No-rinse chemical foam containing clobetasol propionate, and use thereof in the treatment of psoriasis

Abstract

A self-foaming composition is described that includes clobetasol propionate, for a no-rinse topical application and for application to the skin. The composition can include: 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 leave-on topical composition, comprising: (a) at least one intermediate composition B comprising (i) 1% to 10% by weight, relative to the weight of the intermediate composition B, of a gas-generating agent selected from the group consisting of sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate, and mixtures thereof, and (ii) a gelling agent and/or suspending agent; (b) at least one intermediate composition A comprising (i) 0.001% to 95% by weight, relative to the total weight of the intermediate composition A, of an agent for activating the gas-generating agent comprising a citric acid/sodium citrate buffer and sodium dihydrogen phosphate and/or disodium pyrophosphate, and (ii) a gelling agent and/or suspending agent; and (c) 0.001% to 0.5% of clobetasol propionate by weight, relative to the weight of the composition comprising intermediate compositions A and B, wherein the clobetasol propionate is present in intermediate composition A and/or B; and wherein the gas-generating agent of intermediate composition B and the agent for activating the gas-generating agent of intermediate composition A react to produce carbon dioxide gas upon mixing.

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 does not comprise any foaming surfactants selected from the group consisting of anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants of the family of alkylpolyglucosides and glucamides.

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

5. The composition as claimed in claim 1, wherein the citric acid/sodium citrate buffer is present in the intermediate composition A in an amount of less than or equal to 2.4% by weight, relative to the weight of the intermediate composition A.

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

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

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

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

10. 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.

11. 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, gelling agents, complexing agents, neutralizers, non-foaming emulsifying agents, fillers, sequestrants, reducing agents, odor maskers, plasticizers, softeners, moisturizers, pigments, clays, mineral fillers, mineral colloids, polymers, proteins, nacreous agents, propellants, waxes, oils, for instance paraffins, fatty acids, solid esters of fatty alcohols or of fatty acids, gums and wetting agents.

12. A method for treating psoriasis, comprising administering an effective amount of the composition as claimed in claim 1, to the skin of an individual in need thereof.

13. A kit or single multi-compartment container separately comprising: (a) an intermediate composition B comprising (i) 1% to 10% by weight, relative to the weight of the intermediate composition B, of at least one gas-generating agent selected from the group consisting of sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate, and mixtures thereof, and (ii) a gelling agent and/or suspending agent; and (b) an intermediate composition A comprising (i) 0.001% to 95% by weight, relative to the total weight of the intermediate composition A, of at least one agent for activating the gas-generating agent, comprising a citric acid/sodium citrate buffer and sodium dihydrogen phosphate and/or disodium pyrophosphate, and (ii) a gelling agent and/or suspending agent; wherein clobetasol propionate is present at a concentration of between 0.001% and 0.5% by weight, relative to the weight of the composition comprising intermediate compositions A and B; wherein the clobetasol propionate is present in intermediate composition A and/or B; and wherein the gas-generating agent of intermediate composition B and the agent for activating the gas-generating agent of intermediate composition A react to produce carbon dioxide gas upon mixing.

14. The kit or single multi-compartment container as claimed in claim 13, wherein the kit or single multi-compartment container is designed for mixing the intermediate compositions A and B in an A/B weight ratio ranging from 0.5 to 2.

15. A process for preparing a self-foaming composition, the process comprising formulating the composition for a leave-on topical application comprising 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.

16. The composition as claimed in claim 3, wherein the composition does not comprise any foaming surfactants.

17. The composition as claimed in claim 1, wherein the gas-generating agent is sodium bicarbonate.

18. The composition as claimed in claim 1, wherein the gas-generating agent is present in the intermediate composition B in an amount ranging from 2% to 8% by weight.

19. The composition as claimed in claim 4, wherein the pH is basic.

20. The composition as claimed in claim 6, wherein the acidic pH is from 1.0 to 6.0.

21. The composition as claimed in claim 7, wherein the intermediate composition A is in the form of a gel.

22. The composition as claimed in claim 8, wherein the intermediate composition B is in the form of a gel or an emulsion.

23. The kit or single multi-compartment container as claimed in claim 14, wherein the A/B weight ratio is from 0.5 to 1.5.

24. The kit or single multi-compartment container as claimed in claim 14, wherein the A/B weight ratio is from 0.9 to 1.1.

25. The kit or single multi-compartment container as claimed in claim 14, wherein the A/B weight ratio is 1.

26. The process as claimed in claim 15, wherein the A/B weight proportion ranges from 0.5 to 1.5.

27. The process as claimed in claim 15, wherein the A/B weight proportion is 1.

28. The composition of claim 1, wherein the clobetasol propionate is present at a concentration of 0.2% to 0.5% by weight, relative to the weight of the composition comprising intermediate compositions A and B.

29. The composition as claimed in claim 1, wherein: the gas generating agent is sodium bicarbonate; the agent for activating the gas-generating agent comprises citric acid/sodium citrate buffer and disodium pyrophosphate; the citric acid is present in the intermediate composition A at a concentration of greater than or equal to 1.4% by weight, relative to the weight of the intermediate composition A; and the concentrations of sodium bicarbonate, citric acid, sodium citrate, and disodium pyrophosphate satisfy the following relationship:
[C]=2.4[B]−2.4[A]/0.7, wherein: [C]=concentration of disodium pyrophosphate by weight, relative to the weight of the intermediate composition A; [A]=concentration of citric acid by weight, relative to the weight of the intermediate composition A; and [B]=concentration of sodium bicarbonate by weight, relative to the weight of the intermediate composition B.

30. The composition as claimed in claim 1, wherein clobetasol propionate is the sole active agent.

Description

EXAMPLES

Example 1: Formulation Examples

Formulation Example 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 % by weight WATER QS 100 GLYCEROL 8 MAGNESIUM ALUMINUM SILICATE 1 XANTHAN GUM 0.5 CETOSTEARYL ALCOHOL 3 CYCLOPENTASILOXANE 2 CETEARETH-20 3 GLYCERYL DIBEHENATE 3 PPG-11 STEARYL ETHER 20 PHENOXYETHANOL 1 CLOBETASOL PROPIONATE 0.1 DISODIUM EDTA 0.1 ETHOXYDIGLYCOL 1.2 CITRIC ACID 1.75 SODIUM CITRATE 1.3 SODIUM PYROPHOSPHATE 6 POLOXAMER 124 0.2

Example A2

(8) TABLE-US-00002 INCI Name % by weight WATER QS 100 GLYCEROL 8 MAGNESIUM ALUMINUM SILICATE 1 XANTHAN GUM 0.5 CETOSTEARYL ALCOHOL 3 CYCLOPENTASILOXANE 2 CETEARETH-20 3 GLYCERYL DIBEHENATE 3 MINERAL OIL 24 PHENOXYETHANOL 1 CLOBETASOL PROPIONATE 0.1 ETHANOL 10 PHENOXYETHANOL 1 DISODIUM EDTA 0.1 CITRIC ACID 3.5 SODIUM CITRATE 2.7

Example A3

(9) TABLE-US-00003 INCI Name % by weight WATER QS 100 GLYCEROL 8 MAGNESIUM ALUMINUM SILICATE 1 XANTHAN GUM 0.5 CETOSTEARYL ALCOHOL 3 CYCLOPENTASILOXANE 2 CETEARETH-20 3 GLYCERYL DIBEHENATE 3 CAPRYLIC/CAPRIC TRIGLYCERIDE 24 PHENOXYETHANOL 1 CLOBETASOL PROPIONATE 0.1 PROPYLENE GLYCOL 30 PHENOXYETHANOL 1 DISODIUM EDTA 0.1 CITRIC ACID 1.7 SODIUM CITRATE 1.3 DISODIUM PYROPHOSPHATE 6

Example A4

(10) TABLE-US-00004 INCI Name % by weight WATER QS 100 GLYCEROL 8 MAGNESIUM ALUMINUM SILICATE 1 XANTHAN GUM 0.5 CLOBETASOL PROPIONATE 0.1 PROPYLENE GLYCOL 30 PHENOXYETHANOL 1 DISODIUM EDTA 0.1 CITRIC ACID 1.7 SODIUM CITRATE 1.3 DISODIUM PYROPHOSPHATE 6

Example A5

(11) TABLE-US-00005 INCI Name % by weight WATER QS 100 GLYCEROL 8 MAGNESIUM ALUMINUM SILICATE 1 XANTHAN GUM 0.5 CLOBETASOL PROPIONATE 0.1 ETHANOL 10 PHENOXYETHANOL 1 DISODIUM EDTA 0.1 CITRIC ACID 1.7 SODIUM CITRATE 1.3 DISODIUM PYROPHOSPHATE 6

Formulation Example B: Intermediate Compositions Comprising the Gas-Generating Agent, Formulated with a Basic pH

(12) The intermediate formulations were prepared according to the following process:

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

(14) Optional step 2′: In parallel, heat the fatty phase (containing the oils, the waxes and the surfactants) to a temperature above 60° C.

(15) Optional step 3′: At a temperature above 60° C., prepare the emulsion by adding the fatty phase to the main phase.

(16) Step 4′: Add the additives such as the preserving agents or ethanol at a temperature suitable for the additive.

(17) Step 5′: Neutralize the mixture.

(18) Step 6′: At a temperature below 40° C., add the sodium bicarbonate.

Example B1

(19) TABLE-US-00006 INCI Name % by weight WATER QS 100 MAGNESIUM ALUMINIUM SILICATE 2.5 XANTHAN GUM 0.6 TRIETHANOLAMINE 1.2 SODIUM HYDROGEN CARBONATE 5 PHENOXYETHANOL 0.8

Example B2

(20) TABLE-US-00007 INCI Name % by weight WATER QS 100 MAGNESIUM ALUMINUM SILICATE 2.5 XANTHAN GUM 0.5 CETEARETH-20 3 CETOSTEARYL ALCOHOL 3 GLYCERYL DIBEHENATE 3 CAPRYLIC/CAPRIC TRIGLYCERIDE 10 DL-α-TOCOPHEROL 0.05 MINERAL OIL 5 COCONUT (COCOS NUCIFERA) OIL 2 PRUNUS AMYGDALUS DULCIS 5 CYCLOPENTASILOXANE 3 SODIUM HYDROXIDE 0.09 PHENOXYETHANOL 0.8 SODIUM HYDROGEN CARBONATE 5

Example B3

(21) TABLE-US-00008 INCI Name % by weight WATER QS 100 MAGNESIUM ALUMINUM SILICATE 2.5 XANTHAN GUM 0.5 CETEARETH-20 3 CETOSTEARYL ALCOHOL 3 GLYCERYL DIBEHENATE 3 CAPRYLIC/CAPRIC TRIGLYCERIDE 10 DL-α-TOCOPHEROL 0.05 MINERAL OIL 2 PRUNUS AMYGDALUS DULCIS 5 CASTOR OIL 2 DIMETHICONE 3 SODIUM HYDROXIDE 0.09 PHENOXYETHANOL 0.8 SODIUM HYDROGEN CARBONATE 5

Example B4

(22) TABLE-US-00009 INCI Name % by weight WATER QS 100 MAGNESIUM ALUMINUM SILICATE 2.5 XANTHAN GUM 0.5 CETEARETH-20 3 CETOSTEARYL ALCOHOL 3 GLYCERYL DIBEHENATE 3 CAPRYLIC/CAPRIC TRIGLYCERIDE 10 DL-α-TOCOPHEROL 0.05 SHEA BUTTER 3 PRUNUS AMYGDALUS DULCIS 5 DIMETHICONE 2 SODIUM HYDROXIDE 0.09 PHENOXYETHANOL 0.8 SODIUM HYDROGEN CARBONATE 5

(23) TABLE-US-00010 INCI Name % by weight WATER QS 100 MAGNESIUM ALUMINUM SILICATE 2.5 XANTHAN GUM 0.5 CETEARETH-20 3 CETOSTEARYL ALCOHOL 3 GLYCERYL DIBEHENATE 3 CAPRYLIC/CAPRIC TRIGLYCERIDE 6 SODIUM HYDROXIDE 0.09 PHENOXYETHANOL 0.8 SODIUM HYDROGEN CARBONATE 5

Example B5

(24) 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.

(25) TABLE-US-00011 Formulation B Formulation A B1 B2 B3 B4 B5 A1 X X X X X A2 X X X X X A3 X X X X X A4 X X X X A5 X X X X

Example 2: Foam Density

(26) 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 (T0) 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.

Example 3: Comparative Study of Measurement of Irritation

(27) Study Protocol.

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

(29) 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)

(30) The formulations tested are: An intermediate composition of acidic formulation placebo (i.e. not containing clobetasol propionate), An intermediate composition of basic formulation The complete formulation composed of the mixture of the acidic formulation placebo+the basic formulation (in a 50/50 weight ratio), A commercial reference in the form of topical product.

(31) This study showed that all the formulations tested are non-irritant.

Example 4

(32) 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.

(33) TABLE-US-00012 Ratio 1 Ratio 2 Ratio 3 Sodium bicarbonate .sup. 5% 5% .sup. 5% Citric acid 3.5% — — Disodium pyrophosphate — 12 — Sodium dihydrogen — 7.2% phosphate monohydrate

(34) 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.

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

(36) TABLE-US-00013 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 pyrophosphate 0 6% 7.2% 12% 0  3.6% 7.2%

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

(38) TABLE-US-00014 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 .sup. 5% .sup. 5%  5% Citric acid 3.5% 1.5% 0 Sodium citrate 2.7% 0.5% 0 Sodium dihydrogen 0 6.2% 10% phosphate monohydrate

(39) 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

(40) when:

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

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

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

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