WO2003041786A1

WO2003041786A1 - Device for administration of ointment to a skin area

Info

Publication number: WO2003041786A1
Application number: PCT/SE2002/001780
Authority: WO
Inventors: Erik Bengtson; Fredrik Gudmundsson; Carl-Otto Hanssen
Original assignee: Medeikonos Ab
Priority date: 2001-10-01
Filing date: 2002-09-30
Publication date: 2003-05-22
Also published as: SE0103276D0; SE0103276L

Abstract

The present invention relates to a device containing ointment, which device is intended to be attached to a skin area for absorption of the ointment, or of an active substance included in the ointment, in the skin area. The device comprises a surface structure which comprises depressions between tops, said depressions forming a space for holding the ointment and facing the skin area when the device is being used, thereby allowing even absorption of the ointment or of the active substance in the skin area. The invention also relates to a device for applying ointment, a set for assembling such a device, and to use of a surface structure for applying ointment.

Description

DEVICE FOR ADMINISTRATION OF OINTMENT TO A SKIN AREA

Field of the Invention

The invention relates to a device containing ointment, which device is intended to be attached to a skin area for absorption of the ointment, or of an active substance included in the ointment, in the skin area.

The invention also relates to a device for applying ointment to a skin area, comprising a space for holding the ointment. Finally, the invention relates to a set for assembling a device and to use of a device for applying ointment.

Background Art

SE 512,224 discloses a device for administration of delta-amino levulinic acid (ALA) to the skin in cancer detection/treatment and for protecting the skin area provided with ALA against light . The device comprises an opaque sheet which has a space formed against the skin for the ALA substance. Furthermore, the device has borders which are placed in contact with the skin and which are so wide that the dose of photoactive light energy diffused in under the borders and into the area of treatment is less than 0.2 J/cm².

The above-mentioned device is intended to be used in a step of a detection and/or treatment method for treating skin injuries. This step involves application of ointment containing delta-amino levulinic acid (ALA) to the skin with the aid of the device. The ointment is allowed to act for 1-24 hours. During this period of time, the device protects the skin area with the ointment against light. At the same time, a photo-active substance, protoporphyrine IX, forms in the skin under the effect of ALA.

Protoporphyrine IX typically gathers in cells which have somehow been altered, for example in cancer cells. The photo-active properties of protoporphyrine IX can also be used to detect or destroy the altered cells. The altered skin cells are detected by the skin portion being irradiated with light within a certain wavelength range, which makes protoporphyrine IX fluorescent . Then the altered cells can be detected by means of a fluorescence- recording camera. The altered skin cells are destroyed by the skin portion being irradiated with light within other wavelength ranges, whereby protoporphyrine IX disinte- grates into toxic substances, which in turn kill the altered cells.

The above-described device thus fulfils the twofold mission to apply ointment containing ALA and to protect the skin area against light during the time the ALA oint- ment acts on the skin for forming protoporphyrine IX.

However, one problem of the above device is that it is difficult to fill the space intended for the ointment in an even manner, which results in the active substance being unevenly distributed over the skin. Owing to this, the subsequent detection or destruction of the altered skin cells may not be reliable. The problem is aggravated by the fact that it is difficult to obtain even contact between the ointment and the skin. In addition, a great amount of ointment is needed. The object of the present invention is to provide a device for applying ointment to the skin, which device reduces or obviates one or more of the problems identified above .

Summary of the Invention

The above-mentioned object is, according to a first aspect of the invention, achieved by means of a device containing ointment, as stated by way of introduction, which device comprises a surface structure which com- prises depressions between tops, said depressions forming a space for holding the ointment, which space, when the device is being used, is facing the skin area, thereby allowing even absorption of the ointment or of the active substance in the skin area.

When attached, the surface structure prevents the ointment from moving freely in the device, which main- tains the even distribution of the ointment when it is in contact with the skin area.

The problems involved in prior-art technique where a larger space is used to hold the ointment, for example the ointment being unevenly distributed due to exterior pressure or to the ointment running in the space, can thus be obviated or reduced.

Furthermore, the shape and the size of the depressions can be adapted to hold an amount of ointment appropriate to the intended purpose, which makes it easier to dose the ointment.

The surface structure is advantageously made of a dimensionally stable material. Such a material is not, under normal circumstances, compressed when an application device of this type is being used, for example, it is not compressed by a light exterior pressure. This ensures that the surface structure maintains its shape, and thus its function, when the device is being used.

The surface structure is preferably made of a flexible material, so that it will be formable according to the contour of a skin area.

To achieve even distribution of the ointment, the tops are preferably regularly arranged in the surface structure .

The configuration of said depressions and tops is suitably adapted to the diffusion properties of the ointment or the active substance in the skin, so that even absorption of the ointment or the active substance is obtained in the skin area during the time of application of the surface structure. In many medicinal applications, such as the above- described treatment with ALA ointment, it is very important for the ointment to be evenly applied over the entire skin area. To prevent the skin portions located just under the tops of the surface structure from not receiving any ointment, the tops are preferably formed with a relatively small contact surface against the skin. If the contact surface is not very large, the ointment or an active substance included in the ointment can diffuse under the contact surface of the top in amounts sufficient to obtain even absorption of the substance in the skin area . To facilitate the diffusion in the skin, the contact surfaces can advantageously be punctiform. Punctiform is here to be considered in contrast to, for example, line- shaped, and it is not excluded that the actual contact surface has a different shape. The length a certain substance diffuses into the skin is called diffusion length and it depends on the time the substance is allowed to act. Advantageously, the tops are formed so that each top has a maximum contact surface A (top) which is not larger than to allow an active substance in the ointment to diffuse under the surface during the application time of the plaster. Suitably, A (top) can be less than 0.5 mm², preferably less than 0.1 mm², most preferably less than 0.01 mm².

The tops are advantageously formed such that each top has a maximum contact radius R(top) by means of which the top is in contact with the skin area when the plaster is being used and which is shorter than an expected diffusion length of an active substance in the ointment into the skin during the application time of the plaster. Suitably, R(top) can be less than 0.4 mm, preferably less than 0.2 mm, most preferably less than 0.05 mm.

One way of providing punctiform contact surfaces is to use conical tops. Herein, the expression conical not only refers to cones that are circular in cross- section, but also to conically tapering structures which, for example, have an angular or irregular shape in cross- section. Thus, pyramid-shaped tops with square or triangular bases can, for example, be used.

Another way of providing punctiform contact surfaces is to make the tops spherical or partially spherical. Even if punctiform contact surfaces are probably, as mentioned above, those that are most fit for use, it is also conceivable to use line-shaped contact surfaces. When using line-shaped contact surfaces, the width of the line should be adjusted so that an active substance in the ointment is capable of diffusing under the contact surface during the application time of the plaster. Advantageously, the line width can be less than 0.8 mm, more preferably 0.4 mm and most preferably 0.1 mm. The distance between the deepest part of the depressions in the surface structure and the tops, herein referred to as structure depth, depends above all on the desired volume of the ointment. Suitable depths in medicinal applications are in the range of 0.2-2 mm, preferably 0.3-0.5 mm. The distance between two adjacent tops, herein referred to as structure distance L, is suitably in the range of 0.5-4 mm, more preferably 1-3 mm, most preferably 2-3 mm.

A pad can advantageously be arranged in connection with the surface structure to press the same against the skin area. This ensures good contact during use between the surface structure with ointment and the patient's skin. This is particularly important when the device is to be used in concave skin portions, where it is other- wise difficult to obtain even distribution of the ointment. In addition, the pad contributes to the protecting and warming action of the device in the underlying skin area.

According to a second aspect of the invention, a device is also provided, as stated by way of introduction, which is characterised in that the space for holding the ointment is formed of depressions between tops in a surface structure which, when the device is being used, is facing the skin area, thereby allowing even distribution of the ointment over the skin area.

When using a device according to the second aspect of the invention, ointment is applied in the depressions of the surface structure, the ointment easily being evenly distributed in the actual device. The application is suitably effected by an abundant amount of ointment being placed in the surface structure and subsequently spread evenly, for example by means of a spatula, so that the uppermost portions only of the tops in the structure can be seen through the layer of ointment. After filling the depressions of the structure layer with ointment, the device is attached to a skin area. The device according to the second aspect of the invention can advantageously have the same characteristics as those described above in connection with the first aspect of the invention.

A third aspect of the invention relates to a set for assembling a device, comprising a surface structure with depressions and tops, said depressions forming a space for holding ointment .

In a fourth aspect, the invention relates to use of a device according to the invention, the time of application of the device against the skin being adapted to the diffusive properties of the ointment or an active substance in the ointment, so that the ointment or the active substance is capable of diffusing evenly over the skin area during the application time.

A device according to the invention can be used independently by the ointment being distributed in the device when the device is being attached to the skin area of a patient.

Brief Description of the Drawings Fig. 1 is a perspective view of an embodiment of an application device according to the invention.

Fig. 2 is an exploded view of the plaster in Fig. 1. Fig. 3 is a detail view of the surface structure of the application device in Fig. 1.

Fig. 4a is a variant of a surface structure in an embodiment of an application device according to the invention.

Fig. 4b is another variant of a surface structure in an embodiment of an application device according to the invention.

Description of Preferred Embodiments of the Invention

Fig. 1 shows a preferred embodiment of an application device 1 according to the second aspect of the invention, i.e. a device in which ointment has not yet been applied. The application device 1 consists of a plurality of superposed layers. At the top in Fig. 1, a structure layer 2 is arranged which, when the device 1 is being used, will be facing a skin area. The structure layer 2 will be described in more detail below.

Behind the structure layer 2, a light-protective layer 3 is provided, which is preferably an opaque sheet made of metal or plastic. The light-protective layer 3 is useful if the application device 1 is to be used for applying light-sensitive substances, such as ALA ointment. The layer 3 also has a certain heat-insulating action, which can improve the effect of the ointment in the skin.

Behind the light-protective layer 3, there is an elastic plastic film 4 which is provided with adhesive to attach the device 1 to the skin. Instead of the plas- tic film 4, use can be made of a dressing or some other firm attachment method. The plastic film 4 is, however, particularly useful when applied, for example, to skin portions in the face.

The adhesive borders of the plastic film 4 can ini- tially be protected by a protective film. Suitably, the protective film does not cover the structure layer 3 so as to make it possible to spread ointment in the surface structure before the removal of the protective film to attach the device to the skin. The protective film thus forms a frame around the structure layer. One advantage of such a construction is that the protective film will protect the adhesive in case ointment should be spilt when filling the surface structure.

Between the light-protective layer 3 and the plastic film 4, a soft pad 5 is arranged, which is visible in the exploded view in Fig. 2. The pad 5 serves to ensure good contact between the structure layer 2 and the skin area and thus an even effect of the ointment which is to be applied. Furthermore, the pad 5 protects against exterior pressure when the device 1 is being used. The pad 5 also contributes to keeping the skin area under the device warm, which is particularly important in order to obtain a good effect of some medicinal substances.

Since the device 1 is to be arranged on a skin area, it is an advantage if all the layers included are relatively elastic, so that they can be made to follow the contour of the body. This is particularly important when the device is to be used in such skin portions as the nose and the ears. These skin portions are also particularly vulnerable to certain diseases, for example cancer of the skin. With reference to Fig. 3, the structure layer will now be described. The structure layer 2 has a surface structure 6 comprising tops 7 and depressions 8. In this case, the tops 7 are formed as pyramids. When the application device is being used, the surface structure 6 is filled with ointment. Preferably, the ointment is spread, for example, with the aid of a spatula, so that the . depressions 8 will be filled with ointment substantially in their entirety. The amount of ointment is easily determined by the total volume of the depressions 8^'. When the application device 1 is being used, the outer parts of the tops 7 will be in contact with the skin. Each top is in contact with the skin with a contact surface A. The skin portions located just opposite such a contact surface will thus not be provided with ointment directly. However, on condition that the contact surface A is sufficiently small, the ointment can diffuse also into the skin areas which are located under the contact surfaces A of the tops 7, which finally results in an even application of the ointment.

In this case, the structure layer 2 consists of an embossed plastic film. Such a plastic film has the advan- tage of being dimensionally stable as it resists normal exterior pressure without the surface structure being damaged. In addition, it is sufficiently elastic along its surface to be formable according to different skin portions . To ensure good diffusion, the contact surfaces are preferably punctiform. The expression punctiform is here to be considered in contrast to, for example, line- shaped. The geometry of the contact surface can, for example, be circular, triangular or square. But a cir- cular contact surface should yield the best and most even result .

Preferably, the contact surfaces are formed such that a maximum contact radius R of the surface is shorter than the diffusion length of the ointment or the sub- stance in the skin during the application time.

For example, in the surface structure shown in Fig. 3, the contact radius R is less than 0.05 mm.

The space formed by the depressions 8 in the surface structure 6 is adapted to hold the amount of ointment needed to treat the underlying skin area. In this example, the depressions provide a volume of 0.45 mm³ ointment per mm² skin area .

The structure depth from a top 7 to the bottom of the depressions 8 is about 0.5 mm and the distance between the tops 7 about 2 mm.

The pyramid-shaped surface structure 6 shown in Fig. 3 has been found to be particularly useful. The pyramid configuration probably results in a good capacity to retain the ointment owing to the shape of the depressions, at the same time as the contact surface of the tops against the skin is relatively small. A similar effect should be obtained using conical tops.

Nevertheless, other surface structures are also conceivable. Especially a surface structure in which the tops consist of partially spherical projections has been found to produce a satisfactory result. Such surface structures are shown in Figs 4a and 4b.

Also surface structures in which the tops form lines of some kind, with line-shaped contact surfaces against the skin, can be used, even if so far they have been found to yield a somewhat inferior result to those hav- ing punctiform contact surfaces against the skin. The inferior results are most likely due to the fact that the ointment is less evenly distributed if line-shaped, instead of punctiform, contact surfaces are used.

In the description above, the device has been dis- closed as an independent device which is manually filled with ointment. However, according to the first aspect of the invention, the device can also be assembled and filled with ointment in connection with the manufacture of the device. A protective film can then suitably be arranged to keep the ointment in place in the device during the manufacture and handling thereof. This ensures that the intended amount of ointment is arranged in the device and that demands on hygiene and sterility, if any, can be met. Subsequently, when the device with ointment is to be attached to the patient's skin area, the protective film is removed and the device is attached in usual manner to the skin area . Further use of a device according to the invention may involve a surface structure which is adapted as to size and shape to a skin area and which is subsequently provided with ointment and finally attached to the skin area. The invention can be varied in more ways. Besides the above variation of the shape of the tops and depressions of the surface structure, also the parts of the device in the embodiments disclosed herein can be varied. The different layers can, for example, be formed individually or in one piece. The surface structure can be embossed in a light-protective material, thus combining the light-protective layer with the surface structure. It is also possible to exclude the light-protective layer all together, if ointments which are not sensitive to light are used. Furthermore, a device according to the invention can advantageously be provided with the type of light-protective borders which are disclosed in SE 512, 224. The pad can also be designed in different ways. In the description above, use of the invention for applying ointment has primarily been described in situations where ointment containing ALA is used. The device can, however, also be used for applying other types of medicinal ointment which require very even distribution of the ointment. This is specially the case of other light-sensibilising substances which can be used in ointment .

Description of trials Trials have been made to establish the suitability of various embodiments of the invention as a carrier of ALA to the skin for subsequent detection/treatment purposes. These trials will be described below without limiting the scope of the invention. As a reference, use was made of a device according to SE 512,224 which is described by way of introduction and in which ALA ointment is arranged in a rectangular space in the plaster. Test structures used

1) Coarse netting AET P2409

2) Coarse netting AET P1715

3) Embossed plastic structure "pyramid-shaped" AET X220

All the devices are filled with 20 % 5-amino- levulinic-acid in ungentum Merck. The reference device was filled with 2 ml ointment in an even layer. In device 1 and 2, the ointment was applied evenly by means of a spatula, as thick as admitted by the structure so that the depressions in the structure surface were filled and the tops were visible. As a result, device 1 and 2 contained somewhat less than 1 ml ointment .

The three devices were attached to the back of a test subject and the ointment was allowed to act for 3 hours. After this, the application devices were removed and the ointment was wiped off . Two fluorescence images were taken of each skin area corresponding to the respective devices . The mean intensity (m) of the fluorescence and the standard deviation (SD) were measured. In the Table below, the mean intensity (m) is indicated as a ratio of the mean intensity in the area treated with ALA under the respective devices to the intensity in a reference area which had not been treated with ALA.

The devices 1-3 yielded higher total fluorescence levels than the reference device. The devices 1 and 3 yielded a better value of evenness than the reference device. However, these differences are not significant.

The trials show that the devices 1-3 according to the invention yielded the same mean fluorescence level as the reference device, in spite of the fact that only half as much ALA ointment was used in the devices 1-3 as in the reference device.

On the other hand, the netting structures used in the devices 1 and 2 produced visible patterns in the fluorescence. Such patterns were not found in the device 3, which is consequently assumed to be the best embodiment of the invention so far.

The reason why the netting structures produced pat- terns in the fluorescence is not completely known. It is most likely that the netting structure has an influence on the capacity of the active substances to diffuse in the skin. The elongate contact surfaces of the netting structures against the skin allow diffusion only from the longitudinal sides of each area, which results in a smaller total amount of active substance being diffused into the skin than if punctiform contact surfaces are used. It is also possible that the netting structures yield inferior blood flow through the skin, which may result in a lower diffusion capacity.

Besides the pyramid structure described above, a structure having partially spherical tops has also been used. Such a structure can be obtained by using Delnet x 220 from Applied Extrusion Technologies Limited, in the form of netting which is heated to adhere so as to form the desired structure surface.

Claims

1. A device containing ointment, which device is intended to be attached to a skin area for absorption of the ointment, or of an active substance included in the ointment, in the skin area, c h a r a c t e r i s e d in that the device comprises a surface structure (6) which comprises depressions (8) between tops (7) , said depres- sions (8) forming a space for holding the ointment, which space, when the device is being used, is facing the skin area, thereby allowing even absorption of the ointment or of the active substance in the skin area.

2. A device containing ointment as claimed in the preceding claim, wherein the configuration of said depressions (8) and said tops (7) is adapted to the diffusion properties of the ointment or the active substance in the skin, so that even absorption of the ointment or the active substance is obtained in the skin area during the time of application of the surface structure.

3. A device containing ointment as claimed in any one of the preceding claims, wherein the configuration of said depressions (8) is adapted to hold an amount of ointment suitable for the intended purpose of the oint- ment in the skin area.

4. A device containing ointment as claimed in any one of the preceding claims, wherein said tops (7) have a maximum contact surface (A) against the skin area that is not larger than to allow even absorption of the active substance of the ointment in the skin area.

5. A device containing ointment as claimed in claim 4, wherein said contact surface (A) is adapted to the diffusion length of the ointment or the active substance in the skin, so that, during the application time of the device, the ointment or the active substance is capable of diffusing into the portions of the skin area which are in contact with the contact surface (A) of said tops (7) .

6. A device containing ointment as claimed in any one the preceding claims, wherein said tops (7) have a contact radius (R) against the skin area that is not longer than to allow even absorption of the ointment or the active substance in the portions of the skin area which are in contact with said tops (7) .

7. A device containing ointment as claimed in claim 6, wherein said contact radius (R) equals or is shorter than the diffusion length of the ointment or its active substance in the skin during the application time of the device, so that the ointment or the active substance is capable of diffusing into the portions of the skin area which are in contact with said tops.

8. A device containing ointment as claimed in any one of the preceding claims, wherein said ointment contains delta-amino levulinic acid.

9. A device containing ointment as claimed in any one of the preceding claims, wherein said surface structure is part of a dressing intended for applying the ointment to the skin area in a clearly defined region thereof .

10. A device (1) for applying ointment to a skin area, intended to be attached to the skin area for absorption of the ointment, or of an active substance included in the ointment, in the skin area and comprising a space for holding the ointment, c h a r a c t e r i s e d in that said space is formed of depressions (8) between tops (7) in a surface structure (6) which, when the device (1) is being used, is facing the skin area, thereby allowing even absorption of the ointment or the active substance in the skin area.

11. A device as claimed in any one of the preceding claims, wherein the depressions (8) form a continuous space for holding the ointment .

12. A device as claimed in any one of the preceding claims, wherein the surface structure (6) is made of a dimensionally stable material.

13. A device as claimed in any one of the preceding claims, wherein the surface structure (6) is made of a flexible material so as to be formable according to the contour of the skin area.

14. A device as claimed in any one of the preceding claims, wherein the tops (7) are regularly arranged in the surface structure (6) .

15. A device as claimed in any one of the preceding claims, wherein each top (7) has a maximum contact sur- face A (top) by means of which the top is in contact with the skin area when the device (1) is being used, and the contact surface A (top) is punctiform.

16. A device as claimed in any one of the preceding claims, wherein each top (7) has a maximum contact sur- face A (top) by means of which the top (7) is in contact with the skin area when the device (1) is being used, and the contact surface A (top) of each top is less than 0.5 mm², preferably 0.1 mm², most preferably 0.01 mm².

17. A device as claimed in any one of the preceding claims, wherein each top (7) has a maximum contact radius R(top) by means of which the top is in contact with the skin area when the device- (1) is being used, and the maximum contact radius R(top) of each top (7) is less than 0.4 mm, preferably 0.2 mm, most preferably 0.05 mm.

18. A device as claimed in any one of the preceding claims, wherein each top (7) has a maximum contact surface A (top) by means of which the top (7) is in contact with the skin area when the device (1) is being used, and the contact surface A (top) is line-shaped.

19. A device as claimed in claim 15, wherein each line-shaped contact surface A (top) has a line width of less than 0.8 mm, preferably 0.4 mm, most preferably 0.1 mm.

20. A device as claimed in any one of the preceding claims, wherein the total contact surface Atot of all the tops (7) constitutes less than 5 percent of the overall surface of the surface structure .

21. A device as claimed in any one of the preceding claims, wherein the vertical distance between a depression (8) and a top (7) of the surface structure, herein referred to as structure depth, is in the range of 0.2-2 mm, preferably 0.3-1.5 mm, most preferably 0.3-0.5 mm.

22. A device as claimed in any one of the preceding claims, wherein the horizontal distance between two adjacent tops (7) along the structure surface, herein referred to as structure distance L, is in the range of 0.5-4 mm, preferably 1-3 mm, most preferably 2-3 mm.

23. A device as claimed in any one of the preceding claims, wherein the tops (7) are conical.

24. A device as claimed in claim 23, wherein the tops (7) are pyramid-shaped.

25. A device as claimed in any one of the preceding claims, wherein the tops (7) have the shape of completely or partially spherical projections.

26. A device as claimed in any one of the preced- ing claims, wherein the device (1) comprises a pad (5) arranged to press the surface structure (2) against the skin area when the device (1) is being used.

27. A device as claimed in any one of the preceding claims, wherein the device (1) also comprises a light- protective layer (3) arranged to protect the skin area against incident light when the device (1) is being used.

28. A set for assembling a device (1) as claimed in any one of the preceding claims, comprising a surface structure with said depressions (8) and tops (7) .

29. Use of a device as claimed in any one of claims 1-27, containing ointment, wherein the time of application of the device against skin is adapted to the diffusive properties of the ointment or an active substance in the ointment, so that the ointment or the active substance is capable of diffusing evenly over the skin area during the application time.