SI8811326A - Therapeutic system acting through the skin. - Google Patents

Abstract

The present invention relates to a therapeutic method a system that acts through the skin, for the application of the active substances on the skin, with a support layer facing the skin, storage for the active substance, a device for balancing transfer of active substances that regulates the transmission of active substances substances through the system and fixing attachment device therapeutic system to the skin, characterized in that it is storage of the active substance multi-chamber system in which individual chambers (14) have one or more active ones substances.

Description

THERAPY SYSTEM THROUGH SKIN

FIELD OF THE INVENTION

The invention falls within the field of apparatus for introducing agents into the body for application to the body. Labeling according to the International Patent Classification: A 61 M 37/00, 35/00.

Technical problem

The invention solves the problem of how to perform a therapeutic system that acts through the skin, which will ensure a continuous, even and regulated emptying of the container with the active substance, and which will be able to regulate the flow when used, for example, in children and adolescents.

The state of the art

The invention relates to a therapeutic system which acts through the skin to enter the active substances into the patient's body, typically having one base layer against the skin, an active substance container, a device for regulating the transfer of the active substance through the system, as well as an adhesive device for attaching the therapeutic system to the skin.

Such systems acting through the skin with multiple active substance containers are known, for example, from P 36 29 404.0, where one or more individual active substance containers without interconnection are arranged in a single matrix for the distribution of the active substance.

This known construction is particularly suitable for solid or highly viscous materials, wherein the highly concentrated active substance is contained in the matrix for the distribution of the active substance, from which it extends through a possibly glued control membrane.

In the case of liquid active substances, the ratio of active ingredient preparation, the active substance can often be placed in a blow molding in the form of a bag of some matrix, or in a bag made of some regulating membrane or of a foil, and when emptying the container of the active substance it will quickly reach lowering the internal pressure and thus reducing the migration speed of the active substance. Another drawback of systems with large units in the form of bags prepared with liquid active substances is the pressure-sensitive and load-bearing towers

pressure systems .. if. the whole of the active substance to leak out of the thorax uncontrollably into the matrix for distribution of the active substance, and the transfer of the active substance to the skin will no longer be regulated. This is particularly undesirable when it comes to high-potency active substances whose overdose poses risks.

The second is the lack of known systems that they cannot be shared, so that, for example, children and adolescents, or individuals who require less active substances, have to provide different sizes of these systems.

Finally, in the case of patches with large reservoirs, fluid is liable to cause an uneven distribution of fluid due to the effect of the earth, which has a very adverse effect on the uniformity of transfer of the active substance.

The description of the solution of the technical problem is therefore the task of finding that the aforementioned disadvantages of the prior art are avoided and a new therapeutic system acting through the skin is provided, which will enable safe handling, especially of liquid active substances, or preparations thereof.

According to the invention, the problem is solved by a single therapeutic system that acts through the skin, which is characterized by thorns, which is a reservoir of active substance is a multi-chamber system, in which individual chambers contain the active substance.

The multi-chamber system is suitable because the distribution of the active substance is nil, and in the event of cutting off or separation of a part of the therapeutic system acting through the skin, there is no need to fear the leakage or fallout of the entire preparation of the active substance. Further, the liquid preparations of the active substances can only be moved under limited force by the action of gravity or pressure, so that only by the action of the force of gravity can a fairly uniform distribution of the fluid containing the active substances be achieved. If one of the chambers with active substance is sprayed due to pressure, the remaining chambers remain intact, so that the function of the system is still maintained to some extent, which is a precautionary measure to reduce the risk of overdose on high-volume liquid active substances.

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A convenient development of the concept of the invention consists in towers, the individual chambers being at least partially interconnected by channels, so that the contents of the chambers are allowed to flow to equalize the pressures.

It may be advantageous for the connecting ducts between the chambers to have such an inside diameter that they allow the liquid active substance to flow only when acted upon by pressure. This embodiment avoids the spraying of the container and thus the inapplicability of the pressure load system, for example when placed on Animals for veterinary use, when such a pressure distribution device is useful.

It is also possible for a multi-chamber system to be a purely ductile system.

The chambers of the chambers may have different control devices for the transfer of the active substances. This form of embodiment is particularly suitable when using various active substances in a single system, which. needs these active substances to transfer to the skin at different rates of transmission.

The chambers may be constructed in one or more, identical or different matrixes for the distribution of the active substances, which may be arranged side by side or side by side.

The therapeutic system acting through the skin according to the invention has a single, continuous or intermittent, adhesive layer as a device for attachment to the skin.

The skin-acting therapeutic system may still have one or more adhesive layers between the support layer and the attachment device. This is especially necessary and convenient if the matrix for the distribution of the active substance is not sticky and the non-permeable support layer can be placed samp using another adhesive layer.

The system according to the invention is particularly suitable when applied with liquid active substances, or substances, or with their solution.

In multi-chamber systems, tearing lines may be provided between the individual chambers and, possibly, in the support layer and in other layers. These tear-off lines allow the system to be split when less active substance transfer is desired.

This can, for example, avoid holding in storage systems that act through the skin of different sizes and doses.

The chambers can be arranged at different patch levels, as needed, and in different distribution matrices.

The multi-chamber system can be incorporated into some Σερί ivu ivu matrix for the distribution and regulation of the active substance.

A multi-chamber system may consist of a film with a regulating effect, filled with active substances or solutions of active substances, which may be permeable to the active substance, if required, and welded to one multi-chamber system.

The therapeutic system of the invention can be used for the packaging and application of active substances acting through the skin that are used in human and animal medicine as well as in cosmetics.

The container may contain inert auxiliary materials. Inert is meant that the active substance and the auxiliary material do not react with each other. One inert auxiliary material may be some material that has a certain physiological effect, such as, for example, DMSO, or the like, which may increase skin permeability. Supporting materials are materials that make the active substance container insensitive to pressure or stretching, as well as supporting materials.

As active substances can be used active substances which can be applied through the skin. Typical examples are:

- nicotine,

- corticosteroids: hydrocortisone, prenisolone, beclomethasone propionate, flumetason, triamquinolone, triamquinolone-acetonide, fluoquinolone, fluoquinolone-acetonide, fluoquinolone-acetoniacetate, clobetasol-propionate, etc.

- Analgesics and anti-inflammatory drugs, acetaminophen, mefenamino acid, flufenamino acid, diclofenac, diclofenacetrium-alklofenac, oxyphenebutazone, -phenylbutazone, igoprufen, flurbiprofen, salicylic acid, 1-naphthyl, camphoric acid, 1-naphthyl

- hypnotic sedatives: phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepam, lorazepam, haloperidol, etc.

- tranquilizers: flufenazine, thioridazine, lorazepam, flunitrapezam, chlorpromazine, etc.

-.- 5.- High pressure agents: pindolol, bufralol, indenolol, nifedipine, lofexidine, nipradinol, bucumolol, etc.

- high pressure diuretics: hydrothiazide, bendroflumethiazide, cyclobenthiazide, etc.

- antibiotics: penicillin, tetracycline, oxytetracycline, fradiomycinsulfate, erythromycin, chloramphenicol, etc.

- Anesthetics: lidocaine, benzcine, ethylaminobenzate, etc.

- antimicrobial agents: banzalkonium chloride, nitrofurazone, nystatin, acetosulfamine, clotrimazole, etc.

- fungal agents: pentamycin, amphotericin B, pyrrolnitrile, clotrimazole, etc.

- Vitamins: Vitamin A, ergocalciferol, cholecalciferol, octotiamine, riboflavinbutyrate, etc.

- antiepileptic drugs: nitrazepam, meprobamate, clcnazepam, etc.

- coronary-vasodilators: nitroglycenol, dipyridamole, erythritetranitrate, pentaerythritol tetranitrate, propotyl nitrate, etc.

- antihistamines: diphenylhydramine hydrochloride, chlorpheniramine, diphenylimidazole, etc.

- antitussives: dertromethorphan (hydrobromide), terbutaline (sulfate), ephedrine (hydrobromide), salbutanol (sulfate), isoprotenerol (sul fat, hydrochloride), etc.

- sex hormones progesterone, etc.

- timoleptics: doxepin; etc.

- other medicines: 5-fluorouracil, fentanyl) desmopressin, domperdon, scopalamine (hydrobromide), peptide, etc.

- it is understood that this list is neither comprehensive nor conclusive.

It is advantageous for the matrix of the active substance to be made in a layered manner, wherein the layers may be the same or different. The matrix of the active substance may be adhesive, for example some rubber material, such as styrene / isoprene / styrene-block copolymer, silicone rubber or synthetic resins, such as sulols (meth) acrylate, polyurethane, polyvinyl ether, polyester or the like, and inspection of suitable materials for matrices can be found in DE-OS 35 00 508, which is fully referenced. It can be advantageous if the reservoir matrix is sticky, since in this case the installation of a special adhesive attachment device can be avoided. The application of such a sticky matrix depends, inter alia,

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of which is the tolerance between the matrix material and the active substance. Adhesive matrix materials are known.

Suitable non-stick materials for matrices are: polymerizates consisting of poly (meth) acrylate, polyvinylpyrrolidone, ethylcellulose, hydroxylpropylcellulose, hydroxypropylmethylcellulose0gftalate, polyvinylacrylate, vinylurea, or vinylmethyl vinylurea, .

Thus, for example, the chambers may be placed between a layer of reservoir matrix on the back and one layer of reservoir matrix facing the skin.

As a support layer, known materials which do not leak the active substance, such as metal films, plastic films, or laminates thereof, which are known to one skilled in the art, may be used.

Other advantages and features are apparent from the following description, in which the embodiments are explained in more detail with reference to the accompanying drawings. At torne:

Figure 1 shows a cross-sectional view of the therapeutic system of the invention;

Figure 2 shows a cross-section of the following system according to the invention;

Figure 3 shows another system according to the invention in cross-section;

Fig. 4 shows a system according to the invention with channels, in horizontal projection with a removed support layer;

Figure 5 shows another embodiment of the invention in horizontal projection, wherein the support layer is removed from the system;

Figure 6 shows the following embodiment of the invention in cross-section;

Figure 7 shows the following embodiment of the invention with a ducting system with the support layer removed;

Figure 8 shows one embodiment of the system according to the invention in cross-section, wherein it has a system of channels which are not in the same plane;

•. , - A - - '' S '' - - - 7 - ίFigure 9 shows a cross-section of another skin-acting system according to the invention; i

FIG. 10 shows, in a horizontal projection, one embodiment of the invention with the tear-lines and the support layer removed.

Figure 1 shows a first embodiment of a skin-acting system according to the invention, in the form of a patch, and shown in cross-section. The system has a support layer 10, impermeable to the active substance, such as a metal or plastic film, wherein the support layer may consist of a laminate of films of different materials. Below the support layer 10, an active mass distribution matrix 12 is formed, consisting of a material that permeates the active substance. For such an active substance distribution matrix, which is sticky in this embodiment, for example, an acrylate copolymer is provided which becomes mesh itself, although the matrix also depends on the active substance used. Active matrix chambers 14 are filled in the matrix, which are filled with some liquid active substance, such as nicotine solution. Between the individual chambers 14, the layers that comprise the active substance adhere to each other so as to prevent the free flow of nicotine solution into the common chamber system 14. The active substance, here nicotine, dissolves in the matrix, whereby the rate of emptying of the system for action through the skin depends, between , from the rate of diffusion of the active substance in the matrix of the active substance. An adhesive layer 19 is provided below the matrix of active substance, which completely encloses the chambers 14 here, intended to attach the system to the skin.

This adhesive layer is permeable to the active substance and can act as a regulator when necessary to transfer the active substance to the skin.

In Fig. 2, another preferred embodiment, in cross section, of a single therapeutic system for acting through the skin according to the invention, in the form of a patch, is provided, wherein in this system different chambers 14, 14 'are made in two different matrices 12. 12 * active substances, which may contain, for example, various active substances or preparations of active substances. Both active substance matrices can be selected to meet the requirements for the rate of transfer of active substances. The system has a continuous adhesive layer 19 to support

X:: -: 8 on the skin, that is, to attach the system to the skin, in which case the adhesive can exert a certain regulatory effect.

Figure 3 shows one simple manufacturing embodiment of the invention, wherein the chambers 14 are constructed in an adhesive matrix 12 of the active substance whose adhesive properties are sufficient to attach the system to the skin.

Figure 4 shows one embodiment of a therapeutic system for acting through the skin according to the invention, in which .chambers 14 of the active substances are interconnected channels, so that when the local action presses on the system, the fluid contained in the channel system and chambers 14 can flow to the pressure equalized.

Figure 5 shows one system according to the invention in which the multi-chamber system consists of lattice-arranged channels 15 with active substance. Here, too, the backing was removed in order. enabled the active substance container to be displayed.

Figure 6 shows one embodiment of the invention in which the individual adhesive regions 19 are arranged in the matrix 12 of the active substance in order to attach the system to the skin, while the transfer of the active substance would be carried out mainly over non-sticky or poorly sticky surfaces of the matrix of the active substance.

Figure 7 shows one embodiment with concentric chambers 14 in the form of channels, wherein different active substances can be placed in individual annular channels.

Figure 8 shows the following embodiment of a system similar to that of Figure 3 in that it also utilizes a sticky matrix of active substance having a system of 15 channels containing the active substance or a fluid containing it. The 15-channel system is designed with variable height.

This construction is suitable if the patch is exposed to displacements that tighten it, which in a flat duct system without a stretch reserve would result in splashing. Figure 9 shows a similar construction, in which the patch also has an additional adhesive layer 19 for attaching the system to the skin and, if necessary, for further regulating the transfer of the active substance. ··

In the picture. In Fig. 10 shows a structure with containers 14 of the active substance in the vita strip. The drawing represents a horizontal projection of the system according to the invention from which the backing layer TO is removed. Here, the tearing lines 17 are noted, which can be used to reduce or change the dosage of the system. This embodiment is very suitable for tensile-exposed patches.

For all the forms shown in the figures, further limitation of the active substance container can be seen with the help of foils in the form of bags placed between the active ingredient preparation and the matrix to better limit the liquid active substance.

Claims (11)

PATENT APPLICATIONS ί. Therapeutic system acting through the skin for applying the active substances to the skin, with a support layer facing the skin, a storage for the active substance, a device for regulating the transfer of the active substance that regulates the transfer of the active substance through the system, and a fixing device for attaching the therapeutic system to the skin, characterized in that one or more active agents is present in the individual chambers (14). 2. The skin-acting therapeutic system according to claim 1, characterized in that the chambers (14) are at least partially interconnected via channels (15). The skin-acting therapeutic system according to one of the preceding claims, characterized in that the chambers (14) optionally have different devices for regulating the transfer of the active substance. The skin-acting therapeutic system according to one of the preceding claims, characterized in that the chambers (14) are arranged in one or more identical or different matrices (12,12 ') for the distribution of the active substance. The skin-acting therapeutic system according to one of the preceding claims, characterized in that it has a continuous or discontinuous adhesive layer (19) as an attachment device on the skin side. The skin-acting therapeutic system according to one of the preceding claims, characterized in that it has one or more adhesive layers between the support layer (10) and the attachment device (19). The skin-acting therapeutic system according to one of the preceding claims, characterized in that the active substance is present in liquid or in solution. The skin-acting therapeutic system according to one of the preceding claims, characterized in that the multi-chamber system has active substances between the individual chambers (14) and optionally in the support layer (10) and other layers (17) ). The skin-acting therapeutic system according to one of the preceding claims, characterized in that the channels (15) between the chambers (14) have an internal diameter that allows the / M pret flow of the liquid active substance only under pressure. The skin-acting therapeutic system according to one of the preceding claims, characterized in that the multicomponent system is a duct (15). The skin-acting therapeutic system according to one of the preceding claims, characterized in that the chambers (14) are arranged at different patch height levels, optionally in different distribution matrices.