Self-foaming cleansing composition containing clobetasol propionate, and use thereof in the treatment of psoriasis

Abstract

A self-foaming composition for a topical application is described. The composition can include a medium which is cosmetically- or pharmaceutically-compatible with a topical application, and clobetasol propionate. The composition can include a small quantity of foaming surfactants. The composition includes: at least one intermediate composition B including a gas-generating agent; at least one intermediate composition A including an agent for activating the gas-generating agent; and clobetasol propionate being present in at least one of the intermediate compositions A and B. Also described, is a kit or a single container including a plurality of compartments including such a composition.

Claims

1. A self-foaming rinse-off topical composition, comprising: (a) at least one intermediate composition B comprising (i) a gas-generating agent, and (ii) 0.5% to 5% by weight, relative to the weight of intermediate composition B, of one or more gelling agents and/or suspending agents selected from the group consisting of acrylic acid polymers, polysaccharides, cellulose and cellulose derivatives, magnesium aluminum silicates, modified starches, carrageenans, and combinations thereof; (b) at least one intermediate composition A comprising (i) an agent for activating the gas-generating agent, and (ii) 0.5% to 5% by weight, relative to the weight of intermediate composition A, of one or more gelling agents and/or suspending agents selected from the group consisting of mixtures of polyacrylate-13/polyisobutene/polysorbate 20, polysaccharides, cellulose and cellulose derivatives, magnesium aluminum silicates, modified starches, carrageenans, polyvinyl alcohol, and combinations thereof; and (c) 0.001% to 0.5% by weight, relative to the total weight of the composition, of clobetasol propionate, wherein the clobetasol propionate is present in intermediate composition A and/or B.

2. The composition as claimed in claim 1, wherein the clobetasol propionate is present in the intermediate composition A.

3. The composition as claimed in claim 1, wherein the composition comprises foaming surfactants at a concentration of less than or equal to 2.5% by weight, relative to the weight of the total composition.

4. The composition as claimed in claim 1, wherein the gas generated from the gas-generating agent is carbon dioxide.

5. The composition as claimed in claim 1, wherein the gas-generating agent is selected from the group consisting of sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, and mixtures thereof.

6. The composition as claimed in claim 1, wherein the gas-generating agent is present in the intermediate composition B in an amount ranging from 1% to 10% by weight, relative to the weight of the intermediate composition B.

7. The composition as claimed in claim 1, wherein the intermediate composition B has a pH of from 7 to 12.

8. The composition as claimed in claim 1, wherein the agent for activating the gas-generating agent is selected from the group consisting of an acid, a partially salified polyacid salt, a buffer solution of a weak acid and of its conjugate base, and mixtures of these compounds.

9. The composition as claimed in claim 1, wherein the agent for activating the gas-generating agent is selected from the group consisting of citric acid, tartaric acid, malic acid, lactic acid, phosphoric acid, and pyrophosphoric acid, and the salts of these acids.

10. The composition as claimed in claim 1, wherein the agent for activating the gas-generating agent is a citric acid/sodium citrate buffer, alone or as a mixture with sodium phosphate and/or disodium pyrophosphate.

11. The composition as claimed in claim 1, wherein the agent for activating the gas-generating agent is present in the intermediate composition A in an amount ranging from 0.001% to 95% by weight relative to the weight of the intermediate composition A.

12. The composition as claimed in claim 1, wherein the intermediate composition A has an acidic pH.

13. The composition as claimed in claim 1, wherein the intermediate composition A is in the form of a solution, a gel or an emulsion.

14. The composition as claimed in claim 1, wherein the intermediate composition B is in the form of a solution, a gel or an emulsion.

15. A composition in foam form, wherein the composition is obtained by mixing of the intermediate compositions A and B as claimed in claim 1.

16. The composition as claimed in claim 1, wherein the composition further comprises one or more active agents selected from the group consisting of emollients, humectants, free-radical scavengers, anti-inflammatory agents, vitamins, depigmenting agents, antiacne agents, antiseborrheic agents, antifungal agents, keratolytic agents, sunscreens, slimming agents and skin-coloring agents.

17. The composition as claimed in claim 1, wherein the composition further comprises one or more agents selected from the group consisting of dispersants, solubilizers, stabilizers, preserving agents, fatty substances, thickeners, dyes, fragrances, surfactants, gelling agents, complexing agents, neutralizers, foaming emulsifying agents, non-foaming emulsifying agents, fillers, sequestrants, reducing agents, odor maskers, plasticizers, softeners, moisturizers, pigments, clays, mineral fillers, mineral colloids, polymers, proteins, nacreous agents, waxes, oils, for instance paraffins, silicones, fatty acids, solid esters of fatty alcohols or of fatty acids, gums and wetting agents.

18. A cosmetic method comprising topically applying an effective amount of the composition as claimed in claim 1 to the skin of an individual subject in need thereof, followed by removal of the composition by rinsing.

19. The composition as claimed in claim 1, wherein the composition is formulated for use in the treatment of psoriasis.

20. A kit or single multi-compartment container for a self-foaming topical composition, separately comprising at least two intermediate compositions: (a) at least one intermediate composition B comprising (i) a gas-generating agent, and (ii) 0.5% to 5% by weight, relative to the weight of intermediate composition B, of one or more gelling agents and/or suspending agents selected from the group consisting of acrylic acid polymers, polysaccharides, cellulose and cellulose derivatives, magnesium aluminum silicates, modified starches, carrageenans, and combinations thereof; (b) at least one intermediate composition A comprising (i) an agent for activating the gas-generating agent, and (ii) 0.5% to 5% by weight, relative to the weight of intermediate composition A, of one or more gelling agents and/or suspending agents selected from the group consisting of mixtures of polyacrylate-13/polyisobutene/polysorbate 20, polysaccharides, cellulose and cellulose derivatives, magnesium aluminum silicates, modified starches, carrageenans, polyvinyl alcohol, and combinations thereof; and (c) 0.001% to 0.5% by weight, relative to the total weight of the composition, of clobetasol propionate, wherein the clobetasol propionate is present in intermediate composition A and/or B.

21. The kit or container as claimed in claim 20, wherein the kit or container is designed for mixing the intermediate compositions A and B in an A/B weight ratio ranging from 0.5 to 2.

22. A process for preparing a composition in foam form, the process comprising formulating the composition for rinse-off topical application, wherein the composition comprises clobetasol propionate, by mixing the intermediate composition A as defined in claim 1 with the intermediate composition B as defined in claim 1, in relative weight proportions A/B ranging from 0.5 to 2.

23. The composition as claimed in claim 3, wherein foaming surfactants are present and at a concentration of less than or equal to 1% by weight, relative to the total weight of the composition.

24. The composition as claimed in claim 5, wherein the gas-generating agent is sodium bicarbonate.

25. The composition as claimed in claim 6, wherein the gas-generating agent is present in the intermediate composition B in an amount ranging from 2% to 8% by weight, relative to the weight of intermediate composition B.

26. The composition as claimed in claim 7, wherein the pH is basic.

27. The composition as claimed in claim 9, wherein the agent for activating the gas-generating agent is selected from the group consisting of a citric acid/sodium citrate buffer alone, or phosphoric acid, sodium phosphate, and/or disodium pyrophosphate, which are alone or as a mixture with a citric acid/sodium citrate buffer.

28. The composition as claimed in claim 12, wherein the acidic pH is from 1 to 6.

29. The composition as claimed in claim 13, wherein the intermediate composition A is in the form of a gel.

30. The composition as claimed in claim 14, wherein the intermediate composition B is in the form of a gel.

31. The kit or container as claimed in claim 21, wherein the A/B weight ratio is from 0.5 to 1.5.

32. The kit or container as claimed in claim 21, wherein the A/B weight ratio is from 0.9 to 1.1.

33. The kit or container as claimed in claim 21, wherein the A/B weight ratio is 1.

34. The process as claimed in claim 22, wherein the A/B weight proportion ranges from 0.5 to 1.5.

35. The process as claimed in claim 22, wherein the A/B weight proportion is 1.

36. The composition as claimed in claim 1, wherein the composition does not comprise any foaming surfactants.

Description

EXAMPLES

Example 1: Formulation Examples

Formulation Examples A: Intermediate Compositions Containing the Gas-Activating Agent, Formulated with an Acidic pH

(1) Intermediate formulations A were prepared according to the following process:

(2) Step 1: At a temperature above 60 C., add the gelling agents and then the gas-generator activating agent(s) with stirring to the main water phase.

(3) Step 2: In parallel, prepare the active phase by dissolving the clobetasol propionate in the solubilizing/pro-penetrating agent.

(4) Step 3: At a temperature below 30 C., add the active phase to the main phase.

(5) Step 4: Add the additives and the preserving agents, cosmetic active agents and chelating agents.

(6) In the formulation examples below, the amounts are expressed relative to the weight of the intermediate formulation rather than relative to the weight of the total formulation.

Example A1

(7) TABLE-US-00001 INCI Name % WATER QS 100 DISODIUM EDTA 0.1 MAGNESIUM 2.5 ALUMINIUM SILICATE XANTHAN GUM 0.7 CITRIC ACID 1.4 SODIUM CITRATE 1 SODIUM 7.2 PYROPHOSPHATE SODIUM LAURETH 3.6 SULFATE COCO BETAINE 1.3 PROPYLENE 4 GLYCOL ETHOXYDIGLYCOL 1.2 CLOBETASOL 0.1 PROPIONATE SODIUM 0.2 BENZOATE

Example A2

(8) TABLE-US-00002 INCI Name % WATER QS 100 DISODIUM EDTA 0.1 MAGNESIUM 2.5 ALUMINIUM SILICATE XANTHAN GUM 0.7 CITRIC ACID 3.5 SODIUM CITRATE 2.7 SODIUM LAURETH 3.6 SULFATE COCO BETAINE 1.3 PROPYLENE 4 GLYCOL ETHOXYDIGLYCOL 1.2 CLOBETASOL 0.1 PROPIONATE SODIUM 0.2 BENZOATE

Example A3

(9) TABLE-US-00003 INCI Name % WATER QS 100 DISODIUM EDTA 0.1 MAGNESIUM 2.5 ALUMINIUM SILICATE XANTHAN GUM 0.7 CITRIC ACID 3.5 SODIUM CITRATE 2.7 PROPYLENE 4 GLYCOL ETHOXYDIGLYCOL 3 CLOBETASOL 0.1 PROPIONATE SODIUM 0.2 BENZOATE

Example A4

(10) TABLE-US-00004 INCI Name % WATER QS 100 DISODIUM EDTA 0.1 MAGNESIUM ALUMINIUM SILICATE 2.5 GUARD GUM 0.4 HYDROXYETHYL CELLULOSE 0.5 CITRIC ACID 3.5 SODIUM CITRATE 2.7 SODIUM LAURETH SULFATE 3.6 COCO BETAINE 1.3 PROPYLENE GLYCOL 4 ETHOXYDIGLYCOL 1.2 CLOBETASOL PROPIONATE 0.1 SODIUM BENZOATE 0.2

Example A7

(11) TABLE-US-00005 INCI Name % WATER QS 100 DISODIUM EDTA 0.1 XANTHAN GUM 0.7 MAGNESIUM ALUMINIUM SILICATE 2.5 SODIUM BENZOATE 0.2 POLYVINYL ALCOHOL 2 DISODIUM PYROPHOSPHATE 7.2 PHENOXYETHANOL 0.5 CITRIC ACID 1.4 SODIUM CITRATE 1 POLOXAMER 124 0.2 CLOBETASOL PROPIONATE 0.1 PROPYLENE GLYCOL 4.0 FD&C BLUE 1 0.0009

Formulation Examples B: Intermediate Compositions Containing the Gas-Generating Agent

(12) The intermediate formulations are formulated according to the following process:

(13) Step 1: At a temperature above 60 C., add the gelling agents to the main water phase, with stirring.

(14) Step 2: Add the cleansing agents or foaming agents and also the additives such as the preserving agents at a suitable temperature.

(15) Step 3: Neutralize the mixture.

(16) Step 4: At a temperature below 40 C., add sodium bicarbonate.

(17) In a particular embodiment, a fatty phase (containing the oils, waxes and surfactants) may be heated to a temperature above 60 C. and incorporated into the main phase after step 1.

Example B1

(18) TABLE-US-00006 INCI Name % WATER QS100 MAGNESIUM ALUMINIUM 2.5 SILICATE XANTHAN GUM 0.5 DISODIUM EDTA 0.1 DIPOTASSIUM 0.5 GLYCYRRHIZATE ZINC GLUCONATE 0.4 SODIUM C14-16 OLEFIN 2 SULFONATE SODIUM HYDROXIDE 0.1 SODIUM HYDROGEN 5 CARBONATE PHENOXYETHANOL 1 PENTYLENE GLYCOL 5

Example B2

(19) TABLE-US-00007 INCI Name % WATER QS100 MAGNESIUM 2.5 ALUMINIUM SILICATE XANTHAN GUM 0.6 DISODIUM EDTA 0.1 SODIUM HYDROXIDE 0.1 SODIUM HYDROGEN 3 CARBONATE PHENOXYETHANOL 1

Example B3

(20) TABLE-US-00008 INCI Name % WATER QS100 MAGNESIUM 2.5 ALUMINIUM SILICATE XANTHAN GUM 0.5 DISODIUM EDTA 0.1 DIPOTASSIUM 0.5 GLYCYRRHIZATE ZINC GLUCONATE 0.4 SODIUM C14-16 2 OLEFIN SULFONATE SODIUM HYDROXIDE 0.1 SODIUM HYDROGEN 3 CARBONATE PHENOXYETHANOL 1 PENTYLENE GLYCOL 5

(21) The mixtures in a 1:1 weight ratio of the intermediate compositions A and B described above are represented in the table below. A cross at the intersection of two formulation intermediates indicates that the mixture was tested and generated a foam having the desired properties.

(22) TABLE-US-00009 Formulation B Formulation A B1 B2 B3 A1 X A2 X A3 X X A4 X A7 X X

Example 2A: Foam Density

(23) From the formulation examples described in example 1, foam density measurements were taken at the moment of contact of the two intermediate formulations A and B (TO) and then when the chemical reaction generated by bringing the two compositions into contact is complete. These studies showed that the final composition is in the form of a foam with a suitable density.

(24) Measurement of the foam density shows that the volume generated by one of the mixtures proposed in the above table has been increased by a factor of 3 to 5.

Example 2B: Stability

(25) Table I below collates the physical stability data for the intermediate formulation A1 described in example 1, containing clobetasol propionate.

(26) TABLE-US-00010 Example A1 T0 T 1 month T 2 months T 3 months pH 4.24 25 C. 4.23 4.23 4.25 40 C. 4.18 4.14 4.28 Viscosity 10160 25 C. 12020 12530 10700 cP Brookfield 40 C. 11450 10980 13000 RV DVII Spindle 5 speed 20

(27) Tables IIa and IIb below detail the chemical stability data for clobetasol propionate in the intermediate formulations A1 and A2 described in example 1.

(28) TABLE-US-00011 T 2 T 3 Example A1 T0 T 1 month months months W/W % clobetasol 101.4 RT 99.4 99.1 99.0 propionate (HPLC) 40 C. 99.0 103.7 102.9

(29) TABLE-US-00012 T 2 T 3 Example A2 T0 T 1 month months months W/W % clobetasol 101.4 RT 99.5 99.6 100.4 propionate (HPLC) 40 C. 99.9 99.7 99.7

Example 3: Comparative Study of Measurement of Irritation Study Protocol

(30) The study is performed according to the OECD TG 439 protocol in force for the short application time (RHE/product contact time 15 min). This protocol is appropriate for a long application time (RHE/product contact time 18 h).

(31) The objective of this study is to evaluate the tolerance of the supports of the complete and intermediate formulations on reconstructed human epidermides (RHE, Episkin model) through: evaluation of the reduction of MTT (cell viability) measurement of the release of IL-1alpha (irritation marker)

(32) The formulations tested are: An intermediate composition of acidic formulation: example A7 placebo (i.e. not containing clobetasol propionate) and uncolored (i.e. not containing dyes), An intermediate composition of basic formulation: example B1 The complete formulation 1 composed of the mixture: A7 placebo+B1 (in a 50/50 weight ratio) A commercial reference in the form of cleansing gel

(33) TABLE-US-00013 Short exposure Long exposure Conclusion Mixture tested Viability (%) Viability (%) Irritant potential B1 92.5 59.6 Non-irritant A7 placebo 86.0 84.5 Non-irritant Whole formulation 1 93.2 86.8 Non-irritant Commercial ref. 76.6 6.7 Potentially irritant

(34) TABLE-US-00014 Short exposure Long exposure Conclusion Test item IL-1a vs control IL-1a vs control Irritant potential B1 5.5 30.6 Non-irritant A7 placebo 2.2 2.3 Non-irritant Whole 4.5 11.6 Non-irritant formulation 1 Commercial 6.2 113.9 Potentially irritant ref.

(35) The MTT measurements according to the OECD protocol in force indicates that the rinse-out whole formulation tested is non-irritant whereas the Commercial ref. is potentially irritant.

(36) Furthermore, the assay of IL-la after application at long and short exposure times of the whole formulations shows a much lower level of irritation markers on the foam formulations than after application of the commercial reference.

Example 4

(37) The ideal content of citric acid, sodium pyrophosphate and sodium dihydrogen phosphate monohydrate to react with 5% of sodium bicarbonate was established empirically. The values are expressed as weight/weight percentages relative to the weight of each of the two intermediate formulations

(38) TABLE-US-00015 Ratio 1 Ratio 2 Ratio 3 Sodium bicarbonate 5% 5% 5% Citric acid 3.5% Disodium pyrophosphate 12 Sodium dihydrogen 7.2% phosphate monohydrate

(39) In order for the pH of the formulation containing the gas activator to have optimum compatibility with the skin, sodium citrate was added so as to create a citric acid/sodium citrate buffer.

(40) Part of the citric acid/sodium citrate buffer may advantageously be replaced with disodium pyrophosphate and vice versa following the contents cited by way of example in table I below:

(41) TABLE-US-00016 TABLE III the values are expressed as weight/weight percentages relative to the weight of each of the two intermediate formulations. E 1 E2 E 3 E 4 E 5 E 6 E 7 Sodium .sup.5% 5% .sup.5% 5% .sup.3% 3% .sup.3% bicarbonate Citric acid 3.5% 1.75% 1.4% 0 2.1% 1.05% 0 Sodium citrate 2.7% 1.3%.sup. .sup.1% 0 1.6% 1.15% 0 Disodium 0 6% 7.2% 12% 0 3.6% 7.2% pyrophosphate

(42) Part of the citric acid/sodium citrate buffer may advantageously be replaced with sodium dihydrogen phosphate monohydrate and vice versa, following the contents cited by way of example in table IV below:

(43) TABLE-US-00017 TABLE IV The values are expressed as weight/weight percentages relative to the weight of each of the two intermediate formulations. E1 E8 E9 Sodium bicarbonate 5% 5% 5% Citric acid 3.5% 1.5% 0 Sodium citrate 2.7% 0.5% 0 Sodium dihydrogen phosphate 0 6.2% 10% monohydrate

(44) In one particular embodiment, it was determined that when the amount of citric acid is greater than or equal to 1.4, the amount of foam is optimal when disodium pyrophosphate is present in the composition according to the following equation:
[C]=2.4[B]2.4[A]/0.7

(45) when:

(46) [C]=weight content of disodium pyrophosphate in the intermediate composition A

(47) [A]=weight content of citric acid monohydrate in the intermediate composition A

(48) [B]=weight content of sodium bicarbonate in the intermediate composition B

(49) The above equation thus makes it possible to calculate the optimum contents between sodium bicarbonate, citric acid and sodium pyrophosphate.