PAIN-KILLING COMPOSITION COMPRISING A SALICYLIC ACID DERIVATIVE

Abstract

The subject-matter of the present invention is the use of a therapeutic composition comprising, in an applying carrier, at least one essential oil for relieving muscle and/or joint pain in an animal subject, wherein said composition topically treats an area of the skin of said subject, characterized in that said composition comprises methyl salicylate, which constitutes, with at least one essential oil of the composition containing same in only a small amount or not at all, an active agent within which the rate of transport of the methyl salicylate through the skin is increased by virtue of the oil, which is an essential oil.

Claims

1-20. (canceled)

21. Therapeutic monoblock device comprising a polymer matrix topical application carrier and an active agent for inducing relieving muscle and/or joint pain in an human or animal subject, said active agent comprising methyl salicylate provided by wintergreen essential oil, and an auxiliary essential oil, wherein the active agent is incorporated in the polymer matrix, wherein the polymer matrix represents 80 to 90% by weight of the device, and the active agent comprises 52 to 85% by weight of methyl salicylate, the rate of transport of the methyl salicylate through the skin being increased by virtue of the auxiliary essential oil.

22. Therapeutic monoblock device according to claim 21, wherein the auxiliary essential oil of the active agent constitutes between 15 and 48% by weight of the active agent.

23. Therapeutic monoblock device according to claim 21, wherein the polymer matrix is a copolymer of ethylene and vinyl acetate (EVA), whose vinyl acetate content is between 15 and 60% by weight.

24. Therapeutic monoblock device according to claim 22, wherein the polymer matrix is a copolymer of ethylene and vinyl acetate (EVA), whose vinyl acetate content is between 15 and 60% by weight.

25. Therapeutic monoblock device according to claim 21, wherein the polymer matrix is a thermoplastic polymer chosen from a polyether block amide, and ester-based or ether-based thermoplastic polyurethane elastomer, an absorbent-grade copolyimide, an absorbent-grade polyamide, a starch-grafted polyethylene and a vinyl polychlorides.

26. Therapeutic monoblock device according to claim 22, wherein the polymer matrix is a thermoplastic polymer chosen from a polyether block amide, and ester-based or ether-based thermoplastic polyurethane elastomer, an absorbent-grade copolyamide, an absorbent-grade polyamide, a starch-grafted polyethylene and a vinyl polychlorides.

27. Therapeutic monoblock device according to claim 21, wherein the polymer matrix is an isocyanate-based and polyol-based cross-linked polyurethane or an isocyanate-based and polyamine-based polyuria.

28. Therapeutic monoblock device according to claim 22, wherein the polymer matrix is an isocyanate-based and polyol-based cross-linked polyurethane or an isocyanate-based and polyamine-based polyuria.

29. Therapeutic monoblock device according to claim 21, wherein the auxiliary essential oil of the active agent is rosemary essential oil (Rosmarinus officinalis), peppermint essential oil, Ceylan citronella essential oil, coriander essential oil, or a combination thereof.

30. Therapeutic monoblock device according to claim 29, wherein the auxiliary essential oil contains at least one monoterpene alcohol chosen from the group formed by 1,8-cineole, menthol, geraniol and linalool.

31. Therapeutic monoblock device according to claim 21, wherein the essential wintergreen oil constitutes between 1 and 15% by weight of the total essential oil content of the device.

32. Therapeutic monoblock device according to claim 21, wherein the auxiliary essential oil constitutes from 0.15 to 9% by weight of the device.

33. Therapeutic monoblock device according to claim 21, wherein the active agent further comprises at least one formulation additive chosen from a vegetable oil, an inert filler of mineral origin, a dye, a surfactant, a synthetic perfume, a natural perfume, or a mixture thereof.

34. Therapeutic monoblock device according to claim 33, wherein said inert filler of mineral origin is a powder.

35. A method of topically inducing arthritic pain relief comprising applying the therapeutic monoblock device of claim 21 against the skin of a human or animal subject to be treated for a sufficient time to enable the pain relief.

Description

EXAMPLE

[0062] The use of a composition comprising an active agent consisting of essential oils of wintergreen and of officinal rosemary to relieve joint pain in a dog.

[0063] The following products are available:

[0064] A wintergreen essential oil marketed by NATURARUM. This essential oil contains between 98 and 100% by weight of methyl salicylate;

[0065] A official rosemary essential oil marketed by INTERAXION. This essential oil contains between 50 and 55% by weight of 1,8-cineole;

[0066] A refined copra oil marketed by INTERAXION;

[0067] Granules of copolymers of ethylene and vinyl acetate (EVA) marketed by GAZECHIM under the brand EVA ALCUIDA PA-538 which contains 18% by weight of vinyl acetate. The vitreous transition temperature of this polymer is given as 68 C.;

[0068] A chocolate brown colorant in the form of granules sold by ELIAN under the brand P4625C.

[0069] The following equipments are available:

[0070] a PAPPENMEIER cylindrical reactor with a capacity of 8 liters provided with an agitator driven by a variable speed motor;

[0071] a SANDRETTO injection press, Series 8, generating a pressing capacity of 150 tonnes;

[0072] a mold made of steel mounted on said press whose four fingerprint are in the form of a collar having 75 cm long. The temperature diagram of the sheath, from the hopper to the nozzle, is as follows: 115 C. (Zone 1), 125 C. (Zone 2), 130 C. (Zone 3), 135 C. (Zone 4) with a holding time of 3 seconds at 65 bars and a mold temperature of 155 C.

[0073] a VARIAN gas chromatograph, provided with a 20000 Da polyethylene glycol column, Optima-Wax 0.25 - 30 m0.32 mm ID.

[0074] Procedure [0075] aPreparation of the active agent of the composition:

[0076] It is introduced consecutively in a beaker of 250 mL, at ambient temperature, 74 g of wintergreen essential oil and 26 g of rosemary essential oil. 12 g of refined copra oil are added in order to better disperse the two essential oils. Low agitation is performed using a bar magnet in order to obtain a homogenous mixture to obtain the liquid composition.

[0077] 135 mg of the composition obtained above is weighed and applied directly onto the skin of a pig's ear over an area of 7.1 cm.sup.2, according to the procedure previously described. The volume of the Water/Ethanol (50/50) receiving medium is 140 mL. Samples of the receiving medium are taken after 10 minutes and 30 minutes. The chromatogram obtained is shown in FIG. 1.

[0078] FIG. 1: Chromatogram of the composition comprising the active agent according to the invention, deposited on the skin surface of a pig's ear.

[0079] It will be observed that in the presence of officinal rosemary essential oil (REO), the passage speed of the wintergreen essential oil (WEO) is increased. This result confirms that the transcutaneous passage of methyl salicylate is trained by the officinal rosemary essential oil. By contrast, if the composition contains an active agent consisting solely of wintergreen essential oil, the methyl salicylate fails to pass through the skin even after 30 minutes. [0080] bIncorporation of the composition in EVA:

[0081] The reactor is preheated to 70 C. in an oil bath. 830 g of EVA granules are introduced, under slight agitation, until the temperature measured within said granules is around 70 C. Still under slow agitation, introduce the liquid composition previously obtained into the reactor. This is agitated until all of the liquid is completely absorbed by the polymer, then the temperature is reduced to 25 C. On completing incorporation, the EVA granules are dry and slightly swollen. Finally, 20 g of brown colorant, still under slow agitation, are introduced. The reactor is emptied and the compound thus obtained is stored in a pack hermetically sealed against air and humidity. The EVA granules obtained upon completing this step contain 10% by weight of wintergreen essential oil (WEO) and 3.5% by weight of officinal rosemary essential oil (REO). [0082] cShaping the compound into a collar

[0083] The compound obtained at step b) of the procedure is injected into collars weighing around 41 g at the outlet of the nozzle for a length of 75 cm.

[0084] Assessment of the Rate of Transdermal Passage of Methyl Salicylate

[0085] To perform this assessment, the mass of the collar is determined so as to satisfy the conditions of sink handling, i.e., that the maximum rate of active ingredient released into the medium must be less than 10% of the saturating concentration of the active ingredient in this medium. The receiving medium is taken, then analyzed by chromatography.

[0086] 1 g of the collar obtained at step c) of the procedure, having a surface area of 3.1 cm.sup.2, is weighed, in accordance with the above-described procedure. The experiment is performed for 72 hours, then 2 mL of the receiving medium are taken and analyzed by gas chromatography. The mixtures obtained are compared to a standard solution containing 1,8-cineole as a marker of the officinal rosemary essential oil and methyl salicylate as a marker of the wintergreen essential oil. The results are shown in FIG. 2.

[0087] FIG. 2: Chromatogram of the composition according to the invention of which the topical application carrier is an EVA polymer matrix collar containing the composition.

[0088] It will be observed that the methyl salicylate passed through the skin from the collar into the receiving medium because the two markers are detected therein. This shows on the one hand that the polymer matrix is capable of carrying the active agent so that the latter passes into the skin, and on the other hand that the officinal rosemary essential oil efficiently induces the passage of methyl salicylate through the skin of the pig's ear.

[0089] Table 1 below lists the rate transport of the methyl salicylate (MeSa) of the active agent according to the application carrier.

TABLE-US-00001 TABLE 1 Summary of the rate transport of methyl salicylate through the skin Rate Test Active Agent Carrier (g/mL/hour) 1 MeSa + rosemary essential oil EVA collar 0.232 2 MeSa + rosemary essential oil EVA collar 0.102 3 MeSa + rosemary essential oil EVA collar 0.269 4 MeSa + rosemary essential oil Copra oil 327.4 5 MeSa + citronella essential oil Copra oil 383.7 6 MeSa + peppermint essential oil Copra oil 257.7

[0090] Efficacy Tests Performed on Dogs Suffering from Joint and Muscle Pain

[0091] The efficacy of the collar obtained in step c) of the procedure was assessed for a panel of four dogs selected from a kennel from those at least 8 years old showing clear signs of reduced mobility characterized specifically by difficulties in getting up and moving. Each of these four dogs wore, around its neck, a collar whose composition/animal weight ratio was previously determined by the size of the collar.

[0092] The animals were observed every day for six weeks without changing anything with respect to their food or their lifestyle.

[0093] After 48 hours, the most disabled of the four showed itself to be more alert and more reactive towards other dogs and the kennel owner and, moreover, had greater ease of movement.

[0094] After wearing the collar for four days, the four dogs showed significantly improved motor skills which translated into prolonged periods of standing and also spontaneous walks, particularly outside. The collar therefore improved the vitality of the dogs. This vitality effect was observed for six weeks in the most disabled dog.