Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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1BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to an artificial blood vessel
composed of polytetrafluoroethylene, and more specifically, to
a vascular prosthesis of a tubular fibrous construction whose
inner surface consists of finer fibers than its outer surface,
which is expected to expedite the healing of patients after a
surgical operation.
2. Description of the Prior Art
Fabric prostheses composed of a knitted or woven
fabric of DACRON or polytetrafluoroethylene are now utilized, and
where their inner diameters are relatively large, they are gaining
a considerably high degree of success. In particular, good
results have been obtained with vascular prostheses for arteries
which have an inner diameter of at least about 7 mm. Despite this,
few small inner diameter arteries are clinically acceptable. In
venous applications, small inner diameter prostheses show a
lower patency rate than in arterial application. The rate of
blood flow in veins is smaller than in arteries, and to prevent
thrombosis, it is important for artificial veins to inhibit
platelet adhesion. This requirement is not fully met by
presently available artificial veins.
Some tubings made of stretched or expanded polytetra- -
fluoroethylene have been demonstrated to be clinically useful
as vascular prostheses for arteries and veins. This is described,
for example, in Soyer et al., "A New Venous Prosthesis", Surgery,
Vol. 72, page 864 (1972), Volder et al., "A-V Shunts Created in
New Ways", Trans. Amer. Soc. Artif. Int. Organs, Vol. 19, p. 38
~1973), Matsumoto et al., "A New Vascular Prosthesis for a Small
Caliber Artery", Surgery, Vol. 74, p. 519 (1973), "Application of
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1 Æxpanded Polytetrafluoroethylene to Artificial Vessels",
Artificial organs, Vol. 1, p. 44(1972), Ibid., Vol. 2, p. 262
(1973), and I _ .,Vol. 3, p. 337 (1974), Fujiwara et al., "Use of
Goretex Grafts for Replacement of the Superior and Inferior
Venae Canal", The Journal of Thoracic and Cardiovascular Surgerx,
Vol. 67, p. 774 (1974), and Goldfarb, Belgian Patent No. 517,415.
The results of these clinical experimments are summarized
below.
When a suitable porous prosthesis is implanted as a con-
10 duit within the arterial system, the fine pores are clogged byclotted blood, and the inside of the prosthesis is covered with
the clotted blood layer. The clotted blood layer is made up of
fibrin, and its thickness varies according, for example, to the
material of the prosthesis, and the surface structure of the pros-
thesis. Since the thickness of fibrin approaches 0.5 to 1 mm when
a knitted or woven fabric of DACRON or polytetrafluoroethylene is
used as the prosthesis, success is achieved only with those blood
vessels which are not occluded by this increase in the wall thick-
ness by the fibrin layer (that is, arteries having an inside dia-
20 meter of 5 to 6 mm or more). Generally, knitted or woven prosthesishaving smaller inner diameters have not been successful.
A polytetraflUoroethylene tubing which has been
stretched has a microstructure composed of very fine fibers and
nodes connected together by the fibers. The diameters of the
fibers vary depending on various stretching conditions, and can
be made much smaller than fibers of the knitted and woven fabrics
mentioned above.
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1 It has been confirmed clinically that when a structure
composed of fibers and nodes is expressed in terms of pore si2es
and porosities, or fiber lengths and nodular sizes, a polytetra-
fluoroethylene tubing having a pore size of from about 2 ~ to
about 30 ~ (pore size~s below about 2 ~ are undesirable~, a por-
osity of about 78% to about 92%, a fiber length of not more than
about 34 ~ (fiber lengths of about 40 ~ to about 100 ~ are
undesirable), a nodular size of not more than about 20 ~, and a
wall thickness of about 0.3 mm to about 1 mm exhibits a high
patency rate without substantial occlusion, by fibrin deposition.
It has been reported, however, that venous prosthesis
shows a much lower patency rate than arterial prosthesis, and
does not prove to be entirely satisfactory for prosthetic pur-
poses. It has also been reported that when the vascular pro-
sthesis has too high a porosity, a tearing of the prosthesis by
the suture used in joining the prosthesis with the vessel of the
patient tends to occur.
SUMMARY OF THE INVENTION
A primary object of this invention, therefore, is to
provide a vascular prosthesis of a stretched polytetrafluoro-
ethylene tubing inwhich the fibrous structure at the inside sur-
face is made of finer fihers than the fibrous structure at the
outside surface.
Another object of this invention is to provide a vas-
cular prosthesis of a stretched polytetrafluoroethylene tubing
in which the fibers on the outside surface have a diameter at
least two times larger than the fibers on the inside surface so
as to prevent a tearing of the tubing in the longitudinal dir-
ection by the suture in the junction operation.
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1 In the healing of the patient after implantation, the
outer periphery of the polytetrafluoroethylene tubing is first
enveloped by the connective tissue and organizes, and afterwards
the fibrin layer on the inner surface of the tubing organizes. At
this l:ime, there is established a continuity of vessels with the
neoinl:ima of the intimas of the host's vessel at both ends extend
to the inner surface of the vascular prosthesis, and simultaneously,
the fibrin layer is replaced by the fibrous tissue which has
entered the prosthesis through the fine pores from the periphery
10 thereof. Furthermore, after a certain period of time, the neo-
intimas at the inner surface are connected firmly to the connective
tissue lining the outer wall of the prosthesis, thereby completing
the formation of an artery. It is known that this artery formation
requires a period of usually about 4 to 6 months. It is known on
the other hand that with vascular prostheses implanted in veins,
the rate of entry of the connective tissue from the periphery thereof
is slower than for arterial implantation.
Still another object of this invention is, therefore, to
provide a vascular prosthesis of a stretched polytetrafluoroethylene
20 tubing in which the pores on the outside surface are made larger
than the pores on the inside surface thereby to increase the rate
of entry of the connective tissue from the outer periphery. The
smaller size of the pores of the inner surface is believed to reduce
the surface stagnation of blood flow, with the result that platelet
adhesion is reduced and the amount of thrombus formation at the
inner surface decreases, as a result of which the fibrin layer is
very thin and the thickness of the neo-intima on the inner surface
is decreased when compared to the thickness of a similarly di-
mensioned prior art vascular prosthesis.
A further object of this invention is to provide a
vascular prosthesis of a stretched polytetrafluoroethylene tubing in
which the inside surface fibrous structure is finer than the outside
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1 surface fibrous structure, thereby allowing the connective tissue
from the outer periphery to grow and develop fully, and conse
quentl~supplying enough nutrient to the neo-intima formed at the
inner surface to prevent the calcification in the prosthesis
wall that may otherwise occur due to degenerative change with
the lapse of time, thus increasing the patency rate of the pro-
sthesis after implantation.
The prosthesis in accordance with this invention has
a microstructure of fibers and nodes which are produced by
IO stretching a tubing of polytetrafluoroethylene or a copolymer com-
prising tetrafluoroethylene and one or more other olefin mono-
mers or a polymer blend of polytetrafluoroethylene and one or
more other polyolefins of commercially available "fine powder"
grades in at least one direction and then heating at least the
outer surface of the stretched tubingwhile restraining it in the
stretched state to a temperature of at least about 327c(thesInter-
ing temperature of PTFE) but preferably not above about 3~0C
(sintering)while imposing a temperature gradient across the wall
of the tubing.
In a preferred embodiment, the invention provides a
tubular vascular prosthesis of a composite structure having a
pore size of 1 ~ to 5 ~ at the inside surface and at least 3 ~
at the outside surface and an average fiber diameter of 0.1 ~ to
2 ~ at the inside surface and an average fiber diameter at the
outside surface of at least 2 times the value at the inside sur-
face, and the entire prosthesis is defined by a porosity of 70
to ~5% and a fiber length of not more than 40 ~ by stretching
(in the linear directionl at a stretch ratio of preferably about
100 to about 500~ and expanding in the radial direction at a
stretch ratio, followed by the above described sintering step of
about 20 to about 200% radially. Such a vascular prosthesis has
enhanced junction tear strength in the implanting operation, and
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1 permits a thin neo-intima to form on the inner inner surface of the
prosthesis after implantation. The inner cavity is not occluded,
and t:he prosthesis has a high rate of patency. Porosity as de-
scribed herein is determined by measuring the specific gravity by
the method of ASTM D276-72 and the pore size distribution and
bubb:Le point as deseribed herein are determined by the method of
ASTM F316-70.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
The objects and significance of the present invention
will beeome apparent from the following detailed deseription
taken in eonjunetion with the aecompanying drawings in whieh:
Figure 1 is a sehematic view of a vascular prosthesis
that has been implanted;
Figure 2 is a scanning type electron mierophotograph
of the inner surfaee of a vaseular prosthesis of polytetrafluoro-
ethylene in aeeordanee with this invention that has been stretched
only in the linear direetion.
Figure 3 is a seanning type eleetron microphotograph of
the outer surface of the same vaseular prosthesis;
Figure 4 is a scanning type electron microphotograph
of the inner surface of a similar vaseular prosthesis whieh has
~een ~oth stretched linearly and expanded radially; and
Figure 5 is a scanning type electron microphotograph of
the outside surfaee of the same vaseular prosthesis as shown in
Figure 4.
DETAILED DESCRIPTION OF THE INVENTION
.
Turning now to the figures, Figure 1 sehematically
shows the wall in eross section of a prosthesis in cross section
in order to describe the healing eondition after a lapse of 8 to
10 months from the implantation of the prosthesis in a part of a
femoxal artery.
The wall 1 of the prosthesis has an inside surface 2
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1 and an outside surface 3, and a neo-intima 4 uniformly covers
the inside surface 2. On the other hand, a connective tissue 5
composed mainly of a collagen substance adheres firmly to the
out~ide surface 3, and fibroblast growth and capillary ormation
are observed. The fibroblasts contain a spherical nucleus 10,
and are uniformly distributed on the tubular wall 1 as black dots.
The tubular wall of the prosthesis is a composite structure com-
posed of irregularly-shaped nodes 9 and fine fibers ~not shown)
connecting the nodes together.
Figures 2 and 3 are scanning type electron microphoto-
graphs ~1,000 x magnification) of the inside surface 2 and the
outside surface 3 of a prosthesis in accordance with the inven-
tion that has been stretched linearly but not expanded radially.
The nodes 9 composed of polytetrafluoroethylene are interconnected -~
with a number of fibers 11 which are aligned substantially at
right angles to the long-axis direction o~ the ellopsoidal nodes
9. The diameter of the fibers 11 at the inside surface 2 (Fig-
ure 2) of the prosthesis of this invention is not more than 1/2
of the diameterof the fibers 11 at the outside surface 3 ~Figure
3), and in these photographs, the fibers have a diameter of 0.5
to 1.0 ~ at the inside surface, and 1.0 to 3.0 ~ at the outside
surface.
Figure 4 is a scanning type electron microphotograph
~magnification 40Q x) of the inside surface of a biaxially
stretched (i.e., linearly and radially)tubing of polytetrafluoro-
ethylene in accordance with the present invention. It can be
seen from the microphotograph that nodes 9 and fibers 11 of the
polytetrafluoroethylene are both reduced in dimension. The
fibers 11 have a diameter of 0.1 to 0.6 ~.
Figure 5 shows the outside surface of the same pro-
sthesis as shown in Figure 4.
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1 Descriptions with regard to the diameter of each fiber
and the average diameter of the fibers are given below. The
diameters of the individual fibers under a microscope vary
considerably according, for example, to the selection of visual
field, and the manner of developing the photograph of a sample.
The number of fibers appearing in one photograph in Figure 2 or
3 is several hundred, and several fibers aligned in a slightly
deviating manner in the planar direction are overlapping and
look as if they are one thick fiber. For this reason, in order
to determine the average fiber thickness, the diameters of at
least 3,000 fibers must be measured on the basis of at least 10
photographs, and then an average value of the diameters calculated.
At this time, experts in photographic examination can see
relatively easily whether a number of fine fibers are aligned in
parallel, or whether they form one coalesced thick fiber. In the
case of an assembly of fine fibers, transmission (transparency)
increases in the planar direction, and the thickness of the
fibers is not perceived. However, a coalesced thick fiber can
be clearly detected using scanning type electron microphotograph
as a fiber having a thickness. Hence, in determining the average
fiber diameter, fibers aligned in a planar direction and having
a small thickness must be excluded from the calculation, and
only the diameters of distinguishable fibers must be summed to
arrive at the average.
In order to stretch and expand tubings of polytetra-
fluoroethylene, the methods described in Japanese Patent Publi-
cation No. 13560/67 and U.S. Patent 3,953,566 can basically be
utilized. For example, about 15 to 40 vol% of a liquid lubricant
such as mineral oil, liquid paraffin, naphtha, etc., is mixed
with a fine powder ~e.g., a powder having a particle size of about
10~3~403
1 0.1 to about 0.5 ~ and a surface area of about 5 to about 15 m2/g)
of polytetrafluoroethylene, and the mixture extruded into a tubular
form using a ram-type extruder. Any type of polytetrafluoro-
ethylene can be used in this invention and those having a molecular
weight of about 2,000,000 to about 4,0C0,000 are preferred. The
tubing is then stretched in at least one direction while it is
heated at a temperature below the sintering temperature (i.e., about
327C~. Then, while the tubing is fixed so that the tubing does not
shrink, it is heated to a temperature of at least about 327C to set
10 the stretched and expanded structure and thereby to form a tubing
- having increased strength. Without modifying this procedure, how-
ever, a tubing in which the fibrous structure differs between the
inside surface and the outside surface cannot be obtained. In order
to obtain the structure in accordance with this invention, the tubing
should be heated from its outer periphery while being forcibly
cooled at its inside surface to form a temperature gradient through
the thickness of the tube wall increasing in temperature toward
the outer periphery during the sintering process. For this purpose,
the inside surface of the tubing is continuously exposed to cooling
20 air at a temperature ranging from room temperature (about 20 to
30C) to about 327C by continuously introducing such air into the
inside cavity of the tubing either forcibly or by a continuous
pressure reduction in the inside cavity of the tubing in such manner
that the outside surface of the tubing is heated to a temperature of
at least 327C. The inner surface may or may not be heated to
the sintering temperature. However, the inner surface must always
be at a lower temperature than the outer surface during the sintering
process.
Expanding of the tubing in the radial direction thereof
can optionally be performed continuously by reducing the pressure
surrounding the tubing. This may be performed simultaneously with
the lengthwise or linear stretching, but is preferably performed
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1 separately, after linear stretching but before sintering.
Naturally, the number, length, diameter, etc., of fine
fibers formed vary depending on the degrees of stretching and ex-
pansion in the longitudinal and radial directions respectively, and
can be! appropriately selected depending on the desired porosity,
pore size, softness, and tear strength. When the degrees of stretch-
ing and expanding are approximately equal, the fine fibers are uni-
formly distributed radially from spherical nodes, and despite this,
the directions of fiber alignment differ between the inside surface
10 and the outside surface of the tubing. If either of linear stretch-
ing or radial expanding is carried out to a substantially greater
degree than for the other, fine fibers in the direction of higher
stretch or expansion are longer and larger in number. However, but
in a direction at right angles to that direction, the fibers are
shorter and fewer in number.
It can be ascertained from electron-microscopic examination
that the size of the nodes and the diameter of the fibers in a
tubing subjected to stretching and expansion in two directions
show greater changes than those of a tubing subjected to stretching
20 or expansion in only one direction. It can be seen particularly
that the fibers are distributed in a more radial direction at the
inside surface than at the outside surface.
With increasing stretch ratio, the size of the nodes de-
creases progressively. When the tubing is stretched in one direction,
the nodes have the form of elongated ellipsoids. But after treat-
ment in two directions, the size of the nodes becomes 1/3 to 1/10
of that after a stretching in one direction, and in many cases, the
nodes assume a substantially spherical form.
The diameter of the fibers after stretching in one
30 direction is almost constant at 0.5 to 1 ~ regardless of the
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1 stretch ratio, but treatment in two directions causes the fibers
to decrease in diameter to 1/3 to 1/5, whereby the number of
fibers increases correspondingly.
The temperatures used for stretching, expanding and
sintering are described below.
Stretching or expanding causes the tubing to attain a
dimension and a shape which are different at least from the
dimension and shape before the treatment. At least an external
force must be exerted in order to cause this change. Similar to
thermoplastic resins, in general, this force tends to be lower
at higher tube temperatures and higher at lower tube temperatures.
This external force required for deformation is comparable to
the strength which the tubing itself possesses as a result of
being oriented in fibrous form by extrusion. The strength built
up by the extrusion-forming depend-; greatly on the extruding
conditions. When the temperature for deformation of the tubing
by stretching or expanding is below a certain limit, the
external force required for deformation is higher than the
strength of the tubing, and breakage increases during deformation.
On the other hand, when the temperature is above this certain
limit, the external force for deformation becomes lower than the
strength of the tubing, and breakage abruptly decreases.
Accordingly-, in the deformation of the tubing, there is a lower
limit to the temperature depending on the extruding conditions.
The same tendency exists in the rate of deformation
by stretching or expanding. When the rate of deformation
increases, the external force required for deformation increases.
Thus, in order to prevent a breakage of the tubing, it is
necessary to heat the tubing at still higher temperatures.
The minimum temperature for deformation cannot be
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1 definitely set forth because the strength of the tu~ing varies
depending on the tube extruding conditions. Those skilled in
the art, however, can easily determine the minimum deformation
temperature.
The sintering step comprises a heating, e.g., until
completely melted, of a stretched uniaxially, or stretched/ex-
panded biaxially tubing to a temperature of at least 327C while
the tubing is fixed so that shrinkage does not occur. A diff-
erence in the porous fibrous structures of the inside and out-
side surfaces of the tubing can be achieved by heating the out-
side of the tubing while cooling the inside surface of the tubing
by passing air through the cavity of the tubing. By increasing
the amount of air passed through the cavity of the tubing or
reducing the temperature of the air, it is possible to heat the
outside surface of the tubing to a temperature of at least 327C
while at the same time maintaining the inside surface of the
tubing at a temperature below 327C. In such a tubing, only the
outside surface is sintered, and the inside surface remains un-
sintered. Thus, the shapes and sizes of the fibers and nodes
differ greatly between the inside surface and the outside surface.Alternatively, the inside surface of the tubing can be heated
to a temperature of above 327C by decreasing the amount of air
passed through the cavity of the tubing or increasing the temp-
~- erature of the air. This can also be accomplished by increasing
the length of the heating zone or increasing the heating zone
temperature. ~s a result, fibers at the outside surface of the
tubing are exposed to a temperature of at least 327C for long
periods of time, and, while initially they have the same struc-
ture ~particularly, diameter) as~the inside surface, they grad-
uall~ become thicker as those on a result of coalescence. ~or
example, four fibers are fused and coalesced together to form a
single fiber having a diameter twice that of each single fiber
before sintering.
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1 The thickness of the inside surface structure becomes
different from that of the outside surface structure by changing
the amount of cooling air passed through the cavity of the tubing
and th~e amount of heat supplied externally. Increasing the amount
of external heat supplied results in an increase in the outside wall
thickness of the thicker fibrous diameter or large pore size, and
if the amount of cooling air is increased, the inside wall thick-
ness of the thinner fibrous diameter or small pore size increases.
In this case, however, the size of the nodes does not change, and
10 therefore, the size of the nodes at the outside surface is sub-
stantially the same as that of the nodes at the inside surface.
As shown in Figure 4, when a longitudinally stretched
tubing is further expanded in its radial direction, the size of
nodes 9 and the diameter of fibers 11 change drastically.
The nodes 9 in Figures 2 and 3 are ellipsoidal and have
a relatively uniform size. But in the biaxially stretched and
expanded tubing, nodes 9 formed as a result of uniaxial stretching
are divided into smaller portions depending on the degree of
expansion, and fibers 11 occur among the separated nodes. The
20 fibers 11 in Figure 2 or 3 have a diameter of approximately
0.5 ~ to 2 ~, although the diameter varies somewhat depending
on the conditions of tubing preparation. However, the fibers 11
after stretching and expanding biaxially as in Figure 4 have a
diameter of 0.1 ~ to 0.5 ~. As a result of expansion biaxially,
the diameter of the fibers 11 between the nodes 9 becomes 1/3
to 1/5 of that of the fibers of tubing that has been stretched
only uniaxially. Consequently, a single fiber 11 that occurs after
the uniaxial expansion is again divided into 10 to 30 fine
` fibers as a result of the second, radial expansion.
Figure 4 shows the inside surface fibrous structure
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1 of the biaxially expanded tubing. Just as in the relation between
Figures 2 and 3, the fibers at the outside surface attain a
diameter at least two times larger than that of the fibers at
the inside surface by ~intering the tubing while forcibly cooling
the inside surface.
The fiber alignment of the inside surface can be made
drastically different from that of the outside surface by
increasing both the amount of cooling air passed through the
cavity of the tubing and the amount of heat supplied externally.
10 An example is shown in Figure 4 (inside surface) and Figure 5
(outside surface).
The fibrous structure at the outside surface of the
tubing is less dense than that at the inside surface, but each
fiber is thicker and this produces various effects as described
below.
Firstly, this serves to increase the mechanical strength
of vascular prostheses made of such a tubing whereby preventing
a suture from tearing the prosthesis in the longitudinal
direction during implant surgery. It is possible for only
20 the inner surface fibrous structure of the tubing to act
as a bag-like receptacle for transporting blood. But for
application to arteries, the tubing must withstand a blood
pressure of about 120 mmHg, and should not be compressed by
elastic fibroblasts that develop on the outer periphery thereof.
In addition, the tubing must withstand suturing at the time of
surgical operation. The force required to cut the fibers can be
increased by increasing the diameters of the fibers at the
outside surface of the tube, and increasing the number of fibers
that are aligned at right angles to the direction of possible
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1 tearing. In particular, a tubing that has been biaxially
stretched an~ then sintered to increase the fiber diameter has
improved tear strength.
Secondly, as a result of decreasing the dimension of
the fibrous structure at the inside surface of the vascular
prosthesis made of the polytetrafluoroethylene tubing, its sur-
face resistance to flow of blood is reduced, and consequently,
platelet adhesion is reduced. Platelets which have contacted
the surface of the prosthesis and adhered thereto aggregate rever-
sibly with adenosine diphosphate and calcium ion, after which
they become irreversibly adhered and form a thrombus together
with fibrin. The thrombus layer becomes thinner as the amount
of platelets that have adhered decreases. The thickness of the
initial thrombus layer increases as the fibrin deposits onto it,
and this finally causes occlusion. In order, therefore, to obtain
vascular prostheses free from occlusion, it is essential to
decrease the thickness of the initial thrombus layer. This
effect is more pronounced in veins than in arteries. In other
words, a reduction in the thickness of neo-intimas on the inner
surface of the prostheses can be expected.
As a third effect, fibroblasts rapidly enter the pro-
~thesis from the outer periphery of the prosthesis and grow
fully as a result of the increase in the size of the openings in
! the outer surface fibrous structure of the prosthesis. It is
already known that fibroblasts readily enter a vascular prosthesis
made of a knitted or woven fabric of Dacron, or polytetrafluoro-
ethylene, etc., because such a prosthesis has a tubular wall of
a loose structure. However, bleeding occurs through the wall
immediately after implantation, and this results in an increase
in the thickness of the fibrin layer on the inner surface
of the prosthesis. Further increase leads to calcification and
occlusion. In a prosthesis made of polytetrafluoroethylene haviny
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108~4S13
1 the same fibrous structures both at the outside surface and at
the inside surface, it is essential to decrease the thickness of
the fibrin layer that results from platelet adhesion by making
the pore size sufficiently small to prevent bleeding, and there-
fore,t:he easeofentry of fibroblasts from the outer periphery of
the pxosthesis must be sacrificed somewhat.
When the fibrous structure differs between the outside
surface and the inside surface of a prosthesis as defined by its
fiber diameter, i.e., the spaces between the fibers, or pores,
at the outside surface being at least two times that at the
inside surface, as in the present invention, the thickness of
the fibrin layer at the inner surface can be decreased, and at
the same time, entry of fibroblasts from the periphery can be
facilitated. Furthermore, nutrient supply to the neo-intimas
occurring at the inner surface of the prosthesis can be effected
sufficiently through capillaries which densely develop on fully
grown fibroblasts. Thus, it is possible to greatly reduce cal-
cification of the neo-intimas that may result from nutritional
deficiency.
In arterial prostheses, nutrition can be effected not
only through capillaries at the fibroblasts, but also from the
blood within the cavity of the prostheses. However, in venous
prostheses, nutrition from the blood can hardly be expected, and
reliance must be exclusively on the capillaries present on the
fibroblasts that have come through the outer periphery for nut-
rient supply. ~ccordingly, the entry of fibroblasts from the
outer periphery of vascular prostheses is important not only for
the formation of neo-intimas, but also for preventing calcifi-
cation of the neo-intimas which may be caused by a nutritional
deficiency after implantation and thereby for increasing the
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1 patency rate of the prosthesis after operation. This is more
important in venous prostheses.
The relation between the mean pore size and the length
and diameter of fibers among the nodes in a microstructure con-
sisting of very fine fibers of polytetrafluoroethylene and nodes
connected to one another by the fibers is described below.
If the length of each fiber connecting nodes is Q and
the distance between two fibers is d, then the sectional surface
of a rectangle surrounded by the two fibers and the nodes has
0 the following relation with regard to the fluid dynamical e~ui-
valent pore size y.
2 = 1 ~ 1
y Q d
Since Q is usually far larger than d, y becomes approx-
imately equal to 2d. Ultimately, the structure can be described
as a porous structure having a fluid dynamical equivalent pore
size twice the interfiber distance. It is believed that the
number of fibers occurring between two nodes is approximately
the same for both the outside surface and inside surface of the
tubing (before sintering~. Tn order for fibers at the outer
surface to attain a diameter at least two times larger than those
at the inside surface as a result of sintering at 327C or higher
while cooling the inside surface, at least four fibers must be
coalesced to form one thick fiber. At this time, the distance
D between adjacent large diameter fibers becomes approximately
four times the distance d between fine fibers, and as a result,
the fluid dynamical equivalent pore size becomes about fourfold.
Since the distribution of fibers between nodes is not planar as
in the above calculation but three-dimensional, the equivalent
pore size of the outside surface does not become four times the
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1 equivalent pore size of the inside surface. However, the pore
size is certainly at least two times that of the inside surface.
A certain relation exists between the porosity and
fiber length of the wall of a prosthesis, and there is a tendency
for the length of fiber to increase with increasing porosity.
Vascular prostheses must have pore sizes which are small enough
to keep the blood during circulation from leaking through the
tubular wall, and are large enough to permit entry of fibroblasts
from the outer periphery without obstruction. In order to meet
this requirement, the porosity and the fiber length should be
within certain specified ranges.
The length of fiber increases approximately proportion-
ally to the ratio of stretch in the longitudinal direction, and
the ratio of expansion in the radial direction, of a tubing
formed by a ram extruder. Because the fibers occur when the
structure forming the original tubular wall is progressively
split into the nodes, both ends of the fibers join the nodes.
Spaces surrounded by the nodes and the fibers become pores. The
porosity of the tubing is low when the nodular size is large and
the fiber length is small, and the porosity is high when the
nodular size is small and the fiber length is large. When the
tubing is stretched biaxially, the porosity of the tubing can be
much increased than the porosity of a tubing which is stretched
uniaxially and has the same fiber length.
If the porosity is too high, there is a possibility of
blood leaking, and tearing of the tubular wall of the prosthesis
by the suture during suturing operation can occur. Prostheses
having a porosity of more than 96% are not practical, and those
having a porosity of less than 60% have a short fiber length and
prevent entry of fibroblasts after implantation. The most pre-
: --19--
' . ' ' ~ .' . . ' .~ ., ' ~
~08~403
1 ferred porosity is within the range of 70% to 95%. It has been
clinically confirmed that the preferred range somewhat differs
between arterial prostheses and venous prostheses.
As described hereinabove, the fiber length is proport-
ional to the porosity, and prostheses defined by a fiber length
of less than about 40 ~ are preferred in this invention.
Another significant factor for growing neo-intimas on
the inside surface of prostheses and preventing them from de-
generatively changing with time is the thickness of the tubular
wall of the prostheses. With prostheses comprising a fibrous
structure only at the inside surface, there is a certain limitto the distance through which fibroblasts enter the prostheses
from the outside surface. Consequently, the distance over which
nutrient is supplied is also limited. It has been found clin-
ically that the maximum thickness of the tubular wall is about
O.8 mm. In the present invention, the wall thickness of the
fibrous structure at the inside surface and that of the fibrous
structure at the outside surface can be varied depending on the
conditions of preparation of the tubing. For example, by adjusting
~ the thickness of the inside surface layer to 0.4 mm and the out-
side surface layer to 0.4 mm, the distance of fibroblast entry
can be adjusted substantially to 0.4 mm.
The prostheses defined by the properties described
hereinabove serve to facilitate the suturing technique in oper-
ation and expedite the healing of patients after operation.
Since neo-intimas are maintained free from degenerative change
with their use, occlusion does not occur. Accordingly, the pro-
stheses in accordance with this invention contribute greatly to
not only to surgery but also to industry.
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.
1081403
1 The following example is given to illustrate the
invention in greater detail.
EXAMPLE
2 kg of a commercially available polytetrafluoroethylene
(TEFLON 6, a trademark for a product of E.I. du Pont de Nemours
& Co.) and 0.52 kg of a white oil (Sumoil P-55, a trademark for
a product of Muramatsu Sekiyu Kabushiki Kaisha) were mixed, and
the mixture was formed into a tubing having an inside diameter
of 4 mm and an outside diameter of 6 mm using a ram-type extruder.
- 10
The tubing was then heated to a temperature below the boiling
point of the white oil (i.e., 180 - 250C) to remove the white
oil. The tubing (20 cm long) was rapidly stretched to a length
of 100 cm while heating the tubing at 200C. The stretched
tubing was fixed at both ends to prevent shrinkage. At the same
time, a pipe for introducing a cooling air was connected to one
end of the tubing, and the other end was sealed. The tubing was
placed in a furnace, and the temperature of the furnace was
gradually increased. When the temperature reached 320C, air
(at 200C) at a pressure of 0.4 kg/cm2 was abruptly introduced,
and while maintaining the air at this pressure and at the tem-
perature of 200C, the temperature of the furnace was increased
to 440 C at the highest. After confirming the temperature was
440C, the tubing was rapidly cooled to room temperature (about
20 - 30C).
The inside and outside surfaces of the resulting
tubing were photographed using a scanning type electron micro-
scope (1,000 x), and the micr/ophotogra,phs obtained are shown in
~` ~efer ~ec~
Figures 2 and 3. It was oonfirmcd that the fiber diameter was
0.5 to 1.0 ,u at the inside surface and 1.0 to 3.0 u at the outside
surface. The fiber length was 15 to 30 ~u both at the inside and
- 21 -
.
~08~403
1 outside surfaces. The tubing as a whole had a porosity of 81~.
For comparison, a tubing was produced under the same
conditions as set forth above except that air was not introduced
into the inside cavity of the tubing. The resulting tubing
showed a similar structure to Figure 2 at the inside and outside
surfaces, but the porosity had decreased to 76%. The pore size
of the tubing in this comparison was measured, and it was found
that its bubbling point determined using isopropyl alcohol
(according to ASTM F316-70) was 0.15 kg/cm , and its mean pore
size (according to ASTM F316-70) was 2.5 ~. Hence, the comparison
tubing was believed to have much the same pore size as the
inSide surface of the tubing shown in Figure 2.
It was impossible on the other hand to directly measure
the pore size of the outside surface in Figure 3. From the fiber
diameter and the interfiber distance determined ~rom Figure 3,
the means pore size of the outside surface was considered to be
about four times (i.e., about 7 ~u) that of the inside surface.
The tubing stretched to five times at 200C as set
forth above was connected to a pipe for supplying cooling air.
When the temperature of the furnace became 325C, air at a
pressure of 0.9 kg/cm2 was introduced. The tubing was thus
expanded to an outside diameter of 8 mm. After increasing the
temperature of the furnace to 480C at the highest, the tubing
was rapidly cooled. The fiber diameter of the resulting tubing
was 0.4 to 0.8 ,u at the inside surface and 1 to 3 ~ at the
outside surface, and the tubing as a whole had a porosity of 89~.
Air at a pressure of 1.5 kg/cm2 was introduced into
the tubing stretched five times at 200C as set forth above
when the furnace temperature reached 330C. This resulted in
the expansion of the outside diameter of the tubing to 16 mm.
- 22 -
~081403
1 The air pressure was reduced to 0.4 kg/cm2,and the furnace
tempexature was increased to 465C at the highest, after which
the tubing was rapidly cooled. The inside surface of the
resulting tubing was as shown in Figure 4. The fiber diameter
of the inside surface was 0.1 to 0.2 p, and the tubing as a
whole had a porosity of 93~.
While the invention has been described in detail and
with reference to specific embodiments thereof, it will be
apparent to one skilled in the art that various changes and
10 modifications can be made therein without departing from the
spirit and scope thereof.
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