EP3355857A1 - No-rinse chemical foam containing trifarotene, and use thereof in the treatment of acne - Google Patents
No-rinse chemical foam containing trifarotene, and use thereof in the treatment of acneInfo
- Publication number
- EP3355857A1 EP3355857A1 EP16775630.3A EP16775630A EP3355857A1 EP 3355857 A1 EP3355857 A1 EP 3355857A1 EP 16775630 A EP16775630 A EP 16775630A EP 3355857 A1 EP3355857 A1 EP 3355857A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition
- agents
- composition according
- weight
- generating agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 229950008964 trifarotene Drugs 0.000 title claims abstract description 42
- MFBCDACCJCDGBA-UHFFFAOYSA-N 4-[3-(3-tert-butyl-4-pyrrolidin-1-ylphenyl)-4-(2-hydroxyethoxy)phenyl]benzoic acid Chemical compound CC(C)(C)C1=CC(C=2C(=CC=C(C=2)C=2C=CC(=CC=2)C(O)=O)OCCO)=CC=C1N1CCCC1 MFBCDACCJCDGBA-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 208000002874 Acne Vulgaris Diseases 0.000 title claims abstract description 10
- 206010000496 acne Diseases 0.000 title claims abstract description 10
- 239000006260 foam Substances 0.000 title claims description 60
- 239000000126 substance Substances 0.000 title claims description 15
- 239000000203 mixture Substances 0.000 claims abstract description 195
- 238000005187 foaming Methods 0.000 claims abstract description 25
- 230000000699 topical effect Effects 0.000 claims abstract description 15
- 230000003213 activating effect Effects 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 80
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 33
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 28
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 21
- 239000003995 emulsifying agent Substances 0.000 claims description 17
- 239000000872 buffer Substances 0.000 claims description 16
- 229940069078 citric acid / sodium citrate Drugs 0.000 claims description 14
- 235000019820 disodium diphosphate Nutrition 0.000 claims description 14
- GYQBBRRVRKFJRG-UHFFFAOYSA-L disodium pyrophosphate Chemical compound [Na+].[Na+].OP([O-])(=O)OP(O)([O-])=O GYQBBRRVRKFJRG-UHFFFAOYSA-L 0.000 claims description 14
- 229940038485 disodium pyrophosphate Drugs 0.000 claims description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 14
- 239000001569 carbon dioxide Substances 0.000 claims description 13
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 13
- -1 clays Substances 0.000 claims description 12
- 239000004094 surface-active agent Substances 0.000 claims description 12
- 235000015165 citric acid Nutrition 0.000 claims description 11
- 239000003921 oil Substances 0.000 claims description 11
- 239000000839 emulsion Substances 0.000 claims description 10
- 239000003349 gelling agent Substances 0.000 claims description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- 239000002537 cosmetic Substances 0.000 claims description 6
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- 239000000975 dye Substances 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000000194 fatty acid Substances 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
- 150000004665 fatty acids Chemical class 0.000 claims description 6
- 239000003906 humectant Substances 0.000 claims description 6
- 239000001488 sodium phosphate Substances 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 239000003974 emollient agent Substances 0.000 claims description 5
- 239000000945 filler Substances 0.000 claims description 5
- 239000003755 preservative agent Substances 0.000 claims description 5
- 239000007787 solid Chemical class 0.000 claims description 5
- 239000001993 wax Substances 0.000 claims description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical group [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 150000002191 fatty alcohols Chemical class 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 235000010755 mineral Nutrition 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 239000011975 tartaric acid Substances 0.000 claims description 4
- 235000002906 tartaric acid Nutrition 0.000 claims description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 claims description 3
- 239000003380 propellant Substances 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- 206010040829 Skin discolouration Diseases 0.000 claims description 2
- 239000004902 Softening Agent Substances 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002280 amphoteric surfactant Substances 0.000 claims description 2
- 239000003945 anionic surfactant Substances 0.000 claims description 2
- 239000000058 anti acne agent Substances 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 230000002225 anti-radical effect Effects 0.000 claims description 2
- 229940124340 antiacne agent Drugs 0.000 claims description 2
- 239000003429 antifungal agent Substances 0.000 claims description 2
- 229940121375 antifungal agent Drugs 0.000 claims description 2
- 239000007853 buffer solution Substances 0.000 claims description 2
- 239000003093 cationic surfactant Substances 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000000084 colloidal system Substances 0.000 claims description 2
- 239000003086 colorant Substances 0.000 claims description 2
- 239000008139 complexing agent Substances 0.000 claims description 2
- 239000007854 depigmenting agent Substances 0.000 claims description 2
- 239000002270 dispersing agent Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003410 keratolytic agent Substances 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 230000003472 neutralizing effect Effects 0.000 claims description 2
- 239000002736 nonionic surfactant Substances 0.000 claims description 2
- 239000002304 perfume Substances 0.000 claims description 2
- 235000011007 phosphoric acid Nutrition 0.000 claims description 2
- 239000000049 pigment Substances 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 229940005657 pyrophosphoric acid Drugs 0.000 claims description 2
- 239000003352 sequestering agent Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 230000000475 sunscreen effect Effects 0.000 claims description 2
- 239000000516 sunscreening agent Substances 0.000 claims description 2
- 239000002562 thickening agent Substances 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims 2
- 239000004909 Moisturizer Substances 0.000 claims 1
- 239000012764 mineral filler Substances 0.000 claims 1
- 230000001333 moisturizer Effects 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 79
- 239000007789 gas Substances 0.000 description 32
- 210000003491 skin Anatomy 0.000 description 29
- 239000006071 cream Substances 0.000 description 17
- 238000009472 formulation Methods 0.000 description 17
- 229960004106 citric acid Drugs 0.000 description 10
- 239000012530 fluid Substances 0.000 description 10
- 230000007794 irritation Effects 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 9
- 235000019799 monosodium phosphate Nutrition 0.000 description 9
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 9
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- BANXPJUEBPWEOT-UHFFFAOYSA-N 2-methyl-Pentadecane Chemical compound CCCCCCCCCCCCCC(C)C BANXPJUEBPWEOT-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000009792 diffusion process Methods 0.000 description 6
- 210000002615 epidermis Anatomy 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 5
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 5
- 229960001484 edetic acid Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229960005323 phenoxyethanol Drugs 0.000 description 5
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 description 4
- OSCJHTSDLYVCQC-UHFFFAOYSA-N 2-ethylhexyl 4-[[4-[4-(tert-butylcarbamoyl)anilino]-6-[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)NC(C)(C)C)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 OSCJHTSDLYVCQC-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 210000004207 dermis Anatomy 0.000 description 4
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
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- 238000002360 preparation method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
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- DMBUODUULYCPAK-UHFFFAOYSA-N 1,3-bis(docosanoyloxy)propan-2-yl docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCCCCCC DMBUODUULYCPAK-UHFFFAOYSA-N 0.000 description 3
- 229940043268 2,2,4,4,6,8,8-heptamethylnonane Drugs 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
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- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
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- 239000001509 sodium citrate Substances 0.000 description 3
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- BARWIPMJPCRCTP-CLFAGFIQSA-N oleyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC BARWIPMJPCRCTP-CLFAGFIQSA-N 0.000 description 1
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
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- 239000004302 potassium sorbate Substances 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; Salts thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/402—1-aryl substituted, e.g. piretanide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
- A61K9/122—Foams; Dry foams
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Definitions
- Non-rinsed chemical foam containing trifarotene and its use in the treatment of acne
- the present invention relates to a topical product not rinsed in the form of a foam for the pharmaceutical or cosmetic treatment of the skin comprising trifarotene.
- Trifarotene is a new retinoid and corresponds to 3 "-tert-butyl-4 '- (2-hydroxyethoxy) -4" -pyrrolidin-1-yl [1,1', 3 ', 1 "] terphenyl-
- the present invention also relates to the use of the product according to the invention for the treatment of acne.
- compositions for a more practical and fast topical application.
- Foams help to overcome tolerance problems through better dose control, thanks to their spreading properties and low density.
- compositions intended for a known topical application may cause side effects which may limit their use and therefore their effectiveness.
- actives have the major disadvantage of inducing irritation that may result in poor tolerance of the product. This can thus create on the part of the patient a behavior of non-observance of the treatment and the discontent with regard to said treatment. There is therefore a need to develop new dosage forms overcoming the aforementioned drawbacks in terms of tolerance, effectiveness and compliance.
- trifarotene as many retinoids is known to be difficult to tolerate by consumers following acne treatment. This tolerance is very variable depending on the formula used as a vehicle. The patient also often feels that by applying larger amounts of product, he will go towards a faster healing. This behavior leads to excessive irritation, non-compliance and discontinuation of treatment.
- the composition according to the invention has the advantage of being in the form of a foam generated extemporaneously, and very well tolerated. After its application, the composition according to the invention is not removed by rinsing.
- composition is particularly well tolerated, even though it is not rinsed off, as shown in the examples illustrating one of the methods of assessing tolerance presented hereinafter.
- composition also has the advantage of remaining on the surface of the skin (stratum corneum and epidermis essentially), in order to avoid undesirable effects such as irritation and to obtain a foam adapted to the treatment of the skin. acne.
- the effectiveness of an active ingredient is related to the release and kinetics of penetration of the active through the skin.
- the form composition plays its essential role of vehicle of the active ingredient so that it reaches its therapeutic target.
- the release-permeation test described in Example 5 on ex-vivo human skin highlights the advantage of applying a chemical foam containing trifarotene.
- formulations of the invention make it possible to obtain a foam composition making it possible to reduce the undesirable effects and in particular the irritation.
- Aerosols in which the foam is generated by a propellant gas but with the disadvantage of being aerosols with the risks well known to them (pollution, respiratory risks in particular).
- Foaming formulas that are not very rich in foaming surfactants but packaged in a package provided with a mechanical foam generating system (pump with pulvorex type grid). This type of formulation requires the use of foaming surfactants that can induce irritation in rinsed products.
- compositions for topical application containing trifarotene in well-tolerated compositions for application topically in humans particularly a non-rinsed application (i.e., the composition is not rinsed off after application).
- the object of the present invention is therefore to provide a composition that meets these needs.
- Foaming surfactants are defined as surfactants which produce a voluminous, stable and unctuous foam when they are mixed with water according to tests well known to those skilled in the art.
- Foaming surfactants include anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants of the alkylpolyglucoside and glucamide family.
- the pharmaceutical form according to the invention has the advantage of guaranteeing good stability of trifarotene.
- this formulation advantageously leads to the production of a soft, perfectly tolerated and non-irritating foam, which allows a better coverage of the area to be treated and makes it possible to overcome the problems of tolerance by a better control of the dose, thanks to the spreading properties and the low density of the foam.
- this dosage form does not require for its implementation the use of propellants or aerosols.
- aerosol or spray foams are excluded from the scope of the invention.
- foams of the prior art of the type open creams and / or foaming formulas requiring a mechanical foam generating system are also excluded from the invention.
- the present invention finally relates to the cosmetic use of the composition according to the invention, by topical application of this composition to the skin, and a medicament for topical application to the skin, comprising such a composition.
- the subject of the present invention is also the composition according to the invention for its use in the treatment of acne.
- FIG. 1 illustrates the production of a composition in the form of a foam according to the invention.
- the photo on the left represents the moment of mixing (T0) and the photo on the right represents the foam obtained when the acid / base chemical reaction is complete.
- FIG. 2 illustrates Example 5 and represents the comparative penetration-permeation results in the stratum corneum, the epidermis and the dermis of a foam composition according to the invention at 0.01% by weight of trifarotene composed of the mixture of intermediate compositions.
- A2 and B3 described in Example 1 in a ratio of 50/50 by weight
- a Cream Reference containing 0.01% by weight of trifarotene is described in Example 1 (in a ratio of 50/50 by weight) and a Cream Reference containing 0.01% by weight of trifarotene.
- Figure 3 also illustrates Example 5 and shows the comparative penetration-sealing results in the dermis of Figure 1 on an enlarged scale.
- composition according to the invention is capable of taking the form of a foam by the mere fact of its composition and can also be defined as a foaming composition for topical application.
- composition in the form of a foam (also hereinafter referred to as self-foaming composition), is meant a composition of semi-solid consistency having an aerated form comparable to a foam.
- self-foaming composition comprises at least two compositions or intermediate formulas in variable proportions and in particular the following ingredients:
- composition or intermediate formula A comprising an activating agent for the gas generating agent defined below;
- each intermediate composition may have a viscosity (measured at 25 ° C. and at atmospheric pressure) of between 1 cP and 500,000 cP, advantageously between 500 cP and 350000 cP, measured with a conventional method of the brookfield type RV dv II: needle 6 vit 2.
- the gas generated by the gas-generating agent may be any physiologically compatible gas which makes it possible to obtain a foam, such as, for example, carbon dioxide (CO2) or oxygen (O2).
- the gas generated from the gas generating agent is carbon dioxide (CO2).
- the gas concentration can vary, the amount of bubbles in the composition can vary and thus give a composition that can go from unventilated to very highly aerated.
- the term "activating agent of the gas generating agent” means an ingredient which, by chemical reaction with the gas generating agent, releases a gas.
- a gas Preferably it is an acid / base reaction.
- the self-foaming composition may be preferably in all forms ranging from aerated to a very expanded foam.
- composition according to the invention is suitable for topical application and may further comprise a physiologically acceptable medium, that is to say a medium compatible with the skin and superficial body growths. It is preferably a pharmaceutically acceptable medium.
- the composition may comprise any active agent capable of exhibiting an activity, which may be therapeutic.
- active agents may be, among others, chosen from emollient agents, humectants, anti-radical agents, anti-inflammatory agents, vitamins, depigmenting agents, anti-acne agents, anti-seborrhics agents, anti-fungal agents, keratolytic agents, sunscreens, slimming agents, skin coloring agents.
- the composition in the form of foam may have a pH of between 2 and 8, preferably between 4 and 8.
- the present invention relates either to a single compartmentalized container (each compartment hosting an intermediate formula) and preferably comprising 2 or 3 compartments, or a kit comprising each intermediate formula stored independently of one another and physically separated.
- the intermediate composition (or formula) A may be in the form of a solution, an emulsion (lotion, cream, cream without emulsifier, milk, fluid cream) or a gel.
- This composition advantageously contains the activating agent for the gas-generating agent, preferably an acid in sufficient quantity (which may be in the form of an acid / base buffer at acidic pH) which may be by way of non-limiting example the citric acid / sodium citrate couple.
- Formula B can be in the form of a solution, a gel, an emulsion (lotion, cream, cream without emulsifier, milk, fluid cream).
- This composition advantageously contains in sufficient quantity a gas generating agent, which may in particular be sodium bicarbonate.
- a gas generating agent which may in particular be sodium bicarbonate.
- the subject of the invention is also a kit or a single multi-compartment container as defined above, allowing the extemporaneous preparation of a composition in the form of a foam according to the invention, comprising separately at least two intermediate formulas ( or intermediate compositions):
- an intermediate formula A comprising at least one activating agent for the gas generating agent
- an intermediate formula B comprising at least one gas generating agent
- trifarotene is contained in the intermediate composition A.
- the activating agent of the gas-generating agent is a compound which reacts with the gas generating agent by a chemical reaction (preferably an acid-base reaction) releasing a gas. It is advantageously an acid, a partially salified polyacid salt or a weak acid buffer solution and its conjugate base, or a mixture of such compounds.
- the acid / base buffer of said acid may be any acidic buffer / base of the weak acid such as, for example, a citric acid / sodium citrate buffer or a tartaric acid / sodium tartrate buffer.
- a citric acid / sodium citrate buffer or a tartaric acid / sodium tartrate buffer.
- alpha-hydroxy acids which are weak acids preferably having a pKa of between 2 and 6 such as citric acid, tartaric acid, malic acid, lactic acid but also acid phosphoric acid and pyrophosphoric acid and their optionally partially salified salts such as disodium pyrophosphate or sodium dihydrogen phosphate also called monosodium phosphate.
- the gas-activating agent is chosen from a tartaric acid / tartrate salt buffer (for example sodium tartrate); citric acid / sodium citrate buffer alone; phosphoric acid, monosodium phosphate, disodium pyrophosphate alone or as a mixture with a citric acid / sodium citrate buffer.
- the gas-activating agent is a citric acid / sodium citrate buffer alone or in admixture with monosodium phosphate and / or disodium pyrophosphate.
- the content of citric acid / sodium citrate is preferably less than or equal to 2.4% relative to the total weight of the intermediate composition A, so as to limit any risk. tingling.
- the citric acid / sodium citrate buffer is used in admixture with disodium pyrophosphate or sodium dihydrogenphosphate.
- said gas-activating agent may be present in the intermediate formula A in an amount ranging from 0.001% to 95% by weight relative to the total weight of the intermediate composition A.
- gas generating agent any agent that has the property of generating a gas by chemical reaction.
- the gas generated from the gas generating agent present in the intermediate composition B is preferably carbon dioxide or carbon dioxide.
- CO2 carbon dioxide
- CO2 carbon dioxide
- the gas generating agent is preferably selected from sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate and mixtures thereof.
- the intermediate formula B comprises a carbon dioxide generating agent which is particularly preferably sodium bicarbonate.
- Said gas generating agent may be present in the intermediate formula B in an amount ranging from 1% to 10%, preferably from 2% to 8% by weight relative to the weight of the intermediate composition B.
- the intermediate formula A may have an acidic pH, advantageously between 1.0 and 6.0, and the intermediate formula B may have a basic pH, advantageously between 7 and 12.
- one or more intermediate formula (s) comprises trifarotene, either as such or in salt form, in an amount corresponding to 0.00001 to 20% by weight of trifarotene in the form of acid (i.e., 3 "-tert-butyl-4 '- (2-hydroxyethoxy) -4" - pyrrolidin-1-yl [1,1', 3 ', 1 "] terphenyl -4-carboxylic) relative to the total weight of the total composition.
- trifarotene in the form of acid (i.e., 3 "-tert-butyl-4 '- (2-hydroxyethoxy) -4" - pyrrolidin-1-yl [1,1', 3 ', 1 "] terphenyl -4-carboxylic) relative to the total weight of the total composition.
- the total composition (mixture of the intermediate of formulation A with the intermediate of formulation B) contains trifarotene, as is or in the form of salt, in an amount corresponding to 0.00001% to 1% by weight. preferably from 0.0001 to 0.1% by weight and more preferably from 0.001 to 0.1% by weight of trifarotene in acid form, relative to the weight of the total composition.
- total composition or “total formula” means the composition of the product in the form of foam after the mixing of said intermediate compositions.
- the trifarotene is contained in the intermediate composition A which has a better compatibility with the active.
- trifarotene may in certain cases have a lower compatibility with the ingredients constituting formula B, and especially with sodium bicarbonate.
- the intermediate formula A may be in any galenic form compatible with the desired dosage form for the final composition obtained by mixing formula A with formula B.
- Intermediate formula B can be in any galenic form compatible with the desired dosage form for the final composition obtained by mixing formula B with formula A.
- Advantageously formula B can be a gel, a solution, a suspension, a emulsion (cream, cream without surfactant, milk lotion, fluid cream), preferably an emulsion.
- one of the two intermediate formulas is in the form of a gel.
- the other intermediate formula is not in gel form.
- Each intermediate formula of the multi-compartment kit or container as defined above, according to the invention comprises a physiologically acceptable medium, carrying the compound (s), and chosen in such a way that the compounds are capable of reacting with each other. other for forming a self-foaming composition upon mixing of at least intermediate formulas A and B.
- extemporaneous mixing of at least two formulas, for example formula A and formula B creates the composition in form of foam according to the invention.
- the gas-generating agent such as sodium bicarbonate
- the gas-activating agent such as the acid
- composition obtained after mixing at least the formulas A and B it may of course remain gas-activating agent and / or unreacted gas generating agent.
- the kit or the single multi-compartment container according to the invention can be designed so that during the preparation of the composition according to the invention, the intermediate formulas A and B can be mixed in a ratio by weight AB ranging from 0.5 to 2, preferably from 0.5 to 1.5, more preferably close to 1 (that is to say from 0.9 to 1, 1), and even more preferably from 1.
- the kit can be designed to simultaneously release doses (by weight) of intermediate compositions A and B which can be in a ratio by weight ranging from 2 doses of B for 1 dose of A to 2 doses of A for 1 dose of B, preferably 2 doses of B for 1 dose of A at 3 doses of A for 2 doses of B.
- the kit is designed to simultaneously release 1 dose by weight of A and 1 dose by weight of B.
- the kit may be in any form compatible with, on the one hand, a separate preservation of the intermediate formulas A and B and, on the other hand, the ability to make the mixture of A and B extemporaneously.
- intermediate formulas A and B may be packaged in a housing with at least two separate compartments, each containing A or B.
- the kit may be in the form of a syringe to at least two separate bodies, each provided with a piston, said two bodies containing the respective formulas A and B, and being designed to release simultaneously by exercise. of a force on the piston the desired doses of formulas A and B.
- the invention also relates to a process for the preparation of a composition according to the invention, characterized in that to obtain the composition in foam form, an intermediate formula A and an intermediate formula B of the kit are mixed extemporaneously as defined above, in relative proportions by weight AB which can range from 0.5 to 2, preferably from 0.5 to 1.5, and more preferably from 1.
- gas-generating agent preferably sodium bicarbonate
- gas-activating agent preferably citric acid and / or disodium pyrophosphate and / or sodium dihydrogen phosphate or monosodium phosphate.
- the ratio by weight of citric acid / sodium bicarbonate is advantageously between 0.1 and 2, preferably between 0.5 and 1, and very preferred equal to 0.7.
- the ratio by weight of disodium pyrophosphate / sodium bicarbonate is between 0.5 and 5, preferably between 1 and 3, and very preferably is equal to 2.4.
- the ratio by weight of sodium dihydrogenphosphate monohydrate / sodium bicarbonate is between 0.5 and 5, preferably between 1 and 3, and so very favorite is 2.
- Example 4 The exemplification of ratios sodium bicarbonate / citric acid, sodium bicarbonate / sodium pyrophosphate, sodium bicarbonate / sodium hydrogen phosphate is described in Example 4.
- the combination citric acid / sodium citrate, disodium pyrophosphate or sodium dihydrogenphosphate and a gelling system compatible with the dosage form has made it possible to obtain a formula with very stable physicochemical properties and in which the trifarotene is particularly stable, generating no unpleasant sensation on the skin and allowing the release of gas and thus the creation of foam.
- Example 2B below shows that the compositions according to the present invention have excellent physical and chemical stability.
- a composition is considered physically stable when its organoleptic characteristics, pH, viscosity and homogeneity of trifarotene do not change with time under different temperature conditions: ambient temperature (RT, or TA) and 40 ° C.
- the ambient temperature corresponds to a temperature ranging from 15 ° C to 25 ° C.
- a composition is considered chemically stable when the content of active ingredient that it contains does not change with time under the various temperature conditions (RT and 40 ° C.)
- the composition is considered stable when the content of trifarotene (expressed by weight relative to the weight of the intermediate formula) is included in the specifications ranging from 90% to 1 10%.
- composition according to the invention may also comprise one or more agents chosen from dispersing agents, stabilizing agents, preserving agents, fatty substances, thickeners, dyes, perfumes, surfactants, gelling agents, complexing agents, neutralizing agents, non-foaming emulsifying agents, fillers, sequestering agents, reducing agents, odor masks, plasticizing agents, softening agents, moisturizing agents, pigments, clays, fillers mineral, mineral colloids, polymers, proteins, pearlescent agents,, waxes, oils such as paraffins, silicones, fatty acids, solid esters of fatty alcohol or fatty acids, gums , the wetting agents.
- Water-soluble dyes such as FD & C Blue 1 (of formula C37H34N2Na20gS3) and fat-soluble dyes such as Sudan Red III or Red Nile have the advantage of coloring one of the formulation intermediates. This coloration makes it possible to control the good mixture of the two formulation intermediates and to enhance the formation of the foam. This coloration is in particular presented in the examples and in FIG. GELIFYING AGENTS OF THE INTERMEDIATE FORMULA CONTAINING THE GAS ACTIVATOR
- the intermediate composition A advantageously containing at least one gas-activating agent preferably contains at least one gelling agent and / or suspending agent.
- Formulation A can contain high amounts of acid and electrolytes.
- the viscosity and the suspensive power of these formulas are often hard to guarantee over time.
- gelling agents and / or suspending agents that are resistant to both electrolytes and acidic pHs that can be used in compositions A according to the invention, mention may be made of ready-to-use mixtures such as polyacrylate -13 & Polyisobutene & Polysorbate 20 sold by Seppic under the name Sepiplus 400®, Acrylamide / Sodium Acryloyldimethyl Taurate Copolymer & Isohexadecane & Polysorbate 80 sold by Seppic under the name Simulgel 600®, polysaccharides with as non-limiting examples the xanthan gum such as Xantural180® sold by Kelco, gellan gum sold under the name Kelcogel® by Kelco, Sclerotium Gum sold under the name Amigel® by Alban Muller industry, guar gum and its derivatives as that Hydroxy
- the gelling agent as described above may be used at preferential concentrations ranging from 0.001% to 15% and, more preferably, ranging from 0.15% to 5% by weight relative to the weight of the intermediate formula A.
- acrylic acid polymers such as Acrylates / C 10-30 Alkyl Acrylate Crosspolymer such as carbomers known as non-electrolyte sensitive, sold under the name Ultrez 20®, Ultrez 10®, Carbopol 1382® or Carbopol ETD2020NF®, AQUA SF1 ® sold by Lubrizol Company, Ammonium Acrylate / Acrylamide Copolymer & Polyisobutene & Polysorbate 20 sold by Seppic under the name Sepiplus 265®, Acrylamide / Sodium Acryloyldimethyl Taurate Copolymer & Isohexadecane & Polysorbate 80 sold by Seppic under the name Simulgel 600® , polysaccharides with, by way of non-limiting examples, xant
- the gelling agent as described above may be used at preferential concentrations ranging from 0.001% to 15% and, more preferably, ranging from 0.15% to 5% by weight relative to the weight of the intermediate formula B.
- optional compounds are optionally used, without this list being limiting, such as a water-miscible polyol. at ambient temperature (25 ° C.), in particular chosen from polyols having in particular from 2 to 20 carbon atoms, preferably having from 2 to 10 carbon atoms, and preferably having from 2 to 6 carbon atoms, such as glycerol glycol derivatives such as propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, dipropylene glycol, diethylene glycol and mixtures thereof, but also sugars (for example glucose, lactose) , polyethylene glycol (PEG) (for example Lutrol E400®), urea, amino acids (for example serine, citrulline, arginine, asparagine, alanine) .
- PEG polyethylene glycol
- Lutrol E400® Lutrol E400®
- a humectant and / or emollient preferred agent mention may be made of glycerin and propylene glycol.
- the humectants may be used, alone or in combination, at preferential concentrations ranging from 0.001% to 30% and, more preferably, ranging from 0.01% to 10% by weight relative to the weight of the total formula.
- chelating agents that may be mentioned as non-limiting examples are ethylene diamine tetraacetic acid (EDTA), diethylene triamine penta-acetic acid (DTPA) and ethylene diamine di (O-hydroxyphenyl) acid.
- EDTA ethylene diamine tetraacetic acid
- DTPA diethylene triamine penta-acetic acid
- O-hydroxyphenyl ethylene diamine di (O-hydroxyphenyl) acid.
- acetic acid) EDDHA
- H EDTA hydroxy-2-ethylene diamine triacetic acid
- ethyldiamine-di O-hydroxy-p-methyl phenyl
- EDDHMA ethylene diamine-di (5-carboxy-2-hydroxyphenyl) acetic acid
- EPDCHA ethylene diamine-di (5-carboxy-2-hydroxyphenyl) acetic acid
- EDTA ethylene diamine tetraacetic acid
- composition according to the invention may contain one or more cosmetic active agents, for example, without limitation, allantoin with anti-irritant properties, Zinc gluconate anti-acne, Dipotassium Glycyrrhizate for these anti-acne properties. inflammatory or still alpha Bisabolol healing, dimethyl isosorbide for its propenetrating properties.
- cosmetic active agents for example, without limitation, allantoin with anti-irritant properties, Zinc gluconate anti-acne, Dipotassium Glycyrrhizate for these anti-acne properties.
- inflammatory or still alpha Bisabolol healing dimethyl isosorbide for its propenetrating properties.
- Fillers and / or particles can be used to stabilize and boost the foam. Some of them have the particular property of being placed at the interface water / air and thus stabilize this interface.
- fillers mention may be made of talc, metal oxides such as zinc oxide, TiO 2 T2000 titanium dioxide sold by Merck under the name Eusolex® T-2000, clays such as laponites, bentones or bentonites but also cellulose ethers such as Methocel® K100 LV marketed by DOW, silicas such as Aerosil® R972 sold by the company EVONI K or SILICE HDK® H 13L sold by WACKER they can be used at concentrations ranging from 0.01% to 10% by weight relative to the weight of the total formula.
- composition according to the invention may also comprise a fatty phase.
- This fatty phase may be present in one and / or the other of intermediate compositions A and B.
- the fatty phase may according to the dosage form of the intermediate formulas represent from 0% to 95% by weight relative to the weight of each formula intermediate.
- the fatty phase of the composition according to the invention may comprise, for example, vegetable, mineral, animal or synthetic oils, silicone oils, and mixtures thereof.
- mineral oil there may be mentioned, for example, paraffin oils of different viscosities such as Primol 352®, Marcol 82®, Marcol 152® sold by the company Esso.
- paraffin oils of different viscosities such as Primol 352®, Marcol 82®, Marcol 152® sold by the company Esso.
- sweet almond oil such as
- lanolin As animal oil or their substitute of vegetable origin, mention may be made of lanolin, squalene, fish oil, with as derivative perhydrosqualene sold under the name Sophiderm® by Sophim.
- synthetic oil mention may be made of an ester such as cetearyl isononanoate such as the product sold under the name Cetiol SN PH® by Cognis France, isononyl isononanoate such as DUB ININ® sold by Stéarine Dubois, diisopropyl adipate such as the product sold under the name Crodamol DA® by Croda, isopropyl palmitate, such as the product sold under the name Crodamol IPP® by Croda, caprylic capric triglyceride such as Miglyol 812® sold by the company Univar.
- silicone oil there may be mentioned a dimethicone such as the product sold under the name Q7-9120 Silicone Fluid® with a viscosity of 20 to 12500 is by the company Dow Corning, a cyclomethicone such as the product sold under the name ST- Cyclomethicone 5NF® also by Dow Corning.
- a dimethicone such as the product sold under the name Q7-9120 Silicone Fluid® with a viscosity of 20 to 12500 is by the company Dow Corning
- a cyclomethicone such as the product sold under the name ST- Cyclomethicone 5NF® also by Dow Corning.
- oils may be present, alone or in combination, at levels ranging from 0.5 to 50% by weight and preferably from 2 to 30% by weight, relative to the weight of the total composition.
- composition according to the invention may also comprise solid fatty substances such as natural or synthetic waxes, fatty acids such as stearic acid, fatty alcohols such as Speziol C18® pharma or Speziol C16® sold by the company. Cognis, and tribehenate type texture agents, such as Compritol 888® sold by the company
- Gattefossé or hydrogenated castor oils such as Cutina HR® sold by Cognis or glyceryl stearate such as GELEOL® sold by Gattefossé or De 9045 Elastomer Blend® sold by Dow Corning.
- These non-liquid fatty substances may be used alone or as a mixture of 0 to 30% by weight relative to the weight of the total formula.
- GELEOL® sold by Gattefossé or De 9045 Elastomer Blend® sold by Dow Corning.
- fatty alcohols of formula CH 3 (CH 2) n OH (n is between 11 and 23) are present at contents greater than 1% by weight relative to the weight of the total formula .
- composition according to the invention may also comprise one or more nonionic emulsifiers.
- hydrophilic emulsifiers of the Glyceryl Stearate (and) PEG-100 Stearate type sold under the name Arlacel 165FL® by the company Uniquema
- Emulium Kappa® and Emulium Delta® sold by Gattefosse Some emulsifiers can be sold in the form of a mixture such as Emulium Kappa® and Emulium Delta® sold by Gattefosse These emulsifiers can be used alone or in combination so that the HLB of the system can be used. oit greater than 12 and preferably greater than 15.
- Such emulsifiers can be used between 0.01% and 30% by weight relative to the weight of the total composition, preferably between 0.1% and 15%, and more preferably between 0.5% and 7%.
- preservatives examples include benzalkonium chloride, bronopol, chlorhexidine, chlorocresol and its derivatives, ethyl alcohol, phenoxyethanol, potassium sorbate, diazolidinyl urea, benzyl alcohol, parabens, sodium benzoate or mixtures thereof.
- Step 1 At a temperature above 60 ° C, add stirring the gelling agents to the main water phase.
- Step 2 With stirring introduce trifarotene in an annex phase
- Step 3 At the same time melt the fat phase at a temperature above 60 ° C.
- This fatty phase is composed of emulsifiers, waxes, emollient oils
- Step 4 At a temperature above 60 ° C make the emulsion by adding the fat phase to the main phase.
- Step 4 Add the annex phase containing trifarotene in the main phase
- Step 5 Cool and add additives such as dye, cosmetic actives, humectants.
- Example A1 the amounts are expressed in relation to the weight of the intermediate formula and not to the weight of the total formula.
- Step 1 ' At a temperature above 60 ° C, add stirring the gelling agents to the main water phase.
- Step 2 Optional: At the same time heat the fatty phase (containing oils, waxes, and surfactants) to a temperature above 60 ° C.
- Step 3 Optional: At a temperature above 60 ° C make the emulsion by adding the fat phase to the main phase.
- Step 4 Add additives such as preservatives or ethanol at a temperature suitable for the additive.
- Step 5 ' Neutralize the mixture.
- Step 6 ' At a temperature below 40 ° C add sodium bicarbonate
- the table below represents the mixtures in a 1: 1 weight ratio of the intermediate compositions A and B described above.
- a cross at the intersection of two formulation intermediates indicates that the mixture has been tested and generated a foam with the desired properties.
- Density formula A5 placebo, that is to say without trifarorene (but with blue dye) 1 .108
- Tables Ia and Ib below summarize the physical stability data of intermediate formulas A 1 and A 2 described in Example 1, containing trifarotene.
- the objective of this study is to evaluate the tolerance of the supports of complete and intermediate formulas on reconstructed human epidermis (RHE, Episkin model) through:
- the tested formulas are:
- An intermediate composition of acid formulation A7 example placebo (that is to say, not containing trifarotene),
- Measurements of MTT according to the current OECD protocol indicate that all formulas tested are non-irritating.
- the IL-1a assay of the complete formula according to the invention after a short time and a long time of exposure shows a lower level of irritation markers after application of the commercial reference.
- Citric acid 3.5% - -
- citric acid / sodium citrate buffer can advantageously be substituted with disodium pyrophosphate and vice versa, as the contents cited by way of example in the table below:
- Table III the values are expressed in weight / weight percentage with respect to the weight of each of the two intermediate formulas
- citric acid / sodium citrate buffer may advantageously be substituted with sodium dihydrogen phosphate monohydrate and vice versa, as the contents cited by way of example in Table IV below:
- Table IV The values are expressed as a weight / weight percentage relative to the weight of each of the two intermediate formulas
- the amount of citric acid is greater than or equal to 1, 4, the amount of foam is optimal when the disodium pyrophosphate is present in the composition according to the following equation:
- Protocol of the study is to evaluate the penetration and distribution of different formulations according to the invention in human skin. Protocol of the study:
- trifarotene is measured in: the unabsorbed fraction, the stratum corneum, the epidermis, the dermis and the receiving liquid.
- This study makes it possible to study the influence of the formulation on the release of the active ingredient and its permeation through the skin.
- the aim is to compare the distribution of trifarotene in the different layers of the skin in the case of the application of a well-known formula and the application of a composition in the form of chemical foam.
- the tested formulas are:
- the scattering cells used are static diffusion cells, based on Franz model diffusion cell, with the following characteristics:
- the receiving compartment is surrounded by a water jacket heated to 37 ° C ⁇ 1 ° C, ensuring a temperature of 32 ° C ⁇ 1 ° C on the surface of the skin.
- the receptor compartment is separated from the donor compartment by the skin membrane, the epidermal face being on the donor side.
- the Receiver compartment containing a magnetic stirring bar was filled with the receiving fluid so as to prevent any formation of air bubbles. During the diffusion time, the receiving fluid was stirred continuously to ensure homogenization
- Skin samples from donors aged 42, 44 and 69 years were mounted on the diffusion cell with PBS as the receiving fluid.
- the average skin thickness was 0.89 ⁇ 0.07 mm with a maximum of 1.39 mm and a minimum of 0.45 mm. Thicknesses of all specimens.
- TEWL trans-epidermal water-insensitive loss
- the present study confirms the obtaining of a foam which remains on the surface of the skin, in order to avoid undesirable effects such as irritation and to obtain a foam adapted to the treatment of acne.
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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FR1559202A FR3041536B1 (en) | 2015-09-29 | 2015-09-29 | NON-RINSEED CHEMICAL FOAM CONTAINING TRIFAROTENE AND USE THEREOF IN THE TREATMENT OF ACNE |
PCT/EP2016/073009 WO2017055292A1 (en) | 2015-09-29 | 2016-09-27 | No-rinse chemical foam containing trifarotene, and use thereof in the treatment of acne |
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EP3355857A1 true EP3355857A1 (en) | 2018-08-08 |
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EP16775630.3A Withdrawn EP3355857A1 (en) | 2015-09-29 | 2016-09-27 | No-rinse chemical foam containing trifarotene, and use thereof in the treatment of acne |
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US (1) | US11020347B2 (en) |
EP (1) | EP3355857A1 (en) |
JP (1) | JP2018529771A (en) |
KR (1) | KR20180057714A (en) |
CN (1) | CN108289839A (en) |
AU (1) | AU2016330787B2 (en) |
FR (1) | FR3041536B1 (en) |
MX (1) | MX2018003643A (en) |
WO (1) | WO2017055292A1 (en) |
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CN110785161B (en) | 2017-06-23 | 2023-06-20 | 宝洁公司 | Compositions and methods for improving the appearance of skin |
CA3102288A1 (en) | 2018-07-03 | 2020-01-09 | The Procter & Gamble Company | Method of treating a skin condition |
FR3095241B1 (en) * | 2019-04-17 | 2021-06-25 | Safran Aircraft Engines | Turbojet nacelle air inlet comprising a circulation pipe to promote a thrust reversal phase |
WO2021247496A1 (en) | 2020-06-01 | 2021-12-09 | The Procter & Gamble Company | Method of improving penetration of a vitamin b3 compound into skin |
US10959933B1 (en) | 2020-06-01 | 2021-03-30 | The Procter & Gamble Company | Low pH skin care composition and methods of using the same |
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2015
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2016
- 2016-09-27 US US15/763,685 patent/US11020347B2/en active Active
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- 2016-09-27 KR KR1020187012170A patent/KR20180057714A/en not_active Application Discontinuation
- 2016-09-27 MX MX2018003643A patent/MX2018003643A/en unknown
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CN108289839A (en) | 2018-07-17 |
FR3041536A1 (en) | 2017-03-31 |
MX2018003643A (en) | 2018-04-30 |
US20180280297A1 (en) | 2018-10-04 |
FR3041536B1 (en) | 2018-11-30 |
AU2016330787A1 (en) | 2018-05-17 |
KR20180057714A (en) | 2018-05-30 |
JP2018529771A (en) | 2018-10-11 |
AU2016330787B2 (en) | 2022-04-21 |
WO2017055292A1 (en) | 2017-04-06 |
US11020347B2 (en) | 2021-06-01 |
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