NO812642L - DEVICE FOR ADMINISTRATING MEDICALLY ACTIVE SUBSTANCES - Google Patents

Description

Technical area:

The invention relates to a device for administering medically active substances locally to certain body areas of humans or animals.

State of the art:

In certain cases, in order to achieve certain medical effects, it may be beneficial or necessary that a substance be brought

in contact with body tissue for a long time in order for it to be absorbed slowly and thus affect a human or animal body locally or more generally. As an example of a simple type of such treatment, dermatological treatment by applying e.g. an ointment, which is left on for a longer time, and from which the skin absorbs certain active substances. As another example, it can be mentioned that for prophylactic or therapeutic purposes one has impreg-. nert contact lenses of the soft type with a medicine, e.g. an antibiotic, and while wearing the contact lens, this can be absorbed by the eye.

Technical problem:

In both of the aforementioned, known cases, there has been a question of a surface treatment. In the case of an internal treatment, certain difficulties arise in applying these methods. Thus, an application of the medically active substance without a carrier cannot be used for local treatment of mucosa-lined body channels,

at least not when a more prolonged impact is required, while the substance is washed away by the body fluids that moisten the mucous membrane. Nor can the second of the aforementioned, known methods with a carrier part floating at the treatment site be applied in general for the medically active substance. Namely, it is difficult to get a carrier part to lie against the surface of the body channel, particularly during body movements and when body fluid passes through the channel, while the control of the carrier's position is difficult to carry out during internal treatment.

Solution:

The aforementioned problem is solved with the present invention by using a carrier made of a hydrogel, which swells during absorption of body fluid, as a carrier for the medically active substance. With suitable sizing and degree of swelling, the carrier body can be brought to fill the body channel and remain in it by pressure against its walls. In this way, the active substance that is taken up in the body can be allowed to affect the walls of the channel for a longer period of time without the risk of displacement or washing away of the carrier body.

For adaptation of the invention, two special cases are proposed, whereby specific medicinal substances are even indicated, which can provide a sought-after medicinal effect in the application for which there is a question.

Benefits:

The invention thus achieves the advantage that an internal, local treatment can be carried out even when longer exposure times are necessary for the medically active substance. Distinct advantages are achieved in the specified treatment cases using the specified substances.

Description of the drawings:

The attached drawing shows in fig. 1 the device in the inserted position in a first case of use; fig. 2-4 show in longitudinal section three different embodiments of the device intended for the first application case; fig. 5 shows the device in the inserted position in another case of use; and fig. 6 and 7 show in one longitudinal and one cross section an embodiment of the device intended for use case no. 2.

Preferred embodiments:

The device according to the invention is formed by a body of a material which, when brought into contact with a body fluid, separates in terms of volume by at least 20%, measured as linear expansion. Apart from the ability to swell, the body is essentially inert to the body fluids and surrounding tissue. The swelling of the body in contact with body fluid is preferably at least 40%, e.g.

at least 80 The swelling can vary between 20 and 300% linearly. The body is intended to be inserted into cavities in humans and animals,

according to the examples in the cervix and in the fallopian tube.

By the fact that the material in the body is hydrophilic, it can be made to take up water-soluble or emulsifiable substances, and the idea of the invention is also to design the body so that the hydrophilic material contains active substances. As the body, due to its swellability, is well suited for insertion into, and remaining in, body cavities, whereby by suitable dimensioning of size and swelling factor it can be brought to lie well against the walls of the body cavity, it is thereby also well suited as a

for body-active substances, which are suitably supplied locally by keeping the substance in question in contact with the body tissue for a certain period of time. In this case, the body tissue is thus the walls of the cavity, usually a mucous membrane.

As an example of two important areas of application, which will be illustrated in the following, mention can be made of inducing an abortion by introducing a body of the aforementioned kind into the cervix and into the uterus. By the fact that the body is introduced in its unswollen state, it can have small dimensions, and thereby it can be easily introduced while, after absorbing water from the body fluid, it swells and expands the cervix. This facilitates the expulsion of the foetus, which is brought about by the fact that an abortion-inducing substance is supplied directly to the uterus with the help of the aforementioned body. The active substance can be prostaglandins or analogous compounds, which after a certain period of time have an abortion-inducing effect. This results in an extremely effective abortifacient, which entails little risk of damage to the exposed organs. In addition, the active substance is supplied directly to the treatment site and a locally effective dose can be given without human or the animal body is exposed to some significant general influence. If one were to give prostaglandin in the form of a general dose at e.g. injection, in order to produce the intended effect, it had to be given in such a large dose that one would have a general effect in the form of vomiting, malaise and diarrhoea.

In the second embodiment, which is also illustrated in the following, provision of sterilization by occlusion of the fallopian tubes is indicated. It is known that certain substances, namely cytotoxic sclerosing substances, in relatively long-term con-

tact with body tissue, can provide formation of connective tissue.

This effect can be used to block the fallopian tubes for sterilizing purposes. However, it is required that the relevant substance be kept in contact with the mucous membrane for a long time, which is difficult to provide with conventional methods, e.g. brushing or inserting an ointment plug containing the substance. According to the invention, it is therefore proposed that the substance in question be taken up in a body of the aforementioned swellable type, which is inserted into the fallopian tube and allowed to remain there, so that the aforementioned connective tissue formation is initiated. Before the connective tissue has had time to form and occlude the fallopian tube, the body, which is thus held back by swelling and which clogs the fallopian tube, acts as an obstacle to the passage of the egg, thereby producing an initial preventive effect.

The device according to the invention is. thus advantageous for the pharmacological treatment in that the swollen body in its elastic state provides a very good contact with the surrounding body tissue, whereby a very good and well-regulated transfer of the active substance can take place. The soft body is also tissue-friendly and can be left for a long time without irritation. It can be adapted within wide limits for the desired duration of the release of the active substances, as well as the dosage.

In addition to this, as mentioned, expansion or occlude ring.

The geometric shape of the body that is introduced into the cavity is not critical, and the body can, for example, be essentially cylindrical, spherical, egg-shaped or hourglass-shaped. It must

however, have a cross-section and a shape which, after swelling, is adapted to the cross-section and the shape that the channel-shaped cavity has. The cross-section of the unswollen body is adapted to the cross-section of the channel-shaped cavity in such a way that the body can be introduced into the cavity with room to play! or under slight displacement of its walls,

whereby the introduction can take place with the least possible difficulty. A thread is suitably attached to the body, so that it can be removed without operative intervention. This thread can be made of radiopaque (radiopaque) material, so that the body's position can be checked. Alternatively, the body itself may contain X-ray contrast material.

As mentioned, the material in the body swells, in contact with the body fluid, at least 40%, suitably at least 80%, and may even swell as much as 300% or more. The material must otherwise be essentially inert to the body fluid and not be harmful to, or absorbed by, body tissue. A suitable group of materials are hydrogels. These materials swell upon absorption of water from the body fluid. Suitable hydrogels are acrylic-type polymers and copolymers, e.g. cross-linked polyacrylamide, and polymers and copolymers of methacrylic acid esters with at least one hydroxyl group in the side chain. A suitable monomer is 2-hydroxyethyl methacrylate, whereby the ester group may be derived from diethylene glycol or triethylene glycol. Also applicable is e.g. 2,3-dihydroxypropyl methacrylate. As a cross-linking substance, polyfunctional acrylates, e.g. diesters, or corresponding glycols, e.g. ethylene glycol bis-methacrylate, applicable.

Another example of material suitable for the body according to the invention is a copolymer of a hydrophilic monomer and a hydrophobic monomer. With the help of this material, by varying the ratio between the hydrophilic and the hydrophobic monomer, the water absorption capacity and thus the swelling can be varied within wide limits. Examples of the hydrophilic component include monomers from the group consisting of N-vinyl pyrrolidones and vinylpyridines, and examples of the hydrophobic component include monomers from the group consisting of methyl acrylate

and methyl methacrylate. Polymerization takes place suitably by exposing the starting materials to electromagnetic radiation in the UV-y radiation range or by heating. Thereby even ste- . rilisation of the body, which is important in this context so that there is no risk of microorganisms being added to the body tissue. This is important, as the device is intended to be used in internal, and susceptible to infections, body cavities./The supply of the active substance to the body's material can take place by after, the polymerization is carried out in a sterile solution or possibly emulsion with the active substance or substances in water. The body's hydrophilic material will thereby absorb the water solution or the emulsion. If the water is then allowed to evaporate, the active substance remains in the body's material and can later be released when the body is again brought into contact with a water-rich liquid, namely the body fluid after the body has been inserted. By controlling the concentration of the liquid and the duration of the liquid absorption, the body can be impregnated with the active substance to different depths, which leads to different durations of the treatment, namely the body's absorption of the active substance, and also the dosage. It is even possible to carry out the impregnation in several stages for a gradually changing concentration and possibly to vary the type of substance, whereby a time-varying treatment can be provided.

The body should be essentially elastic and only plastic to a very small extent. In the unswollen (non-hydrated) state, it can be stiff and/or hard, but should soften upon swelling. The body may contain agents that make it more x-ray-resistant, e.g. salts of barium or bismuth or metal powder (e.g. silver).

In its inserted position, the body is firmly anchored in the body canal or cavity into which it is inserted, after the body's material has absorbed body fluid and swelled. However, this takes a certain amount of time, and by the time this has happened, the body shows room for maneuver in relation to the surrounding tissue walls. As mentioned, the body in its unswollen state is in such a way adapted to the channel that it can easily be introduced into the body cavity in question.,

However, this means that the body does not always get a secure anchorage before the swelling has occurred, and therefore a period of uncertainty can arise immediately after the insertion, as the body can move under unfavorable circumstances due to the flow of body fluid through the channel or movements of the individual carrying the insert body. The body can, however, be provided with at least one member of a material with adapted stiffness. This organ exhibits external parts which, at least in the unswollen state of the body, protrude outside the body, and so far that they come into contact with the walls of the surrounding cavity when the insertion of the body is carried out in the desired manner. In this way, these protruding parts thus act as locking devices, which, during suspension, retain the body in the place where it is inserted. These springing means are suitably designed with a locking action, so that they spring away in the direction of insertion, but tend to expand upon movement out of the channel.

The protruding parts of the organ thus serve as anchorage exclusively, or mainly, until the body has reached its swollen state. They can therefore have such a dimension that they will for the most part be inside the surface of the body when it has reached its swollen state, and are held by this. In this way, it is avoided that the protruding parts are excessively pressed into the surrounding body tissue as long as the body remains in place, when the body has acquired its swollen state, and also not during extraction.

A device 1 according to the invention which is intended for insertion into the cervical canal of a woman is shown in fig. 1-4. It is formed by an elongated body 2 of the aforementioned swellable material with a narrow end 3 and a central part 7 and an outer, pear-shaped end 4. In the body 2 is inserted a thread 5 which preferably consists of polyamide fibers, which is terminated within the end 3 , but extends from the body at the end 4 with a free part 6. It should be radiopaque. A drainage channel 8 with openings 9 and 10 can run through the body.

As an example of suitable dimensions for the body 2 in the described application, a length, apart from the free part 6 of the wire, of 70 mm and a largest diameter of 4 mm at the end 4, as well as 12 mm for the middle part 7 can be mentioned.

In fig. 3 shows a variant for the device for insertion into the cervical canal and into the uterus. If the arrangement of the one in fig. The embodiment shown in 2 can be said to have a mushroom shape, so the device according to fig. 3 more hourglass-shaped, thus with both ends extended and the middle part designed as a narrower waist.

One or more organs 11 for the aforementioned anchoring of the body, which here is close to cylindrical, are shown in fig. 4. The organ extends through the same and exhibits in the unswollen state of the body 2 protruding parts 12. The central part from which the outer parts 12 proceed is located inside the material of the body 2 even in its unswollen state and thus forms an anchorage for the organ 11. In addition, the thread 5 extends through a hole 13 in the organ, whereby an extremely effective anchoring of the organ and the thread 5 in the material of the body 2 is mutually achieved.

A body 31 according to the invention, which is intended for insertion into a woman's fallopian tube, is shown in longitudinal section in fig.

5 and 6. It is formed by an elongated cylindrical (cf. fig. 6) body 32 of the aforementioned swellable material with an inner, rounded end 33 and an outer, pear-shaped end 34. In the body 32

a thread 35 is inserted, which terminates within the inner end 33, but extends from the body at the end 34 with a free part 36.

The wire 35 is preferably made of polyamide fiber, at least partially rendered opaque to X-rays, or

the body can be provided with an X-ray shadowing reinforcement element.

Even in this case, the body acts as a carrier of a medically active substance. It thereby aims to provide a connective tissue formation in the fallopian tube, so that it is blocked.

For this, a substance is needed that initiates the body to form connective tissue. For this purpose, certain chemotherapy drugs are available. Of such cytotoxic sclerosing substances, quinacrine hydrochloride and ethanol formalin can be mentioned. Quinacrine hydrochloride in particular has a specific effect on the fallopian tube's mucous membrane, so that it is initiated to form connective tissue, which leads to a permanent, non-reversible blockage of the fallopian tube. However, in order for such to be established, it is necessary

that the remedy has an effect for a considerable period of time, of the order of a few weeks. This can thus be provided by the carrier body being introduced into the fallopian tube and anchored there by its swelling, so that it remains long enough for the aforementioned connective tissue formation to take place.

Even in this case of use, the body can be provided with the aforementioned blocking means, as shown in fig. 4.

In fig. 1 shows the device 1 according to fig. 3. lodged in the cervix of a woman. The uterine cavity is denoted 20 and the cervix with the cervical canal 24. As can be seen from the figure, the device's knob-shaped extension 4 is located in the uterine cavity, while its other part extends through the cervix. After the body is introduced, it absorbs water from the body fluid and. sleepers. In doing so, it fills the cervix and dilates it. On contact with the surrounding body tissues, these take up the active substance carried by the body's material, in this case thus prostaglandins, or analogous substances which after a period of time have an abortion-inducing effect. Fluid that is formed and is not absorbed by the body's material can escape through the drainage channel 8. As can be seen from the figure, the thread 5 extends through the uterine plug 21, whereby an indication is obtained that the device remains in place and is an opportunity to pull the body out when the treatment is to end. It is naturally within the scope of the invention that a device of a similar type to device 1 can be used for insertion into the uterus for the treatment of inflammations. The body must thereby be a carrier of e.g. some kind of antibiotic.

In fig. 5 shows how the device 31 is inserted into the fallopian tubes 37 of a woman. On the right, it is shown how, immediately after insertion, the body 31 still retains its elongated, narrow shape, in which it is easily introduced into the fallopian tube 37.

On the left, it is shown how the body, after being placed in contact with body tissue for some time, has swollen due to the absorption of body fluid, whereby it completely blocks the channel and achieves a good anchorage to it. The free part 36 of the wire 35 extends down into the uterus 38 and enables easy removal of the device and also checking that it stays in place.

After insertion, the body 31 clogs the fallopian tube 37, so that a preventive effect is provided in that eggs cannot pass down through the fallopian tube and neither can sperm up through it. After a while, however, with the help of the previously described substance, a connective tissue formation is initiated in the fallopian tube, which eventually clogs it. After this has happened, the body 31 is no longer needed. It-can, however, be left as it exerts no harmful influence. If it should be pushed out after connective tissue formation has occurred, this has no effect on fertility.

In the above, some examples of how the device can be made and how it can be used are shown. In addition to this, however, other designs and other applications are conceivable within the scope of the invention that has been indicated. The different elements of the device, like different form elements, the pull-out thread and the anchoring means do not have to be tied to each other in the manner indicated, but can also be combined in other areas.

Claims (7)

1. Device for supplying medically active substances, comprising a body (2,31), which is provided with the medically active substance and arranged for placement against the body tissue of a human or an animal, whereby the medically active substance is of such type that it has the ability to be taken up by the body tissue when the substance is placed with the help of the body and held against the body tissue for a period of time, characterized in that the body (2,31) is preferably elongated. in its shape and arrangement to be able to be introduced in a body channel (24,37), that the material in the body consists of a hydrogel, which in contact with fluid-releasing body tissue absorbs body fluid and thereby swells in terms of volume by at least 40% linearly, and that the body's cross-sectional dimension in an unswollen state is arranged as follows that it can be introduced into the body canal and in the swollen state expand beyond the body canal's normal cross-section, so that the body, after it has been inserted, is anchored in the canal and pressed against its walls and the a transfer of the medically active substance to the body tissues surrounding the body is provided. 2. Device as specified in claim 1, characterized in that an indicator and pull-out wire (5,35) is attached to the body (2,31), which with a free end (6,36) protrudes outside the body (2) ,31). 3. Device as stated in claim 1 or 2, characterized in that a blocking member (12) is inserted into the body (2) with outer end parts which are arranged in such a way that they bend when the body is introduced in the direction of introduction into the body channel (24 ,37), but that they block out when trying to move the body towards the direction of insertion, as the organ (12) is arranged in the body (2) in such a way that the end parts protrude a relatively long distance outside the body in its unswollen state, but protrude a short distance or located entirely within the surface of the body in its swollen state. 4. Device as stated in any of the preceding claims, characterized in that the hydrogel in the body (2,31) consists of a copolymer of a hydrophilic monomer and a hydrophobic monomer, whereby the swelling ability of the body is adjusted using the ratios between both monomers. 5. Device as specified in any of the preceding claims, characterized in that the body (2) is designed to be at least partially contained in a woman's cervix and that the medically active substance is an abortifacient substance, e.g. prostaglandins or an analogue substance. 6. Device as stated in claim 5, characterized in that the body (2) has a cylindrical or slightly conical first part (3,7) at its middle part and at least at one end a further, knob-shaped end part (4), whereby the first part is arranged so that it will rest in the cervix while the second part, the end part respectively -the parts are arranged in such a way that they (t) are adjacent to its end or endings.. 7. Device as stated in any one of claims 1 to 4, characterized in that the body (31) is arranged to its dimensions so that it can be accommodated in a woman's or an animal's fallopian tube (37) and that the medically active substance is a sclerosing subject of cytotoxic type, e.g. quinine hydrochloride or ethanol formalin.