MXPA98004617A - Pharmaceutical preparation stabilized on the surface to be applied on the p - Google Patents

Abstract

A transdermal pharmaceutical preparation containing an active substance and a predetermined contact area comprises a back layer without adhesive and a layer of adhesive, which adheres to the skin. The preparation is characterized in that the back layer contains at least one third of the total amount of active substance contained in the preparation.

Description

PHARMACEUTICAL PREPARATION STABILIZED ON THE SURFACE TO BE APPLIED ON THE SKIN DESCRIPTION OF THE INVENTION The invention relates to a pharmaceutical preparation for the administration of active substances through the skin in the human body.

BACKGROUND Already since the Middle Ages, it is known that pharmaceutical substances penetrate through human skin and, consequently, when applying or extending the corresponding preparations of pharmaceutical active substances on the skin, medicinal effects can be achieved. These effects are not limited to the skin and the tissues underneath it, but can also be extended in the case of substances appropriate to nearby organs, since the active substances are distributed according to their absorption by the blood circulation. On the market are, for example, ointments and creams that contain hormones. In addition, semisolid preparations with antirheumatic effect are also commercially available, which after spreading on the skin produce a therapeutic effect over local or systemic effects. In this, not only the concentration of active substance is what determines the magnitude of the absorption of active substance, but also among other things the size difficult to control of the skin surfaces subjected to treatment. Also, the thickness of the layer that contributes to the therapeutic success of the applied preparation can hardly be determined with precision by the user. Therefore, therapeutic measures with these forms contain defects that should not be tolerated. The transdermal therapeutic systems, which precisely define among other things, in addition to the concentration of active substance, also the application surface, do not have this disadvantage. Among the partially known transdermal therapeutic systems there are some fundamental points in common: 1. To protect against the unwanted administration of volatile components of the transdermal therapeutic system outwardly, in addition also to protect against the disadvantageous repercussions when making contact with other surfaces and not in the last term to guarantee the mechanical stability of the transdermal therapeutic system, it is It raises a non-adhesive, non-adhesive return layer for the components of the transdermal therapeutic system. 2. Since the transdermal therapeutic systems must adhere to each other in intimate contact with the skin, the layer that gives the skin is at least partially self-adhesive. 3. Due to its self-adhesive properties, a removable adhesive protective layer is applied for storage before use. The return layer is generally composed of suitable materials such as for example plastic films, but papers, nonwovens or textile products are also considered. Despite the progress made, the aforementioned transdermal therapeutic systems may present some disadvantages. In this way, for example, a return layer impermeable to the surface stabilizing active substance creates a limitation for patients in terms of the convenience of using said systems. Through the rigidity of the films used, undesirable surface limitations can occur. Since for a number of pharmaceutical active substances the share of transport related to the surface through the skin may be relatively small, it is desirable, however, a larger system surface to also provide for said active substances transdermal therapeutic systems the sufficiently effective. Incidentally, attempts were made to improve the comfort to carry these transdermal therapeutic systems by utilizing elastic materials for the return layer (for example, US 5,246,705). However, in this case it was expressly limited to the materials, which were impervious to the medicament. Another disadvantage of the transdermal therapeutic systems corresponding to the current state of the art is, depending on the circumstances, its thickness considered subjectively unpleasant by patients. Since, according to the conventional structure, essentially only the matrix, the adhesive layer or possibly existing deposit layers are used for storage and administration of the active substance, a return layer impermeable to the active substance according to the definition has no function whatsoever in this respect.OBJECTIVES AND DESCRIPTION OF THE INVENTION The task of the invention is the provision of a pharmaceutical preparation that adheres to the skin with a predetermined size of application surface, comprising a non-payable return layer and a deposit containing the active substance formed from a layer that adheres to the skin and that does not present the disadvantages of the current state of the art. This task is solved according to the invention because the layer contains at least one third of the amount of active substance contained in total in the preparation. Advantageously, the inclusion of the return layer in the diffusion process results in the fact that the return layer present in the system according to the invention has a double function: It forms on the one hand a part of the deposit of active substance and on the other hand, a return layer that prevents the patch from sticking to textile products and other objects. It was surprising that the inevitable permeability to the active substance does not represent a disadvantage in general, because only in cases of active substances and / or volatile auxiliary substances there is an appreciable loss through the return layer around it. As examples for such pharmaceutical active substances, nicotine or nitroglycerin can be named. Ethanol, propandiol and other low olecularity alcohols, menthol eucalyptus, limonene and many other terpenes, low molecular weight fatty acids such as capric acid, dimethyleulfoxide, are named as examples for typical accessory substances in such preparations that leave more or less firmly of the preparation through the return layer. However, unexpectedly, a reservation is considered essentially unfounded, with which one generally has to meet (for example, EP 0 366 240, page 3, line 24 or EP 0 402 407, page 5, line 4) against a return layer permeable to the active substance, because much more active substance leaves the return layer through the payable layer towards the skin that outward. Due to the small thickness as well as the possibility of using very flexible materials as base material of the return layer, the preparations according to the invention are clearly different, in addition to another functionality, also as regards the appearance of other transdermal therapeutic systems. of classic construction. Since fine wrinkling of the skin is again caused by the preparation, the impression of a thin layer appears on the skin as opposed to a rigid adhesive film. As long as the object of the invention accepts an intermediate form between a transdermal therapeutic system and an ointment applied on a "Hautareal". By means of a manufacturing process in which an essential part of the active substance is applied already in the manufacture in the return layer, the migration processes which in certain circumstances can lead to the formation of wrinkles by swelling processes are avoided. Many materials are suitable for a return layer of this type: polyvinyl alcohol, styrene-diene-block-copolymer, polyurethane, polyvinyl chloride, polymethacrylate and many other substances are in principle appropriate to name just a few examples. With an advantageous embodiment, the return layer is covered by a protective release layer after application, adhesive and which adheres to the entire surface of said layer. As pharmaceutical active substances, steroid hormones, active substances having an effect on the central nervous system or on Alzheimer's disease, antirheumatics or acetylsalicylic acids can be advantageously used.

Examples: Example 1: A) 10 g of styrene-isoprene-styrene-copolymer (Cariflex (), TR 1107) are completely dissolved in 20 g of benzine with a boiling range between 80 and 100 ° C. 100 mg of 17-ß-estradiol is added, dissolved in 5 g of ethylacetate and the dough is coated after a homogeneous mixture in a slit width of approximately 150 μm on an adhesive polyester film, so that after a four hour drying at 35 ° C a layer emerges uniform with a surface weight of SO g / m2. B) In a separate process, a solution of 20 g of rosin glycerol ester resin (Staybelite Ester (R), 5E) and 8 g of styrene-isoprene-styrene-copolymer (Cariflex (R), TR 1107) is prepared in 10 g of ethylacetate and 10 g of benzine with a boiling range between 80 and 100 ° C, in which 0.12 g of 17-ß-estradiol are added and completely diluted at room temperature. The dough is covered in a slit width of approximately 100 μm on an adhesive polyester film, so that after a half-hour drying at 35 ° C and a subsequent drying of 15 minutes at 60 ° C a uniform layer emerges with a surface weight of 23 g / m2. The layers made in this way from Phase A (return layer) and from phase B (deposit) are placed one on top of the other by adhesive coating and adhere spontaneously until an intimate non-detachable adhesion is reached manually. The adhesive polyester film of phase B and the adhesive layer as well as the return layer are die-cut in a manner known to those skilled in the art in a contour corresponding to the geometrical shape of the preparation and the outer debris is removed. The medication is individually packaged in sealed bags. The user removes the medication from the container, removes the protective layer (Ralease Liner) from the adhesive layer, sticks the medication form on an appropriate place on the skin and finally removes the adhesive polyester film used as the protective layer from the return layer. . Next, the structure of a preparation according to the invention is explained with the aid of exemplary embodiments according to figures 1 to 3. Figure 1 shows the fundamental structure of the transdermal patch in section with the return layer containing active substance and is permeable to the active substance (2) and to the reservoir containing the active substance formed with an adhesive layer (3).

Figure 2 shows the patch according to Figure 1, but with the support layer (1) which adheres completely to the return layer (2). Figure 3 shows the patch according to Figure 1 and Figure 2, but additionally with a complete coating of the adhesive layer (3) with a removable backing layer, repellent to the adhesive (4), (Ralease Liner) for the layer adhesive (3).

Claims (10)

1. Transdermal pharmaceutical preparation containing active substance with a predetermined size of the application surface, comprising a return layer permeable to the non-adhesive active substance and an adhesive layer which adheres to the skin, wherein the return layer contains at least one third of the amount of active substance contained in total in the preparation.

2. Pharmaceutical preparation according to claim 1, wherein the return layer is covered by a removable backing layer after application, adhesive, which adheres to the entire surface of said layer.

3. Pharmaceutical preparation according to claim 1 or 2, wherein the adhesive layer is covered by a protective layer repellent to the adhesive, removable before application on the skin and adhering to the entire surface of said layer.

4. Pharmaceutical preparation according to one or more of the preceding claims, wherein the adhesive layer and the return layer together have a thickness of less than 80 μm, preferably less than 40 μm.

5. Pharmaceutical preparation according to one or more of the preceding claims, wherein said preparation contains as a pharmaceutical active substance a steroid hormone.

6. Pharmaceutical preparation according to one or more of claims 1 to 4, wherein said preparation contains as pharmaceutical active substance a similar active substance with effect on the central nervous system.

7. Pharmaceutical preparation according to one or more of claims 1 to 4, wherein said preparation contains as pharmaceutical active substance a similar active substance with effect in Alzheimer's disease.

8. Pharmaceutical preparation according to one or more of claims 1 to 4, wherein said preparation contains an antirheumatic pharmaceutical active substance.

9. Pharmaceutical preparation according to one or more of claims 1 to 4, wherein said preparation contains acetylsalicylic acids as a pharmaceutical active substance.

10. Process for the manufacture of the transdermal pharmaceutical preparation according to the preceding claims, wherein a polymer used as a base material in the solution is placed by the addition of solvents or a broth is prepared by heating and a it incorporates at least one third of the expected quantity of active substance, is mixed homogeneously, the adhesive support film is covered in a uniform layer and dried, and in a separate working phase the brush-applied adhesive composition is covered, which contains the residue of the active substance on the adhesive protective film and is dried and laminated on one another over the layers produced in this manner and patches are formed by die cutting.