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This invention is in the field of puncturable, self-resealing septum
closure mechanism for containers; more specifically, this invention
relates to septums especially useful in medical applications, e.g., for
sealing subcutaneously implanted drug delivery devices, particularly
liquid delivery devices which are refillable via a hypodermic needle or
conduit.
It is known in the art of drug therapy to implant a fluid delivery device
beneath the skin, i.e., a penetrable receptacle, depot, port, hollow
capsule or container. The receptacle is filled from time to time by
hypodermic needle injection with a multidose quantity of a drug delivered
through the wall of the receptacle or through a discrete penetrable
area/septum which is part of the wall. The drug is then released slowly
and continuously, e.g., via an outlet catheter or drug permeable membrane,
to a site in the body requiring medication. Using this technique, the drug
is supplied to the site relatively undiluted by body fluids, and the drug
is more effective than when injected intramuscularly or into the blood
stream. This technique is especially useful with certain cytotoxic drugs
used in cancer chemotherapy and also has the advantage of decreasing the
number of times the skin must be punctured, thereby reducing the risk of
trauma and infection. The device also can be used to collect a body fluid,
and the fluid can be withdrawn by needle.
One of the problems with implantable drug delivery devices is the tendency
of the devices to develop leaks after being punctured. Sometimes a needle
will remove a core of the septum material when the needle is removed, or
the structural integrity of the septum material simply breaks down after
multiple needle insertions. Regardless of the septum failure mechanism, it
will be evident that drug leaks are unacceptable.
Various steps have been taken to construct a drug delivery port which can
be punctured, but which reseals upon needle removal and does not leak
after many punctures. Silicone rubber has been useful in this regard, and
under the proper circumstances it can be punctured, but reseals itself.
Elastomeric materials, such as silicone rubber, have been employed as the
penetrable wall material in several drug delivery ports described in the
prior art. Such applications are reported in U.S. Pat. Nos. 3,310,051;
3,640,269; and 4,710,174, for example. However, it has been known for some
time that walls so constructed tend to develop leaks, especially if the
drug is added to the port under some pressure from the syringe or an
external infusion pump. It is known that a pressure of 60-100 psi can be
developed by an individual operator injecting liquid into a port using a 2
cc syringe. These pressures can easily deform, expand, and cause an
unsupported silicone rubber depot to rupture. This problem has been
enunciated in U.S. Pat. No. 4,190,040, for example.
In meeting this problem, various modifications have been made. For example,
textile materials can be incorporated to strengthen the elastomeric wall
material according to U.S. Pat. No. 3,971,376. Alternatively, a wall
structure utilizing a silicone gel sandwiched between discrete silicone
rubber sheets is disclosed in U.S. Pat. No. 4,190,040. The converse, a
silicone rubber sheet coated with a flexible silicone layer is disclosed
in U.S. Pat. No. 4,710,167. All of these modifications tend to restore or
improve the elastomeric sealing quality of the wall inherent in the
material of which it is constructed. However, in order to remain
self-sealing, the wall must be relatively thick, which detracts from the
flexibility and compliance of the drug depot, as well as the small size
required in an implanted port. In addition, care must be taken to use only
small diameter needles.
In another approach to the problem, it is disclosed in U.S. Pat. No.
4,543,088 that the interior of the drug chamber within the depot can be
designed in such a way that fluid pressure within the chamber, tending to
bulge it, creates compressive forces which seal needle punctures in the
depot wall. However, the resultant depot has thick, heavy walls, producing
patient discomfort.
In yet another attempt to solve the problem, a wall of the drug delivery
depot may be provided with a discrete penetrable septum area within which
all needle punctures are received. Discrete septums are generally
incorporated into depots having otherwise hard, impenetrable walls. Such
septums are described in U.S. Pat. Nos. 4,465,178 and 4,673,394. In these
applications, an elastomeric septum, typically silicone rubber, is affixed
to the depot in a physically compressed state, so that punctures are
resealed, not only because the elastomer inherently tends to fill the void
created as the needle is withdrawn, but also because of the external
physical forces acting upon it. The depots which utilize discrete septums
of this type are relatively noncompliant, leading to some patient
discomfort, due in part to the bulky components required to retain the
septum under the proper compressive forces. On the other hand, the
discrete septums generally provide reliable self-sealing even though the
drug is added to the depot under pressure, and there are few restrictions
on the size needle that can be used.
Thus, it is the primary objective of this invention to overcome the various
problems associated with the transfer of fluids to or from a penetrable,
sealed container using a hollow conduit. Although the invention is of
broad application to penetrable, sealed containers in general, it is
especially directed to the problems associated with implanted drug
delivery devices or conduits. Within this latter context, specific
objectives include providing a new septum material which overcomes the
structural weakness of unsupported silicone rubber and affords reliable
resealing after multiple needle punctures, as reliable as a discrete
septum under compression, but which does not simultaneously require that
the device be rigid and noncompliant. Another objective is to provide a
septum material which can be readily adapted and conformed to various
desired sizes and shapes. Yet another objective is the provision of a drug
delivery device which includes a large septum area, penetrable from many
angles, but which retains the reseal reliability and structural integrity
of septums maintained under compression, even when subjected to high
internal fluid pressures.
These objectives, and others not explicitly stated, are attained in a novel
material, one embodiment of which is a sheet-like consruction which
incorporates both the flexibility and conformability of a relatively thin,
resilient elastomeric depot wall with the reliable resealing associated
with a discrete elastomeric septum under compression. Other embodiments of
the novel material include various shaped articles, including drug
delivery devices, such as receptacles, ports and depots. The new material
is referred to herein as a "matrix" or "compound" septum, and the
construction includes (1) at least one penetrable, resilient, elastomeric
layer having front and back faces; (2) a plurality of webs having
peripheries framing perforations, each web being in contact with at least
one layer face; together with (3) means for urging the webs toward each
other, thereby compressing the layer without substantially obstructing the
perforations.
Thus, the septum of this invention, viewed face-on, resembles a matrix of
lines or the compound eye of an insect, each perforation of the web
framing an individual, penetrable, self-sealing cell in the matrix or
compound septum. Each cell of the resilient layer, under compression from
its framing web periphery, functions as an individual septum, the
resealing characteristics of which are taught in U.S. Pat. No. 4,464,178.
The features of the new matrix septum, as well as the manner of making it
and using it, will be clarified by reference to the drawings which
accompany this specification and to the detailed description which follows
.
In the drawings:
FIG. 1 is a diagrammatic perspective view of one portion of a matrix septum
material of this invention embodied in a sheet-like construction.
FIG. 2 is a top view of the septum material shown in FIG. 1.
FIG. 3 is a cross-sectional view taken along lines 3--3 in FIG. 2.
FIG. 4 is a perspective view showing an implantable drug delivery device
which includes a matrix septum material of this invention.
FIG. 5 is a cross-sectional view taken along lines 5--5 in FIG. 4.
FIG. 6 illustrates a method by which the matrix septum material for the
drug delivery device of FIG. 4 is made.
Referring now primarily to FIGS. 1-3, matrix or compound septum material 20
includes resilient, elastomeric, needle penetrable layer 25, which is
contacted on front face 26 by web 30 and on back face 27 by web 31. Means
50 are also provided for urging webs 30 and 31 toward each other,
compressing layer 25, producing a multi-septum matrix or compound septum.
The perforations 32 framed by the web periphery 34 create individual,
penetrable, self-sealing cells in the compound system.
With regard to layer 25, a number of materials are of potential use,
depending upon the application. Layer 25 must be a solid, i.e., it cannot
spontaneously flow, and it must exhibit reasonable tensile strength and
elongation and be capable of compression without permanent deformation
under the force applied to compress it. Natural and synthetic rubbers,
including butadiene polymers and copolymers, neoprene, chloroprene, and
the equivalents thereof, are all potentially useful where the matrix
septum material will be employed in general closure applications. Such
applications include the closure of containers containing sterile
materials, biologically dangerous agents, pyrophoric chemicals,
hygroscopic reagents, etc., which are liquid and are sampled from time to
time using a needle and syringe.
In medical applications, however, the choice of materials for layer 25 is
more limited, since the material must be medically acceptable for the
specific application. In the case of implantable devices, silicone rubbers
have won acceptance for use in drug delivery ports. Thus, layer 25 may be
constructed of suitable silicone rubbers, many of which are available
commercially, e.g., from Dow Corning Corporation, Midland, Mich., but
other medically acceptable elastomeric materials may also be employed. For
most infusion port applications the matrix septum of this invention
preferably incorporates a relatively soft silicone rubber, e.g., about
30-60 Shore A. This silicone rubber is to be distinguished from the
silicone gel described in U.S. Pat. No. 4,190,040, such gels being much
softer in general and exhibiting near zero tensile strength and
elongation. Layer 25 may be reinforced internally with an embedded, woven
polyester fabric or other fabric or screen, e.g., titanium screen.
The thickness of layer 25 will be tailored to the specific application. In
many infusion device applications layer 25 will be in the range 0.08-0.3
inch thick, e.g., 0.125 inch thick.
Webs 30 and 31 can each be made of the same material or different
materials, and the perforations 32 may or may not be of the same size or
shape. In addition, it is not necessary that the perforations in the webs
be in register. However, ease of fabrication is enhanced if the webs have
the same type of perforations and they are in register as shown in FIGS.
1-3.
Dependent upon the web material, the flexibility inherent in layer 25 may
or may not be retained in the matrix septum. Webs 30 and 31 may be made of
loosely woven natural or synthetic, including fibrous polymeric, organic
or inorganic fabric, especially fabric made with thread which is
relatively inelastic. In medical applications, for example, fabric made of
polyester thread is satisfactory, as are fabrics made from suture
materials, such as silk, but other fibers such as graphite or glass may
also be used. The thread denier and composition are selected so that the
web will undergo little or no stretching under the compressive force
applied to layer 25.
Another type of web material which may be used is metal wire screen. Such
wire screen may be made of any suitable medically acceptable metal, such
as titanium or stainless steel, for example. Standard grade type 316L
stainless steel wire cloth, which is available commercially, can be
employed with good results. Although such screen in various weave patterns
can be used, basketweave screen is very satisfactory.
The aforesaid types of webs, which are especially useful to make sheet-like
embodiments of the matrix septum materials, may also be used to produce
various three-dimensional shaped articles. Such articles can be producted,
e.g., by bending, folding or draping a preformed sheet-like matrix septum
and fastening it in place. Alternatively, such articles can be produced by
employing at least a nest pair of webs, which may be made of wire, for
example, and which reflect the desired shape, and inserting the
elastomeric layer between them. In any event, means are also provided for
urging the webs together, toward each other, in order to compress the
elastomeric layer between them.
The perforation size in webs may vary in the same way, whether made of
fabric or screen, or whether the matrix septum is sheet-like or an
arbitrary three-dimensional shape, depending upon specific details of the
application. The larger the perforation area, the thicker and/or softer
the elastomeric layer should be, and/or the greater the force urging the
webs toward each other. Thread or wire mesh with about 6-14 perforations
per inch and thread or wire diameters in the range of about 0.015-0.065
inch is satisfactory. With these mesh and web sizes, the perforations
generally range from about 0.040 to about 0.132 inch in length and width,
although the length and width of the perforations can differ if desired,
and the perforations need not be square, but they can be rectangular,
triangular, hexagonal, circular, planar, curved, etc. The size of the
perforations will, of course, be selected to pass the desired size needle
or conduit. Furthermore, there is no upper limit to the number of
perforations a matrix septum of this invention may contain, the number
only being limited by the physical size of the construction it is possible
to handle. As to the lower limit, it is only necessary that a matrix
septum of this invention carry at least one perforation.
In addition to the possibility that one or both of the webs can be made of
fabric, screen, or wire, it is also possible to construct either web of
acceptable perforated metal or plastic sheet. However, these materials in
general are less desirable, since the flat surfaces between perforations
act to impede transit of a needle. On the other hand, threads or wires
having round cross sections tend to deflect a needle which strikes them.
Webs made of fabric are more likely to lead to a matrix septum which is
very flexible than would the use of perforated plate webs. Wire or wire
screen webs can lead to relatively flexible or rigid matrix septums
depending upon the type and size of the wire. In general, it is preferred
that the areas of faces 26 and 27 which are performations as 32 be greater
than the areas which are web peripheries as 34.
A number of means may be employed to force webs 30 and 31 toward each
other, compressing layer 25. For example, webs 30 and 31, in contact with
the faces of layer 25, can be forced toward each other mechanically, e.g.,
in a press, compressing layer 25 at periphery 34 of each cell 28. The
amount of compression required will depend upon the nature of layer 25 and
the size of the perforations 32 in the webs 30 and 31. For example, a
silicone layer nominally 0.125 inch thick faced with webs of 0.020 in.
diameter stainless steel basketweave wire having perforations about 0.150
in..times.0.150 in. is compressed to about 0.080 in. at the periphery of
each cell, while the central portion of each cell is about 0.150 in.
thick.
With layer 25 forced into a compressed state, any of several different
means may be employed for maintaining the compression and urging the webs
toward each other, but without substantially obstructing the perforations.
For example, if the web is relatively stiff, e.g., wire screen, only the
outer edges of the webs need be welded or otherwise adhered together. In
another method, the webs can be sewn together through layer 25 at the
number of points sufficient to maintain the desired compression; in that
case, thread such as about 0.010 in. diameter stainless steel or
nickel/brass wire can be employed, but polyester, silk or other natural or
synthetic polymeric thread materials can also be used. Such sewing,
pulling the stitches uniformly tight, can also suffice to urge the webs
agaisnt layer 25 in the absence of external force applied to compress the
construction. Alternatively, rods 50 can be passed through layer 25 and
affixed to webs 30 and 31 by welding or adhesive bond 51; for example,
stainless steel rods in the range of about 0.010 in. to about 0.025 in. in
diameter can be used as shown in FIGS. 1-3. In addition, it may be
desirable to sew, wire, weld, glue, or otherwise attach webs 30 and 31
together circumferentially along the edge of the matrix septum, as
mentioned above.
Although the matrix septum material illustrated in FIGS. 1-3 includes a
single elastomeric layer and a pair of webs, each in contact with one face
of the single layer, the requirements of some resealable closures may
demand that more than one elastomeric layer be employed, i.e., that the
layers be stacked. In this event it may be desirable to contact, not only
each exposed face, but also unexposed faces of the stacked layers, with
one or more webs between the layers. That is, it may be desirable to
employ a plurality of webs, each web being in contact with at least one
layer face: e.g., webs between layers may be in contact with two faces.
Furthermore, in certain applications, e.g., applications in which the
turbulence or pattern of fluid flow across the matrix septum is critical,
it may be desirable to embed the matrix septum, i.e., one or both sides,
with a coating which smooths the surface. In this regard, a silicone
potting resin or curable coating may be employed.
In addition to the matrix or compound septum material described above,
which is of general use in sealing applications, this invention includes
implantable drug delivery devices which include the matrix septum
material. A drug delivery port of this invention is shown in FIGS. 4 and
5. Although drug delivery devices of this invention can take many shapes
and forms because of the versatility of matrix septum material 20, a drug
delivery port 60, in which drug reservoir 61 is shaped like a truncated
cone, is a desirable shape. Drug reservoir 61 is enclosed by matrix septum
20 and suture flange 62, drug outlet catheter 63 being provided to perform
its usual function. Matrix septum 20 is coated with silicone layer 66. It
will be noted the incorporation of matrix septum 20 permits needle 70 to
access the drug reservoir from almost any angle and with confidence that
the puncture will be reliably sealed when the needle is withdrawn.
The matrix septum material of this invention can be incorporated into a
drug delivery device or other arbitary three-dimensional article in a
number of different ways. One of these ways is illustrated in FIG. 6.
Preformed webs 30 and 31, desirably made of metal wire and sized to nest
in contact with elastomeric layer 25, are forced together, compressing
layer 25. The webs are urged toward each other after the force is removed
by welding the edges together along wire 65, which is led
circumferentially about the septum terminus. The septum terminus is
affixed to and against flange 62 with adhesive/potting resin 64.
Alternatively, the matrix septum material in sheet form can be affixed to
a truncated cone framework by sewing, etc. and reservoir 61 created by
attaching the framework to suture flange 62.
EXAMPLE 1
A circular piece of 0.125 in. thick silicone rubber made from Dow Corning
SILASTIC MDX-4-4210 Medical Grade Elastomer was compressed using pliers to
about 0.060 in. between two stainless steel, basket weave screens made
from wire 0.028 in. in diameter and having 0.097 in. square perforations.
While compressed, the screens were secured together at about every other
steel wire intersection using 0.009 in. diameter nickel/brass wires passed
through the silicone rubber, around the steel wire intersections on either
side of the silicone layer, and tied with square knots. The resultant
matrix septum material was formed into a dome, which was affixed to a
rigid plastic base to form an enclosed receptacle. A catheter-like outlet
tube was led into the receptacle, and the entire port was then potted in a
thin layer of the MDX-4-4210 silicone rubber. The receptacle was
pressurized via the outlet tube with air at 10 psi, and the port was
immersed in water; no air leaks were observed. The receptacle was then
punctured under water through the same 0.097 in..times.0.097 in.
perforation 20 times with a 19 guage Huber point needle. The port was
tested with air at 10 psi after each puncture and was found to not leak.
A device of the aforesaid type was tested for failure under pressure by
applying air at various increasing pressures to the receptacle through the
outlet tube; the device withstood 84 psi before a leak developed.
EXAMPLE 2
Silicone rubber sheet, 0.125 in. thick and the same as that employed in
Example 1, was formed into a dome-shaped receptacle. The receptacle was
affixed to a rigid plastic base, and an outlet tube was led into the
receptacle. The entire port was then potted in a thin layer of the same
silicone rubber. As in Example 1, the receptacle was pressurized via the
tube with air at 10 psi, and the port was immersed in water. No leaks were
observed, but after a single puncture of the receptacle with a 19 guage
Huber point needle, the receptacle would not retain air at 10 psi.
A device of the same type swelled markedly under the application of
increasing air pressure and ruptured at 12 psi.
EXAMPLE 3
A construction consisting of silicone gel, 0.120 in. thick (Dow Corning
Q7-2167/Q7-2168 in 3:1 ratio), was sandwiched between 0.040 in. thick
sheets of Dow Corning SILASTIC MDX-4-4210 Medical Grade Elastomer cured
inplace. The construction was formed into a dome-shaped receptacle and
affixed to a rigid base; an outlet tube was provided from the enclosed
receptacle. As in Examples 1 and 2, the device was tested with air at 10
psi and found not to leak. When punctured under water with a 19 guage
Huber point needle, water followed the needle into the gel space and, when
the needle was withdrawn, air from the receptacle followed the needle into
the gel space. After two needle punctures the device would not retain air
at 10 psi.
A device of the same type ruptured at 22 psi when subjected to increasing
air pressures.
It will be evident that a number of variations in both the septum material
pe se and in implantable drug delivery devices incorporating the septum
material can be made while remaining within the spirit and scope of this
invention. It will be appreciated, therefore, that the scope of the
invention is broader than the specific embodiments set forth herein to
illustrate it.
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