Stable composition, methods and uses thereof

Abstract

A stable emulsified composition, namely a pharmaceutical or cosmetic compositions, comprising a bioactive mixture, a phospholipid as an emulsifier, an oil component and at least one diol with enhanced stability, moisturizing effect, antioxidant benefits, and antimicrobial properties for application on skin, hair, nails, and / or scalp. The composition comprises a carefully selected blend of emulsifiers, antioxidants, and antimicrobial agents, ensuring the stability of the emulsion over time and promoting a suitable treatment for beauty healthcare.

Description

STABLE COMPOSITION, M ETHODS AND USES THEREOFTECHNICAL FIELD

[0001] The present disclosure relates to a stable and safe emulsified waterless composition, namely a pharmaceutical or cosmetic composition, to enhance specific attributes of the skin, hair, nail, and / or scalp. This stable composition has a better shelf stability, moisturizing, antioxidant, antimicrobial properties and promotes microbiome balance on the skin and scalp.BACKGROUND

[0002] Stable compositions often face challenges related to instability, susceptibility to oxidation, and microbial contamination, which can compromise their efficacy and safety. The present disclosure addresses these challenges by providing a stable emulsified composition with enhanced moisturizing, antioxidant and antimicrobial properties, suitable for various cosmetic / pharmaceutical applications.

[0003] These facts are disclosed in order to illustrate the technical problem addressed by the present disclosure.GEN ERAL DESCRIPTION

[0004] A stable emulsified composition, namely a pharmaceutical or cosmetic composition, is disclosed herein, formulated to provide enhanced stability, antioxidant benefits, and antimicrobial properties for application on skin, hair, nails, and / or scalp. The composition comprises a carefully selected blend of emulsifiers, antioxidants, and antimicrobial agents, ensuring the stability of the emulsion over time and promoting skin health.

[0005] The present disclosure pertains to stable emulsified waterless composition comprising a green solvent, which can be a naturally occurring product, a mixture of them or a NAtural Deep Eutectic Solvent (NADES), serving as a solvent itself or to extract bioactive compounds, along with an emulsifier (e.g. phospholipids), an oil phase, and at least one soluble auxiliary, such as a diol. Furthermore, the composition of the present disclosure may further include a peptide, a cosmetic / pharmaceutic component, or a combination thereof, with the intent of addressing and enhancing specific attributes of hair, nail, scalp, and skin.

[0006] The stable emulsified composition disclosed herein can be formulated into various skincare, haircare, nail care, and scalp care products, including but not limited to lotions, creams, serums,shampoos, conditioners, and treatments. Its stability, antioxidant activity, and antimicrobial efficacy make it suitable for use in a wide range of cosmetic / pharmaceutic formulations, catering to diverse consumer needs.

[0007] NADES are a type of solvent formed by mixing two or more naturally occurring compounds at a certain ratio, resulting in a eutectic mixture with unique properties. They are gaining attention as environmentally friendly alternatives to traditional solvents in various applications, including pharmaceuticals, cosmetics, and green chemistry with high efficiency in extracting natural components.

[0008] The present disclosure relates to a stable emulsified composition that provides a synergistic blend of stability, moisturizing, antioxidant, and antimicrobial properties, thereby positioning it as a valuable component for crafting premium cosmetic products.

[0009] The present disclosure relates to a stable emulsified composition, comprising: a bioactive mixture; a phospholipid as an emulsifier; and di-alcohol as a solvent; wherein bioactive mixture comprises a green solvent as NADES and an active cosmetic compound; wherein the NADES is a mixture of lactic acid and glycerol. Preferably for better results the composition does not comprise water.

[0010] Phospholipids (unsaturated or hydrogenated) are used as skin-friendly emulsifier agents. They help to repair and restore our skin's natural protective barrier. They mimic the lamellar structure of the extracellular matrix and form a protective layer, preventing water loss from the skin. Phospholipids themselves can be used as a powerful cosmetic / pharmaceutic active ingredient for skin protection and skin rejuvenation, and as a carrier system for cosmetic / pharmaceutic active ingredients improving their skin interaction, resulting in a long-lasting cosmetic effect.

[0011] Green solvents (e.g. NADES) as bio-solvents to dissolve cosmetic ingredients or to prepare natural extracts from plants or insects are used in cosmetic products with several antioxidant and antimicrobial activity.

[0012] Alcohols such as a diol, are versatile ingredients used as solvents and viscosity decreasing agents in cosmetic formulations. They are also used as moisturizing agents, emollients and humectants in cosmetics products.

[0013] The oil phase influences the final characteristics of a cosmetic / pharmaceutical product, including its spreading behaviour and sensory properties. It can provide also antioxidant and antimicrobial properties.

[0014] An aspect of the present disclosure relates to a stable emulsified composition, namely a pharmaceutical or cosmetic composition, comprising: a bioactive mixture; a phospholipid as an emulsifier; and di-alcohol as a solvent;wherein the bioactive mixture comprises a green solvent and an active cosmetic / pharmaceutical compound; wherein the green solvent is selected from a list consisting of a mixture of at least two of: lactic acid, glycolic acid, decanoic acid, citric acid, maleic acid, malic acid, oxalic acid, tartaric acid, oleic acid, palmitic acid, enanthic acid, formic acid, caprylic acid, ethylene glycol, propylene glycol, glycine, glycerol, glucose, transcutol, menthol, sodium lactate, sodium acetate, sodium citrate, xylitol and sorbitol more preferably lactic acid, glycolic acid, glycine, glycerol, ethylene glycol and propylene glycol.

[0015] The stable emulsified composition of the present disclosure provides enhanced stability, antioxidant benefits, and antimicrobial properties for application on skin, hair, nails, and / or scalp. Unexpectedly, the composition of the present disclosure also promotes microbiome balance on the skin and scalp, leveraging the synergistic interaction between green solvents, active cosmetic / pharmaceutical compound, and phospholipids for improved dermatological health and aspect.

[0016] In an embodiment for better results, the cosmetic composition may comprise:0.01 to 30% (w / w) of a bioactive mixture;0.01 to 50% (w / w) of a phospholipid as an emulsifier;0.01 to 40% (w / w) of a di-alcohol as a solvent.

[0017] In an embodiment for better results, the cosmetic / pharmaceutic composition may comprise:10 to 30% (w / w) of the bioactive mixture;10 to 50% (w / w) of the phospholipid as an emulsifier;10 to 40% (w / w) of the di-alcohol as a solvent.

[0018] In an embodiment for better results, the cosmetic / pharmaceutic composition may comprise:15 to 20% (w / w) of the bioactive mixture;20 to 50% (w / w) of the phospholipid as an emulsifier, preferably 20 to 40% (w / w);20 to 30% (w / w) of the di-alcohol as a solvent.

[0019] In an embodiment for better results, the phospholipid is selected from a list consisting of: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, lecithin including unsaturated as well as hydrogenated phospholipids, or mixtures thereof.

[0020] In an embodiment for better results, the phospholipid is selected from a list consisting of: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lecithin or mixtures thereof; lecithin.

[0021] In another embodiment for better results, the phospholipid is selected from a list consisting of: phosphatidylcholine and / or lecithin.

[0022] In an embodiment for better results, the amount of an active cosmetic compound ranges from 0.01 to 10 % (w / w).

[0023] In an embodiment for better results, the amount of an active cosmetic / pharmaceutic compound; ranges from 0.01 to 5 % (w / w).

[0024] embodiment for better results, the amount of an active cosmetic / pharmaceutic compound ranges from 0.5 to 2 % (w / w).

[0025] In an embodiment for better results, the at least two components of the bioactive mixture are selected from a list consisting of : lactic acid, glycolic acid, decanoic acid, citric acid, maleic acid, malic acid, oxalic acid, tartaric acid, oleic acid, palmitic acid, enanthic acid, formic acid, caprylic acid, ethylene glycol, propylene glycol, glycine, glycerol, glucose, transcutol, menthol, sodium lactate, sodium acetate, sodium citrate, xylitol and sorbitol more preferably lactic acid, glycolic acid, glycine, glycerol, ethylene glycol and propylene glycol, choline chloride, or mixtures thereof.

[0026] In an embodiment for better results, the di-alcohol is selected from a list consisting of: 1,2- Propanediol; 1,3-Propanediol; 1,2-Butanediol; 1,3-Butanediol; 1,4-Butanediol; 2,3-Butanediol; 1,2- Hexanediol; 1,6-Hexanodiol; 1,5-Pentanediol; 1,2-Octanediol; 1,8-Octanediol; 1,2-Decanediol; 1,10- Decanediol; Methylpropanediol; 2-Butyl-2-ethyl-1,3-propanediol, Isopentyldiol and Ethane-1,2-diol or mixtures thereof.

[0027] In an embodiment for better results, the di-alcohol is selected from a list consisting of: 1,2- Propanediol; 1,3-Propanediol; 1,2-Butanediol; 1,3-Butanediol; 1,4-Butanediol; 2,3-Butanediol; 1,2- Hexanediol; 1,6-Hexanodiol; more preferably 1,3-Propanediol, 1,2-Butanediol and 1,2-Hexanediol, or mixtures thereof.

[0028] In an embodiment for better results, the composition may further comprise a natural oil, a propellant, a fragrance, an oil, or mixtures thereof.

[0029] In an embodiment for better results, the composition may further comprise an essential oil, an insect-based oil, a plant-based oil, or mixtures thereof.

[0030] In an embodiment for better results, the composition may further comprise a peptide preferably at least a peptide 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence selected from a list consisting of:SEQ ID No 552: YGGFL;SEQ. ID No 553: YPWF;SEQ. ID No 554: YGGFM;SEQ. ID No 555: YPFF;SEQ ID No 556: EEMQRR;SEQ ID No 557: MGWCTASVPPQCYG;SEQ. ID No 558: ATAKAWLKGIGAGAGAGA;SEQ. ID No 559: RRQMEEGAGAGAGA;SEQ ID No 560: GGVCGPSPPCITTATAKAWLKGI;SEQ ID No 561: GGVCGPSPPCITTGAGAGAGATAKAWLKGI;SEQ ID No 562: ATAKAWLKGIGGVCGPSPPCITT;SEQ ID No 563: ATAKAWLKGIAGAGAGAGGVCGPSPPCITT;SEQ ID No 564: GGVCGPSPPCITTATAKAWLKGIRRQMEE;SEQ ID No 565: RRQMEEATAKAWLKGIGGVCGPSPPCITT;SEQ ID No 566: GGVCGPSPPCITTRRQMEE;SEQ ID No 584: GGVCGPSPPCITTGAGAGAGARRQMEE;SEQ ID No 585: RRQMEEGGVCGPSPPCITT;SEQ ID No 586: RRQMEEGGVCGPSPPCITTGRKKRRQRRRPPQ;SEQ ID No 587: GRKKRRQRRRPPQGGVCGPSPPCITTRRQMEE;SEQ ID No 568: RRQMEEGAGAGAGAGGVCGPSPPCITT;SEQ ID No 569: ATAKAWLKGIMGWCTASVPPQCYG;SEQ ID No 570: RRQMEEMGWCTASVPPQCYG;SEQ ID No 2: GGVCGPSPPCITTVPGVGVPGVGVPGVGVPGVGVPGVGVPGVG;SEQ ID No 549: GGVCGPSPPCITTGAGAGSGAGAGSVPAVGVPAVGVPAVG;SEQ ID No 5: GGVCGPSPPCITTGPTGPTGPAGPRGLQGLQGLQGERGEQGPT;SEQ ID No 4: GGVCGPSPPCITTGGRPSDSYGAPGGGN;SEQ ID No 6: GGVCGPSPPCITTGGFGGMGGGSGGFGGMGGGSGGFGGMGGGS;SEQ ID No 45: GGVCGPSPPCITTAKAKAKAKAKAKAKAKAKAKAKAKAKAKAK;SEQ ID No 46: GGVCGPSPPCITTLKLKLKLKLKLKLKLKLKLKLKLKLKLKLK;SEQ ID No 573: GGVCGPSPPCITTRCAERCSEASIQDRCLKYCGICCEK;SEQ ID No 574: GGVCGPSPPCITTGTYGNKDECPCYRDMKNSKGKGKCP;SEQ ID No 572: GGVCGPSPPCITTGTCYINDDEGCTKRCQGIYIYRREAVMGHC;SEQ ID No 588: LKLKLKLKLKLKLKLKLKLK;SEQ ID No 589: LELELELELELELELELELE;SEQ ID No 571: YGRKKRRQRRR;SEQ ID No 575: GRKKRRQRRRPPQ;SEQ ID No 576: RQIKIWFQNRRMKWKK;SEQ ID No 590: RKKNPNCRRH;SEQ ID No 577: RIMRILRILKLAR;SEQ ID No 578: LLIILRRRRIRKQAHAHSK;SEQ ID No 579: GVCGPSPPCITTDRDDQAAWFSQY;SEQ. ID No 580:MVYYPNPCSPYPCRNGGTCKKRGLYSYKCYCRKGYTGKNCQYNACFPNPCLNGGTCGYVYGYPYYKCSCPYGYY GKQCQLKKYGGVCGPSPPCITT;SEQ. ID No 581: GGVCGPSPPCITTERSRSSDGKSSSQVNRSRHENTSQVPLQESRTRKRRGSRVSQDRDSEGH;SEQ ID No 582:GGVCGPSPPCITTDGTRHSGSRHHEASSQADSSRHSQVGQGQSSGPRTSRNQGSSVSQDSDSQGH; SEQ ID No 583:ERSRSSDGKSSSQVNRSRHENTSQVPLQESRTRKRRGSRVSQDRDSEGHGGVCGPSPPCITTDGTRHSGSRHHEA SSQADSSRHSQVGQGQSSGPRTSRNQGSSVSQDSDSQGH; or sequences of table 2 or 3, or mixtures thereof.

[0031] In an embodiment for better results, the amount peptide ranges from 0.0001 % to 20 % (w / w).

[0032] In an embodiment for better results, the amount peptide ranges from 0.001% to 5 % (w / w).

[0033] In an embodiment for better results, the amount peptide ranges from 0.1% to about 1% (w / w).

[0034] In an embodiment for better results, the green solvent is a natural deep eutectic solvent.

[0035] In an embodiment for better results, the composition does not contain water.

[0036] In an embodiment for better results, the composition may further comprise at least one excipient suitable for dermatological use.

[0037] In an embodiment for better results, the at least one excipient suitable for dermatological use may be selected from the following list: preservative, thickener, organic polymer, humectant, silicone, oil, fragrance, vitamin, buffer, antimicrobial agent, antibacterial agent, disinfectant, chelating agent or mixtures thereof.

[0038] In an embodiment for better results, the at least one excipient suitable for dermatological use is selected from the following list: ethanol, benzyl alcohol, diol molecule, urea, ammonium thioglycolate, thioanisole, tris(hydroxymethyl)aminomethane, phosphate buffer, sodium hydroxide, sodium chloride, citrate buffer, or a combination of two or more thereof.

[0039] An aspect of the present disclosure relates to the use of the composition as described in the present disclosure as an antimicrobial agent against infection.

[0040] In an embodiment for better results, the composition as described in the present disclosure may be used against infections of Trichophyton mentagrophytes strain, and / or toenails infections.

[0041] In an embodiment for better results, the composition may be a pharmaceutical or a cosmetic composition.

[0042] An aspect of the present disclosure relates to the use of the composition described in the present disclosure in skin, nail, hair or scalp treatment; namely for the prevention or treatment of diseases or disorders in skin, nail, hair or scalp (human or animal).

[0043] An aspect of the present disclosure relates to a shampoo, lotion, serum, cream, conditioner, foam, elixir, oil, aerosol or mask comprising the composition described in the present disclosure.

[0044] An aspect of the present disclosure relates to the use of the composition described in the present disclosure in skin, nail, hair or scalp treatment (human or animal).

[0045] An aspect of the present disclosure relates to the use of the composition described in the present disclosure for the manufacture of a medicament for the prevention or treatment of diseases or disorders in skin, nail, hair or scalp (human or animal).

[0046] An aspect of the present disclosure relates to a method for treating or preventing of diseases or disorders in skin, nail, hair or scalp in a subject (human or animal), the method comprising administering the composition of the present disclosure.

[0047] In an embodiment for better results, the composition may further comprise a propellant, a fragrance, an oil, or mixture thereof.

[0048] In an embodiment for better results, the composition of the present disclosure may be used in hair or scalp treatment.

[0049] In an embodiment for better results, the composition of the present disclosure may be used as a cosmetic product; namely as a cosmetic for hair, nails, skin or scalp.

[0050] In an embodiment for better results, the composition of the present disclosure may be a shampoo, a lotion, a serum, a cream, a conditioner, a foam, an elixir, an oil, an aerosol or a mask comprising the cosmetic composition described in the present disclosure. In an embodiment, the components of the described cosmetic composition may be enriched with active components for sensations of warm, cold, freshness, relaxing, pain relive, lightness and well-being, preferably selected from a list comprising: a peptide, icilin, menthol, carboxylated icilin, carboxylated menthol, baicalin, curcumin, caffeine, or mixtures thereof, among others.

[0051] Another aspect of the present disclosure relates to the use of a cosmetic composition as described in the present disclosure as a cosmetic product, namely as a cosmetic for hair, nails, skin or scalp.

[0052] Further particular and preferred aspects are set out in the accompanying independent and dependent claims. Features of the dependent claims may be combined with features of the independent claims as appropriate, and in combinations other than those explicitly set out in the claims.BRI EF DESCRI PTION OF THE DRAWINGS

[0053] The following figures provide preferred embodiments for illustrating the disclosure and should not be seen as limiting the scope of invention.

[0054] Figure 1: Schematic representation of a stable formulation comprising a green solvent, a phospholipid as an emulsifier, an oil phase, and at least one soluble auxiliary, such as a diol.

[0055] Figure 2: Assessment of the stability of an emulsified formulation by centrifugation (1100 g, 30 minutes at room temperature) by visual inspection.

[0056] Figure 3: Antimicrobial activity of a formulation with the composition of Example 2 against Trichophyton mentagrophytes strain, Candida parapsilosis, Klebsiella pneumoniae, and Staphylococcus aureus by disc-diffusion antibiotic susceptibility.

[0057] Figure 4: Visual inspection of the anti-fungal activity of a formulation in toenails with the composition of Example 2.DETAI LED D ESCRI PTION

[0058] The present disclosure provides a stable emulsified composition comprising a green solvent, an emulsifier, an oil phase, and at least one soluble auxiliary; preferably a waterless stable composition. The green solvent can be a naturally occurring product, a mixture of natural solvents, or a Natural Deep Eutectic Solvent (NADES), serving either as a solvent or as a medium to extract bioactive compounds. The emulsifier, such as phospholipids, ensures the stability of the emulsion, while the oil phase delivers essential moisturizing properties. The composition may further include a peptide, a cosmetic component, or a combination thereof to target and enhance specific attributes of hair, nails, scalp, and skin. This composition provides long-lasting stability, antioxidant benefits, and antimicrobial properties, making it suitable for various cosmetic applications.

[0059] A stable emulsified composition with enhanced stability, antioxidant benefits, and antimicrobial properties for application on skin, hair, nails, and / or scalp. The composition comprises a carefully selected blend of emulsifiers (e.g., phospholipids), antioxidants, and antimicrobial agents, ensuring the stability of the emulsion over time and promoting skin, hair, nails, and / or scalp health.

[0060] A stable emulsified composition comprising a bioactive mixture, a phospholipid as an emulsifier, an oil component and at least one diol with enhanced stability, moisturizing effect, antioxidant benefits, and antimicrobial properties for application on skin, hair, nails, and / or scalp. The composition comprises a carefully selected blend of emulsifiers, antioxidants, and antimicrobial agents, ensuring the stability of the emulsion over time and promoting a suitable treatment for beauty healthcare.Example 1:

[0061] In example 1, it was prepared an emulsified composition with:10% (w / w) of rosemary NADES extract as a bioactive mixture (where NADES is glycerol:lactic acid, 4:1 mass ratio);50% (w / w) of phosphatidylcholine as an emulsifier;20% (w / w) of 1,3-Propanediol as a solvent;20% (w / w) of tea tree oil as a bioactive oil phase.0.01% (w / w) SEQ ID No 4: GGVCGPSPPCITTGGRPSDSYGAPGGGN.Example 2:In example 2, it was prepared an emulsion with:20% (w / w) of a thymol and carvacrol solution in NADES as a bioactive mixture (where NADES is glycerol:lactic acid, 4:1 mass ratio);25% (w / w) of phosphatidylcholine as an emulsifier;10% (w / w) of 1,2-Hexanediol as a solvent;20% (w / w) of 1,3-Propanediol as a solvent;25% (w / w) of tea tree oil as a bioactive oil phase;0.01% (w / w) SEQ. ID No 8: GGVCGPSPPCITT.Example 3:In example 3, it was prepared an emulsion with:10% (w / w) of lavender NADES extract as a bioactive mixture (where NADES is glycerol:lactic acid, 4:1 mass ratio);50% (w / w) of lecithin as an emulsifier;10% (w / w) of 1,2-Butanediol as a solvent;10% (w / w) of 1,2-Propanediol as a solvent;20% (w / w) of tea tree oil as a bioactive oil phase.0.01% (w / w) SEQ ID No 33: GPTGPTGPAGPRGLQGLQGLQGERGEQGPT.

[0062] Table 1. Assessment of the antioxidant activity * and quantification of total phenolic and flavonoid contents.* BRS device - Multiparametric portable device based on electrochemistry designed to measure antioxidant capacity.

[0063] Table 2. Non-Limiting Example Peptide Sequences.

[0064] Table 3. Non-Limiting Example Peptide sequences that can be added to the composition of the present disclosure.Stability and antimicrobial activity studies of stable composition formulationsStability assay

[0065] The stability of examples formulations was conducted in a plastic container closure system selected for proposed for packaging, storage and distribution. The long-term storage conditions were evaluated after 12 months.

[0066] Table 4. Stability results of Example 1, 2 and 3 formulations after 12 months, at room temperature.*Stability evaluated as no phase separation after centrifugation at 1100 g for 30 min, room temperature.

[0067] Fig. 2 illustrates the visual inspection of the stability analysis conducted using centrifugation. The visual inspection focuses on identifying potential signs of instability, such as phase separation, creaming, sedimentation, or changes in texture and homogeneity. The images in Fig. 2 provide a clear comparison of the formulation before and after centrifugation and no signs of instability are observed.Antimicrobial activity

[0068] Antimicrobial activity against two different bacteria and fungus species was analysed by in vitro antimicrobial susceptibility test (disk diffusion method). The results are represented by the diameter of the growth inhibition zone (cm).

[0069] Table 5. Antimicrobial activity results of PBS buffer, NADES and Example 2 formulation against different microbial species.

[0070] *NADES is glycerol:lactic acid, 4:1 molar ratio

[0071] In Fig. 3, the images of the in vitro antimicrobial susceptibility test are displayed, illustrating the results of the experiment. These images provide a visual representation of the antimicrobial activity, highlighting differences in the size and clarity of the inhibition zones, which correlate with the potency of a formulation with the composition of Example 2.

[0072] In Fig. 4 it can be observed by visual inspection the anti-fungal activity of Example 2 formulation in nails with toenails infection.

[0073] The term "comprising" whenever used in this document is intended to indicate the presence of stated features, integers, steps, components, but not to preclude the presence or addition of one or more other features, integers, steps, components or groups thereof.

[0074] Methods for the alignment of sequences for comparison are well known in the art, such methods include GAP, BESTFIT, BLAST, FASTA and TFASTA. GAP uses the algorithm of Needleman and Wunsch ((1970) J Mol Biol 48: 443-453) to find the global (over the whole the sequence) alignment of two sequences that maximizes the number of matches and minimizes the number of gaps. The BLAST algorithm (Altschul et al. (1990) J Mol Biol 215: 403-10) calculates percent sequence identity and performs a statistical analysis of the similarity between the two sequences. The software for performing BLAST analysis is publicly available through the National Centre for Biotechnology Information (NCBI). Global percentages of similarity and identity may also be determined using one of the methods available in the MatGAT software package (Campanella et al., BMC Bioinformatics. 2003 Jul 10; 4:29. MatGAT: an application that generates similarity / identity matrices using protein or DNA sequences). Minor manual editing may be performed to optimise alignment between conserved motifs, as would be apparent to a person skilled in the art. The sequence identity values, which are indicated in the present subject matter as a percentage were determined over the entire amino acid sequence, using BLAST with the default parameters.

[0075] As used in the specification and claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a sample" includes a plurality of samples, including mixtures thereof.

[0076] Whenever the term "at least," "greater than," or "greater than or equal to" precedes the first numerical value in a series of two or more numerical values, the term "at least," "greater than" or "greater than or equal to" applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0077] The terms "determining," "measuring," "evaluating," "assessing," "assaying," and "analyzing" are often used interchangeably herein to refer to forms of measurement. The terms include determining if an element is present or not (for example, detection). These terms can include quantitative, qualitative or quantitative and qualitative determinations. Assessing can be relative or absolute. "Detecting the presence of" can include determining the amount of something present in addition to determining whether it is present or absent depending on the context.

[0078] As used herein, the term "about" a number refers to that number plus or minus 10% of that number. The term "about" a range refers to that range minus 10% of its lowest value and plus 10% of its greatest value.

[0079] As used herein, the terms "pharmaceutically acceptable" and "cosmetically acceptable" are used interchangeably and refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beingsand animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit / risk ratio. More specifically, pharmaceutically acceptable refers to a material, compound, or composition which is suitable for use in contact with the skin, scalp, or hair. Pharmaceutically acceptable materials are known to those of ordinary skill in the art.

[0080] As used herein, the terms "treatment" or "treating" are used in reference to a pharmaceutical or other intervention regimen for obtaining beneficial or desired results in the recipient. Beneficial or desired results include but are not limited to a therapeutic benefit and / or a prophylactic benefit. A therapeutic benefit may refer to eradication or amelioration of symptoms or of an underlying disorder being treated. Also, a therapeutic benefit can be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. As used herein, the term "treatment" or "treating" refers to the therapeutic intervention, management, or alleviation of a disease, disorder, or condition in a subject. Unless otherwise specified, the term encompasses both human and animal subjects. A prophylactic effect includes delaying, preventing, or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof. For prophylactic benefit, a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease may undergo treatment, even though a diagnosis of this disease may not have been made.

[0081] Whenever the term "at least," "greater than," or "greater than or equal to" precedes the first numerical value in a series of two or more numerical values, the term "at least," "greater than" or "greater than or equal to" applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0082] Furthermore, it is to be understood that the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc., from one or more of the claims or from relevant portions of the description is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim.

[0083] Furthermore, where the claims recite a composition, it is to be understood that methods of using the composition for any of the purposes disclosed herein are included, and methods of making the composition according to any of the methods of making disclosed herein or other methods known in the art are included, unless otherwise indicated or unless it would be evident to one of ordinary skill in the art that a contradiction or inconsistency would arise.

[0084] Where ranges are given, endpoints are included. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and / or the understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. It is also to be understood that unless otherwise indicated or otherwise evident from the context and / or the understanding of one of ordinary skill in the art, values expressed as ranges can assume any subrange within the given range, wherein the endpoints of the subrange are expressed to the same degree of accuracy as the tenth of the unit of the lower limit of the range.

[0085] The disclosure should not be seen in any way restricted to the embodiments described and a person with ordinary skill in the art will foresee many possibilities to modifications thereof.

[0086] The above-described embodiments are combinable.

[0087] The following claims further set out particular embodiments of the disclosure.

Claims

AMENDED CLAIMS received by the International Bureau on August 5, 2025 (05.08.2025)1. Stable emulsified composition, comprising:0.01 to 30% (w / w) of a bioactive mixture; 10 to 50% (w / w) of a phospholipid as an emulsifier; and 10 to 40% (w / w) of a di-alcohol as a solvent; wherein the bioactive mixture comprises a green solvent and an active cosmetic / pharmaceutical compound; wherein the green solvent is selected from a list consisting of a mixture of at least two of: lactic acid, glycolic acid, decanoic acid, citric acid, maleic acid, malic acid, oxalic acid, tartaric acid, oleic acid, palmitic acid, enanthic acid, formic acid, caprylic acid, ethylene glycol, propylene glycol, glycine, glycerol, glucose, transcutol, menthol, sodium lactate, sodium acetate, sodium citrate, xylitol and sorbitol.

2. Composition according to the previous claim comprising:15 to 20% (w / w) of the bioactive mixture;20 to 40% (w / w) of the phospholipid as an emulsifier;20 to 30% (w / w) of the di-alcohol as a solvent.

3. Composition according to any of the previous claims, wherein the green solvent is selected from a list consisting of a mixture of at least two of: lactic acid, glycolic acid, glycine, glycerol, ethylene glycol and propylene glycol.

4. Composition according to any of the previous claims, wherein the phospholipid is selected from a list consisting of: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, lecithin including unsaturated as well as hydrogenated phospholipids, or mixtures thereof.

5. Composition according to the previous claim, wherein the phospholipid is selected from a list consisting of: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lecithin or mixtures thereof; preferably lecithin.

6. Composition according to the previous claim, wherein the phospholipid is selected from a list consisting of: phosphatidylcholine and / or lecithin.

7. Composition according to any of the previous claims, wherein at least two components of the green solvent mixture is glycolic acid and glycerol or lactic acid and glycerol.

8. Composition according to any of the previous claims, wherein the mass ratio between the two components of green solvent ranges from 20:1 - 1:20.

9. Composition according to the previous claim wherein the mass ratio between the two components of green solvent ranges from 10:1 to 1:10.

10. Composition according to the previous claim wherein the mass ratio between the two components of green solvent ranges from 1:2 to 1:4.

11. Composition according to any of the previous claims, wherein the active compound is selected from: a peptide, icilin, menthol, carboxylated icilin, carboxylated menthol, baicalin, curcumin, caffeine, or mixtures thereof.

12. Composition according to any of the previous claims, wherein the amount of the active compound ranges from 0.01 to 10 % (w / w).

13. Composition according to any of the previous claims, wherein the amount of the active compound ranges from 0.01 to 5 % (w / w).

14. Composition according to the previous claim, wherein the amount of the active compound ranges from 0.5 to 2 % (w / w).

15. Composition according to any of the previous claims, wherein the di-alcohol is selected from a list consisting of: 1,2-Propanediol; 1,3-Propanediol; 1,2-Butanediol; 1,3-Butanediol; 1,4-Butanediol; 2,3-Butanediol; 1,2-Hexanediol; 1,6-Hexanodiol; 1,5-Pentanediol; 1,2-Octanediol; 1,8-Octanediol; 1,2-Decanediol; 1,10-Decanediol; Methylpropanediol; 2-Butyl-2-ethyl-1,3-propanediol, Isopentyldiol andEthane-1,2-diol or mixtures thereof.

16. Composition according to the previous claim, wherein the di-alcohol is selected from a list consisting of:1,2-Propanediol; 1,3-Propanediol; 1,2-Butanediol; 1,3-Butanediol; 1,4-Butanediol; 2,3-Butanediol;1,2-Hexanediol; 1,6-Hexanodiol, or mixtures thereof.

17. Composition according to the previous claim, wherein the di-alcohol is selected from a list consisting of:1,3-Propanediol, 1,2-Butanediol and 1,2-Hexanediol; or mixtures thereof.

18. Composition according to any of the previous claims, further comprising a natural oil, a propellant, a fragrance, an oil, or mixtures thereof.

19. Composition according to any of the previous claims, further comprising an essential oil, an insect- based oil, a plant-based oil, or mixtures thereof.

20. Composition according to any of the previous claims, further comprising a peptide, preferably wherein the peptide is at least a peptide 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or100% sequence identity to a sequence selected from a list consisting of:SEQ ID No 552: YGGFL;SEQ ID No 553: YPWF;SEQ ID No 554: YGGFM;SEQ ID No 555: YPFF;SEQ ID No 556: EEMQRR;SEQ ID No 557: MGWCTASVPPQCYG;SEQ ID No 558: ATAKAWLKGIGAGAGAGA;SEQ ID No 559: RRQMEEGAGAGAGA;SEQ ID No 560: GGVCGPSPPCITTATAKAWLKGI;SEQ ID No 561: GGVCGPSPPCITTGAGAGAGATAKAWLKGI;SEQ ID No 562: ATAKAWLKGIGGVCGPSPPCITT;SEQ ID No 563: ATAKAWLKGIAGAGAGAGGVCGPSPPCITT;SEQ ID No 564: GGVCGPSPPCITTATAKAWLKGIRRQMEE;SEQ ID No 565: RRQMEEATAKAWLKGIGGVCGPSPPCITT;SEQ ID No 566: GGVCGPSPPCITTRRQMEE;SEQ ID No 584: GGVCGPSPPCITTGAGAGAGARRQMEE;SEQ ID No 585: RRQMEEGGVCGPSPPCITT;SEQ ID No 586: RRQMEEGGVCGPSPPCITTGRKKRRQRRRPPQ;SEQ ID No 587: GRKKRRQRRRPPQGGVCGPSPPCITTRRQMEE;SEQ ID No 568: RRQMEEGAGAGAGAGGVCGPSPPCITT;SEQ ID No 569: ATAKAWLKGIMGWCTASVPPQCYG;SEQ ID No 570: RRQMEEMGWCTASVPPQCYG;SEQ ID No 2: GGVCGPSPPCITTVPGVGVPGVGVPGVGVPGVGVPGVGVPGVG;SEQ ID No 549: GGVCGPSPPCITTGAGAGSGAGAGSVPAVGVPAVGVPAVG;SEQ ID No 5: GGVCGPSPPCITTGPTGPTGPAGPRGLQGLQGLQGERGEQGPT;SEQ ID No 4: GGVCGPSPPCITTGGRPSDSYGAPGGGN;SEQ ID No 6: GGVCGPSPPCITTGGFGGMGGGSGGFGGMGGGSGGFGGMGGGS;SEQ ID No 45: GGVCGPSPPCITTAKAKAKAKAKAKAKAKAKAKAKAKAKAKAK;SEQ ID No 46: GGVCGPSPPCITTLKLKLKLKLKLKLKLKLKLKLKLKLKLKLK;SEQ ID No 573: GGVCGPSPPCITTRCAERCSEASIQDRCLKYCGICCEK;SEQ ID No 574: GGVCGPSPPCITTGTYGNKDECPCYRDMKNSKGKGKCP;SEQ ID No 572: GGVCGPSPPCITTGTCYINDDEGCTKRCQGIYIYRREAVMGHC;SEQ ID No 588: LKLKLKLKLKLKLKLKLKLK;SEQ ID No 589: LELELELELELELELELELE;SEQ ID No 571: YGRKKRRQRRR;SEQ ID No 575: GRKKRRQRRRPPQ;SEQ ID No 576: RQIKIWFQNRRMKWKK;SEQ ID No 590: RKKNPNCRRH;SEQ ID No 577: RIMRILRILKLAR;SEQ ID No 578: ILRRRRIRKQAHAHSK;SEQ ID No 579: GVCGPSPPCITTDRDDQAAWFSQY;SEQ ID No 580:MVYYPNPCSPYPCRNGGTCKKRGLYSYKCYCRKGYTGKNCQYNACFPNPCLNGGTCGYVYGYPYYKCSCPYGYYGKQCQLKKYGGVCGPSPPCITT;SEQ ID No 581:GGVCGPSPPCITTERSRSSDGKSSSQVNRSRHENTSQVPLQESRTRKRRGSRVSQDRDSEGH;SEQ ID No 582:GGVCGPSPPCITTDGTRHSGSRHHEASSQADSSRHSQVGQGQSSGPRTSRNQGSSVSQDSDSQGH;SEQ ID No 583:ERSRSSDGKSSSQVNRSRHENTSQVPLQESRTRKRRGSRVSQDRDSEGHGGVCGPSPPCITTDGTRHSGSRHHEASSQADSSRHSQVGQGQSSGPRTSRNQGSSVSQDSDSQGH,SEQ. ID No 8: GGVCGPSPPCITT; or sequence of table 2 or 3, or mixtures thereof.

21. Composition according to the previous claim, wherein the amount peptide ranges from 0.0001 % to20 % (w / w).

22. Composition according to the previous claim, wherein the amount peptide ranges from 0.001% to 5% (w / w).

23. Composition according to the previous claim, wherein the amount peptide ranges from 0.1% to about1% (w / w).

24. Composition according to any of the previous claims, wherein the green solvent is a natural deep eutectic solvent.

25. Composition according to any of the previous claims, wherein the composition does not contain water.

26. Composition according to any of the previous claims, comprising at least one excipient suitable for dermatological use.

27. Composition according to the previous claim, wherein the at least one excipient suitable for dermatological use is selected from the following list: preservative, thickener, organic polymer, humectant, silicone, oil, fragrance, vitamin, buffer, antimicrobial agent, antibacterial agent, disinfectant, chelating agent or mixtures thereof.

28. Composition according to the previous claim, wherein the at least one excipient suitable for dermatological use is selected from the following list: ethanol, benzyl alcohol, diol molecule, urea,ammonium thioglycolate, thioanisole, tris(hydroxymethyl)aminomethane, phosphate buffer, sodium hydroxide, sodium chloride, citrate buffer, or a combination of two or more thereof.

29. Composition according to any of the previous claims, for use as antimicrobial agent against infection.

30. Composition according to any of the previous claims, for use against infections of Trichophyton mentagrophytes strain, and / or toenails infections.

31. Composition according to any of the previous claims, wherein the composition is a pharmaceutical or a cosmetic composition.

32. Composition according to any of the previous claims, for use in skin, nail, hair or scalp treatment; namely for the prevention or treatment of diseases or disorders in skin, hair or scalp.

33. A shampoo, lotion, serum, cream, conditioner, foam, elixir, oil, aerosol or mask comprising the composition described in any of the previous claims.

34. Composition according to any of the previous claims, for use in skin, nail, hair or scalp treatment.

35. The use of the composition according to any of the previous claims for the manufacture of a medicament for the prevention or treatment of diseases or disorders in skin, nail, hair or scalp.

36. A method for treating or preventing of diseases or disorders in skin, nail, hair or scalp in a subject, the method comprising administering the composition of any of the previous claim 1 to the subject.

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