Note: Descriptions are shown in the official language in which they were submitted.
~037~0~
This invention relates to a medicament-containing intra-
uterine contraceptive for human use.
Medicament-containing contraceptives for intra-uterine
use have been proposed in an attempt to provide contraceptives
which, without preventing ovulation, are reliable in action with
smaller quantities of medicaments that are required when the same
medicaments are administered via the gastro-intestinal tract. The
human organism can then be subjected to a reduced quantity of
medicinal material with the result that side effects should be
reduced or eliminated.
It has long been proposed to introduce into the uterus -
for preventing conception devices formed of a very wide variety of ~ ;
materials, having a variety of shapes and being designed to act in
a variety of different ways. However, the mechanism of action of
these previously proposed contraceptives for intra-uterinal use
has not been definitively clarified.
A device capable of intra-uterinal use for preventinq
conception was developed in 1920 by GRAFENBERG. The device was
made of a wire material consisting of an alloy of copper and silver.
Later on various synthetic plastics materials, such as
nylon, polyethylene and polyethylene/vinyl acetate, alone or with
added barium sulphate, were used to form a very wide variety of
contraceptives for intra-uterinal use, but they were very cumber-
some and bulky for the uterine cavity. Examples of such devices
are the MARGULIS Spiral (U.S. Patent No. 3,200,815; Federal German
Patents Nos. 1,416,942 and 1,441,359), BIRNBERG's Bow (U.S. Patent
No. 3,253,590), Saf-T-C~il (a trademark) (U.S. Patents Nos.
3,234,938 and 3,374,788) and LIPPES LOOP (a trademark) (U.S. Patent
No. 3,250,271).
With the development of T-shaped contraceptives (U.S.
Patent No. 3,533,406), DALXON-Shield (a trademark) (German Offen-
legungsschrift No. 1,956,701) and LIPPES LOOP D (a trademark),
there became known contraceptives for intra-uterinal use made from
synthetic plastic material and
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smaller in linear dimension and volume than previously proposed
devices. The reliability in action of these contraceptives was
increased by applying metallic copper to the surface of the
device [compare Zipper, Amer.J.Obst.Gynec. 105, 1274-1278 (1969)
and Jecht et al., Contraception, 7(5), 381 (1973)] or by the
incorporation of medicaments in the synthetic plastic material. -
There were dispersed as medicaments in the synthetic plastic
material copper powder or steroid hormones having a gestagenic
action. One construction of the DALKON Shield, for example, contain- -
ed copper highly dispersed in the synthétic plastic carrier. The
COPPER-T and COPPER-7 (U.S. Patent No. 3,563,235) were partially
bound with copper wire, and the COPPER TCu 220 C (U.S. Patent No.
3,533,406) was partially covered with copper sleeves (U.S. Patent
No. 3,563,235). The reliability in contraceptive action of the
devices for intra-uterinal administration provided with copper ~ ;
on their surfaces was increased by the additional application of
zinc or silver [see U.S. Patent No. 3,563,235; Zipper et al.,
Amer.J.Obst.Gynec. 105, 529-534 (1969); Zipper et al., Human
fertility control through the use of endouterine metal antagonism -
of trace elements in control of human fertility, Nobel 15, Almquist
& Wiksell, Stockholm 1971, pp. 199].
There have also been proposed intra-uterine contraceptives
consisting of a device formed of a synthetic plastic material and
having connected thereto a capsule of silicone rubber containing
medicament. Such combination-contraceptives are also intended for
application in the cavum uteri lInt.J.Fert. 15 (1970) 210].
It has been fou~d, however, that previously proposed
contraceptives containing medicaments for intra-uterinal use, and
also similarly shaped devices free from medicament, lead during the
period of use to undesired side effects such as haemorrhages and
pains lFORTIER et al., J.Amer.Obstet.Gynec. 115 (1973) 291; TATUM,
contraception 6 (1972) 179; MISHELL et al., Amer.J.Obstet.Gynec.
116 (1973) 1092].
- 2 -
1037E306
Disadvantages of previously proposed contraceptives for
intra-uterinal use are a risk that spontaneous expulsion will occur,
a need to remove the contraceptive on medical grounds and the
occurrence of pregnancies. A need to remove the contraceptive on
account of side effects tends to occur especially at the beginning
of the period of use [see AVERY, Rep.Popul.Family Plan 4,6: (1973)
139]-
The most frequent side effects of known contraceptivesfor intra-uterinal use are haemorrhages and pains. The number of
removals of intra-uterinally applied contraceptives necessitated
by occurrence of these troubles is greater for the bulky devices
formed of synthetic plastics than for the less bulky devices such
as the DALKON-Shield (a trademark), T-shaped contraceptives or
LIPPES LOOP D (a trademark).
Side effects, removals necessitated by side effects and
expulsions of the intra-uterine contraceptives made of synthetic
plastic materials do not, however, result solely from the unfavour-
able shape and dimensions of the devices. Other important factors
in this connection are the elasticity and hardness of the synthetic
plastic material. Devices made of synthetic plastic material of too
low an elasticity and of high hardness cause frequent pains and
spasms. The devices must be made in different sizes to correspond
to the dimensions of the cavum uteri. Contraceptives made of a
synthetic plastic material that is too soft may twist within the
uterus and are then often spontaneously expelled. Occasionally,
they penetrate the uterine musculature. Fragments of such intra-
uterinally used contradeptives and intact devices, if they have
penetrated the wall of the uterus, enter the peritoneal cavity and
there lead to further injuries or ligature the intestinal con-
volutions.
Statistical studies have shown that, with the lessbulky intra-uterine contraceptives made of synthetic plastic
material, the frequency of side effects and spontaneous expulsions
is lower
. .. . . . . , . ~ ~ , , ; . ..
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than for bulky contraceptive devices. The absolute number of
undesired side effects and spontaneous explusions, however, is
too high to be tolerable for either type of intra-uterine contra-
ceptive device. Moreover, in the case of the less bulky intra-
uterine contraceptives, there have been observed side effects
such as the occurence of dysmenorrhoea, metromenorrhagia and
leucorrhoea associated with continuous pain and occasionally
convulsive pain [compare, for example, Ostergard et al., Contra-
ception 4(5), 313 - 317 (1971); Portruff et al., Am.J.Obst.Gynec.
114(7), 934-937 (1972); Taylor et al., Obst.Gynec. 41(3), 404-413, ~ :
(1973); Buchmann, Fert. Steril. 21(4), 348-355 (1970)]. The
pregnancy rate calculated by the life-table method [Tietze, Intra- ;
Uterine Contraception, Recommended Prodecures for Data Analysis
Studies in Family Planning, No. 18 (Suppl.), The Population
Council, New York, 1967] when these contraceptives are used
is such as to cast doubt on their reliability (Fuchs et al.,
Contraception 5(2), 119-127 (1972), Baeyertz, Austr.N.Z.J. Obst.
Gynec. 11 117-121 (1971); Davis, Amer.J.Obst.Gynec. 114(1), 134-151
(1972)]. ~
Moreover, perforation of the wall of the uterus has 7" '
frequently been observed with this type of contraceptive (Buchmann, ;
Fert.Steril. 21(4), 348-355 (1973)].
Rigidly formed intra-uterine contraceptives may break ;
in the uterus because of the alternating bending stresses to which `
they are subjected. The broken pieces may be expelled spontan-
eously without being noticed or, as in the case of undamaged
devices, penetrate the wall of the uterus and enter the perintoneal
cavity [Last, J.Obst.Gynec.Brit.Commonw. 79(2), 190-191 (1972); -
Domany et al., Brit.Med.J. 1 549 (1973)].
The use of medicament-containing intra-uterine contrace- -
ptives such as the TCu 200 or TCu 220C, the contraceptive contain-
ing copper and zinc, or a device containing progesterone (German
Patent Specification No. 2,247,949) or dl-11~-ethyl-17~-ethinyl-
-- 4 --
. ~ . . . ~:
10378Q6
17~-hydroxy-gon-4-en-3-one, results in an observed reduction in
the pregnancy rate as compared with intra-uterine contraceptives
made only of synthetic plastic material.
However, such medicament-containing intra-uterine contra-
ceptives, like the similarly shaped devices free from medicament,
lead during the period of use to undesired side effects such as
haemorrhages and pains IFortier et al., J.Amer. Obst.Gynec. 115
(3), 291-297 (1973); Tatum, Contraception 6(3), 179-189 (1972);
Mishell et al., Amer.J.Obst.Gynec. 116(8), 1092-1096 (1973)].
It is common to all T-shaped devices that because of the
tendency of synthetic plastics to acquire a permanent set, they
cannot be sterilized in the applicator. Furthermore, it is hardly
possible to insert the device in the applicator under aseptic
conditions, because the device and applicator are not fitted
together in a suitable manner.
The device and applicator together can cause injuries
during application, since the fold-up device and the upper edge of
the insertion tube have sharp edges. The DALKON-Shield (a trade-
mark) and the applicator developed for this device are so con-
stituted that it is only possible to introduce the contraceptive
with considerable stretching of the cervical canal.
In addition to the large number of enforced removals of
the contraceptive because of side effects, there are also spontan-
eous expulsions [Fortier et al., Amer.J.Obst.Gynec. 115(3), 291-
297 (1973); Johannisson, Contraception 8(2), 99-112 (1973); Snowden
et al., Contraception 7(2), 91-104 (1973); Horowitz~ Contraception
7(1), 1-10 (1973)]. S~ontaneous expulsions have been observed with
a few of these devices [DALKON Shield (a trademark); German Offen-
legungsschrift No. 1,956,701; Ostergard et al., Obst.Gynec. 41(2),
257-2S8 (1973); T-shaped contraceptives, COPPER-7: Newton et al.,
Lancet 1972/II No. 7784, 951-954; Bernstein et al., Contraception
6(2), 99-107
lQ378Q6
(1972)], even through they are so shaped that they have abutments
arranged to oppose the direction of expulsion. IJones et al.,
Brit.Med.J., 3, 143 (1973)1. In the DALKON Shield (a trademark)
the abutments are fixed lateral projections in the form of fingers
and prongs on a ring. Intra-uterine contraceptives thus formed -
naturally have the risk of causing injuries to the uterus during
application, during the period of use IKoetsawang, Contraception
7(4), 327-332 (1973); Johannisson, Contraception 8(2), 99-112 ~-
(1973); Lehfeldt et al., Obst.Gynecol. 37(6), 826-831 (1971); ;
Brooks et al., Amer.J.Obst.Gynecol. 113(1), 104-106 (1972); Sprague
et al., Obst.Gynecol. 41(1), 80-82 (1973); Rienprayura et al.,
Contraception 7(6), 515-521 (1973)] and during removal ISnowdon et
al., Contraception 7(2), 91-104 (1973)]. KAMAL et al. [Fert.
Steril. _ (3), 165-169 (1973)] described as trivial the injuries
to the wall of the uterus caused by the two horizontal ends of the -
T-formed contraceptive device (U.S. Patent No. 3,533,406), which
anchor the device in the wall of the uterus, and even as being
favourable to the action and fixing of the contraceptive device.
In the case of intra-uterine contraceptives containing
copper, such as the COPPER-T, the copper wire may break as a re-
sult of mechanical stress or become separated from the body of
synthetic plastic material. The resulting fragments of copper wire
may cause injuries. They may penetrate the wall of the uterus,
pass into the peritoneal cavity and, being fragments, are difficult
to locate. With the COPPER-TCu 220 C the risk of perforation of
the wall of the uterus with subsequent separation of the copper
cylinder and the copper cylinder remaining in the peritoneal cavity
is especially great.
~ The hitherto proposed contraceptives also have dis-
advantages in that their total weight or the distribution of weight
within the device tend to cause spontaneous expulsion. The COPPER-
TCu 220 C weighs 612 mg, and one construction of the LIPPES LOOP
(a trademark)
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~78~6
weighs 665 mg. Metal-containing intra-uterine contraceptives,
such as that described in German Offenlegungsschrift No. 2,207,939,
are easily expelled spontaneously (the metal rings all being fixed
on the shaft of the synthetic plastic body).
Other contraceptives, for example, those proposed in
German Patent Specification No. ~441,359 or German Offenlegungssch-
rift No. 2,207,939, have an extension of the spiral to be applied
intra-uterinally, which extension extends out of the cavum uteri
through the cervical canal into the vagina. Such devices are made
entirely of synthetic plastic material. However, the synthetic
plastic suitable for forming the spiral is too rigid for the part
located within the cervix and within the vagina. Therefore, with
such contraceptives, which extend into the cervical canal, very
many side effects have been observed, such as spasmodic pain and
haemorrhages [WILLSON, Amer.J.Obstet.Gynecol. 92(1965)62]. The
consequence of spasms of the uterus is frequently an unnoticed
spontaneous explusion and a subsequent pregnancy.
A further disadvantage of the known medicament-containing
contraceptives is that the long term release of non-metallic
active substances does not occur with the regularity necessary for
maintaining the contraceptive action within certain predetermined
limits. The large scale manufacture of contraceptives of this type
is also technically difficult and necessitates the taking of many
precautionary measures.
The pregnancy rate, which has been calculated by the
life-table method [TIETZE, Intra-Uterine Contraception, Recommended
Proc. for Data Analyses Sltudies in Family Planning No. 18 (Suppl.),
The Population Council, New York, 1967], when the hitherto proposed
intra-uterine contraceptives are used is such that they do not
achieve as high a reliability in action as the known contraceptives
administered ~ os, which contain hormones as medicinally active `~
substances [DAVIS, Amer.J.Obstet.Gynec. 114(1972) 134; FUCHS et al.,
Contraception 5(1972) 119].
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)37~Q~
It is an object of the present invention to make it poss- -
ible to provide a universal and uncomplicated medicament-containing
contraceptive for human intra-uterinal use which is reliable in
action. The contraceptive should be capable of being used without
risk continuously over a period of several years without physical -
or psychological injury for all expected dimensions of the cavum
uteri in nulliparae, nulligravidae, multiparae and multigravidae.
It should also be so constituted that, during its period of use,
it does not check or impair subsequent fertility. The use of the - ~-
medicament-containing contraceptive should not entail the risk of -
undesired side effects such as dysfunctional haemorrhages,
infections, spasmodic pain, translocations including perforations - -
and migrations, and the risk of spontaneous explusions. The
intra-uterine contraceptive should be so shaped, while taking into
account all expected dimensions of the cavum uteri, that it cannot -
twist in the uterus both at high motility of the uterus and in a
small cavum uteri and cannot become undesirably placed, that its
position can be simply and definitely ascertained if necessary by
X-rays, and is so constituted with a sufficient degree of inherent
stability and the flexibility necessary for application, use and
extraction having regard to the form and the material used for its
..
manufacture, that there is substantially no risk that mechanical o
injury to the uterus will occur. It should be possible to introduce
the contraceptive under aseptic conditions into the uterus in a
simple and painless manner without appreciable dilatation of the
cervical canal and without the use of further medicaments. '--
The applicator for the intra-uterine contraceptive should
be so constituted and correlated to the device that `the contraceptive `;
can be administered under aseptic conditions.
Such medicament-containing contraceptives should be capable ~;
of being manufactured and sterilized in large numbers industrially ~
in a simple and reliable manner. This type of contraceptive should, ~ -
above all, be so constituted that the probability of undesired ;
....
- 8 -
^` 103~7806
pregnancies duirng the period of use is as far as possible
equal to zero.
According to the present invention there is provided
an intra-uterine contraceptive device which comprises a Y-shaped
member formed of synthetic plastics material, the free end of
each branch of the Y terminating in a rounded head member, the
stem of the Y being formed with a plurality of rounded enlarge-
ment members which are spaced apart from one another along the
length of the stem, the angle subtended between the branches
of the Y and the angles subtended between the branches and the
stem of the Y each being obtuse and the resilience of the Y-
shaped member being such that the branches of the Y can be so
resiliently deformed as to bring them into substantially axial
alignment with the stem of the Y.
The present invention substantially provides a con-
traceptive consisting of round rods connecting a plurality of
spheres of synthetic plastic of high elasticity, tensile strength
and medium hardness having a maximum weight of 0.5 gram, and
incorporating one or more pharmacologically active substances,
and optionally having an intra cervical appendage of synthetic
plastic, preferably LTV-silicone elastomer, in the form of a
thread or filament.
The physical properties of the synthetic plastics
material should be as follows:
Modulus of elasticity (ASTM D 747 RESP. 638):
900 to 2,900, preferably, 1,000 to 2,750, kilograms
per squar~ centimetre.
, Tensile strength (ASTM D 638 RESP. 412):
50 to 120, preferably, 60 to 105, for silicone -
elastomers and 150 to 550 kilograms per square
_ centimetre for thermoplastics.
Shore hardness: A 35 to 85, preferably, 40 to 75,
~_9_ ' ;'
A
-.
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1037B06
(DIN 53 505) for silicone elastomers, and D to
40 to 70, preferably, 45 to 60 (ASTM D 676) for
thermoplastics.
J Several forms of intra-uterine contraceptive device
constructed in accordance with the invention will now be
described with reference to the accompanying drawings, in which:
Figures 1 and 2 are side views of two forms of device.
Referring to Fig. 1, the first form of device is
generally Y-shaped and has a total length of 3 to 4 cm. Three
roads 2, 3, and 4 extend outwardly from a central sphere 1 having
a diameter of 2.5 to 3.0 mm. The rods 2, 3 and 4 terminate in
spheres, and have different lengths and diameters of 1.0 to 1.5
mm. The length of the rod 3 is 0.8 to 1.2 cm, and the rod 4
is 0.5 - 0.8 cm long. The spheres 5 and 6 at the end of rods
3 and 4 have diameters of 4 to 5 mm and 1.5 - 2.0 mm, respective
ly. The rods 3 and 4 are ~- -
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at an obtuse angle to the third rod 2. The stem of the Y is formed
by the third rod 2 which continues into an assembly of three rods
7, 8, and 9 interconnecting four spheres 10, 11, 12 and 13 having
a diameter of 2 to 3 mm, the stem terminating in a bean-like end-
piece 14 having a length of 4 to 5 mm and a diameter of 2 to 3
mm. The piece 14 is provided with a central bore 15 having a
diameter of 0.5 to 1.5 mm. The angle between the axes of the rods
3 and 4 does not exceed 130 and preferably does not exceed 127.
Moreover, the angle between the axes of the rods 3 and 4 is
advantageously at least 120 and preferably at least 121. The
angle between the axes of rods 2 and 3 is substantially equal to
the angle between the axes of the rods 2 and 4.
The bore or eye 15 is provided for receiving a thread
18 of suitable material, for example, nylon or polyester. The
thread 18 serves as an indicator thread for indicating in a simple
manner the presence of the contraceptive device.
Figure 2 illustrates a second form of contraceptive
device similar to the first form of device, except that another
thread or filament 19 of synthetic plastic serves as an intra-
cervical appendage which is passed through the central bore 15and secured to the end-piece 14, and also contains one or more
pharmacologically active ingredients.
For making the synthetic plastic body for the contra-
ceptive of the invention there may be used synthetic plastics,
which release one or more pharmacologically active ingredients
contained in admixture or conjunction with the synthetic plastic
and have adequate mechanical properties such as, for example,
tensile strength, elasticity and cold stretchability, and can eas-
ily be formed into suitable shapes. Such plastics include, for
example, polyethylene, ethylene/vinyl acetate copolymers,
ionomeric resins derived from polyethylene, polyamides, polyether-
ester elastomers on a terephthalate base, polyethylene terephtha]ate, ~ ;
~ ~ .
~037~06
and also silicone rubbers. The synthetic plastics may be usedsingly or in combination, for example, in layers. The pharma-
cologically active ingredients incorporated in the intra-uterine
contraceptive may be metals, metal alloys or non-metallic pharma-
cologically active ingredients of natural or synthetic origin
which are located on the surface of the synthetic plastic body or
contained in a synthetic plastics base.
Suitable metallic active ingredients include, for example,
metals such as, for example, copper, silver, nickel, combinations
of such metals with one another and mixtures of the pure metals
with the corresponding metal alloys. The metal or metal alloys
may be uniformly dispersed in the entire synthetic plastic body or
only in certain parts thereof or may be applied partially and/or
in alternation to the surface of the contraceptive in a suitable
manner.
The metallic pharmacologically active ingredients may be -
~incorporated in or applied to the synthetic plastic bodies in
known manner, for example, by electro-deposition, treatment with
steam, reductive separation, optionally with the aid of an adhesive
agent or by dispersing. In applying the metal or metals by electro-
deposition, the metal may separate in various forms and layers of
different metals may be applied one upon another. The thickness of
the layer of metal applied should be such that the metal does not
become detached from the synthetic plastics body when the contracep-
tive is subjected in the uterus to large alternating bending
stresses.
In a preferred form of the contraceptive, a metallic
pharmacologically active ingredient is applied to the spheres 5, 6,
10, 11, 12 and 13, and the metal on different spheres may be the ~ -
same or different. The arrangement of metals on the different
spheres may be in groups or alternating. Especially advantageous
is an alternating arrangement of copper and nickel.
-- 11 --
~- . . ;:
37806
The non-metallic pharmacologically active ingredients
which may be used in contraceptives of the invention are preferably
compounds having hormonal activity, local anaesthetics and weakly
basic buffer substances. Such ingredients include, for example,
~4-pregnen-3,20-dione (Progesterone), d-13-ethyl-17~-ethinyl-17~-
hydroxy-4-gonen-3-one (d-norgestrel) and esters thereof, 17~-ethinyl-
19-nortestosterone (norethisterone) and esters thereof, 6-chloro-
17-hydroxy-1~,2~-methylene-pregna-4,6-dien-3,20-dione (cyproterone)
and esters thereof, 3-methoxy-19-nor-17~-pregna-1,3,5(10)-trien-20
-yn-17-ol (mestranol), 18-methyl-19-nor-~4-pregnen-17~-ol-3,20-dione,
-17~-caproate, 3-hydroxy-1,3,5(10)-oestratien-17-one (oestrone),
17-acetoxy-6~,7~-epoxy-1~,2~-methylene-4-pregnen-3,20-dione,
4,6-dichloro-17-acetoxy-16a-methyl-4,6-pregnadien-3,20-dione,
17-hydroxy-6-methyl-pregna-4,6-dien-3,20-dione acetate (megestrol
acetate), l9-nor-5~-pregnan-3,20-dione, 3~-hydroxy-19-nor-5~- ~
pregnan-20-one, l9-norhydroxyprogesterone and esters thereof, ;
6-chloro-17-hydroxy-pregna-4,5-dien-3,20-dione acetate (chloro-
madinone acetate), 1,3,5tlO)-oestratrien-3,17~-diol (oestradiol), -.
1,3,5(10)-oestratrien-3,16a,17~-triol (oestriol), 17~-hydroxy-4-
androsten-3-one (testosterone) and esters thereof, 21-hydroxy-5~
-pregnan-3,20-dione and esters thereof, 17~-acetoxy-6~-methyl- -
progesterone (medroxy-progesterone acetate), 10~-pregna-4,6-dien
-3,20-dione (dydrogesterone), 17~-oestradiol, and xylocaine,
novocaine, triethanolamine, disodium ethylene diamine tetracetate
and phosphate buffers of Sorensen.
The non-metallic pharmacologically active ingredients -~
may be in admixture or conjunction with the synthetic plastic body.
- For example, they may be dispersed homogeneously in the synthetic
plastic body, if desired using auxiliary substances, or contained
in separate parts of the contraceptive device in suitable quantities
with or without the auxiliary substances for example, as a core
in a part of the synthetic plastic body. Such auxiliary substances
- 12 -
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1~$7B06
may be, for example, tenside, highly dispersed silicon dioxide,
anti-foaming agents, solubilisers, resorption retarders, X-ray
contrast agents, and ferro-magnetic substances for assisting in
ascertaining the location of the contraceptive device.
A preferred form of the contraceptive contains d-13-ethyl-
17~-ethinyl-17~-nydroxy-4-gonen-3-one (d-norgestrel) homogeneously
dispersed in a silicon rubber base that vulcanizes at a slightly
elevated temperature, contains 5~ by weight of barium sulphate and
is strengthened with highly dispersed silicon dioxide.
Another form of the contraceptive of the invention contains
in the spheres 5, 6, 10, 11, 12 and 13 cores that consist of a
mixture of 6-chloro-17-hydroxy-1~, 2~-methylene-pregna-4,6-dien-3,
20-dione acetate (cyproterone acetate) and lac~ose, the synthetic
plastic body of this contraceptive consisting of an ethylene/vinyl
acetate copolymer. The core members may have a cylindrical surface
and end faces of which the radius of curvature is within the range
of from the radius of the cylindrical surface (giving substantially
spherical core members) to infinity (giving cylindrical core
members).
The pharmacologically active ingredients contained in the
thread-shaped appendage 19 are arranged to be released in a
controlled manner from the carrier material of synthetic plastic
at a given level within certain predetermined limits over a limited
period, that is to say, in the first months of use of the contracep-
tive, and subsequently the contraceptive action is derived from the
contraceptive device, which, containing an active ingredient is also
active on its own.
The appendage 19 can also be used with other contraceptive
devices capable of intra-uterine use, which are suitable according
to known practice for connection, for example, by knotting, adhesion
or welding, to an intra-cervical thread-shaped medicament carrier.
There may be mentioned more especially contraceptives described in
- 13 -
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S1~7806
U.S. Patent No. 3,533,406, German Offenlegungsschrift No. 1,956,701,
U.S. Patent No. 3,563,235 and German Offenlegungsschrift No.
2,207,939.
The dimensions of the thread or filament are so chosen
that the thread can extend into the cervical canal, but not into é
the vagina. The thread or filament has a diameter of 0.2 to 1.0 mm
and a length of 1.0 to 5.0 cm. The thread or filament has a
pharmacologically active ingredient content of from 10 to 70~. ~
The non-metallic medicaments present in the thread-shaped --
10intra-cervical appendage are preferably compounds having hormonal
activity, for example, A4-pregnen-3,20-dione (progesterone), d-13-
ethyl-17a-ethinyl-17~-hydroxy-4-gonen-3-one (d-norgestrel) and
esters thereof, 17a-ethinyl-19-nortestosterone (norethisterone) and
esters thereof, 6-chloro-17-hydroxy-la, 2a-methylene-pregna-4,6- - ~
dien-3,20-dione (cyproterone) and esters thereof, 3-methoxy-19-nor - -
-l7a-pregna-l~3~5(lo)-trien-2o-yn-l7-ol (mestranol), 18-methyl-19-
nor-~4-pregnen-17a-ol-3,20-dione-17a-caproate, 3-hydroxy-1,3,5(10)
oestratrien-17-one (oestrone), 17-acetoxy-6~,7~-epoxy-la,2a-methy-
lene-4-pregnen-3,20-dione, 4,6-dichloro-17-acetoxy-16a-methyl-4,
6-pregnadien-3,20 dione, 17a-hydroxy-6-methyl-pregna-4,6-dien-3,20-
dione acetate (megestrol acetate), l9-nor-5a-pregnan-3,20-dione,
3~-hydroxy-19-nor-5a-pregnan-20-one, l9-norhydroxy-progesterone
and esters thereof, 6-chloro-17-hydroxy-pregna-4,6-dien-3,20-dione
acetate(chlormadinone-acetate), 15, 16a- and 15,16~-methylene-17~-
hydroxy-18-methyl-17a-ethinyl-4-oestren-3-one, 17~-hydroxy-4-
androsten-3-one (testosterone) and esters thereof, 21-hydroxy-5~- -
pregnan-3,20-dione and eslters thereof, 17a-acetoxy-6a-methyl-
progesterone (medroxy-progesterone acetate and 10a-pregna-4,6- `
dien-3,20-dione (dydrogesterone).
Preferred are steroid hormones having a gestagenic activity, -
such as d-norgestrel and progesterone, norethisterone, cyproterone
acetate, norhydroxyprogesterone, and 15,16a- and 15,16~-methylene-
- 14 -
~137~Q~
d-norgestrel.
The non-metallic pharmacologically active ingredients in
the thread or filament are dispersed homogeneously therein, if
desired with the addition of auxiliary substances. Such auxiliary
substances may be, for example, tenside, anti-foaming agents,
solubilisers and resor~tion retarders such, for example, as highly
dispersed silicon dioxide.
As synthetic plastics for making the medicament-containing
appendage 19 there may be used, more especially, LTV-silicone
rubber two-component compositions such as can be prepared, for
example, by the process of U.S. Patent No. 2,823,218 [see also the
article by W. Noll, Chemie and Technologie der Silicone, 1968,
page 341, and Chemiker-Zeitung 97 ~1973), pages 176 et seq].
Especially suitable are those compositions which contain from 89%
to 91% of linear dimethyl-polysiloxane containing a maximum of
0.5 mol% of methyl-vinyl-siloxane units and g - 11% of dimethyl-
polysiloxane containing Si-H bonds and having a molecular weight
of 500 to 1000, which may contain up to three Si-H bonds and are
catalyzed with platinum or platinum compounds such as, for example, -
hexachloroplatinic acid (elastomer composition I), or one which
contains 85 - 89~ of dimethyl-polysiloxane having a maximum of
0.5 mol % of methyl-vinyl-siloxane units, 5 - 6% of dimethyl- ~ -
polysiloxane containing Si-H bonds, and 5 - 10~ of a cross-linking
and strengthening dimethyl-polysiloxane resin having a maximum
of 1.2 mol % methyl-vinyl-siloxane units, and which is catalyzed -~-
with a platinum-ethanol complex compound (elastomer composition
II).
The contraceptives of the invention are superior to the
known contraceptives in their long-term action since their pregnancy
rate during application, determined on the basis of the life-table
method, is markedly lower and fewer spontaneous explusions and
other side effects occur.
. '
- 15 -
378~6
The expulsion rate of the contraceptives of the invention
is extraordinarily low, although the devices contain no abutments
acting against explusive movement and their shape does not permit
anchoring in the mucous membrane or musculature of the uterus.
In contradistinction to intra-uterine contraceptives free from
pharmacologically active ingredients, a large surface of contact
between the device and the endometrium can be dispensed with without
impairing activity, because a better activity is obtained by the
addition of one or more active ingredients.
By the use of known synthetic plastics but not hitherto
usual for making intra-uterine contraceptives, it is possible to
produce, for example, gestagen-containing contraceptives, which
over periods from months to years have a rate of release of
medicament at a dosage within the limits required for intra-uterine
contraception. The contraceptives, independently of the size of
the cavum uteri, are capable of universal use. The devices are
so constructed that they do not penetrate or even push or cut into
the musculature of the uterus.
An advantage of the contraceptive device of the invention ~ -
having filamentary appendage containing a substance having gesta-
genic activity is that the tranquillizing action of gestagens has
a favourable effect on the uterus tUFER, J., Hormontherapie in der
Frauenheilkunde, Verlag Walter De Gruyter Berlin, 1972, p. 124).
The physiological increase in the motility of the musculature of
the uterus that occurs after inserting a foreign body is in this
way reduced. Also, in thlis way, the rate of early explusions
is lowered and, as a result of this, the number of pregnancies that
occur is also reduced. Thus, the disadvantage hitherto associated
with all intra-uterine contraceptives of a high failure rate in the
first few months of use is eliminated, that is to say, the first
critical phase in the use of intra-uterine pessaries can be
bridged. ;
- 16 -
. ~
~: . , :, .
.. . . .
378l~6
The intra-uterine contraceptive devices of the invention
are formed in a manner favourable for application. One form of
suitable applicator is the known insertion tube 16 having an
internal diameter of 3.5 mm and a wall thickness of 0.5 mm, and ~ - -
:. .. .
formed of high-pressure polyethylene or another suitable synthetic
plastic. The contraceptive is inserted under aseptic conditions up
to the point of connection of the sphere 5 with the indicator thread
18 fastened in the eye 15 and the pull and push rod 17 connected
thereto. Thus, aseptic conditions can be maintained, because the
contraceptive device can be inserted into the applicator tube
by pulling the rod 17 and without removing the bag in which the
device has been stored or touching the device itself. The sphere
5 of the device forms a ball closure for the application unit
consisting of the contraceptive and applicator. Since the edge of
the insertion tube 16 is covered, primary injuries during application ~;
are eliminated. Moreover, the ball-shaped end having a diameter
of 4 to 5 mm prevents the fundus uteri from being cut into.
Application of the contraceptive device can easily be carried out
by a professional person. It can be carried out under aseptic cand~-
tions without anaèsthesia or the use af further medicaments or dilat-
ion of the cervical canal without causing spasmodic pain, even in the
case of women who have not given birth.
The following examples illustrate the invention.
Example 1
An intra-uterine contraceptive device including a synthetic
plastic body consisting of a thermoplastic polyether-ester elastomer
sprayed onto a terephthallate base and having the structure shown
in Figure 1 has the following dimensions: total length-3.6 cm,
diameter of the sphere 5-4.8 mm, diameter of the sphere 6-1.5 mm, ~ ;
diameter of each of the spheres 1 and 10 to 13-2.8 mm, diameter of
the round rod 4-1.3 mm, diameters of the round rods 2 and 3 and 7
to 9-1.5 mm, lengths of the round rods 3 and 4-0.85 cm and 0.65 cm,
.. : .
- 17 - i ~;
1~7~0t:~
respectively, length and diameter of the end piece 14-4.5 mm and
2.8 mm, respectively, and total weight of the synthetic plastics
body 220 mg. The angle between the axes of the rods 3 and 4 is
123~. The angle between the axes of the rods 2 and 3, and the
angle between the axes of the rods 2 and 4 are equal.
The physical properties of the device are as follows:
Elongation at break : 200~.
Tensile strength : 365 kilograms per square centimetre.
Shore hardness : D 55.
Modulus of elasticity : 1410 kilograms per square -
centimetre.
Coefficient of restitution : 55~.
Flexural modulus : 2100 kilograms per square centimetre. ~ -
The surfaces of the spheres of the synthetic plastic
body are electroplated with the aid of an adhesive underlayer. The
spheres 5, 6, 7, 10, 11, 12 and 13 are galvanically coated with
nickel having a layer thickness of 100 ~m, and the spheres 5, 11
and 13 are in addition galvanically coated with copper having a
layer of 100 ~m.
Example 2
A synthetic plastic body having the dimensions given
in Example 1 is formed from a thermoplastic synthetic plastic ;
material derived from polyethylene, which material contains
carboxyl groups connected by copolymerization to the chain molecules
of the polymer and is cross-linked with sodium ions. The spheres
5, 6 and 10 to 13 of the synthetic plastic body are chemically
coppered on the surface, the layer thickness being about 0.5 ~m,
with the interposition of an adhesive underlayer of highly
dispersed iron. Nickel is electro-deposited, the layer thickness
being 80 ~m, on the chemically deposited copper layer. The spheres
5, 11 and 13 are in addition galvanically coated with copper having
a layer thickness of 60 ~m.
- 18 -
-~ . ,
. .~, ~ .
- ,. . ..
- ~ , '
37~
Example 3
75.0 g of a thermoplastic polyether-ester elastomer
on a terephthalate base present in the form of a very fine granulate
are uniformly mixed with 12.5 g of highly dispersed copper powder
and 12.5 g of highly dispersed nickel powder. From the above
mixture, there is formed a contraceptive device having the shape,
dimensions and physical properties specified in Example l. -
Example 4
60.0 g of a catalyzed silicone rubber two-component
mixture of low temperature vulcanizing type (LTV) are mixed with
40.0 g of highly dispersed silicon dioxide. From the suspension,
there is produced, by vulcanizing the moulded mass for one hour
at ll~qC a contraceptive device having the dimensions given in -~
Example 1, except that the angle between the axes of the rods
3 and 4 is 125.
.. ~
The physical properties of the device are as follows: ;
Elongation at break: 290%
Tensile strength: 70 kilograms per square centimetre. ;~
Shore hardness: D40.
Coefficient of restitution: 45%
In the manner described in Example 2, the synthetic ~ ;
plastic bodies are partially and in alternation galvanically surface
coated with copper and nickel. -
Example 5
An intra-uterine contraceptive device, which includes
surfaces partially and in alternating order copper and silver coated,
is produced in the following manner:
From high pressure polyethylene, synthetic plastic bodies
are formed having the structure shown in Figure 1 and the following
30 dimensions: total length 3.4 cm, diameter of sphere 5-4.6 mm, dia-
meter of sphere 6-1.6 mm, diameter of each of the spheres 1 and 10
to 13-2.6 mm, diameter of the rod 4-1.2 mm, diameter of each of the
rods 2, 3 and 7 to 9-1.6 mm, length of the rod 3-0.9 cm, length of
the rod 4-0.7 cm, length of the end-piece 14-4.5 mm and diameter of
- 19-- ' ' ' '
7bl06
the end-piece 14-2.6 mm.
On the spherical parts 5, 6 and 10 to 13 of the synthetic
plastic body silver is deposited by reduction, the layer thickness
being about l~m. On the silver layer, copper is electro-deposited,
the layer thickness being about 90 ~m, and the surface of each of
the spheres 5, 11 and 13 is also galvanically coated with silver,
the layer thickness being 70 ~m.
Example 6
A synthetic plastic body having the dimensions given
in Example 5 (the angle between the axes of the rods 3 and 4
being 123, and the angle between the axes of the rods 2 and 3
being equal to the angle between the axes of the rods 3 and 4),
the structure shown in Figure 1 and the physical properties given
in Example 1 is formed by injection moulding a thermoplastic poly-
ether-ester elastomer based on a terephthalate base. The partial
metal coating of the synthetic plastic body with copper and silver
in alternating order is applied using the procedure described in
Example 2, with the aid of an adhesive underlayer and subsequent ~ -
electro-deposition. The spheres 5, 6 and 10 to 13 are coated with
a layer of copper hauing a thickness of 100 ~m, and the spheres
5, 11 and 13 are additionally coated, on top of the 100 ~m copper `
layer, with a layer of silver having a thickness of 75 ~m.
Example 7
A synthetic plastic body of thermoplastic polyether-ester
elastomer based on terephthalate is formed with the outline shown
in Figure 1 and the dimehsions and physical properties given in
Example 1. The spheres 6, 10 and 12 are galvanically coated,
after applying a conductive silver lacquer having a layer thick-
ness of 10 ~m, with nickel in a layer thickness of 90 ~m. The
30 spheres 5, 11 and 13 are also coated, over a layer of conductive
silver lacquer having a thickness of about 10 ~m, with silver
having a layer thickness of 80 ~m.
-20-
.. . . .
: . . .. : . . . . . , ~
1037806
Example 8
35.0 g of micronized d-13-ethyl-17~-ethinyl-17~-hydroxy-
4-gonen-3-one and 5.0 g of highly dispersed barium sulphate are
uniformly mixed with 60.0 g of very finely granulated high pressure
polyethylene having a particle size of about 500 ~m. From the
mixture, there is formed an intra-uterine contraceptive device
having the structure given in Figure 1 and the dimensions mentioned
in Example 5. ~
Example 9 ~ -
30.0 g of micronized d-13-ethyl-17~-ethinyl-17~-hydroxy-
4-gonen-3-one (d-Norgestrel) are incorporated in a mixture of 5.0 g
of highly dispersed barium sulphate, 20.0 g of highly dispersed
silicon dioxide and 45.0 g of catalyzed LTV-silicone rubber two-
component composition. The suspension is shaped and vulcanized for
one hour at 110C to form d-norgestrel- containing synthetic
plastic bodies having the outline shown in Figure 1 and the dim-
ensions specified in Example 1, except that the angle between the
axes of the rods 3 and 4 is 125. The physical properties of the
device are as specified in Example 4.
Example 10
From a mixture of 50.0 g of micronized progesterone and ~ ~ ;
49.1 g of lactose with the addition of 0.1 g of lubricant, there
are made by injection moulding generally cylindrical mouldings of
2 mm diameter, the end faces being convex and having a radius of
curvature of 3 mm. The progesterone mouldings are inserted as
cores in the spherical palrts 5 and 10 to 13 of an intra-uterine ;
contraceptive device, of which the structure is as shown in Figure 1
and the dimensions are as specified in Example 5, except that the
angle between the axes of the rods 3 and 4 is 125. Apart from
the mouldings already referred to, the device is made from a
mixture of 5.0 g of barium sulphate, 35.0 g of highly dispersed
silicon dioxide and 60.0 g of catalyzed LTV-silicone rubber two-
,
-21-
l037~aG
component composition by vulcanization for one hour at a temp-
erature of 100C in conjunction with moulding. The physical
properties of the device are as specified in Example 4.
Example 11
A homogeneous mixture of 40.0 g of 6-chloro-17-hydroxy-
la,2~-methylene-pregna-4,6-dien-3,20-dione acetate with 59.8 g of
lactose and 0.2 g of a lubricant mixture is moulded under pressure
to form generally cylindrical mouldings having a diameter of 2 mm,
the end faces being convex and having radius of curvature of 3 mm.
The mouldings are incorporated as cores in the spheres 5 and 10 to
13 of an intra-uterine contraceptive device, of which the body has
the outline shown in Figure 1 and which has the dimensions spec-
ified in Example 5, and which is made of high pressure polyethylene
with the addition of 5% of barium sulphate.
Example 12
With the mixture described in Example 9, there is made by
moulding and vulcanizing for 2 hours at 100C a medicament-contain-
ing synthetic plastic body, from which is made by extraction in
succession with 10 ml of`ethanol of 96% strength for 90 minutes
and ethanol of 70, 50, 30 and 10% strength for 30 minuies an intra-
uterine contraceptive device of which the core of the synthetic
plastic body is enriched with _-norgestrel. The physical properties x
of the device and the angle between the axes of the rods 3 and 4
are as specified in Example 4. ~
Example 13 ~ -
50.0 g of micronized 17~-ethinyl-19-nortestosterone-
oenanthate are homogeneously mixed with 10.0 g of highly dispersed
silicon dioxide, 5.0 g of barium sulphate and 35.0 g of catalyzed
LTV-silicone rubber two-component composition. The mixture is
moulded to form a Y-shaped body having a rod diameter of 1 mm and
a total length of 3 cm, and is vulcanized for 10 hours at 60C,
and serves as the core member of an intra-uterine contraceptive ` ~
-22- ~ -
device having the outline shown in Figure 1. The medicament-
containing body is encased with high pressure polyethylene in such
a manner that a contraceptive having the dimensions specified in
Example 5 is obtained. The angle between the axes of the rods 3 -
and 4 is 125. The physical properties of the device are as
specified in Example 4.
Example 14 ~ -
30.0 g of d-13-ethyl-17~-ethinyl-17~-hydroxy-4-gonen-3-
one are mixed with 10.0 g of barium sulphate and 60.0 g of a very ~-
finely granulated copolymer of ethylene and vinyl acetate, and the ~-
mixture is shaped to form a Y-shaped body having a rod diameter of `
1 mm and a total length of 3 cm. The medicament-containing body is
encased with a mixture consisting of 45.0 g of highly dispersed
silicon oxide, 10.0 g of barium sulphate and 45.0 g of catalyzed
LTV-silicone rubber two-component composition so as to have the
dimensions given in Example 1, except that the angle between the
axes of the rods 3 and 4 is 126, and the outline shown in Figure 1,
and is vulcanized for one hour by hQating at 100C. '
The physical properties of the device are as follows:
Elongation at break: 600%
Tensile strength: 211 kilograms per square centimetre.
Shore hardness: D 35
Modulus of elasticity: 1,270 kilograms per square centi-
metre.
Example 15
A synthetic pl~stic body injection moulded from thermo-
plastic polyether-ester elastomer based on terephthalate has the
structure shown in Figure 1 and the following dimensions: `~
total length 3.6 cm, diameter of the sphere 5-4.8 mm, diameter of ~-
30 the sphere 6-1.5 mm, diameters of each of the spheres 1 and 10 to
13-2.8 mm, diameter of the rod 4-1.3 mm, diameter of each of the
rods 2, 3 and 7 to 9-1.5 mm, lengths of the rods 3 and 4-0.85 cm
-23-
,_ . . . - . . . . . . . .. . .
~03~06
and 0.65 cm, respectively, length of the end-piece 14-4.5 mm,
diameter of the end-piece 14-2.8 mm, and total weight of the syn-
thetic plastic body 220 mg. The angle between the rods 3 and 4 is
123 and the physical properties of the device are as specified in
Example 1.
The surfaces of the spheres of the synthetic plastic body
are electroplated with the aid of an adhesive ground layer. The
spheres 5, 6 and 10 to 13 are galvanically coated with silver having
a layer thickness of 100 ~m and the spheres 6, 10 and 12 are gal-
vanically coated, in addition, with copper having a layer thicknessof 100 ~m.
Example 16
` In order to form an intra-uterine contraceptive device, a
synthetic plastic body having the dimensions specified in Example 1
is formed from a thermoplastic synthetic plastic material derived
from polyethylene, which material contains carboxyl groups connected
by copolymerization to the chain molecules of the polymer and is
cross-linked with sodium ions. The surfaces of the spheres 5, 6
, and 10 to 13 of the synthetic plastic body are coppered chemically -~
with the interposition of an adhesive underlayer containing highly
, ~ , .
dispersed iron (layer thickness about 0.5 ~m). Onto the chemically
deposited copper layer, silver is electro-deposited to a thickness -
of 80 ~m. The spheres 6, 10 and 12 are galvanically coated, in
addition, with copper having a layer thickness of 80 ~m.
Example 17
; 75.0 g of ther~oplastic polyether-ester elastomer based
:; :
~ on terephthalate in the form of a very fine granulate are uniformly ~
~;,i :
mixed with 12.5 g of highly dispersed copper powder and 12.5 g of
highly dispersed silver powder. The mixture is formed into an
intra-uterine contraceptive device having the dimensions and physical
properties specified in Example 1.
'
:-- .:
~37~0~;;
Example 18
60.0 g of a catalyzed silicone rubber two-component
mixture of the low temperature vulcanizing type (LTV) are mixed
with 40.0 g of highly dispersed silicon dioxide. Synthetic
plastic bodies having the dimensions given in Example 1, except
- that the angle between the axes of the rods 3 and 4 is 125, are
made with the suspension by vulcanizing the shaped mass for one
hour at a temperature of 110C. The physical properties of the
device are as specified in Example 4.
In the manner described in Example 2, the synthetic
plastic bodies are partially and in alternation galvanically coated
on the surface with copper and silver.
' -,.'~,
Example 19
An intra-uterine contraceptive device, which contains on
the surface partially and in alternating order copper and silver,
is made as follows:
,
Synthetic plastic bodies of high pressure polyethylene
are formed having the outline shown in Figure 1 and the following
dimensions: total length 3.4 cm, diameter of the sphere 5-4.6 mm, - :
diameter of the sphere 6-1.6 mm, diameter of each of the spheres
1 and 10 to 13-2.6 mm, diameter of the rod 4-1.2 mm, diameter of
each of the rods 2, 3 and 7 to 9-1.6 mm, lengths of the round rods
3 and 4-0.9 cm and 0.7 cm, respectively, length of the end-piece
14-4.5 mm and diameter of the end-piece 14-2.6 mm. -
On the spheres 5, 6 and 10 to 13 of the synthetic plastic
body, the surface of thelsynthetic plastic material is activated -~
by treatment with an ionic solution of palladium. Upon the activat-
ed surface, copper is chemically deposited to a layer thickness of
about 1 - 2 ~m. Silver is then electro-deposited by a customary
process of galvanizing synthetic plastic to a layer thickness of
about 80 ~m on the spheres 6, 10 and 12, in addition, 100 ~m of
copper.
., `'"' ' , . .
-25-
.. ''.
~ ,. . ~ . . . .
~37~0~;
Example 20
A synthetic plastic body having the dimensions given in
Example 5, except that the angle between the axes of the rods 3
and 4 is 123, and the outline shown in Figure 1 is made by in-
jection moulding a thermoplastic polyether-ester elastomer based
on terephthalate. The synthetic plastic body is partially coated
with metal consisting of copper and silver in alternating order,
as described in Example 19, by chemical and electrolytic deposition
on the surfaces, which have previously been activiated with ionic
palladium solution, of the spheres 5, 6 and 10 to 13. The elec-
trolytically deposited silver layer has a layer thickness of about
90 ~m, and the electrolytically deposited copper layer has a thick-
ness of about 60 ~m. The device has the physical properties spec-
ified in Example 1.
Example 21
A synthetic plastic body consisting of thermoplastic
polyether-ester elastomer based on terephthalate partially met-
. ~.,
allized with copper and silver in alternating order and having theoutline shown in Figure 1 and the dimensions given in Example 1,
is, after activation of the synthetic plastic surface with ionic
20 pa~ladium solution, chemically coppered to a layer thickness of r''
about 1 to 2 ~m. There are then electro-deposited, in succession,
100 ~m of silver and 80 ~m of copper. With the aid of a suitable
screening lacquer, the metal coating of all the round rods, of the
end-piece 14 and of the central sphere 1 is removed in a two-stage
process, the metallization of the spheres 5, 11 and 13 remaining
:' I . ..
complete and that of the spheres 6, 10 and 12 being retained with
the exception of the 80 ~m copper layer. The physical properties
- of the device are as specified in Example 1.
Example 22 ;~
30.0 g of micronized _-13-ethyl-17~-ethinyl-17~-hydroxy- - -
4-gonen-3-one ~d-norgestrel) and 70.0 g of LTV-silicone rubber two-
- component composition (elastomer type I) are worked up into a
- -26-
`~: . '
10;17~6
suspension free from air bubbles. The suspension is passed through
a jet to form a filament and vulcanized by being heated at a temp-
erature of 100C for two hours. A filament having a diameter of
0.5 mm is obtained and is cut into lengths of 4 cm, one of which,
after attachment to an intra-uterine contraceptive as shown in
Figure 2, leaves a free length of 2 cm. The filament together with
the contraceptive is sterilized in superheated steam for 30 minutes
and packed sterile.
Example 23
In a manner similar to that specified in Example 22, a
filament having the dimensions specified in that Example is made.
The filament contains, as a gestagenically active steroid hormone,
25% of 17~-acetoxy-17-ethinyl-4-oestren-3-one (norethisterone
acetate), and may be attached to an intra-uterine contraceptive -
device as shown in Figure 2.
Example 24
An intra-cervical filament is made using 40 parts by
weight of very finely micronized progesterone which is mixed with -
60 parts by weight of catalyzed LTV-silicone rubber two-component
composition (elastomer composition II), by shaping the progesterone
suspension and then heating for one hour at 100C. The thread is ~-
2.5 cm in length and has a diameter of 0.5 mm. It may be attached ~
to an intra-uterine contraceptive device as shown in Figure 2.
Example 25
In a manner similar to that described in Example 22, a ;
filament is made having the length specified in that Example but ;
; a diameter of 0.4 mm. The filament contains, as a gestagenically
active steroid hormone, 30% of 17-hydroxy-19-norpregn-4-en-3,20- ;~ ,
dione (norhydroxy-progesterone). It may be attached to an intra-
uterine coneraceptive device as shown in Figure 2.
.. ~',-
-27-
. I .
- , ,;: , ~, ,-!O;r- . -
: ' ' . ~ ' . ' ' ::
