NO164895B - ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE DICHLORANILIN DERIVATIVES. - Google Patents

Abstract

Therapeutically active compounds of the general formula (I). wherein X represents a bond, a C 1-4 alkyl2_g-alkenylene or C 1-4 alkynylene chain and Y represents a bond, or a C 1-4 alkylene, C 1-4 alkenylene or C 1-4 alkynylene chain, provided that the total sum of carbonate trees in X and Y are not more than 8, Ar represents a phenyl group substituted by one or more substituents selected from nitro, 3 - 34 - (CH 2) R [where R is C 1 -alkoxy, -NR R (where R and R each represents a hydrogen atom, or a C 1-4 alkyl group, or -NR R forms a saturated heterocyclic amino group having 5-7 ring elements and optionally in the ring contains one or more atoms selected from -O- or -S- or an -NH- or N (CH 2) group), -NR 5COR 6 (wherein R 5 represents a hydrogen atom or a C-alkyl group, and R 1 represents a hydrogen atom or a C 1-4 alkyl-, C-acoxy- or -NR 3 R 4 group), and q represents an integer of 1-3], - (CH 2) R 2 [where R 2 represents -NRSO (where represents a C 1-4 alkyl-, -phenyl- or -NRR- group) , -NR5COCH2N (R5) 2 (where each of the groups ^ represents a hydrogen atom or a C 1-4 alkyl group), -COR 9 (where R represents hydroxy, C 1-4 alkoxy or NR R), -SR (where R is a hydrogen atom, or 34 ' A C 1-4 alkyl group optionally substituted with hydroxy, C 1-4 alkoxy or NR R), -SOR, -, R, -CN or -NR 11 R 12 (wherein Rog R represents a hydrogen atom or a C , -alkylgrup ^ e ,. of which at least one is C 2-4 alkyl substituted by a hydroxy, C 1-4 alkoxy or NR 3 R 4 group),. and r represents an integer of 0-3], -0 (CH2) gCOR9 (where q and Rer as indicated above), or. -0 (CH 2). R [where R represents hydroxy, NR 3 R 4 | NR 11 R 12 or a C 1-4 alkoxy group 3 optionally substituted by hydroxy, C 1-4 alkoxy or NR R, and t is an integer 2 or 31. 1 R and R 1 each represent a hydrogen atom car a C 1-4 alkyl group, with it. provided that the total sum of carbon atoms in R 1 and R 2 is not more than 4, and physiologically satisfactory salts. and solvates (e.g. hydrates) thereof. The compounds have a stimulating effect on the β-adrenoreceptor and can be used in the treatment of diseases associated with reversible airway obstruction such as asthma and chronic bronchitis.

Description

Intrauterine contraceptive.

The invention relates to an intrauterine object consisting of a closed rod figure of a non-tissue-irritating, elastically compliant molding material, e.g. polyethylene.

Intrauterine devices have been known for centuries and after introduction into the uterus serve to prevent unwanted pregnancy.

Several designs for intrauterine articles are known. Currently, the best known is the so-called "spiral" consisting of an almost ribbon-shaped rod shaped after a zigzag line. Intrauterine items in the form of closed rod figures are also known, of which the best known are those that have a circular or more oval shape.

Common to all hitherto known intrauterine devices is that they are in many cases expelled by the uterus, usually during one of the first three menstruations following the introduction of the uterine device.

This exclusion is all the more unfortunate, as it is difficult for the woman to feel whether the subject is in place or not. To enable such a sensation, it is known to supply the intrauterine device with a piece of thread or a small punch, which extends out of the uterus, into the vagina, but this involves a risk of infection and can cause lesions.

In addition, the introduction of the known intrauterine objects requires special, usually tubular insertion devices, which are guided up into the uterus through the cervical canal, after which the object is pushed up into it with the help of a rod. This will often require a prior dilatation of the cervical canal

The purpose of the invention is to produce an intrauterine item consisting of a closed rod figure of a non-tissue-irritating elastic yielding molding material, which item has a significantly lower tendency to be expelled than the hitherto known intrauterine items, and which at the same time can be easily placed in place by the doctor or another person specialized therein. A further purpose of the invention is to make it possible from the outside, i.e. without intervention in the vagina to determine whether the body is in place or not.

The intrauterine object according to the invention" is characterized by the fact that the rod figure consists of an upper part comprising two colliding upper legs, which between them form an internal angle of between 90° and 125°, and a lower part comprising two lower legs, each of which at its upper end goes over in a member of the two upper legs forming an internal angle between 90° and 125° and between them forming an internal angle of between 25° and 75°, and which lower legs at their lower ends are interconnected by a cross piece, where the collision point between the two upper legs and the collision points between each upper leg and the adjacent lower leg are shaped in such a way that the bar figure's resistance to bending is less at these collision points than in the legs themselves.

This achieves partly that the upper legs, when the lower legs e.g. with the help of forceps are pressed against each other, will also be pressed against each other, so that the object assumes probe deformation and can easily be introduced into the uterus, where, when the forceps are removed, it will expand and assume its normal shape, so that firmly held in the uterus. Furthermore, when it in the walls of the uterus, such as e.g. is the case during menstruation, wave-shaped pulsations occur from the inside out, which, when they hit the subject's upper legs, try to press them downwards, which, however, due to the subject's slight flexibility in the places of impact, will cause an expansion of the body in the width direction, so that during these pulsations it squeezes more firmly into the uterus and therefore has no tendency to be expelled.

The intrauterine object is also easy to remove Again, as you can use a hook, which is introduced into the uterus, to grasp the transverse piece, and a pull on this will cause the object to assume an elongated shape, so that it easily slides out of the cervical canal.

The arc-shaped crosspiece, which serves to ensure that the workpiece at its lowest end has a width greater than the width of the cervical canal, so that it does not slide out of the uterus by itself, should according to the invention at least have a less thickness measured in the plane of the figure than the legs, so that it is relatively easy to bend and we can follow during the drawing of the subject with the help of the hook. The aforementioned design also means that the intrauterine object during insertion through the cervical canal can be pressed together in such a way that it fills as little as possible.

In and of itself, there is nothing in the way of the legs being more or less curved and curved inwards as well as outwards. However, it has proven most appropriate that the legs are individually as close as possible to a straight line, which means that the subject can be compressed as much as possible, so that it fills as little as possible during the introduction into the uterus.

According to the invention, it may further be appropriate that the stane figure is symmetrical about an axis, which passes through the point of impact between the upper legs and intersects the cross-piece. It is possible that, with a non-symmetrical design, one will be able to give the object a shape that matches the shape of the uterus even more precisely, but this will again require the object to be introduced into the uterus in a fairly specific position, which is difficult to achieve in practice.

In order to ensure the best possible retention inside the uterus, it may further according to the invention be appropriate that in the normal position the subject's maximum height is between 1.0 and 1.7 times its maximum width.

The design of the object with relatively rather long linear legs makes it further possible that a rod-shaped body of a magnetizable material can be completely enclosed in at least one of the legs or the cross-piece. This means that with the help of a suitable instrument from the outside it is easy to ascertain whether the intrauterine object is located in the uterus. Most expediently, according to the invention, this rod-shaped body is made up of a permanent magnet, whereby the presence of the intrauterine object can be ascertained, e.g. using a compass.

The detailed mechanism of action of intrauterine objects is in all cases largely unknown, but it is known that the effect depends on the object's side-facing contact areas. The object according to the invention has been shown to have the necessary contact area, but if desired, this can be further increased according to the invention by fins extending from one or more of the legs inwards towards the center of the rod body.

In the following, the invention will be described in more detail with reference to the drawing, on which

fig. 1 shows an embodiment of an intrauterine object according to the invention, seen from the side on an enlarged scale,

fig. 2 a section along the line II—II in fig. 1, fig. 3 partly in cross-section of a part of an insertion device, in which in fig. 1 item shown is inserted in a compressed state for use for introduction into the uterus and

fig. 4-6 schematically show three further embodiments of the subject viewed from the side.

That in fig. The object shown in 1-3 has two upper legs 10 and 12, which between them form an internal angle a of approx. 110°, and two lower legs 14 and 16, which between them form an internal angle b of approx. 40°, and which with the adjacent upper leg respectively 10 and 12 form an internal angle c of 105°.

The lower legs 14 and 16 are interconnected at their lower ends at the heel of an almost circular arc-shaped cross-piece 18 whose cross-sectional area at the middle is smaller than the cross-sectional area of the lower legs 14 and 16 and from the middle increases evenly to both sides. Both the upper legs 10 and 12 and the lower legs 14 and 16 have, as can be seen from Fig. 2, a somewhat elongated cross-section, so that they have a greater tendency to bend in the plane of the forming polygon-like figure than across it.

At the collision point 20 between the lower legs 14 and 16, their cross-sectional area is reduced by means of an internally rounded recess 22 so that an easily bendable place or hinge is formed at the collision point 20. In the same way, by means of recesses 24 and 26, the points of contact 28 between the upper leg 10 and the lower leg 14, and 30 between the upper leg 12 and the lower leg 16 are designed as a kind of hinges.

These hinges 20, 28 and 30 mean that if one of the upper legs 10 and 12 or both of these are simultaneously affected in a downward direction, the figure shown will try to expand in width, and thus, if it is introduced into the uterus, tries to squeeze still more firmly in the uterus than before the aforementioned influence-Furthermore, as shown in fig. 3, by pressing the legs 14 and 16 in towards each other, it is possible to make the body assume an almost probe-like shape, so that it is easy to insert into the outer end of a tubular insertion member 36, from which it can be pressed out using by a manually operated piston 38. The insertion device 36 is designed at its outermost end with a collar 40, which ensures that during the introduction of the intrauterine object 1 uterus, the insertion device 36 will remain outside the portio, and only the object and the outermost end of the piston 38 will be guided into the cervical canal. The intrauterine object can thus be introduced into the uterus, without an expansion of the cervical canal being necessary, which constitutes a significant advantage.

Molded into the lower leg 14 is a small permanent magnet 34. This means that if a compass is held against the woman's body outside the uterus, and the object is placed in it, the compass needle will make an impact, which proves that the object is in place.

Instead of a permanent magnet, a rod 34 of other metallic material can also be introduced, provided that this is magnetisable, so that it will be able to react to external magnetic influences.

It should be noted that with the help of special instruments, the use of a stane 34, regardless of whether it in itself emits a magnet or is only magnetisable. for a lay owner it is possible not only to ascertain the presence of the subject in the uterus, but also the exact position of the subject in the uterus.

As indicated in fig. 1, from legs 10-16 fins 38' extending inwards towards the center of the figure can extend to increase the contact area of the workpiece.

Fig. 4 to 6 show three examples of further options chosen for the design of the intrauterine object according to the invention.

Claims (8)

1. Intrauterine contraceptive consisting of a closed figure formed in one plane of rod-shaped non-tissue-irritating elastic, yielding molding material, e.g. polyethylene, characterized in that the rod figure consists of an upper part comprising two colliding upper legs (10 and 12), which between them form an internal angle (a) of between 90° and 125°, and a lower part comprising two lower legs ( 14 and 16), each of which at its upper end passes into one of the two upper legs forming an internal angle (c) between 90° and 125° and between them forms an internal angle (b) between 25° and 75 °, and which lower legs at their lower ends are interconnected by an arc-shaped crosspiece (18), where the collision point (20) between the two upper legs and the collision points (28 and 30) between each upper leg and the adjacent lower leg are so shaped that the rod figure resistance to bending is less at these collision points than in the legs themselves. 2. Intrauterine object according to claim 1, characterized in that the legs (10, 12, 14 and 16) have an elongated cross-section with the smallest extent in the plane of the figure. 3. Intrauterine object according to claim 1 or 2, characterized in that the cross piece (18) at least at its center has a smaller thickness measured in the plane of the figure than the legs. 4. Intrauterine object according to any one of the claims 1-3, characterized in that the rod figure is symmetrical about an axis, which passes through the joint support (20), between the upper legs (10 and 12) and intersects the cross-piece (18) 5. Intrauterine object according to any one of claims 1-4, characterized in that in the normal position its maximum height is between 1.0 and 1.7 times its maximum width. 6. Intrauterine object according to any one of Claims 1-5, characterized by a rod-shaped body (34) made of a magnetisable metal completely enclosed in at least one of the legs (14) or the cross-piece. 7. Intrauterine object according to claim 6, characterized in that the rod-shaped body (34) consists of a permanent magnet. 8. Intrauterine subject according to any one of claims 1-7, characterized in that from one or more of the legs (10, 12, 14 and 16) extend fins (38') inwards towards the center of the rod body.