U.S. patent number 3,839,743 [Application Number 05/406,547] was granted by the patent office on 1974-10-08 for method for maintaining the normal integrity of blood.
Invention is credited to Andor Schwarcz.
United States Patent |
3,839,743 |
Schwarcz |
October 8, 1974 |
METHOD FOR MAINTAINING THE NORMAL INTEGRITY OF BLOOD
Abstract
Thromboresistant biomedical articles are provided which are
useful in the fields of subdermal surgical implants, laboratory
apparatus and blood containers. These articles have at least a thin
surface coating of an organic polymeric material having fluoroalkyl
side chains and simple anionic side groups.
Inventors: |
Schwarcz; Andor (Schenectady,
NY) |
Family
ID: |
26937895 |
Appl.
No.: |
05/406,547 |
Filed: |
October 15, 1973 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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246327 |
Apr 21, 1972 |
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Current U.S.
Class: |
424/422; 623/1.1;
433/169; 428/421 |
Current CPC
Class: |
A61K
6/884 (20200101); A61F 2/0077 (20130101); A61L
33/066 (20130101); A61F 2/06 (20130101); A61K
6/887 (20200101); Y10T 428/3154 (20150401) |
Current International
Class: |
A61F
2/00 (20060101); A61F 2/06 (20060101); A61K
6/02 (20060101); A61K 6/083 (20060101); A61K
6/08 (20060101); A61L 33/06 (20060101); A61L
33/00 (20060101); A61f 001/24 (); A61f 001/22 ();
A61m 005/00 () |
Field of
Search: |
;3/1,DIG.1-DIG. 3/ ;3/36
;128/214R,214D,334R,348,349R,35R,335.5,303
;117/124R,138.8A,124D,124E |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Gaudet; Richard A.
Assistant Examiner: Frinks; Ronald L.
Parent Case Text
This is a continuation-in-part of application Ser. No. 246,327,
filed Apr. 21, 1972 and now abandoned.
Claims
Having thus described my invention and in what manner it may be
manufactured and used, what I claim and desire to protect by
Letters Patent is:
1. A method or maintaining the normal integrity of blood which
comprises placing it in contact with a physiologically acceptable
article at least the surface of which consists of an organic
polymeric material having fluoroalkyl side chains of the formula
C.sub.n F.sub.2n.sub.+1 C.sub.m H.sub.2m --, wherein n and m are
integers, n ranging 1 to 28, and the sum of n and m from 2 to 28,
the number of said fluoroalkyl side chains relative to the number
of main chain atoms in one recurring unit ranges from 1:2 to 1:10;
and said polymeric material having another side group chemically
bonded to the main chain, said side group being selected from the
group consisting of Hydrogen, hologen, aryl, lower alkyl and
anionic groups.
2. The method defined in claim 1 wherein the said fluoroalkyl side
chains are linear, the said integers n and m range from 8 to 28 and
the sum of n and m from 8 to 28.
3. The method defined in claim 1 wherein the said integer n ranges
from 1 to 7, the sum of n and m from 2 to 28 and the said side
group is an anionic group.
4. The method defined in claim 1 wherein said physiological
acceptable article comprises a substrate portion and a surface
coating portion, said surface coating portion at least being of
said polymeric material defined in claim 1.
5. The method defined in claim 1 wherein the said anionic group is
a member selected from the group consisting of the acid form of a
carboxylate, sulfonate, sulfate, phosphate, phosphite and the salt
forms of these groups.
6. The method defined in claim 1 wherein the ratio of the number of
said fluoroalkyl side chains to the number of said anions is in the
range of 1:1 to 20:1.
7. The method defined in laim 1 wherein the said fluoroalkyl side
chain is bonded to the main chain of the said organic polymeric
material by an intermediate divalent radical.
8. The method defined in claim 1 wherein the said anionic group is
bonded to the said organic polymeric material by an intermediate
divalent radical.
9. The method defined in claim 7 wherein the said intermediate
divalent radical is a member selected from the group consisting of
--O--, --CO--, --SO--, --SO.sub.2 --, --SO.sub.2 NH--, --CH.sub.2
O--, --COO--, --NHCO--, --NHCONH--, --POCH.sub.3 --, --POC.sub.2
H.sub.5 --, --SO.sub.2 NCH.sub.3 --, --SO.sub.2 NC.sub.2 H.sub.5
--.
10. The method defined in claim 8 wherein the said intermediate
divalent radical is a member selected from the group consisting of
--CH.sub.2 --, --C.sub.2 H.sub.4 --, --OC.sub.2 H.sub.4 --,
--(CH.sub.2).sub.8 --, --(CF.sub.2).sub.15 --, --SO.sub.2 NHChd
2H.sub.4 --.
11. The method defined in claim 1 wherein said physiologically
acceptable article is a subdermal surgical implant.
12. The method defined in claim 1 wherein said physiologically
acceptable article is a surgical instrument.
13. The method defined in claim 1 wherein said physiologically
acceptable article is a laboratory apparatus used for handling
blood.
14. The method defined in claim 1 wherein said physiologically
acceptable article is a blood container.
15. The method defined in claim 4 wherein the said substrate
portion is selected from the group consisting of plastics, rubbers,
metals, glass and ceramics.
16. The method defined in claim 1 wherein said organic polymeric
material is selected from the group consisting of copolymers
prepared from a fluoroalkyl acrylate and acrylic acid, a
fluoroalkyl methacrylate and methacrylic acid and the mixtures of
these monomers.
17. The method defined in claim 16 wherein said polymeric acrylates
are selected from the group consisting of:
poly(1,1- dihydropentacosafluorotridecyl acrylate)
poly(1,1-dihydropentatetracontafluorotricosyl methacrylate)
polyco(1,1-dihydropentadecafluorooctyl methacrylate -- 10% sodium
acrylate)
polyco(1,1,2,2-tetrahydrotrifluoropropyl acrylate -- 5% maleic
acid)
polyco(1,1,2,2-tetrahydropentadecafluorononyl acrylate -- 30%
methacrylic acid -- 15% sodium methacrylate)
18. The method defined in claim 1 wherein said organic polymeric
material is selected from the group consisting of:
poly(methyl-1,1,2,2-tetrahydrotriacontafluorooctadecyl
siloxane)
poly[di(1,1,2,2-tetrahydrotricosafluorotridecyl) siloxane].
poly(carboxyethyl-1,1,2,2-tetrahydrotrifluoropropyl siloxane)
and
poly(methyl-3,3,3- trifluoropropyl siloxane) wherein a minor part
of the methyl groups is replaced with carboxyethyl groups.
19. The method defined in claim 1 wherein said organic polymeric
material is selected from the group consisting of:
polymers of fluoroalkyl esters, amides and imides of maleic and
fumaric acids,
the copolymers with ethylene, styrene, methylvinyl ether and vinyl
acetate of fluoroalkyl esters, amides and imides of maleic and
fumaric acids,
the copolymers with maleic, fumaric and acrylic acids and their
anhydrides of fluoroalkyl esters, amides and imides of maleic and
fumaric acids.
Description
BACKGROUND OF THE INVENTION
1. Field of the invention
This invention relates to biomedical articles that resist the
clotting of human blood and generally that of warm blooded animals.
It describes the structure of these articles and the various modes
of their manufacture. One of such articles is a subdermal implant.
Examples are subdermal prosthesis such as artificial blood vessels
to correct atherosclerotic shrunken passageways or to eliminate
aneurisms in cardiac assist devices and in artifical hearts and
heart valves to replace or augment the function of the natural
heart. Other subdermal prosthetic devices of this invention include
reinforced and non reinforced sheetings, rubbers to reconstruct
fractures, coronary arteries, denture soft liners, denture base
materials, sponge subdermal implant materials, mammary prosthesis,
testicular prosthesis, atoplasty prosthesis, rhinoplasty implants,
scleral buckler designed for use with Everett technique, rubbers
used to remedy defects following facial trauma and coiled capillary
tubing membrane oxygenators for complete cardio-pulmonary bypass;
also suction drainage of orthopedic wounds, arterial venous shunts,
abdominal drains, catheters for intravenous administration of
fluids for withdrawal of serial blood samples, for percutaneous
flow-guided cardia catheterization, continuous monitoring of blood
glucose, intestinal decompression tubes, various catheters and
thoriac drains. Other implanted articles of this invention include
circulatory assist devices, tubes for blood transfusion, the
implants of electrical devices and mechanical devices such as
prosthetic valves and sutures. Other biomedical articles of this
invention include thromboresistant surgical instruments, laboratory
apparatus used for blood handling and blood handling and blood
containers for storage.
2. Description of the Prior Art
One of the most striking property of blood is its tendency to
undergo clotting, or thrombosis. This has been the major problem
encountered in the use of subdermal prosthesis.
The detailed mechanisme of thrombosis is still not established. Its
normal course involves a series of complex reactions that, once
initiated result in the formation of thrombosis. Two processes may
occur:
1. The absorption of proteins leading to coagulation;
2. The adhesion of platelets at first to the solid, foreign
surface, and then to each other. The growing mass of platelets
forms a thrombosis which adheres to the solid surface.
Those surfaces that do not cause or significantly prolong the time
of thrombosis are commonly called nonthrombogenic or
thromboresistant surfaces. A major need exists for a great variety
of thromboresistant articles. Various attempts have been made to
find a suitable material which exhibits nonthrombogenic properties
or a method of treating known materials to render them
thromboresistant. Organic polymers are generally thrombogenic and
therefore require the use by the patient of anticoagulant drugs
such as heparin and coumarin derivatives.
Various organic polymers have been coated recently with heparin.
Although this material displays some degree of thromboresistance,
the coating eventually washes away with the flow of blood and it is
difficult to fabricate.
There have been attempts to obtain thromboresistant biomedical
articles from fluorinated polymers and sulfonated polymers.
However, none of them are performing in a satisfactory manner. This
is due, in the opinion of the author of the present invention, to
the disposition, the length and the relative lengths of the various
groups in the polymer.
SUMMARY OF THE INVENTION
My invention provides thromboresistant biomedical articles useful
in the fields of subdermal implants, surgical instruments,
laboratory apparatus and blood containers. These articles are
composed, at least on their surface, of an organic polymeric
material having side chains of the formula C.sub.n F.sub.2n.sub.+1
C.sub.m H.sub.2m --, wherein n and m are integers, n ranging from 1
to 28 and the sum of n and m from 1 to 28, and an anionic
group.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The biomedical articles of this invention are characterized by
their thromboresistant surface. The surface of the said articles
are characterized by an organic polymeric material having
fluoroalkyl side chains of the formula C.sub.n F.sub.2n.sub.+1
C.sub.m H.sub.2m --, wherein n and m are integers, the range of n
extending from 1 to 28 and the sum of n and m from 2 to 28. The
number of fluoroalkyl side chains relative to the number of
main-chain-atoms in one recurring unit ranges from 1:2 to 1:10,
preferably from 1:2 to 1:5. The atoms that are in the main or
linear direction of the polymer such as the carbon atoms in
polyethylene and poly(vinyl alcohol), are the only ones considered
main-chain-atoms. Linear fluoroalkyl side chains with values of the
integer n ranging from 8 to 28 are particularly effective ones to
give the articles of this invention a high degree of
thromboresistance.
The presence of another, generally shorter side chain, which is an
anion or one comprising an anion, generally enhances the
thromboresistivity of the polymer. However, its presence is
required only in the cases wherein the said fluoroalkyl side chain
is branched (non linear) and in cases wherein the value of the
integer n ranges from 1 to 7.
A feature of the said organic polymeric materials of this invention
is that their thromboresistant character is provided by the side
chains, the main chain having an essentially supportive role. This
might be due to the fact that the fluoroalkyl side chained polymers
of this invention have simultaneously low surface tension and
negative zeta potential, properties thought necessary for
thromboresistance according to certain theories.
The invention is described hereinafter in greater detail by
reference to the examples which show preferred embodiments of the
invention. It should be understood however that the examples
hereinafter given are for the purposes of illustration only and
that the invention in its broader aspects is not limited
thereto.
Examples of the said fluorinated side chains are CF.sub.3
(CF.sub.2).sub.7 --, CF.sub.3 (CF.sub.2).sub.11 (CH.sub.2).sub.16
--, CF.sub.3 (CF.sub.2).sub.22 CH.sub.2 --, i-C.sub.4 F.sub.9
(CH.sub.2).sub.10 --, CF.sub.3 (CH.sub.2).sub.2, C.sub.3 F.sub.7
--.
The anionic groups can be either in their acidic form, their salt
or their partially neutralized form. Example of simple anionic
groups are carboxylate, sulfonate, sulfate, phosphate and
phosphites. Examples of the salt forming positive ions are sodium,
potassium, lithium, ammonium, magnesium, tertiary amines such as
N-methylmorpholine.
The ratio of the number of the said fluoroalkyl groups to the
number of said anionic groups ranges from 0.5:1 to 50:1, preferably
from 1:1 to 20:1. In general, this ratio decreases as the ionic
strength decreases. The number, strength and degree of
neutralization of said anionic groups should be limited in order to
avoid solvation or excessive swelling of the fluorinated polymer by
the blood.
The said fluoroalkyl side chain may be directly attached to the
main chain of the organic polymer. It can also be attached by an
intermediate divalent radical, such as --O--, --CO--, --SO--,
--SO.sub.2 --, --SO.sub.2 NH--, --CH.sub.2 O, --COO--, --NHCO--,
--NHCOO--, --NHCONH--, --POCH.sub.3 --, --POC.sub.2 H.sub.5, --,
--SO.sub.2 NCH.sub.3 --, --SO.sub.2 NC.sub.2 H.sub.5 --.
Similarly, the anionic group may be directly attached to the main
chain of the organic polymer or through an intermediate divalent
radical. Such radicals are exemplified by --CH.sub.2 --, --C.sub.2
H.sub.4 --, --OC.sub.2 H.sub.4 --, --(CH.sub.2).sub.8 --,
--SO.sub.2 NHC.sub.2 H.sub.4 --,--(CF.sub.2).sub.15 --.
Biomedical articles of this invention may be entirely composed of
the said organic polymeric materials with the fluoroalkyl side
chains. However, the particular mechanical and electrical
properties required of the various biomedical articles, or the
higher cost involved may require them to comprise a surface portion
and a substrate portion. The surface portion is composed of the
said thromboresistant organic polymer. The substrate portion may be
any solid material that satisfies the properties required of the
biomedical article. Thus, substrate materials comprise plastics,
rubbers, metals, glass, ceramics. The use of a coating technic is
particularly advantageous for making surgical instruments,
laboratory apparatus, blood containers and heart valves.
Examples of plastic substrates are isotactic polyolefins, such as
polypropylene, polystyrene, polyethylene, poly(4-methylpentane);
polyesters such as poly(1,4-cyclohexylene terephthalate),
poly(ethylene terephthalate); polyacrylates such as
polymethylmethacrylate, polyco (ethylacrylate-acrylic acid);
polyurethanes such as the ones prepared from a hydroxy terminated
polyether or polyester and methylenebis (phenylisocyanate);
polycarbonates such as poly(2,2-propanebis(4-phenyl carbonate);
fluorinated polyolefins such as poly(tetrafluoroethylene);
chlorinated polyolefins such as polyvinylchloride; proteins such as
wool, casein; cellulose, cellulose derivatives such as cellulose
acetate, cellulose acetate butyrate and other polysaccharides.
Examples of rubber substrates are silicone rubbers such as
poly(dimethylsiloxane poly(methylphenyl siloxane); hydrocarbon
rubbers such as butyl rubber, ethylene-propylene rubber; nitrile
rubbers such as polyco(butadieneacrylonitrile); fluorinated rubbers
such as fluorinated ethylene-propylene rubber, fluorinated
polyurethanes; urethane rubbers such as the ones prepared from
hydroxy terminated polyethers or polyesters and
methylenebis(phenylisocyanate); polyether rubbers such as poly
(propylene oxide) and chlorosulfonated rubbers such as
chlorosulfonated ethylene-propylene rubber.
Metallic substrates include stainless steel, aluminum, alloys of
chromium, nickel, cobalt and magnesium.
Examples of the said organic polymeric materials having linear
fluoroalkyl side chains wherein the said integer n ranges between 8
and 28, the sum of n and m between 8 and 28 and the said polymer
has no anionic groups attached to the main chain are:
poly(1,1,2,2- tetrahydropentadecafluorononyl acrylate)
poly(1,1-dihydropentacosafluorotridecyl acrylate)
poly(1,1-dihydropentatetracontafluorotricosyl methacrylate)
poly(1,1,2,2-tetrahydrononacosafluorohexadecyl vinyl ehter)
poly (vinylperfluorooctadecane)
poly (perfluoro-1-octadecene)
poly(vinyl perfluorostearate)
poly(N-1,1-dihydropentatriacontafluorooctadecyl hexamethylene
urea)
poly(methyl-1,1,2,2-tetrahydrotritriacontafluorooctadecyl
siloxane)
poly [di(1,1,2,2-tetrahydrotricosafluorotridecyl) siloxane]
poly(N-1,1-dihydropentatriacontafluorooctadecyl hexamethylene
adipamide).
Examples of said organic polymeric materials having linear or
branched fluoroalkyl side chains wherein the said integer n ranges
between 1 and 28, the sum of n and m between 2 and 28 and the said
anionic group is bonded to the main chain of the polymer, are (the
propertion of monomers in the copolymers are expressed in mole
%):
polyco(1,1-dihydropentadecafluorooctyl methacrylate -- 10% sodium
acrylate)
polyco (1,1,2,2,-tetrahydrotrifluoropropyl acrylate -- 5% maleic
acid)
polyco(1,1,2,2-tetrahydropentadecafluorononyl acrylate -- 30%
methacrylic acid -- 15% sodium methacrylate)
poly(carboxyethyl-1,1,2,2-tetrahydrotrifluoropropyl siloxane)
polyco(methyl-3,3,3-trifluoropropyl siloxane -- 20%
carboxyethyl-methyl siloxane)
polymers of fluoroalkyl esters, amides and imides of maleic and
fumaric acids
The copolymers with ethylene, styrene, methylvinyl ether and vinyl
acetate of fluoroalkyl esters, amides and imides of maleic and
fumaric acids
The copolymers with maleic, fumaric and acrylic acids and their
anhydrides of fluoroalkyl esters, amides and imides of maleic and
fumaric acids
the 1,1-dihydronanafluoropentyl monoester of polyco (50% ethylene
-- 23% maleic acid -- 23% potassium maleate)
the 1,1-dihydropentadecafluorooctyl monoamide of polyco (80%
methylvinyl ether -- 10% fumaric acid -- 10% sodium fumarate)
polyco(vinyl 1,1-dihydropentatriacontafluorooctadecyl carbamate --
15% vinyl disodium phosphite)
polyco (vinyl perfluoropropianate -- 10% acrylic acid)
These compounds are all linear organic polymers having intrinsic
viscosity values higher than 0.04, preferably higher than 0.07.
They can be prepared by conventional polymerization techniques such
as the free radical and ionic addition polymerization techniques or
condensation polymerization techniques of the monomers. Another
method consists of introducing an anionic group to the polymer by
carboxylation, sulfonation, phosphorilation, etc, and further
reacting with a fatty fluorinated compound containing a functional
group. Such compounds are, for example, perfluorooctadecanoyl
chloride and 1,1-dihydrotricosafluorododecyl alcohol. These
techniques are well documented in the art of polymer synthesis.
After preparation, the polymer is then shaped into the desired
biomedical articles, e.g. heart valves, blood vessel, tubings etc.
The shaping can be done by any conventional means, uch as
extruding, molding, casting. After proper sterilization, the
biomedical article is ready for use.
An effective way to prepare a thromboresistant biomedical article
of this invention is to react the polymeric material of this
invention containing the said anionic group with a
stochiometrically defective amount of a cationic type polymer, such
as poly-2-vinylpyridine, poly(vinylbenzyldimethylamine),
polyco(styrene-4-vinylpyrridine).
Another way to prepare a thromboresistant biomedical article of
this invention is to coat the potentially blood contacting surfaces
of the shaped article made of a plastic, a rubber, a metal or glass
with the said organic polymeric material having the fluoroalkyl
side chains exemplified above. Any of the conventional coating
procedures can be used, such as coating from a solution, emulsion,
suspension followed by solvent evaporation, or a hot melt coating
technique. The bond between he substrate and the coating can be
improved, if necessary, by conventional surface treatment
techniques, such as corona discharge, flame treatment, irradiation,
or priming with a polar polymeric substance. These coating and
priming procedures are well documented in the art of coating
technology.
A biomedical article of this invention can be prepared by the use
of still another technique. This technique consists of coating the
shaped article, made of a plastic, a rubber, a metal or glass, with
the monomers from which the said organic polymeric materials,
having the fluoroalkyl side chains, and examplified above, are
prepared, and let the polymerization proceed on the surface.
Similar coating and priming procedures can be used as the ones
described above. The polymerization on the surface of the article
can be carried out by conventional techniques used in the art of
polymer synthesis and coatings, such as the use of catalysts, heat,
oxygen, moisture, radiation, peroxides etc.
Still another way to achieving the objectives of this invention is
to graft an anionic group and the said perfluoroalkyl group C.sub.n
F.sub.2n.sub.+1 C.sub.m H.sub.2m --, onto the surface of a shaped
biomedical article made of a plastic or a rubber. Examples of such
surface grafting reactions are as follows:
the grafting of perfluorooctadecanoyl chloride onto a shaped
biomedical article made of poly(tetramethylene urea),
poly(tetramethylene hexamethylene dicarbamate), cellulose fibers,
wool, silk, nylon;
the grafting of sulfuric acid and perfluorohexadecanoic acid onto
the shaped article made of poly(vinylalcohol), cellulose,
casein;
the grafting of 1,1,2,2-tetrahydroheptafluoropentanol, onto a
preshaped article made of polyco(acrylic acid -- 10% sodium
acrylate);
the grafting of 1,1-dihydropentacosafluorotridecyl iodide onto a
shaped article made of polyco(ethylene-monosodium maleate), and
onto sodium cellulose sulfate;
the radiation grafting of
1,1,2,2-tetrahydrotritriacontafluorooctadecyl vinylether to a
shaped article made of poly(ethylene terephtalate);
the grafting of 1,1-dihydrohencosafluoroundecyl amine onto a shaped
biomedical article made of polyethylene which has been previously
sulfonated with concentrated sulfuric acid and the sulfonate groups
partially neutralized with a buffer solution having a pH of
7.5.
There are still other means to prepare the polymers of this
invention. For example polymers having unbranched higher alkyl side
chains can be fluorinated with fluorine gas. Examples of such
polymers are polyvinylstearate, polyco(vinylacetate-docosylmaleate
sodium salt).
EXAMPLE 1
Ninety (90) grams (0.1 moles) of
1,1-dihydrotritriacontafluoroheptadecyl acrylate and 1.14 grams
(0.01 moles) of 1-hexenoic acid are copolymerized by using 0.5%
azobisisobutyronitrile as the initiator and toluene as the solvent
medium. The reaction is carried out in crew cup vials at
75-80.degree.C. for 16 hours. The copolymer is then purified by
adding methanol to the solution, filtered, redissolved in
1,2,2-trichlorotrifluoroethane, and this procedure is repeated
three times. The solid polymer is then dried in a vacuum oven at
60.degree.C. for 64 hours. The intrinsic viscosity measured in
hexafluorodimethyl benzene is 0.2.
A glass tube is then treated with a 5% trichlorotrifluoroethylene
solution of the copolymer by filling the tube, inverting it and
allowing the excess liquid to drain out. Following evaporation of
the solvent, the coated test tube is sterilized.
Five (5) ml of freshly drawn whole blood from the lower vena cava
of a rabbit as added and the test tube is periodically tipped to
observe clot formation. No evidence of clot formation is observed
for several hours. A control test tube, not coated with a layer of
the copolymer, is tested in an identical manner, and clotting
occurs within 7 minutes.
EXAMPLE 2
A 1:1 molar mixture of potassium acrylate and
1,1-dihydroheptatriacontafluorononadecyl acrylate is grafted onto a
bidirectionally oriented poly(ethylene terephtalate) film
previously subjected to 2 MeV radiation at -80.degree.C. A blood
bag is formed from the surface-grafted film and sterilized. Plasma
from the blood of a human donor is stored in the said bag for an
extended period at 5.degree.C. The plasma shows no signs of
thrombus formation and it is physiologically acceptable for human
use.
EXAMPLE 3
A copolymer of octadecyl vinyl ether with 1-dodecenoic acid sodium
salt is used to coat, from a 5% toluene solution, a commercially
available fluoropolymer heart valve previously submitted to
electron radiation to obtain better adhesion. It is then
fluorinated in the dark by exposure to 5% fluorine diluted with 95%
nitrogen at room temperature for 2 weeks. The coated heart valve is
then sterilized and when implanted in an animal, such as a dog, the
implant, in accordance with this invention, will be found to
sustain the life of the animal.
EXAMPLE 4
A silicone rubber having a fluoroalkyl side chain is prepared by
the following customary procedure. Methyl trichlorosilane is
reacted with 1,1,2,2,3,3,4,4-octahydropentadecafluorohexadecyl
magnesium chloride, the dichloro product separated from the
reactive mixture by vacuum distillation and followed by
polymerization with the addition of water. It is then mixed with 2%
dimethyltindilaurate catalyst, molded into a tube of 0.05 inch
inside diameter and cured at 150.degree.C. for 48 hours under
nitrogen.
The tubing is tested in vivo using a jugular vein of a dog. The
vein is exposed and severed in a standard surgical manner. The
tube, after sterilization, is formed into a loop and to each end of
the vein is attached one end of the tubing. Circulation through the
vein is resumed and blood now is passing through the tubing.
The implanted artifical vein, in accordance with this invention,
will not be found to be harmful to the life of the animal.
EXAMPLE 5
1-perfluorooctadecene, 88.1 g (0.1 mol), is copolymerized with
maleic anhydride, 9.6 g(0.1 mole), using a technique similar to
that described in Example 1. The copolymer is then boiled in an
aqueous sodium hydroxide solution containing a small amount of a
fluorinated anionic surfactant. This reaction yields the sodium
salt of the maleic acid portion of the polymer. The polymer is then
purified by a repeated solutionpreceipitation technique.
A cannula made of polypropylene is surface oxidized in a
circulating air oven at 110.degree. C. to obtain better adhesion.
It is then coated with a 5% trichlorotrifluoroethylene solution of
the polymer prepared in this example and the solvent evaporated in
an air iven at 60.degree.C. After sterilization, the cannula is
used as conduit replacement in a heart-lung machine. After several
months of use no evidence of thrombus formation on the cannula will
be reported.
EXAMPLE 6
Poly(vinyl alcohol) of 120,000 molecular weight, 45 g(1 mole), is
sulfated with sulfur trioxide dissolved in sulfuric acid to yield
the sulfate ester. As deduced by titration with sodium hydroxide
one out of every 10 hydroxyl groups is sulfated. The polymer is
further reacted with perfluorohexadecanoyl chloride in N-methyl
morpholine to yield polyco(vinyl perfluorohexadecanoate-vinyl
sulfate N-methylmorpholine salt), which then is purified by
successive crystallizations. The copolymer is then coated on a
Nylon cannula and sterilized, all in the similar way as described
in Example 5. The coated cannula is used as conduit tubing in a
blood machine. Equivalent results to those described in Example 5
are obtained.
EXAMPLE 7
A 1:1 copolymer of methylvinylether maleic anhydride, 15.6 g (0.1
mole) having an intrinsic viscosity of 2.5 in methylethyl ketone,
is reacted in 500 ml of methylethyl ketone at the boil with
1,1,2,2-tetrahydrohencosafluorododecyl amine, 66.3 g (0.1 mole).
The fluorinated acid-amid is then precipitated in methanol,
filtered, washed, and reacted with sodium hydroxide dissolved in
alcohol. The polymer thus obtained is polyco[methylvinyl
ether-sodium salt of maleic acid
mono(1,1,2,2-tetrahydrohencosafluorododecyl)amide], which is then
purified by repeated solvation-precipitation.
The fluorinated copolymer is then molded in a hot press into a 0.05
in. inside diameter catheter having a wall thickness of 0.005 in.
and sterilized. When surgically implanted in the jugular vein of a
dog, similar results to those obtained in Example 4 will be
reported.
EXAMPLE 8
Vinyl perfluorodocosyl ether, 11.8 g (0.1 mole) is polymerized and
purified using a technique similar to that described in Example 1.
The intrinsic viscosity measured in trichlorotrifluoroethane is
0.2. A stainless steel tubing is coated with a 5%
trichlorotrifluoroethylene solution of this polymer, and the
solvent evaporated at 60.degree.C. in a vacuum oven. After
sterilization the tubing is used as an arterialvenous bypass in a
hemidialysis machine. No thrombus formation will be evident after
usage of the machine for several months.
EXAMPLE 9
A cannula made of polyethylene is phosphorilated on the surface
with phosphorous trichloride at 60.degree.C. in the presence of
oxygen, and then boiled in aqueous sodium hydroxide. This procedure
provides sodium phosphate groups at the surface. A subsequent
grafting of perfluorotetradecene using an electron radiation
techniques yields the desired surface, which is then cleaned with
bis(trifluoromethyl) benzene and ethanol. After through
sterilization, the cannula, when tested in a heart-lung machine,
will yield comparable result to those obtained in Example 5.
EXAMPLE 10
101.6 grams (0.1 mole) of perfluorooctadecyl-perfluorovinyl ether
and 16 grams (0.02 moles) of perfluoro-1-hexadecenoic acid are
dissolved in bis(trifluoro)benzene and coated on a commercially
available silicone rubber heart valve previously primed to obtain
better adhesion. After solvent evaporation, the coated heart valve
is then irradiated with an electron beam of 5 MeV under argon to
polymerize the coating. Following extraction of the residual
monomers and sterilization, the heart valve, when evaluated as in
Example 3, yields similar results.
It will be apparent that many widely different embodiments of this
invention may be made without departing from the spirit and scope
thereof. Therefore, the invention is not intended to be limited
except as indicated in the appended claims.
EXAMPLE 11
Polyco(methacrylic acid-3,3,3,3',3',3'-hexafluoroisobutyl
methacrylate) is prepared in emulsion at 65.degree.C for 6 hours
with the following recipe, added in the order shown:
Parts Water 30.0 Trimethyloctodecylammonium bromide 1.0 Methacrylic
acid 2.0 hexafluoroisobutyl methacrylate 10.0 Acetone 5.0
Azodiisobutyramidine dihydrochloride 0.2
A cannula made out of chlorosulfonated ethylene-propylene rubber is
coated with a thin layer of polyco(styrene-2-vinylpyrridine) of 0.9
intrinsic viscosity. It is subsequently coated with a latex
prepared in this example to leave at the surface a thin film of the
fluorinated polymer chemically bonded to the underlaying polymeric
substance and said fluorinated polymer having free, unreacted
carboxyl groups. The coated cannula is used as a conduit in a blood
machine. Equivalent results to those described in Example 5 are
obtained.
EXAMPLE 12
A thromboresistant artificial heart is molded from
poly(methyl-3,3,3-trifluoropropyl siloxane) wherein about one fifth
of the methyl groups is replaced with carboxyethyl groups. This
copolymer is prepared as follows: Methyldichlorosilane is reacted
with acrylonitrile under reflux conditions (60-115.degree.C) for
about ten hours by using catalytic amounts of the following
materials: cuprous chloride, tetramethylethylene diamine and
triethylamine. The reaction product, which is
cyanoethyl-methyldichlorosilane, is hydrolyzed in the presence of a
10% HC1 solution under reflux conditions until complete
diappearance of the nitrile group. After separation from the
aqueous layer, the organic layer consists of
poly(carboxyethylmethylsiloxane). This is equilibrated at
60-100.degree.C, for 4-6 hours, with 20% by weight of
3,3,3-trifluoropropyl-methylsiloxane fluid commercially available
from Dow Corning Co., Inc until constant viscosity is reached. The
product is then washed with aqueous sodium carbonate, water,
separate from the aqueous layer, and stripped off from the low
boilers by distillation. It is then blended with 100 phr finely
divided silica and 1 phr dicumyl peroxide, molded into a human
heart and cured at 125 C for 5 hours.
EXAMPLE 13
Acrylic acid, 20 mole % is copolymerized with 80 mole % of bis
[2-(N-ethyl perfluorohexylsulfonamido) ethyl] itaconate, as in
Example 1. After purification and coating on a test tube, the
polymer passes the same test as the one described in Example 1.
* * * * *