TITLE: Polymer alloy blood compatible surface
United States Patent 4312920

ABSTRACT:
A blood contacting layer and a blood contacting interface consisting of
a solvent cast polyurethane alloyed with a filler-free silicone rubber.
In the above, the alloy interface comprises an interpenetrating polymer
network consisting of polyurethane and filler-free silicone rubber at
the molecular level. The process or method of making the layer consists
of preheating a metal mold such as an aluminum mold and filling it with
a wax. After the wax form is removed, polished and cleaned, it is
dipped first in a filler-free silicone rubber which is cured. It is
then dipped in segmented polyurethane with curing of 150° F. for about
one hour to evaporate the polyurethane solvent. Multiple dips are
utilized up to 5 or 7 for implementing the polyurethane. The form
containing both silicone rubber and polyurethane is finally cured for a
day or 24 hours at about 150° F. and the wax form is removed. Finally,
the silicone rubber lining is removed, leaving the binary alloy blood
contacting surfaced polyurethane sac.

INVENTORS:
Pierce, William S. (Hummelstown, PA)
Donachy, James H. (Annville, PA)

APPLICATION NUMBER: 06/092102
PUBLICATION DATE: 01/26/1982
FILING DATE: 11/07/1979

ASSIGNEE: The United States of America as represented by the Department of Health
(Washington, DC)
PRIMARY CLASS: 428/425.5
OTHER CLASSES: 264/255, 264/305, 623/921
INTERNATIONAL CLASSES: A61L27/18; B29C41/14; (IPC1-7): B32B27/40
FIELD OF SEARCH: 525/440, 525/452, 525/460, 428/425.5, 264/255, 264/305, 3/1, 3/1.4,
3/1.7, 128/1D, 128/214R, 128/348

US PATENT REFERENCES:
4057595 Method of modifying the physical properties of urethane
elastomers November, 1977 Rauner 525/460
3562352 N/A February, 1971 Nyilas 525/460
3246048 Organosiloxane-polyether urethanes April, 1966 Haluska 525/460

OTHER REFERENCES:
Ward et al., "Production of Biomedical Polymers, In Organometallic
Polymers", 1978, Academic Press Inc., New York, pp. 219-229.
Kolobow et al., "Superior Blood Compatibility of Silicone Rubber Free
of Silica Filler in the Membrane Lung", Trans. Amer. Soc. Artif. Int.
Organs, 1974, vol. XX, pp. 269-277.
Boretos et al., "Surface and Bulk Characteristics of a Polyether
Urethane for Artificial Hearts", In J. Biomed. Mater. Res., vol. 9,
1975, pp. 327-340.
Baier, "Key Events in blood Interactions at Nonphysiologic Interfaces-A
Personal Primer", Artificial Organs, vol. 2, No. 4.
Wilkes, "Necessary Considerations for Selecting a Polymeric Material
for Implanting with Emphasis on Polyurethane", Poly. Sci. & Tech., vol.
8, pp. 45-75

PRIMARY EXAMINER: Derrington, James H.
Attorney, Agent or Firm:
Roberts Jr., John S.

CLAIMS:
We claim:
1. A blood contacting polyurethane layer having only one of its
surfaces modified by alloying silicone rubber on only that modified
surface and completely contained within 40 microns of said surface.
2. The blood contacting polyurethane layer according to claim 1 which
comprises a segmented polyurethane alloyed with a filler-free silicone
rubber.
3. A blood contacting polyurethane according to claim 1, wherein said
alloying is a segmented polyurethane with an interpenetrating amount of
a filler-free silicone rubber.

DESCRIPTION:
This invention relates to a blood contacting layer and a blood
contacting interface consisting of a segmented polyurethane alloyed
with a filler-free silicone rubber. In the above, the alloy comprises
an interpenetrating polymer network consisting of polyurethane and
filler-free silicone rubber at the molecular level. The process or
method of making the layer consists of preheating a metal mold such as
an aluminum mold and filling it with wax. The wax form is removed,
polished, cleaned and then dipped first in a filler-free silicone
rubber and cured. Then the form is dipped in segmented polyurethane
solution with solvent evaporation at 150° F. for about one hour.
Multiple dips are utilized up to 5 or 7 to provide the desired
thickness of the polyurethane. After the wax form is removed and
cleaned, it is dipped. The form containing both silicone rubber and
polyurethane is finally cured for a day or 24 hours at about 150° F.
and the wax form is removed. Finally, the silicone lining is removed,
leaving the binary alloy blood contacting surface.
At or very close to the interface, experiments have shown that most of
the silicone rubber is congregated in the molecular alloy and that
there is very little silicone rubber away from the direct blood
contacting surface that is in the bulk polymer or external surface. It
has been calculated that 99.9% or thereabouts of the silicone rubber
present is present in the area delimited by a maximum of 40 microns
from the blood contacting surface, In this area, by weight percent, the
silicone rubber percentile may be as high as 50 to 75%.
The present application is targeted to a method and resulting product
of a blood contacting surface, which at the point of contact is a
modified segmented polyurethane. The term segmented polyurethane is now
well established (cf. Boretos, J. W. and Pierce, W. S., Segmented
Polyurethane--A New Elastomer for Biomedical Application, Science,
158:1481, 1967). The term segmented polyurethane applies to a
transparent polyether type polymer with no plasticizers or fillers and
has been described as containing alternating hard segments (HS) and
soft segments (SS). It appears that the polyurethane solvent (in this
case, N--N dimethyl acetamide but similar effects are broadened with
other organic solvents and chemically related solvents such as
formamide, tetrahydrofuran, etc.) has a modifying effect on the
filler-free silicone rubber and permit the migration of the
polyurethane and silicone rubber species. The interface of the present
material is known as an interpenetrating polymer network (IPN). As
such, there is a migration across the barrier of molecular species from
the second component; namely, silica-free silicone rubber. The
resulting product is not a mixture nor a copolymer, and the IPNs have
been described in the literature as in Polymer Science and Technology,
Volume 10, "Polymer Alloys" edited by Daniel Klempner and Court C.
Frisch (1977) in the preface at page v. It is of some importance that
the actual blood contacting surface, which is our preferred modus is
achieved by adding and removing a silicone polymer by interpenetration
provides a polymer alloy blood compatible surface consisting of the
filler-free silicone rubber alloy to a segmented polyurethane.
The development of segmented polyurethanes and the addition of some
type of silicone rubber to modify the aspects deleterious to blood
contacting surface is about 10 years old. The polyurethanes themselves
have good rubber qualities, but poorer blood contacting properties than
pure filler-free silicone rubber. The polyurethanes, for example, are
illustrated by Biomer (Johnson & Johnson, a bipolymer) and previously
Lycra (DuPont, a spandex fiber of polyurethane). The silicone rubber
which does not have the desired elastomeric properties of polyurethane,
however, does have excellent blood contacting properties probably due
to the utilization of dimethyl silicone rubber and the methyl groups
close to the surface. It has been found that solvent cast polyurethane
cured in juxtaposition to filler-free silicone rubber yields desired
alloys and not mixtures or polymers.
It has been found that with the present alloy, 50 to 75% of the
dimethyl silicone rubber is crowded very close to the blood contacting
layer toward an area up to 40 microns from the actual contact line.
Prior Art Statement
U.S. Pat. No. 3,562,352 to Nyilas, Avco Corporation, describes block
copolymers of polyurethane and polysiloxane. It is noted in the
Abstract that both polyether and polyester polyurethanes may be
utilized.
Transactions American Society of Artificial Internal Organs, Volume 20,
1974, page 269, T. Kolobow et al, entitled "Superior Blood
Compatibility of Silicone Rubber Free of Silica Filler in the Membrane
Lung."
J. Biomed. Mater. Res., Vol. 9, pp. 327-340 (1975), John W. Boretos,
William S. Pierce, Robert E. Baier, Andre F. Leroy and Howard J.
Donachy entitled "Surface and Bulk Characteristics of a Polyether
Urethane for Artificial Hearts."
Artificial Organs, Vol. 2, no. 4, page 1, Robert E. Baier, entitled
"Key Events in Blood Interactions at Nonphysiologic Interfaces--a
Personal Primer."
Organometallic Polymers, 1978, Academic Press, Inc., New York, pp,
219-229.
Polymer Science and Technology, Vol. 8, pp. 45-75, Garth L. Wilkes,
entitled "Necessary Considerations for Selecting a Polymeric Material
for Implantation with Emphasis on Polyurethane."
Products claiming relationship to the above patent, U.S. Pat. No.
3,562,352, are marketed by Roche under the tradename Avcothane. The
purpose of the Avcothane and the patent was to combine the good
elastomeric properties of the segmented polyurethane with the good
blood contacting properties of the silicone rubber.
The surfaces and polymers of the present invention may be presently
used as surfaces in artificial hearts and heart assist pumps. In
addition, the following uses for the novel layers are closely linked to
the aforesaid artificial hearts and ventricular assist pumps; namely,
intravenous catheters, blood oxygenators, heart lung machine tubing,
inter-aortic balloon pumps and artificial blood vessel grafts.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows two mold halves ready for assembly and pouring of hot wax.
FIG. 2 shows the molds separated and the wax form ready for removal.
FIG. 3 shows a hollow form as removed from the mold.
FIG. 4 shows a sanded and polished wax form ready for dipping in
filler-free silicone rubber.
FIG. 5 shows the form subsequently coated with a layer of filler-free
silicone rubber.
FIG. 6 shows the form coated with 5-7 layers of polyurethane, depending
upon the required sac thickness.
FIG. 7 shows the sac after removal of the wax form and silicone rubber
contacting surface.
FIG. 8 is a cross-section of the sac showing the epolene wax, the
filler-free silicone rubber boot and 5-7 coats of segmented
polyurethane to provide the desired sac thickness.
PROCESS
A preferred process for the production of the polymers, layers and the
surfaces is as follows:
Step I--refer to FIG. 1. An aluminum mold was preheated to a desired
temperature of 270° to 300° F. and then hot wax was poured (Epolene
C10, which is a low molecular weight polyethylene resin of Shell
Chemical Co.) in a preheated mold, filling completely. The mold was
allowed to cool until the desired wall thickness jelled. Then, excess
wax was poured from the form. The form is then cooled to room
temperature. The hollow wax form was removed from the mold. See FIG. 2.
Step II--refer to FIG. 3. The wax form was removed from the mold with
flash lines and slight imperfection. The form was sanded and fine
polished to accomplish as smooth a surface as possible. FIG. 4 shows
the sanded and polished form.
Step III--the form was cleaned with a lower alkanol (propyl alcohol)
and dried with deionized air. The form was kept in a laminar flow air
hood and dipped in filler-free silicone rubber. The cure took 4 hours
or longer. This step blended the surface giving a high gloss and a
non-adhering surface for the polyurethane to be coated against. FIG. 5
shows the clear coating of filler-free silicone rubber on the wax form.
Step IV--the form was then dipped in segmented polyurethane solvent and
cured on a rotisserie at 150° F. for 1 hour. This process was repeated
until the desired sac thickness was acquired. Normally, this required 5
to 7 dips. FIG. 6 shows this step when completed.
Step V--The form was then placed in a circulating oven for 24 hours at
a curing temperature of 150° F. After curing, the wax form was crushed
into pieces by hand pressure and removed from inside of the sac. The
filler-free silicone lining (boot) was then removed, leaving an
internal sac surface that is a blood contacting surface (FIG. 7). The
blood sac was then fitted into a rigid case of a blood pump.