FI93922C - Device for delivery of active substance - Google Patents

Description

93922

ACTIVE SUBSTANCE DISSEMINATION DEVICE - ANORDING FOR AVAILABILITY

The invention relates to a ring for intraperitoneal use of an active substance, such as a hormone, which can be either closed or open and which is made of a flexible polymeric material into which the active substance can be mixed.

A commonly used intrauterine contraceptive is a plastic T-shaped body surrounded by a partially wound copper wire capable of releasing copper ions. The device is inserted into the uterus with a separate applicator.

10 A wire is attached to the device that is so long that it extends out of the cervix when the device is inserted.

Various non-ring-type intrauterine hormone-donating devices are also known in the literature.

US 3656483 describes a hormone-donating IU (intra-uterine) device with laterally extending wings in place.

U.S. Pat. No. 4,014,988 describes hormone-releasing IU devices in which the active ingredient is dissolved in a liquid carrier in a container. The layer surrounding the container is a suitable polymer. IU devices are not annular but T-, 7-, or S-shaped.

U.S. Patents 4,264,575 to 4,246,578 all apply to IU devices in which the active ingredient is dispersed in a silicone polymer.

No device structures are disclosed in these patents, but the text portions of the patents referred to devices disclosed in earlier U.S. patents. None of these reference patents relates to a single ring, but to structures of a completely different type.

U.S. Pat. No. 3,896,819 relates to a device for intrauterine use, which may, for example, be of the octagonal shape, in which the active substance is present dissolved in a container from which it is released through the membrane by diffusion.

U.S. Pat. No. 4,180,064 also relates to an intrauterine device, for example an octagonal device, in which the active ingredient is dispersed in a biodegradable polymer.

US 4871543 and US 4888074 both describe rings having a core which is an active substance (hormone or other) dispersed in a polymer, e.g. polysiloxane, and a film surrounding the core, e.g. silicone, which does not contain the active substance. However, these rings are intended for vaginal insertion, and there is no mention or indication in the patents that the described rings are also suitable for insertion into the uterus.

15 T-shaped and other non-ring-shaped devices with sharp parts can cause pain to the wearer and even damage to the uterine wall.

The devices described in U.S. Patents 3,896,819 and 4,180,064 are of no practical significance. The system 20 of U.S. Pat. No. 3,896,819 involves high risks: if the container in which the active ingredient is dissolved breaks, then the entire amount of drug is released simultaneously and causes a state of poisoning to the user. In order for such a container to remain intact during the placement of the device, it will be appreciated that its shape must be quite inflexible. This would easily cause damage to the cervix during insertion and removal of the device. The biodegradable polymer-based ring described in U.S. Patent 4,180,064 could not be considered in practice. Biodegradable polymers are hard and inelastic, so it would be very difficult to place rings made of such a material. Breakage of the annular structure of the device during the disintegration process would make it very difficult to remove the device, as the device has lost its shape and hard, broken parts would cause

II

3 95922 vat tissue damage.

It is an object of the present invention to obviate the drawbacks of the above devices and to provide a new intrauterine drug delivery ring made of a highly flexible polymeric material in which the active ingredient is blended.

The invention thus relates to an intrauterine active substance delivery ring, which may be either closed or open, to which a pull-out thread 10 is attached, the ring being made of an elastic polymeric material intended to contain the active substance. It is characterized in that the cross-section of the ring is shaped so as to provide the most uniform rate of active substance delivery so that the travel of the active substance to the circumference of the cross-section at different points in the cross-section is substantially the same length.

To insert the ring according to the invention into the uterus, the applicator described in more detail here can be used. The applicator comprises 20 elongate bodies, the end of the uterus of which is shaped according to the ring sheath so that the ring remains well in place at the shaped end during insertion of the ring, a handle facing away from the body and a locking member on the opposite side .

If desired, the ring according to the invention can be coated with a separate polymer film controlling the rate of release of the active substance. The polymer film can be made of the same or different polymer or polymer blend as the active ingredient-containing polymer matrix. It is essential that the polymer used in both the matrix and the film be very flexible, and therefore silicone polymers are particularly suitable.

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In principle, any active ingredient can be administered with the ring according to the invention. However, the device is specifically intended for the delivery of hormones for the treatment of menopausal disorders or for the prevention of pregnancy.

5 The hormones in question are estrogens and progestins.

The ring according to the invention can be either closed or slightly open. For example, applying the manufacturing method described in U.S. Patent 4,888,074, open rings are obtained by cutting a helical extrudate in the direction of the coil axis. Individual open rings can be closed if desired, but alternatively they can be used as is.

For example, the ring of the invention may be circular, oval, elliptical, or otherwise curved.

For example, the cross-section of rings used intrauterinely may be circular, oval, elliptical, or otherwise suitably shaped. The circular cross-section has the disadvantage that the rate of delivery of the active substance decreases over time due to the fact that the diffusion distance of the substance in the middle of the circle is considerably longer than that of the circumferential substance. In order to obtain the most uniform rate of active substance delivery possible, the cross-section of the ring according to the present invention is shaped so that the travel of the active substance to the circumference at different points of the cross-section is substantially the same length. A preferred cross-sectional shape 30 is a star, for example a four-pointed star with slightly rounded tips to avoid tissue damage.

The shape of the cross-section is mainly relevant only in tires in which the active substance-containing I! 93922 5 The polymer matrix is not coated with a separate film. If, on the other hand, a separate polymer formula is used, this controls the rate of release of the active substance.

Most preferably, the ring according to the invention has an outer diameter of about 18 mm and a cross-section of the ring with a diameter of about 1.5 mm.

Due to the particularly high flexibility of the ring according to the invention, it is easy to insert it also in menopausal women with a narrow cervix. The applicator can also be made very small.

The invention is described in more detail in the following figures, in which

Figure 1 shows a ring according to the invention inserted into the uterus

Figure 2 shows an applicator suitable for inserting a ring

Figure 3 shows another embodiment of an applicator suitable for inserting a ring

Figures 4-7 show the insertion of a ring 20 Figure 8 shows an embodiment of a cross section of a ring

Attached to the ring 12 is a pull-out wire 11 surrounding the sheath of the ring 12 so that both wire ends 11 'and 11' 'are long enough to lock the applicator locking member 19 during insertion. After insertion, the wire ends may be shortened somewhat, but so long that they extend well out of the cervix even when the ring is inserted into the uterus 10. In this case, the ring can be removed.

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Figure 2 shows an applicator suitable for inserting a ring, the elongate body 15 of which consists of a tube through which a channel 16 passes. The handle 17 of the applicator forms an integral part with the body 15. The handle 17 is also provided with a through channel 16 ', which is suitably an extension of the channel 16. The end 18 of the body 15 is shaped so that the ring 12 resting on it remains well in place when the wire ends 11 'and 11' 'are tightened and locked in place by a locking member 19, which is shown only schematically in this figure. A ring 12 having a circular cross-section 22 in the example shown here is shown cut away. The channels 16 and 16 'may be holes passing through the bodies 15, 17 or grooves made in these bodies.

Figure 3 shows another embodiment of the applicator, in which the body 15 consists of a rod. The end 18 of the rod entering the uterus is shaped to support the ring 12. The end 18 is preferably provided with a channel 20, which may be a hole or a groove, for the passage of the pull-out wire. The tightening and locking of the wire ends 11 'and 11' '20 is done in the same way as in the solution shown in Fig. 2. Alternatively, the ring may be placed at the end of the rod so that the point of attachment of the wire will be located at the opposite position of the end 18. The ring is brought into this position by turning the 25 rings shown in Fig. 3 180 °. By pulling the wire, even before inserting the applicator and the ring fitted to it, the ring can be prestressed and brought into a substantially rectangular shape as shown in Fig. 7.

Figures 4-7 show the insertion of the ring 12 into the uterus.

The wire ends 11 'and 11' 'are tightened and locked by means of a locking member 19, whereby the ring rests against the end 18 of the applicator. The applicator is inserted through the cervix until a stop 21 located in the applicator body between the handle 17 and the body end 18 indicates that the ring is in the upper portion of the uterus. The tension of the wire ends 11 'and 11' 'is removed by pressing 93922 7 by tapping the wire ends from the locking member. The applicator is pulled out and the ring remains in the uterus. It can be seen from Figures 5 and 7 that the ring is very flexible. Due to the low compression pressure or low traction, the circumference of the ring is substantially rectangular, the long sides 12 'and 12' 'of which run very close to each other. Figure 4 shows the insertion of the tire without prestressing. Figure 7 shows the insertion of a prestressed ring.

Figure 8 shows a preferred shape of the cross-section 22 10, i.e. a four-pointed star with slightly rounded tips to avoid tissue damage.

The polymers and active ingredients used in the ring of the invention are components commonly used in vaginal rings. The passage of the active substance in the polymer-15 matrix and its release rate through the polymer film follow the same patterns as in the known vaginal rings described e.g. U.S. Patent 4,871,543.

It will be apparent to one skilled in the art that various embodiments of the invention may vary within the scope of the claims set forth below.

Claims (5)

93922 An intrauterine active substance delivery ring (12), which may be either closed or open, to which a pull-out thread (11) is attached, the ring being made of an elastic polymeric material containing the active substance, characterized in that the ring cross-section ( 22) is designed so as to provide the most uniform rate of delivery of the active substance so that the travel of the active substance to the circumference of the cross-section at different points of the cross-section is substantially the same length. A ring according to claim 1, characterized in that the shape of the cross-section (22) is substantially a star, preferably a four-pointed star with slightly rounded tips. Ring according to Claim 1 or 2, characterized in that it is coated with a separate polymer layer which regulates the rate of release of the active substance. A ring 20 according to claim 1, 2 or 3, characterized in that the ring (12) is so elastic that the circumference of the ring (12) can be shaped into a substantially rectangle under the effect of low compression pressure or low traction so that its long sides (12) ', 12' ') run very close together. Ring according to one of Claims 1 to 4, characterized in that the polymeric material is a silicone polymer. Il 95922