International Patent Classification: TM), European (AL, AT, BE, BG, CH
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( International Patent Classification: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, A61K 9/107 (2006.01) A61P 17/00 (2006.01) EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, A61K9/06 (2006.01) A61Q 19/00 2006.01) MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, A61K 47/10 (2017.01) A61K 8/04 (2006.01) TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, A61K 47/14 (2017.01) A61K 8/06 (2006.01) KM, ML, MR, NE, SN, TD, TG). A61K 47/44 (2017.01) A61K 8/37 (2006.01) A61K 31/192 (2006.01) A61K 8/92 (2006.01) Published: A61K 31/498 (2006.01) A61K 8/86 (2006.01) — with international search report (Art. 21(3)) A61K 31/7048 (2006.01) A61K 47/32 (2006.01) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of (21) International Application Number: amendments (Rule 48.2(h)) PCT/EP20 19/075876 (22) International Filing Date: 25 September 2019 (25.09.2019) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 18/01015 28 September 2018 (28.09.2018) FR 18/01017 28 September 2018 (28.09.2018) FR 18/01018 28 September 2018 (28.09.2018) FR (71) Applicant: GALDERMA RESEARCH & DEVELOP¬ MENT [FR/FR]; 2400 Route des Colles Les Templiers, 06410 BIOT (FR). (72) Inventors: MALLARD, Claire; Domaine de la Jouven- celle, 1122 Chemins du Chateau, 06250 Mougins (FR). WINCKLE, Gareth; 3 me Fontaine du Pin, 06160 Juan les Pins (FR). GUTIERREZ, Emmanuelle; 72 1avenue du General De Gaulle, Le Hameau des Pomarels B3, 06700 Saint-Laurent-du-Var (FR). (74) Agent: MANNAERTS, Jaap; Nederlandsch Octrooibu- reau, Postbus 29720, 2502 LS Den Haag (NL). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (54) Title: PHARMACEUTICAL COMPOSITION IN THE FORM OF A WATER-IN-OIL EMULSION (W/O) AND ITS USES (57) Abstract: The invention relates to a composition in the form of a water-in-oil (W/O) emulsion suitable for topical administration. The invention is characterised by the fact that the composition is a composition comprises an aqueous phase representing 60% to 98% by weight of the composition and a fat phase comprising one or a plurality of oils and an emulsifying system PHARMACEUTICAL COMPOSITION IN THE FORM O F A WATER-IN-OIL EMULSION (W/O) AND ITS USES Technical field The present invention relates to the field o f emulsions in the form o f a wa†er-in-oil emulsion and more preferably compositions, possibly pharmaceutical, suitable for topical o r oral administration. If relates in particular †o a composition in the form o f a n emulsion, a s well a s its cosmetic and food uses o r a composition for its use a s a medicinal product, more particularly in the prevention and/or treatment o f dermatological diseases, in particular human skin diseases. Prior art Emulsions are used to carry both water-soluble and fat-soluble substances and are therefore particularly suitable for use in the food, cosmetics, pharmaceutical and veterinary sectors, and in the detergents sector. In the field o f topically applied pharmaceutical compositions, cosmetic o r food compositions, there is a requirement o n by the user o f products in the form o f emulsions to have emulsions that exhibit appropriate sensory characteristics. Emulsions that provide a feeling o f freshness and that are felt especially when applied to the skin a s not "sticky" are particularly sough† after. Emulsions are classified according †o the nature o f the continuous phase (also referred to a s the "external phase"), in which droplets o f the other phase (referred to a s the "internal phase") are dispersed. In the case where the oil droplets are dispersed in a continuous aqueous phase, the system is called a n "oil-in-wa†er" (O/W) emulsion. In the case where the water droplets are dispersed in a continuous oily phase, the emulsion is o f the "wa†er-in-oil" (W/O) type. In general, among these two types o f emulsions, it is easier †o manufacture oil-in-wa†er (O/W) type emulsions because W/O type emulsions are inherently thermodynamically unstable. Indeed, if equal quantities o f water and oil are mixed, the formation of a n aqueous continuous phase emulsion is always observed, because the cohesive forces between wafer molecules are stronger than those between oil molecules. When these compositions are used for food purposes, W/O emulsions are advantageously used a s spreads such a s buffer or margarine. Margarine is a W/O emulsion containing droplets of wafer or skimmed milk in a mixture of vegetable oils and fats. Oily continuous phase (W/O) emulsions have many benefits: the separation between wafer droplets reduces the possibility of the proliferation of microorganisms. The use of antiseptics, essential when the continuous phase is aqueous, can be avoided; they can be stored well a † low temperatures, being much less sensitive in this respect than H/W type emulsions; the continuous oily phase covers the skin and protects if from dehydration and external substances. In the development of a n oily continuous phase emulsion system, two types of modifications were considered: mechanical modifications concerning the combination of phases (order of addition of phases, flow control during phase combination, phase temperature, agitation speed, etc.); chemical modifications, which consist of the addition of new ingredients or different contents resulting in the stabilisation of the emulsion. With regard †o mechanical modifications, the operating protocols used †o prepare W/O emulsions generally require: a significant energy supply in the form of thermal activation (aqueous and fa† phases are typically heated †o 80°C), which must sometimes be followed by a well-controlled progressive cooling; and/or the creation of turbulence in the two-phase emulsifying medium (high agitation speed (thousands of revolutions per minute) and high shear caused by specific agitator geometries). With regard †o chemical modifications, we can mention: - the use of microcrysfalline waxes, such a s ozokerite, which absorb the oil and prevent its exudation; the use of liquid paraffins a s a fa† phase, a s they are easier to emulsify; the addition of mineral salts such a s sodium chloride or magnesium chloride, in particular, to increase the cohesion of the interfacial film. Document FR2852257 describes a n emulsion consisting of a n oily outer phase and a gelled aqueous phase, said aqueous phase representing 60 †o 98% by weight, preferably 80 †o 98% by weight, of the composition, a s well a s the process for manufacturing such a n emulsion. W/O emulsions with a very high proportion of aqueous phase (80 †o 98%) have a sensory lightness and hydration associated with a cushion effect. Some W/O emulsions marketed in particular by the company SEPPIC™ include: a n aqueous phase dispersed in very high concentration and requiring the presence of a n electrolyte polymer; and a continuous fa† phase containing a n emulsifying system such a s those marketed under the name EASYNOV™ or FLUIDANOV™ and no† necessarily requiring heating. Unlike so-called conventional W/O emulsions, these compositions have the advantage of being prepared a † room temperature depending o n the melting points of the ingredients used. Indeed, emulsions are commonly prepared ho† and their implementation generally requires complex preparation processes, a significant heating before emulsification a s well a s a precise control of the cooling process. In addition to being economical and simpler since it can be carried out a † room temperature, the preparation process associated with these W/O emulsions requires only low shear, whereas high shear rates must generally be applied throughout the emulsification process. In addition, this technology can be free from the use of water-soluble salts typically used in the aqueous phase for emulsion stabilisation. In addition, it is not necessarily useful to add lipophilic thickeners (waxes) typically used to thicken the external fat phase to ensure good physical stability. For this purpose, the emulsifying systems EASYNOV™ or FLUIDANOV™ necessarily include octyldodecyl xyloside, octyldodecanol and possibly PEG- 30 DPFIS (PEG-30 Macrogol 30 dipolyhydroxystearate or dipolyhydroxystearate), and the aqueous phase necessarily includes a polyelectrolyte type polymer. Thus, W/O emulsions containing these emulsifying systems are necessarily intended for cosmetic application insofar a s octyldodecyl xyloside does not belong †o any pharmacopoeia. The GELTRAP™ technology, for example, described by the company SEPPIC™, cannot be used for pharmaceutical application because the ready-†o-use emulsifying mixture EASYNOV™ or FLUIDANOV™ are not registered in a monograph and do not have a pharmaceutical certification status.