AU2002364437B2 - Gel comprising at least a retinoid and benzoyl peroxide - Google Patents
Gel comprising at least a retinoid and benzoyl peroxide Download PDFInfo
- Publication number
- AU2002364437B2 AU2002364437B2 AU2002364437A AU2002364437A AU2002364437B2 AU 2002364437 B2 AU2002364437 B2 AU 2002364437B2 AU 2002364437 A AU2002364437 A AU 2002364437A AU 2002364437 A AU2002364437 A AU 2002364437A AU 2002364437 B2 AU2002364437 B2 AU 2002364437B2
- Authority
- AU
- Australia
- Prior art keywords
- composition according
- benzoyl peroxide
- retinoid
- stirring
- composition
- 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.)
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- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 title claims description 87
- 239000004342 Benzoyl peroxide Substances 0.000 title claims description 86
- 235000019400 benzoyl peroxide Nutrition 0.000 title claims description 86
- 150000004492 retinoid derivatives Chemical class 0.000 title claims description 34
- 239000000203 mixture Substances 0.000 claims description 126
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 64
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 39
- 238000003756 stirring Methods 0.000 claims description 33
- 239000012071 phase Substances 0.000 claims description 23
- 239000003349 gelling agent Substances 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 206010000496 acne Diseases 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 18
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 229960002916 adapalene Drugs 0.000 claims description 16
- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
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- 230000000149 penetrating effect Effects 0.000 claims description 13
- BANXPJUEBPWEOT-UHFFFAOYSA-N 2-methyl-Pentadecane Chemical compound CCCCCCCCCCCCCC(C)C BANXPJUEBPWEOT-UHFFFAOYSA-N 0.000 claims description 12
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 12
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- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 10
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- KUVMKLCGXIYSNH-UHFFFAOYSA-N isopentadecane Natural products CCCCCCCCCCCCC(C)C KUVMKLCGXIYSNH-UHFFFAOYSA-N 0.000 claims description 6
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
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- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 3
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- FWFUWXVFYKCSQA-UHFFFAOYSA-M sodium;2-methyl-2-(prop-2-enoylamino)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(C)(C)NC(=O)C=C FWFUWXVFYKCSQA-UHFFFAOYSA-M 0.000 description 3
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- DWHIUNMOTRUVPG-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCO DWHIUNMOTRUVPG-UHFFFAOYSA-N 0.000 description 2
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- 150000003408 sphingolipids Chemical class 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 201000004647 tinea pedis Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
-
- 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
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
-
- 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
- A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
-
- 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
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61P17/16—Emollients or protectives, e.g. against radiation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Description
WO 03/055472 PCT/FR02/04233 GEL COMPRISING AT LEAST ONE RETINOID AND BENZOYL
PEROXIDE
The invention relates to a composition comprising, in a physiologically acceptable medium, at least one retinoid, dispersed benzoyl peroxide and at least one pH-independent gelling agent.
The use of several classes of active principles is a therapeutic tool that is frequently employed, especially for treating dermatological disorders.
Specifically, it is known practice in the treatment of dermatitis to use corticosteroids such as, for example, hydrocortisone, miconazole or betamethasone valerate, antihistamines mizolastine) and/or keratolytic agents, for instance salicylic acid. Various antifungal agents, for instance allylamine derivatives, triazoles, antibacterial agents or antimicrobial agents such as, for example, antibiotics, quinolones and imidazoles, are also conventionally combined in the treatment of dermatological diseases. Peroxides, D vitamins and retinoids are also described for the topical treatment of various pathologies associated with the skin or mucous membranes, in particular acne.
The combination of several local treatments (antibiotics, retinoids, peroxides and zinc) is also used in dermatology to increase the efficacy of the active principles and to reduce their toxicity (Cunliffe J. Dermatol. Treat., 2000, 11 (suppl2), pp. 13-14) The multiple application of various dermatological products may be relatively burdensome and restricting for the patient.
The value in seeking to obtain a novel treatment that is effective on dermatological complaints in a stable composition offering good cosmetic utility, allowing a single application and a utilization that the patient finds pleasant, may thus be appreciated.
Among this panoply of treatments proposed to a person skilled in the art, there was nothing to encourage him to combine, in the same composition, benzoyl peroxide and a retinoid.
However; formulating such a composition poses several problems.
Firstly, the efficacy of benzoyl peroxide is associated with its decomposition when it is placed in contact with the skin. Specifically, it is the oxidizing properties of the free radicals produced during this decomposition that lead to the desired effect. Thus, in order to maintain the optimum efficacy of benzoyl peroxide, it is important to prevent its decomposition before use, i.e. during storage.
Benzoyl peroxide is an unstable chemical compound, making it difficult to formulate it in finished products.
The solubility and stability of benzoyl peroxide were studied by Chellquist et al. in ethanol, propylene glycol and various mixtures of polyethylene glycol 400 (PEG 400) and water (Chellquist E.M. and Gorman Pharm. Res., 1992, Vol 9: 1341-1346).
Benzoyl peroxide is particularly soluble in PEG400 and ethanol, as shown in the following table: Solvent Benzoyl peroxide solubility (mg/g) PEG 400 39.6 Ethanol 17.9 Propylene glycol 2.95 Propylene glycol/water (75:25) 0.36 Glycerol 0.15 Water 0.000155 The said document moreover states that the stability of benzoyl peroxide is greatly influenced by the chemical composition of the formulation and by storage temperature. Benzoyl peroxide is extremely reactive and degrades in solution at low temperature on account of the instability of its peroxide bond.
The authors thus state that benzoyl peroxide in solution degrades more or less quickly in all the solvents studied as a function of the type of solvent and of its concentration.
The degradation times for benzoyl peroxide in PEG 400 mg/g), in ethanol and in propylene glycol are, respectively, 1.4, 29 and 53 days at 40 0
C.
Such a degradation does not allow the preparation of a product intended for sale.
It is moreover known that benzoyl peroxide is more stable in water and propylene glycol when it is in suspension in dispersed form), since it is not degraded after storage for 90 days in these solvents.
Thus, in order to limit the problem of rapid instability of benzoyl peroxide in solution, it has been found to be advantageous to formulate benzoyl peroxide in dispersed form. However, this type of formulation is not entirely satisfactory since degradation of the benzoyl peroxide in the finished product is still observed.
Another difficulty to be overcome in preparation of a composition comprising both benzoyl peroxide and a retinoid is that most retinoids are particularly sensitive to natural oxidation, to visible light and to ultraviolet light, and, since benzoyl peroxide is a strong oxidizing agent, the chemical compatibility of these compounds in the same formulation poses numerous problems in terms of physical and chemical stability.
A study of the stability of two retinoids was performed by combining two commercial products, one containing a retinoid (tretinoin or adapalene) and the second based on benzoyl peroxide Martin et al., Br.J.Dermatol. (1998) 139, (suppl. 52), 8-11).
The presence of the formulation based on benzoyl peroxide results in very rapid degradation of the oxidation-sensitive retinoids: it is measured that of the tretinoin is degraded in 2 hours, and 95% in 24 hours. In the composition in which the retinoid is adapalene, no degradation of the adapalene was measured over 24 hours. This study confirms that benzoyl peroxide becomes degraded and degrades oxidationsensitive retinoids over time, gradually releasing benzoic acid into the finished products.
In contrast, no indication is given regarding the physical stability of the two compositions placed in contact, or regarding the therapeutic activity that may finally be obtained by combining the two active principles in the same composition.
There was no encouragement for combining these two active agents in order to obtain a stable composition of gel type, given that it was commonly known that the presence of benzoyl peroxide chemically and physically destabilized this type of composition.
Now, it is clear that the degradation of benzoyl peroxide and retinoids is not desirable since it impairs the efficacy of the composition containing them.
Moreover, a finished product, in particular when it is a pharmaceutical or cosmetic composition, must maintain throughout its shelf life precise physicochemical criteria for ensuring its pharmaceutical or cosmetic quality, respectively. Among these criteria, it is necessary for the rheological properties to be maintained. They define the behaviour and texture of the composition during application, but also the active principle's release properties [1998 SFSTP Commission Report] and the homogeneity of the product when the active principles are present therein in dispersed form.
In particular, the formulation of benzoyl peroxide and of a retinoid in gel form is advantageous for topical treatments, such as the treatment of acne, since it especially avoids a greasy feel being left on the skin.
Another difficulty to be overcome in preparing a composition especially comprising benzoyl peroxide, when it is in gel form, is that the gelling agents are destabilized by the benzoic acid released during the degradation of the benzoyl peroxide.
Specifically, the thickeners most commonly used for formulating these compositions with benzoyl peroxide are acrylic acid polymers (Carbomer) and celluloses alone or combined with silicates.
Now, the use of carbomers in compositions of aqueous gel type does not give good results in terms of chemical stability of the benzoyl peroxide or in terms of rheological stability. As described by Bollinger (Bollinger, Journal of Pharmaceutical Science, 1977, vol it has been observed that from 5% to benzoyl peroxide is lost after 2 months at 40 0
C
depending on the neutralizer of the carbomer used.
Furthermore, the release of benzoic acid results in depolymerization of the carbomers, leading to a drop in viscosity which may result in phase separation.
In other gels consisting of a mixture of hydroxypropylcellulose and aluminium magnesium silicate, a drop in viscosity over time is also observed, resulting in sedimentation of the active agents as a suspension and heterogeneity of the dispersion in the finished product.
This instability of benzoyl peroxide gels impairs their efficacy and their cosmetic utility.
There is thus still a need for a physically stable gelled composition containing benzoyl peroxide and a retinoin.
The Applicant has now, surprisingly, produced a composition that satisfies this need, which comprises dispersed, free or encapsulated benzoyl peroxide, at least one retinoid and a pH-independent gelling agent with good physical stability, i.e. not showing a drop in viscosity over time and at temperatures of between 4 and 40 0 C, and maintaining good chemical stability of 00 8 00 the two active agents (benzoyl peroxide and retinoid), i.e. no degradation of the active agents over time and at temperature of between 4 and 40 0 C is observed.
The Applicant has also discovered, surprisingly, that total dispersion of the active principles can be obtained c by following a particular preparation process. This 0 preparation process performed without heat makes it CI possible to obtain an optimum particle size and uniform dispersion of the two active agents in the composition, while at the same time ensuring the physical stability of the product.
The invention thus relates to a composition comprising, in a physiologically acceptable medium, at least one retinoid, dispersed benzoyl peroxide and at least one pH-independent gelling agent.
More specifically, the present invention provides composition comprising, in a physiologically acceptable medium, at least one retinoid, dispersed benzoyl peroxide and at least one pH-independent gelling agent, said pH-independent gelling agent being selected from the group consisting of the polyacrylamide family, the family of acrylic polymers coupled to hydrophobic chains, the family of modified starches and mixtures thereof.
The composition according to the invention is preferably in the form of an aqueous gel.
N:MeboumelCases\Patentl53OOD-53999kP53O25 AU\Specis\53025AU Speificafion 2008-7-l.doc 10107/08 00 8A 00 The term "aqueous gel" means a composition containing, in an aqueous phase, a viscoelastic mass formed from colloidal suspensions (gelling agent).
The expression "pH-independent gelling agent" means a gelling agent capable of giving the composition a viscosity that is sufficient to keep the retinoid and the O benzoyl peroxide in suspension, even under the influence C1 of a variation in pH caused by the release of benzoic acid by the benzoyl peroxide.
Non-limiting examples that may be mentioned N:\MelboumeCases\Patentl53000-53999\P53025.AU\SpecisP53025 AU Specfication 2008-7.1.doc 10/07/08 include the gelling agents of the polyacrylamide family, such as the mixture of sodium acryloyldimethyltaurate copolymer/isohexadecane/polysorbate 80 sold under the name Simulgel 600 by the company SEPPIC, the mixture of polyacrylamide/isoparaffin C13-14/laureth-7 such as, for example, the product sold under the name Sepigel 305 by the company SEPPIC, the family of acrylic polymers coupled to hydrophobic chains, such as the PEG-150/decyl/SMDI copolymer sold under the name Aculyn 44 (polycondensate comprising at least, as components, a polyethylene glycol containing 150 or 180 mol of ethylene oxide, decyl alcohol and methylenebis(4cyclohexyl isocyanate) (SMDI), at 35% by weight in a mixture of propylene glycol and water the family of modified starches, such as the modified potato starch sold under the name Structure Solanace, or mixtures thereof.
The preferred gelling agents are derived from the polyacrylamide family, such as Simulgel 600 or Sepigel 305, or mixtures thereof.
The gelling agent as described above may be used in preferential concentrations ranging from 0.1% to 15% and more preferably ranging from 0.5% to The composition according to the invention contains at least one retinoid.
The term "retinoid" means any compound that binds to the RAR and/or RXR receptors.
Preferably, the retinoid is a compound chosen from the family of benzonaphthalene retinoids as described in patent application EP 0 199 636. In particular, adapalene and also precursors and/or derivatives thereof will be preferred.
The expression "retinoid precursors" means the immediate biological precursors or substrates thereof, and also the chemical precursors thereof.
.0 The expression "retinoid derivative" means both their metabolic derivatives and their chemical derivatives.
Other retinoids may be chosen from those described in the applications: US EP 0 232 199, EP EP 0 359 621, EP EP 0 584 191, EP EP 0 661 258, EP EP 0 679 630, EP EP 0 728 739, EP EP 0 776 881, EP EP 0 816 352, EP EP 0 915 823, EP EP 0 952 974, EP following patents or patent 4,666,941, 260 409 514 658 708 732 823 826 882 162, 728, 264, 553, 100, 328, 903, 657, 033, US 4,581,380, EP 0 292 348, EP 0 409 740, EP 0 514 269, EP 0 679 628, EP 0 709 382, EP 0 740 937, EP 0 832 057, EP 0 874 626, EP 0 850 909, EP 0 947 496, EP 0 210 929, EP 0 325 540, EP 0 552 282, EP 0 661 260, EP 0 679 631, EP 0 722 928, EP 0 776 885, EP 0 832 081, EP 0 934 295, EP 0 879 814, WO 98/56783, 0 905 118, WO 99/10322, WO 99/50239, WO 99/65872.
Needless to say, the amount of the two active agents, benzoyl peroxide and retinoid, in the composition according to the invention will depend on the combination chosen and thus particularly on the retinoid under consideration and the quality of the desired treatment.
The preferred retinoid concentrations are between 0.0001% and 20% by weight relative to the total weight of the composition.
Benzoyl peroxide may also be used in free form or in an encapsulated form in a form adsorbed onto, or absorbed in, any porous support. It may be, for example, benzoyl peroxide encapsulated in a polymer system consisting of porous microspheres, such as, for example, microsponges sold under the name Microsponges P009A Benzoyl peroxide by the company Advanced Polymer System.
To give an order of magnitude, the composition according to the invention advantageously comprises between 0.0001% and 20% by weight of benzoyl peroxide and between 0.0001% and 20% by weight of retinoid relative to the total weight of the composition, and preferably, respectively, between 0.025% and 10% by weight of benzoyl peroxide and between 0.001% and 10% by weight of retinoid relative to the total weight of the composition.
For example, in compositions for treating acne, the benzoyl peroxide is preferably used at concentrations ranging from 2% to 10% by weight and more particularly from 2.5% to 5% by weight, relative to the total weight of the composition. As regards the retinoid, it is used in this type of composition at concentrations generally ranging from 0.05% to 1% by weight relative to the total weight of the composition.
Advantageously, the particle size of the retinoid and of the benzoyl peroxide is such that at least 80% in numerical terms of the particles, and preferably at least 90% in numerical terms of the particles, have a diameter of less than 25 pm and at least 99% in numerical terms of the particles have a diameter of less than 100 pm.
According to the invention, the gel containing benzoyl peroxide and a retinoid advantageously comprises at least water and may also comprise a pro-penetrating agent and/or a liquid wetting surfactant.
The compositions of the invention may contain one or more pro-penetrating agents in preferential concentrations ranging from 0 to 20% and more preferably ranging from 2% to 6% by weight, relative to the total weight of the composition. They should generally not dissolve the active agents at the percentage used, should not cause any exothermic reactions harmful to the benzoyl peroxide, should aid in the satisfactory dispersion of the active agents, and should have antifoaming properties. Among the propenetrating agents preferably used, without this list being limiting, are compounds such as propylene glycol, dipropylene glycol, propylene glycol dipelargonate, lauroglycol and ethoxydiglycol.
The pro-penetrating agent that is particularly preferred is propylene glycol.
Advantageously, the compositions according to the invention may also contain one or more liquid wetting surfactants in preferential concentrations ranging from 0 to 10% and more preferably ranging from 0.1% to The wetting power is the tendency of a liquid to spread over a surface.
They are preferably surfactants with an HLB (Hydrophilic-Lipophilic Balance) value from 7 to 9, or nonionic surfactants such as polyoxyethylenated and/or polyoxypropylenated copolymers. They should be liquid so as to be readily incorporated into the composition without it being necessary to heat them.
Among the wetting agents that are preferably used, without this list being limiting, are compounds of the Poloxamer family and more particularly Poloxamer 124 and/or Poloxamer 182.
The liquid wetting surfactant that is particularly preferred is Poloxamer 124.
The composition may also comprise any additive usually used in the cosmetics or pharmaceutical field, such as sequestering agents, antioxidants, sunscreens, preserving agents, fillers, electrolytes, humectants, colorants, common mineral or organic acids or bases, fragrances, essential oils, cosmetic active agents, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds such as DHA, and calmants and protective agents for the skin such as allantoin. Needless to say, a person skilled in the art will take care to select this or these optional additional compound(s), and/or the amount thereof, such that the advantageous properties of the composition according to the invention are not, or are not substantially, adversely affected.
These additives may be present in the composition in a proportion of from 0 to 20% by weight relative to the total weight of the composition.
Examples of sequestering agents that may be mentioned include ethylenediaminetetraacetic acid (EDTA), and also derivatives or salts thereof, dihydroxyethylglycine, citric acid and tartaric acid, or mixtures thereof.
Examples of preserving agents that may be mentioned include benzalkonium chloride, phenoxyethanol, benzyl alcohol, diazolidinylurea and parabens, or mixtures thereof.
Examples of humectants that may be mentioned include glycerol and sorbitol.
In particular, the invention also relates to a pharmaceutical or cosmetic composition for topical application to the skin, the integuments or mucous membranes, in the form of an aqueous gel, characterized in that it contains, in a physiologically acceptable medium that is compatible with topical application to the skin, the integuments or mucous membranes, an active phase comprising (expressed in percentages by weight): 0 to 90%, preferably 5% to 25% and especially 10% to of water; 0 to 10%, preferably 0 to 2% and especially 0 to of liquid wetting surfactant; 0 to 20%, preferably 0 to 10% and especially 2% to of pro-penetrating agent; 0.0001% to 20% and preferably 0.025% to 10%, of benzoyl peroxide; 0.0001% to 20% and preferably 0.001% to 10%, of retinoid; and an aqueous phase comprising a pH-independent gelling agent, and water.
The aqueous phase of the emulsion according to the invention may comprise water, a floral water such as cornflower water, or natural mineral or spring water chosen, for example, from eau de Vittel, waters of the Vichy basin, eau d'Uriage, eau de la Roche Posay, eau de la Bourboule, eau d'Enghien-les-Bains, eau de Saint Gervais-les-Bains, eau de N6ris-les-Bains, eau d'Allevard-les-Bains, eau de Digne, eau de Maizieres, eau de Neyrac-les-Bains, eau de Lons-le- Saunier, les Eaux Bonnes, eau de Rochefort, eau de Saint Christau, eau des Fumades, eau de Tercis-lesbains, eau d'Avene or eau d'Aix les Bains.
The said aqueous phase may be present in a content of between 10% and 90% by weight and preferably between 20% and 80% by weight, relative to the total weight of the composition.
A composition that is preferred according to the invention comprises in water: 2.50% benzoyl peroxide, 0.10% adapalene, 0.10% disodium EDTA, 4.00% glycerol, 4.00% propylene glycol, 0.05% sodium docusate, 0.20% Poloxamer 124, 4.00% sodium acryloyldimethyltaurate copolymer isohexadecane polysorbate sodium hydroxide, qs pH A subject of the present invention is also the composition as described above, as a medicinal product.
The invention also relates to the use of the novel composition as described above in cosmetics and dermatology.
A subject of the invention is also a process for preparing a composition of aqueous gel type, comprising the production of an active phase, of an aqueous phase and of a gelling phase, at room temperature i.e. between 20 and 25°C, and successively comprising the following steps: a) the preparation of an aqueous phase comprising water and optionally a chelating agent and/or a propenetrating agent and/or a humectant; b) the preparation of an active phase comprising the mixture in water of the retinoid, of benzoyl peroxide and, optionally, of a liquid wetting surfactant and/or of a pro-penetrating agent, with stirring; c) the introduction of the active phase into the aqueous phase, with stirring; and d) the introduction of the gelling agent into the mixture obtained from step with stirring.
In one embodiment, the process for preparing the aqueous gel composition, comprising the production of an active phase, of an aqueous phase and of a gelling phase, at room temperature, successively comprises the following steps: a) the preparation of an aqueous phase comprising water and optionally a chelating agent and/or a propenetrating agent and/or a humectant; b) the preparation of two active agents, one comprising the mixture in water of the retinoid, the other comprising the mixture in water of benzoyl peroxide and, optionally, of a liquid wetting surfactant and/or of a pro-penetrating agent, with stirring; c) the introduction of the active phases into the aqueous phase, with stirring; and d) the introduction of the gelling agent into the mixture obtained from step with stirring.
The aqueous gel prepared according to one of these procedures was found to provide many advantages over the preparation of other already-known aqueous gels, especially since it is simpler, and, since the incorporation of the gelling agent into the end of the process makes it possible to obtain better dispersion of the particles by enclosure, these gels may also be film-forming and may thus limit perspiration. At least in numerical terms of the particles and preferably at least 90% in numerical terms of the particles have a diameter of less than 25 pm and at least 99% in numerical terms of the particles have a diameter of less than 100 pm in the composition.
On account of the keratolytic, bactericidal and antiinflammatory activity of benzoyl peroxide and the pronounced activity of retinoids in the fields of cell differentiation and proliferation, the compositions of the invention are particularly suitable in the following therapeutic fields: 1) for treating dermatological complaints associated with a keratinization disorder relating to differentiation and proliferation, especially for treating common acne, comedones, polymorphonuclear leukocytes, acne rosacea, nodulocystic acne, acne conglobata, senile acne, secondary acnes such as solar acne, medication-related acne or occupational acne, and suppurative hydradenitis, 2) for treating other types of keratinization disorder, especially ichtyosis, ichtyosiform conditions, Darier's disease, palmoplantar keratoderma, leukoplakia and leukoplakiform conditions, and cutaneous or mucous (buccal) lichen, 3) for treating other dermatological complaints associated with a keratinization disorder with an inflammatory and/or immunoallergic component, and especially all forms of psoriasis, whether cutaneous, mucous or ungual psoriasis, and even psoriatic rheumatism, or cutaneous atopy, such as eczema, or respiratory atopy, or even gingival hypertrophy; the compounds may also be used in certain inflammatory complaints not exhibiting a keratinization disorder, such as folliculitis, 4) for treating all dermal or epidermal proliferations, whether benign or malignant, and whether of viral origin or otherwise, such as common warts, flat warts, molluscum contagiosum and verruciform epidermodysplasia, oral or florid papillomatoses and proliferations that may be induced by ultraviolet radiation, especially in the case of actinic keratosis, 5) for repairing or combating ageing of the skin, whether photoinduced or chronological ageing, or for reducing pigmentation, or any pathology associated with chronological or actinic ageing, 6) for preventively or curatively treating cicatrization disorders and skin ulcers, for preventing or repairing stretch marks, or for promoting cicatrization, 7) for combating sebaceous function disorders such as the hyperseborrhoea of acne or simple seborrhoea, 8) in the treatment of any complaint of fungal origin on the skin, such as tinea pedis and tinea versicolor, 9) in the treatment of dermatological complaints with an immunological component, in the treatment of skin disorders caused by exposure to UV rays, and 11) in the treatment of dermatological complaints associated with inflammation or infection of the tissues surrounding the hair follicles, caused especially by microbial colonization or infection, especially impetigo, seborrhoeic dermatitis, folliculitis or sycosis barbae, or involving any other bacterial or fungal agent.
The compositions according to the invention are particularly suitable for preventively or curatively treating common acne.
A subject of the invention also relates to the manufacture of a pharmaceutical preparation for preventing or treating dermatological complaints associated with cell differentiation and/or proliferation disorders and/or keratinization disorders, and also to the manufacture of a pharmaceutical preparation for preventing or treating common acne.
The compositions according to the invention also find an application in cosmetics, in particular for treating acne-prone skin, for regrowth of the hair, for preventing hair loss, for combating the greasy appearance of the skin or the hair, in protecting against the harmful effects of sunlight or in the treatment of physiologically dry skin, or for preventing and/or combating photoinduced or chronological ageing.
The compositions according to the invention also find an application in body and hair hygiene.
The present invention thus relates also to the cosmetic use of a composition according to the invention for treating acne-prone skin, for regrowth of the hair or for preventing hair loss, for combating the greasy appearance of the skin or the hair, in protecting against harmful effects of sunlight or in treating physiologically dry skin, or for preventing and/or controlling photoinduced or chronological ageing.
The formulation examples below illustrate the compositions according to the invention without, however, limiting its scope. Examples of processes for preparing the compositions according to the invention, mentioned in a non-limiting manner, and also examples illustrating the physical and chemical stability of the compositions, are also described.
I. FORMULATION EXAMPLES In the compositions below (Examples 1 to the proportions of the various constituents are expressed as percentages by weight relative to the total weight of the composition.
Example 1: Phase Components Active BENZOYL PEROXIDE 5.00% ADAPALENE 0.10% DIPROPYLENE GLYCOL 4.00% PURIFIED WATER POLOXAMER 182 0.20% Aqueous PURIFIED WATER qs 100% SILICA 0.02% GLYCEROL 2.00% MICROSPONGES 4.00% Gelling POLYACRYLAMIDE (and) C13-14 3.50% ISOPARAFFIN (and) LAURETH-7 Example 2: Phase Components Active BENZOYL PEROXIDE ADAPALENE 0.10% PURIFIED WATER 10.00% PROPYLENE GLYCOL 2.00% POLOXAMER 124 0.20% Aqueous PURIFIED WATER qs 100% DISODIUM EDTA 0.10% GLYCEROL 4.00% PROPYLENE GLYCOL 2.00% SODIUM DOCUSATE 0.05% Gelling SODIUM ACRYLOYLDIMETHYLTAURATE 4.00% COPOLYMER ISOHEXADECANE POLYSORBATE Example 3: Phase Components Active BENZOYL PEROXIDE 2.50% ADAPALENE 0.10% PURIFIED WATER 10.00% PROPYLENE GLYCOL 2.00% POLOXAMER 124 0.20% Aqueous PURIFIED WATER qs 100% DISODIUM EDTA 0.10% GLYCEROL 4.00% PROPYLENE GLYCOL 2.00% SODIUM DOCUSATE 0.05% Gelling SODIUM ACRYLOYLDIMETHYLTAURATE 4.00% COPOLYMER ISOHEXADECANE POLYSORBATE pH modifier SODIUM HYDROXIDE qs pH 5.00 Example 4: Phase Components Active BENZOYL PEROXIDE 5.00% ADAPALENE 0.10% PURIFIED WATER 10.00% PROPYLENE GLYCOL 2.00% POLOXAMER 124 0.20% Aqueous PURIFIED WATER qs 100% DISODIUM EDTA 0.10% GLYCEROL 4.00% PROPYLENE GLYCOL 2.00% SODIUM C14-16 OLEFIN SULFONATE 0.05% Gelling PEG-150/decyl/SMDI copolymer 3.50% Example Phase Components Active 1 BENZOYL PEROXIDE 2.50% PURIFIED WATER 20.00% PROPYLENE -GLYCOL 1.00% POLOXAMER 124 0.10% Phase ADAPALENE 0.10% Active 2 PROPYLENE GLYCOL 1.00% POLOXAMER 124 0.10% Aqueous PURIFIED WATER qs 100% DISODIUM EDTA 0.10% GLYCEROL 4.00% PROPYLENE GLYCOL 2.00% SODIUM DOCUSATE 0.05% Gelling SODIUM ACRYLOYLDIMETHYLTAURATE 4.00% COPOLYMER ISOHEXADECANE POLYSORBATE pH modifier SODIUM HYDROXIDE qs pH 5.00 II. EXAMPLES OF A PREPARATION PROCESS Example 6: The examples of a preparation process are given in a non-limiting manner.
The preparation presented is that of the composition that is the subject of Example 3: PROCEDURE PARAMETERS Introduce the following into TO: RT °C beaker (Phase STIRRER: Rayneri purified water PADDLE: deflocculating disodium EDTA STIRRING: 350 rpm glycerol TIME: 10 min Introduce the following into a TO: RT °C related beaker: STIRRER: stirring plate propylene glycol PADDLE: magnetic bar sodium docusate TURBOMIXER: N.A.
Place under magnetic stirring TIME: 45 min until the sodium docusate is fully dissolved Active phase: Introduce the T: RT cold water bath following into a related beaker ST STIRRER: disperser of suitable size: PADDLE: Polytron propylene glycol (PG) STIRRING: 9 000 rpm STIRRING: 9 000 rpm Poloxamer 124 TIME: 30 m TIME: 30 min purified water benzoyl peroxide adapalene Stir using a Polytron stirrer until the active agents are fully dispersed, in a bath of cold water to avoid overheating of the active agents.
1 When the mixture of sodium docusate PG is fully dissolved, incorporate it into Phase 1.
Next, add the active phase.
Stir with a Rayneri stirrer until a homogeneous mixture is obtained.
RT °C STIRRER: Rayneri PADDLE: deflocculating STIRRING: 400-500 rpm TIME: 20 min Finally, add the following: Simulgel 600 Stir with a Rayneri stirrer for the time required for good homogeneity of the finished product.
RT °C STIRRER: Rayneri PADDLE: deflocculating STIRRING: 1 000-1 200 rpm TIME: 25 min Neutralisation: Adjust the pH to 5.00 0.3 with: sodium hydroxide, qs RT °C STIRRER: Rayneri PADDLE: deflocculating STIRRING: 1 000-1 200 rpm TIME: 25 min The preparation given is that of the composition that is the subject of Example PROCEDURE PARAMETERS Introduce the following into a TO: RT °C beaker: STIRRER: Rayneri purified water PADDLE: deflocculating disodium EDTA STIRRING: 350 rpm sodium docusate TIME: 50 min propylene glycol Place under magnetic stirring until the sodium docusate is fully dissolved Next, introduce the following: glycerol RT °C STIRRER: stirring plate PADDLE: deflocculating STIRRING: 350 rpm TIME: 5 min Active phase 1: Introduce the following into a related beaker of suitable size: propylene glycol (PG) Poloxamer 124 purified water benzoyl peroxide Stir until the active agent is fully dispersed, in a cold water bath to avoid overheating.
RT cold water bath PADDLE: Ultra-Turrax STIRRING: 13 500 rpm TIME: 30 min Active phase 2: Introduce the following into a related beaker of suitable size: propylene glycol (PG) Poloxamer 124 adapalene.
RT cold water bath PADDLE: Ultra-Turrax STIRRING: 9 500 rpm TIME: 15 min Incorporate the active phase 2 into the aqueous phase.
Next, add the active phase 1.
Stir using a Rayneri stirrer until a homogeneous mixture is obtained.
TO: RT °C STIRRER: Rayneri PADDLE: deflocculating STIRRING: 300 rpm TIME: 20 min Finally, add the following: TO: RT °C Simulgel 600 STIRRER: Rayneri Stir using a Rayneri stirrer for PADDLE: deflocculating the time required for good STIRRING: 680 rpm homogeneity of the finished TIME: 35 min product.
Neutralization: Adjust the pH to RT °C 5.00 0.3 with: STIRRER: Rayneri sodium hydroxide, qs PADDLE: deflocculating STIRRING: 680 rpm TIME: 25 min III. STABILITY STUDY Example 6: Physical stability of the composition by measuring the flow threshold (in Pa.s 1 The tests performed are viscosity measurements for plotting curves known as rheograms, which make it possible, for a given rate gradient y, to measure a shear stress T, and for a given shear stress T, to measure a rate gradient y ("Initiation a la rheologie" [Introduction to rheology] Gouarraze Grossiord 1991; "La viscosit6 et sa mesure dans les pharmacopees" [Viscosity and its measurement in pharmacopoeias]; L. Molle, Journal Pharma Belg. 1975, 5-6, 597-619).
The term "yield value" means the force required (minimum shear stress) to overcome the cohesion forces of Van der Waals type and to bring about flow.
The yield value (tO) is extrapolated either visually (y-axis at the origin of the rheograms) or by calculation (application of mathematical models).
Composition of the gels used: Aqueous gel based on carbomer Constituents PURIFIED WATER qs 100% DISODIUM EDTA 0.10 SODIUM DOCUSATE 0.05 SILICA (AEROSIL 200) 0.02 CARBOMER (CARBOPOL 980) 0.85 GLYCEROL 4.00 PROPYLENE GLYCOL 4.00 POLOXAMER 124 0.20 BENZOYL PEROXIDE MICROSPONGES qs 2.5% BPO ADAPALENE 0.10 SODIUM HYDROXIDE 2.00 qs pH Aqueous gel based on hydroxypropylcellulose Constituents PURIFIED WATER qs 100% DISODIUM EDTA 0.10 SILICA (AEROSIL 200) 0.02 GLYCEROL 4.00 CLAY (VEEGUM K) 2.00 XANTHAN GUM (KELTROL T) 0.50 HYDROXYPROPYLCELLULOSE (NATROSOL HHX) 1.50 PROPYLENE GLYCOL 4.00 SODIUM DOCUSATE 0.05 POLOXAMER 124 0.20 BENZOYL PEROXIDE MICROSPONGES qs 2.5% BPO ADAPALENE 0.10 Example 2 in Aqueous gel Aqueous gel based accordance based on on hydroxypropylwith the carbomer cellulose and invention aluminium magnesium silicate Temperature RT T40 0 C RT T40"C RT T initial 137 111 170 T 1 month 139 137 135 111 183 93 T 2 months 147 121 158 T 3 months 149 127 100 76 147 34 RT: room temperature 0 C: storage at 40 0
C
The yield value of the composition according to the invention is stable over time and with temperature, unlike the other two examples of aqueous gel, whose viscosity falls rapidly over time, both at room temperature and at 40 0 C. These results demonstrate the very good physical stability of the composition according to the invention over time, unlike the standard compositions of aqueous gels.
Example 7: Stability of benzoyl peroxide over time and as a function of the storage temperature by measuring the amount of benzoyl peroxide in the composition (in percentages) The percentages of benzoyl peroxide (BPO) presented in the table below were obtained by measuring the benzoyl peroxide concentration by iodometry.
A suitable amount of composition is first dissolved in purified water and then in acetonitrile, and subjected to the action of a potassium iodide solution.
When the potassium iodide is added, a colour change from white to brown takes place, indicating the presence of benzoyl peroxide in the composition.
The iodine released is titrated using 0.1N sodium thiosulphate solution: 12 2 Na 2
S
2 0 3 2 Nal Na 2 S40 6 The percentages of benzoyl peroxide given in the table below correspond to the percentage of benzoyl peroxide measured in the product relative to the theoretical amount introduced.
Example 2 in Aqueous gel Aqueous gel based accordance with based on on hydroxypropylthe invention carbomer cellulose and aluminium magnesium silicate Temperature RT T40 0 C RT T40 0 C RT T40 0
C
BPO at T 100 94.3 101.7 initial BPO at T Not 102.5 95.7 90.3 94.9 1 month performed BPO at T Not 99.1 94.3 85.5 87.3 2 months performed BPO at T 102.4 100.3 94 78.3 99.7 85.8 3 months In the composition of Example 2, the percentage of benzoyl peroxide over time remains stable and equivalent to 100% both at room temperature and at 40 0 C. The benzoyl peroxide present in the other two examples of prior-art aqueous gels degrades significantly over time. After 3 months, a loss of benzoyl peroxide that is up to 6% at room temperature and at least 14% at T40 0 C may be observed.
These results demonstrate that the compositions according to the invention allow very good stability of benzoyl peroxide over time, even at 40 0 C, unlike standard compositions.
It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art, in Australia or any other country.
In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.
H: \yvettec\keep\Specifications\P53025AmendedPages.doc26/o4/06
Claims (19)
1. Composition comprising, in a physiologically acceptable medium, at least one retinoid, dispersed benzoyl peroxide and at least one pH-independent c gelling agent, said pH-independent gelling agent being 0 selected from the group consisting of the polyacrylamide CI family, the family of acrylic polymers coupled to hydrophobic chains, the family of modified starches and mixtures thereof.
2. Composition according to Claim 1, characterized in that it contains between 0.1% and 15% of pH-independent gelling agent.
3. Composition according to either of Claims 1 and 2, characterized in that the pH-independent gelling agent is a polyacrylamide.
4. Composition according to one of Claims 1 to 3, characterized in that it contains between 0.0001% and of retinoid.
5. Composition according to one of Claims 1 to 4, characterized in that the retinoid is adapalene.
6. Composition according to one of Claims 1 to characterized in that it contains between 0.0001% and of benzoyl peroxide.
7. Composition according to one of Claims 1 to 6, characterized in that the benzoyl peroxide is N:\Melboume\Cases\Paten\53000-53999\P53025AU\Specis\P53025.AU Specification 2008-7-1.doc 10/07/08 00 33A- 00 encapsulated or free.
8. Composition according to any one of the preceding claims, characterized in that it contains a pro- penetrating agent. 5 9. Composition according to Claim 8, 7t• N:\Melboume\CasesPatent\53000-53999\P53025AU\Specis\P53025 AU Specification 2008-7-l.doc 10/07/08 characterized in that it contains between 0 and 20% of pro-penetrating agent. Composition according to Claim 8 or 9, characterized in that the pro-penetrating agent is propylene glycol.
11. Composition according to any one of the preceding claims, characterized in that it contains a liquid wetting surfactant.
12. Composition according to Claims 1 to characterized in that it contains between 0 and 10% of liquid wetting surfactant.
13. Composition according to Claim 11 or 12, characterized in that the liquid wetting surfactant is a poloxamer.
14. Composition according to any one of the preceding claims, characterized in that it comprises, in water: 2.50% benzoyl peroxide, 0.10% adapalene, 0.10% disodium EDTA, 4.00% glycerol, 4.00% propylene glycol, 0.05% sodium docusate, 0.20% Poloxamer 124, 4.00% sodium acryloyldimethyltaurate copolymer isohexadecane polysorbate sodium hydroxide, qs pH Composition according to any one of Claims 1 to 14, as a medicinal product.
16. Process for preparing the composition according to any one of the preceding claims, characterized in that it successively comprises the following steps performed at room temperature: a) the preparation of an aqueous phase comprising water and optionally a chelating agent and/or a pro- penetrating agent and/or a humectant; b) the preparation of an active phase comprising the mixture in water of the retinoid, of benzoyl peroxide and, optionally, of a liquid wetting surfactant and/or of a pro-penetrating agent, with stirring; c) the introduction of the active phase into the aqueous phase, with stirring; and d) the introduction of the gelling agent into the mixture obtained from step with stirring.
17. Process for preparing the composition according to any one of Claims 1 to 15, characterized in that it successively comprises the following steps performed at room temperature: a) the preparation of an aqueous phase comprising water and optionally a chelating agent and/or a pro- penetrating agent and/or a humectant; b) the preparation of two active agents, one comprising the mixture in water of the retinoid, the other comprising the mixture in water of benzoyl peroxide and, optionally, of a liquid wetting surfactant and/or of a pro-penetrating agent, with stirring; c) the introduction of the active phases into the aqueous phase, with stirring; and d) the introduction of the gelling agent into the mixture obtained from step with stirring.
18. Use of a composition according to any one of Claims 1 to 15, for the manufacture of a pharmaceutical preparation for preventing or treating dermatological complaints associated with cell differentiation and/or proliferation disorders and/or keratinization disorders.
19. Use of a composition according to any one of Claims 1 to 15, to manufacture a pharmaceutical preparation for preventing or treating common acne. Cosmetic use of a composition according to any one of Claims 1 to 14, for treating acne-prone skin, for regrowth of the hair or for preventing hair loss, for combating the greasy appearance of the skin or the hair, in protecting against the harmful effects of sunlight or in the treatment of physiologically dry skin, or for preventing and/or combating photoinduced or chronological ageing.
21. A method for preventing or treating dermatological complaints associated with cell differentiation and/or proliferation disorders and/or keratinization disorders which comprises topically applying a composition according to any one of Claims 1 to to a subject in need thereof.
22. A method for treating acne-prone skin, for regrowth of the hair or for preventing hair loss, for combating the greasy appearance of the skin or the hair, in protecting against the harmful effects of sunlight or in the treatment of physiologically dry skin, or for preventing and/or combating photoinduced or chronological ageing which comprises topically applying a composition according to any one of Claims 1 to 15 to a subject in need thereof.
23. Compositions, processes for their preparation or uses or methods involving them, substantially as herein described with reference to the examples. Dated this 2 6 th day of April 2006 GALDERMA RESEARCH DEVELOPMENT, S.N.C. By their Patent Attorneys GRIFFITH HACK Fellows Institute of Patent and Trade Mark Attorneys of Australia H: \yvettec\keep\Specifications\P53O25AmendedPages .doc26/04/06
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2008246274A AU2008246274B2 (en) | 2001-12-21 | 2008-11-21 | Gel comprising at least a retinoid and benzoyl peroxide |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0116747A FR2833841B1 (en) | 2001-12-21 | 2001-12-21 | GEL COMPRISING AT LEAST ONE RETINOID AND BENZOYL PEROXIDE |
| FR0116747 | 2001-12-21 | ||
| PCT/FR2002/004233 WO2003055472A1 (en) | 2001-12-21 | 2002-12-09 | Gel comprising at least a retinoid and benzoyl peroxide |
Related Child Applications (1)
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|---|---|---|---|
| AU2008246274A Division AU2008246274B2 (en) | 2001-12-21 | 2008-11-21 | Gel comprising at least a retinoid and benzoyl peroxide |
Publications (2)
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| AU2002364437A1 AU2002364437A1 (en) | 2003-07-15 |
| AU2002364437B2 true AU2002364437B2 (en) | 2008-08-21 |
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| AU2008246274A Expired AU2008246274B2 (en) | 2001-12-21 | 2008-11-21 | Gel comprising at least a retinoid and benzoyl peroxide |
Family Applications After (1)
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| AU2008246274A Expired AU2008246274B2 (en) | 2001-12-21 | 2008-11-21 | Gel comprising at least a retinoid and benzoyl peroxide |
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| EP (1) | EP1458369B1 (en) |
| JP (2) | JP4889922B2 (en) |
| KR (1) | KR101014586B1 (en) |
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| FR2628319B1 (en) * | 1988-03-09 | 1990-12-07 | Oreal | PHARMACEUTICAL AND COSMETIC COMPOSITIONS BASED ON BENZOYL PEROXIDE AND QUATERNARY AMMONIUM SALTS |
| US5470884A (en) * | 1994-05-19 | 1995-11-28 | Procter & Gamble | Anti-acne compositions |
| FR2787322B1 (en) * | 1998-12-18 | 2002-10-18 | Galderma Res & Dev | OIL-IN-WATER EMULSION COMPRISING A MICRONIZED ACTIVE AGENT AND AN APPROPRIATE EMULSION SYSTEM |
| EP1239838B1 (en) * | 1999-12-20 | 2007-06-27 | Henkel Kommanditgesellschaft auf Aktien | Method for tabletting thickening systems |
| FR2833841B1 (en) * | 2001-12-21 | 2005-07-22 | Galderma Res & Dev | GEL COMPRISING AT LEAST ONE RETINOID AND BENZOYL PEROXIDE |
-
2001
- 2001-12-21 FR FR0116747A patent/FR2833841B1/en not_active Expired - Fee Related
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2002
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- 2002-12-09 DE DE122008000041C patent/DE122008000041I1/en active Pending
- 2002-12-09 KR KR1020047008461A patent/KR101014586B1/en active IP Right Grant
- 2002-12-09 MX MXPA04005918A patent/MXPA04005918A/en active IP Right Grant
- 2002-12-09 CN CNB028258460A patent/CN1329025C/en not_active Expired - Lifetime
- 2002-12-09 EP EP02799797A patent/EP1458369B1/en not_active Expired - Lifetime
- 2002-12-09 PL PL372270A patent/PL220838B1/en unknown
- 2002-12-09 HU HU0500006A patent/HU230439B1/en unknown
- 2002-12-09 DK DK02799797T patent/DK1458369T3/en active
- 2002-12-09 JP JP2003556050A patent/JP4889922B2/en not_active Expired - Lifetime
- 2002-12-09 RU RU2004122429/15A patent/RU2320327C2/en active
- 2002-12-09 CA CA2466321A patent/CA2466321C/en not_active Expired - Fee Related
- 2002-12-09 SI SI200230454T patent/SI1458369T1/en unknown
- 2002-12-09 DE DE60216634T patent/DE60216634T2/en not_active Expired - Lifetime
- 2002-12-09 AT AT02799797T patent/ATE347354T1/en active
- 2002-12-09 BR BRPI0214264A patent/BRPI0214264B8/en not_active IP Right Cessation
- 2002-12-09 WO PCT/FR2002/004233 patent/WO2003055472A1/en active IP Right Grant
- 2002-12-09 ES ES02799797T patent/ES2275948T3/en not_active Expired - Lifetime
- 2002-12-09 PT PT02799797T patent/PT1458369E/en unknown
- 2002-12-18 AR ARP020104930A patent/AR038026A1/en not_active Application Discontinuation
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2004
- 2004-05-17 ZA ZA2004/03759A patent/ZA200403759B/en unknown
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2007
- 2007-01-29 CY CY20071100120T patent/CY1107583T1/en unknown
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2008
- 2008-06-05 FR FR08C0024C patent/FR08C0024I2/fr active Active
- 2008-11-21 AU AU2008246274A patent/AU2008246274B2/en not_active Expired
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2010
- 2010-11-26 JP JP2010264093A patent/JP5478468B2/en not_active Expired - Lifetime
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| US4189501A (en) * | 1977-10-07 | 1980-02-19 | A. H. C. Pharmacal, Inc. | Composition and method for the treatment of acne |
| USRE34805E (en) * | 1985-04-11 | 1994-12-06 | Centre International De Recherches Dermatologiques (Cird) | Benzonaphthalene derivatives and their use in therapeutic and cosmetic compositions |
| WO1993007856A1 (en) * | 1991-10-16 | 1993-04-29 | Richardson-Vicks, Inc. | LOW pH AQUEOUS COSMETIC GEL CONTAINING NON-IONIC POLYACRYLAMIDE DERIVATIVES |
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| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |