WO2010010240A2

WO2010010240A2 - Dermal patch for applying dry active agents

Info

Publication number: WO2010010240A2
Application number: PCT/FR2009/000819
Authority: WO
Inventors: Jean Claude Millet
Original assignee: Millet Innovation
Priority date: 2008-07-23
Filing date: 2009-07-02
Publication date: 2010-01-28
Also published as: WO2010010240A3; FR2934162A1; FR2934162B1

Abstract

The invention relates to a dermal patch (1) that comprises an adhesive layer (11) made of a polymer gel and having an adhesive surface (21) to be applied onto the skin, and an active layer (2) having smaller dimensions than those of the adhesive layer, applied onto the adhesive surface and containing the active agent in a solid form and containing one or more active substances. The active layer (2) is capable of releasing active substances via the disintegration thereof induced by the hydration thereof or the addition of any other solvent through the adhesive layer (11).

Description

DERMAL STAMP FOR THE APPLICATION OF DRY ACTIVE ASSETS

The present invention relates to a dermal patch for medical or cosmetic use, ensuring the diffusion to the skin of an active ingredient.

It is known to apply to the skin films making it possible to provide the skin, and where appropriate, to gradually penetrate the skin by transdermy, pharmaceutical products (allopathic and / or homeopathic and / or herbal medicine), and / or cosmetics, especially in the form of aqueous solutions.

Thus, composite films having several successive layers have already been proposed, including a so-called "reservoir layer", generally placed in contact with the skin and containing an active product comprising one or more treating substances.

In patent EP 0 412 869, this reservoir layer consists of a partially polymerized polymer matrix of silicone, the active product being mixed with the reservoir layer before or during the polymerization. The polymer is only partially polymerized and has a self-adhesive character.

The quantity of active product that can be mixed with the reservoir layer is necessarily limited to a relatively small value, less than 5% by weight of the reservoir layer. Beyond a certain value, the polymerization making it possible to obtain a matrix structure does not occur. It has also been observed that certain active ingredients, even in a very small proportion, block the polymerization.

A rechargeable dermal patch has been described in the patent application FR 2,884,143 (also published in English under number US 2008/044460). The dermal patch includes a reservoir layer of a polymeric gel for receiving a liquid containing an active ingredient, and an outer receiving layer attached to the reservoir layer. The receiving layer is provided to receive the liquid containing an active product and to transmit it to the reservoir layer. Such rechargeable stamps can significantly increase the concentration of the reservoir layer in active product. On the other hand, they require that the user of the stamp himself handle the liquids containing the active products, and dose the amount of liquid introduced into the patch. In addition, refillable patches accept only active products miscible with the residual liquid phase of the polymer gel, naturally or via an emulsion. Finally, whether they are refillable or not, skin patches do not accept a wide variety of active products, and only in a relatively low concentration.

It is therefore desirable to make a dermal patch that is rechargeable in a simple and reliable manner for the user, and that accepts any type of active product, even in high concentration.

In one embodiment, there is provided a dermal patch comprising a polymeric gel adhesive layer having an adhesive face for application to the skin. According to one embodiment, the patch comprises an active layer of dimensions smaller than those of the adhesive layer, placed on the adhesive face, and containing an active product in solid form comprising one or more active substances.

According to one embodiment, the active layer comprises a solid film at least partially soluble in water and containing the active product. According to one embodiment, the film of the active layer comprises one or more polysaccharides.

According to one embodiment, the film of the active layer is obtained by dehydration of a gel.

According to one embodiment, the film of the active layer comprises at least one element of the set comprising chitin, chitosan, amigel and hyaluronic acid.

According to one embodiment, the active layer comprises solid particles containing the active product.

According to one embodiment, the adhesive layer is self-adhesive. According to one embodiment, the adhesive layer comprises a polymethylsiloxane result of polymerizing ^"Part of a mixture of silicone oils.

According to one embodiment, the adhesive layer has a thickness of a few tens to a few hundred micrometers. According to one embodiment, the patch comprises a non-adhesive outer layer assembled on the face opposite to the adhesive face of the adhesive layer.

According to one embodiment, the outer layer comprises an elastic fabric.

According to one embodiment, the outer layer is in a non-adhesive polymer gel.

In one embodiment, there is also provided a method for manufacturing a dermal patch comprising a step of manufacturing a polymeric gel adhesive layer having an adhesive face intended to be applied to the skin. According to one embodiment, the method comprises steps of manufacturing an active layer comprising an active product in solid form comprising one or more active substances, and arranging the active layer on the adhesive side of the adhesive layer.

According to one embodiment, the active layer comprises a film at least partially soluble in water and containing the active product.

According to one embodiment, the film of the active layer comprises one or more polysaccharides. According to one embodiment, the method comprises a step of dehydrating a gel to obtain the film of the active layer.

According to one embodiment, the film of the active layer comprises at least one element of the set comprising chitin, chitosan, amigel and hyaluronic acid. According to one embodiment, the active layer comprises solid particles containing the active product.

According to one embodiment, the adhesive layer is self-adhesive.

According to one embodiment, the manufacture of the adhesive layer comprises a step of partially polymerizing a mixture of silicone oils to obtain a polymethylsiloxane.

According to one embodiment, the adhesive layer has a thickness of a few tens to a few hundred micrometers.

According to one embodiment, the method comprises a step of assembling a non-adhesive outer layer on the face opposite to the adhesive face of the adhesive layer. According to one embodiment, the outer layer comprises an elastic fabric.

According to one embodiment, the method comprises a step of forming a non-adhesive outer layer of polymer gel, on the opposite side to the adhesive side of the adhesive layer.

According to one embodiment, the method comprises a step of introducing into the adhesive layer a liquid for modifying the interface conditions of the patch with the skin.

In one embodiment, a dermal patch is also provided for application to the skin. According to one embodiment, the patch consists of a film comprising an active product comprising one or more active substances and that it is capable of dissolving at least partially in the presence of a suitable solvent.

According to one embodiment, the film is soluble in water. According to one embodiment, the film comprises one or more polysaccharides.

According to one embodiment, the film is obtained by dehydration of a gel.

According to one embodiment, the film comprises at least one element of the set comprising chitin, chitosan and hyaluronic acid.

According to one embodiment, the film has a thickness of a few tens to a few hundred micrometers.

According to one embodiment, the film comprises solid particles containing the active product.

In one embodiment, there is also provided a method for applying an active substance to the skin, implemented for non-therapeutic aesthetic reasons. According to one embodiment, the method comprises the application to the skin of a dermal patch as defined above, the active layer containing an active substance slowly releasing in contact with the skin.

According to one embodiment, the patch comprises an outer fabric layer, the method comprising a step of introducing into the patch by the outer layer of a liquid capable of modifying the interface conditions of the patch with the skin. According to one embodiment, the method comprises successive steps of removing the patch from the skin, depositing on the adhesive side of a new active layer, and applying the patch to the skin.

Exemplary embodiments of the invention will be described in the following, by way of nonlimiting example, with reference to the appended figures among which:

FIG. 1 represents in perspective a dermal patch according to one embodiment,

FIG. 2 is a cross-sectional view of the dermal patch of FIG. 1, and

- Figure 3 is a sectional view of a portion of the human body and the dermal patch of Figure 1, illustrating an application of the latter.

FIGS. 1 and 2 show a dermal patch 1 comprising a layer 11 made of a polymer gel comprising an adhesive face 21 intended to be applied to the skin, and an active layer 2 of dimensions smaller than those of the layer 11 placed on the adhesive face 21, substantially in the center thereof. Layer 2 contains an active product in solid form comprising one or more active substances.

The layer 11 can be made from a partially polymerized mixture of several silicone oils, which has the advantage of being self-adhesive on the skin. This self-adhesive nature, in itself conventional, results from the polymerization process of the mixed silicone oils which is not complete. In this way, the material has, after polymerization, a matrix structure retaining unpolymerized silicone oils.

The gel forming the layer 11 has, for example, a matrix structure made of polymethylsiloxane and in particular polydimethylsiloxane (PDMS) which retains the unpolymerized silicone oils, which comprise dimethicone or a mixture of dimethicone and vinyl dimethicone. The thickness of the layer 11 is preferably between 0.2 and 2 mm, for example of the order of 0.4 mm.

The layer 11 may for example be made of EPITHELIUM 28® or EPITHELIUM 27®, materials developed by MILLET INNOVATION. These materials and in particular EPITHELIUM 28® have a remarkable adhesive power. The layer 2 containing the active product in solid form can be in the form of a film, a powder or particles. The dimensions of the layer 2 are relatively small compared to the layer 11 so that the surface of the layer 11 in direct contact with the skin is sufficient to ensure proper maintenance of the patch on the skin. The film has a thickness of a few tens to a few hundred microns, for example from 20 to 200 microns.

In the form of a film, the layer 2 can be obtained from a gel containing the active product, which is dehydrated. The active product is mixed with the gel before dehydration in the form of suspension, and / or emulsion and / or solution. The gel receiving the active product may be based on polysaccharides such as, for example, chitin, chitosan, hyaluronic acid or amigel. The amigel is a homopolysaccharide comprising an assembly of a single glucose monomer, forming a triple helix and having a molecular weight of between 5 and 6000 Daltons. The glucose monomer is a beta 1-3 D-glucose on a main chain, on which a D-glucose molecule is bonded every three units by a beta 1-6 bond.

When the layer 2 has the form of a film, it may also include an oily product to reduce the fragility of the film and thus facilitate its handling.

It should be noted that chitin, chitosan or hyaluronic acid have therapeutic properties and it is therefore not necessary to add other active substances. Thus, the layer 2 may be entirely formed of a film of hyaluronic acid which has in particular moisturizing properties of the skin, and which promotes the reconstitution of tissues. The layer 2 may also be entirely formed of chitosan which is known in particular for its action promoting the healing of open and difficult wounds. It is also advantageous to combine it with other active substances because of its ability to vector biologically active molecules.

The layer 2 may also comprise an effervescent component in contact with water, in order to release the active substances in the form of gas.

The outer face 22 of the layer 11 may also be adhesive, especially when the layer 11 is formed of a self-adhesive material. In this case, the outer face 22 is protected by an outer layer 12. The layer 12 may comprise a polymer film, for example polyethylene, or be made of an elastic material in a single direction or in two different directions, to allow the patch to fit the shape of the skin area where it is applied. The elastic material may be for example a non-adhesive silicone gel formed at the same time as the layer 11. The elastic material may also be a fabric such as a woven-type polyamide elastane fabric (having woven stitches) comprising for example 80% of polyamide and 20% elastane, with a basis weight of about 180 g / m 2. Under these conditions, the thickness of the outer layer 12 is for example of the order of 0.6 mm. When the layer 12 is formed of a fabric, it can be assembled with the layer 11 by a layer of adhesive 13, for example a silicone adhesive. The stamp is intended to be stuck on the skin thanks to the adhesive side

21. The shape and dimensions of the stamp 1 are adapted to the surface of the body that is meant to be exposed to its effects. Thus the surface of the stamp can range from a few centimeters to a few hundred centimeters.

The occlusive nature of the layer 11 tends to cause exudation, which leads to gradual disintegration by dissolution of the layer 2 containing the active product. The active product is thus released gradually and can then migrate to the skin. The active product could migrate to the layer 12, the skin and the layer 12 constituting two porous systems, one being rather loaded with water and the other with oil. However, if the layer 2 and in particular the active product are hydrophilic, the active product will be attracted to the skin.

If the outer layer 12 is made of fabric, the patch 1 can receive from the outer layer liquids that migrate to the layer 11. Thus, it is possible to introduce in the patch 1 a liquid adapted to modify the interface conditions with the skin. The liquid introduced into the patch by the outer layer 12 may be a solvent adapted to the composition of the layer 2, in order to accelerate the disintegration of the layer 2. This liquid may also aim at modifying the pH of the zone of the skin in contact with the patch, and thus promote the release of the active substances contained in the layer 2 if the composition of the latter is sensitive to PH. The layer 2 may be disposed on the adhesive face 21 of the layer 11 at the time of manufacture of the patch or be packaged separately and assembled to the layer 11 at the time of its use. The patch 1 can thus be reused several times, with several doses of successive active product provided by new layers 2. For this purpose, the patch can be cleaned with soapy water to remove any residues of the previously used layer 2, then left to dry naturally. Such washing makes it possible to completely restore the adhesive properties of the layer 11. The layer 2 may thus be in the form of a dermal patch intended to be used with the patch 1.

The stamp 1 which has just been described has many applications. Thus, the patch 1 may for example be used to perform allergic sensitivity tests for certain substances. For this purpose, a collection of layers 2 can be prepared containing all kinds of reagents, such as dust, pollen, etc. The layer 2 comprising the chosen reagent is placed in the center of the adhesive face 21 of the layer 11. The patch 1 is then adhered to the skin and left in place the time necessary for the reaction of the reagent with the skin. For the detection of allergies, it may also be envisaged to juxtapose several layers 2 containing different substances, simply taking the precaution of spacing them sufficiently from each other so that the inflammations do not cross.

The patch 1 can also be used to treat an injury. In this case, the layer 2 contains haemostatic products, adapted bacteriostatic products, as well as products promoting skin reconstruction such as chitin. The patch can also be used against plantar-piercing disease associated with hyperkeratosis. Figure 3 shows in section a part of the foot 30 with a lesion 32 in the dermis caused by a perforation of the skin 31 resulting from a hyperkeratosis 33. The patch 1 is applied to the injured part of the skin 33 with a layer 2 containing skin-promoting products such as chitin, skin-moisturizing and budding products and bacteriostatic products. The layer 11 provides here also a mechanical protection of the injured part which is furthermore hydrated by exudation caused by the occlusive power of the layer 11.

Another application concerns the care of pimples causing itching (hives, insect bites). The layer 2 chosen comprises antihistaminic and / or anti-inflammatory products. The layer 11 of the patch then provides skin protection and prevents the scratching of the button.

The patch 1 can also be used against wrinkles. The layer 2 chosen then comprises moisturizing agents or promoting the hydration of the skin. By its occlusion, the layer 11 also provides a moisturizing role. Tests have shown that the patch thus allows skin hydration multiplied by a factor of 30.

It will be apparent to those skilled in the art that the present invention is susceptible to various embodiments and applications. In particular, the invention is not limited to a dermal patch comprising an active layer (2) of uniform shape and composition. Thus, the active layer may be in the form of a powder whose particles are maintained at least partly on the adhesive layer 11 by the adhesive power of the adhesive face 21. When the active layer 2 is in the form of a film, it is not necessary that the film is soluble in water. Indeed, the polymer gel layer is entirely adapted to receive and transfer to the active layer 2 a liquid capable of disintegrating or completely dissolve the active layer.

Moreover, the active layer 2 in film form does not necessarily contain polysaccharides. Any other composition capable of forming a solid film capable of disintegrating or dissolving in contact with a suitable solvent may be suitable.

Claims

1. Dermal patch (1) comprising an adhesive layer (11) made of polymer gel having an adhesive face (21) intended to be applied to the skin, characterized in that it comprises an active layer (2) of dimensions smaller than those of the adhesive layer (11), placed on the adhesive side (21), and containing an active product in solid form comprising one or more active substances.

2. Stamp according to claim 1, wherein the active layer (2) comprises a solid film at least partially soluble in water and containing the active product.

3. Stamp according to claim 2, wherein the film of the active layer (2) comprises one or more polysaccharides.

4. Stamp according to claim 2 or 3, wherein the film of the active layer (2) is obtained by dehydration of a gel.

5. Stamp according to one of claims 2 to 4, wherein the film of the active layer (2) comprises at least one element of the set comprising chitin, chitosan, amigel and acid hyaluronic.

The patch of claim 1, wherein the active layer (2) comprises solid particles containing the active product.

7. Stamp according to one of claims 1 to 6, wherein the adhesive layer (11) is self-adhesive.

The patch of claim 1 or 7, wherein the adhesive layer (11) comprises a polymethylsiloxane resulting from the partial polymerization of a silicone oil mixture.

9. Stamp according to one of claims 1 to 8, wherein the layer adhesive (11) has a thickness of a few tens to a few hundred micrometers.

10. Stamp according to one of claims 1 to 9, comprising a non-adhesive outer layer (12) assembled on the opposite face (22) to the adhesive side (21) of the adhesive layer (11).

The patch of claim 10, wherein the outer layer (12) comprises an elastic fabric.

The patch of claim 10, wherein the outer layer (12) is a non-adhesive polymeric gel.

13. A method of manufacturing a dermal patch (1) comprising a step of manufacturing an adhesive layer (11) made of polymer gel having an adhesive face (21) intended to be applied to the skin, characterized in that comprises steps of manufacturing an active layer (2) comprising an active product in solid form comprising one or more active substances, and arranging the active layer on the adhesive side (21) of the adhesive layer (11).

14. The method of claim 13, wherein the active layer (2) comprises a film at least partially soluble in water and containing the active product.

The method of claim 14, wherein the film of the active layer (2) comprises one or more polysaccharides.

16. The method of claim 14 or 15, comprising a dehydration step of a gel to obtain the film of the active layer (2).

17. Method according to one of claims 14 to 16, wherein the film of the active layer (2) comprises at least one element of the set comprising chitin, chitosan, amigel and acid. hyaluronic.

18. Method according to one of claims 13 to 17, wherein the active layer (2) comprises solid particles containing the active product.

19. Method according to one of claims 13 to 18, wherein the adhesive layer (11) is self-adhesive.

20. A method according to one of claims 13 to 19, wherein the manufacture of the adhesive layer (11) comprises a step of partially polymerizing a mixture of silicone oils to obtain a polymethylsiloxane.

21. Method according to one of claims 13 to 20, wherein the adhesive layer (11) has a thickness of a few tens to a few hundred micrometers.

22. Method according to one of claims 13 to 21, comprising a step of assembling a non-adhesive outer layer (12) on the opposite face (22) to the adhesive face (21) of the adhesive layer (11). .

The method of claim 22, wherein the outer layer (12) comprises an elastic fabric.

24. Method according to one of claims 13 to 21, comprising a step of forming an outer layer (12) non-adhesive polymer gel on the opposite side (22) to the adhesive side (21) of the adhesive layer. (11).

25. Method according to one of claims 13 to 24, comprising a step of introducing into the adhesive layer (11) of a liquid for modifying the interface conditions of the patch with the skin.

26. Dermal patch (2) intended to be applied to the skin, characterized in that it consists of a film comprising an active product comprising one or more active substances and that it is capable of dissolving at least partially into presence of a suitable solvent.

The dermal patch of claim 26, wherein the film is water soluble.

The dermal patch of claim 26 or 27, wherein the film comprises one or more polysaccharides.

29. Skin patch according to one of claims 26 to 28, wherein the film is obtained by dehydration of a gel.

30. Skin patch according to one of claims 26 to 29, wherein the film comprises at least one element of the set comprising chitin, chitosan and hyaluronic acid.

31. Dermal patch according to one of claims 27 to 30, wherein the film has a thickness of a few tens to a few hundred micrometers.

The dermal patch of claim 26, wherein the film comprises solid particles containing the active product.

33. A method for applying an active substance to the skin, implemented for non-therapeutic aesthetic reasons, characterized in that it comprises the application to the skin of a dermal patch (1) according to one of claims 1 at 12, the active layer (2) containing an active substance is released slowly in contact with the skin.

34. The method of claim 33, wherein the patch comprises an outer layer (12) fabric, the method comprising a step of introduction into the stamp by the outer layer of a liquid adapted to modify the interface conditions of the stamp with the skin.

35. The method of claim 33 or 34, comprising successive steps of removing the patch (1) from the skin, deposition on the face adhesive (21) of a new active layer (2), and application of the patch on the skin.