WO2004112759A2

WO2004112759A2 - Skin patches

Info

Publication number: WO2004112759A2
Application number: PCT/GB2004/002519
Authority: WO
Inventors: Peter William Richards
Original assignee: Peter William Richards
Priority date: 2003-06-17
Filing date: 2004-06-11
Publication date: 2004-12-29
Also published as: WO2004112759A3

Abstract

A transdermal skin patch (1) comprises drug storage means (3), securing means to secure the skin patch to the skin of a user, and drug release means, the drug release means being operative, in use, when the patch is secured to the user, to vary the amount of the drug released from the drug storage means (3) in dependence upon the temperature of the skin of the user. The drug release means comprises a solution containing the drug, the solution having a solubility which varies in dependence upon the temperature of the skin of the user, the amount of the drug released from the drug storage means (3) varying as the solubility varies. The drug release means may alternatively comprise a drug permeable film (5), the permeability of the film (5) to the drug increasing as skin temperature increases, the drug storage means, the securing means, and the drug permeable film comprising a single composite layer.

Description

SKIN PATCHES

The present invention relates to skin patches and particularly but not exclusively relates to skin patches containing a drug which passes from the skin patch and through the skin of the user over a period of time.

The delivery of drugs transdermally (through the skin) has several important advantages over traditional oral and intravenous delivery routes. Transdermally delivered drugs avoid the risk and inconvenience of intravenous drug therapy, and can reduce the chance of an overdose or under dose of the drug being administered. It is also relatively easy to terminate the administration of the drug as the skin patch can simply be removed from the skin of the user.

During illness the temperature of the human body rises to assist in its defence from, for example, micro-organisms such as bacteria and viruses. The resultant rise in temperature can be harmful and unpleasant.

Some children can suffer "febrile convulsions" i.e. they suffer a fit as their body temperature rises. Once a febrile convulsion has occurred there is a risk it will happen again when the patient becomes febrile. A traditional treatment for such fits is to give orally an anti-pyretic drug such as Ibuprofen. The administration of a drug can be very difficult if the child is fitting or vomiting.

According to a first aspect of the invention there is provided a transdermal skin patch comprising drug storage means, securing means to secure the skin patch to the skin of a user, and drug release means, the drug release means being operative, in use, when the patch is secured to the user, to vary the amount of the drug released from the drug storage means in dependence upon the temperature of the skin of the user. Preferably the drug release means is operative to release an increasing amount of the drug from the drug storage means as the temperature of the skin of the user increases. Most preferably the amount of drug released from the drug storage means decreases as the temperature of the skin of the user falls to normal.

Preferably the drug release means is operative such that the amount of the drug released from the drug storage means is zero when the skin temperature of the user is normal.

In a first embodiment of the invention, the drug release means comprises a drug permeable film, the permeability of the film to the drug increasing as skin temperature increases. By a drug permeable film we mean any film that can allow a drug to pass through, to penetrate, or be absorbed into the film.

Preferably the film comprises a plurality of drug permeable pores, the pores increasing in size so as to open as the skin temperature increases above normal. Increasing pore size results in increasing permeability of the drug permeable film to the drug concerned.

Preferably the drug storage means, the securing means and the drug permeable film comprise separate layers, such that the skin patch is of generally laminate form.

Alternatively the drug storage means, the securing means and the drug permeable film comprise a single, composite layer.

Preferably the securing means comprises an adhesive. In a second embodiment of the invention, the drug release means comprises a solution containing the drug, the solution having a solubility which varies in dependence upon the temperature of the skin of the user, the amount of the drug released from the drug storage means varying as the solubility varies.

Preferably in use, the solubility of the drug varies such that as the body temperature of the user increases, the skin temperature of the user increases and the amount of the drug that is released from the solution increases so as to pass from the skin patch and through the skin of the user.

Preferably the physical properties of the drug vary in dependence upon the skin temperature of the user. Preferably the change of physical properties of the drug is such that changes in the skin temperature of the user cause the drug to change from a solid state to a liquid state, more of the drug being released when the drug is in a liquid state than when the drug is in a solid state.

Alternatively the drug is an active drug, changes in the skin temperature of the user changing the amount of the active drug that is released.

Preferably the drug is bio-chemically altered as the temperature of the user increases so that the amount of the active drug released increases.

Preferably the skin patch further comprises temperature display means which provides an indication of the temperature of the skin of the user.

Preferably the drug stored in the drug storage means is an anti-pyretic drug such as, for example, Ibuprofen. According to a second aspect of the invention there is provided a dosage pack comprising a plurality of the skin patches of the first aspect of the invention.

Preferably the dosage pack comprises a plurality of skin patches of different sizes, the dose provided by each skin patch being determined by the size of each skin patch.

Other aspects of the present invention may include any combination of the features or limitations referred to herein.

The present invention may be carried into practice in various ways, but embodiments will now be described by way of example only with reference to the accompanying drawings in which:

Figure 1 is a schematic exploded perspective view of a first embodiment of a skin patch in accordance with the present invention; and

Figure 2 is a schematic exploded perspective view of a second embodiment of a skin patch in accordance with the present invention.

Referring initially to Figure 1 , a skin patch 1 comprises drug storage means in the form of a drug reservoir 3. The drug reservoir 3 is sandwiched between a permeable film 5 and a sealing layer 7.

The drug is encapsulated in a gel or liquid within the drug reservoir 3. The permeable film 5 comprises drug release means in the form of a drug permeable material provided with a plurality of pores that are permeable to the drug under certain temperatures, but are impermeable to the drug under lower temperatures. The film 5 can be of a type that the size of the pores changes in dependence upon the temperature, although any other suitable material providing a similar function could alternatively be used. The permeability of the pores may alternatively or in addition be dependant on the shape of the pores, and/or on how the pores are connected to one another.

The film 5 can be manufactured from any suitable material including fluoropolymers , thermoplastic resin, elastomers, urethanes, protein or gel based materials, or woven materials.

The sealing layer 7 seals the drug reservoir 3 to the permeable film 5 and prevents the drug from leaking from the drug reservoir 3. The sealing layer 7 can be waterproof to enable the skin patch 1 to be used when the user is in water. The sealing layer can be in the form of a film, a foam layer or a non-woven layer, and could be made, for example, from EVA (Ethylene Vinyl Acetate) , PE (Polyethylene), Polyester (Polyethylene Terephthalate) , PP (Polypropylene), PU (Polyurethane) , and other Polyolefins.

Securing means is provided comprising an adhesive layer for securing the skin patch 1 to the skin of a user. In the embodiment shown in Figure 1 , the adhesive is provided on a sheet secured to the permeable film 5 on the opposite side of the skin patch 2 to the sealing layer. Any other suitable securing means can alternatively be provided to secure the skin patch 1 to the skin of the user although is has been found that adhesive is generally convenient. A cover sheet (not shown) can be provided to cover the adhesive when the skin patch 1 is not in use. When the skin patch 1 is to be used, the cover sheet is peeled from the adhesive and the skin patch 1 is pressed firmly onto the skin of the user. The adhesive thus secures the skin patch 1 to the skin of the user.

The patch can be applied centrally on the body, so that the local temperature surrounding the patch accurately reflects body temperature. Care must be taken that it is not placed over heating pads, under heavy bedding or near any other object that could serve to affect the temperature surrounding the patch. The patch can be applied to the forehead. The patch may be applied to other parts of the body provided that the patch is modified so as to account for the variation in body temperature that can occur away from the centre of the body.

In use the temperature of the skin of the user affects the temperature of the skin patch 1. The drug release means comprising the drug permeable film 5 is operative such that when the temperature of the skin of the user is normal, the pores of the film 5 are not permeable to the drug contained in the drug reservoir 3 and thus the drug contained on the drug reservoir does not pass through the film 5 and through the skin of the user. Normal skin temperature is typically approximately 33°C which corresponds to a body temperature which is normal between 36.5°C and 38°C.

As the temperature of the skin of the user rises, as might be the case when the body of the user is fighting an infection or virus, the pores of the film 5 expand so as to allow some of the drug contained in the drug reservoir 3 to pass through the film 5 and through the skin of the user.

Thus as the temperature of the skin of the user increases, the skin patch 1 begins to administer some of the drug to the user. Further increases in the temperature of the skin of the user causes the pores of the film 5 to further expand so that the skin patch 1 administers a larger amount of the drug. Likewise, as the skin temperature falls back to normal, the pores of the film 5 contract so that the skin patch 1 administers a smaller amount of the drug. The type of film 5 will be chosen such that at normal skin temperature the film 5 is impermeable to the drug in question, and also so that the maximum amount of drug administered by the skin patch 1 can be limited so that an overdose of the drug can not be administered.

Referring now to Figure 2 an alternative embodiment of the skin patch is shown with like features being given like references. In this embodiment the drug reservoir 3 is omitted. Instead the drug to be administered is part of a drug adhesive mixture which is integral with the permeable film 5 and the sealing layer 7 so that the alternative skin patch 1 ' forms a single composite layer. The integrated nature of the skin patch 1 renders the skin patch 1 smaller and slimmer for a given amount of drug storage capacity in comparison to the skin patch 1 of Figure 1.

In this embodiment, the film 5 can function as described above in relation to the embodiment of Figure 1.

Alternatively, the drug may be stored in a solution where the solubility of the drug in that solution is dependant on the temperature of that solution. The solution could comprise a single adhesive, or multiple adhesives, and/or excipients (ingredients that have no pharmacological effect). Examples of excipients are solubilizers, stabilizers, permeation enhancers, fillers, and binders. The solution can contain excipients that affect how much of the drug is released in dependence upon the temperature of the user. Thus at normal skin temperature, the solubility is such that the drug remains in solution and cannot pass through the permeable film 5. However, as the skin temperature rises above normal, the drug begins to fall out of solution and thus passes through the permeable film 5. Further temperature increases cause more of the drug to fall out of solution, pass through the permeable film 5 and through the skin of the user. So in this embodiment of the invention, the drug release means comprises a combination of a fixed or variable permeability film 5, and a variable solubility drug solution.

Either of the embodiments of the invention could be modified to include a temperature display indicative of the temperature of the skin of the user of the skin patch. Such a temperature display could be a digital display or a selection of graded colour boxes which illuminate as the skin temperature increases.

It is envisaged that such skin patches would be sold in dosage kits containing a plurality of patches of different sizes, each size containing a different dose of the drug in question. Thus the dosage kit could contain sufficient patches for a family of adults and children for example.

It is envisaged that the above described skin patches would be used to administer anti-pyretic drugs such as ibuprofen or paracetamol which are used to reduce the temperature of the human body. However, it is envisaged that the skin patches could also be used to administer other types of drug in any situation where the amount of the drug required is to some extent dependant on the temperature of the skin of the user.

Claims

1. A transdermal skin patch (1) comprising drug storage means (3) , securing means to secure the skin patch to the skin of a user, and drug release means, the drug release means being operative, in use, when the patch (1) is secured to the user, to vary the amount of the drug released from the drug storage means (3) in dependence upon the temperature of the skin of the user, the drug release means comprising a solution containing the drug, the solution having a solubility which varies in dependence upon the temperature of the skin of the user, the amount of the drug released from the drug storage means (3) varying as the solubility varies.

2. The transdermal skin patch (1) of claim 1 wherein in use, the solubility of the drug varies such that as the body temperature of the user increases, the skin temperature of the user increases and the amount of the drug that is released from the solution increases so as to pass from the skin patch and through the skin of the user.

3. The transdermal skin patch (1) of any one of the preceding claims wherein the physical properties of the drug vary in dependence upon the skin temperature of the user.

4. The transdermal skin patch (1) of claim 3 wherein the change of physical properties of the drug is such that changes in the skin temperature of the user cause the drug to change from a solid state to a liquid state, more of the drug being released when the drug is in a liquid state than when the drug is in a solid state.

5. The transdermal skin patch (1) of any one of claims 1 to 4 wherein the drug is an active drug, changes in the skin temperature of the user changing the amount of the active drug that is released.

6. The transdermal skin patch (1) of claim 5 wherein the drug is bio-chemically altered as the temperature of the user increases so that the amount of the active drug released increases.

7. A transdermal skin patch (1) comprising drug storage means, securing means to secure the skin patch to the skin of a user, and drug release means (5), the drug release means (5) being operative, in use, when the patch (1) is secured to the user, to vary the amount of the drug released from the drug storage means in dependence upon the temperature of the skin of the user, the drug release means comprising a drug permeable film (5) , the permeability of the film (5) to the drug increasing as skin temperature increases, the drug storage means, the securing means, and the drug permeable film comprising a single composite layer.

8. The transdermal skin patch (1) of claim 7 wherein the drug release means is operative to release an increasing amount of the drug from the drug storage means as the temperature of the skin of the user increases.

9. The transdermal skin patch (1) of claim 8 wherein the amount of drug released from the drug storage means decreases as the temperature of the skin of the user falls to normal.

10. The transdermal skin patch (1) of any one of claims 7 to 9 wherein the drug release means is operative such that the amount of the drug released from the drug storage means is zero when the skin temperature of the user is normal.

11. The transdermal skin patch (1) of any one of claims 7 to 10 wherein the film (5) comprises a plurality of drug permeable pores, the pores increasing in size so as to open as the skin temperature increases above normal.

12. The transdermal skin patch (1) of any one of claims 1 to 11 wherein the securing means comprises an adhesive.

13. The transdermal skin patch (1) of any one of the preceding claims further comprising temperature display means which provides an indication of the temperature of the skin of the user.

14. The transdermal skin patch (1) of any one of the preceding claims wherein the drug stored in the drug storage means is an anti-pyretic drug.

15. A dosage pack comprising a plurality of the skin patches (1) of claims 1 to 6 and 12 to 14.

16. A dosage pack comprising a plurality of the skin patches (1) of claims 7 to 11 and 12 to 14.

17. The dosage pack of claim 15 or claim 16 further comprising a plurality of skin patches (1) of different sizes, the dose provided by each skin patch (1) being determined by the size of each skin patch.