| (11) | EP 2 922 528 B1 |
(12) | EUROPEAN PATENT SPECIFICATION |
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(54) | TOPICAL DAPSONE AND DAPSONE/ADAPALENE COMPOSITIONS AND METHODS FOR USE THEREOF TOPISCHES DAPSON UND DAPSON-/ADAPALENZUSAMMENSETZUNGEN SOWIE VERFAHREN ZUR VERWENDUNG DAVON COMPOSITIONS TOPIQUES DE DAPSONE ET DE DAPSONE/ADAPALÈNE ET LEURS MÉTHODES D'UTILISATION |
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Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). |
FIELD
BACKGROUND
SUMMARY
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 presents the impact of an acrylamide/sodium acryloyldimethyltaurate copolymer emulsion viscosity builder on color change.
Figure 2 presents the impact of an acrylamide/sodium acryloyldimethyltaurate copolymer emulsion viscosity builder on dapsone crystal growth.
Figure 3 presents the impact of anti-oxidants and chelating agents on color change.
DETAILED DESCRIPTION
EMBODIMENTS
Embodiment 1. A composition comprising dapsone, a first solubilizing agent which is diethylene glycol monoethyl ether, optionally at least one second solubilizing agent, a polymeric viscosity builder, comprising acrylamide/sodium acryloyldimethyltaurate copolymer water, wherein the dapsone is present in the composition at a concentration of 3% w/w to 10% w/w.
Embodiment 2. The composition of embodiment 1, wherein the diethylene glycol monoethyl ether is present at a concentration of about 10% w/w to about 40% w/w.
Embodiment 3. The composition of embodiment 1, wherein the diethylene glycol monoethyl ether is present at a concentration of about 20% w/w to about 30% w/w.
Embodiment 4. The composition of embodiment 1, wherein the diethylene glycol monoethyl ether is present in the composition at a concentration of about 25% w/w.
Embodiment 5. The composition of embodiment 1, further comprising adapalene.
Embodiment 6. The composition of embodiment 5, wherein the adapalene is present at a concentration of about 0.1% w/w to about 0.3% w/w.
Embodiment 7. The composition of embodiment 1 wherein the second solubilizing agent is selected an alcohol, a glycol, an ester, or an ether.
Embodiment 8. The composition of embodiment 1, wherein the second solubilizing agent is PEG 400, lactic acid, dimethyl isosorbide, propylene glycol, propylene carbonate, hexylene glycol, isostearyl alcohol, diethyl sebacate, or ethanol.
Embodiment 9. The composition of embodiment 8, wherein the second solubilizing agent is propylene glycol.
Embodiment 10. The composition of embodiment 9, wherein the propylene glycol is present in the composition at a concentration of about 5% w/w.
Embodiment 11. The composition of embodiment 8, wherein the second solubilizing agent is propylene carbonate.
Embodiment 12. The composition of embodiment 11, wherein the propylene carbonate is present in the composition at a concentration of about 5% w/w.
Embodiment 13. The composition of embodiment 8, wherein the second solubilizing agent is ethanol.
Embodiment 14. The composition of embodiment 13, wherein the ethanol is present in the composition at a concentration of about 3% w/w.
Embodiment 15. The composition of embodiment 1, wherein the polymeric viscosity builder comprises an acrylamide/sodium acryloyldimethyltaurate copolymer.
Embodiment 16. The composition of embodiment 1, wherein the polymeric viscosity builder is present at a concentration of about 2% w/w to about 6% w/w.
Embodiment 17. The composition of embodiment 1, wherein the polymeric viscosity builder is present at a concentration of about 4% w/w.
Embodiment 18. The composition of embodiment 1, further comprising methyl paraben.
Embodiment 19. The composition of embodiment 1, further comprising Carbomer interpolymer type A, Carbomer interpolymer type B, or Carbomer Homopolymer Type C.
Embodiment 20. The composition of embodiment 19, wherein the Carbomer Homopolymer Type C is present at a concentration of about 0.7% w/w to about 1.5% w/w.
Embodiment 21. The composition of embodiment 19, wherein the Carbomer Homopolymer Type C is present at a concentration of about 0.85% w/w to about 1.5% w/w.
Embodiment 22. The composition of embodiment 19, wherein the Carbomer interpolymer Type A is present at a concentration of about 1% w/w to 2% w/w.
Embodiment 23. The composition of embodiment 19, wherein the Carbomer interpolymer Type B is present at a concentration of about 0.1% w/w to about 0.5% w/w.
Embodiment 24. The composition of embodiment 1, further comprising a neutralizing agent.
Embodiment 25. The composition of embodiment 24 wherein the neutralizing agent is NaOH or triethanolamine.
Embodiment 26. The composition of embodiment 1 further comprising a chelating agent.
Embodiment 27. The composition of embodiment 26, wherein the chelating agent is ethylene diamine tetraacetic acid.
Embodiment 28. The composition of embodiment 27, wherein the ethylene diamine tetraacetic acid is present at a concentration of about 0.02% w/w to about 0.04% w/w.
Embodiment 29. The composition of embodiment 27, wherein the ethylene diamine tetraacetic acid is present in the composition at about 0.03% w/w.
Embodiment 30. The composition of embodiment 1 wherein the composition is in the form of a gel, a suspension, an emulsion, a cream, a liquid, a paste, a lotion, a nanoemulsion, a microemulsion, a reverse emulsion, or a liposomal cream.
Embodiment 31. A composition of embodiment 1 for use in a method for treating a dermatological condition comprising administering to a subject in need thereof a therapeutically effective amount of a composition of embodiment 1.
Embodiment 32. The composition of embodiment 31 wherein the condition is acne vulgaris, rosacea, atopic dermatitis, treatment of chronic wounds, bed sores, keratosis piralis, sebaceous cysts, inflammatory dermatoses, post inflammatory hyperpigmentation, eczema, xerosis, pruritis, lichen planus, nodular prurigo, dermatitis, eczema, or miliaria.
Embodiment 33. The composition of embodiment 32 wherein the condition is acne vulgaris.
Embodiment 34. The composition of embodiment 1, 2, 3, or 4, further comprising adapalene.
Embodiment 35. The composition of embodiment 34, wherein the adapalene is present at a concentration of about 0.1% w/w to about 0.3% w/w.
Embodiment 36. The composition of embodiment 1, 2, 3, 4, 34, or 35, wherein the second solubilizing agent is selected an alcohol, a glycol, an ester, or an ether.
Embodiment 37. The composition of embodiment 1, 2, 3, 4, 34, 35, or 36, wherein the second solubilizing agent is PEG 400, lactic acid, dimethyl isosorbide, propylene glycol, propylene carbonate, hexylene glycol, isostearyl alcohol, diethyl sebacate, or ethanol.
Embodiment 38. The composition of embodiment 37, wherein the second solubilizing agent is propylene glycol.
Embodiment 39. The composition of embodiment 38, wherein the propylene glycol is present in the composition at a concentration of about 5% w/w.
Embodiment 40. The composition of embodiment 37, wherein the second solubilizing agent is propylene carbonate.
Embodiment 41. The composition of embodiment 40, wherein the propylene carbonate is present in the composition at a concentration of about 5% w/w.
Embodiment 42. The composition of embodiment 37, wherein the second solubilizing agent is ethanol.
Embodiment 43. The composition of embodiment 42, wherein the ethanol is present in the composition at a concentration of about 3% w/w.
Embodiment 44. The composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43, wherein the polymeric viscosity builder comprises an acrylamide/sodium acryloyldimethyltaurate copolymer.
Embodiment 45. The composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or 44, wherein the polymeric viscosity builder is present at a concentration of about 2% w/w to about 6% w/w.
Embodiment 46. The composition of embodiment 45, wherein the polymeric viscosity builder is present at a concentration of about 4% w/w.
Embodiment 47. The composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, or 46, further comprising methyl paraben.
Embodiment 48. The composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, or 47, further comprising Carbomer interpolymer type A, Carbomer interpolymer type B, or Carbomer Homopolymer Type C.
Embodiment 49. The composition of embodiment 48, wherein the Carbomer Homopolymer Type C is present at a concentration of about 0.7% w/w to about 1.5% w/w.
Embodiment 50. The composition of embodiment 48, wherein the Carbomer Homopolymer Type C is present at a concentration of about 0.85% w/w to about 1.5% w/w.
Embodiment 51. The composition of embodiment 48, wherein the Carbomer interpolymer Type A is present at a concentration of about 1% w/w to 2% w/w. Embodiment 52. The composition of embodiment 48, wherein the Carbomer interpolymer Type B is present at a concentration of about 0.1% w/w to about 0.5% w/w.
Embodiment 53. The composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52, further comprising a neutralizing agent.
Embodiment 54. The composition of embodiment 53 wherein the neutralizing agent is NaOH or triethanolamine.
Embodiment 55. The composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, or 54, further comprising a chelating agent.
Embodiment 56. The composition of embodiment 55, wherein the chelating agent is ethylene diamine tetraacetic acid.
Embodiment 57. The composition of embodiment 56, wherein the ethylene diamine tetraacetic acid is present at a concentration of about 0.02% w/w to about 0.04% w/w.
Embodiment 58. The composition of embodiment 56, wherein the ethylene diamine tetraacetic acid is present in the composition at about 0.03% w/w.
Embodiment 59. The composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, or 58, wherein the composition is in the form of a gel, a suspension, an emulsion, a cream, a liquid, a paste, a lotion, a nanoemulsion, a microemulsion, a reverse emulsion, or a liposomal cream.
Embodiment 60. A composition according to the present invention for use in a method for treating a dermatological condition comprising administering to a subject in need thereof a therapeutically effective amount of a composition of embodiment 1, 2, 3, 4, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, or 59.
Embodiment 61. A composition of embodiment 60 wherein the condition is acne vulgaris, rosacea, atopic dermatitis, treatment of chronic wounds, bed sores, keratosis piralis, sebaceous cysts, inflammatory dermatoses, post inflammatory hyperpigmentation, eczema, xerosis, pruritis, lichen planus, nodular prurigo, dermatitis, eczema, or miliaria.
Embodiment 62. A composition of embodiment 60 wherein the condition is acne vulgaris.
EXAMPLES
Example 1
Formulation # | ENA | ENC |
Dapsone | 7.5 | 7.5 |
Diethylene glycol monoethyl ether | 30 | 30 |
Carbomer homopolymer type C. | -- | 1 |
acrylamide / sodium acryloyldimethyltaurate copolymer based thickener | 4 | -- |
Methyl paraben | 0.2 | 0.2 |
pH adjusting solution | pH 5.5-7 | pH 5.5-7 |
Purified Water | Q.S 100 | Q.S 100 |
Example 2
Composition # | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
Dapsone | 5-10 | |||||||||
Adapalene | --- | 0.1-0.3 | ||||||||
Diethylene glycol monoethyl ether | 30 | 35 | 40 | 30 | 35 | 30 | 35 | 40 | 30 | 35 |
Carbomer homopolymer type C | --- | 0.85-1.5 | --- | --- | --- | 0.85-1.5 | ||||
Acrylamide/sodium acryloyldimethyltaurate copolymer emulsion | 4 | --- | 4 | --- | ||||||
Methyl paraben | 0.2 | |||||||||
NaOH/ pH adjusting solution | pH 5.5-6.5 | |||||||||
Purified Water | Q.S 100 |
Example 3
Composition # | A5 | A6 | A7 |
Dapsone | 7.5 | ||
Diethylene glycol monoethyl ether | 35 | 40 | 35 |
carbomer homopolymer type C | 1.25 | --- | 1.25 |
Acrylamide/sodium acryloyldimethyltaurate copolymer emulsion | --- | 4 | --- |
EDTA | 0.05 | --- | |
Anhydrous Citric Acid | 0.1 | --- | |
Sodium Metabisulfite | --- | 0.2 | |
Methyl paraben | 0.17 | 0.2 | |
Propyl paraben | 0.03 | --- | |
NaOH/ pH adjusting solution | pH 5.5-6.5 | ||
Purified Water | Q.S 100 |
Composition # | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
Dapsone | 5-10 | |||||||||
Adapalene | --- | 0.1-0.3 | ||||||||
Diethylene glycol monoethyl ether | 30 | 35 | 40 | 30 | 35 | 30 | 35 | 40 | 30 | 35 |
carbomer homopolymer type C | --- | 0.85-1.5 | --- | 0.85-1.5 | ||||||
Acrylamide/sodium Acryloyldimethyltaurate copolymer emulsion | 4 | --- | 4 | --- | ||||||
EDTA | 0-0.1 | |||||||||
Citric Acid | 0-0.1 | |||||||||
Sodium Metabisulfite | 0-0.5 | |||||||||
Methyl paraben | 0.2 | |||||||||
NaOH/ pH adjusting solution | pH 5.5-6.5 | |||||||||
Purified Water | Q.S 100 |
Example 4
Materials | % w/w | |||||
5-1 | 5-2 | 5-3 | 5-4 | 5-5 | 5-6 | |
Dapsone | 7.5 | |||||
Adapalene | --- | 0.3 | -- | |||
Diethylene glycol monoethyl ether | 30 | 35 | 40 | 30 | 40 | 25 |
carbomer homopolymer type C | 1 | |||||
Methylparaben | 0.2 | |||||
Triethanolamine (TEA) Q.S. | pH 5.5-6.5 | |||||
Hydrochloric Acid Q.S | pH 5.5-6.5 | |||||
Purified Water | q.s.a.d.100 |
Example 4
% w/w | ||||||
Materials | 6-1 | 6-2 | 6-3 | 6-4 | 6-5 | 6-6 |
Dapsone | 7.5 | 10 | 7.5 | |||
Adapalene | -- | 0.3 | ||||
Diethylene glycol monoethyl ether | 25 | 35 | 35 | 25 | 30 | 40 |
Propylene glycol | 5 | |||||
Propylene Carbonate | 5 | |||||
Ethanol (absolute) | 3 | -- | 3 | |||
EDTA | 0.03 | |||||
Carbomer Interpolymer Type A | -- | 1.5 | ||||
Carbomer Interpolymer Type B | -- | 0.3 | ||||
Acrylamide/sodium acryloyldimethyltaurate copolymer emulsion | 4 | -- | 4 | |||
Methyl Paraben | 0.2 | |||||
Triethanolamine | -- | Q.S. pH 5.5 - 6.5 | ||||
Purified Water | q.s.a.d.100 |
Example 5
Ingredient | Amount (% w/w) |
Dapsone | 5-8 |
Adapalene | 0.1-0.3 |
Diethylene glycol monoethyl ether | 40.00 |
Propylene glycol | 5.00 |
Ethanol (absolute) | 3.00 |
Ethylene Diamine Tetraacetic acid (EDTA) | 0.03 |
Methyl Paraben | 0.20 |
Sepineo P 600 | 4.00 |
Purified Water | Q.S. |
Example 6