Note: Descriptions are shown in the official language in which they were submitted.
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IMPROVEMENT TO FRAMELESS INTRAUTERINE DEVICES AND SYSTEMS
The invention relates to a new and improved "frameless"
copper-releasing or hormone-releasing intrauterine
contraceptive device or system (IUD/IUS).
The known frameless copper intrauterine device, called
GyneFix ' has six copper tubes, each 5 mm long and 2.2 mm
wide, threaded on a length of thread or suture material.
This was generally disclosed in US 4,708,134 or EP
0191747. The proximal end of the device is provided with
an anchoring means for its fixation to the uterine wall in
order to prevent that the device is pushed out by the
uterus.
Another known device or system is the frameless hormone-
releasing FibroPlant which is similar to the GyneFix IUD
but instead of copper cylinders, as the active component,
is provided with a fiber or several fibers or loops held
together in one assembly zone, and which releases the
hormone in the uterine cavity. The hormone, such as
steroid hormone, is a contraceptive and/or a therapeutic
agent. An anchoring means similar to the above mentioned
one is also provided for its fixation in the uterine wall.
This was generally disclosed in US 5,433,218 or EP0445150.
These devices are remarkably well tolerated by any uterus,
irrespective of its size and shape, due to the absence of
a rigid frame, which eliminates dimensional
incompatibility with the uterine cavity.
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In order to retain the IUD/IUS in the uterine cavity,
there is therefore a means to suspend the device to
prevent its expulsion from the uterus. The preferred means
is to suspend the IUD or IUS in the uterine cavity simply
by providing a knot in the anchoring thread and then
pushing such in the wall of the uterus by means of an
applicator comprising, for example, a stylet-tip
cooperating with a small loop extending from the knot.
A knot in the context of the present invention consists of
a location of the thread were the thread has been deformed
and/or multiply folded in such a way to produce a
localised stable mass or lump of thread comprising at
least a loop extending from this mass in order to provide
a way for a hooking point of a stylet-tip during the
insertion process. The mass of thread may be produced by
intertwining and/or its stability enhanced by local fusion
of the thread which is made at least partially of
thermoplastic component. The dimension of the knot is
larger than the diameter of the thread, for example 3 to 6
times larger, typically between 0.8 and 2.0 mm. The
proximal end of the thread becomes a short appendix
extending from the knot. The knot or deformation in the
thread is small in volume and of a form suitable to allow
its withdrawal under the effect of sufficient pulling,
form the tissue of the uterus without damaging the latter.
Both active substances, copper and the hormone-releasing
fibrous delivery system, can be visualized and their
position in the uterine cavity can be checked by
ultrasound.
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The anchor in the tissue however cannot be visualized, or
insufficiently, in many instances. The proper position of
the anchor in the wall of the uterus is extremely
important as the performance of the IUD/IUS depends on it.
It can become expelled or the anchor can be inserted too
deep, perforating the wall of the uterus. Perforation of
the uterus is a serious adverse event which can lead to
pain complaints, infection in the abdomen and pregnancy as
there is no protection anymore if the IUD/IUS is not in
situ.
In order to solve this problem and make it possible for
the doctor to check the correct position of the anchor,
according to the invention, a means has been provided to
visualize the anchoring knot.
According to a preferred embodiment of the invention,
there is indeed threaded a tiny metal tube on the
anchoring thread immediately below the anchoring knot.
Studies have shown that steel is more echogenic on
ultrasound than copper and therefore the stainless steel
tube can be kept extremely small. It is also important
that the right material is used as the material should be
biocompatible because the tiny steel tube will remain in
the uterine wall for months or years until the IUD/IUS is
removed.
It has been surprisingly found that this tiny metal tube
in the fundus is well tolerated and does not affect the
other properties of the frameless IUD/IUS.
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Another aspect of the current improvement to frameless
copper devices is related to the size of the copper
elements loaded onto the IUD.
The abovementioned device known as GyneFix comprises
copper cylinders and is very efficient as the inner
surface of the copper cylinders is in contact with the
uterine environment, thereby increasing the effective
copper surface area, as there is no plastic frame. This,
as mentioned, is different from other known copper IUDs.
This standard prior art "frameless" IUD has an effective
copper surface area of approximately 330 mm2 and is a
highly effective intrauterine contraceptive system. In
randomized clinical trials, it has been shown to be more
effective that the most effective copper IUD available on
the market. In addition, with this IUD, because of its
smaller size and flexibility, the effect on menstrual
blood loss is reduced when compared with the larger,
conventional copper-releasing IUDs.
An important drawback of IUDs is indeed their tendency to
cause heavy, sometimes painful, menstrual bleeding. Heavy
bleeding is the commonest cause for IUD discontinuation.
Discontinuation rates for bleeding vary from 7.0 to 12.0
during the first year of use. In the USA, an estimate of
36% of IUD users terminate during the first year for
reasons other than the desire for pregnancy, including
heavy menstrual bleeding and pain. Heavy menstrual
bleeding may have a deleterious effect on health among
normally healthy women. This is especially the case in
women living in deprived developing countries where
increased menstrual blood loss may precipitate or
aggravate iron deficiency anaemia. It has been reported
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that even minute increases in menstrual blood loss may
adversely affect the health of women especially during
long-term use of IUD contraception.
Anaemia is common according to a recent report of the WHO
(World Health Organization). The incidence of anaemia in
Western Europe and the USA is about 8%, in the other
European countries about 20-30%, South America about 20-
300.
It has now been found that the use of a still reduced size
of the contraceptive device produces surprisingly even
less menstrual blood loss (MBL) than the already small
frameless IUD previously known, with a copper surface area
of about 330 _2.
According to another aspect of the invention it has
therefore been found that reducing the size of a device of
the prior art further results in an intrauterine device
which is surprisingly still highly reliable and efficient,
due to its high effective copper surface area, and is well
tolerated, with minimal effect on menstrual blood loss,
because of its very small size.
According to still another aspect of the invention, an IUD
device is provided with a means to increase the release of
copper from the smaller device.
It is known that noble metals such as gold and silver can
influence the release of copper. This effect has already
been described in the patent document PCT/HU90/00009. The
essence of this patent is that the active body is made of
at least two metals forming a plurality of galvanic cells
in the uterine environment and is accomplished by making
an alloy or microscopic mixture of the different metals.
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It has been shown that it is especially desirable to
design a device of which the active substance is copper
and to add at least one metal which has a higher
electropositivity such as gold. The copper elements then
form the anode and the gold the cathode of the galvanic
cell. The uterine environment functions thereby as the
electrolyte.
With the GyneFix -type IUD of the present invention, the
improvement is obtained not by providing an alloy or
mixture but surprisingly it is simply accomplished by
alternating copper cylinders with small gold cylinders,
creating these galvanic cells. In this way, the device
remains, as intended, highly flexible resulting in optimal
tolerance by the patient.
Previous dissolution studies of the GyneFix 330 IUD
yielded a minimal dissolution rate, per copper tube, of
2.4 mg per year. The addition of gold increases the copper
ion release in the uterine environment thereby enhancing
the contraceptive effectiveness based on the increased
inactivation of the spermatozoa.
The primary aim of the present invention is to provide
a means to make the current anchor visible on ultrasound
and x-ray to allow the provider to check if the anchor is
properly placed in the wall of the uterus since the
performance of the frameless IUD/IUS depends on correct
placement of the anchor. The visualization of the anchor
thereby significantly increases the safety of the
anchoring concept.
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This goal is reached by adding a tubular metal
element to the anchor fixed onto the anchoring thread just
below the anchoring knot and/or on the appendix of the
anchoring knot.
If a tube is threaded on the anchoring thread, this
method of realization does not hinder the anchor for
suspending the copper IUD or of the hormone-releasing IUS
when inserted with an applicator into the musculature of
the uterine fundus.
According to a particular embodiment, the anchoring
knot may also be treated with metal dust attached or
incorporated in the material of the anchoring knot or
deformation of the thread serving as anchor. In this case
the anchoring knot is preferably created by heat
deformation during which small particles of metal are
added.
The secondary aim of the present invention is to
provide a copper IUD to minimize the impact on menstrual
blood loss. This device has a smaller total (nominal)
surface area but a large effective copper surface area,
when compared to the effective copper surface area of the
high-load conventional copper IUDs.
According to one characteristic of the invention, the
total surface area of the IUD does not exceed 275 mm2.
According to one preferred embodiment it will not exceed
200 mm2.
According to an additional characteristic of the
invention, the effective copper surface area equals the
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nominal copper surface area which should be at least 200
mm2.
According to yet another aspect of the invention, the
components are copper cylinders and are not longer than 6
to 8 mm in order to allow easier direct contact between
theinner surface of the cylinders and the uterine
environment.
According to yet another characteristic of the
invention, all copper cylinders are kept inplace by two
small copper clips, one above and one below
the copper cylinders, crimped onto the anchoring thread.
The clips may be cylinders identical to the copper
cylindersbut which have been crimped. The design of the
device and the manufacturing process may therefore be
simplified.
According to still another additional characteristic
of the invention, the total length of the closely
approximated copper elements of the IUD is not longer than
2.6 cm.
According to still another additional characteristic
of the invention, the total length of the IUD is not
longer than 3.0 cm when the copper elements are freely
separated.
According to an embodiment, the hollow elements are
separated from each other by a small space to enhance the
contact between the inner part of the cylinders and the
uterine environment.
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According to yet another characteristic of
theinvention, the hollow elements are not larger than 3.0
mm in diameter in order to allow easy insertion in the
uterinecavity.
According to another characteristic of the invention,
the inner diameter of the hollow elements is at least 1.6
mm in diameter to allow a high total (inner and outer)
effective copper surface area similar to high-load copper
IUDs.
The number of elements may be between 2 and 10,
preferably between 3 to 6. Particularly preferred is a
structure comprising 4 cylindrical elements, each
approximately 5 mm in length, in a row of which the first
and last have been crimped onto the anchoring thread.
According to another aspect of the invention there is
provided a way to increase the copper release to enhance
the inactivation by the copper ions on the sperm cells
which is the main mechanism of action of copper IUDs. As
mentioned before, copper and gold (or silver) enter into
an electrochemical reaction. An alloy of copper and noble
metal (silver, gold) creates a multitude of local tiny
galvanic (alkaline) batteries when in contact with the
uterine environment (which serves as an electrolyte).
Copper act as an anode, while the noble metals (Ag, Au)
serve as cathode. The resulting weak electrical activity
has a negative effect on sperm cell motility, capacitation
and survival, while the foreign body reaction, also
stimulated electrically, increases leucocyte infiltration
in the endometrium and further increases the number of
macrophages in the uterine cavity (enhanced spermicidal
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effect). Silver and gold ions, dissolved in trace
quantities, exhibit in situ bactericidal and
fungicidal effects (oligodynamic effects), which are
expected to lessen the risk of pelvic inflammatory disease
(infection).
With the frameless IUD, the use of metal alloys is less
practical than to use tubular elements which can simply
be treaded on the anchoring suture. In view of the above
considerations, practically, gold tubes with length
varying between 1.6 and 2.0 mm are added between the
copper tubes of the small IUD (GyneFix type) at three
possible locations : first, below the first "crimped"
copper tube; second, between the "loose" (noncrimped)
copper tubes; and thirdlyabove the lower "crimped" copper
tube.
According to particular embodiment at least one short
2.0-3.0 mm gold tube is crimped onto the suture thread,
for example one above and/or one below the four copper
tubes.
An additional purpose of the invention is to reduce the
risk of expulsion in cases where the uterine wall is soft
(e.g., postpartum) by the provision of biodegradable
material added to the anchoring knot. This can be
realized by putting a cap on the assembled anchoring
knot. The cap covers preferably the upper part of the
knot and leaves a loop extending therefrom for permitting
the insertion process with an inserter. The biodegradable
cap will degrade in weeks or a few months, leaving only
the anchoring knot for retention of the contraceptive
device in the uterine cavity at the time the uterus has
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involuted. Exemplary biodegrable material is a
polylactide or polycaprolactone.
These and other characteristics of the invention will
be more readily understood when referring to the
description as well as the accompanying drawings which
represent, merely by way of examples, several embodiments
of the invention, and in which:
FIG.1 is an enlarged schematic sectionalview of the anchor
provided with a thin tube which is threaded just below the
anchoring knot.
FIG. 2 represents the anchor as in Fig. 1 provided
with a thin tube threaded and affixed onto the appendix of
the anchor.
FIG. 3 is a schematic cross sectional view of the
uterus with a preferred embodiment of an IUD according to
the invention, and Fig. 3' is a schematic cross sectional
view of the uterus with a preferred embodiment of a
hormone-releasing IUS according to the invention.
FIG. 4 represents a view of a preferred embodiment of
a copper-releasing IUD according to the invention,
compared with a conventional copper-T IUD, showing the
significantdifference in size between the two IUDs,
FIG. 5 is a transversal sectional view of a copper
element of the invention,
FIG. 6 is another view of an embodiment according to
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the invention of which the copper elements are separated
from each other to enhance the contact between the inner
surface of the hollow cylinders and the uterine fluid,
FIG. 7 represents another view of embodiments
according to the invention of which the copper elements
are separated from each other by gold or silver tubes
forming galvanic cells in succession,
FIG.8 is a sectional schematic view of a mode of
realization where a biodegradable cap is added and covers
the anchoring knot for enhanced retention in the fundal
part of the uterus.
Referring now more particularly to Fig. 1, an anchor
is provided by making a knot 5 in a suture thread 3 of
which one of the ends is cut, leaving a relatively short
appendix 4 extending from the knot. Below the knot,
threaded onto the suture thread is a tiny tube 6 of
maximum 2 mm long and less than double the size of the
suture thread to allow its easy insertion in the wall of
the uterus with a specially designed inserter. Also
illustrated is a small loop 12 extending from the knot 5
and designed to cooperate with an inserter for pushing the
not into the fundal tissue of the uterus.
According to another characteristic of the invention,
the metal tube 6 is threaded on the appendix 4 of the
anchoring knot 5 as shown in Fig. 2, and kept in place by
slightly crimping the tube on the appendix.
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Referring now particularly to FIG. 3, an IUD is
made of a material which is physiologically active in the
uterine cavity, consisting of 4 hollow longitudinal
members 2, open at both ends, and arranged in a sequence
in order to form a longitudinal flexible body. The
elements 2 are threaded on a length of thread 3, for
example a polypropylene suture material. The sleeve
members or elements 2 are prevented from sliding off the
material by the upper and lower sleeves which are at least
partially crimped onto the thread. The proximal end of
the thread is provided with a fixing means 5 which is
pierced by about 1 cm in the fundal part of the uterine
cavity 1 to secure the IUD therein and prevent expulsion.
The resulting device has no rigid plastic body, making it
a completely flexible and supple unit.
Preferably the IUD is made of hollow elements of
which the total surface area is at least two times smaller
when compared to a well-known conventional IUD (TCu380A)
as shown in FIG. 5.
Fig. 4 shows the same anchoring technology as in Fig.
3, according to the invention, but the copper tubes are
replaced by a fibrous delivery system 7 affixed to the
anchoring thread by means of a metal cylinder 8 crimped
onto the anchoring thread.
FIG. 6 is a transversal sectional view of an
elementof the invention, showing the possibility of
exchange ofcontact between the inner surface of the hollow
cylindersand the uterine fluid. In the center is a cross
sectional view of a metal element consisting of a noble
metal which forms a galvanic cell with a copper cylinder.
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As shown in FIG. 7, which illustrates a IUD according
to one embodiment, which comprises 4 hollow elements,
open at both ends, separated from each other by a spacer
9, being provided crimped onto the thread or not, to
enhance the contact with the uterine environment 11.
According to one embodiment such crimped elements can be
made of a noble metal.
Figure 8 is one of the preferred embodiments of the
invention in order to increase the inactivating impact on
sperm cells, bacteria and viruses. The cross sectional
view shows a copper-releasing IUD according to the
invention consisting of hollow copper elements, open at
both ends, separated from each other by hollow gold
elements creating relatively highly active galvanic cells
due to the fact that all surfaces are open to the uterine
environment, being the electrolyte.
Figure 9 is a sectional view of a preferred mode of
realization of the "enhanced" anchor showing a cross
sectional view of the anchoring knot with biodegradable
bell-shaped cap 13 pushed over it.
The present invention discloses, among others, in a
non limitative way :
- an intrauterine contraceptive device (IUD) comprising: a
plurality of elongated hollow, metabolically active
members, open at both ends and arranged longitudinally
onto a thread, one end of which comprises an anchoring
means to retain to the fundal part of the uterine cavity
such device forming a non-rigid structure of limited
dimensions, characterised in that: the structure has a
total surface area not exceeding 275 mm2; the length of
the structure, when the hollow members are closely
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approximated is less than 2.6 cm, and not more than 3.0 cm
when the members are freely separated along said thread,
and its diameter is not more than 3.30 mm, preferably not
more than 3.00 mm; and the hollow members have an inner
diameter of at least 1.6 mm but less than 2.5 mm, and/or
- an intrauterine contraceptive device for insertion in
the uterus comprising: a plurality of hollow,
metabolically active elements, arranged longitudinally to
form a non-rigid structure of limited dimensions; a
structure of which the elements are copper cylinders are
at least 2.4 mm in diameter and maximum 2.8 mm in length;
a structure of which the wall thickness of each or part of
the copper cylinders is at least 0.4 mm, with the following
additional optional features :
- the hollow members are hollow cylinders or sleeves, the
length thereof being equal to or less than 8 mm;
- the wall of the hollow members is partially cut out or
perforated;
- the hollow members are made of copper;
- one or some of the hollow members (2) are made of
copper and the other(s) of gold and/or silver;
- the hollow members 2 are kept in place by two small
crimped clips, one above and one below the hollow
elements;
- the clips are also hollow elements, possibly of shorther
length, having been crimped or flattened onto the thread;
- the number of members 2 is between 3 to 8, preferably
around 4;
- the total copper load is minimally 350 mg;
- retaining thread is made of polypropylene and/or has
at least 0-gauge size US;
- the total length of the hollow members does not exceed
2.5 cm;
- the effective copper surface area is between 220 mm2
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and 280 mm2;
- there is provided a hollow member or thin tube which is
threaded just below the anchoring knot;
- the hollow member is made of copper and has a length
between 1 and 9 mm and a diameter which is between 0.1 and
0.3 mm larger than the size of the suture thread (3) on
which the tiny metal tube is threaded;
- there is provided a further crimped hollow member at an
appendix of the anchoring means,
- the hollow members are copper cylinders and the wall
thickness of each or part of the copper cylinders is at
least 0.4 mm.
The invention has been described and illustrated
merely by way of examples which are in no way restrictive.
Novel features can be taken separately or in any possible
combination. More particularly the present invention
discloses generally, separately or in any combination a
frameless intrauterine device having
- a metallic element such as a steel cylinder at the
anchoring location inside the tissue of the uterus;
- very small dimensions compared to the prior art device;
- noble metal cylinders, such as gold or silver cylinders,
threaded adjacent to copper elements;
- a knot for anchoring the device which is capped by a
biodegradable component, such knot being not necessarily
completly embedded in the biodegrable component.
Numerous changes in the detailed conception of the
invention may be made without departing from the scope of
the invention.
