Device and Formulation for Topical Treatment of Pain Affecting the Vulvar Area of the Female Human Genital Organ

Abstract

The present invention relates to a device for the topical treatment of pain affecting the vulvar area of the female human genital organ, a formulation for use in the device according to the invention, and a kit comprising the device according to the present intention. Additionally, the present invention relates to a method of topical treatment of pain affecting the vulvar area of the female human genital organ, said method using the device according to the present invention. The device is a layered article shaped to be placed in use inside a female undergarment and at least partially in skin contact with the female vulvar area and comprises a topical formulation.

Claims

1. A device (1) for the topical treatment of pain affecting the vulvar area of the female human genital organ, wherein the device (1) is a layered article shaped to be placed in use inside a female undergarment and at least partially in skin contact with the female vulvar area, said article having a longitudinal direction (L), a transverse direction (T), a front end (F), a back end (B), and two longitudinal sides (S, S), and said device (1) comprises at least a) a formulation-impermeable outer layer (2) having an outer surface (2a) and an inner surface (2b); b) a carrier layer (5) having an inner carrier surface (5a) and a skin-contacting surface (5b), wherein said inner carrier surface (5a) faces in the direction of the inner surface (2a) of the formulation-impermeable outer layer (2); and c) a topical formulation comprising at least one active agent for treating pain affecting the vulvar area of the female human genital organ.

2. The device according to claim 1, wherein the carrier layer is at least partially impregnated with the topical formulation.

3. The device according to claim 1, further comprising d) a formulation-impermeable rim layer (3), wherein said rim layer (3) is superimposed on the inner surface (2b) of formulation-impermeable outer layer (2) and does not cover an inner section thereof thereby defining a channel (4) extending in the longitudinal direction (L) of the article; and e) a carrier layer (5) having an inner carrier surface (5a) and a skin-contacting surface (5b), said carrier layer (5) being superimposed on the formulation-impermeable rim layer (3) and the channel (4) such that the inner carrier surface (5a) faces in direction of the formulation-impermeable rim layer (3) and the channel (4); wherein the carrier layer (5) is at least partially impregnated with the topical formulation and/or at least one dispensing unit (6) is positioned interposed between the formulation-impermeable outer layer (2) and the formulation-impermeable rim layer (3) adjacent to the channel (4) and said dispensing unit (6) contains a topical formulation to be released into the channel (4).

4. The device according to claim 3, wherein the channel (4) has a lower end (9) facing the back end (B) of the device (1) and extending in essentially traversal direction, and the dispensing unit (6) is positioned adjacent to the lower end (9) of the channel (4).

5. The device according to claim 3, wherein the dispensing unit (6) is pressure-activated.

6. The device according to claim 3, wherein the dispensing unit comprises a reservoir comprising topical formulation contained in a rupturable pouch.

7. The device according to claim 3, wherein the channel (4) has an upper end (10) facing the front end (F) of the device and the width of the channel (4) is increased at least in sections of the channel along its length in direction to the front end (F) compared to the width of the channel (4) at the lower end (9).

8. The device (1) according to claim 1, wherein the outer layer (2) further comprises at least one undergarment fastener (7).

9. The device (1) according to claim 1, wherein the outer layer comprises a wing area (8) at each of the longitudinal sides (S, S) of the article (1), each of said wing areas (8) comprising at least one undergarment fastener (7).

10. The device (1) according to claim 1, wherein the undergarment fastener (7) is an area of pressure-sensitive adhesive positioned on the outer surface (2a) of the liquid impervious outer layer (2).

11. The device according to claim 1, wherein the device comprises a removable first release liner (11) fastened to the outer surface (2a) of the outer layer (2).

12. The device according to claim 11, wherein the device comprises a removable second release liner fastened (12) to the first release liner (11) and covering the skin contact surface (5b) of the carrier layer (5).

13. The device according to claim 1, wherein the formulation-impermeable outer layer (2) comprises a first liquid impermeable material selected from the group consisting of non-porous materials, porous materials rendered liquid impermeable, microporous materials and closed cell foam materials or combinations thereof.

14. The device according to claim 1, wherein the formulation-impermeable rim layer (3) comprises a second liquid impermeable material from the group consisting of non-porous materials, porous materials rendered liquid impermeable, microporous materials and closed cell foam materials or combinations thereof.

15. The device according to claim 1, wherein the carrier layer (5) comprises at least one porous or semi-porous material.

16. The device according to claim 1, wherein the active agent in the topical formulation is an agent having an analgesic desensitizing effect when used topically.

17. A topical formulation for treatment of pain affecting the vulvar area of the female human genital organ, wherein the topical formulation comprises a) at least one voltage-gated sodium channel blocker; b) at least one mast cell stabilizer and/or a skin-desensitizing, non-histaminergic alkaline or alkaline earth metal compound; and c) at least one pharmaceutical carrier or excipient, wherein the topical formulation has a viscosity within the range of 5 to 600 cps as measured by a Brookfield LVT Viscometer #1 Spindle at 60 RPM at 25 C. and a pH-value in the range of 3.5 to 4.5.

18. The topical formulation according to claim 17, wherein the voltage-gated sodium channel blocker is selected from the group consisting of lidocaine, benzocaine, pramoxine, doxepin, benzydamine, dyclonine, bupivacaine, prilocaine, tetracaine, procaine or cinchocaine; amitriptyline, doxepin, GTX2,3 and GTX1,4, neosaxitoxin and tetrodoxin, or combinations thereof.

19. The topical formulation according to claim 17, wherein the voltage gated sodium channel blocker is selected from the group consisting of lidocaine, benzocaine and pramoxine.

20. The topical formulation according to claim 17, wherein the mast cell stabilizer is selected from the group consisting of cromolyn and nedocromil and the skin-desensitizing, non-histaminergic alkaline or alkaline earth metal compound is a potassium or strontium salt, preferably, potassium nitrate or strontium chloride.

21. A kit for the topical treatment of pain affecting the vulvar area of the female human genital organ, wherein the kit comprises a device (1) that is a layered article shaped to be placed in use inside a female undergarment and at least partially in skin contact with the female vulvar area said article having a longitudinal direction (L), a transverse direction (T), a front end (F), a back end (B), and two longitudinal sides (S, S), and said device (1) comprises at least a) a formulation-impermeable outer layer (2) having an outer surface (2a) and an inner surface (2b); b) a carrier layer (5) having an inner carrier surface (5a) and a skin-contacting surface (5b), wherein said inner carrier surface (5a) faces in the direction of the inner surface (2a) of the formulation-impermeable outer layer (2); said kit further comprising a topical formulation according to claim 17, wherein the topical formulation is to be applied to the skin-contacting surface of the carrier layer prior to use of the device.

22. A method of treating vulvodynia, wherein the method comprises the step of topical application of an active agent to the female vulvar area by means of the device or kit according to claim 1.

Description

[0057] In the following, the invention will be further described by means of selected examples and with reference to FIGS. 1 to 4. These examples and figures are included for illustrative purposes only and are not to be construed as in any way limiting the scope of the present invention as outlined in the claims.

[0058] FIG. 1 shows an exploded view of a first embodiment of the device according to the invention.

[0059] FIG. 2 shows a longitudinal cross sectional cut through the device shown in FIG. 1.

[0060] FIG. 3 shows an alternative design for a formulation-impermeable outer layer (2) with wing areas at each of its longitudinal sides.

[0061] FIG. 4 show a longitudinal cross sectional cut through another embodiment of the inventive device comprising a second release liner.

LIST OF REFERENCE NUMERALS AS USED IN THE FIGURES

[0062] (1) Device [0063] (L) longitudinal direction of device (1) [0064] (T) transverse direction of device (1) [0065] (F) front end of device (1) [0066] (B) back end of device (1) [0067] (S, S) longitudinal sides of device (1) [0068] (2) formulation-impermeable outer layer [0069] (2a) outer surface of formulation-impermeable outer layer (2) [0070] (2b) inner surface of formulation-impermeable outer layer (2) [0071] (3) rim layer [0072] (4) channel [0073] (5) carrier layer [0074] (5a) inner carrier surface of carrier layer (5) [0075] (5b) skin-contacting surface of carrier layer (5) [0076] (6) dispensing unit [0077] (7) undergarment fastener [0078] (8) wing area [0079] (9) lower end of channel (4) [0080] (10) upper end of channel (4) [0081] (11) first release liner [0082] (12) second release liner [0083] (13) pressure-sensitive adhesive

[0084] FIG. 1 shows a first example of the device according to the invention. The device (1) has the form of a conventional panty liner with a longitudinal direction (L) and a transverse direction (T). FIG. 2 shows a view of a cross sectional cut along the longitudinal direction (L) of the device according to the example shown in FIG. 1. The device (1) has a front end (F), a back end (B) and longitudinal sides (S, S). The device comprises a carrier layer 5 the outer surface of which defines skin-contacting surface (5b). This is the surface of the device which during use will at least partially be brought into skin contact with the user. Overlaying carrier layer (5) on its inner carrier surface (5a), i.e. the surface opposite to skin-contacting surface (5b), is formulation-impermeable rim layer (3). An inner section of the material forming formulation-impermeable rim layer (3) has been cut out to form a channel (4). Overlying formulation-impermeable rim layer (3) is formulation-impermeable outer layer (2), on the outside surface (2a) of which a strip of pressure-sensitive adhesive has been applied to act as a garment fastener (7). Before the device is brought into position for use, garment fastener (7) is protected by a release liner (11), which is removed when the device is made ready for use. Channel (4) in formulation-impermeable rim layer (3) runs in the longitudinal direction and has a lower end (9) facing in the direction of the back end (B) of the device, and an upper end (10) facing in the direction of the front end (F) of the device (1). The width of channel (4) varies such that an essentially circular section is formed near the front end (F) of the device. The form of channel (4) is adapted to the anatomy of the vulvar area so that the vestibule area of the vulvar is covered by the area of carrier layer (5) corresponding to channel (4). Adjacent to lower end (9) of channel (4) in direction of the back end (B) of device (1) lies, interposed between formulation-impermeable rim layer (3) and outer formulation-impermeable layer (2), dispensing unit (6), which in this example is in the form of a pouch made out of a membrane material that can be ruptured by applying pressure on the pouch and that is also impermeable to the formulation. Carrier layer (5), formulation-impermeable rim layer (3), formulation-impermeable outer layer (2) and dispensing unit (6) are adhered to each other, where desired, using conventional methods commonly used e.g. in the art of disposable absorbent articles. Formulation-impermeable outer layer (2) and carrier layer (5) are not adhered to each other in the area defined by channel (4) of rim layer (3) leaving a void space between the two layers thereby forming the channel (4) into which the topical formulation can be released and will be easily distributed therein. Being placed directly adjacent to lower end (9) of channel (4), the pouch forming dispensing unit (6) will rupture in this area and release an amount of the formulation contained therein into the channel (4) when sufficiently high pressure is applied thereon, because this is the section of the pouch which is not or only to a lower degree additionally reinforced by the over- and underlying materials of the formulation impermeable outer layer (2) and rim layer (3). The formulation released by the dispensing unit (6) into channel (4) is distributed therein and is absorbed into carrier layer (5) via the area of inner carrier surface (5a) situated below the channel (4). The topical formulation is transported to the skin-contacting surface (5b) of layer (5) and thereby administered to the treatment area. Because the form of the channel (4) has been adapted to the anatomy of the vulvar area, the topical formulation is efficiently administered to those areas of the vulvar in need of treatment.

[0085] The formulation-impermeable outer layer (2) and the formulation-impermeable rim layer (3) can for instance be made of a white LDPE-foil, the carrier layer (5) of a full cotton batting non-woven with a 3 mm thickness. For the dispensing unit, a LDPE foil with a thickness of 1.5 mil or less can be used. The device can be assembled by die-cutting the different layers from sheets of the respective materials and adhering them to each other using conventional adhesive technologies commonly used in the art of disposable personal hygiene articles, such as sanitary napkins and panty liners. The prefabricated and filled pouch can be adhered in between the formulation-impermeable outer layer and the rim layer.

[0086] FIG. 3 shows an alternative design for a formulation-impermeable outer layer (2) for use in a device according to the invention. The outer layer (2) additionally comprises a wing area (8) at each of its longitudinal sides (S, S). These wing areas (8) each comprise an additional strip of pressure-sensitive adhesive on the outside surface thereof, which also act as garment fasteners (7). When the device is placed inside the undergarment of the patient for use, the garment fastener (7) located centrally on the outside surface (2a) of the outer layer (2) is adhered to the inside of the undergarment. The wing areas are then folded around the undergarment at the leg openings and adhered to the outside of the undergarment via the garment fasteners (7) located on the wing areas (8) to provide additional support in keeping device (1) in the predetermined position of the undergarment during use.

[0087] FIG. 4 shows a cross sectional view along a longitudinal cut of a second example of a device according to the invention. The device according to this example is essentially identical with the previous example but comprises an additional second release liner (12) which protects the skin-contacting surface (5b) of the carrier layer (5) when the device is not in use. The second release liner is releasably adhered to the first release liner using a pressure-sensitive adhesive (13), whereby the two release liners (11, 12) form a protective pouch for those parts of the device which in use are placed inside the undergarment of the user.

EXAMPLE 1

[0088] a) A 28 year old white female had complained of an 18 month history of vulvar pain. She described a generalized stinging sharp pain localized in her labia and vestibule and usually triggered by touch, contact with tights garments, and sexual intercourse. She also complained of a sensation of hypersensitivity to touch in the anterior vestibule. On an average, she rated her overall vulvar pain at 6-7 on the numerical pain scale 0-10, where 10 corresponds to the worst pain imaginable and 0 to no pain.

[0089] Gynecological evaluations and imaging studies, including an MM of the pelvis were unrevealing for any specific etiology, such as infections, dermatological inflammatory conditions and structural pelvic pathologies. She was diagnosed as having vulvodynia. Multiple trials of treatments, including: 1) oral drugs such as tricyclic antidepressants, gabapentin, pregabalin, duloxetine; 2) a variety of OTC creams, 3) pudendal nerve blocks provided either intolerable side effects and/or no significant benefit.

[0090] She reported some mild relief (about 25%) of short duration (about 20 minutes) from the application of a cotton ball soaked in a compounded preparation of liquid lidocaine. She was however reluctant to use the cotton ball remedy. First, because the application of liquid lidocaine was followed by a local burning sensation lasting for about 3-5 minutes before any noticeable pain relief could occur. Secondly, it was awkward for her to apply the cotton ball multiple times during daily activities. She then received a set of pads, in the form of feminine sanitary pads. A compounded gel with 4 g lidocaine, 4 g cromolyn and 0.2 g Aloe Vera, 0.05 g methylparaben NF, 0.253 g propyleneparaben NF and purified water, USP, q.s. per 100 ml gel, was applied to each pad. She tried the pads and she kept each pad for a few hours. She reported improved benefit over time. The relief was more noticeable at the time a fresh pad was applied. Overall she reported 75% pain relief and no irritation of discomfort from the pad use.

[0091] b) A 32 year old white female had complained of more than 12 month history of vulvar pain. She was also known to suffer from anal fissures and ulcerative colitis. She described her vulvar pain as constant and burning. She complained of hypersensitivity associated to a sensation of rawness localized in her vestibule. The pain was made worse by sexual intercourse. She underwent multiple medical evaluations. No specific causes of her vestibular pain were identified. On an average, she rated her overall vulvar pain at 8-9 on the numerical pain scale 0-10, where 0 is no pain and 10 the worst pain imaginable. Her pain failed to respond to antidepressants, anticonvulsants, pelvic floor muscle therapy. Application of cotton balls soaked in liquid lidocaine caused an intolerable burning sensation in the vulvar region and then only short-lasting mild relief. She received a set of pads, in the form of feminine sanitary pads along with a compounded gel, pH balanced for vaginal use (pH between 3.5-4.5), containing per 100 ml gel benzocaine 4 g , pramoxine 1 g, strontium chloride 2.6 g and poloxamer 407 30 g, methylparaben 0.05 g, propylparaben 0.253 g, EDTA 0.03 g and purified water, USP, q.s. She tried the combination of pad and gel and she was happy to report satisfactory long lasting benefit. She experienced some local numbness, but the pad application did not cause burning or intolerable side effects. Overall she reported more than 50% pain relief.