Compositions containing hydrophilic active ingredients in oil

Abstract

A composition comprising: i) 2-5% by weight of an aqueous solution containing a hydrophilic active ingredient; ii) 1-2% by weight of methyl glucose sesquistearate; iii) 10-12% by weight of a polyglyceryl-3 ester of a fatty acid; and iv) at least 83% by weight of an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate, all weight percentages being based on the total weight of the composition, and the sum of i), ii), iii), and iv) not exceeding 100% by weight. A method for dispersing a hydrophilic active ingredient in an oil. A cosmetic or dermopharmaceutical formulation comprising the initial composition. A method for cosmetic, non-therapeutic treatment and / or care of the skin, hair, nails, and / or mucous membranes of a subject, the method comprising topically administering a cosmetically effective amount of the composition.

Description

[Technical Field]

[0001] The present invention relates to compositions comprising hydrophilic active ingredients, more particularly hydrophilic cosmetic and dermopharmaceutical active ingredients, in an oil system. The compositions are useful in cosmetic and dermopharmaceutical preparations for topical application of the active ingredient to the skin.

[0002] A method for dispersing hydrophilic active ingredients in oil is also disclosed. [Background technology]

[0003] Hydrophilic or water-soluble active ingredients are widely used in the cosmetic and pharmaceutical industries. Some ingredients are highly hydrophilic and lipophobic, meaning that they are soluble in water but have poor solubility or insolubility in formulations with high oil content.

[0004] However, many formulations, especially those that can be used to apply active ingredients on skin, have high oil content and are highly hydrophobic.In fact, in some industries, such as the cosmetics industry, there is a tendency to reduce the amount of water in formulations, and anhydrous products are becoming more and more common.Formulating hydrophilic active ingredients into products that are essentially hydrophobic presents formulators with significant challenges, because this product does not allow hydrophilic active ingredients to dissolve, and may cause their stability to be impaired.

[0005] Dispersion and emulsion formulations are commonly used to solve the problem of incorporating hydrophilic active ingredients into highly hydrophobic systems.However, such formulations often have poor stability, are chemically unstable, tend to phase separation, may have inconsistent performance, may require a large amount of emulsifier, surfactant, or preservative, may be opaque and visually unattractive to consumers, or do not have a good feel when applied to skin.Different formulations containing hydrophilic active ingredients are disclosed in, for example, WO2015066877(A1) and WO20221132(A1).

[0006] Therefore, there is a need to provide compositions that allow for the dispersion of hydrophilic active ingredients in oil systems. Furthermore, there is a need to obtain compositions that are clear or transparent and allow the incorporated active ingredients to remain stable over time. Summary of the Invention [Means for solving the problem]

[0007] The present invention overcomes some or all of the above problems and provides compositions that include hydrophilic active ingredients and that can be stably formulated in oil systems. Advantageously, the compositions of the present invention are clear and more visually appealing to consumers.

[0008] In a first aspect, the present invention provides a method for producing a medicament for the treatment of a pulmonary arthritis, comprising: i) an aqueous solution containing 2 to 5% by weight of a hydrophilic active ingredient; ii) 1 to 2% by weight of methyl glucose sesquistearate; iii) 10 to 12% by weight of polyglyceryl-3 esters of fatty acids; iv) at least 83% by weight of an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate; All weight percentages are based on the total weight of the composition. The sum of i), ii), iii), and iv) does not exceed 100% by weight.

[0009] In a second aspect, the present invention provides a method for dispersing a hydrophilic active ingredient in an oil, the method comprising: (i) dissolving a hydrophilic active ingredient in an aqueous solution; (ii) mixing the aqueous solution obtained in step i) with an oil system comprising a combination of methyl glucose sesquistearate, polyglyceryl-3 esters of fatty acids, and an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate.

[0010] In a third aspect, the present invention provides a cosmetic or dermopharmaceutical formulation comprising a composition according to the first aspect together with at least one cosmetically or dermopharmaceutical acceptable excipient or adjuvant.

[0011] In another aspect, the present invention provides a method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, the method comprising topically administering a cosmetically effective amount of a composition according to the first aspect or a cosmetic formulation according to the third aspect.

[0012] In another aspect, the present invention provides the use of a composition according to the first aspect for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject. DETAILED DESCRIPTION OF THE INVENTION

[0013] definition In the context of the present invention, "skin" is understood to mean the layers that make up the skin, including both the top layer or stratum corneum and the bottom layer or subcutaneous tissue. These layers are composed of different types of cells, such as keratinocytes, fibroblasts, melanocytes, mast cells, neurons and / or adipocytes, among others. The term "skin" also includes the scalp. The term "skin" includes mammalian skin, including human skin. Similarly, the term "hair, nails and mucous membranes" includes mammalian, e.g., human, hair, nails and mucous membranes.

[0014] As used herein, the term "treatment," without the proviso "cosmetic, non-therapeutic," refers to therapeutic methods including methods directed to the administration of a compound according to the present invention to reduce or eliminate a disease or disorder, or to reduce or eliminate one or more symptoms associated with the disease or disorder. The term "treatment," without the proviso "cosmetic, non-therapeutic," also encompasses therapeutic methods directed to reducing or eliminating the physiological consequences of a disease or disorder.

[0015] The terms "treatment" and "care," when used with the proviso "cosmetic non-therapeutic," mean that the treatment or care is aimed at improving or maintaining the aesthetic appearance of the skin, hair, nails, and / or mucous membranes. In particular, the treatment may have the objective of improving the cosmetic properties of the skin, hair, nails, and / or mucous membranes, such as, but not limited to, hydration level, elasticity, firmness, lustre, color, or texture, which are properties that affect the aesthetic appearance of the skin, hair, nails, and / or mucous membranes. The term "care" in the context of this specification refers to the maintenance of the properties of the skin, hair, nails, and / or mucous membranes, which are subjects that are improved or maintained by cosmetic treatment and / or care of the skin, hair, nails, and / or mucous membranes, both in healthy subjects and in subjects exhibiting diseases and / or disorders of the skin, hair, nails, and / or mucous membranes.

[0016] The term "prevention" as used herein refers to the ability of a compound or composition to prevent, delay, or hinder the appearance or development of a disease or disorder, or to prevent, delay, or hinder changes in the cosmetic properties of the skin, mucous membranes, and / or hair. The term "prevention" as used herein is interchangeable with the term "inhibition," i.e., refers to the ability of a compound of the present invention to inhibit the appearance or development of a disease or disorder, or to inhibit changes in the cosmetic properties of the skin, hair, nails, and / or mucous membranes. Prevention also relates to partially or completely avoiding the onset of a condition in a subject by taking measures to reduce the effects of the etiology associated with the development of such a disorder. Therefore, it is common to use the term prevention to mean "reducing the risk of a disorder," i.e., reducing the probability of contracting a disorder.

[0017] In the context of the present invention, the term "aging" refers to the changes that the skin undergoes as a result of the intrinsic aging process (i.e., chronoaging) or as a result of the extrinsic aging process of the skin induced by environmental factors (i.e., environmental factors such as exposure to the sun (photoaging) or cigarette smoke, extreme climatic conditions of cold or wind, chemical pollutants or pollutants). In the context of the present invention, ageing includes all external and / or tactile perceptible changes such as, for example but not limited to, the development of discontinuities on the skin such as wrinkles, fine lines, expression lines, stretch marks, deep wrinkles, unevenness or roughness, an increase in pore size, loss of moisture, loss of elasticity, loss of firmness, loss of smoothness, loss of ability to recover from deformations, loss of resilience, sagging skin such as sagging cheeks, the appearance of dark circles or a double chin, changes in skin color such as age spots, redness, dark circles or the appearance of hyperpigmented areas such as age spots or freckles, abnormal differentiation, hyperkeratinization, elastosis, hyperkeratosis, hair loss, orange peel skin, loss of collagen structure and other histological changes in the stratum corneum, dermis, epidermis, vasculature (e.g. the appearance of spider veins or telangiectasias) or in tissues close to the skin, among others. The term "photoaging" encompasses a series of processes resulting from prolonged exposure of skin to ultraviolet radiation that results in premature aging of the skin, which exhibits the same physical characteristics as aging, including, but not limited to, laxity, sagging, changes in color or pigmentation irregularities, abnormalities, and / or excessive keratinization. The sum of various environmental factors, such as exposure to cigarette smoke, exposure to pollution, and climatic conditions, such as cold and / or wind, also contribute to skin aging.

[0018] As used herein, the term "comprising" is inclusive or open-ended and does not exclude additional, unrecited elements or method steps, and is intended to encompass the phrases "consisting essentially of" and "consisting of" as alternative embodiments, where "consisting of" excludes any elements or steps not specified, and "consisting essentially of" permits the inclusion of additional, unrecited elements or steps that do not materially affect the essential or basic and novel characteristics of the composition or method under consideration.

[0019] Except in the examples, or where otherwise expressly indicated, all quantities in this description specifying amounts of ingredients, reaction conditions, molecular weights, number of carbon atoms, etc., should be understood to be modified by the word "about." As used herein, the term "about," when referring to, for example, a measurable value (e.g., the amount or weight of a particular ingredient, or temperature), refers to a variation of ±20%, ±10%, ±5%, ±1%, ±0.5%, or particularly ±0.1% of the specified amount. Unless otherwise indicated, all quantities in this description specifying amounts or proportions of ingredients are by weight.

[0020] hydrophilic active ingredient In a first aspect, the present invention provides a composition comprising: i) an aqueous solution containing 2 to 5% by weight of a hydrophilic active ingredient; ii) 1 to 2% by weight of methyl glucose sesquistearate; iii) 10 to 12% by weight of polyglyceryl-3 esters of fatty acids; iv) at least 83% by weight of an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate; All weight percentages are based on the total weight of the composition. The sum of i), ii), iii), and iv) does not exceed 100% by weight.

[0021] The present invention provides compositions that allow for the stable formulation of hydrophilic active ingredients in oils. The composition of the invention is suitable for topical application, and therefore in particular the composition is a composition for topical application. The terms "active ingredient," "active compound," or "active substance," as used herein, refer to a compound that, when administered in an effective amount, provides a benefit to a subject, particularly a mammal, more particularly a human subject. Active ingredients can be administered alone or in combination with other ingredients.

[0022] The term "effective amount" is understood to mean a non-toxic but sufficient amount of the active ingredient to provide the desired effect. For example, a "cosmetically effective amount" is understood to be an amount sufficient to improve or maintain the aesthetic appearance of the skin, hair, nails, and / or mucous membranes, and a "pharmaceutically effective amount" is understood to mean an amount sufficient to prevent or treat a disease or condition. The terms "pharmaceutically effective" and "therapeutically effective" are used interchangeably herein. The effective amount of the compound of the present invention to be administered, as well as the dosage of the compound, depends on numerous factors, including the age, condition of the patient, the nature or severity of the condition, the disorder or disease being treated and / or cared for, the route, site, and frequency of administration, and the specific nature of the components used. Such amounts can be determined by those skilled in the art by using routine methods, for example, by means of in vitro, ex vivo, or in vitro tests.

[0023] To achieve the desired effect, the active ingredient used in the compositions of the present invention at a cosmetically or dermatologically effective concentration may be, for example, in an amount of 0.00000001% (by weight) to 20% (by weight), 0.000001% (by weight) to 15% (by weight), 0.00001% (by weight) to 10% (by weight), or 0.0001% (by weight) to 5% (by weight) based on the total weight of the composition. In particular, the active ingredient may be in an amount of at least 0.001% by weight, more specifically at least 0.01% by weight, based on the total weight of the composition. The active ingredient may be in a concentration of 0.001 to 1% by weight, 0.01 to 0.5% by weight, 0.05 to 0.25% by weight, or 0.1 to 0.2% by weight, based on the total weight of the composition.

[0024] In particular, the aqueous solution containing the hydrophilic active ingredient is in a concentration of 2 to 3% by weight, more particularly 2 to 2.5% by weight, based on the total weight of the composition.

[0025] The term "hydrophilic", as used herein, refers to an active ingredient that is soluble in distilled water (or equivalent) at 25°C and atmospheric pressure at at least 0.001% by weight, particularly 0.1% by weight. Hydrophilic active ingredients are known to be lipophobic. The term "lipophobic", as used herein, refers to an active ingredient that is insoluble in oil at 25°C and atmospheric pressure at at least 0.001% by weight, particularly at least 0.1% by weight.

[0026] An advantageous feature of the present invention is that the compositions are clear or transparent compared to conventional water-in-oil emulsions. The terms clear or transparent (i.e., transparency) are intended by the present invention to mean their normal dictionary definition, and thus, a clear composition, for example, of the present invention, allows objects behind it to be immediately visible. In contrast, a translucent composition will allow light to pass through, but the light will be scattered, preventing a clear view of objects behind the translucent composition. For example, the optical clarity of the compositions of the present invention can be measured using a turbidity meter after allowing the composition to stand at room temperature for at least 24 hours, and is desirably better than 50 NTU when measured at room temperature (20°C to 25°C). Thus, the present invention provides compositions that are more appealing to consumers than conventional water-in-oil emulsions, which typically have a translucent or opaque, cloudy appearance.

[0027] The aqueous solution may contain water and a small amount of water-soluble organic solvent, particularly less than 10% by weight, or less than 5% by weight, or less than 1% by weight based on the total weight of the aqueous solution. More specifically, the aqueous solution lacks organic or inorganic solvents other than water, i.e., the aqueous solution contains only water, more specifically distilled water or purified water, as a solvent. In one embodiment, the aqueous solution essentially consists of water and a hydrophilic active ingredient, or even consists of them.

[0028] Optionally, the pH can be adjusted to be within the range of 4.0 to 8, more specifically 6.0 to 7.0.

[0029] Non-limiting examples of hydrophilic active ingredients include humectants or moisture-retaining substances, agents that stimulate healing, agents that stimulate re-epithelialization, agents that synthesize dermal or epidermal macromolecules, firming and / or density enhancing and / or restructuring agents, cytokine growth factors, anti-glycation agents, antioxidants, free radical scavengers and / or antifouling agents, reactive carbonyl species scavengers, 5α-reductase inhibitors, lysyl- and / or prolyl hydroxylase inhibitors, defensin synthesis stimulators, bactericides and / or bacteriostatic agents and / or antimicrobial agents and / or bactericides and / or antiseptic agents. or fungicides and / or fungistatics, antivirals, antiparasitics, antihistamines, desquamating or keratolytic and / or exfoliating agents, comedolytics, antipsoriatics, antidandruff agents, anti-inflammatory and / or analgesics, anesthetics, anti-wrinkle and / or anti-aging agents, cosmetic and / or absorbent and / or anti-body odor deodorants, antiperspirants, agents inhibiting vascular permeability, hydrolytic epithelial enzymes, skin lightening or skin bleaching agents, agents inhibiting sweat decomposing enzymes, agents capable of filtering ultraviolet rays, agents stimulating or regulating keratinocyte differentiation, antipruritics, agents stimulating or regulating the synthesis of melanin agents that inhibit pigmentation, pigmentation promoters, self-tanning agents, agents that stimulate melanocyte proliferation, liquid propellants, vitamins and vitamin derivatives, amino acids, skin relaxants, agents that can reduce or treat dark circles under the eyes, agents for the treatment and / or care of sensitive skin, astringents, agents that regulate sebum production, anti-stretch mark agents, lipolytic agents or agents that stimulate lipolysis, venous tonics, anti-cellulite agents, soothing agents, agents that improve the dermal-epidermal junction, agents that induce hair growth or retard hair loss, agents that inhibit or retard body hair growth, stimulators of heat shock protein synthesis, muscle relaxants These include relaxants, muscle contraction inhibitors, agents that inhibit the aggregation of acetylcholine receptors, anticholinergics, elastase inhibitors, matrix metalloproteinase inhibitors, chelating agents, mineral salts, cell extracts, emulsifiers, agents that stimulate the synthesis of lipids and stratum corneum components (such as ceramides and fatty acids), agents that modulate the skin's microflora or microbiome, agents that modulate the circadian rhythm of skin cells, skin conditioners, immunomodulators, agents that improve skin radiance or luster, agents that improve skin microcirculation, angiogenesis, and / or skin oxygenation, and / or mixtures thereof.

[0030] The nature of these active ingredients can be synthetic, natural, or naturally occurring derivatives. Non-limiting examples of natural ingredients include plants or plant extracts, purified ingredients (i.e., phytochemical compounds) obtained from plants or plant extracts, protein hydrolysates, marine extracts, and ingredients obtained from biotechnological processes. In the context of the present invention, a biotechnological process is understood to be any process that produces an active ingredient or a part of an active ingredient in an organism or a part thereof. In particular, the organism may be a microorganism. The ingredient can also be obtained from a combination of a synthetic process and a biotechnological process.

[0031] Surprisingly, it has been found that the combination of components of the composition according to the invention further improves the stability of active ingredients, such as water-soluble peptides, in oil-based formulations compared to other oil-based systems in which peptides are less stable and more susceptible to degradation. Thus, of particular interest as active ingredients in the context of the present invention are peptides or peptide derivatives of natural or synthetic origin.

[0032] In particular, the peptide can be a tripeptide, tetrapeptide, pentapeptide, hexapeptide, heptapeptide, octapeptide, nonapeptide, and / or mixtures thereof.

[0033] In particular, hydrophilic active ingredients include: R1-Glu-Glu-Met-Gln-Arg-Arg-R2 (SEQ ID NO: 1), R1-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-R2 (SEQ ID NO: 2), R1-Glu-Glu-Met-Gln-Arg-Arg-Ala-R2 (SEQ ID NO: 3), R1-Arg-Arg-Gln-Met-Glu-Glu-R2 (SEQ ID NO: 4), R1-Arg-Arg-D-Gln-Met-Glu-Glu-R2 (SEQ ID NO: 5), R1-Arg-Arg-Gln-D-Met-Glu-Glu-R2 (SEQ ID NO: 6), R1-Arg-Arg-D-Gln-D-Met-Glu-Glu-R2 (SEQ ID NO: 7), R1-Phe-Trp-Met-Lys-Arg-Lys-Arg-Val-Pro-R2 (SEQ ID NO: 8), R1-Tyr-D-Ala-Gly-Phe-Leu-R2 (SEQ ID NO: 9), and R1-Leu-Pro-Val-Thr-R2 (SEQ ID NO: 10), wherein R1 is selected from the group consisting of H and R5-CO-, and R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl, R2 is —NR3R4 or —OR3, and R3 and R4 are independently selected from the group consisting of H and C1-C 16 alkyl.

[0034] R1 is attached to the amino terminus (N-terminus) of the peptide, and R2 is attached to the carboxy terminus (C-terminus) of the peptide.

[0035] The abbreviations used for amino acids herein follow the rules of the IUPAC-IUB Commission of Biochemical Nomenclature as specified in Eur. J. Biochem., (1984), 138, 9-37. Thus, for example, Gly represents NH-CH-COOH, Gly- represents NH-CH-CO-, -Gly represents -NH-CH-COOH, and -Gly- represents -NH-CH-CO-. Thus, a hyphen representing a peptide bond eliminates the OH in the 1-carboxyl group of an amino acid (represented here in conventional non-ionized form) when positioned to the right of the symbol, and eliminates the H in the 2-amino group of an amino acid when positioned to the left of the symbol; both modifications can be applied to the same symbol (see Table 1).

[0036] [Table 1]

[0037] As used herein, the term "alkyl" includes both saturated, straight-chain and branched-chain alkyl groups, and the groups can be substituted (mono- or poly) or unsubstituted. The alkyl group is attached to the remainder of the molecule by a single bond. The alkyl group has 1 to 24, preferably 1 to 16, more preferably 1 to 14, even more preferably 1 to 12, and even more preferably 1, 2, 3, 4, 5, or 6 carbon atoms. The term "alkyl" includes, for example, methyl, ethyl, isopropyl, isobutyl, tert-butyl, 2-methylbutyl, heptyl, 5-methylhexyl, 2-ethylhexyl, octyl, decyl, dodecyl, lauryl, hexadecyl, octadecyl, and amyl.

[0038] As used herein, the term "alkenyl" refers to a group containing one or more carbon-carbon double bonds, which may be straight or branched, substituted (mono- or poly-) or unsubstituted. Preferably, an alkenyl has one, two, or three carbon-carbon double bonds. When more than one carbon-carbon double bond is present, the double bonds may be conjugated or unconjugated. Preferably, an alkenyl group has 2 to 24, preferably 2 to 16, more preferably 2 to 14, even more preferably 2 to 12, and even more preferably 2, 3, 4, 5, or 6 carbon atoms. An alkenyl group is attached to the remainder of the molecule by a single bond. The term "alkenyl" includes, for example, vinyl (-CH2=CH2), allyl (-CH2-CH=CH2), prenyl, oleyl, linoleyl, and the like.

[0039] The term "cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group, which may be substituted (mono- or poly) or unsubstituted. A cycloalkyl group has 3 to 24, preferably 3 to 16, more preferably 3 to 14, even more preferably 3 to 12, and even more preferably 3, 4, 5, or 6 carbon atoms. A cycloalkyl group is attached to the remainder of the molecule by a single bond. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methylcyclohexyl, dimethylcyclohexyl, octahydroindene, decahydronaphthalene, dodecahydrophenalene, and similar groups.

[0040] As is understood in the art, some degree of substitution may be present in the groups described above. In particular, where explicitly indicated, any of the above-identified groups may be substituted. The above-referenced substituents (radicals) are groups (or radicals) that are substituted at one or more available positions with one or more substituents. Preferably, the substitution is at one, two, or three positions, more preferably at one or two positions, and even more preferably at one position. Suitable substituents include, for example, C1-C4 alkyl, hydroxyl, C1-C4 alkoxyl, amino, amino-C1-C4 alkyl, C1-C4 carbonyloxyl, C1-C4 oxycarbonyl, halogen such as fluoride, chlorine, bromine, or iodine, cyano, nitro, azido, C1-C4 alkylsulfonyl, thiol, C1-C4 alkylthio, aryloxy such as phenoxyl, -NR b (C=NR b )NR b R c In particular, the following compounds are included: b and R c are independently H, C1-C4 alkyl, C2-C4 alkenyl, alkynyl, C3-C 10 Cycloalkyl, C6-C 18 Aryl, C7-C 17 It is selected from the group formed by aralkyl, 3- to 10-membered heterocyclyl, or a protecting group for an amino group.

[0041] The amino acids that make up a peptide can have the stereoconfiguration L- or D-. Generally, unless otherwise specified, amino acids are in the L-configuration. For example, if an amino acid is described as Arg, it is understood to be Arg or L-Arg, and if it is described as D-Arg, it is in the D-configuration.

[0042] R1 is H and R5-CO- (wherein R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 the group consisting of cycloalkyl, or C1-C 16 Alkyl, C2-C 18 The R5-CO- group can be selected from the group consisting of acetyl (CH3-CO-, abbreviated herein as "Ac-"), myristoyl (abbreviated herein as "Myr-") (CH3-(CH2) 12 —CO—), and palmitoyl (CH—(CH), abbreviated herein as “Palm-”) 14 -CO-) and other alkanoyl groups.

[0043] R1 can be selected from the group consisting of H and acetyl, tert-butanoyl, prenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl.

[0044] R1 is H and R5-CO- (wherein R5 is C1-C 16 Alkyl or C2-C 18 alkenyl).

[0045] R1 is H and R5-CO- (wherein R5 is C1-C 15 and the aryl group may be selected from the group consisting of alkyl.

[0046] R1 can be selected from the group consisting of H, acetyl and palmitoyl.

[0047] R2 is -NR3R4 or -OR3 (where R3 is H and R4 is H and C1-C1, including methyl, ethyl, hexyl, dodecyl, and hexadecyl); 16 alkyl).

[0048] R2 is -OH, -NH2, and -NHR4 (wherein R4 is C1 to C 16 alkyl, or C1-C3 alkyl, or C1-C2 alkyl).

[0049] R2 can be -OH or -NH2.

[0050] R1 is H and R5—CO— (wherein R5 is C1 to C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl), and R2 can be selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0051] R1 can be selected from the group consisting of H and acetyl, tert-butanoyl, prenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl; R2 can be -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C6. 16In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0052] R1 is H and R5—CO— (wherein R5 is C1 to C 16 Alkyl or C2-C 18 alkenyl), and R2 can be selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0053] R1 can be selected from the group consisting of H, acetyl, myristoyl, or palmitoyl; R2 is -NR3R4 or -OR3, wherein R3 and R4 are independently H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0054] R1 is H and R5—CO— (wherein R5 is C1 to C 15 alkyl), and R2 can be selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0055] R1 can be selected from the group consisting of H, acetyl, or palmitoyl; R2 is -NR3R4 or -OR3, where R3 and R4 are independently H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0056] In one embodiment, R1 is acetyl and R2 is NH2.

[0057] In one embodiment, R1 is H and R2 is OH.

[0058] In particular, the peptide may be selected from the group consisting of R1-Glu-Glu-Met-Gln-Arg-Arg-R2, R1-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-R2, R1-Arg-Arg-Gln-D-Met-Glu-Glu-R2, R1-Phe-Trp-Met-Lys-Arg-Lys-Arg-Val-Pro-R2, and R1-Tyr-D-Ala-Gly-Phe-Leu-R2, and mixtures thereof. More particularly, the peptide may be selected from the group consisting of R1-Glu-Glu-Met-Gln-Arg-Arg-R2, R1-Arg-Arg-Gln-D-Met-Glu-Glu-R2, R1-Tyr-D-Ala-Gly-Phe-Leu-R2, and mixtures thereof.

[0059] The peptide is R1-Glu-Glu-Met-Gln-Arg-Arg-R 2.The peptide can be: R1-Arg-Arg-Gln-D-Met-Glu-Glu-R2. The peptide can be H-Tyr-D-Ala-Gly-Phe-Leu-R2. The peptide can be R1-Tyr-D-Ala-Gly-Phe-Leu-R2.

[0060] More specifically, the peptide Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2(PEP-1), Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH2(PEP-2), Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-NH2(PEP-3), Ac-Arg-Arg-Gln-Met-Glu-Glu-NH2(PEP-4), Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2(PEP-5), Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2(PEP-6), Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2(PEP-7), H-Phe-Trp-Met-Lys-Arg-Lys-Arg-Val-Pro-NH2(PEP-8), H-Tyr-D-Ala-Gly-Phe-Leu-OH(PEP-9), and H-Leu-Pro-Val-Thr-OH (PEP-10).

[0061] In particular, the peptide can be selected from the group consisting of PEP-1, PEP-2, PEP-6, PEP-8, PEP-9, and mixtures thereof. More particularly, the peptide can be selected from the group consisting of PEP-1, PEP-6, and PEP-9. The peptide can be PEP-1. The peptide can be PEP-6. The peptide can be PEP-9.

[0062] Cosmetically or pharmaceutically acceptable salts of peptides in the context of the present invention are also found within the field of the present invention. The term "cosmetically or pharmaceutically acceptable salts" means salts approved for their use in animals, for example mammals, more particularly humans, and includes base addition salts (which may be inorganic, such as, but not limited to, lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc, or aluminum, among others, or which may be organic, such as, but not limited to, ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine, or piperazine, among others), or acid addition salts (which are either organic, such as, but not limited to, acetate, citrate, lactate, malonate, maleate, tartrate, fumarate, benzoate, aspartate, glutamate, succinate, oleate, trifluoroacetate, oxalate, pamoate, or gluconate, among others, or inorganic, such as, but not limited to, chloride, sulfate, borate, or carbonate, among others). The nature of the salt is not critical, provided that it is cosmetically or pharmaceutically acceptable. Cosmetically or pharmaceutically acceptable salts of peptides can be obtained by conventional methods well known in the prior art [Berge SM et al., "Pharmaceutical Salts", (1977), J. Pharm. Sci., 66, 1-19].

[0063] The synthesis of peptides and / or their cosmetically or pharmaceutically acceptable salts can be carried out according to conventional methods known in the prior art, such as solid-phase peptide synthesis [Stewart JM and Young JD, "Solid Phase Peptide Synthesis, 2nd edition", (1984), Pierce Chemical Company, Rockford, Illinois; Bodanzsky M. and Bodanzsky A., "The practice of Peptide Synthesis", (1994), Springer Verlag, Berlin; Lloyd-Williams P. et al., "Chemical Approaches to the Synthesis of Peptides and Proteins", (1997), CRC, Boca Raton, FL, USA], solution synthesis, enzymatic synthesis [Kullmann W. "Proteases as catalysts for enzymic synthesis of opioid peptides", (1980), J. Biol. Chem., 255(17), 8234-8238], or any combination thereof. The compounds of the present invention can also be obtained by fermentation of bacterial strains that have or have not been genetically modified to produce the desired sequence, or by controlled hydrolysis of proteins of animal or plant origin, preferably plant origin, which results in free peptide fragments containing the desired sequence.

[0064] For example, the method of obtaining the peptide described in any of the above embodiments comprises: - coupling of an amino acid with a protected N-terminus and a free C-terminus with an amino acid with a free N-terminus and a C-terminus that is protected or bound to a solid support, -elimination of the N-terminal protecting group, - repeated coupling of sequences and elimination of the N-terminal protecting group until the desired peptide sequence is obtained; - removal of the C-terminal protecting group or cleavage of the solid support.

[0065] Preferably, the C-terminus is attached to a solid support and the process is carried out in the solid phase and therefore involves coupling an N-terminally protected, C-terminally free amino acid with an N-terminally free, C-terminally attached amino acid attached to a polymeric support, removing the N-terminal protecting group, and repeating this procedure as many times as necessary to obtain a compound of the desired length, followed finally by cleavage of the synthesized compound from the original polymeric support.

[0066] The functional groups of the side chains of the amino acids are conveniently protected by temporary or permanent protecting groups maintained throughout the synthesis and can be deprotected simultaneously or orthogonally with the cleavage process of the peptide from the polymer support.

[0067] Alternatively, solid-phase synthesis can be carried out using a convergent strategy in which a polymer support is coupled to a peptide, or a peptide or amino acid pre-bound to a polymer support is coupled to a peptide. Convergent synthesis strategies are widely known to those skilled in the art and are described in Lloyd-Williams P. et al., "Convergent Solid-Phase Peptide Synthesis", (1993), Tetrahedron, 49(48), 11065-11133.

[0068] The above process may include additional steps of deprotecting the N- and C-termini and / or cleaving the peptide from the polymer support in any order, using standard procedures and conditions known in the art, after which the functional groups at these termini may be modified. Optional modifications of the N- and C-termini may be carried out with the peptide of formula (I) attached to the polymer support or once the peptide has been separated from the polymer support.

[0069] Optionally, R1 can be introduced by reacting the N-terminus of the compound of the present invention with an R1-X compound by nucleophilic substitution in the presence of a suitable base and solvent, wherein fragments bearing functional groups not involved in N-C bond formation are suitably protected by temporary or permanent protecting groups, where R1 is as defined above and X is a leaving group, such as, but not limited to, tosyl, mesyl, and halogen, among others.

[0070] Optionally and / or additionally, the R radical can be introduced by reaction of the compound HR with a complementary fragment corresponding to the peptide of formula (I) (wherein R is -OH) in the presence of a suitable solvent and base, such as N,N-diisopropylethylamine (DIEA) or trimethylamine, or an additive, such as 1-hydroxybenzotriazole (HOBt) or 1-hydroxyazabenzotriazole (HOAt), and a dehydrating agent, such as a carbodiimide, uronium salt, phosphonium salt, or amidinium salt, among others, or by prior formation of an acyl halide, for example, with thionyl chloride, to give the peptide of formula (I), where the fragment bearing functional groups not involved in N-C bond formation is suitably protected by a temporary or permanent protecting group. Alternatively, other R radicals can be introduced by simultaneous incorporation into the peptide cleavage process from the polymer support. R2 is -OR3, -NR3R4 or -SR3, where R3 and R4 are as defined above.

[0071] Those skilled in the art will readily understand that the C-terminal and N-terminal deprotection / cleavage steps and their subsequent derivatization can be performed in different orders according to methods known in the prior art.

[0072] The term "protecting group" refers to a group that blocks an organic functional group and can be removed under controlled conditions. Protecting groups, their relative reactivities and the conditions under which they remain inert are known to those skilled in the art.

[0073] Representative examples of protecting groups for amino groups are amides, such as acetate, benzoate, pivalate, among others; benzyloxycarbonyl (Cbz or Z), 2-chlorobenzyl (ClZ), para-nitrobenzyloxycarbonyl (pNZ), tert-butyloxycarbonyl (Boc), 2,2,2-trichloroethyloxycarbonyl (Troc), 2-(trimethylsilyl)ethyloxycarbonyl (Teoc), 9-fluorenylmethyloxycarbonyl (Fmoc) or allyloxycarbonyl (allyloxycarbonyl). carbamates such as 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl (Dde), 1-(4,4-dimethyl-2,6-dioxo-cyclohexylidene)-3-methylbutyl (ivDde), 1-(1-adamantyl)-1-methylethoxycarbonyl (Adpoc), preferably Boc or Fmoc.

[0074] Representative examples of protecting groups for carboxyl groups are esters such as tert-butyl ester (tBu), allyl ester (All), triphenylmethyl ester (Trt ester), cyclohexyl ester (cHx), benzyl ester (Bzl), ortho-nitrobenzyl ester, para-nitrobenzyl ester, para-methoxybenzyl ester, trimethylsilylethyl ester, 2-phenylisopropyl ester, fluorenylmethyl ester (Fm), 4-(N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino)benzyl ester (Dmab), among others. Preferred protecting groups of the present invention are All, tBu, cHex, Bzl, and Trt esters.

[0075] The side chains of the trifunctional amino acids can be protected during the synthesis process by temporary or permanent protecting groups that are orthogonal to the N- and C-terminal protecting groups.

[0076] The hydroxyl group of the tyrosine side chain can be protected with, among others, 2-bromobenzyloxycarbonyl (2-BrZ), tBu, All, Bzl, or 2,6-dichlorobenzyl (2,6-diClZ). In a preferred embodiment, the protecting group strategy used is one in which the amino group is protected with Boc, the carboxyl group is protected with an ester of Bzl, cHx, or All, and the tyrosine side chain is protected with 2-BrZ or Bzl. In another preferred embodiment, the protecting group strategy used is one in which the amino group is protected with Fmoc, the carboxyl group is protected with a tBu, All, or Trt ester, and the tyrosine side chain is protected with tBu.

[0077] The amino group of the tryptophan side chain can be protected, for example, with formyl (For) or Boc. In one embodiment, when the amino group is protected with Fmoc, the tryptophan side chain can be unprotected, i.e., the amino acid is incorporated as Fmoc-Trp-OH, protected with Boc, i.e., the amino acid is incorporated as Fmoc-Trp(Boc)-OH, or protected with For, i.e., the amino acid is incorporated as Fmoc-Trp(For)-OH. In one embodiment, the amino group is protected with Boc and the tryptophan side chain can be protected with For, i.e., the amino acid is incorporated as Boc-Trp(For)-OH.

[0078] Examples of these and other protecting groups, their introduction and removal can be found in the literature [Atherton B. and Sheppard RC, "Solid Phase Peptide Synthesis: A practical approach", (1989), IRL Oxford University Press]. The term "protecting group" also includes polymer supports used in solid phase synthesis.

[0079] When the synthesis is carried out wholly or partly in the solid phase, possible solid supports that can be used in the process of the present invention include polystyrene supports, polyethylene glycol grafted to polystyrene, and similar supports, such as, but not limited to, p-methylbenzhydrylamine resin (MBHA) [Matsueda G.R. et al., "A p-methylbenzhydrylamine resin for improved solid-phase synthesis of peptide amides", (1981), Peptides, 2, 45-50], 2-chlorotrityl resin Barlos K. et al., "Improved synthesis of peptide fragments under solid-phase substitution of triphenylmethyl-Hara", (1989), Tetrahedron Lett., 30, 3943-3946; Barlos K. et al., "Improved synthesis of peptide fragments under solid-phase substitution of triphenylmethyl-Hara", (1989), Tetrahedron Lett., 30, 3943-3946]. 2-Chlorotritylchlorid zur Synthese von Leu1-Gastrin I", (1989), Tetrahedron Lett., 30, 3947-3951], TentaGel® resin (Rapp Polymere GmbH), ChemMatrix® resin (Matrix Innovation, Inc.) and similar supports, which are based on 5-(4-aminomethyl-3,5-dimethoxyphenoxy) valeric acid (PAL) [Albericio F. et al.,"Preparation and application of the 5-(4-(9-fluorenylmethyloxycarbonyl)aminomethyl-3,5-dimethoxy-phenoxy)valeric acid(PAL)handle for the solid-phase synthesis of C-terminal peptide amides under mild 2-[4-aminomethyl-(2,4-dimethoxyphenyl)]phenoxyacetic acid (AM) [Rink H., "Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin", (1987), Tetrahedron Lett., 28, 3787-3790], [Wang SS, “p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycarbonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide The polymer may or may not include a labile linker such as "Fragments," (1973), J. Am. Chem. Soc., 95, 1328-1333" and the like, which allows for simultaneous deprotection and cleavage of the compound from the polymer support.

[0080] Methylglucose sesquistearate The present invention provides a composition comprising at least methyl glucose sesquistearate, which is a mixture of monoesters and diesters of methyl glucoside and stearic acid. Non-limiting examples of methyl glucose sesquistearate useful in the context of the present invention include Glucate™ SS emulsifier from Lubrizol Advanced Materials, Inc. Methyl glucose sesquistearate may be present in a concentration of 1 to 2% by weight, particularly 1 to 1.5% by weight, based on the total weight of the composition, and particularly 1, 1.1, 1.2, 1.4, or 1.5% by weight, based on the total weight of the composition.

[0081] Polyglyceryl-3 esters of fatty acids The present invention provides compositions comprising at least one ester of a fatty acid. In particular, the compositions of the present invention comprise at least one polyglyceryl-3 ester of a fatty acid. These can be represented by the following general formula:

[0082] [ka] In the formula, the R chain represents the acyl radical of a fatty acid.

[0083] Particularly useful polyglyceryl-3 esters of fatty acids in the context of the present invention are polyglyceryl-3 caprylate, polyglyceryl-3 caprate, polyglyceryl-3 laurate, polyglyceryl-3 myristate, polyglyceryl-3 palmitate, polyglyceryl-3 stearate, polyglyceryl-3 arachidate, polyglyceryl-3 behenate, polyglyceryl-3 palmitoleate, polyglyceryl-3 oleate, and polyglyceryl-3 linoleate. In particular, the polyglycerol-3 esters of fatty acids are selected from the group consisting of polyglyceryl-3 caprylate, polyglyceryl-3 caprate, polyglyceryl-3 laurate, polyglyceryl-3 myristate, and polyglyceryl-3 palmitate. More specifically, the polyglycerol-3 esters of fatty acids can be polyglyceryl-3 laurate, also known as triglycerol laurate. A non-limiting example of a triglycerol laurate useful in the context of the present invention is Hydramol™ TGL from Lubrizol Advanced Materials, Inc. The polyglycerol-3 ester of a fatty acid may be in a concentration of 10 to 12% by weight based on the total weight of the composition. In particular, the concentration may be 10, 11, or 12% by weight based on the total weight of the composition.

[0084] Ester oil The composition of the present invention further comprises an ester oil, in particular the ester oil is selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, ethylhexyl palmitate, and mixtures thereof. Examples of these ingredients that may be mentioned are Schercemol™ CO Ester (cetyl ethylhexanoate) from Lubrizol Advanced Materials, Inc., Schercemol™ 318 Ester (isopropyl isostearate) from Lubrizol Advanced Materials, Inc., and DUB™ PO (ethylhexyl palmitate) from Stearinerie Dubois.

[0085] Advantageously, cetyl ethylhexanoate has been found to make it possible to obtain a composition completely free of sediment, which is more visually appealing to the consumer. Thus, in particular, the ester oil can be cetyl ethylhexanoate.

[0086] The ester oil can be at a concentration of at least 83 wt %, based on the total weight of the composition. The ester oil can be at a concentration of 85-87 wt %, or 86-87 wt %, based on the total weight of the composition.

[0087] In particular, the present invention provides a composition comprising 2-3 wt. % of an aqueous solution containing a hydrophilic active ingredient, particularly a peptide; 1-2 wt. % of methyl glucose sesquistearate; 10-12 wt. % of polyglyceryl-3 ester of a fatty acid; and 85-87 wt. % of an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate, all weight percentages being based on the total weight of the composition, and the sum of i), ii), iii), and iv) not exceeding 100 wt. %.

[0088] In particular, the present invention provides a composition comprising 2-3% by weight of an aqueous solution containing a hydrophilic active ingredient, particularly a peptide, 1-2% by weight of methyl glucose sesquistearate, 10-12% by weight of triglycerol laurate, and 85-87% by weight of an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate. All weight percentages are based on the total weight of the composition, and the sum of i), ii), iii), and iv) does not exceed 100% by weight.

[0089] In particular, the present invention provides a composition comprising 2-3% by weight of an aqueous solution containing a hydrophilic active ingredient, particularly a peptide, 1-2% by weight of methyl glucose sesquistearate, 10-12% by weight of polyglyceryl-3 esters of fatty acids, and 85-87% by weight of cetyl ethylhexanoate. All weight percentages are based on the total weight of the composition, and the sum of i), ii), iii), and iv) does not exceed 100% by weight.

[0090] In particular, the present invention provides a composition comprising 2-3% by weight of an aqueous solution containing a hydrophilic active ingredient, particularly a peptide, 1-2% by weight of methyl glucose sesquistearate, 10-12% by weight of triglycerol laurate, and 85-87% by weight of cetyl ethylhexanoate. All weight percentages are based on the total weight of the composition, and the sum of i), ii), iii), and iv) does not exceed 100% by weight.

[0091] Cosmetic and dermatological preparations The compounds of the present invention can be administered for their application by any means which brings about contact between the compounds and the site of action in the body of a subject, preferably a mammal, preferably a human, and in the form of a cosmetic or dermopharmaceutical formulation or product containing them together with a cosmetically or dermopharmaceutical acceptable excipient or adjuvant.

[0092] The terms "cosmetically acceptable excipient" and "dermatologically acceptable excipient" are well known to those skilled in the art and include compounds, materials, compositions, carriers, vehicles, and / or dosage forms that, when mixed with a composition, improve application to the skin without undue toxicity, irritation, allergic reaction, or other problems or complications, consistent with a reasonable benefit / risk ratio. Suitable excipients or adjuvants can be found in standard cosmetic or pharmaceutical textbooks known to those skilled in the art, such as "Harry's Cosmeticology", Seventh Edition, (1982), Wilkinson JB, Moore RJ, ed. Longman House, Essex, GB, or "Handbook of Pharmaceutical Excipients", Raymond C Rowe, Paul J Sheskey and Sian C Owen, Royal Pharmaceutical Society of Great Britain London, UK.

[0093] The composition according to the first aspect of the present invention may be contained in a cosmetic or dermopharmaceutical formulation in an amount of 0.001 to 10% by weight, specifically 0.01 to 5% by weight, more specifically 0.1 to 2% by weight, based on the total weight of the cosmetic or dermopharmaceutical formulation.

[0094] Cosmetic or dermopharmaceutical formulations for topical or transdermal application can be made into any solid, liquid, or semi-solid formulation, for example, but not limited to, creams, multiple emulsions, including but not limited to, oil-in-water and / or silicone-in-water emulsions, water-in-oil and / or water-in-silicone emulsions, water / oil / water or water / silicone / water emulsions, and oil / water / oil or silicone / water / silicone emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balsams, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, liniments, serums, soaps, shampoos, conditioners, serums, polysaccharide films, ointments, mousses, pomades, powders, bars, pencils, and sprays or aerosols (sprays), including leave-on and rinse-off formulations.

[0095] In particular, the present invention provides cosmetic or dermopharmaceutical preparations in the form of a cream, multiple emulsion, foundation, solution, anhydrous formulation, dispersion, oil, milk, balsam, lotion, gel, cream gel, liniment, conditioner, serum, stick, ointment, mousse, pomade, powder, bar, pencil, spray, aerosol or mask.

[0096] The cosmetic or dermopharmaceutical formulations can also be incorporated into textiles, nonwovens, and medical or cosmetic devices that come into direct contact with the skin. Examples of textiles, nonwovens, clothing, medical or cosmetic devices, and means for immobilizing compounds thereon, among others, are the delivery systems and / or sustained release systems mentioned above, which can be found in the following documents and are known in the prior art: Schaab CK (1986) HAPPI May 1986; Nelson G., "Application of microencapsulation in textiles", (2002), Int. J. Pharm., 242 (1-2), 55-62; "Biofunctional Textiles and the Skin" (2006) Curr. Probl. Dermatol. v. 33, Hipler UC and Elsner P., eds. S. Karger AG, Basel, Switzerland; Malcolm RK et al., "Controlled release of a model antibacterial drug from a novel self-lubricating silicone" "biomaterial", (2004), J. Cont. Release, 97(2), 313-320]. Preferred textiles, nonwovens, garments, and medical devices are bandages, gauze, T-shirts, socks, tights, underwear, girdles, gloves, diapers, sanitary napkins, bandages, bedspreads, wipes, adhesive patches, non-adhesive patches, occlusive patches, microelectric patches, and / or face masks.

[0097] The cosmetic or dermopharmaceutical formulation may contain sugars, surfactants, moisturizers, petrolatum, mineral oil, fatty alcohols, fatty ester emollients, waxes and silicone-containing waxes, silicone oils, silicone fluids, silicone surfactants, volatile hydrocarbon oils, quaternary nitrogen compounds, amine-functionalized silicones, conditioning polymers, rheology modifiers, antioxidants, sunscreen actives, about C 10 ~C 22 Di-long chain amines, approximately C 10 ~C 22long chain fatty amines, fatty alcohols, ethoxylated fatty alcohols, as well as two-tailed phospholipids.

[0098] Representative sugars include nonionic or cationic sugars, such as agarose, amylopectin, amylose, arabinan, arabinogalactan, arabinoxylen, carrageenan, gum arabic, carboxymethyl guar gum, carboxymethyl (hydroxypropyl) guar gum, hydroxyethyl guar gum, carboxymethyl cellulose, cationic guar gum, cellulose ethers including methylcellulose, chondroitin, chitin, chitosan, chitosan pyrrolidone carboxylate, chitosan glycolate, chitosan lauroyl cellulose, chitosan laurate ... Citrate, Cocodimonium Hydroxypropyloxyethylcellulose, Colominic Acid (Poly-N-acetyl-neuraminic Acid), Corn Starch, Curdlan, Dermatan Sulfate, Dextran, Furcellan, Dextran, Cross-Linked Dextran, Dextrin, Emulsan, Ethyl Hydroxyethylcellulose, Flaxseed Saccharide (Acid), Galactoglucomannan, Galactomannan, Glucomannan, Glycogen, Guar Gum, Hydroxyethyl Starch, Hydroxypropyl Methylcellulose, Hydroxyethylcellulose , Hydroxypropyl cellulose, Hydroxypropyl starch, Hydroxypropylated guar gum, Gellan gum, Gellan, Gatti gum, Karaya gum, Tragancanth gum (Tragacanthin), Heparin, Hyaluronic acid, Inulin, Keratin sulfate, Konjac mannan, Modified starch, Laminaran, Lauryldimonium hydroxypropyloxyethyl cellulose, Okra gum, Oxidized starch, Pectic acid, Pectin, Polydextrose, Polyquaternium-4, Polyquaternium-10, Polyquaternium-28, Potato Potato starch, protopectin, psyllium seed gum, pullulan, sodium hyaluronate, starch diethylaminoethyl ether, starch hydroxypropyltrimonium chloride, hydroxypropyl starch phosphate, steardimonium hydroxyethylcellulose, raffinose, rhamsan, tapioca starch, welan, levan, scleroglucan, sodium alginate, stachyrose, succinoglycan, wheat starch, xanthan gum, xylan, xyloglucan, and mixtures thereof.Microbial sugars can be found in Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Vol. 16, John Wiley and Sons, NY pp. 578-611 (1994), which is incorporated by reference in its entirety. Complex carbohydrates can be found, for example, in Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Vol. 4, John Wiley and Sons, NY pp. 930-948, 1995. More specifically, the formulation can include microcrystalline cellulose. One suitable microcrystalline cellulose is Vivapur® CS 9 GM from JRS-J. Rettenmaier & Söhne GmbH & Co. KG.

[0099] The cosmetic or dermatological preparation of the present invention may contain a surfactant.Surfactant typically comprises a surface-active substance that provides the preparation with a cleaning function or simply acts as a wetting agent.Surfactant can generally be classified into anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants, and zwitterionic surfactants.The anionic surfactants useful herein include those disclosed in U.S. Patent No. 5,573,709, which is incorporated herein by reference.

[0100] The anionic, cationic, nonionic, amphoteric, or zwitterionic surfactant used in the cosmetic or dermatological compositions of the present invention is typically used in an amount of about 0.1 to 50 weight percent, preferably about 0.5 to about 40 weight percent, and more preferably about 1 to about 20 weight percent.

[0101] The cosmetic or dermopharmaceutical formulations of the present invention may also contain fatty alcohols (typically monohydric alcohols), ethoxylated fatty alcohols, and di-tailed phospholipids, which can be used to stabilize the cosmetically acceptable emulsion or dispersion of the composition. They also provide a cosmetically or pharmaceutically acceptable viscosity. Examples include stearyl alcohol, cetyl alcohol, cetostearyl alcohol, myristyl alcohol, behenyl alcohol, arachidyl alcohol, isostearyl alcohol, and isocetyl alcohol.

[0102] The cosmetic or dermatological preparation of the present invention may contain a moisturizing agent that acts as a moisture absorbent and increases the amount of water absorbed, retained, and retained.Moisturizing agents suitable for the preparation of the present invention include, but are not limited to, acetamide MEA, ammonium lactate, chitosan and its derivatives, colloidal oatmeal, galactoarabinan, glucose glutamate, glerecyth-7, glygeryth-12, glycereth-26, glycereth-31, glycerin, lactamide MEA, lactamide DEA, lactic acid, methyl gluceth-10, methyl gluceth-20, panthenol, propylene glycol, sorbitol, polyethylene glycol, 1,3-butanediol, 1,2,6-hexanetriol, hydrogenated starch hydrolysate, inositol, mannitol, PEG-5 pentaerythritol ether, polyglyceryl sorbitol, xylitol, sucrose, sodium hyaluronate, sodium PCA, and combinations thereof.Glycerin is a particularly preferred moisturizing agent. The humectant may be present in the formulation at a concentration of about 0.5 to about 40 weight percent, specifically about 0.5 to about 20 weight percent, and more specifically about 0.5 to about 12 weight percent.

[0103] The cosmetic or dermopharmaceutical formulations of the present invention may contain petrolatum or mineral oil components, generally USP or NF grade, if selected. Petrolatum can be partially replaced with a mixture of hydrocarbon materials, which can be formulated to resemble petrolatum in appearance and consistency. For example, mixtures of petrolatum or mineral oil with different waxes can be combined. Specific waxes include bayberry wax, candelilla wax, ceresin, jojoba butter, lanolin wax, montan wax, ozokerite, polyglyceryl-3-beeswax, polyglyceryl-6-pentastearate, microcrystalline wax, paraffin wax, isoparaffin, petrolatum solid paraffin, squalene, oligomeric olefins, beeswax, synthetic candelilla wax, synthetic carnauba, synthetic beeswax, etc., and may be blended together. Alkylmethylsiloxanes with various degrees of substitution can be used to increase water retention by the skin. Siloxanes such as stearyl dimethicone, known as 2503 wax, C30-45 alkyl methicone, known as AMS-C30 wax, and stearoxytrimethylsilane (and) stearyl alcohol, known as 580 wax, are each available from Dow Corning® (Midland, Michigan, USA). Additional alkyl and phenyl silicones can be used to enhance moisturizing properties. Resins such as dimethicone (and) trimethylsiloxysilicate, known as Dow Corning® 593, or cyclomethicone (and) trimethylsiloxysilicate, known as Dow Corning® 749 fluid, can be used to enhance film formation in skin care products. When used, petrolatum, wax or hydrocarbon, or oil components are included in the formulation at a concentration of about 0.1 to about 20 weight percent, more preferably about 1 to about 12 weight percent. When used, silicone resins can be present in an amount of about 0.1 to about 10.0 weight percent.

[0104] Emollients are defined as agents that help maintain the soft, smooth, and supple appearance of skin. Emollients function by their ability to remain on the skin surface or in the stratum corneum. The cosmetic and dermopharmaceutical formulations of the present invention may contain fatty ester emollients listed in the International Cosmetic Ingredient Dictionary, Eighth Edition, 2000, pp. 1768-1773.

[0105] Specific examples of fatty acid esters suitable for use in the formulations of the present invention include isopropyl myristate, isopropyl palmitate, caprylic / capric triglyceride, cetyl lactate, cetyl palmitate, hydrogenated castor oil, glyceryl esters, hydroxycetyl isostearate, hydroxycetyl phosphate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, PPG-5-ceteth-20, 2-ethylhexyl isononoate, 2-ethylhexyl stearate, C12-C16 fatty alcohol lactate, isopropyl lanolate, 2-ethylhexyl salicylate, and mixtures thereof. Currently preferred fatty acid esters are isopropyl myristate, isopropyl palmitate, PPG-5-ceteth-20, caprylic / capric triglyceride, and isostearyl isostearate. When used, fatty ester emollients are preferably included in the formulations of the present invention at a concentration of from about 0.1 to about 99 weight percent, more preferably from about 1 to about 40 weight percent.

[0106] The cosmetic or dermopharmaceutical formulations of the present invention may also contain a silicone compound. Preferably, the viscosity of the silicone component at a temperature of 25°C is about 0.5 to about 12,500 cps. Examples of suitable materials are dimethylpolysiloxane, diethylpolysiloxane, dimethylpolysiloxane-diphenylpolysiloxane, cyclomethicone, trimethylpolysiloxane, diphenylpolysiloxane, and mixtures thereof. Dimethicone, a dimethylpolysiloxane endblocked with trimethyl units, is one preferred example. Dimethicone, having a viscosity of 50 to 1,000 cps, is particularly preferred. When used, silicone oils are preferably included in the formulations of the present invention at a concentration of 0.1 to 15 weight percent, more preferably 0.5 to 5 weight percent.

[0107] The cosmetic or dermopharmaceutical formulations of the present invention may contain volatile and non-volatile silicone oils or fluids. The silicone compound can be either a linear or cyclic polydimethylsiloxane having a viscosity of about 0.5 to about 100 centistokes. The most preferred linear polydimethylsiloxane compound has a viscosity range of about 0.5 to about 50 centistokes. An example of a linear, low molecular weight, volatile polydimethylsiloxane is octamethyltrisiloxane, available under the trade name Dow Corning® 200 Fluid, having a viscosity of about 1 centistoke. When used, silicone oils are preferably included in the formulations of the present invention at a concentration of 0.1 to 30 weight percent, more preferably 1 to 20 weight percent.

[0108] The cosmetic and dermopharmaceutical formulations of the present invention may contain volatile, cyclic, low-molecular-weight polydimethylsiloxanes (cyclomethicones). Preferred cyclic, volatile siloxanes are polydimethylcyclosiloxanes having an average repeating unit of 4 to 6 and a viscosity of about 2.0 to about 7.0 centistokes, and mixtures thereof. Preferred cyclomethicones are available from Dow Corning (Midland, Michigan, USA) under the trade names Dow Corning® 244 Fluid, Dow Corning® 245 Fluid, Dow Corning® 246, Dow Corning® 344 Fluid, and Dow Corning® 345 Fluid, and from General Electric (Waterford, NY, USA) under the trade names Silicone SF-1173 and Silicone SF-1202. When used, silicone oils are preferably included in the formulations of the present invention at a concentration of 0.1 to 30 weight percent, more preferably 1 to 20 weight percent. Silicone surfactants or emulsifiers with polyoxyethylene or polyoxypropylene side chains can also be used in the formulations of the present invention. Preferred examples include dimethicone copolyols, such as Dow Corning® 3225C and 5225C Formulation Aids available from Dow Corning (Midland, Michigan, USA) and Silicone SF-1528 available from General Electric (Waterford, New York, USA). The side chains can also contain alkyl groups, such as lauryl or cetyl. Preferred are lauryl methicone copolyol, known as Dow Corning® 5200 Formulation Aid, and cetyl dimethicone copolyol, known as Abil EM-90, available from Goldschmidt Chemical Corporation (Hopewell, Va.). Lauryl dimethicone, known as Belsil LDM 3107 VP, available from Wacker-Chemie (Munchen, Germany).When used, silicone surfactants are preferably included in the formulations of the present invention at a concentration of 0.1 to 15 weight percent, more preferably 1 to 5 weight percent. Amine-functional silicones and emulsions can be utilized in the present invention. Preferred examples include Dow Corning® 8220, Dow Corning® 939, Dow Corning® 949, and Dow Corning® 2-8194, all available from Dow Corning (Midland, Michigan, USA). Silicone SM 253, available from General Electric (Waterford, NY, USA), is also preferred. When used, amine-functional silicones are preferably included in the formulations of the present invention at a concentration of 0.1 to 5 weight percent, more preferably 0.1 to 2.0 weight percent.

[0109] Cosmetic or dermopharmaceutical formulations may contain volatile hydrocarbon oils. Volatile hydrocarbons contain approximately C6 to C22 atoms. Preferred volatile hydrocarbons are aliphatic hydrocarbons having a chain length of approximately C6 to C16 carbon atoms. An example of such a compound is isohexadecane, available from Presperse (South Plainfield, NJ, USA) under the trade name Permethyl 101A. Another example of a preferred volatile hydrocarbon is C12 to C14 isoparaffin, available from Exxon (Baytown, Texas, USA) under the trade name Isopar M. In one embodiment, the hydrocarbon is a C9 to C12 alkane. One example is SilSense™ Bio 5 emollient from Lubrizol Advanced Materials, Inc. When used, volatile hydrocarbons are preferably included in the formulations of the present invention at a concentration of 0.1 to 99 weight percent, more preferably 1 to 40 weight percent.

[0110] Cosmetic or dermopharmaceutical formulations may contain cationic and amphoteric conditioning polymers.Such examples include, but are not limited to, those listed in the International Cosmetic Ingredient Dictionary published by the Cosmetic, Toiletry, and Fragrance Association (CTFA), 1101 17th Street, NW, Suite 300, Washington, DC 20036.Common examples include quaternary derivatives of cellulose ethers, quaternary derivatives of guar, homopolymers and copolymers of DADMAC, homopolymers and copolymers of MAPTAC, and quaternary derivatives of starch. Specific examples, using the CTFA designations, include, but are not limited to, Polyquaternium-10, guar hydroxypropyltrimonium chloride, starch hydroxypropyltrimonium chloride, Polyquaternium-4, Polyquaternium-5, Polyquaternium-6, Polyquaternium-7, Polyquaternium-14, Polyquaternium-15, Polyquaternium-22, Polyquaternium-24, Polyquaternium-28, Polyquaternium-32, Polyquaternium-33, Polyquaternium-36, Polyquaternium-37, Polyquaternium-39, Polyquaternium-45, Polyquaternium-47, and polymethacrylamidopropyltrimonium chloride, Polyquaternium-55, and mixtures thereof. When used, conditioning polymers are preferably included in cosmetically acceptable compositions of the present invention at a concentration of from 0.1 to 10 weight percent, preferably from 0.2 to 6 weight percent, and most preferably from 0.2 to 5 weight percent.

[0111] The cosmetic or dermopharmaceutical formulations of the present invention may contain one or more rheology modifiers. Rheology modifiers that can be used in the present invention include high molecular weight crosslinked homopolymers of acrylic acid and acrylates / C10-30 alkyl acrylate crosspolymers, such as the Carbopol® and Pemulen® series, both available from Lubrizol Advanced Materials, Inc.; anionic acrylate polymers such as Salcare® AST and cationic acrylate polymers such as Salcare® SC96, available from Ciba Specialties (High Point, NC, USA); acrylamidopropyltrimonium chloride / acrylamido; hydroxyethyl methacrylate polymers, steareth-10 allyl ether / acrylate copolymers; and acrylates copolymers from Rohm and Haas / International. Acrylates / Beheneth-25 Methacrylate Copolymer, known as Aculyn® 28, available from Specialties (Wayne, NJ, USA); glyceryl polymethacrylate, acrylates / steareth-20 methacrylate copolymer; bentonite; gums such as alginate, carrageenan, acacia gum, gum arabic, gum ghatti, gum karaya, gum tragacanth, and guar gum; guar hydroxypropyltrimonium chloride, xanthan gum, or gellan gum; sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxymethyl These include, but are not limited to, cellulose derivatives such as carboxyethyl cellulose, hydroxymethyl carboxypropyl cellulose, ethyl cellulose, sulfated cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, microcrystalline cellulose, and the like; agar; pectin; gelatin; starch and its derivatives; chitosan and its derivatives such as hydroxyethyl chitosan; polyvinyl alcohol, PVM / MA copolymer, PVM / MA decadiene crosspolymer, poly(ethylene oxide)-based thickeners, sodium carbomer, and mixtures thereof.When used, rheology modifiers are preferably included in the formulations of the present invention at a concentration of 0.01 to 12 weight percent, preferably 0.05 to 10 weight percent, and most preferably 0.1 to 6 weight percent.

[0112] The cosmetic or dermopharmaceutical formulations of the present invention may contain one or more antioxidants, including, but not limited to, ascorbic acid, BHT, BHA, erythorbic acid, bisulfite, thioglycolate, tocopherol, sodium metabisulfite, vitamin E acetate, and ascorbyl palmitate. The antioxidant is present in an amount of 0.01 to 5 weight percent, preferably 0.1 to 3 weight percent, and most preferably 0.2 to 2 weight percent of the formulation.

[0113] The cosmetic or dermopharmaceutical preparations of the present invention may contain one or more preservatives. Examples of preservatives include, but are not limited to, 1,2-dibromo-2,4-dicyanobutane (also known as methyldibromoglutaronitrile, MERGUARD®, Ondeo Nalco Company, Naperville, Ill., USA), benzyl alcohol, imidazolidinyl urea, 1,3-bis(hydroxymethyl)-5,5-dimethyl-2,3-imidazolidinedione (e.g., DMDM ​​hydantoin, known as GLYDANT®, Lonza, Fairlawn, NJ, USA), methylchloroisothiazolinone and methylisothiazolinone (e.g., Kathon®, Rohm & Haas Co., Philadelphia, Pa., USA), methylparaben, propylparaben, phenoxyethanol, and sodium benzoate, and mixtures thereof.

[0114] The cosmetic or dermopharmaceutical formulations of the present invention may contain any other ingredients commonly used in cosmetics, including, but not limited to, buffering agents, fragrance ingredients, chelating agents, pigments, color additives that may serve to color the composition itself or keratin, sequestrants, emollients, foam synergists, foam stabilizers, sun filters, sunscreens, peptizers, electrolytes such as aluminum chlorohydrate or alkali salts, or salts with organic acids.

[0115] The cosmetic or dermopharmaceutical formulations of the present invention may contain water and any cosmetically acceptable solvent. Examples of acceptable solvents include, but are not limited to, monoalcohols, such as alkanols having 1 to 8 carbon atoms (e.g., ethanol, isopropanol, benzyl alcohol, and phenylethyl alcohol), polyalcohols, such as alkylene glycols (e.g., glycerin, ethylene glycol, and propylene glycol), and glycol ethers, such as mono-, di-, and tri-ethylene glycol monoalkyl ethers, e.g., ethylene glycol monomethyl ether and diethylene glycol monomethyl ether, used alone or in mixtures. These solvents may be present in an amount of up to about 70 weight percent, e.g., 0.1 to 70 weight percent, based on the weight of the total composition.

[0116] The cosmetic or dermopharmaceutical formulations of the present invention may contain agents that increase the percutaneous absorption of the active ingredient, including, but not limited to, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, surfactants, Azone (1-dodecylazacycloheptan-2-one), alcohol, urea, ethoxydiglycol, acetone, propylene glycol, or polyethylene glycol, among others. Furthermore, the cosmetic or dermopharmaceutical formulations of the present invention may be applied to the local area to be treated by iontophoresis, sonophoresis, electroporation, microelectric patching, mechanical pressure, osmotic gradient, occlusive cure, microinjection, or needleless injection by pressure, such as oxygen pressure injection, or any combination thereof, to achieve better penetration of the active ingredient. The area of ​​application is determined by the nature of the condition, disorder, and / or disease to be treated and / or cared for.

[0117] The cosmetic or dermopharmaceutical formulations of the present invention may contain additional active ingredients that can be found in the solution or dispersion. Non-limiting examples include amino acids, peptides, proteins, hydrolyzed proteins, enzymes, hormones, vitamins, mineral salts, sugars, nucleotides, nucleic acids, molecules and extracts of biological and biotechnological origin, plant extracts, cell extracts, essential oils, molecules of synthetic or natural origin, isoflavones, polyphenols, retinol, hyaluronic acid, and / or mixtures thereof. In particular, the cosmetic or dermopharmaceutical formulations may contain dimethylmethoxychromanol, such as the Lipochroman™ molecule from Lipotec SA.

[0118] In particular, the cosmetic or dermopharmaceutical preparations of the invention may comprise, in addition to the composition of the invention, a C9-12 alkane and / or coco-caprylate / caprate.

[0119] In particular, the cosmetic or dermopharmaceutical formulations of the present invention may contain, in addition to the compositions of the present invention, C9-12 alkanes, coco-caprylate / caprate, AlgaPur™ High Stability High Oleic (HSHO) algal oil, jojoba seed oil, tocopheryl acetyl acetate, methyl glucose dioleate, and / or mixtures thereof. Optionally, the formulations may contain fragrances and / or antioxidants. More specifically, the formulations include C9-12 alkane, coco-caprylate / caprate, AlgaPur™ High Stability High Oleic (HSHO) algal oil, jojoba seed oil, tocopheryl acetyl acetate, and methyl glucose dioleate.

[0120] In particular, the cosmetic or dermopharmaceutical formulations of the present invention may contain, in addition to the composition of the present invention, a C9-12 alkane, coco-caprylate / caprate, dimethicone / vinyl dimethicone crosspolymer, and / or mixtures thereof. More particularly, the formulations may further contain frangances and / or preservatives.

[0121] In particular, the cosmetic or dermopharmaceutical formulations of the present invention may contain, in addition to the composition of the present invention, C9-12 alkane, coco-caprylate / caprate, silica dimethyl silylate, dimethicone / vinyl dimethicone crosspolymer, polyglyceryl-3 polyricinoleate, methyl glucose dioleate, polyhydroxystearic acid, neopentyl glycol diethylhexanoate, isododecane, disteardimonium hectorite, propylene carbonate, titanium dioxide, iron oxide, propanediol, glyceryl caprylate, magnesium sulfate, and sodium benzoate. More specifically, the formulations may further contain fragrance and / or preservatives.

[0122] In particular, the cosmetic or dermopharmaceutical formulations of the present invention may contain, in addition to the composition of the present invention, caprylic / capric triglyceride, neopentyl glycol diethylhexanoate, isostearyl isostearate, and / or mixtures thereof. More specifically, the formulations may contain caprylic / capric triglyceride, polyurethane-79, neopentyl glycol diethylhexanoate, isostearyl isostearate, silica, wax, and glyceryl caprylate. More specifically, the wax is carnauba wax, candelilla wax, bran wax, and / or mixtures thereof.

[0123] In particular, the cosmetic or dermopharmaceutical preparations of the present invention may comprise, in addition to the composition of the present invention, isododecane, isostearyl isostearate, microcrystalline cellulose, at least one C9-C12 alkane, and / or mixtures thereof.

[0124] method In one aspect, the present invention provides a method for dispersing a hydrophilic active ingredient in an oil, the method comprising: (i) dissolving a hydrophilic active ingredient in an aqueous solution; (ii) mixing the aqueous solution obtained in step i) with an oil system comprising a combination of methyl glucose sesquistearate, polyglyceryl-3 esters of fatty acids, and an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate.

[0125] In particular, the hydrophilic active ingredient may be dissolved in the aqueous solution at a concentration of 0.1 to 100 mg / mL, or 1 to 10 mg / mL, or 2.5 to 7.5 mg / mL.

[0126] In particular, the aqueous solution consists essentially of or even consists of water. More particularly, the water is distilled water or purified water.

[0127] In particular, the oil system (ii) is heated to 40 to 70°C, in particular 50 to 65°C, before being mixed with the aqueous solution containing the hydrophilic active ingredient of i).

[0128] In particular, the aqueous solution containing the hydrophilic active ingredient (i) is slowly added onto the oil system (ii) with continuous mechanical stirring, and the resulting mixture is mixed with continuous mechanical stirring until the temperature cools to 20-25°C.

[0129] The polyglyceryl-3 ester may in particular be triglycerol laurate. The ester oil may in particular be cetyl ethylhexanoate. Thus, in one embodiment, the present invention provides a method for dispersing a hydrophilic active ingredient in oil, the method comprising the steps of (i) dissolving the hydrophilic active ingredient in an aqueous solution, and (ii) mixing the aqueous solution obtained in step i) with an oil phase comprising a combination of methyl glucose sesquistearate, triglycerol laurate, and cetyl ethylhexanoate. More specifically, the oil phase is heated to 40-70°C, preferably 50-65°C, prior to mixing.

[0130] Purpose The compositions described herein are useful for delivering hydrophilic active ingredients for the treatment of skin, hair, nails, and / or mucous membranes. The compositions are particularly useful for delivering hydrophilic cosmetic active ingredients.

[0131] Thus, in one aspect, the present invention provides a method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails, and / or mucous membranes of a subject, the method comprising topically administering a cosmetically effective amount of a composition or cosmetic formulation according to the preceding aspect.

[0132] Non-limiting examples of cosmetic non-therapeutic treatments and / or care in the context of the present invention include treatment and / or prevention of skin aging, treatment and / or prevention of skin wrinkles, maintaining and improving skin firmness, stimulating collagen synthesis and / or preventing collagen loss, treatment and / or prevention of the appearance of sagging skin, reduction and / or prevention of facial asymmetry, increasing adipose tissue volume and / or preventing and / or alleviating the effects of adipose tissue loss, treatment and / or prevention of photoaging of the skin, promoting the self-renewal properties of the skin, regulating the skin microflora, preventing and / or treating dandruff, maintaining and / or improving skin hydration and / or moisturization, maintaining and / or improving skin microcirculation, maintaining and / or improving skin brightness and / or radiance, skin lightening and / or reduction of dark spots, treatment and / or prevention of skin fatigue, maintaining and / or improving skin barrier function, maintaining and / or improving skin tone and / or revitalizing the skin.

[0133] In particular, the cosmetic non-therapeutic treatment and / or care method may be the treatment and / or prevention of skin ageing and / or the reduction and / or prevention of skin wrinkles.

[0134] The present invention also provides the use of a composition according to the first aspect for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, in particular for the treatment and / or prevention of skin ageing and / or the reduction and / or prevention of skin wrinkles. [Example]

[0135] The present invention is illustrated by the following non-limiting examples, which are included for illustrative purposes only and should not be construed as limitations on the invention claimed herein.

[0136] Examples 1 to 5 Different compositions containing PEP-1 were prepared, including the ingredients listed in Table 2.

[0137] The procedure consisted of mixing two phases: a water phase (Phase A) and an oil phase (Phase B). Phase A is a solution of peptides in water. Phase B is a dispersion of Lubrizol Advanced Materials, Inc.'s Glucate™ DO emulsifier and Lubrizol Advanced Materials, Inc.'s Algapur™ High Stability High Oleic (HSHO). Phase A is slowly added to Phase B while mixing.

[0138] The stability of the formulations was determined by visual inspection and by quantification of the amount of active ingredient by high performance liquid chromatography (HPLC). - Visual inspection: The results are classified as OK or KO according to the physical appearance. OK represents a clear solution at t=0 hours, with small particles at the bottom after 24 hours. KO represents a solution that is completely separated into phases, is cloudy, or has an unacceptable sediment at the bottom. Stability: The peptide concentration was determined by HPLC after storing the composition at room temperature for 1 week. The composition was diluted 10 times with 1 g of dimethyl sulfoxide (DMSO). 25 microliters of the solution was then injected onto a Kromasil 100 Å, C-8, 5 μm, 250 × 4.6 mm column. The solvents used were solvent A, HO / TFA, and solvent B, acetonitrile / TFA.

[0139] The separation gradient was as follows:

[0140] [Table A]

[0141] The concentration of the peptides was determined by correlating the sum of the areas of the peaks corresponding to the non-oxidized and oxidized peptides with that of peptide standards.

[0142] The recovery rate of the peptide was calculated as follows:

[0143]

number

[0144] The theoretical concentration of the peptide in the composition was 0.05% by weight in Example 1 and 0.125% by weight in Examples 2-5.

[0145] [Table 2]

[0146] In Examples 1, 4, and 5, the peptide could be dispersed in oil and the appearance was acceptable at time 0. However, over 20% of the peptide concentration was lost after one week at room temperature, which is considered unacceptable. Therefore, the results indicate that the stability of the peptide in oil was compromised.

[0147] Examples 6 to 11 Examples 6 to 11 shown in Tables 3a and 3b were prepared to test the effect of emulsifiers on the stability of the compositions. Compositions that were visually stable after 24 hours were stored at different temperatures for 3 months to determine their long-term stability.

[0148] The process for preparing the composition involved mixing two phases: an aqueous phase (Phase A) and an oil phase (Phase B). Phase A is a solution of peptide in water. Phase B is a dispersion of Schercemol™ CO ester from Lubrizol Advanced Materials, Inc., an emulsifier (either Glucate™ SS, Glucamate™ SSE-20, or Glucate™ DO from Lubrizol Advanced Materials, Inc.), and Hydramol™ TGL ester from Lubrizol Advanced Materials, Inc. Phase B is heated to 50-65°C and cooled. At room temperature, Phase A is slowly added to Phase B with mixing.

[0149] [Table 3a]

[0150] [Table 3b]

[0151] Glucate™ SS emulsifier was tested at concentrations of 0% to 3% by weight based on the total weight of the composition (Examples 6-11). When used at 0%, 0.5%, and 3%, unacceptable sediment was observed at the bottom, but at concentrations of 1% to 2%, the composition was stable.

[0152] When the same compositions were tested using 1 wt. % Glucamate™ SSE-20 emulsifier (Example 12) or 1 wt. % Glucate™ DO emulsifier (Example 13), unacceptable sediment was observed in both compositions.

[0153] The sample with 1 wt% Glucate™ SS emulsifier (Example 8) was analyzed by HPLC and virtually all concentrations of peptide were recovered after 3 months of stability (Table 4).

[0154] [Table 4]

[0155] Examples 14 to 18 Different compositions shown in Table 5 were prepared to evaluate the effect of solubilizers in the oil phase on the stability of the compositions.

[0156] Hydramol™ TGL Ester was tested at concentrations of 5% to 15% by weight (Examples 14-17). When used at 5%, 8%, and 15%, unacceptable sediment was observed at the bottom, but at concentrations of 10% to 12%, the composition was stable.

[0157] When the same composition was tested using Plurol Diisostearique CG from Gattefosse at 10% (Example 18), unacceptable sedimentation was observed.

[0158] [Table 5]

[0159] Examples 19 to 22 Different compositions were prepared to determine the effect of the amount of water in the composition.

[0160] Water concentrations ranging from 2% to 7% by weight were tested. When used at 2% by weight (Example 19) and 7% by weight (Example 22), unacceptable sediment was observed at the bottom. However, at concentrations of 2.5% to 5% by weight, the composition was stable.

[0161] [Table 6]

[0162] Examples 23 to 25 To determine the relevance of the ester oil, different compositions were prepared (Table 7).

[0163] Isopropyl isostearate and ethylhexyl palmitate (Examples 23 and 24, respectively) were tested at 86.375% by weight. After 24 hours, some particles were observed at the bottom. Diisopropyl adipate (Example 25) was tested as a solvent at 86.375% and unacceptable sediment was observed immediately after mixing.

[0164] [Table 7]

[0165] Examples 26 to 28 Different peptides with known cosmetic properties were tested using the optimal concentrations of the ingredients previously determined.

[0166] PEP-2, PEP-8, and PEP-9 (Examples 26, 27, and 28, respectively) had good compatibility, resulting in compositions with acceptable physical appearance.

[0167] [Table 8]

[0168] Example 29 An oil serum containing the composition of Example 8 was prepared containing the following ingredients:

[0169] [Table 9]

[0170] Example 30 A makeup cream foundation containing the composition of Example 8 was prepared containing the following ingredients:

[0171] [Table 10]

[0172] Example 31 A facial serum stick containing the composition of Example 8 was prepared containing the following ingredients:

[0173] [Table 11]

[0174] Example 32 A cream to powder mousse was prepared containing the following ingredients:

[0175] [Table 12]

[0176] Example 33 A biphasic serum was prepared containing the following ingredients:

[0177] [Table 13]

[0178] The present invention can be further described by the following numbered clauses: 1. A composition comprising: i) an aqueous solution containing 2 to 5% by weight of a hydrophilic active ingredient; ii) 1 to 2% by weight of methyl glucose sesquistearate; iii) 10 to 12% by weight of polyglyceryl-3 esters of fatty acids; iv) at least 83% by weight of an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate; All weight percentages are based on the total weight of the composition; The sum of i), ii), iii), and iv) does not exceed 100% by weight of the composition. 2. The composition described in clause 1, wherein the polyglycerol-3 ester of a fatty acid is triglycerol laurate. 3. The composition according to clause 1 or 2, wherein the ester oil is cetyl ethylhexanoate. 4. A composition according to any one of the preceding clauses, wherein the active ingredient is a cosmetically active ingredient. 5. A composition according to any one of the preceding clauses, wherein the active ingredient is a peptide, a plant extract, or an ingredient obtained from a biotechnological process. 6. The composition of clause 5, wherein the peptide is selected from the group consisting of tripeptides, tetrapeptides, pentapeptides, hexapeptides, heptapeptides, octapeptides, and nonapeptides. 7. Peptides are R1-Glu-Glu-Met-Gln-Arg-Arg-R2 (SEQ ID NO: 1), R1-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-R2 (SEQ ID NO: 2), R1-Glu-Glu-Met-Gln-Arg-Arg-Ala-R2 (SEQ ID NO: 3), R1-Arg-Arg-Gln-Met-Glu-Glu-R2 (SEQ ID NO: 4), R1-Arg-Arg-D-Gln-Met-Glu-Glu-R2 (SEQ ID NO: 5), R1-Arg-Arg-Gln-D-Met-Glu-Glu-R2 (SEQ ID NO: 6), R1-Arg-Arg-D-Gln-D-Met-Glu-Glu-R2 (SEQ ID NO: 7), R1-Phe-Trp-Met-Lys-Arg-Lys-Arg-Val-Pro-R2 (SEQ ID NO: 8), R1-Tyr-D-Ala-Gly-Phe-Leu-R2 (SEQ ID NO: 9), and R1-Leu-Pro-Val-Thr-R2 (SEQ ID NO: 10), wherein R1 is selected from the group consisting of H and R5-CO-, and R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl, R2 is —NR3R4 or —OR3, and R3 and R4 are independently selected from the group consisting of H and C1-C 16 7. The composition of claim 6, wherein the alkyl is selected from the group consisting of alkyl. 8. The peptide is Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2(PEP-1), Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH2(PEP-2), Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-NH2(PEP-3), Ac-Arg-Arg-Gln-Met-Glu-Glu-NH2(PEP-4), Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2(PEP-5), Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2(PEP-6), Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2(PEP-7), H-Phe-Trp-Met-Lys-Arg-Lys-Arg-Val-Pro-NH2(PEP-8), H-Tyr-D-Ala-Gly-Phe-Leu-OH(PEP-9), and 8. The composition of claim 6 or 7, wherein the one or more peptides are selected from the group consisting of H-Leu-Pro-Val-Thr-OH (PEP-10). 9. The peptide is Ac-Glu-Glu-Met-Gln-Arg-Arg-NH 2, 9. The composition according to clause 8, wherein the amino acid sequence is H-Tyr-D-Ala-Glu ... 10. The composition of clause 9, wherein the peptide is Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2. 11. The composition according to any one of the preceding clauses, wherein the amount of aqueous solution i) is 2 to 3% by weight, based on the total weight of the composition. 12. The composition according to any one of the preceding clauses, wherein the amount of aqueous solution i) is 2 to 2.5% by weight, based on the total weight of the composition. 13. The composition of any one of the preceding clauses, wherein the amount of methyl glucose sesquistearate is 1 to 1.5% by weight, based on the total weight of the composition. 14. The composition of any one of the preceding clauses, wherein the active ingredient is in an amount of 0.01 to 0.5% by weight, or 0.05 to 0.25% by weight, or 0.1 to 0.2% by weight, based on the total weight of the composition. 15. A method for dispersing a hydrophilic active ingredient in oil, comprising: (i) dissolving a hydrophilic active ingredient in an aqueous solution; (ii) mixing the aqueous solution obtained in step i) with an oil system comprising a combination of methyl glucose sesquistearate, polyglyceryl-3 esters of fatty acids, and an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate. 16. The method according to clause 15, wherein the oil phase is heated to 50-65°C before mixing. 17. The method of clause 15 or 16, wherein the active ingredient is a peptide. 18. The method of any one of clauses 15 to 17, wherein the polyglyceryl-3 ester of a fatty acid is triglycerol laurate. 19. The method of any one of clauses 15 to 18, wherein the ester oil is cetyl ethylhexanoate. 20. The method of any one of clauses 15 to 19, wherein the active ingredient is dissolved in water. 21. A cosmetic or dermopharmaceutical preparation comprising a composition according to any one of clauses 1 to 14 together with at least one cosmetically or dermopharmaceutical acceptable excipient or adjuvant. 22. A cosmetic or dermopharmaceutical preparation according to clause 21, in which the concentration of the composition according to clauses 1 to 14 is in an amount of 0.001 to 10% by weight, preferably 0.004 to 5% by weight, based on the total weight of the cosmetic or dermopharmaceutical preparation. 23. Cosmetic or dermopharmaceutical preparations according to clauses 21 or 22, in the form of a cream, multiple emulsion, foundation, solution, anhydrous preparation, dispersion, oil, milk, balsam, lotion, gel, cream gel, liniment, conditioner, serum, stick, ointment, mousse, pomade, powder, bar, pencil, spray, aerosol or mask. 24. A cosmetic or dermopharmaceutical preparation according to clause 21 or 22, wherein the preparation is incorporated into a textile or device. 25. A method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, comprising topically administering a cosmetically effective amount of a composition according to any one of clauses 1 to 14 or a cosmetic formulation according to any one of clauses 21 to 24. 26. The method according to clause 25, wherein the cosmetic non-therapeutic treatment and / or care is the treatment and / or prevention of skin ageing, reduction and / or prevention of skin wrinkles. 27. Use of a composition according to any one of clauses 1 to 14 for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject.

Claims

1. 1. A composition comprising: i) an aqueous solution containing 2-5% by weight of a hydrophilic active ingredient; ii) 1-2% by weight of methyl glucose sesquistearate; iii) 10-12 wt. % of polyglyceryl-3 esters of fatty acids; iv) at least 83% by weight of an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate; All of the above weight percentages are based on the total weight of the composition; The sum of i), ii), iii), and iv) does not exceed 100% by weight of the composition.

2. 2. The composition of claim 1, wherein the polyglycerol-3 ester of a fatty acid is triglycerol laurate.

3. 3. The composition of claim 1, wherein the ester oil is cetyl ethylhexanoate.

4. The composition according to any one of claims 1 to 3, wherein the active ingredient is a cosmetic active ingredient.

5. The composition according to any one of claims 1 to 4, wherein the active ingredient is a peptide.

6. The peptide is R １ -Glu-Glu-Met-Gln-Arg-Arg-R ２ (SEQ ID NO: 1), R １ -Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-R ２ (SEQ ID NO: 2), R １ -Glu-Glu-Met-Gln-Arg-Arg-Ala-R ２ (SEQ ID NO: 3), R １ -Arg-Arg-Gln-Met-Glu-Glu-R ２ (SEQ ID NO: 4), R １ -Arg-Arg-D-Gln-Met-Glu-Glu-R ２ (SEQ ID NO: 5), R １ -Arg-Arg-Gln-D-Met-Glu-Glu-R ２ (SEQ ID NO: 6), R １ -Arg-Arg-D-Gln-D-Met-Glu-Glu-R ２ (SEQ ID NO: 7), R １ -Phe-Trp-Met-Lys-Arg-Lys-Arg-Val-Pro-R ２ (SEQ ID NO: 8), R １ -Tyr-D-Ala-Gly-Phe-Leu-R ２ (SEQ ID NO: 9), and R １ -Leu-Pro-Val-Thr-R ２ (SEQ ID NO: 10), Here, R １ is H and R ５ -CO-, and R ５ is C １ ~C １８ Alkyl, C ２ ~C ２４ Alkenyl, C ３ ~C ２４ cycloalkyl; R ２ is -NR ３ R ４ Or -OR ３ and R ３ and R ４ are independently H and C １ ~C １６ 6. The composition of claim 5, wherein the alkyl is selected from the group consisting of alkyl.

7. the one or more peptides Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ２ (PEP-1)、 Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH ２ (PEP-2)、 Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-NH ２ (PEP-3)、 Ac-Arg-Arg-Gln-Met-Glu-Glu-NH ２ (PEP-4)、 Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2 (PEP-5), Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH ２ (PEP-6)、 Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH ２ (PEP-7)、 (PhemTrppMett-yserr g-;ysmArggmall-roomｨ ２ (..0.0.8)、 H-Tyr-D-Ala-Gly-Phe-Leu-OH (PEP-9), and 7. The composition according to claim 5 or 6, wherein the hydroxybenzoate is selected from the group consisting of H-Leu-Pro-Val-Thr-OH (PEP-10).

8. The composition according to any one of claims 1 to 7, wherein the amount of aqueous solution i) is 2 to 3 wt. %, preferably 2 to 2.5 wt. %, based on the total weight of the composition.

9. The composition according to any one of claims 1 to 8, wherein the amount of methyl glucose sesquistearate is 1 to 1.5% by weight, based on the total weight of the composition.

10. 10. The composition of any one of claims 1 to 9, wherein the active ingredient is in an amount of 0.01 to 0.5 wt. %, or 0.05 to 0.25 wt. %, or 0.1 to 0.2 wt. %, based on the total weight of the composition.

11. 1. A method for dispersing a hydrophilic active ingredient in oil, comprising: (i) dissolving a hydrophilic active ingredient in an aqueous solution; (ii) mixing the aqueous solution obtained in step i) with an oil system comprising a combination of methyl glucose sesquistearate, polyglyceryl-3 esters of fatty acids, and an ester oil selected from the group consisting of cetyl ethylhexanoate, isopropyl isostearate, and ethylhexyl palmitate.

12. A cosmetic or dermopharmaceutical preparation comprising a composition according to any one of claims 1 to 10 together with at least one cosmetically or dermopharmaceutical acceptable excipient or adjuvant.

13. 13. The cosmetic or dermopharmaceutical formulation according to claim 12, wherein the concentration of the composition according to any one of claims 1 to 10 is in an amount of 0.001 to 10% by weight, preferably 0.004 to 5% by weight, based on the total weight of the cosmetic or dermopharmaceutical formulation.

14. A method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, comprising topically administering a cosmetically effective amount of a composition according to any one of claims 1 to 10, or a cosmetic formulation according to claim 12 or 13.

15. Use of a composition according to any one of claims 1 to 10 for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject.

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