a different type than said first component, said polymer additive being characterized by a y less than said base polymer and said - 3a -~2ai6~i68 polymer admixture being characterized by a ~c between about 10 and 35 dyne/cm; and (b) solidifying said polymer admixture.
In yet a further aspect, the invention provides, in a method of forming the exposed blood-contacting surface of a biomedical device, or components thereof, the steps of (a) thoroughly dispersing no yreater than about 5 volume %
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a ~c less than said base polymer and said polymer admixture being characterized by a ~c between about 10 and 35 dyne/cm.; and (b) solidifying said polymer admixture and forming it into the blood-contacting surface of a biomedical device or component thereof.
The invention also provides a method of forming a polymer of low surface free energy comprising the steps of (a) reacting about 0.0002 to 2 volume % of a homopolymer additive with at least 98 volume % of a base polymer, while said homopolymer additive and base polymer are in fluid form to form a fluid polymer admixture of at least 95 volume % pure base polymer and, thoroughly dispersed in said base polymer, no greater than 5 volume % of a copolymer of said base polymer and said nomo-polymer additive, and 3b -~,...
~2iC~6~6~
(b) solidifying said polymer admixture, said homopolymer additive being characterized by a ~ less than said base polymer and said polymer admixture being characterized by a ~ between about 10 and 35 dyne/cm.
In yet a further aspec-t, the invention provides, in a method of forming a polymer admixture of iow surface free energy from a base polymer and polymer additive wherein said base polymer includes end groups capable of hydrogen bonding or reacting with protein, the steps of (a) fractionating a base polymer to remove a lower molecular weight fraction to reduce the Yc of the remaining base polymer, (h) thoroughly dispersing no greater than about 5 volume %
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a ~ less than said base polymer and said polymer admixture being characterized by a ~c between about 10 and 35 dyne/cm.; and (c) solidifying said polymer admixture.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
One major feature of the presen-t invention is to provide a technique for lowering the surface free energy of a ~ood structural polymer to convert a su~face formed from such material from one which is blood incompatible to one which is hl~od .;?~ _ 3c compatible. As used herein, the term "base polymer" will refer to the polymer whose surface characteristics is so modified.
Typical base polymers whose surfaces may be improved by the present technique include polyurethanes, polysulfones, poly-carbonates, polyesters, polyethylene, polypropylene, polystyrene poly(acrylonitrile-butadiene-styrene), polybutadiene, polyisoprene, styrene-butadiene-styrene block copolymers, styrene-isoprene-styrene block copolymers, poly-~-methylpen-tene, polyisobutylene, - 3d -polymethyl-methacrylate, polyvinylacetate, polyacrylo-nitrile, polyvinyl chloride, polyethylene terephthalate, cellulose and its esters and derivatives, and the like.
The base polymer is of a type capable of being formed into a sel~-supporting structural body, a self-supporting film, or deposited as a coating onto a self-supporting body. The end use of the final product is the surface of a biomedical d~vice or component.
Another characteri~tic of the base polymer is that it includes a critical surface tension (Yc) in excess of that desirable for a blood contact surface and in excess of the polymer additive to be described below which reduce5 its ~c value. As defined herein, Yc measurements -are performed by the direct method using a contact angle meter of the Kernco or Rame-Hart type and a series of seven solvents according to the Zisman procedure as set forth in A.W. Adamson, Physical Chemistry for Surfaces 339-357, 351-~3d Ed.). Measurements are made at room temperature usingadvancing angles on solvent cast films annealed at 60C for four hours. The mean contact angles are fitted to a Zisman plot using a linear regression calcula~or program.
.
In accordance with the present invention, a base polymer of the foregoing type is mixed with a polymer additive as set out below to lower its surface free energy. The polymer additive with a substantially lower Yc value than that of the base polymer is thoroughly dispersed into ~he base polymer while in fluid form to form a fluid polymer admix-ture. Thereafter, the polymer admixture is solidified and formed into the blood contacting surface of a biomedical device or component. A suitable broad range of surface free energies of the polymer admixture is from 10 ~o 35 dyne/cm.
while a preferred range is from 20 to 30 dyne/cm. An optimum range is 20-25 dyne/cm.
The polymer additive includes at least two different homopolymer chain components of different functional characteristics. One homopolymer chain, herein the "first component", has a relatively low Yc value, less than that of both the base polymer and the second component and causes reduction in the Yc f the polymer admixture as set out below. Such material typically has a tendency to exudate from the base polymer in admixture.
To prevent exudation, at least a second homopolymer chain, herein the ~second component~, is chemically bonded to the first component in the polymer additive to lower this tendency to exuâate~ The second componen~ may be selected from the group of nhard block~ polymer segments useful in the preparation of thermoplastic block copolymers as set out in A. Noshay and J.E. McGrath, Block Copolymers Overview and Critical Survey ~Academic Press 1977). For biomedical applications, the hard blocks are characterized by a crystal line melting point greater than about 37C and/or a glass transition temperature also greater ~han about 37C. This second component has a higher surface free energy than the first one. For compatibility, the second component is preferably formed of a polymer sf the same type as the base copolymer.
It has been found that the homopolymer component of the additive with the lowest y~ value controls the Yc value of the entire polymer additive. Thus, for example, if the first component has a Yc value of 25 and the second component a Yc value of 35, the total Yc f the annealed additive i5 approxima~ely 25.
Suitable homopolymers for the first component are those with a Yc val~e in the desired range to lower the value of the base pol~mer to that desired for blood compatibilitY-Thus, it is preferable that such first component be charac-terized by a ~ value les~ than 30 dyne~cm. One particularly effec~ive homopolymer for this purpoe $s a polydimethylsiloxane with a Y~ on ~he order of 22 dynefcm. Techniques for ~orming siloxane copolymers for use in the presen~ invention are known, e.g., as described in WO Noll, ChemistrY and Technolo~y of Silicones ~Academic Press, 196B). Suitable first component homopolymer include other polydialkylsiloxanes, polyfluoroalkyl alkylsiloxanes, polyal~ylene oxides, polyolefins, polydienes and polyfluoro-carbon~O
Where the polymer admixture of the present invention is Eormed by mixi~g a preormed polymer additive o.~ the foregoing type wit~ base polymer, ~ueh polymer addi~ive~
~ui~ably f~rmed of block copolymers of alterna~ing ~irst and seeond ~omponents interlinked by chemi~al bonds in accordance with known techniquesO For example~ ~uch block copolymerQ may be ~ormed in accordance with th2 foregoing Noshay and McGrat~ publi~ation. A suitable number of repea~ing units of each homopolymer of the first component is that ~ufficient to retain the y~ value of the homopoly-mer a~ evidenced by re~ntion of approximately the same glass tran ition temperature as its pure homopolymer.
Typically, ~his number is on the order o~ 5 to 10 units or more. Similarly, there should be a sufficie~t number of repeating unit~ ~f the ~econd component in a segment so that the polymer additive i~ ~olid 3~ ro~m ~emperature.
The preparation of bloc~ cop~lymers t~r multipolymers) may be performed by ~everal proeedures which ~if~er in the degree to which the ~truc~cure of the resulting produet may be de~ined.
One proced~re ~nvolves ~he coupling of two (~r more~
preformed blocks which are prepared in E;eparate reactic~ns prior to 1:he coupling reactionl This procedure involves a ~3 ~7 very well def ined ~tructure ~f ~he ~oupling re~ction pre-cludes l~ke blo6}c~ ~rom reactin~ witl themselves but only -3110ws diss~milar blocics ~o ~ouple to one another.
5 A ~lightly le~s well deined Etruc~cure result~ ~f the two pre~ormed block~ posse~ the abili~y (via the coupling reaction) to react ~ith hemselve~ as well a~ w~th the di~similar block. .
10 An even le~s well defined ~ru~ture results when ~ single (or more ) pre ormed Iblodc i~ soupled with a ~econd block ~rea~ed during tbe ¢:oupling reaction. In ~his case the ~ ni ~ial leng~ch o~ the pre~ormed block i~ lcnown ~by v~rtue of 'che ~eparate reaetion u~ed ~o prep~re it) bu~ ~he ~equen~e distr~bution of the copoly~Der i~ not known ~xactly since . both ~oupling ~nd ~bain growth ~8 possible in the reaction.
wh~ch produces the ~e~ond blocl;. 8uitable ~ethods of forming the e ~nd other ~uch copolymer~ for u~e ln the presen~ inven~isn ~re ~et out ~n ~he ~rementione~ Noshay and Mc~rath publ~stiDn.
~n~ unigue ~peci~ic ~dmixture ~o~ording to the present ~n-~ention include~ ~ blGck or gr~f~ copolymer of poly~dial~yl--~iloxane); fipeci~ic~lly poly(di~ethyl6iloxane), ~ the ~is6t componen~ ~nd p~lyurethane ~s ~he ~eco~d componentO As u ed here~n, the ~erm ~polyuretha~e~ encompasse~ polyetherureD
~haneurea~p~lye her urethan~sO p~lye ter urethan2s, or any ~u of the other ~nown polyure~hane~, e.g., a~ ~et forth ~
Nyilas ~.S. Patent 3,562~352 ~Col. 2, line 66-Col~ 3, line 37). This ~opolymer may ~ blended wi~h ~ny base p~l~mer of de~ired phy ~eal propert~e~ It ~ paxticularly effec~ive ~or ~ w~th the ~ame type of ba e pol~mer ~ the ~econd ~omponent t~ pr~v~de ~mpr~ved ~mpatibilityD
35 If desired, thre~ or more type~ o~ pol~mer chains may be employed ~n s2guence ~o long ~6 ~t leas~ one t~pe ha~ a l~w ~2~ i8 Y~ value~ An excellent terpolymer additive includes a block copolymer seyment o the first and ~econd components.
The second component is linked to a segment formed of specîfically either polyethylene oxide or polyethylene oxid~-copolypropylene oxide, herein the ~hydrophilic com-ponen~, In this instance, ~he ~econd componPnt is a hard block with a crystaIline melting point above 37C or a glass transition teMperature above 37DCo In a terpolymer sf this type, the second component link~ the first component and the hydrophilic component. In one excellent terpolymer, the first component i~ a poly(dialkylsiloxane~, the second component ~s any of a broad group including polyure~hane ~r polyureaure~hane, ~nd ~he hydrophili~ componen~ is either polyethylene oxide ~r polyethylene oxide-copolypropylene oxideO This ~erpolymer provides unexpec~edly ~uperior improv~ment in blood compatibility for a base polymer of the de~ired structural characteristics, ~uch ~ a hard polymer o~ ~he same type as the second component~ .
Other forms of iinked first ~nd ~econd homopolymer~ are of the graft copoly~e~etype~ Either the first ~r ~econd copolymer may ~ved ~ the ~ubstrate upon which the pendant chains of the other ~ype of ~omopolymer are grafted.
Th~ mode of ~orming graft copolymer~ i~ well known to those skilled in the polymer field. For example, see pp. 13-23 of the aforementioned Noshay ~nd ~cGr~th publi~ation. The third mechanism in Table ~-1 illustrates a bac~bon~ structure suitable for grafting a hydroxyalkyl-terminated polydimethyl-siloxane (e.g.~ through a urethane linkage using a diisocyanate`
The ratio of first and ~econd components ~n the polymer ~dditive ~ay vary to a con idera~le extent ~ long as there is sufficient ~mount of first component to reduce the ~c value ~nd sufficient amount of ~econd homopolymer to prevent ~udation of ~he polymer ~dditive. It ~s preferable 6~
_9_ that the polymer additive include at least about 20 volume ~ of the first component. A suitable ratio is from 20 to 80 volume ~ of the first type of component and about 20 to 80 volume ~ of the second type of polymer component.
The total amount of polymer additive required to reduce the Yc value of the base polymer to that desired for the polymer admixture is very low. For example, it has been found that less than 5 volume % and preferably less than 1 to 2 volume % of total polymer additive for silicone as the first component performs this function even though the first component typically comprises about half or less of the polymer additi~e~ A suitable ratio of polymer additive to ~ base ~ ~ on the order of 0.00002 to 2 volume % polymer additive based on the total polymer admixture. Experimental results have indicated that even though the polymer additive is initially ~ixed in bulk into the base polymer, it migrates to the surface to form an exceptionally thin (monomolecular) film which provides the desired surface characteristics.
23 Sufficient polymer additive should be included to provide this uniform layer. The presence of an adequate amount of polymer additive is hown by a dramatic drop in the ~c value of the polymer admixture to approximately that of the first component~ While the required amount varies from system to ~ystem, it is generally less than 1 volume % of the first component based on the total polymer admixture.
It is advantageous to use such low amounts of polymer additive as large amounts of the first component can be detrimental to the physical properties of the polymer admixture.
It has been found that the required minimum amount of polymer additive m2y be 2p?ro~ C~ by 2 ~.n~ cs~ o tne film thickness of a polymer additive monolayer and the ~urface area to bulk volume ratio of the fabrica~ed material.
This is based on the simplifying assumption that prior to surface saturation, essentially all of the polymer additive migrates to the surface. By simple calculationO this minimum amount may b precalculated based on this knowledge~
A number of techniques may be employed for mixing the polymer additive with the base polymer in accordance with the present inventi~n. I~ one technique, both the base polymer and polymer additive are thermoplastic and are melted at elevated temperatures to perform the mixing.
Thereafter, the polymer is solidified by cooling. If desired, the bulk polymer may be simultaneously processed into he desired final form. Alternatively, the material may be solidified for subsequent formation of the material into the desired form by thermoplasti~ methods such as injection molding and extrusion.
Another technique for mixinq of the polymer additive and base polymer is by dissolving both of them in solvent and thereafter evaporating the solvent to form the solid product of he present invention. This product may also be sub~equently processed by thermoplastic techniques if desired.
A third technique for forming the polymer admixture of the -present invention is to polymerize in place with a vast excess (e.gO~ at lea~t 95 volume %) of base polymer and a minor amount (e.g., no greater than 5 volume ~3 of a homo- -polymer additive of the first component type ~et out aboYe.
For example, low molecular weight polydimethylsiloxane having hydroxypropyl end groups is substituted for a small amount of polyetherglycol in the synthesis ~f a typical polyether urethane. Bere the reaction produ~t can contain enough silicone~ polyurethane block copolymer to provide the desired surface characteristics. The conc~ntration of the polymer additive would be o low that the great majority (e.g., at least 95 volume %) ~f the base polymer would not be linked to the addi~ive polymer.
.
~he polymer additive o ~he present invention ~ust be ~horoughly dispersed in the base polymerO ~or this pur- .
pose, it is preferable that the polymer additive be thermo- .
plastic~ soluble in organic solvents, and relatively S unc~osslinked.
For ~oslt biomedical applications, ~he base polymer~ o the present in~en~ion sh~uld be thermoplas'c~c ~o thak they may be readlly proces~ed as desired" ~oweve~, ~here are certain ~ppl~cation~ in wh~ch ~h~ polymers may be fabricated while 1uid and therea~ter solidified ~n ~he form of ~he fabricated part whi~h cannot ~gain be placed into ~che fluid ~osm. For example, ~uch base polymer ~nay compri~e her~o-set'cing sy~tems whicb are cured or vulcanized immediately following disper~ion o$ the polymer addit~ve. Such sy~tems may include ~wo componerlt polyurethanes or epoxy re~in ~y~tems .
One advantageous ~ystem an accordance with the present
2(, . invention comprisçs ~n admiYture of a polymer addiSive formed of a poly (dialkylsiioY.ane) segment chemically bonded to a polyurethane s~gment ~e.g., in ~ blc~ck or graft eopolyo ~er) ~nd ~dmixed wiith a ui~cable base poly~er, e.g., the Eame type of polyurethane a~ in ~h~ copolymer~, ~ particu-larly e~fe~tive ~3y~tem ~ncludes a polymer additive c:>mpri~ing a block copolymer o~ ~bo~t 50 weigh~ ~ polydimethylsiloxane and 50 w@ight ~ polyure~hane ~ peci~ica~ly polyes~erure~hane~
in a base polymer o~ polyurethane (speci~ically polyester-urethane). A ~uitable ratio i5 99.~4 polyester urethane base polymer ~nd 0~1~ of the block ~op~lyzner.
One mode ~f pretreating al ba~e polymer t~ lower i~ ~urf ace ~ree energy i~ believed ~ be e~fectiYe w~ base polymer -wh$ch ~nclude~ high energy end group~, ~;peci~ically ones ~5 capable of hy~ogen bondin~ or reac~ing with pro~ein. In thi~ lnstance, the l~ase p~lymer 16 fir~;t fractiorated to i68 remove a lower molecular weight fraction and thereby may reduce the hydrogen bonding capacity of the remaining base polymer. Suitable techniques for accomplishing this are set out in Manfred J.R. Cantow, Polymer Fractionation, Academic Press (New ~ork - London 1967). Such techniques liquid chromatography, particularly gel permeation chromatography.
It has been found that variations in processing conditions which would otherwise'af~ec~ the surface free energy to a signjficant extent may be minimized as a factor in systems of the present invention by the use of a short heat ~reatment following surface formation. Fo~ example, in a system comprising-a base polymer of'polyether urethane and a block copolymer of polyether.urethane/polyalkylsiloxane, annealing for four hours at 759C yields a Yc value approximately equal to.~hat of pure 'polysiloxane while it takes a consider-a.bly longer..period of time to accomplish this objective at room tëmperature.
. .
It has further been found that the polarity of the environ-ment of formation affects the y value of the surface.
c Thus an air equilibrated sur~.ace provides a lower Yc than one which has been equilibrated in water.
. . .
The polymer admixtures of the present invention are pa.rti-cularly effective for use as a blood-contacting sur~ace of a biomedical device or component. Such devices include auxiliary ventricles, intra-aortic balloons, and various types of blood pumps.
A further disclssure of the nature of the present invention is provided by the following specific examples o$ the practice of ~he inven~ion. I~ should be understood that the data disclosed serve only as examples and are not intended to limit the scope of the invention.
s~
A typical synthesi~ o~ P~lydimethyl~iloxane-Polyurethane Block Copolymer.
~o a 500 ~ our~necked ~lask equipped wi~h s~irrer, Dean and St'ark trap,-,dropping funnel, drying ~ube, ther-mometer and inert gas inlet iæ placed ~ ~ixture of 50 ~lo dime~hylformamide and 140 ml7 o~ rahydrofuran~ The mix~ure i~ hea~ed to re~lux snd approxim~tely 40 ~ et~a-hydrofur~n is dis~illed o~P. The ~eac~ion mix~ure i ~ooled dow~ ~rld 12.513 gm (0.05 ~ola~ of ~e~hylene bi~ ~4~ph nyl) ~ocyanat~ ~M~ added ~o g~v~ a cle~r ~lu~ionO ~rom he dropping unnel 15.000 9~. 60.015 mole) o 3-hydroxypropyl terminated polydisethylsiloxane (Mol. Wt ~ 1,000) i5 added drop~ise. The rea~t~on ~ixture is heated ~t 105 190C ~or 1 hour, followed by dropwi~e addition o~ 3.15 gm lo.a35 mole~ of 1-4, butane diol oYer a period o~ 45 ~inutesO The polymerizat~on is carried out ~or 15 ~ninute~ ore, ~ooled 20 down and prgcipitated by pour~ng into water in a blender.
The ~lish'cly yellow~h polymer i~ washed with water ~nd iEinally with ethanol~ dried in ~ ~acuum oven ~t 50C ~o aford ~ 30--31 gm of polymer ~9~ -1004)o lnJ ~n te ra-hydro . uran at 2s0e i8 IDol9 !~E!L~ ' By replacing ~ome o~ ~he hydroxyproply ~er~ina~ed poly~
di~thyl~iloxane with polyethylene glycol, ~ polydimethyl-3û 6iloxane/polyethylene oxide/polyurethane terpolymer-is prepared .
3S ~y replaclng the DMF ~olvent wi ~h dime'chylaceta~ide ~nd ~ub-~tituting ~thylene ~iamine ~Eor but~ne dic~l ~n Example 2 polyd ime~chyl ~ i loxane~p~ly~ thyl ene o~ ~ de/poly ure au re th ane ~erpolymer i5 prepAret3.
Example 4 This example illustrates solution fabrication. A ~olution is prepared containing about 10 weight % admixture in a solvent system consisting o~ 90~ tetrahydrofuran (vol/vol) and 10% dimethylformamide. The admixture consists of 99.9 weight ~ purified polyesterurethane and 0.1 weight %
silicone/ polyuretha~e block copolymer. ~he block copolymer consists of about 50 weight % polydimethylsiloxane and 50 weight ~ polyurethane from diphenylmethane diisocyanate and butane diol.
.
The solution i8 coated onto tapered ~tainless steel mandrels by multiple dippin~. The solvent is allowed to evaporate and the film is remo~ed from-the mandrel. the resulting ~alloon~ is mounted on a pre-drilled catbeter and is useful as a cardiac arrest device when placed in the descending aorta and inflated and deflated with CO2 in counterpulsation to the beart.
The Yc of the balloon film is 20 to 22 dyne~cm.
~xample 5 Small test tubes are co~ted on their inner surface wi~h two different polymer solutions (in TH~) at 10 weight concentration. One solution consists o~ polyetherurethane in the ~olvent. The second solution consists of 90 weight solvent, 9.9 weight ~ polyetherurethane and 0.1 weight %
copolymer addi~ive. The copolymer consists of about 50 polydimethyl-siloxane and 504 polyethylene oxide co-polypropylene oxide available ~rom Petrarch Systems under the trade designation PS 072.
After solven~ evapora~ion and about 16 hours equilibration in distilled water~ ~resh wbole ~lood is placed in three tubes of each ~ype.
~.z~
Tubes coated with the unmodified polyetherurethane give mean whole blood clotting times of 39 minutes. Tubes coated with polyetherurethane containing the block copolymer additive give mean whole blood clotting times greater than 70 minutes.
The Yc f the unmodified polyetheruretbane is about 28 dyne/cm~ The Yc f the polyetherurethane containing th~ block copolymer additive is about 20 dyne/cm.
Example 6 .
This example illustFates thermoplastic fabrication.
A thermoplastic polyurethane is mixed in a single screw extruder at about 400F with.a block copolymer additive zonsisting of about 5~ weight ~ polydimethylsiloxane and 50 weight ~ polyetherurethane such that the total silicone . concentration of the mixture is OoOl weight %. The ad-20 mixture is extruded into the shape of tubin~ suitable forthe transfer of bloodO The tubing has a Yc of about 21 dyne/cm after being annealed at S0C for six hoursO
ExamPle 7 This example illustrates two component vulcanizing~
DuPont Adiprene ~-167 polyetherurethane isocynate terminated prepolymer i5 prepared according to the manufacturer~s recommendations for a polyol cure, using a slight stoi-chiometric def iciency of butane diol/trimethylol propane mixture. While s'cill liquid 0.1 weigh~ % of the block copolymer additive of Example 1 is mixed with ~he reactants and an amine catalyst.
Th~ resulting admix~ure i~ ooated on a prev~ously primed ti~nium connector and cured ~n an oven aS 100C.
The coated ~onnector has ~ Yc Of abou~ 20 dyne/c~. ~nd ~s used ~n contaet wlth blood to connect a conduit to a left ventricular assi~t d~vice wh~ch is u~ed to treat low cardiac.outpu~ ~yndr~me.
Exam~le 8 ' 10 A 4 ~m tubular prosthesis was formed by ~oating ~ xtainless ~teel ~andre~ with a polymer ~ix~ure consisting of 99.9 weight % poly~etherurethane urea) ~nd 0.2 weight 4 polydimethyl-~loxane/polyuret~ane block copolymer containing 50~ poly-dimethylsiloxane, 50% polyurethan~; in a dimethylace~mide~olu~on. After ~olvent ~vaporation~ ~he resultang ~ube w~s.
removed ~rsm ~he ~andrel, extracted ~ith di~tilled water at 60C for 16 hour~ dried and annealed ~or 4 hours at 63C.
After ethylen~ oxide fi~rilazation the tube was ~utured ~o the carotid. ~rtery of a ~oat~ .
U~ing ~n establi~hed radiolab~led platelet teehnique no enh~ncement in pla~elet ~urn~ve~ wa~ ~e~sured relative So a ~ham experime~t. A simil~r ~xperiment ea~ily ~e~ect~
changeQ in pla~let turnover ~n polyvinylchloride tubing ~hi~h is known to have low bl~od ~ompatibi~i~y.
in a base polymer o~ polyurethane (speci~ically polyester-urethane). A ~uitable ratio i5 99.~4 polyester urethane base polymer ~nd 0~1~ of the block ~op~lyzner.
One mode ~f pretreating al ba~e polymer t~ lower i~ ~urf ace ~ree energy i~ believed ~ be e~fectiYe w~ base polymer -wh$ch ~nclude~ high energy end group~, ~;peci~ically ones ~5 capable of hy~ogen bondin~ or reac~ing with pro~ein. In thi~ lnstance, the l~ase p~lymer 16 fir~;t fractiorated to i68 remove a lower molecular weight fraction and thereby may reduce the hydrogen bonding capacity of the remaining base polymer. Suitable techniques for accomplishing this are set out in Manfred J.R. Cantow, Polymer Fractionation, Academic Press (New ~ork - London 1967). Such techniques liquid chromatography, particularly gel permeation chromatography.
It has been found that variations in processing conditions which would otherwise'af~ec~ the surface free energy to a signjficant extent may be minimized as a factor in systems of the present invention by the use of a short heat ~reatment following surface formation. Fo~ example, in a system comprising-a base polymer of'polyether urethane and a block copolymer of polyether.urethane/polyalkylsiloxane, annealing for four hours at 759C yields a Yc value approximately equal to.~hat of pure 'polysiloxane while it takes a consider-a.bly longer..period of time to accomplish this objective at room tëmperature.
. .
It has further been found that the polarity of the environ-ment of formation affects the y value of the surface.
c Thus an air equilibrated sur~.ace provides a lower Yc than one which has been equilibrated in water.
. . .
The polymer admixtures of the present invention are pa.rti-cularly effective for use as a blood-contacting sur~ace of a biomedical device or component. Such devices include auxiliary ventricles, intra-aortic balloons, and various types of blood pumps.
A further disclssure of the nature of the present invention is provided by the following specific examples o$ the practice of ~he inven~ion. I~ should be understood that the data disclosed serve only as examples and are not intended to limit the scope of the invention.
s~
A typical synthesi~ o~ P~lydimethyl~iloxane-Polyurethane Block Copolymer.
~o a 500 ~ our~necked ~lask equipped wi~h s~irrer, Dean and St'ark trap,-,dropping funnel, drying ~ube, ther-mometer and inert gas inlet iæ placed ~ ~ixture of 50 ~lo dime~hylformamide and 140 ml7 o~ rahydrofuran~ The mix~ure i~ hea~ed to re~lux snd approxim~tely 40 ~ et~a-hydrofur~n is dis~illed o~P. The ~eac~ion mix~ure i ~ooled dow~ ~rld 12.513 gm (0.05 ~ola~ of ~e~hylene bi~ ~4~ph nyl) ~ocyanat~ ~M~ added ~o g~v~ a cle~r ~lu~ionO ~rom he dropping unnel 15.000 9~. 60.015 mole) o 3-hydroxypropyl terminated polydisethylsiloxane (Mol. Wt ~ 1,000) i5 added drop~ise. The rea~t~on ~ixture is heated ~t 105 190C ~or 1 hour, followed by dropwi~e addition o~ 3.15 gm lo.a35 mole~ of 1-4, butane diol oYer a period o~ 45 ~inutesO The polymerizat~on is carried out ~or 15 ~ninute~ ore, ~ooled 20 down and prgcipitated by pour~ng into water in a blender.
The ~lish'cly yellow~h polymer i~ washed with water ~nd iEinally with ethanol~ dried in ~ ~acuum oven ~t 50C ~o aford ~ 30--31 gm of polymer ~9~ -1004)o lnJ ~n te ra-hydro . uran at 2s0e i8 IDol9 !~E!L~ ' By replacing ~ome o~ ~he hydroxyproply ~er~ina~ed poly~
di~thyl~iloxane with polyethylene glycol, ~ polydimethyl-3û 6iloxane/polyethylene oxide/polyurethane terpolymer-is prepared .
3S ~y replaclng the DMF ~olvent wi ~h dime'chylaceta~ide ~nd ~ub-~tituting ~thylene ~iamine ~Eor but~ne dic~l ~n Example 2 polyd ime~chyl ~ i loxane~p~ly~ thyl ene o~ ~ de/poly ure au re th ane ~erpolymer i5 prepAret3.
Example 4 This example illustrates solution fabrication. A ~olution is prepared containing about 10 weight % admixture in a solvent system consisting o~ 90~ tetrahydrofuran (vol/vol) and 10% dimethylformamide. The admixture consists of 99.9 weight ~ purified polyesterurethane and 0.1 weight %
silicone/ polyuretha~e block copolymer. ~he block copolymer consists of about 50 weight % polydimethylsiloxane and 50 weight ~ polyurethane from diphenylmethane diisocyanate and butane diol.
.
The solution i8 coated onto tapered ~tainless steel mandrels by multiple dippin~. The solvent is allowed to evaporate and the film is remo~ed from-the mandrel. the resulting ~alloon~ is mounted on a pre-drilled catbeter and is useful as a cardiac arrest device when placed in the descending aorta and inflated and deflated with CO2 in counterpulsation to the beart.
The Yc of the balloon film is 20 to 22 dyne~cm.
~xample 5 Small test tubes are co~ted on their inner surface wi~h two different polymer solutions (in TH~) at 10 weight concentration. One solution consists o~ polyetherurethane in the ~olvent. The second solution consists of 90 weight solvent, 9.9 weight ~ polyetherurethane and 0.1 weight %
copolymer addi~ive. The copolymer consists of about 50 polydimethyl-siloxane and 504 polyethylene oxide co-polypropylene oxide available ~rom Petrarch Systems under the trade designation PS 072.
After solven~ evapora~ion and about 16 hours equilibration in distilled water~ ~resh wbole ~lood is placed in three tubes of each ~ype.
~.z~
Tubes coated with the unmodified polyetherurethane give mean whole blood clotting times of 39 minutes. Tubes coated with polyetherurethane containing the block copolymer additive give mean whole blood clotting times greater than 70 minutes.
The Yc f the unmodified polyetheruretbane is about 28 dyne/cm~ The Yc f the polyetherurethane containing th~ block copolymer additive is about 20 dyne/cm.
Example 6 .
This example illustFates thermoplastic fabrication.
A thermoplastic polyurethane is mixed in a single screw extruder at about 400F with.a block copolymer additive zonsisting of about 5~ weight ~ polydimethylsiloxane and 50 weight ~ polyetherurethane such that the total silicone . concentration of the mixture is OoOl weight %. The ad-20 mixture is extruded into the shape of tubin~ suitable forthe transfer of bloodO The tubing has a Yc of about 21 dyne/cm after being annealed at S0C for six hoursO
ExamPle 7 This example illustrates two component vulcanizing~
DuPont Adiprene ~-167 polyetherurethane isocynate terminated prepolymer i5 prepared according to the manufacturer~s recommendations for a polyol cure, using a slight stoi-chiometric def iciency of butane diol/trimethylol propane mixture. While s'cill liquid 0.1 weigh~ % of the block copolymer additive of Example 1 is mixed with ~he reactants and an amine catalyst.
Th~ resulting admix~ure i~ ooated on a prev~ously primed ti~nium connector and cured ~n an oven aS 100C.
The coated ~onnector has ~ Yc Of abou~ 20 dyne/c~. ~nd ~s used ~n contaet wlth blood to connect a conduit to a left ventricular assi~t d~vice wh~ch is u~ed to treat low cardiac.outpu~ ~yndr~me.
Exam~le 8 ' 10 A 4 ~m tubular prosthesis was formed by ~oating ~ xtainless ~teel ~andre~ with a polymer ~ix~ure consisting of 99.9 weight % poly~etherurethane urea) ~nd 0.2 weight 4 polydimethyl-~loxane/polyuret~ane block copolymer containing 50~ poly-dimethylsiloxane, 50% polyurethan~; in a dimethylace~mide~olu~on. After ~olvent ~vaporation~ ~he resultang ~ube w~s.
removed ~rsm ~he ~andrel, extracted ~ith di~tilled water at 60C for 16 hour~ dried and annealed ~or 4 hours at 63C.
After ethylen~ oxide fi~rilazation the tube was ~utured ~o the carotid. ~rtery of a ~oat~ .
U~ing ~n establi~hed radiolab~led platelet teehnique no enh~ncement in pla~elet ~urn~ve~ wa~ ~e~sured relative So a ~ham experime~t. A simil~r ~xperiment ea~ily ~e~ect~
changeQ in pla~let turnover ~n polyvinylchloride tubing ~hi~h is known to have low bl~od ~ompatibi~i~y.
Claims (41)
1. In a method of forming the exposed blood-contacting surface of a biomedical device, or components thereof, the steps of (a) thoroughly dispersing no greater than about 5 volume % of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm.;
and (b) solidifying said polymer admixture and forming it into the blood-contacting surface of a biomedical device or component thereof.
and (b) solidifying said polymer admixture and forming it into the blood-contacting surface of a biomedical device or component thereof.
2. The method of Claim 1 in which said first component is characterized by a .gamma.c less than 30 dyne/cm. and a tendency to exudate, and said second component lowers said tendency to exudate.
3. The method of Claim 1 in which said first component is a homopolymer selected from the group consisting of polydialkylsiloxanes, polyfluoroalkyl alkylsiloxanes, polyalkylene oxides, polyolefins, polydienes and poly-fluorocarbons.
4. The method of Claim 3 in which said first component is poly(dimethylsiloxane).
5. The method of Claim 1 in which said first component is a polydialkylsiloxane, and said second component is a polyurethane.
6. The method of Claim 1 in which said second com-ponent and said base polymer are formed of the same type of homopolymer.
7. The method of Claim 1 in which said base polymer includes end groups capable of hydrogen bonding or reacting with protein, together with the step of fractionating said base polymer to remove a lower molecular weight fraction to reduce the hydrogen bonding capacity of the remaining base polymer prior to said dispersion step.
8. The method of Claim 1 together with the step of annealing said polymer admixture.
9. The method of Claim 1 in which about 0.00002 to 2 volume % polymer additive is added to said base polymer based on the total polymer admixture.
10. The method of Claim 1 in which said polymer additive comprises at least about 20 volume % of said first component.
11. The method of Claim 1 in which said polymer additive comprisese about 20 to 80 volume % of said first component and about 20 to 80 volume % of said second component.
12. The method of Claim 1 in which said polymer admixture is deposited as a film onto a biomedical device or component thereof.
13. The method of Claim 1 in which said additive and base polymer are in molten form during dispersion and solidify on cooling.
14. The method of claim 1 in which said polymer admixture is dissolved in solvent during mixing and said solvent is removed to solidify said polymer admixture.
15. The method of claim 1 in which said base polymer comprises a curable thermosetting fluid polymer which is solidified by curing.
16. The method of claim 1 in which said polymer additive comprises a linear multiblock copolymer with blocks of at least said first and second components.
17. The method of claim 1 in which said polymer additive comprises a graft copolymer with a substrate formed of said first component and pendant chains formed of said second component.
18. The method of claim 1 in which said polymer additive comprises a graft copolymer with a substrate formed of said second component and pendant chains formed of said first component.
19. A method of forming a polymer of low surface free energy comprising the steps of (a) reacting about 0.0002 to 2 volume % of a homopolymer additive with at least 98 volume % of a base polymer, while said homopolymer additive and base polymer are in fluid form to form a fluid polymer admixture of at least 95 volume % pure base polymer, and thoroughly dispersed in said base polymer, no greater than 5 volume % of a copolymer of said base polymer and said homopolymer additive, and (b) solidifying said polymer admixture, said homopolymer additive being characterized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm.
20. The method of claim 19 in which said polymer admixture is formed into the blood-contacting surface of a biomedical device or component thereof.
21. A biomedical device, or component thereof, having a blood-compatible, blood-contacting surface, the said surface formed of a polymer admixture comprising at least 95 volume % of a base polymer and no greater than 5 volume % of a polymer additive comprising a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being dispersed throughout said base polymer and being character-ized by a .gamma.c less than said base polymer, said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm.
22. The biomedical device of claim 21 in which said first component is characterized by a .gamma.c less than 30 dyne/cm. and a tendency to exude, and said second component lowers said tendency to exude.
23. The biomedical device of claim 21 in which said first component is a homopolymer selected from the group consisting of polydialkylsiloxanes, polyfluoroalkyl alkylsiloxanes, polyalkylene oxides, polyolefins, polydienes and polyfluorocarbons.
24. The biomedical device of claim 21 in which said first component is poly(dimethylsiloxane).
25. The biomedical device of claim 21 in which said first component is a polydialkylsiloxane and said second component is a polyurethane.
26. The biomedical device of Claim 21 characterized by blood compatibility in the form of a blood contact device or component thereof.
27. The biomedical device of Claim 21 characterized by blood compatibility in the form of a blood contact layer adhered to the surface of a blood contact device.
28. The biomedical device of Claim 21 in which a portion of said polymer additive is in the form of a continuous layer on the surface of a blood contact device.
29. The biomedical device of Claim 21 in which a portion of said polymer additive comprises a linear multi-block copolymer with blocks of at least said first and second component on the surface of a blood contact device.
30. The biomedical device of Claim 21 in which a portion of said polymer additive comprises a graft copolymer with a substrate formed of said first component and pendant chains formed of said second component on the surface of a blood contact device.
31. The biomedical device of Claim 21 in which a portion of said polymer additive comprises a graft copolymer with a substrate formed of said second component and pendant chains formed of said second component on the surface of a blood contact device.
32. In a method of forming a polymer admixture of low surface free energy from a base polymer and polymer additive wherein said base polymer includes end groups capable of hydrogen bonding or reacting with protein, the steps of (a) fractionating a base polymer to remove a lower molecular weight fraction to reduce the .gamma.c of the remaining base polymer, (b) thoroughly dispersing no greater than about 5 volume % of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a first homo-polymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being charac-terized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm.; and (c) solidifying said polymer admixture.
33. A blood-compatible polymer admixture comprising at least 95 volume % of a base polymer and no greater than 5 volume % of a polymer additive comprising a poly(dialkyl-siloxane) segment chemically bonded to a polyurethane segment, said polymer additive being dispersed throughout said base polymer and being characterized by a .gamma.c less than said base polymer, said polymer admixture being charac-terized by a .gamma.c between about 10 and 35 dyne/cm.
34. The polymer admixture of Claim 33 in the form of the blood contacting surface of a biomedical device or component.
35. The polymer admixture of Claim 33 In which said polymer additive is a graft copolymer.
36. The polymer admixture of Claim 33 in which said polymer additive is a block copolymer.
37. The polymer admixture of claim 33 in which said base polymer is a polyurethane.
38. In a method of forming a blood-compatible polymer admixture, the steps of (a) thoroughly dispersing no greater than about 5 volume %
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a poly(dialkylsiloxane) segment component chemically bonded to a polyurethane segment, said polymer additive being characterized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm.; and (b) solidifying said polymer admixture.
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a poly(dialkylsiloxane) segment component chemically bonded to a polyurethane segment, said polymer additive being characterized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm.; and (b) solidifying said polymer admixture.
39. A blood-compatible polymer admixture comprising at least 95 volume % of a base polymer and no greater than 5 volume % of a polymer additive comprising a copolymer of a first homo-polymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm.
40. A method of forming a polymer admixture of low surface free energy form a base polymer and polymer additive comprising the steps of (a) thoroughly dispersing no greater than about 5 volume %
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a copolymer of a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm; and (b) solidifying said polymer admixture.
of a polymer additive throughout at least 95 volume % of a base polymer, while said polymer additive and base polymer are in fluid form, to form a polymer admixture, said polymer additive comprising a copolymer of a first homopolymer chain component chemically bonded to at least a second homopolymer chain component of a different type than said first component, said polymer additive being characterized by a .gamma.c less than said base polymer and said polymer admixture being characterized by a .gamma.c between about 10 and 35 dyne/cm; and (b) solidifying said polymer admixture.
41. The method of claim 40 wherein said second homopolymer chain component is the base polymer, and wherein said polymer additive is formed in situ in the base polymer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000473726A CA1211878A (en) | 1980-02-29 | 1985-02-07 | Polymer surfaces for blood-contacting surfaces of a biomedical device |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12584580A | 1980-02-29 | 1980-02-29 | |
| US125,845 | 1980-02-29 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000473726A Division CA1211878A (en) | 1980-02-29 | 1985-02-07 | Polymer surfaces for blood-contacting surfaces of a biomedical device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1206668A true CA1206668A (en) | 1986-06-24 |
Family
ID=22421689
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000371214A Expired CA1206668A (en) | 1980-02-29 | 1981-02-18 | Polymer surfaces for blood-contacting surfaces of a biomedical device, and methods for forming |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JPS56136565A (en) |
| AT (1) | AT385041B (en) |
| AU (1) | AU548194B2 (en) |
| CA (1) | CA1206668A (en) |
| DE (1) | DE3153664C2 (en) |
| FR (2) | FR2491938B1 (en) |
| GB (2) | GB2073219B (en) |
| IL (1) | IL62183A (en) |
| IT (1) | IT1210997B (en) |
| MX (1) | MX159062A (en) |
| NL (1) | NL8100975A (en) |
| ZA (1) | ZA811107B (en) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4861830A (en) * | 1980-02-29 | 1989-08-29 | Th. Goldschmidt Ag | Polymer systems suitable for blood-contacting surfaces of a biomedical device, and methods for forming |
| US4675361A (en) * | 1980-02-29 | 1987-06-23 | Thoratec Laboratories Corp. | Polymer systems suitable for blood-contacting surfaces of a biomedical device, and methods for forming |
| DE3273433D1 (en) * | 1981-06-22 | 1986-10-30 | Kanegafuchi Chemical Ind | Thermoplastic elastomers for medical use as moulded articles brought into direct contact with blood |
| JPS57211358A (en) * | 1981-06-22 | 1982-12-25 | Kanegafuchi Chemical Ind | Anti-thrombus elastomer and method |
| DE3130646C2 (en) * | 1981-07-28 | 1983-09-15 | Wilfried Dr.-Ing. 1000 Berlin Lemm | Process for the production of articles from polyurethane which are enriched in certain surface areas with polydimethylsiloxane |
| JPS58185647A (en) * | 1982-03-17 | 1983-10-29 | Nippon Zeon Co Ltd | Stable polymer emulsion composition giving antithrombotic surface and preparation thereof |
| DK103483A (en) * | 1982-04-15 | 1983-10-16 | Ethicon Inc | SILICONE COATED SURGICAL PAPER |
| JPS6045357A (en) * | 1983-08-23 | 1985-03-11 | 日本ゼオン株式会社 | Blood contact medical instrument and its production |
| JPH0622591B2 (en) * | 1983-10-13 | 1994-03-30 | 日本ゼオン株式会社 | Method for manufacturing blood contact medical device |
| CA1257425A (en) * | 1984-05-21 | 1989-07-11 | Th. Goldschmidt Ag | Moisture vapor permeable materials |
| US4911691A (en) * | 1984-09-21 | 1990-03-27 | Menlo Care, Inc. | Assembly for adminstering IV solution |
| US4883699A (en) * | 1984-09-21 | 1989-11-28 | Menlo Care, Inc. | Polymeric article having high tensile energy to break when hydrated |
| JPS6176152A (en) * | 1984-09-25 | 1986-04-18 | 学校法人東京女子医科大学 | Medical tube |
| JPS61154674A (en) * | 1984-12-28 | 1986-07-14 | 日本ゼオン株式会社 | Anti-thrombotic material |
| US5512650A (en) * | 1986-06-20 | 1996-04-30 | Minnesota Mining And Manufacturing Company | Block copolymer, method of making the same, diamine precursors of the same, method of making such diamines and end products comprising the block copolymer |
| US5214119A (en) * | 1986-06-20 | 1993-05-25 | Minnesota Mining And Manufacturing Company | Block copolymer, method of making the same, dimaine precursors of the same, method of making such diamines and end products comprising the block copolymer |
| US5221724A (en) * | 1987-08-12 | 1993-06-22 | Wisconsin Alumni Research Foundation | Polysiloxane polyurea urethanes |
| US4906465A (en) * | 1987-10-19 | 1990-03-06 | Massachusetts Institute Of Technology | Antithrombogenic devices containing polysiloxanes |
| US4939007A (en) * | 1988-03-07 | 1990-07-03 | Becton, Dickinson And Company | Article having a hemocompatible surface |
| US4840796A (en) * | 1988-04-22 | 1989-06-20 | Dow Corning Corporation | Block copolymer matrix for transdermal drug release |
| US4951657A (en) * | 1988-04-22 | 1990-08-28 | Dow Corning Corporation | Heat sealable membrane for transdermal drug release |
| GB8811868D0 (en) * | 1988-05-19 | 1988-06-22 | Ici Plc | Release film |
| DE3922079C2 (en) * | 1989-07-05 | 1996-06-13 | Hanse Chemie Gmbh | Polysiloxane dispersion, process for its preparation and its use |
| AU4033893A (en) * | 1992-04-24 | 1993-11-29 | Polymer Technology Group, Inc., The | Copolymers and non-porous, semi-permeable membrane thereof and its use for permeating molecules of predetermined molecular weight range |
| DE4217165C1 (en) * | 1992-05-23 | 1993-08-19 | Rehau Ag + Co, 8673 Rehau, De | |
| US5670598A (en) * | 1995-03-24 | 1997-09-23 | Minnesota Mining And Manufacturing Company | Diblock and triblock polydiorganosiloxane-polyurea block copolymers |
| DE19641335A1 (en) * | 1996-10-08 | 1998-04-09 | Inst Textil & Faserforschung | Triblock terpolymer, its use in surgical sutures and manufacturing methods |
| AUPO251096A0 (en) | 1996-09-23 | 1996-10-17 | Cardiac Crc Nominees Pty Limited | Polysiloxane-containing polyurethane elastomeric compositions |
| DE19641334A1 (en) * | 1996-10-08 | 1998-04-09 | Inst Textil & Faserforschung | Triblock terpolymer, its use in medical products and manufacturing processes |
| US5863627A (en) * | 1997-08-26 | 1999-01-26 | Cardiotech International, Inc. | Hydrolytically-and proteolytically-stable polycarbonate polyurethane silicone copolymers |
| DE69840178D1 (en) * | 1998-01-30 | 2008-12-11 | Kaneka Corp | Balloon catheter and manufacturing process |
| US20050220835A1 (en) * | 2004-03-30 | 2005-10-06 | Jayaraman Ramesh B | Agent eluting bioimplantable devices and polymer systems for their preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3562352A (en) * | 1968-09-06 | 1971-02-09 | Avco Corp | Polysiloxane-polyurethane block copolymers |
| JPS5314103B2 (en) * | 1972-07-15 | 1978-05-15 | ||
| US4002794A (en) * | 1975-07-18 | 1977-01-11 | Nashua Corporation | Adhesive material and articles incorporating same |
| US4100309A (en) * | 1977-08-08 | 1978-07-11 | Biosearch Medical Products, Inc. | Coated substrate having a low coefficient of friction hydrophilic coating and a method of making the same |
| US4196731A (en) * | 1978-03-17 | 1980-04-08 | Baxter Travenol Laboratories, Inc. | Silicone-containing thermoplastic polymers for medical uses |
-
1981
- 1981-02-18 CA CA000371214A patent/CA1206668A/en not_active Expired
- 1981-02-19 ZA ZA00811107A patent/ZA811107B/en unknown
- 1981-02-20 IL IL62183A patent/IL62183A/en unknown
- 1981-02-23 AU AU67551/81A patent/AU548194B2/en not_active Ceased
- 1981-02-23 GB GB8105685A patent/GB2073219B/en not_active Expired
- 1981-02-24 MX MX186106A patent/MX159062A/en unknown
- 1981-02-24 AT AT0083581A patent/AT385041B/en not_active IP Right Cessation
- 1981-02-25 JP JP2670781A patent/JPS56136565A/en active Granted
- 1981-02-27 DE DE3153664A patent/DE3153664C2/de not_active Expired - Lifetime
- 1981-02-27 NL NL8100975A patent/NL8100975A/en not_active Application Discontinuation
- 1981-02-27 IT IT8120027A patent/IT1210997B/en active
- 1981-02-27 FR FR8103961A patent/FR2491938B1/en not_active Expired
-
1982
- 1982-02-08 FR FR8201981A patent/FR2497217B1/en not_active Expired
-
1984
- 1984-03-22 GB GB08407417A patent/GB2140444B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2073219B (en) | 1985-02-27 |
| ATA83581A (en) | 1987-07-15 |
| IT8120027A0 (en) | 1981-02-27 |
| DE3153664C2 (en) | 1991-07-25 |
| GB2140444B (en) | 1985-06-05 |
| NL8100975A (en) | 1981-10-01 |
| FR2491938B1 (en) | 1985-10-25 |
| IL62183A (en) | 1984-10-31 |
| FR2497217B1 (en) | 1986-05-23 |
| MX159062A (en) | 1989-04-14 |
| FR2497217A1 (en) | 1982-07-02 |
| ZA811107B (en) | 1982-03-31 |
| AU548194B2 (en) | 1985-11-28 |
| AU6755181A (en) | 1981-09-03 |
| GB2073219A (en) | 1981-10-14 |
| IL62183A0 (en) | 1981-03-31 |
| JPH0214062B2 (en) | 1990-04-06 |
| FR2491938A1 (en) | 1982-04-16 |
| GB2140444A (en) | 1984-11-28 |
| AT385041B (en) | 1988-02-10 |
| GB8407417D0 (en) | 1984-05-02 |
| IT1210997B (en) | 1989-09-29 |
| JPS56136565A (en) | 1981-10-24 |
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