U.S. patent application number 09/737765 was filed with the patent office on 2003-01-16 for biodegradable surgical implants and devices.
Invention is credited to Pohjonen, Timo, Rokkanen, Pentti, Talja, Martti, Tormala, Pertti, Vainionpaa, Seppo.
Application Number | 20030014127 09/737765 |
Document ID | / |
Family ID | 26158448 |
Filed Date | 2003-01-16 |
United States Patent
Application |
20030014127 |
Kind Code |
A1 |
Talja, Martti ; et
al. |
January 16, 2003 |
Biodegradable surgical implants and devices
Abstract
A surgical implant, device, or part thereof, made of
biodegradable material for performing at least one function
selected from the group consisting of supporting, joining and
separating tissue and keeping open a tissue cavity. One
biodegradable rod which is wound around a winding center into a
helical configuration in a manner that between successive winds
there is provided a space free of material of the biodegradable
rod, and which is reinforced with biodegradable reinforcement
element in a biodegradable matrix said reinforcement elements being
oriented substantially in a longitudinal direction of the
biodegradable rod.
Inventors: |
Talja, Martti; (Lahti,
FI) ; Tormala, Pertti; (Tampere, FI) ;
Rokkanen, Pentti; (Helsinki, FI) ; Vainionpaa,
Seppo; (Helsinki, FI) ; Pohjonen, Timo;
(Tampere, FI) |
Correspondence
Address: |
KENYON & KENYON
ONE BROADWAY
NEW YORK
NY
10004
US
|
Family ID: |
26158448 |
Appl. No.: |
09/737765 |
Filed: |
December 18, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09737765 |
Dec 18, 2000 |
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08304082 |
Sep 6, 1994 |
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6171338 |
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08304082 |
Sep 6, 1994 |
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07681529 |
Jul 9, 1991 |
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Current U.S.
Class: |
623/23.75 ;
606/151; 623/23.7 |
Current CPC
Class: |
A61F 2230/0026 20130101;
A61F 2230/0078 20130101; A61L 31/127 20130101; A61B 2017/0649
20130101; A61B 17/11 20130101; A61F 2230/0006 20130101; A61F
2230/0076 20130101; A61L 31/148 20130101; A61F 2230/005 20130101;
A61F 2230/0023 20130101; A61F 2/88 20130101; A61F 2230/0021
20130101; A61F 2002/30289 20130101; A61L 31/14 20130101; A61L
31/129 20130101; A61F 2002/30062 20130101; A61F 2002/30199
20130101; A61F 2/30965 20130101; A61F 2230/0008 20130101; A61F
2230/0091 20130101; A61F 2210/0004 20130101; A61F 2/90 20130101;
A61F 2002/30291 20130101; A61B 2017/00004 20130101; A61F 2230/0063
20130101 |
Class at
Publication: |
623/23.75 ;
623/23.7; 606/151 |
International
Class: |
A61F 002/02 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 10, 1988 |
FI |
885164 |
Nov 7, 1989 |
FI |
PCT/F189/00204 |
Claims
What is claimed is:
1. A surgical implant comprising: a biodegradable material
internally reinforced in a longitudinal direction having a helical
configuration.
2. The surgical implant of claim 1, wherein the internal
reinforcement comprises elements selected from the group consisting
of microfibrils and fibrils.
3. The surgical implant of claim 1, wherein the internal
reinforcement comprises elements selected from the group consisting
of fibers, wires, braids, and ribbons.
4. The surgical implant of claim 1, wherein the helical
configuration includes a screw-threaded configuration.
5. The surgical implant of claim 1, further comprising a second
biodegradable material internally reinforced in a longitudinal
direction having a second helical configuration, wherein the
helical configuration and the second helical configuration are at
least partially nested within each other.
Description
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent
application Ser. No. 07/681,529, the entire disclosure of which are
hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to biodegradable surgical
implants and/or devices.
BACKGROUND OF THE INVENTION
[0003] In surgery, it is known to employ at least partially
biodegradable, elongated (typically tubular) surgical implants for
supporting, connecting or separating elongated organs, tissues or
parts thereof, such as canals, ducts, tubes, intestines, blood
vessels, nerves, among others. In this context, a biodegradable,
absorbable and/or resorbable, material refers to a material whose
decomposition and/or dissolution products leave the system through
metabolic ducts, kidneys, lungs, intestines and/or skin by
secretion.
[0004] Examples of at least partially biodegradable implants
include U.S. Pat. No. 3,108,357 to Liebig which suggests a tubular
device to be implanted in animals and humans, comprising a
resilient woven tube which contains biologically absorbable
oxidized cellulose.
[0005] Additionally, U.S. Pat. No. 3,155,095 to Brown suggests
hollow cylindrical anastomosis joints which are made of an
absorbable material.
[0006] Further, U.S. Pat. No. 3,272,204 to Artandi and Bechtol
suggests collagen-made flexible tubes which can be externally
reinforced with a plastic coil or plastic rings.
[0007] Other examples of at least partially biodegradable implants
include U.S. Pat. No. 3,463,158 to Schmitt and Polistina which
suggests fiber-made tubular surgical devices which are at least
partially made of absorbable polyglycolic acid (PGA).
[0008] U.S. Pat. No. 3,620,218 to Schmitt and Polistina also
suggests PGA-made surgical devices, such as tubes.
[0009] Still further examples of at least partially biodegradable
implants include WO 84/03034 to Barrows which suggests
longitudinally openable, porous, coarse-surfaced biodegradable
tubes used as a remedy for the nerves.
[0010] Additionally, the publication Plast. Rec. Surg. 74 (1984)
329, Dabiel and Olding, suggests an absorbable anastomosis device
which comprises cylindrical, tubular, complementary parts.
[0011] However, known tubular, at least partially biodegradable
surgical implants and devices involve several drawbacks and
limitations. As for the implants including biostable parts, such as
polymeric, and the like fibers, plastic or metallic coils or rings,
or the like, such biostable parts or components remain in a
patient's system even after a tissue or an organ has healed. Such
components can later be harmful to a patient by causing infections,
inflammatory reactions and like foreign matter reactions, and/or
they might release particles, corrosion products, or the like which
can wander in the system and/or cause harmful cellular level
reactions.
[0012] Known tubular biodegradable implants manufactured by melt
working technique or a like method are often massive and stiff and
create, in resilient tissues, such as ducts, tubes, blood vessels,
among others, an undesirable stiff, non-physiological bracing
effect which can lead to harmful alterations in the properties of a
tissue braced. In addition, the massive, tubular implants create a
heavy local foreign matter loading the system at the installation
site thereof and such loading can also contribute to harmful
alterations in an operated tissue, such as canal, tube, duct, blood
vessel, or the like.
[0013] On the other hand, the tubular structures constructed from
biodegradable fibers by braiding, knitting, weaving or some other
similar technique do not posses the structural rigidity and/or
resilience often required of a support implant to be fitted inside
or outside a tubular tissue.
SUMMARY OF THE INVENTION
[0014] It has been surprisingly discovered in the present invention
that the deficiencies and drawbacks of known, at least partially
biodegradable surgical implants and devices used for supporting,
connecting or separating organs, tissues or parts thereof can be
substantially eliminated with an implant, device or part thereof
which is mainly characterized by comprising an at least partially
biodegradable elongated member which is at least partially wound at
least once around a center of rotation into a helical configuration
and which is at least partially reinforced with biodegradable
reinforcing elements.
[0015] An implant, device or part thereof (hereinbelow "device")
according to the present invention can be conceived, having been
formed in a manner that around a certain center point is wound some
elongated member at a distance of a certain winding radius from the
center point. If the winding center is stationary and the winding
radius increases as the winding angle increases, the configuration
of an obtained device is a spiral configuration, especially if the
winding radius remains in the same plane. Provided that the winding
radius is constant and the winding center travels during the
turning of an elongated member along a certain, for example, linear
path, the device obtained has a circle-cylindrical screw-threaded
configuration, or helix. On the other hand, if the winding radius
changes while the winding center travels along a certain path,
there will be produced a spiral configuration whose external
surface is in conical shape. It is obvious that the implant, device
or part thereof can include the above shapes and configurations as
a combination and, for example, a combination of a spiral and a
cylindrical screw-threaded configuration. The implant, device or
part thereof can also be provided with members of other shapes in
addition to a screw-threaded configuration, such as, for example,
plates or sleeves.
[0016] The present invention relates also to a method for
manufacturing an implant, device or part thereof ("device")
including at least partially winding at least once an elongated
blank formed by a biodegradable polymer matrix and biodegradable
reinforcement elements.
[0017] The invention relates also to the use of an implant, a
device and part thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The present invention is described in more detail in the
following specification with reference made to the accompanying
drawings. In the drawings,
[0019] FIG. 1 represents a schematic perspective view of the
formation of an array of lamellae turning into a fibrillated
structure of a material micro-structure in an embodiment of a
device of the invention;
[0020] FIG. 2 represents an intra- and inter-fibrillary molecular
structure;
[0021] FIG. 3 represents a schematic view of the micro-structure of
a fibrillated polymer;
[0022] FIG. 4 represents a schematic view of the molecular
structure of fibrillated devices according to embodiments of the
present invention;
[0023] FIGS. 5 and 6 represent schematic perspective views of
spiral-shaped embodiments of an embodiment of a device according to
the present invention;
[0024] FIGS. 7a-9b represent schematic perspective views of conical
embodiments of devices according to the present invention;
[0025] FIGS. 10a and 10b represent schematic perspective views of a
cylindrical embodiment of a device according to the present
invention;
[0026] FIGS. 10c and 10d represent further embodiments of a
cylindrical device according to the present invention;
[0027] FIGS. 11a-11l represent preferred cross sectional shapes and
surface patterns for an elongated member, or blank, of embodiments
of devices according to the present invention shown in FIGS.
5-10;
[0028] FIGS. 12 and 13 represent a schematic perspective view of an
embodiment of the invention;
[0029] FIG. 14 represents a schematic view of an embodiment of a
test arrangement according to the present invention described in
example 1;
[0030] FIG. 15 represents a surgical operation described in Example
3;
[0031] FIG. 16 represents a surgical operation described in Example
4;
[0032] FIG. 17 represents a schematic view of an embodiment of a
device according to the present invention described in example
5;
[0033] FIG. 18 represents another embodiment of a device according
to the present invention;
[0034] FIG. 19 represents a cross-sectional view of an implant
according to an embodiment of the present invention as it is being
drawn;
[0035] FIG. 20 represents a cross-sectional view of the implant
shown in FIG. 19 after being bent;
[0036] FIG. 21 represents a cross-sectional view of an implant
according to an embodiment of the present invention at the time of
implanting into a bile duct of a patient; and
[0037] FIG. 22 represents a cross-sectional view of the implant
shown in FIG. 21 at some point after implantation, showing the
expansion of the device.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0038] In the context of the present invention, the biodegradable
reinforcing elements refer to the following:
[0039] a) oriented or aligned structural units included in the
micro-structure or molecular structure of a material such as
oriented parts of molecules or parts thereof or microfibrils,
fibrils or the like oriented structural units formed thereby;
[0040] b) biodegradable organic filaments, fibers, membrane fibers
or the like, or structures constructed thereof, such as bands,
braids, yarns, fabrics, non-woven structures or the like; or
[0041] c) biodegradable inorganic (ceramic) filaments, fibers,
membrane fibers or the like, or structures constructed thereof.
[0042] A particularly preferred embodiment of the present invention
is such an implant or device which is structurally self-reinforced.
A self-reinforced biodegradable structure is defined in U.S. Pat.
No. 4,743,257 to Torml et al. In a self-reinforced structure, a
biodegradable polymer matrix is reinforced with biodegradable
reinforcement elements or units having the same proportional
elemental composition as the matrix. The reinforcement elements are
typically oriented molecules or parts thereof or the like obtained
by orientation of fibrils, microfibril, fibers, filaments or the
like structures constructed thereof.
[0043] Reinforcement elements inside the microstructure of a
self-reinforced polymer material are produced, for example, by
orienting the molecular structure of a material either in melt
state or in solid state. In such conditions, the
structure-reinforcing orientation remains at least partially,
permanently in material either as a result of the rapid cooling
and/or solid state of the melt and/or as a result of the prevention
of molecular movements (relaxation) of the melt. The
self-reinforcement based on draw orientation is described in the
invention PCT/FI87/00177, Torml et al., as follows.
[0044] A partially crystalline, non-oriented piece of polymer
typically consists of crystal units, that is, spherolites and
amorphous areas thereinside and/or therebetween.
[0045] The orientation and fibrillation of a polymer system
possessing a spherolitic crystalline structure is a process that
has been extensively studied in connection with the production of
thermoplastic fibers. For example, U.S. Pat. No. 3,161,709 suggests
a three-step drawing process for transforming a melt-worked
polypropene filament into a fiber having a high tensile
strength.
[0046] The mechanism of orientation and fibrillation is basically
as follows (C. L. Choy et al. Polym. Eng. 30 Sci. 23, 1983, p.
910). As a partially crystalline polymer is being drawn, the
molecular chains of crystal lamellae quickly begin to parallel, or
orient, themselves in the drawing direction. In other words, the
reinforcement elements lie substantially parallel to the
longitudinal axis of the rod. The drawing orients the reinforcement
elements to the longitudinal direction of the rod. The first phase
of the drawing of an implant according to an embodiment of the
present invention is illustrated in FIG. 19. As can be seen in FIG.
19, the fibers of the matrix are oriented in the longitudinal
direction of the device, the same direction as the drawing, which
is indicated by the arrows.
[0047] Simultaneously, the spherolites extend in length and finally
break. Crystal blocks detach from lamellae and join together as
queues by means of tight tie-molecules which are formed through the
partial release of polymer chains from crystal lamellae. The
alternating amorphous and crystalline zones, together with tight
tie-molecules, form long, thin approximately 100 .ANG. wide
microfibril which are paralleled in the drawing direction. Since
the intrafibrillar tie-molecules form in the phase boundaries
between crystal blocks, they will be mainly located on the external
surface of microfibrils. Those tie-molecules, which link various
lamellae in an isotropic material prior to the drawing, serve in a
fibrillated material to link various microfibrils together, that
is, become interfibrillar tie-molecules which are located in
boundary layers between adjacent microfibrils.
[0048] The rod is then bent by winding to a helical configuration.
The bending actually creates a "pre-stress" condition to the wound
rod which then tends to open the helix beyond the diameter it was
wound. FIG. 20 illustrates the bending and the forces on the
implant. The arrows to the right and left of the implant indicate
the direction the implant tends to move in response to the bending.
In other words, the arrows represent an opening force.
[0049] FIG. 1 illustrates, schematically, the transformation of an
array of lamellae into a fibrillar structure (a fibril consisting
of a bunch of microfibrils) due to the action of water. FIG. 2
shows some of the molecular structure inside and between
microfibrils. FIG. 3 illustrates, schematically, some of the
structure of a fibrillated polymer. The Figure shows several
fibrils one being dyed grey for the sake of clarity, which comprise
a plurality of microfibrils having a length of several microns.
[0050] Orientation is initiated right at the start of drawing and
also a fibrillated structure is formed at rather low drawing ratios
.lambda., wherein .lambda.=(length of a piece after
drawing)/(length of piece prior to drawing). For example,
HD-polyethene is clearly fibrillated at .lambda. value 8 and
polyacetal (POM) at .lambda. value 3.
[0051] As the drawing of a fibrillated structure is continued
further (this stage of the process is after referred to as
ultra-orientation), the structure is further deformed with
microfibrils sliding relative to each other to further increase the
proportional volume of straightened interfibrillar tie-molecules.
If the drawing is effected at a sufficiently high temperature, the
oriented tie-molecules crystallize and build axial crystalline
bridges which link together crystalline blocks.
[0052] The excellent strength and modulus of elasticity properties
of a fibrillated structure are based on the vigorous orientation of
polymer molecules and polymer segments in the direction of drawing
(in the direction of the longitudinal axis of microfibrils)
characteristic of the structure.
[0053] The fibrillation of macroscopic polymeric blanks, such as
rods or tubes, is prior known in the cases of biostable polyacetal
and polyethene (See K. Nakagawa and T. Konaka, Polymer 27, 1986, p.
1553 and references included therein). What has not been prior
known, however, is the orientation and fibrillation of at least
partially helical and/or spiral or similarly shaped members or
pieces manufactured from biodegradable polymers.
[0054] The at least partial orientation and/or fibrillation of a
biodegradable helical and/or spiral or similar piece can be
effected, for example, by rapidly chilling a flowing state polymer
melt, for example, in an injection mold, into a solid state in a
manner that the orientation of molecules existing in the flowing
melt in flowing direction is not allowed to discharge through
molecular movements either entirely or partially into a state of
random orientation.
[0055] A more vigorous orientation and fibrillation and, thus, also
improved mechanical qualities are generally provided for a polymer
piece by mechanically working the material (orientation), and
generally drawing or hydrostatic extrusion or die-drawing in such a
physical condition (usually in solid state). Under these
conditions, it is possible for the material to undergo dramatic
structural deformations in its crystalline structures and amorphous
areas occurring at the molecular level for creating orientation and
fibrillation. As a result of fibrillation, for example, a
restorable polymer material produced by injection molding or
extrusion and initially possessing mainly a spherolitic crystalline
structure, transforms into a fibrillated structure which is
vigorously oriented in the direction of drawing and comprises, for
example, elongated crystalline microfibrils as well as
tie-molecules linking them as well as oriented amorphous areas. In
a partially fibrillated structure, the amorphous areas between
microfibrils make up a more substantial portion of the material
than in an ultra-oriented material which, in most preferred case,
only includes amorphousness as crystal defects. As a result of
orientation, fibrillation and ultra-orientation, the values of
strength and modulus of elasticity of a material are multiplied
compared to a non-fibrillated structure.
[0056] Orientation and the resulting fibrillation can be used for
treating biodegradable polymers, copolymers and polymer
compositions so as to form self-reinforced composites in which
nearly the entire material stock is oriented in a desired fashion
and the portion of amorphous matrix is small. The stock orientation
and small amount of matrix result in such materials having
extremely high quality strength properties in orientation direction
with a bending strength, for example, up to 400-1500 MPa and
modulus of elasticity 20-50 GPa. Thus, the orientation and
fibrillation can be used to provide helixes or spirals or the like
devices with multiple strength values compared to those of normal
melt-processed biodegradable materials, which are typically in the
order of 30-80 MPa.
[0057] As in the fibrillated structure of polymer fibers, in the
structure of fibrillated devices, there can be found, for example,
the following structural units, which are schematically shown in
FIG. 4: crystalline blocks, the stock therebetween comprising an
amorphous material, for example, loose polymer chains, chain ends
and molecular folds; tie-molecules which link the crystalline
blocks together, the number and tightness of these increases as
drawing ratio .lambda. increases; as well as possible crystalline
bridges between crystalline blocks. Bridges can form during the
drawing as tie-molecules orient and group themselves as bridges (C.
L. Choy et al., J. Polym. Sci., Polym. Phys. Ed., 19, 1981, p.
335).
[0058] The oriented fibrillated structure shown in FIGS. 1-4 is
already developed by using so-called "natural" drawing ratios 3-8.
As drawing is then continued as ultra-orientation, the portion of
crystalline bridges can increase to be quite considerable whereby,
in the extreme case, the bridges and crystal blocks provide a
continuous crystalline structure. However, the effects of
tie-molecules and bridges are often similar and, thus, the exact
distinction thereof from each other is not always possible.
[0059] Orientation and fibrillation can be experimentally
characterized by the application of several different methods.
Orientation function (fc), which can be determined by X-ray
diffraction measurements, characterizes orientation of the
molecular chains of a crystalline phase. Generally, fc already
reaches a maximum value of 1 by natural drawing ratios
(.lambda.<6). For polymer materials having a spherolitic
structure fc<<1.
[0060] Double-refraction (.DELTA.) measured with a polarization
microscope is also a quantity which represents the orientation of
molecular chains. It generally increases at natural drawing ratios
(.lambda.<6) vigorously and, thereafter, in ultra-orientation
more slowly, which indicates that the molecular chains of a
crystalline phase orient vigorously in the drawing direction at
natural drawing ratios and orientation of the molecules of an
amorphous phase continues further at higher drawing ratios (C. L.
Choy et al., Polym Eng. Sci., 23, 1983, p. 910).
[0061] The formation of a fibrillous structure can also be
demonstrated visually by studying the fibrillated material by means
of optical and/or electrical microscopy (see e.g. T. Knoda et al.,
Polymer, 26, 1985, p. 462). Even the individual fibrils consisting
of microfibrils can be clearly distinguished in scanning electron
microscope images of a fibrillated structure.
[0062] An oriented and/or fibrillated and/or ultra-oriented piece
(blank) is then rotated at least once around a center of rotation
into helical configuration to form "a device" of the invention by
shaping the blank at least partially by means of an external force
or pressure and/or external heat and/or by means of heat inducible
in the piece, for example, by radiowave radiation. In practice, the
rotation of winding of the device is effected in a manner that an
elongated blank is wound around a suitable, if necessary heated
mold, for example, a mold of cylindrical shape). Such a mold is
typically round in cross-section so as to produce helical shapes
having a circular cross-section. The cross-sectional shape of a
mold can also be, for example, elliptical, oval, or angular to
produce helical shapes having various cross-sections. Orientation,
fibrillation or ultra-orientation can also be effected in a
continuous action and/or simultaneously with winding in a manner
that an elongated blank is being drawn and the drawn section is
simultaneously wound around a cylindrical mold.
[0063] At least partially oriented and/or fibrillated and,
particularly, ultra-oriented biodegradable devices are an example
of an oriented, self-reinforced biodegradable (U.S. Pat. No.
4,743,257, Torml et al.) composite material, wherein the oriented
reinforcement elements, such as fibrils, microfibrils, crystal
blocks, tie-molecules or crystallized bridges, among others, are
formed and/or grouped during a mechanical working and a phase
binding. The oriented reinforcement elements comprise, for example,
of the following structural elements: amorphous phase, interfaces
between crystal blocks as well as interfaces between bridges and
microfibrils, a typical feature of which is also a vigorous
orientation in a drawing direction.
[0064] Another method for using biodegradable reinforcement
elements in devices of the invention is the reinforcement thereof
with fibers manufactured from polymer, copolymer or a polymer
composition, with film fibers, filaments or structures constructed
thereof, such as braids, threads, ribbons, non-woven structures,
fabrics, knittings or the like, by combining readymade fibers with
a suitable polymer matrix. Such fibers can be manufactured, for
example, from biodegradable polymers set forth in Table 1. The
fibers can also be biodegradable ceramic fibers, such as calcium
phosphate fibers (see e.g. S. Vainionp{umlaut over (aa)} et al.,
Progr. Polym. Sci., in printing).
[0065] Various plastic technological methods can be applied to
manufacture devices of the present invention reinforced with
biodegradable organic and/or inorganic fibers or with structures
constructed thereof. The manufacturing may be carried out by
binding the reinforcement structures at least partially to each
other with biodegradable polymer, copolymer or a polymer
composition (matrix) in such conditions which serve to produce a
sufficiently equal quality composite from the matrix and
reinforcement elements. The matrix is usually in solution or melt
state. Methods for combining reinforcement fibers or the like and a
matrix as well as for processing them into semi-finished products
and/or devices include, among others, injection molding, extrusion,
pultrusion, winding, and compression molding.
[0066] An at least partially spirally shaped, at least partially
biodegradable device according to the present invention can be used
in a versatile manner for supporting, expanding, joining or
separating organs, tissues or parts thereof. A device according to
the present invention offers a plurality of benefits over the prior
art implants and devices. When using a device according to the
invention, the amount of foreign matter remains smaller than with
traditional implant tubes. Devices according to the present
invention are more flexible and resilient than the rigid prior art
tubes and, on the other hand, devices according to the present
invention are stronger under compression and retain their shape
better that fiber-constructed tubular devices, whereby devices
according to the present invention are capable of being used for
retaining open or even expanding the medullary cavity of tubular
tissues.
[0067] Devices of the present invention can be manufactured from
biodegradable polymers, copolymers and polymer compositions. Table
1 shows a number of prior known biodegradable polymers, which or
mixtures of which can be used as raw material for devices of the
present invention both as a matrix (or binder polymers) and/or
reinforcement elements.
1TABLE 1 Biodegradable polymers 1. Polyglycolide (PGA) Copolymers
of glycolide 2. Glycolide/lactide copolymers (PGA/PLA) 3.
Glycolide/trimethylene carbonate copolymers (PGA/TMC) Polylactides
(PLA) Stereoisomers and copolymers of PTA 4. Poly-L-lactide (PLLA)
5. Poly-D-lactide (PDLA) 6. Poly-DL-lactide (PDLLA) 7.
L-lactide/DL-lactide copolymers L-lactide/D-lactide copolymers
Copolymers of PLA 8. Lactide/tetramethylene glycolide copolymers 9.
Lactide/trimethylene carbonate copolymers 10.
Lactide/.delta.-valerolactone copolymers 11. Lactide/e-caprolactone
copolymers 12. Polydepsipeptides (glycine-DL-lactide copolymer) 13.
PLA/ethylene oxide copolymers 14. Asymmetrically 3,6-substituted
poly-1,4-dioxane-2,5-diones 15. Poly-.beta.-hydroxybutyrate (PHBA)
16. PHBA/.beta.-hydroxyvalerate copolymers (PHBA/PHVA) 17.
Poly-.beta.-hydroxypropionate (PHPA) 18. Poly-.beta.-dioxanone
(PDS) 19. Poly-.delta.-valerolactone 20. Poly-e-caprolactone 21.
Methylmethacrylate-N-vinylpyrrolidone copolymers 22.
Polyesteramides 23. Polyesters of oxalic acid 24.
Polydihydropyranes 25. Polyalkyl-2-cyanoacrylate- s 26.
Polyuretanes (PU) 27. Polyvinyl alcohol (PVA) 28. Polypeptides 29.
Poly-.beta.-maleic acid (PMLA) 30. Poly-.beta.-alkanoic acids 31.
Polyethylene oxide (PEO) 32. Chitin polymers Reference: S.
Vainionp{umlaut over (aa)}, P. Rokkanen and P. Torml, Progr. Polym.
Sci., in printing
[0068] It is obvious that biodegradable polymers other than those
set forth in Table 1 can also be used as raw materials for
implants, devices or parts thereof. For example, the biodegradable,
absorbable polymers described in the following publications can be
used for the above purposes: U.S. Pat. No. 4,700,704 to Jamiolkows
and Shalaby; U.S. Pat. No. 4,655,497 to Bezwada, Shalaby and
Newman; U.S. Pat. No. 4,649,921 to Koelmel, Jamiolkows and
Bezewada; U.S. Pat. No. 4,559,945 to Koelmel and Shalaby; U.S. Pat.
No. 4,532,928 to Rezada, Shalaby and Jamiolkows; U.S. Pat. No.
4,605,730 to Shalaby and Jamiolkows; U.S. Pat. No. 4,441,496 to
Shalaby and Koelmel; U.S. Pat. No. 4,435,590 to Shalaby and
Jamiolkows; and U.S. Pat. No. 4,559,945 to Koelmel and Shalaby.
[0069] It is also natural that devices of the present invention may
contain various additives and adjuvants for facilitating the
processability of the material such as, for example, stabilizers,
antioxidants or plasticizers; for modifying the properties thereof
such as, for example, plasticizers or powdered ceramic materials or
biostable fibers such as, for example, carbon fibers; or for
facilitating the manipulation thereof such as, for example,
colorants.
[0070] According to one preferred embodiment, devices of the
present invention may contain some bioactive agent or agents, such
as antibiotics, chemotherapeutic agents, wound-healing agents,
growth hormone, contraceptive agent, anticoagulant, such as
heparin. Such bioactive devices are particularly preferred in
clinical applications since, in addition to mechanical effect, they
have biochemical, medical and the like effects in various
tissues.
[0071] Devices of the present invention can also be advantageously
combined with other types of biodegradable implants and devices.
For example, by inserting a helical device as shown in FIGS. 7-10
into a tube woven or knitted from biodegradable and/or biostable
thread there is obtained a firm and resilient tube which has a
variety of applications in surgery for replacing or supporting
tissues and/or for keeping open the cavities within or between
tissues.
[0072] A device according to the present invention can also be
fitted with long biodegradable rods which extend parallel to the
longitudinal axis of, for example, a helically-shaped device. Thus,
if necessary, the device can be braced to form a tubular
structure.
[0073] A device according to the invention can also be fitted with
various other accessories, such as flat, perforated plates at the
ends of a device for securing the ends of a device firmly to the
surrounding tissues by means of surgical stitches.
[0074] Devices according to the present invention can have various
geometrical configurations. For example, FIG. 5 illustrates a flat
or planar (in imaginary plane 1) spiral 2 that can be used as a
resilient separating material between tissues. The helixes of
spiral 2 can also be connected with each other by means of
biodegradable radial wires, rods 3 or the like as shown in FIG. 6.
The spiral has a high strength in the direction of plane 1 but is
resilient in the direction perpendicular to that plane.
[0075] A device according to the present invention can also vary in
its dimensions in various sections thereof. For example, FIGS.
7a-10a and 7b-10b schematically illustrate a few such devices.
These devices may be used for providing external and/or internal
support for organs or their parts of various shapes such as liver,
spleen, kidneys, intestines, among others.
[0076] A device shown in FIG. 7a is wound into a conical body. The
conical body can have a side face outline which is either straight
or arched or a combination thereof according to the intended
application. Devices shown in FIGS. 8a and 9a include two conical
bodies joined to each other either at the base of conical bodies as
shown in FIG. 8a, or at the apex thereof, as shown in FIG. 9a. FIG.
10 illustrates a device having its outer face wound into a
cylindrical configuration.
[0077] FIGS. 7b, 8b, 9b and 10b illustrate device configurations
matching those of FIGS. 7a, 8a, 9a and 10a and fitted rods 3
connecting the turns of helical body.
[0078] Furthermore, FIG. 10c shows an embodiment in which the
device is comprised of two nested device elements VO1 and VO2 wound
into a helical configuration preferably in opposite directions.
Each has a cylindrical helical configuration. FIG. 10d shows an
embodiment of a device, wherein a number of device elements wound
into a helical configuration have been twined together. The device
elements are adapted to run alternately over and under each other
to form a tubular structure.
[0079] FIGS. 11a-11l illustrate some types of cross-sections for a
blank. A blank for manufacturing devices of the present invention
can have a cross-section which is, for example, circular (11a)
elliptical (11b, 11c), flat (11d, 11e), angular (11f, 11g, 11h) or
asteroid (11i). By varying the cross-section of a blank it is
possible to effect, for example, on the mechanical properties of a
device, the growth of tissues on the surface of a blank and the
growth of tissues through the device. The thickness of a blank can
also vary in different sections of a blank or it can be provided
with holes R (11j) or similar structures, such as recesses L (11k)
or slots (11l) for facilitating the fastening or securing thereof
to tissues.
[0080] According to one preferred embodiment, a device of the
present invention is manufactured by winding or rolling a flat
blank having a cross-section shown in FIG. 12 into a tube as shown
in FIG. 13. Since the longitudinal edges of a blank as shown in
FIGS. 12a and 13a are provided with folded or other gripping means
T which engage each other, during the winding, there will be formed
a flexible tube that can be used in the treatment of, for example,
a windpipe or the like flexible tissue channels as a temporary
prothesis.
[0081] According to one preferred embodiment, devices of the
present invention can be used to join together tissues, organs or
parts thereof, such as muscular tissue or the other soft tissues.
Such an embodiment is illustrated in FIG. 18. FIG. 18a shows a
cross-section of a tissue K1 and a tissue K2 which should be joined
with each other. The joining can be effected by using a
sharp-pointed spiral S which is driven the same way as a corkscrew
through the tissues (FIG. 18b). By locking the top portion of a
spiral in position after the turning, for example, by stitching the
spiral firmly to surrounding tissues by means of surgical stitches
dissolving through the holes made in the spiral blank, the spiral
serves to secure tissues K1 and K2 to each other preventing the
separation or sliding thereof relative to each other.
[0082] Unexpectedly, embodiments of the present invention will
expand upon implantation into tissue. The expansion may, therefore,
provide the surprising advantage of helping to lock the implant in
place. This expansion is the result, at least in part, of the
composition and manufacturing technique of the invention and of the
reaction of the invention to the body temperatures to which the
invention may be subjected to after implantation. The expansion of
the implant may be at least about 15% when it is implanted in
conditions of living tissue.
[0083] The present invention and its applicability is described in
more detail by means of the following examples.
EXAMPLE 1
[0084] Some polymers set forth in Table 1 were used to prepare
helical devices of the present invention. An example, such as that
shown in FIG. 10, includes blank thickness 1 mm, outer diameter of
helix 6 mm, inner diameter 4 mm, pitch angle 15 degrees and length
of device 15-20 mm. The polymeric melt is subjected to injection
molding to produce blanks having a diameter (.phi.) of 1.5-2.0 mm
by drawing (orientation and self-reinforcement) then at a
temperature of TM>T>Tg, wherein Tg is polymer glazing
temperature and Tm is polymer (possibly) melting temperature, to
the .phi. reading of 1 mm and by winding them in hot state around a
metal pipe of diameter 4 mm. The device is then cooled and the
finished device is removed from the surface of the metal pipe.
[0085] Reference materials were made by using similar polymers to
prepare tubular pieces including a tube length of 10 mm, outer
diameter of 6 mm and inner diameter of 4 mm by injection molding
polymer melt into cooled tubular mold. The compression strength of
the devices and that of the corresponding tubes were compared to
each other by squeezing a device (FIG. 14b) or a tube (FIG. 14a)
placed between two steel plates with an external force in the
direction orthogonal to its longitudinal axis. The bending of a
device in lateral direction was prevented by prepressing the device
into a compact bundle between two vertical plates (FIG. 14b).
[0086] The compression load strengths of a tube (FIG. 14a) a device
(FIG. 14b) made of the same polymer and having equal weights were
compared to each other. This was followed by the determination of
the relative compression load strength (SP) of the device using the
formula: (force required to fracture the device)/(force required to
fracture the tube). Devices and tubes were manufactured by using
the following biodegradable polymers, copolymers and polymer
compositions: polyglycolide (Mw 60,000), glycolide/lactide
copolymer (Mw 40,000), glycolide/trimethylenecarbonate copolymer
(Mw 60,000), PLLA (Mw 260,000), PDLLA (Mw 100,000),
lactide/.delta.-valerolactone copolymer (Mw 60,000),
lactide/.epsilon.-capro-lactone copolymer (Mw 60,000), PHBA (Mw
700,000), PHPA (Mw 50,000) and PDS (Mw 40,000). Resulting values
for SP were ranging between 1.8-12.
EXAMPLE 2
[0087] Devices of the invention such as that shown in FIG. 10 were
prepared by using a biodegradable polymer matrix as well as
biodegradable reinforcing fibers included therein as reinforcements
A bundle of parallel fibers and fine particulate thermoplastic
polymer powder of particle size 1-10 .mu.m mixed therein were
compression molded in a rod-shaped mold of length 8 cm, .phi.1.5 mm
above the melting point for partially crystalline polymers, or
glazing point, for amorphous polymers of the matrix polymer. The
amount of reinforcing fibers was 40-60% by volume. The rod blanks
were helically wound in a heated condition around a hot cylindrical
mold with an outer diameter of helix 8 mm and the mold was cooled.
When using an n-butylcyano acrylate reaction polymer as a matrix,
the bundle of reinforcing fibers was rapidly impregnated with
cyanoacrylate and the uncured wetted bundle of threads was wound
helically around a teflon-coated steel pipe followed by wetting and
removing the device. A corresponding device was made by using just
cyanoacrylate.
[0088] Impregnation technique was also applied when using a matrix
containing segmented polyurethane (S. Gogolewski and A. Pennings,
Makromol. Chem. Rapid Comm. 4, 1983, p. 213) which was dissolved in
N,N"-dimethylformamide/tetrahydrofurane solution, weight ratio 3/2.
Then, the bundle of fibers, helically wound on the surface of a
teflon-coated pipe, was impregnated at 80 degrees with a
polyurethane solution and the pipe was immersed in a mixture of
ethanol/distilled water (1:1). This process was repeated several
times for preparing the device. A corresponding device was made by
using just polyurethane.
[0089] Devices corresponding to such reinforced devices were also
manufactured from mere thermoplastic matrix polymers by the
application of melt working technique.
[0090] Table 2 illustrates the matrix polymers and fibrous
reinforcements for the devices prepared.
2TABLE 2 Structural components for fiber-reinforced biodegradable
devices. Matrix polymer Fiber reinforcement PDS PGA -"- PGA/TMC -"-
PGA/PLLA -"- PLLA -"- PHBA -"- PHBA/HVA -"- Chitin fiber -"- PDS
PDLLA PGA -"- PGA/TMC -"- PGA/ PLLA -"- PLLA -"- PHBA -"- PHBA/HVA
-"- PDS -"- PDLLA PLLA PGA -"- PGA/TMC -"- PLLA PVA PGA -"- PGA/TMC
-"- PGA/PLLA -"- PLLA -"- PHBA -"- PHBA/HVA -"- PDS -"- Chitin
fibres PGA/TMC PGA -"- PGA/TMC PHBA PGA -"- PGA/TMC -"- PHBA
Poly-e-caprolactone PGA -"- PGA/TMC -"- PHBA Methymetacrylate- PGA
N-vinylpyrrolidone Polyurethane PGA Collagen (catgut) PEO PGA -"-
PGA/TMC -"- PGA/PLA -"- PLLA n-butylcyano- Collagen (catgut)
acrylate PGA
[0091] The devices were secured by their ends to a tension
apparatus and were drawn until broken in the direction of
longitudinal axis of the device which corresponds to the winding
axis of the blank. This was followed by the determination of the
relative tensile load-bearing strength (SV) of a reinforced device
using the formula: (force required to fracture a reinforced
device)/(force required to fracture a corresponding non-reinforced
device). The SV values were ranging between 1.5-8.
EXAMPLE 3
[0092] Preparation of a self-reinforced polyactide device as shown
in FIG. 10 (hereinbelow "helix" (KR)) was formed using a raw
material of poly-L-lactide/poly-DL-lactide copolymer (PLLA/PDLLA
molar ratio 80/20, Mw 60,000). The helix (KR) was manufactured from
a thick, extrusion-made PLLA/PDLLA rod, which was drawn to a
drawing ratio of .lambda.=7 at a temperature of 90 degrees for
self-reinforcing the material. A thus prepared self-reinforced rod
having a thickness of 1 mm was then wound to form "a helix" as
described in Example 1. The helix was cut into lengths of 12 mm for
the following examination.
[0093] Under general anaesthesia, the gastric cavity of a dog was
opened, the intestines were set aside and the bile duct (ST) was
exposed by preparation, (see FIG. 15). A roughly 6 mm long incision
(AK1) was made in the duct. As shown in FIG. 15a, a distance of 5
mm of this incision was provided with non-resorbable stitches (KO),
which pucker up the duct and narrow it permanently together with a
cicatricial tissue formed on incision (AK1). This was followed by
closing the gastric cavity, stitching the skin and, after waking up
from the anaesthesia, the dog was allowed to move freely in its
cage.
[0094] After one month, the dog was re-anaesthetized, the gastric
cavity was incised and the blocked bile duct was prepared to
re-expose it. The duct was opened with a longitudinal incision
(AK2) at the region of cicatricial pucker and a helix having an
inner diameter of 2 mm and an outer diameter of 3 mm was inserted.
The helix was inserted such that both of its ends were located in
healthy bile duct and its central portion within the incised pucker
region. The bile duct was closed with a stitch (O), whereby its
walls extended around the spiral. The situation is schematically
illustrated in FIGS. 15c, 21 and 22.
[0095] After the operation, the bile duct was normal in volume. In
other words, the implant has expanded. Such an expansion of, in
this example, the bile duct is a manifestation of the unexpected
result that based, at least in part upon the manufacturing
technique of the present invention and the reaction of the present
invention to body temperatures the present invention is subjected
to after an operation, the biodegradable implant of the present
invention may expand upon implantation in tissue. This expansion
will lock the implant in place. FIGS. 21 and 22 illustrate this
aspect of the invention. FIG. 21 represents the implant at the time
of implantation and FIG. 22 represents the implant after expansion
due to the body conditions has caused the implant to expand. If the
implant did not expand, the duct would remain as shown in FIG. 21,
with the narrower portion defined by the implant. The gastric
cavity and skin were closed the same way as in the first operation.
The dog was put away after 14 months by which time the helix had
nearly disappeared and the bile duct had a normal extent and volume
and the pucker was no longer macroscopically observable.
EXAMPLE 4
[0096] Under general anaesthesia the right hind femoral vein (RL in
FIG. 16a) of a dog was cut. The base portion of the more distal
vein was threaded into the interior of a biodegradable, reinforced
device ("helix") having an inner diameter of 8 mm, an outer
diameter of 9 mm and a length of 2 cm. The device, being like the
one shown in FIG. 10 (reinforcing fibers: Ca/P-fibers; matrix
polymer PLLA, Mw 100,000; fiber/polymer weight ratio=30/70 (w/w)
and vein (LO), was stitched with end-to-end technique by using a
resorbable 6-0 yarn to make a tight seam with no bleeding. After
the operation, due to the flabbiness of the walls, the vein tended
to collapse within the region of the stitched seam. This leads to a
poorer circulation in the vein resulting easily in the development
of a coagulation or clot formed by blood particles within the
region of the seam and, thus, the veins will be blocked. The
situation is illustrated in the schematic view of FIG. 16a from the
side of stitched seam, and in FIG. 16b from above a stitched seam.
Therefore, a biodegradable helix (KR) was pulled over the seam
portion with the stitched seam remaining at the half-way point of
helix (KR). The wall of a vein was attached at the stitched seam
over its entire circumference to the helix by means of
non-restorable support stitches (TO) (FIG. 16c). This way, the vein
was tensioned to its normal extent with the help of a support
provided by the device. After the seam had healed, especially after
the inner surface of a blood vessel or endothelium had healed,
there is no longer a risk of developing a clot and helix can resorb
away with no harm done. After 6 months, the dog was put away and
the femoral vein had healed with a pucker or clot.
EXAMPLE 5
[0097] The test animals used in this example were male rabbits
weighing 3 kg. The animals were anesthetized for the operation with
im. ketamin and iv. pentobarbital preparations. A polylactide blank
(.phi.1 mm) was used to prepare a helix having an outer diameter of
8 mm and a length of 15 mm and an extension formed by a thin
tubular neck section, 10 mm, followed by two helical coils (FIG.
17).
[0098] The anesthetized test animals were subjected to a surgical
incision of the urinary bladder through abdominal covers. Through
the opened bladder, the prosthesis was threaded into position with
the narrow neck section remaining within the region of closure
muscle and the helical coil ends on the side of the urinary
bladder.
[0099] The prothesis was fitted in 15 test animals which were under
observation for 3 months. The study verified that an implant of the
invention can be used for preventing a lower urethra obstruction
caused by the enlargement of forebland.
EXAMPLE 6
[0100] The test animals in this example were male rabbits weighing
approximately 3 kg. The animals were anesthetized for the operation
with im. ketamin and iv. pentobarbital preparations.
[0101] The implants employed were PLLA helixes as described in
Example 1 (cross-section of blank circular, thickness of blank 1
mm, outer diameter of helix 6 mm and length 15 mm).
[0102] On the anesthetized test animals was performed scission of
the blind urethra to the extent sufficient for a prothesis. The
prothesis was placed on the distal side of closure muscle. In
connection with the operation an antibiotic was administered as a
single dose: ampicillin 100 mg/kg.
[0103] The prothesis was fitted in 15 animals which were put away
with iv overdose of anesthetic 2 weeks, 3 months, 6 months, 1 year
and 2 years after the implantation. The urethra was dissected and
tissue samples were taken for histological and electron microscopic
analysis.
[0104] Histological studies indicated that PLLA had caused only
slight foreign matter reaction in tissues. Two years after the
implantation the helix had nearly completely biodegraded and the
urethra was almost normal in its dimensions (i.e. the implant has
expanded). This state of the bile duct would not be possible if the
bile duct had not expanded at the helix. If the helix had not
expanded, there would be a constriction in the duct corresponding
to the thickness of the helix wall, as shown in FIG. 21.
EXAMPLE 7
[0105] Cloggings in the ureters leading from kidney to bladder will
become more common as a result of the increased observation surgery
of upper urethras. The ureter has a good regeneration ability when
subjected longitudinal incision but its healing requires an
internal support. Transverse incision or short deficiency always
leads to the development of a clogging.
[0106] The purpose of this example was to examine the applicability
of a helix made of a biodegradable material both the healing of a
longitudinal dissection of the urethra and to the healing of a
transverse deficiency.
[0107] The test animals were female rabbits weighing approximately
3 kg. The animals were anesthetized. Incision of the abdominal
cavity was performed on the flank without opening, however, the
actual abdominal cavity.
[0108] a) the urethra having a diameter of ca. 4 mm was dissected
lengthwise over a distance of ca. 2 cm followed by threading a
self-reinforced PGA-helix (blank thickness 1 mm) inside the
urethra, the helix having an outer diameter of 4 mm and a length of
20 mm. The region of dissection was covered with fat.
[0109] b) a length of ca. 1 cm was cut off the urethra, the
remaining ends were dissected over a distance of 0.5 cm and the
above-described prothesis was threaded in, so that the remaining
defect zone of the tissue was 1 cm. The defect zone was covered
with surrounding fat. After 1 month, 3 months and 1 year from the
operation a tracer imaging of the kidneys was performed for
observing the healing of the urethra. The operated urethras had
healed to almost normal condition over the period of 1 year (on the
basis of tracer imaging).
[0110] In this disclosure, there is shown and described only the
preferred embodiments of the invention, but, as aforementioned it
is to be understood that the invention is capable of use in various
other combinations and environments and is capable of changes or
modifications within the scope of the inventive concept as
expressed herein.
* * * * *